enalapril and Myocardial-Infarction
enalapril has been researched along with Myocardial-Infarction* in 196 studies
Reviews
15 review(s) available for enalapril and Myocardial-Infarction
Article | Year |
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Efficacy of Sacubitril-Valsartan in Patients With Reduced Left Ventricular Ejection Fraction.
Topics: Aged; Aminobutyrates; Angiotensin Receptor Antagonists; Angiotensin-Converting Enzyme Inhibitors; Biphenyl Compounds; Cardiovascular Diseases; Drug Combinations; Enalapril; Enzyme Inhibitors; Female; Heart Failure; Hospitalization; Humans; Male; Middle Aged; Myocardial Infarction; Neprilysin; Ramipril; Severity of Illness Index; Stroke Volume; Valsartan; Ventricular Dysfunction, Left | 2021 |
[The use of angiotensin converting enzyme inhibitors in patients after myocardial infarction].
Nowadays angiotensin-converting enzyme inhibitors (ACE-Is) are considered to be a cornerstone in the treatment of congestive heart failure (CHF). These agents have been shown to improve survival and functional status of patients with CHF. It is logical to start therapy with ACE-Is in the first hours or days of acute myocardial infarction (MI) to further improve survival and prevent CHF after MI. The several randomized placebo-controlled trials were performed to assess the effects of early therapy with ACE-Is on the outcomes of MI. Mortality after MI was significantly reduced only in these trials in which therapy with ACE-Is was introduced 3-16 days after MI in patients with clinical evidence of CHF or left ventricular systolic dysfunction as well as in patients with noneffective thrombolysis (or without thrombolysis) or diabetes mellitus. Topics: Aged; Angiotensin-Converting Enzyme Inhibitors; Captopril; Diabetes Complications; Enalapril; Heart Failure; Humans; Indoles; Middle Aged; Myocardial Infarction; Ramipril; Randomized Controlled Trials as Topic; Time Factors; Treatment Outcome; Ventricular Dysfunction | 2008 |
Organic nitrates in cardiovascular disease.
Therapeutic activation of the vascular NO/cGMP pathway is induced by a variety of stimuli/mediators including physical activity, supplementation with the precursor L-arginine and organic nitrates which generate NO in the vasculature. The necessity of an enzymatic reduction for NO generation from these drugs as well as differences in the activity of the NO/cGMP pathway within the vascular tree determine the unique hemodynamic changes elicited by organic nitrates. These changes include preferential venodilation, vessel-size specific arterial dilation and improvement of the aortic distensibility and Windkessel-function. Some animal experiments and clinical investigations suggest that nitrates may also be endowed with cardioprotective and/or vasoprotective effects. "Early entry" therapy with nitrates do not significantly improve survival in myocardial infarction but increases the beneficial effects of the ACE-inhibitor enalapril by 50%. Furthermore, nitrates have been shown to improve survival in heart failure, but prognostic effects in stable angina pectoris are unknown. Short-term experimental and clinical investigations suggest that nitrate tolerance induced by nitroglycerin is associated with toxic effects in the vasculature, but this is not true for pentaerythrityl tetranitrate and isosorbide mononitrate. The observed endothelial dysfunction induced by a continuous treatment with nitroglycerin may be an additional risk for patients who receive continuous nitroglycerin to treat conditions such as unstable angina and acute heart failure. In general, nitrates are remarkably safe drugs and are well tolerated. Appropriate clinical trials are needed to answer the question whether nitrates can do more than symptomatic relief in cardiovascular disease. Topics: Angina, Unstable; Animals; Cardiovascular Diseases; Cyclic GMP; Enalapril; Endothelium, Vascular; Hemodynamics; Humans; Myocardial Infarction; Nitrates; Nitric Oxide; Nitroglycerin; Platelet Aggregation | 2005 |
[Angiotensin-converting enzyme inhibition and cardiovascular prevention: more than twenty years of clinical success].
Angiotensin-converting enzyme (ACE) inhibitors are widely used for the treatment of cardiovascular disease since they improve blood pressure control in patients with hypertension and prolong survival in patients with acute myocardial infarction, asymptomatic left ventricular dysfunction and congestive heart failure. Most of the information about the therapeutic role of ACE-inhibitors has been achieved during the last 20 years since the publication of some pivotal trials mostly involving the use of ACE-inhibitors like captopril and enalapril. In particular the treatment with enalapril has considerably improved the clinical outcome of patients with either mild-to-moderate (SOLVD studies) or severe (CONSENSUS trial) congestive heart failure. The benefit of ACE-inhibitors in patients with congestive heart failure has also involved a remarkable reduction in the rate of hospitalization, thus contributing to improve the pharmaco-economic approach to the disease. Most of the beneficial effect of ACE-inhibitors in clinical practice is dependent on their capacity of inhibiting the renin-angiotensin system, although some recent trials have supported a primary role for such drugs (in particular enalapril) in the prevention of atrial fibrillation. After more than 25 years from their discovery, ACE-inhibitors must be again considered among the first-line treatment in many patients with cardiovascular disease. Topics: Angiotensin-Converting Enzyme Inhibitors; Atrial Fibrillation; Captopril; Cardiovascular Diseases; Enalapril; Heart Failure; Humans; Hypertension; Myocardial Infarction; Myocardial Ischemia; Renin-Angiotensin System; Ventricular Dysfunction | 2005 |
[Preventive therapy with ACE inhibitors for coronary patients].
The results of the major clinical outcome trials related to the potential antiatherosclerotic effects of the angiotensin convertase (ACE) inhibitors are reviewed after the recently published EUROPA trial results. In the postinfarction clinical situation mortality reduction was revealed in the ISIS-4 (captopril), GISSI-3 (lisinopril), AIRE (ramipril), TRACE (trandolapril), CONSENSUS (enalapril), SAVE (captopril) and in the SOLVD (enalapril) trials. In the HOPE trial performed in a high risk population the preventive antiatherosclerotic, endothel-preserving effects of ramipril resulted in a significant mortality and morbidity reduction. In the EUROPA trial a lower risk population--symptomfree coronary patients--were treated by perindopril, and it was proven also in this cohort, that the long term ACE inhibitor treatment decreased the combined endpoint of cardiovascular mortality, myocardial infarction and resuscitated sudden death. Based on the above data it can be advised, that all coronary patients regardless of left ventricular function and symptoms should receive long term ACE inhibitor treatment besides the other established preventive medications (platelet aggregation inhibitors + statins + beta receptor blockers). Topics: Angiotensin-Converting Enzyme Inhibitors; Antihypertensive Agents; Captopril; Clinical Trials as Topic; Coronary Disease; Death, Sudden, Cardiac; Enalapril; Humans; Indoles; Lisinopril; Myocardial Infarction; Perindopril; Ramipril; Treatment Outcome | 2004 |
Aldosterone antagonism and congestive heart failure: a new look at an old therapy.
More than 5 million people in the United States alone have congestive heart failure, and an estimated 40 million have established risks and warrant therapy. Mineralocorticoid antagonists have emerged as a new paradigm for the treatment of congestive heart failure. They have established benefits among patients with chronic symptomatic systolic dysfunction, and recent studies have demonstrated substantial effect on the morbidity and mortality among patients with heart failure after myocardial infarction. The exact biologic mechanism is thus far unknown.. Within the last 5 years, efforts have intensified to help define better the biologic mechanisms by which mineralocorticoid receptor antagonisms exert the observed clinical benefit. Elegant human studies have demonstrated some important observations. First, under conditions of increased plasma aldosterone concentrations, the heart will extract aldosterone. Second, aldosterone extraction in the heart stimulates increased collagen turnover culminating in ventricular remodeling. Third, among people with chronic systolic or diastolic heart failure, aldosterone is actually produced and secreted by the heart. Finally, antagonism of the mineralocorticoid receptor will attenuate or abrogate many of these deleterious effects.. Combined clinical and detailed mechanistic investigations have established mineralocorticoid receptor antagonism as the new treatment paradigm for congestive heart failure. Recent clinical data have demonstrated that treatment of patients with a combination of mineralocorticoid receptor antagonism (eplerenone) and angiotensin converting enzyme-inhibitor (ACE-I) results in substantial reduction in left ventricular mass. Furthermore, a federally funded initiative to treat more than 6000 patients with diastolic heart failure with spironolactone is in its final phases of planning. It is foreseeable that, along with ACE-I and beta-blockers, mineralocorticoid receptor antagonism will become part of the treatment paradigm for people across the entire spectrum of cardiovascular disease. Topics: Angiotensin-Converting Enzyme Inhibitors; Drug Therapy, Combination; Enalapril; Eplerenone; Heart Failure; Humans; Mineralocorticoid Receptor Antagonists; Myocardial Infarction; Randomized Controlled Trials as Topic; Spironolactone; Treatment Outcome; Ventricular Function, Left; Ventricular Remodeling | 2004 |
[Angiotensin-converting enzyme inhibitors :from vasoactive drugs to cardiovascular prevention tools].
Abundant evidence showed that angiotensin-converting enzyme (ACE)-inhibitors reduce long-term cardiovascular morbidity and mortality rates in patients with heart failure and myocardial infarction. More recent studies revealed clinical benefits also in hypertensive patients with comorbidity and lead to an extension of clinical indications. Indeed in patients with severe hypertension differences between drugs are hardly detectable because the risk reduction is mainly related to the control of blood pressure values independent of the type of therapy. Conversely in the presence of comorbid conditions, especially in diabetics, the association of ACE-inhibitors with antihypertensive treatments proved its efficacy in reducing cardiovascular morbidity and mortality so that the role of mechanisms extending beyond blood pressure reduction can be postulated. Topics: Angiotensin-Converting Enzyme Inhibitors; Captopril; Clinical Trials as Topic; Drug Therapy, Combination; Enalapril; Heart Diseases; Heart Failure; Humans; Hypertension; Myocardial Infarction; Survival Rate; Treatment Outcome | 2003 |
Using ACE inhibitors appropriately.
When first introduced in 1981, angiotensin-converting enzyme (ACE) inhibitors were indicated only for treatment of refractory hypertension. Since then, they have been shown to reduce morbidity or mortality in congestive heart failure, myocardial infarction, diabetes mellitus, chronic renal insufficiency, and atherosclerotic cardiovascular disease. Pathologies underlying these conditions are, in part, attributable to the renin-angiotensin-aldosterone system. Angiotensin II contributes to endothelial dysfunction. altered renal hemodynamics, and vascular and cardiac hypertrophy. ACE inhibitors attenuate these effects. Clinical outcomes of ACE inhibition include decreases in myocardial infarction (fatal and nonfatal), reinfarction, angina, stroke, end-stage renal disease, and morbidity and mortality associated with heart failure. ACE inhibitors are generally well tolerated and have few contraindications. (Am Fam Physician 2002;66:473.) Topics: Angiotensin-Converting Enzyme Inhibitors; Antihypertensive Agents; Benzazepines; Captopril; Cardiovascular Diseases; Clinical Trials as Topic; Contraindications; Diabetic Nephropathies; Drug Costs; Enalapril; Fosinopril; Heart Failure; Humans; Hypertension; Indoles; Isoquinolines; Lisinopril; Meta-Analysis as Topic; Myocardial Infarction; Perindopril; Quinapril; Ramipril; Renin-Angiotensin System; Risk; Tetrahydroisoquinolines; United States | 2002 |
[Congestive heart failure and acute myocardial infarction: latest trials with beta-blocking agents].
Topics: Adrenergic beta-Antagonists; Aged; Angiotensin-Converting Enzyme Inhibitors; Carbazoles; Carvedilol; Confidence Intervals; Death, Sudden, Cardiac; Enalapril; Female; Follow-Up Studies; Heart Failure; Hospitalization; Humans; Male; Meta-Analysis as Topic; Middle Aged; Myocardial Infarction; Placebos; Propanolamines; Randomized Controlled Trials as Topic; Recurrence; Risk Factors; Time Factors; Ventricular Dysfunction, Left; Ventricular Function, Left | 2002 |
Management of asymptomatic left ventricular dysfunction.
Asymptomatic left ventricular dysfunction should be treated as an early stage on the continuum that is chronic heart failure. The author presents the clinical trial data on which current management with angiotensin-converting enzyme inhibitors and beta-blockers is based. Issues surrounding screening are also discussed. Topics: Adrenergic beta-Antagonists; Aged; Aged, 80 and over; Angiotensin-Converting Enzyme Inhibitors; Antihypertensive Agents; Captopril; Coronary Disease; Drug Therapy, Combination; Echocardiography; Enalapril; Female; Heart Failure; Humans; Hypertension; Indoles; Male; Middle Aged; Myocardial Infarction; Norepinephrine; Ramipril; Randomized Controlled Trials as Topic; Retrospective Studies; Risk Factors; Ventricular Dysfunction, Left; Ventricular Function, Left | 2001 |
[Role of converting enzyme inhibitors in myocardial infarction].
Topics: Angiotensin-Converting Enzyme Inhibitors; Captopril; Enalapril; Humans; Myocardial Infarction; Randomized Controlled Trials as Topic | 1995 |
The role of ACE inhibitors in preventing myocardial infarction: potential mechanisms and clinical implications.
Topics: Angiotensin-Converting Enzyme Inhibitors; Cardiomegaly; Enalapril; Humans; Hypertension; Myocardial Infarction; Myocardial Ischemia; Peptidyl-Dipeptidase A; Polymorphism, Genetic | 1995 |
[Angiotensin converting enzyme inhibitors during acute phase of myocardial infarct].
Up to September, 1993, several questions were open on the use of angiotensin converting enzyme (ACE) inhibitors after myocardial infarction. The SAVE trial has shown that patients with left ventricular dysfunction and a recent (mean 11 days) myocardial infarction benefit from assuming captopril per os during the subsequent clinical course. The SOLVD trials have indicated that therapy with enalapril per os increases the survival of patients with left ventricular dysfunction, a history of myocardial infarction and hemodynamic decompensation. However, the CONSENSUS II trial has not shown similar results on patients with all range left ventricular function, treated within 24 hours of infarction with i.v. enalaprilat and then enalapril per os. In this study, 6-month mortality has been slightly better in the placebo group, and there seems not to be any subgroup benefitting from the ACE inhibitor. In October and November, 1993, the International Cardiologic Community has received the results of 3 large multicenter trials on postinfarction patients: the AIRE (ramipril per os), the GISSI 3 (lisinopril per os) and the ISIS 4 (captopril per os) studies. These trials has pointed out the followings: 1) prompt therapy (within 24 hours of chest pain) with ACE inhibitors is able to improve short term survival in patients with clinical evidence of heart failure, in women and old patients; 2) ACE inhibitors and nitro derivatives are complementary therapies in the acute and subacute phase of infarction, and their association produces the best improvement in short-term survival. There seems to be no intelligible reason, up to now, to deem that any ACE inhibitor should be considered better than another one in the acute phase of infarction, but still during the first 72 hours after the onset of chest pain the advantages have been shown only with lisinopril and captopril. The negative results of the CONSENSUS II trial are probably dependent on the excessively abrupt acute hypotensive effect of i.v. enalaprilat. This last "large trial" decade has taught us that many treatments can be advantageous for acute myocardial infarction but, apart from thrombolysis, all other medical therapies should not be given extensively, but to peculiar patients carefully selected on clinical grounds. Guidelines from official consensus conferences are expected now, to segregate different patterns of clinical presentations to be treated differently. Topics: Administration, Oral; Aged; Angiotensin-Converting Enzyme Inhibitors; Captopril; Clinical Trials as Topic; Enalapril; Female; Humans; Injections, Intravenous; Lisinopril; Male; Multicenter Studies as Topic; Myocardial Infarction; Nitroglycerin; Ramipril; Thrombolytic Therapy; Time Factors | 1994 |
The role of beta-adrenergic blocking agents in preventing sudden cardiac death.
The failure of encainide and flecainide to reduce mortality after infarction in the Cardiac Arrhythmia Suppression Trial and the failure of low-dose amiodarone to prevent sudden cardiac death in patients with a low left ventricular ejection fraction has shifted attention to other strategies, such as beta-adrenergic blocking agents, to prevent sudden cardiac death. Evidence suggesting that beta-adrenergic blocking agents might be useful, especially in patients with low left ventricular ejection fraction, is accumulating. Previous data from studies using beta-adrenergic blocking agents and the mechanisms by which beta-adrenergic blocking agents might be of value in preventing sudden cardiac death are reviewed. These considerations and the availability of new investigational beta-adrenergic blocking agents with vasodilator properties provide a new opportunity to test the hypothesis that beta-adrenergic blocking agents are useful in preventing sudden cardiac death, especially in patients with a low left ventricular ejection fraction. Topics: Adrenergic beta-Antagonists; Arrhythmias, Cardiac; Cardiac Output, Low; Cardiomyopathy, Dilated; Catecholamines; Clinical Trials as Topic; Coronary Disease; Death, Sudden, Cardiac; Diuretics; Enalapril; Heart Ventricles; Humans; Magnesium; Myocardial Infarction | 1992 |
Haemodynamic responses to specific renin-angiotensin inhibitors in hypertension and congestive heart failure. A review.
The renin-angiotensin system is an important regulator of vascular resistance in many patients with hypertension and congestive heart failure. To quantitatively evaluate this contribution requires correlation of markers of the renin-angiotensin system with haemodynamic parameters, notably blood pressure, cardiac output, and calculated systemic vascular resistance. In addition, to determine ventricular loading properties, assessment of cardiac filling pressures is also required. The availability of specific pharmacological inhibitors of the renin-angiotensin system greatly enhances such correlation, as the haemodynamic consequence of blocking the renin-angiotensin system can then more fully identify its contribution. In the last decade, highly specific pharmacological inhibitors have become available to serve such a purpose. Renin inhibitory peptides, and renin-specific antibodies can block the rate-limiting step of the renin-angiotensin cascade: namely, the cleavage of 4 amino acids from the angiotensinogen substrate by renin. However, this method of blockade is still at the early stages of investigation. More readily available are converting enzyme inhibitors which block the formation of angiotensin II, the potent vasoconstrictor which mediates increased systemic vascular resistance, and angiotensin II analogues which compete with endogenous angiotensin II for vascular and adrenal receptors. Although hypertension and chronic congestive heart failure are clinically distinct entities in many respects, their common bond is the fact that both pathological mechanisms are mediated by an increase of systemic vascular resistance. The implications of blocking the resulting vasoconstriction in both entities are therefore quite similar. This review summarises our present knowledge of the contribution of the renin-angiotensin system to the vasoconstriction of hypertension and congestive heart failure, and also summarises the haemodynamic consequences of such inhibition. The implications of the response to these specific pharmacological probes, as well as their limitations, are discussed. Their importance rests not only in their therapeutic application, but also in their contribution as probes for pathophysiological mechanisms of vasoconstriction in cardiovascular disease. Topics: Angiotensin II; Angiotensin-Converting Enzyme Inhibitors; Angiotensinogen; Captopril; Dipeptides; Enalapril; Heart Failure; Hemodynamics; Humans; Hypertension; Hypertension, Pulmonary; Kinetics; Liver Cirrhosis; Mineralocorticoid Receptor Antagonists; Myocardial Infarction; Renin; Renin-Angiotensin System; Teprotide | 1984 |
Trials
71 trial(s) available for enalapril and Myocardial-Infarction
Article | Year |
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Leptin levels are not affected by enalapril treatment after an uncomplicated myocardial infarction, but associate strongly with changes in fibrinolytic variables in men.
Leptin, an adipocyte-derived hormone, is involved in the regulation of body weight and is associated with obesity-related complications, notably cardiovascular disease (CVD). A putative link between obesity and CVD could be induction of plasminogen activator inhibitor-1 (PAI-1) synthesis by leptin. In this study, we hypothesized that the beneficial effect of the angiotensin-converting enzyme inhibitor (ACE Topics: Aged; Angiotensin-Converting Enzyme Inhibitors; Antihypertensive Agents; Double-Blind Method; Enalapril; Female; Fibrinolysis; Gene Expression Regulation; Humans; Leptin; Male; Middle Aged; Myocardial Infarction; Obesity; Plasminogen Activator Inhibitor 1; Protein Binding; Sex Factors; Signal Transduction; Tissue Plasminogen Activator | 2020 |
Imidapril and enalapril similarly inhibit plasma matrix metalloproteinase activities and attenuate left ventricular remodeling in patients with acute myocardial infarction.
Matrix metalloproteinase (MMP) plays a critical role in the development of ventricular remodeling after acute myocardial infarction (AMI). Imidapril, an angiotensin-converting enzyme inhibitor, has been shown to inhibit MMP activity. We investigated whether imidapril inhibits plasma MMP activities and attenuates ventricular remodeling in patients with AMI in comparison with enalapril. We enrolled 70 patients with AMI. All patients underwent primary percutaneous coronary intervention and were randomly assigned either to imidapril (n = 35) or to enalapril (n = 35) treatment. Left ventriculography was performed in acute (day 14) and chronic (6 months) phases, and plasma MMP-2 and MMP-9 activities were measured by zymography. Any changes in left ventricular end-diastolic volume index and ejection fraction from acute to chronic phases did not differ between the 2 groups. The plasma MMP-2 and MMP-9 activities at day 14 were both significantly decreased compared with those at day 1 in both groups (all P < 0.05). At 6 months, MMP-9 activity still remained decreased in both groups (P < 0.05 vs. day 1). Overall, there were no differences between the 2 groups both in plasma MMP-2 and MMP-9 activities. These results demonstrate that imidapril exerts inhibitory effects on plasma MMP activities and attenuates left ventricular remodeling in patients with AMI similar to enalapril. Topics: Aged; Angiotensin-Converting Enzyme Inhibitors; Enalapril; Female; Humans; Imidazolidines; Male; Matrix Metalloproteinase Inhibitors; Matrix Metalloproteinases; Middle Aged; Myocardial Infarction; Ventricular Remodeling | 2014 |
Effects of telmisartan on markers of ventricular remodeling in patients with acute myocardial infarction: comparison with enalapril.
Enalapril is effective in the suppression of left ventricular remodeling after acute myocardial infarction (AMI), but the effect of telmisartan is unclear. The consecutive 163 AMI patients underwent primary percutaneous coronary intervention and were randomized to telmisartan (n = 82) or enalapril (n = 81). Left ventriculography was performed in the acute and chronic (6 months) phases. Matrix metalloproteinase (MMP)-2 and MMP-9 activities were measured by zymography in the acute (days 1, 7, and 14) and chronic (6 months) phases. Plasma pentraxin3 (PTX3), a marker of vascular inflammation, was also measured. There were no adverse effects in the telmisartan group. The analysis of the left ventriculograms in the acute and chronic phases revealed no difference between the two groups. MMP-9 activities at days 7 and 14 and in the chronic phase were decreased compared to that at day 1 in both groups. MMP-2 activity was also decreased in the acute phase, but increased in the chronic phase in both groups. There was no difference in the plasma PTX3 level in the acute phase, but in the chronic phase, PTX3 was significantly lower in telmisartan than in enalapril group (2.6 ± 1.4 vs. 3.2 ± 1.6 ng/ml, p = 0.04). Telmisartan is well tolerated, shows similar effects on the markers of left ventricular remodeling to those of enalapril, and suppresses vascular inflammation more effectively than enalapril in AMI patients. Telmisartan can be an alternative to angiotensin converting enzyme inhibitor in patients with AMI. Topics: Aged; Angiotensin II Type 1 Receptor Blockers; Angiotensin-Converting Enzyme Inhibitors; Benzimidazoles; Benzoates; Biomarkers; C-Reactive Protein; Chi-Square Distribution; Enalapril; Female; Humans; Inflammation Mediators; Japan; Male; Matrix Metalloproteinase 2; Matrix Metalloproteinase 9; Middle Aged; Myocardial Infarction; Prospective Studies; Radiography; Serum Amyloid P-Component; Stroke Volume; Telmisartan; Time Factors; Treatment Outcome; Ventricular Function, Left; Ventricular Remodeling | 2010 |
Effects of enalapril and losartan in left ventricular remodeling after acute myocardial infarction: a possible mechanism of prevention of cardiac events by angiotensin-converting enzyme inhibitors and angiotensin receptor blockers in high-risk myocardial
Angiotensin-converting enzyme inhibitors (ACE-I) and angiotensin II receptor blockers (ARB) have been shown to have a significant cardioprotective effect in high-risk patients after myocardial infarction (MI). However, there are few data on the effects of these drugs on left-ventricular (LV) remodeling after MI in Japanese patients.. We randomly assigned 100 patients with anterior-wall MI who had received reperfusion therapy to treatment with either enalapril (n=50) or losartan (n=50), and calculated the LV ejection fraction (LVEF) and LV end-diastolic volume index (LVEDVI) in these patients at baseline and after 6 months of treatment. While a significant increase in the LVEF as compared with that at the baseline was observed in both groups, no significant difference was found in the rate of change of this parameter between the two groups. However, inverse correlations were observed between the baseline LVEF and LVEDVI and also the rates of change of the two parameters, suggesting that the greater the compromise of the LV function at baseline, the greater the preventive effect of both classes of drugs on LV remodeling.. The results of this study suggest that neither enalapril nor losartan is superior to the other in terms of the effect on LV remodeling after MI in Japanese patients. In addition, the suppressive effect of both classes of drugs on LV remodeling was greater in patients with more extensive infarction and greater compromise of LV function at baseline. Topics: Aged; Angiotensin II Type 1 Receptor Blockers; Angiotensin Receptor Antagonists; Cardiotonic Agents; Enalapril; Female; Humans; Losartan; Male; Middle Aged; Myocardial Infarction; Receptors, Angiotensin; Risk Factors; Ventricular Remodeling | 2009 |
Impact of neurohormonal blockade on association between body mass index and mortality.
The prognostic impact of body mass index (BMI) in patients following acute myocardial infarction (AMI) may be altered by neurohormonal blockade.. The impact of neurohormonal blockade on the association between BMI and mortality was examined in 5548 patients following AMI (CONSENSUS II), 50% receiving enalapril and 7% beta-blockade, and in 4367 patients with coronary artery disease (CAD) (4S), 79% with prior AMI, 12% receiving ACEi and 67% beta-blockade. Median follow-up was 0.4 and 5.2 years, respectively. Patients were categorized into 4 BMI groups: Underweight, < 22.00; normal-weight, 22.00-24.99; overweight, 25.00-29.99; obese, > or = 30.00 kg/m2. Multivariable analysis adjusted for demographics, patient history, physical examination, biochemistry and medication.. CONSENSUS II: Overall, adjusted mortality (n=301) risk was similar across BMI groups. Comparing overweight with normal-weight patients, the hazard ratios (HRs) for mortality differed significantly (P=0.028) between patients randomized to placebo (HR 1.41) and enalapril (HR 0.75). 4S: Overall, adjusted mortality (n=421) risk was similar for normal-weight, overweight and obese patients. In a time-dependent analysis for drug use, comparing obese with normal-weight patients, the HRs for mortality differed significantly (P=0.047) between patients without (HR 1.86) and those with (HR 0.97) neurohormonal blockade.. In patients after AMI or with CAD, high BMI was associated with increased mortality risk among patients not receiving neurohormonal blockade, but with decreased or neutral mortality risk among those receiving neurohormonal blockade. Tests for interaction indicate that neurohormonal blockade may attenuate the relationship between high BMI and increased mortality risk. Neurohormonal blockade may thus partly explain the so-called obesity paradox. Topics: Adrenergic beta-Antagonists; Aged; Antihypertensive Agents; Body Mass Index; Coronary Artery Disease; Enalapril; Female; Humans; Male; Middle Aged; Myocardial Infarction; Obesity; Prognosis; Proportional Hazards Models; Risk Factors | 2007 |
Low doses of intracoronary enalaprilat suppress reperfusion-associated ventricular arrhythmias after primary percutaneous coronary interventions for acute myocardial infarction.
In the era of early reperfusion therapy, life-threatening ventricular arrhythmias (VA) remain common after recanalization of an occluded coronary artery. Experimental studies reported that angiotensin-converting (ACE) inhibitors suppress reperfusion-induced VA. However, whether ACE inhibitors lower the incidence of reperfusion clinical VA is unknown. We examined the effects of low doses of intracoronary (i.c.) enalaprilat (EN) as an adjunct to direct percutaneous coronary interventions (PCI) on reperfusion VA in the acute phase of myocardial infarction (MI).. We randomly assigned 22 patients with a first acute MI, who underwent successful direct PCI, to EN, 50 mug, i.c., or placebo (PL), administered immediately after reperfusion. VA were manually edited and counted from 24-hour Holter recordings begun upon hospital admission.. There were no significant between-groups differences in clinical characteristics. Mean RR interval before and after PCI, and the incidence of VA before PCI were similar in both groups. After PCI the incidence of reperfusion-induced VA was significantly lower in the EN-treated group (VPB/h: PL 29.9 +/- 12 vs EN 43.2 +/- 42, P < 0.05; couplets/h: EN 0.9 +/- 0.7 vs PL 4.1 +/- 5.0, P < 0.01; triplets/h: EN 0.3 +/- 0.2 vs PL 1.2 +/- 1.5, P < 0.05; ventricular tachycardia/h: EN 0.3 +/- 0.1 vs PL 0.8 +/- 0.5, P < 0.01).. Compared with PL, i.c. EN significantly lowered the incidence of reperfusion-associated VA. This previously unrecognized antiarrhythmic effect might be an important therapeutic benefit conferred by ACE inhibitors, beyond limitation of infarct size. Topics: Aged; Angioplasty, Balloon, Coronary; Antihypertensive Agents; Arrhythmias, Cardiac; Coronary Artery Disease; Enalapril; Female; Humans; Male; Middle Aged; Myocardial Infarction; Myocardial Reperfusion; Prospective Studies | 2007 |
[MRT assessment of metabolic and thrombolytic therapy effects on postinfarction left ventricular remodeling].
To examine effects of trimetasidine on morphofunctional indices of the left ventricle (LV) in myocardial infarction (MI) patients on combined treatment.. Seventy five patients with primary macrofocal MI were randomized into 2 groups. Patients of group 1 (n = 38) received a combination of bisoprolol (beta-blocker) with enalapril (ACE inhibitor) in individual doses under control of blood pressure and blood creatinine level. Group 2 (n = 37) patients received the same combination of drugs and, in addition, trimetasidine in a dose 70 mg/day from postmyocardial day 7-10 for 6 months. Two subgroups from the groups were given systemic thrombolytic therapy (STLT) with streptokinase. MRT and cine-MRT of the heart were made for measurement of LV morphofunctional parameters.. Low-field MRT of the heart in MI patients treated with adjuvant STLT (1500000 U within 6 hours after MI onset) and trimetasidine (preductal MB) in a dose 70 mg/day from the disease day 7-10 registered a significant inhibition of pathological LV postinfarction remodeling: a decrease of body surface indexed LV end diastolic volume by 10.3%, systolic volume--by 15.4%, LV myocardial tension--by 14.0%, sphericity index--by 7.1%; an increase in the index of relative wall thickness by 5.3%, cardiac index--by 9.2% compared to the group treated without trimetasidine.. 6-month therapy with trimetasidine of MI patients leads to a significant regress of morphofunctional changes accompanying LV remodeling. Pathological LV postinfarction remodeling inhibits significantly in MI patients combined treatment of whom included STLT (streptokinase in a dose 1500,000 U within 6 hours after acute MI onset and trimetasidine in a dose 70 mg/day on postmyocardial infarction day 7-10). Topics: Adrenergic beta-Antagonists; Adult; Aged; Angiotensin-Converting Enzyme Inhibitors; Bisoprolol; Drug Therapy, Combination; Enalapril; Female; Fibrinolytic Agents; Follow-Up Studies; Humans; Magnetic Resonance Imaging; Male; Middle Aged; Myocardial Infarction; Prospective Studies; Streptokinase; Treatment Outcome; Ventricular Remodeling | 2006 |
Comparison of the effect of enalapril and losartan in conjunction with surgical coronary revascularisation versus revascularisation alone on systemic endothelial function.
To investigate the effect of enalapril, losartan, and surgical coronary revascularisation on endothelial function, and the role of the angiotensin converting enzyme (ACE) insertion (I)/deletion (D) polymorphism.. Randomised, controlled, blinded end point study.. University tertiary referral cardiac centre.. 49 men awaiting coronary artery bypass grafting (CABG) were randomly assigned to treatment with losartan, enalapril, or control for two months before and three months after surgery.. Endothelial function was blindly analysed by brachial artery flow mediated dilatation (FMD) and ACE I/D genotype was determined.. FMD was impaired at baseline (1.0-1.7%) and after five months had improved to 5.2% with enalapril (p = 0.015), 5.0% with losartan (p = 0.0004), and 3.0% with CABG alone (p = 0.05). Patients with the II genotype had lower baseline FMD than those with DI or DD (0.1% v 1.7%, p = 0.038) and after enalapril or losartan treatment had greater improvement in FMD (mean (SEM) 7.1 (1.1)%) than patients with DI (3.1 (1.3)%, p = 0.024) or DD genotype (3.1 (1.1)%, p = 0.02).. Enalapril and losartan, with surgical coronary revascularisation, significantly improve systemic endothelial function. Revascularisation alone produces a quantitatively smaller, but still significant, improvement. The ACE genotype significantly modulates this response. Patients with the II genotype have a more pronounced impairment in endothelial function at baseline and a greater improvement in response to treatment with these agents. Topics: Angiotensin II Type 1 Receptor Blockers; Angiotensin-Converting Enzyme Inhibitors; Coronary Artery Disease; Double-Blind Method; Enalapril; Endothelium, Vascular; Genotype; Humans; Losartan; Male; Middle Aged; Mutation; Myocardial Infarction; Myocardial Revascularization; Risk Assessment; Risk Factors | 2005 |
Enalapril suppresses ventricular remodeling more effectively than losartan in patients with acute myocardial infarction.
Ventricular remodeling after acute myocardial infarction (AMI) is associated with increased morbidity and mortality. ELITE II study showed that losartan, an angiotensin receptor blocker, shows a survival benefit to the same degree as captopril, an angiotensin-converting enzyme inhibitor, does in patients with heart failure. However, recent OPTIMAAL study showed that clinical outcomes after losartan are not superior to those after captopril in patients with AMI. We examined the effect of losartan on ventricular remodeling after AMI comparatively with that of enalapril.. We enrolled 203 consecutive patients with AMI (mean age 62 +/- 11 years). All patients underwent primary percutaneous coronary intervention and were randomly assigned to losartan (25-50 mg, n = 101) or enalapril (2.5-10 mg, n = 102) treatment. Biplane left ventriculography was performed just after primary percutaneous transluminal coronary angioplasty (acute phase) and 6 months after the onset of AMI.. Any of the maximal creatine kinase level, left ventricular end-diastolic volume index, end-systolic volume index, and ejection fraction measured at acute phase was not different between losartan and enalapril groups. However, changes in left ventricular end-diastolic index (18 +/- 25 vs 8 +/- 24 mL/m2) and left ventricular end-systolic volume index (10 +/- 20 vs 2 +/- 18 mL/m2) from acute phase to 6 months were significantly greater in losartan than in enalapril group. Change in left ventricular ejection fraction (0.2% +/- 10.3% vs 3.4% +/- 11.6%) from acute phase to 6 months was significantly smaller in losartan than in enalapril group. The plasma level of brain natriuretic peptide at 6 months was significantly higher in losartan than in enalapril group (all P < .05).. These indicate that enalapril suppresses ventricular remodeling after AMI more effectively than losartan. Topics: Angioplasty, Balloon, Coronary; Angiotensin-Converting Enzyme Inhibitors; Enalapril; Female; Humans; Losartan; Male; Middle Aged; Myocardial Infarction; Ventricular Function, Left; Ventricular Remodeling | 2005 |
Questioning a class effect: does ACE inhibitor tissue penetration influence the degree of fibrinolytic balance alteration following an acute myocardial infarction?
There is a common belief in a class effect among angiotensin-converting enzyme (ACE) inhibitors. This is unsubstantiated for acute myocardial infarction (AMI). Because vascular tissue is a source of the endogenous fibrinolytic markers, and ACE inhibition in vascular tissue favorably influences the fibrinolytic system, the authors hypothesized that a high-tissue-penetrating ACE inhibitor would provide a more favorable reduction in plasminogen activator inhibitor-1 (PAI-1) and an increase in tissue plasminogen activator (t-PA) after AMI compared to a low-tissue-penetrating ACE inhibitor. In a randomized open-label trial, patients received the high-tissue-penetrating quinapril (n = 15) or low-tissue-penetrating enalapril (n = 15) immediately following an AMI. PAI-1 and t-PA antigen (ng/mL) were measured at baseline and through 14 days of treatment. There was no difference in baseline PAI-1 or t-PA antigen between treatments. PAI-1 antigen trended toward being lower with quinapril versus enalapril on day 1 (24.44 +/- 14.96 vs. 36.94 +/- 19.49, respectively, p = 0.059) and was significantly lower on day 3 (17.32 +/- 9.57 vs. 27.49 +/- 9.61, respectively, p = 0.009). Analysis of PAI-1 antigen over time by two-factor ANOVA with replication found significantly lower concentrations of PAI-1 antigen over the entire treatment period with quinapril versus enalapril (p < 0.003). This investigation of ACE inhibitor tissue-penetrating influence on markers of reinfarction risk suggests there may be a greater early reduction in PAI-1 with a more highly tissue-penetrating ACE inhibitor. Topics: Analysis of Variance; Angiotensin-Converting Enzyme Inhibitors; Enalapril; Female; Humans; Male; Middle Aged; Myocardial Infarction; Permeability; Plasminogen Activator Inhibitor 1; Quinapril; Tetrahydroisoquinolines; Tissue Plasminogen Activator | 2004 |
Effects of immediate versus delayed antihypertensive therapy on outcome in the Systolic Hypertension in Europe Trial.
To assess the impact of immediate versus delayed antihypertensive treatment on the outcome of older patients with isolated systolic hypertension, we extended the double-blind placebo-controlled Systolic Hypertension in Europe (Syst-Eur) trial by an open-label follow-up study lasting 4 years.. The Syst-Eur trial included 4695 randomized patients with minimum age of 60 years and an untreated blood pressure of 160-219 mmHg systolic and below 95 mmHg diastolic. The double-blind trial ended after a median follow-up of 2.0 years (range 1-97 months). Of 4409 patients still alive, 3517 received open-label treatment consisting of nitrendipine (10-40 mg daily) with the possible addition of enalapril (5-20 mg daily), hydrochlorothiazide (12.5-25 mg daily), or both add-on drugs. Non-participants (n = 892) were also followed up.. Median follow-up increased to 6.1 years. Systolic pressure decreased to below 150 mmHg (target level) in 2628 participants (75.0%). During the 4-year open-label follow-up, stroke and cardiovascular complications occurred at similar frequencies in patients formerly randomized to placebo and those continuing active treatment. These rates were similar to those previously observed in the active-treatment group during the double-blind trial. Considering the total follow-up of 4695 randomized patients, immediate compared with delayed antihypertensive treatment reduced the occurrence of stroke and cardiovascular complications by 28% (P = 0.01) and 15% (P = 0.03), respectively, with a similar tendency for total mortality (13%, P = 0.09). In 492 diabetic patients, the corresponding estimates of long-term benefit (P < 0.02) were 60, 51 and 38%, respectively.. Antihypertensive treatment can achieve blood pressure control in most older patients with isolated systolic hypertension. Immediate compared with delayed treatment prevented 17 strokes or 25 major cardiovascular events per 1000 patients followed up for 6 years. These findings underscore the necessity of early treatment of isolated systolic hypertension. Topics: Aged; Antihypertensive Agents; Blood Pressure; Calcium Channel Blockers; Diabetes Mellitus; Dihydropyridines; Double-Blind Method; Drug Administration Schedule; Drug Therapy, Combination; Enalapril; Europe; Female; Follow-Up Studies; Heart Failure; Humans; Hydrochlorothiazide; Hypertension; Incidence; Linear Models; Male; Myocardial Infarction; Nitrendipine; Stroke; Survival Rate; Time Factors; Treatment Outcome | 2004 |
Exploring the effects of ACE inhibitor tissue penetration on vascular inflammation following acute myocardial infarction.
Questions remain as to the existence of a class effect amongst angiotensin converting enzyme (ACE) inhibitors, and some literature suggests that pharmacological effects and outcomes may be determined by an ACE inhibitor's propensity to penetrate and inhibit the ACE enzyme at the vascular tissue level. Because vascular inflammation contributes to adverse outcomes following acute myocardial infarction (AMI), and angiotensin II influences inflammation at the vascular level, we hypothesized that high-tissue penetrating ACE inhibitors would provide more favorable effects on C-reactive protein (CRP) after AMI compared to low-tissue penetrating ACE inhibitors.. In a randomized open-label trial, patients received the high-tissue penetrating quinapril (n = 15) or low-tissue penetrating enalapril (n = 15) following AMI. C-reactive protein was measured at baseline and periodically over 14 days following drug initiation. All baseline characteristics and blood pressure response to treatment between groups were equivalent. Prior to initiating study medication, CRP concentrations (mg/g) were similar between enalapril and quinapril (0.327 +/- 0.571 versus 0.273 +/- 0.380, respectively, p = 0.77). The percent magnitude of change in CRP concentrations favored quinapril at all time points, starting 12 h after treatment initiation. When characterizing CRP production during treatments, the time courses were significantly different and demonstrated lower CRP concentrations with quinapril (p = 0.0107).. Overall, this investigation into the importance of ACE inhibitor tissue penetration on a common marker of vascular inflammation, suggests a potential vascular anti-inflammatory benefit with a more highly tissue penetrating ACE inhibitor following AMI. Further investigation into the true pharmacological similarities and differences amongst this class of drugs is warranted. Topics: Adult; Angiotensin-Converting Enzyme Inhibitors; C-Reactive Protein; Chi-Square Distribution; Coronary Vessels; Enalapril; Female; Humans; Inflammation; Male; Middle Aged; Myocardial Infarction; Quinapril; Tetrahydroisoquinolines | 2004 |
Comparison of effects of quinapril versus enalapril on vasoactive substances following acute myocardial infarction.
The true existence of a class effect in angiotensin-converting enzyme (ACE) inhibitors remains controversial. The present trial explored the effects of 2 ACE inhibitors after acute myocardial infarction and found no difference in endothelin-1 production but a greater increase in the production of total nitric oxide with quinapril than with enalapril. Topics: Angiotensin-Converting Enzyme Inhibitors; Blood Vessels; Enalapril; Endothelin-1; Humans; Middle Aged; Myocardial Infarction; Nitric Oxide; Quinapril; Tetrahydroisoquinolines | 2004 |
Treatment of acute coronary syndromes in patients with type 2 diabetes mellitus with beta-adrenoblockers and angiotensin-converting enzyme inhibitors: cardiohemodynamic effects and impact for prognosis.
Long-term oral treatment of patients with acute coronary syndromes and type 2 diabetes mellitus with beta-adrenoblockers and angiotensin-converting enzyme inhibitors is associated with positive, though ambiguous changes in the left-ventricular structure and function. These changes should be the reason for choosing optimal therapy ensuring better prognosis in this patient population. Topics: Adrenergic beta-Antagonists; Adult; Aged; Angina, Unstable; Angiotensin-Converting Enzyme Inhibitors; Bisoprolol; Diabetes Mellitus, Type 2; Drug Therapy, Combination; Enalapril; Female; Heart; Hemodynamics; Humans; Male; Middle Aged; Myocardial Infarction; Prognosis | 2004 |
Intensive blood pressure control reduces the risk of cardiovascular events in patients with peripheral arterial disease and type 2 diabetes.
Peripheral arterial disease (PAD) and diabetes are both associated with a high risk of ischemic events, but the role of intensive blood pressure control in PAD has not been established.. The Appropriate Blood Pressure Control in Diabetes study followed 950 subjects with type 2 diabetes for 5 years; 480 of the subjects were normotensive (baseline diastolic blood pressure of 80 to 89 mm Hg). Patients randomized to placebo (moderate blood pressure control) had a mean blood pressure of 137+/-0.7/81+/-0.3 mm Hg over the last 4 years of treatment. In contrast, patients randomized to intensive treatment with enalapril or nisoldipine had a mean 4-year blood pressure of 128+/-0.8/75+/-0.3 mm Hg (P<0.0001 compared with moderate control). PAD, which is defined as an ankle-brachial index <0.90 at the baseline visit, was diagnosed in 53 patients. In patients with PAD, there were 3 cardiovascular events (13.6%) on intensive treatment compared with 12 events (38.7%) on moderate treatment (P=0.046). After adjustment for multiple cardiovascular risk factors, an inverse relationship between ankle-brachial index and cardiovascular events was observed with moderate treatment (P=0.009), but not with intensive treatment (P=0.91). Thus, with intensive blood pressure control, the risk of an event was not increased, even at the lowest ankle-brachial index values, and was the same as in a patient without PAD.. In PAD patients with diabetes, intensive blood pressure lowering to a mean of 128/75 mm Hg resulted in a marked reduction in cardiovascular events. Topics: Antihypertensive Agents; Blood Pressure; Cardiovascular Diseases; Cohort Studies; Comorbidity; Death, Sudden, Cardiac; Diabetes Mellitus, Type 2; Enalapril; Female; Follow-Up Studies; Humans; Hypertension; Male; Middle Aged; Myocardial Infarction; Nisoldipine; Odds Ratio; Peripheral Vascular Diseases; Risk Assessment; Stroke; Treatment Outcome | 2003 |
Prospective evaluation comparing the effects of enalapril and losartan in left ventricular remodeling after acute myocardial infarction.
Previous studies have compared angiotensin receptor blockers and angiotensin-converting enzyme inhibitors in patients with heart failure, but there are few data about the effect of these drugs regarding left ventricular remodeling after myocardial infarction.. Fifty-two consecutive patients with first anterior wall myocardial infarction within 24 hours of evolution were randomized to receive enalapril (as much as 20 mg; mean, 14.6 mg), or losartan (as much as 50 mg; mean, 48 mg). Left ventricular ejection fraction and ventricular volumes were analyzed in 2 serial radionuclide ventriculograpies, carried out within 4 days after the infarction (mean, 97.4 +/- 114.2 hours) and after 6 months (mean, 177.7 +/- 16.7 days). Ventriculographies were analyzed by a single blinded observer. Mainly because of the unexpected large SD values obtained, the power of the study to demonstrate equivalence between the groups was only 15.7%.. The differences obtained between the first and the second ventriculographies, for the enalapril and losartan groups, were: for left ventricular ejection fraction, -0.4% +/- 6.6% versus -1.1% +/- 5.9% (P =. 67; 95% CI, 2.77-4.23); for final systolic volume, 0.07 +/- 7.7 mL/m(2) versus -0.2 +/- 6.1mL/m(2) (P =. 85; 95% CI, -3.57-4.26); for final diastolic volume -0.7 +/- 12.1 mL/m(2) versus -3.6 - 9.9 mL/m(2) (P =. 34; 95% CI, -3.22-9.17).. This study, although underpowered, suggests that neither enalapril nor losartan was superior as compared with each other for left ventricular remodeling after myocardial infarction; however, powerful evidence of equivalence was not provided. Topics: Angiotensin Receptor Antagonists; Angiotensin-Converting Enzyme Inhibitors; Captopril; Enalapril; Female; Humans; Losartan; Male; Middle Aged; Myocardial Infarction; Radionuclide Ventriculography; Stroke Volume; Ventricular Function, Left; Ventricular Remodeling | 2003 |
Improved fibrinolysis after one year of treatment with enalapril in men and women with uncomplicated myocardial infarction.
To study long-term effects of enalapril on mass concentrations of tissue plasminogen activator (tPA), plasminogen activator inhibitor (PAI-1), tPA/PAI-1-complex and von Willebrand factor (vWF) in both genders with uncomplicated myocardial infarction.. More than three months after an uncomplicated myocardial infarction 82 survivors (46 males, 36 females) were randomised to enalapril/placebo. PAI-1, tPA, tPA/PAI-1-complex and vWF were measured after two weeks, six and 12 months following randomisation. PAI-1 decreased significantly in both genders in the enalapril-treated group after two weeks, with a maximum decrease at six months (mean reduction: 31% equal to 9.8 microg x L(-1), CI: 5.2 to 14.5 microg x L(-1), p = 0.0001) and remained significantly lower at 12 months. Mass concentration of tPA decreased significantly (mean reduction: 1.81 microg x L(-1), CI: 0.903 to 2.708 microg x L(-1), p < 0.001) after two weeks treatment in both genders but returned to baseline values at 12 months. The tPA/PAI-1-complex decreased and was significantly lower (mean reduction 0.96 microg x L(-1), CI: 0.36 to 1.56 microg x L(-1), p = 0.003) in the enalapril group after two weeks and six months (p = 0.037). No decrease of vWF was seen in the enalapril group.. Enalapril treatment up to one year depressed mass concentrations of PAI-1 and transiently tPA and tPA/PAI-1 complex indicating an improvement of the fibrinolytic balance in both genders with uncomplicated myocardial infarction. Topics: Aged; Angiotensin-Converting Enzyme Inhibitors; Biomarkers; Double-Blind Method; Enalapril; Female; Fibrinolysis; Follow-Up Studies; Humans; Macromolecular Substances; Male; Middle Aged; Myocardial Infarction; Plasminogen Activator Inhibitor 1; Risk Factors; Sex Factors; Tissue Plasminogen Activator; von Willebrand Factor | 2002 |
Comparison of effects of losartan versus enalapril on fibrinolysis and coagulation in patients with acute myocardial infarction.
Topics: Aged; Aged, 80 and over; Angioplasty, Balloon, Coronary; Blood Coagulation Factors; Double-Blind Method; Enalapril; Female; Fibrinolysis; Humans; Losartan; Male; Middle Aged; Myocardial Infarction; Plasminogen Inactivators; Thrombolytic Therapy; Thromboplastin; Tissue Plasminogen Activator | 2001 |
Tolerance to ACE inhibitors after cardiac surgery.
Several studies have shown angiotensin-converting enzyme (ACE) inhibitors to confer significant mortality and morbidity benefits in heart failure. First-dose hypotension may necessitate interruption of such therapy. This is more likely to occur if the ACE inhibitor is administered early after coronary artery bypass grafting (CABG). The purpose of this study was to analyse the haemodynamic tolerance to early post-operative treatment with perindopril and enalapril in patients with impaired renal and ventricular function.. Eighty one consecutive CABG patients with a previous myocardial infarction, impaired pre-operative left ventricular ejection fraction (LVEF) on ventriculography and moderately impaired renal function (serum creatinine of 115-150 micromol/l) were randomised into three groups to receive oral placebo, perindopril (4 mg) or enalapril (5 mg) once daily. Groups were subdivided into those with mild ventricular dysfunction (LVEF = 35-65%, n = 20) and significant ventricular dysfunction (LVEF < 35%, n = 7). Exclusion criteria included oliguria (<0.5 ml/kg per h) or inotrope dependance at the point of entry on the first post-operative day. Intolerance to ACE inhibitor was defined as hypotension (<95 mmHg systolic blood pressure or a decrease exceeding 25 mmHg in systolic blood pressure) leading to oliguria (<0.5 ml/kg per h) which was unresponsive to intravenous furosemide (20 mg). In such cases ACE inhibitor treatment was discontinued and patients commenced on dopamine.. In the groups with mild ventricular dysfunction (LVEF = 35-65%) perindopril was discontinued in 1/20 and enalapril in 4/20 patients (P = n.s). However, in the groups with significant ventricular dysfunction (LVEF < 35%) perindopril was discontinued in 2/7 and enalapril in 7/7 patients (P = 0.02).. Our results suggest that after CABG, patients with moderately impaired renal function and significant ventricular dysfunction do not tolerate ACE inhibitors well when these were commenced on the first post-operative day. However, perindopril was associated with less haemodynamic deterioration than enalapril and consequently may be advantageous in this setting. rights reserved. Topics: Administration, Oral; Angiotensin-Converting Enzyme Inhibitors; Coronary Artery Bypass; Drug Hypersensitivity; Enalapril; Feasibility Studies; Follow-Up Studies; Heart Failure; Hemodynamics; Humans; Indoles; Length of Stay; Middle Aged; Myocardial Infarction; Perindopril; Prognosis; Renal Insufficiency | 1999 |
Angiotensin-converting enzyme inhibition reduces monocyte chemoattractant protein-1 and tissue factor levels in patients with myocardial infarction.
We investigated the effects of enalapril therapy on plasma tissue factor (TF), tissue factor pathway inhibitor (TFPI) and monocyte chemoattractant protein-1 (MCP-1) levels in patients with acute myocardial infarction.. Macrophages express TF in human coronary atherosclerotic plaques. Both TF and TFPI are major regulators of coagulation and thrombosis. Monocyte chemoattractant protein-1 is a monocyte and macrophage chemotactic and activating factor.. In a randomized, double-blind, placebo-controlled study beginning about two weeks after myocardial infarction, 16 patients received four weeks of placebo (placebo group) and another 16 patients received four weeks of enalapril 5 mg daily therapy (enalapril group). We performed blood sampling after administration of the doses.. There were no significant differences in the serum angiotensin-converting enzyme (ACE) activity, plasma TF, free TFPI or MCP-1 levels before administration between the enalapril and placebo groups. In the enalapril group, ACE activity (IU/liter) (14.0 before, 5.2 on day 3, 5.8 on day 7, 6.3 on day 28), TF levels (pg/ml) (223, 203, 182, 178) and MCP-1 levels (pg/ml) (919, 789, 790, 803) significantly decreased by day 28. However, the free TFPI levels (ng/ml) (28.2, 26.5, 26.8, 28.4) did not change. These four variables were unchanged during the study period in the placebo group.. This study demonstrated that administration of enalapril reduces the increased procoagulant activity in patients with myocardial infarction associated with inhibition of the activation and accumulation of macrophages and monocytes. Topics: Aged; Aged, 80 and over; Angiotensin-Converting Enzyme Inhibitors; Anticoagulants; Chemokine CCL2; Double-Blind Method; Enalapril; Enzyme-Linked Immunosorbent Assay; Female; Humans; Lipoproteins; Macrophages; Male; Middle Aged; Monocytes; Myocardial Infarction; Thromboplastin | 1999 |
Beneficial effects of long-term treatment with enalapril on cardiac function and heart rate variability in patients with old myocardial infarction.
The beneficial effects of the early use of angiotensin-converting enzyme inhibitors (ACEis) in patients with acute myocardial infarction (MI) are well documented. However, the effects of ACEis in patients with an old MI and preserved cardiac function have not yet been studied. We examined the effects of 12 months of enalapril treatment in patients with previous MI.. Thirteen patients with an old MI and no overt congestive heart failure (CHF), aged 70 +/- 2 years, were treated with enalapril for 12 months. We also included 13 age- and sex-matched control patients who had a similar clinical background but were not treated with enalapril. Holter electrocardiography and echocardiography were performed at entry and after 12 months of treatment. Heart rate variability, low- and high-frequency powers (LF and HF), and the ratio between LF and HF (LF/HF) were analyzed. Changes from baseline to 12 months in HF, LF/HF, left ventricular end-diastolic dimension (LVEDD), and end-systolic dimension (LVESD) were significantly different in the enalapril group (HF, 8.1 +/- 0.9 to 9.3 +/- 0.9 milliseconds: LF/HF, 1.65 +/- 0.11 to 1.53 +/- 0.16; LVEDD, 57.2 +/- 1.6 to 54.7 +/- 1.6 mm; LVESD, 40.0 +/- 2.4 to 36.3 +/- 1.9 mm) compared with the control group (HF, 8.9 +/- 0.9 to 8.5 +/- 0.7 milliseconds; LF/HF, 1.78 +/- 0.18 to 1.88 +/- 0.15; LVEDD, 52.3 +/- 2.5 to 55.9 +/- 2.2 mm; LVESD, 32.5 +/- 2.6 to 36.1 +/- 2.6 mm; P < .05). The delta change (delta) in LVESD between the end and the start of study correlated inversely with deltaHF (r = -0.56; P < .05) and positively with deltaLF/HF (r = 0.65; P < .01).. Our results suggest possible ongoing structural changes in patients with old MI even in the absence of overt CHF. Enalapril seemed to prevent such changes and to restore cardiac autonomic tone toward normal. Further prospective studies using a larger sample size are warranted to confirm potential beneficial effects of ACEis in patients with previous MI and preserved left ventricular function. Topics: Aged; Angiotensin-Converting Enzyme Inhibitors; Chi-Square Distribution; Drug Administration Schedule; Electrocardiography; Electrocardiography, Ambulatory; Enalapril; Female; Follow-Up Studies; Heart Rate; Hemodynamics; Humans; Japan; Linear Models; Long-Term Care; Male; Myocardial Infarction; Reference Values; Statistics, Nonparametric; Treatment Outcome; Ventricular Function, Left | 1999 |
The effect of nisoldipine as compared with enalapril on cardiovascular outcomes in patients with non-insulin-dependent diabetes and hypertension.
It has recently been reported that the use of calcium-channel blockers for hypertension may be associated with an increased risk of cardiovascular complications. Because this issue remains controversial, we studied the incidence of such complications in patients with non-insulin-dependent diabetes mellitus and hypertension who were randomly assigned to treatment with either the calcium-channel blocker nisoldipine or the angiotensin-converting-enzyme inhibitor enalapril as part of a larger study.. The Appropriate Blood Pressure Control in Diabetes (ABCD) Trial is a prospective, randomized, blinded trial comparing the effects of moderate control of blood pressure (target diastolic pressure, 80 to 89 mm Hg) with those of intensive control of blood pressure (diastolic pressure, 75 mm Hg) on the incidence and progression of complications of diabetes. The study also compared nisoldipine with enalapril as a first-line antihypertensive agent in terms of the prevention and progression of complications of diabetes. In the current study, we analyzed data on a secondary end point (the incidence of myocardial infarction) in the subgroup of patients in the ABCD Trial who had hypertension.. Analysis of the 470 patients in the trial who had hypertension (base-line diastolic blood pressure, > or = 90 mm Hg) showed similar control of blood pressure, blood glucose and lipid concentrations, and smoking behavior in the nisoldipine group (237 patients) and the enalapril group (233 patients) throughout five years of follow-up. Using a multiple logistic-regression model with adjustment for cardiac risk factors, we found that nisoldipine was associated with a higher incidence of fatal and nonfatal myocardial infarctions (a total of 24) than enalapril (total, 4) (risk ratio, 9.5; 95 percent confidence interval, 2.7 to 33.8).. In this population of patients with diabetes and hypertension, we found a significantly higher incidence of fatal and nonfatal myocardial infarction among those assigned to therapy with the calcium-channel blocker nisoldipine than among those assigned to receive enalapril. Since our findings are based on a secondary end point, they will require confirmation. Topics: Adult; Aged; Angiotensin-Converting Enzyme Inhibitors; Calcium Channel Blockers; Cardiovascular Diseases; Diabetes Mellitus, Type 2; Double-Blind Method; Enalapril; Female; Humans; Hypertension; Logistic Models; Male; Middle Aged; Myocardial Infarction; Nisoldipine; Prospective Studies; Treatment Outcome | 1998 |
Long-term effects on cardiac output and peripheral resistance in patients treated with enalapril after acute myocardial infarction. CONSENSUS II Multi-Echo Study Group. Cooperative New Scandinavian Enalapril Survival Study.
In the Cooperative New Scandinavian Enalapril Survival Study (CONSENSUS II), in which enalapril treatment was initiated intravenously within 24 h after acute myocardial infarction, there was a neutral effect on 6-month mortality, whereas a beneficial effect on the progression of congestive heart failure was noted. We studied the effect of enalapril on left ventricular systolic function in terms of cardiac output and mean acceleration time measured by pulsed-wave Doppler in the left ventricular outflow tract and peripheral resistance. Early angiotensin-converting enzyme inhibition after acute myocardial infarction did not result in a general improvement of cardiac output. However, a small increase in cardiac output was observed in a subgroup of enalapril-treated patients with ejection fraction > or = 45%, probably due to a reduction in peripheral resistance in these patients. Topics: Aged; Angiotensin-Converting Enzyme Inhibitors; Blood Pressure; Cardiac Output; Chi-Square Distribution; Clinical Trials, Phase II as Topic; Echocardiography, Doppler, Pulsed; Enalapril; Female; Heart Rate; Humans; Male; Middle Aged; Myocardial Infarction; Prospective Studies; Scandinavian and Nordic Countries; Statistics, Nonparametric; Vascular Resistance; Ventricular Dysfunction, Left | 1998 |
Antihypertensive therapy in type 2 diabetes: implications of the appropriate blood pressure control in diabetes (ABCD) trial.
As the population ages, the incidence of type 2 diabetes will increase as will the incidence of concomitant vascular complications. Hypertension substantially increases the risk of cardiovascular disease in patients with diabetes. Results from the recent Appropriate Blood Pressure Control in Diabetes (ABCD) trial demonstrated an advantage of an angiotensin-converting enzyme (ACE) inhibitor (enalapril) over a long-acting calcium antagonist (nisoldipine) with regard to the incidence of cardiovascular events over a 5-year follow-up period in hypertensive persons with type 2 diabetes. This trial was a prospective, randomized, blinded study comparing the effects of moderate blood pressure control (target diastolic pressure 80-89 mm Hg) with those of intensive control (target diastolic pressure 75 mm Hg) on the incidence and progression of diabetic vascular complications. The study also compared nisoldipine with enalapril as first-line antihypertensive therapy in terms of prevention and progression of complications of diabetes. In 470 hypertensive patients, the incidence of fatal and nonfatal myocardial infarctions was significantly (p = 0.001) higher among those receiving nisoldipine (n = 25) compared with those receiving enalapril (n = 5). Comparison with previous studies suggests that the difference observed between nisoldipine and enalapril resulted from a beneficial effect of enalapril rather than a deleterious effect from nisoldipine. Since these findings in the ABCD trial are based on a secondary endpoint, they require confirmation. Nevertheless, they suggest that ACE inhibitors should be the initial antihypertensive medication used in patients with type 2 diabetes and hypertension. Topics: Aged; Angiotensin-Converting Enzyme Inhibitors; Antihypertensive Agents; Blood Pressure; Calcium Channel Blockers; Diabetes Mellitus, Type 2; Enalapril; Female; Humans; Hypertension; Incidence; Male; Middle Aged; Myocardial Infarction; Nisoldipine; Prospective Studies; Single-Blind Method; Treatment Outcome | 1998 |
Long-term effects of the angiotensin-converting enzyme inhibitor enalapril on chronic heart failure. Examination by 123I-MIBG imaging.
To examine the long-term effects of the angiotensin-converting enzyme (ACE) inhibitor enalapril on chronic heart failure, 10 patients (7 men and 3 women, mean age: 62 +/- 11 years) with chronic stable heart failure, classified as New York Heart Association (NYHA) functional class 2-3 for more than 3 months, and a left ventricular ejection fraction less than 45% were treated with 2.5-5.0 mg of enalapril once a day for 3-15 months (mean 7 months). The causes of heart failure were old myocardial infarction (n = 7), hypertension (n = 2), and atrial fibrillation (n = 1). Radioiodinated metaiodobenzyl guanidine (123I-MIBG) imaging, radionuclide angiography, and treadmill exercise test were performed before and after the treatment. With enalapril treatment, (1) left ventricular ejection fraction (LVEF) increased significantly from 38.3 +/- 6.9% to 47.5 +/- 14.7%; (2) sub-maximal exercise time increased significantly from 205 +/- 112 to 272 +/- 120 seconds; (3) the heart to mediastinum (H/M) ratio of 123I-MIBG increased significantly (early image: 1.99 +/- 0.38 versus 2.20 +/- 0.50; delayed image: 1.86 +/- 0.44 versus 2.09 +/- 0.51); and (4) the washout rate of 123I-MIBG decreased slightly from 29.1 +/- 9.1% to 25.4 +/- 7.0%. The improvement rate of LVEF was significantly correlated with the improvement rates of the H/M ratio and washout rate after treatment with enalapril. Thus, the long-term effects of enalapril can be observed in the cardiac sympathetic nervous system, and 123I-MIBG imaging appears to be useful for evaluating the therapeutic effects of enalapril on the cardiac sympathetic nervous system in patients with chronic heart failure. Topics: 3-Iodobenzylguanidine; Aged; Angiotensin-Converting Enzyme Inhibitors; Antihypertensive Agents; Atrial Fibrillation; Chronic Disease; Enalapril; Female; Heart Failure; Humans; Hypertension; Iodine Radioisotopes; Male; Middle Aged; Myocardial Infarction; Radionuclide Imaging; Radiopharmaceuticals; Stroke Volume; Ventricular Function, Left | 1998 |
Effects of nisoldipine and/or enalapril on left ventricular function and exercise capacity in patients with recent anterior myocardial infarction and mild cardiac dysfunction.
Treatment of abnormal remodeling and dysfunction of left ventricle after myocardial infarction is one of the major goals of recent therapeutic interventions. The current study, the Nisoldipine Enalapril Anterior Myocardial infarction Study pilot investigation, was designed to investigate the effects of 12 weeks of treatment with enalapril or nisoldipine or their combination on left ventricular (LV) function and exercise capacity in patients with recent (< 1 month) anterior myocardial infarction and mild LV dysfunction (LV ejection fraction [EF] 38% to 48%). Forty-six patients were studied and received, by random assignment, enalapril (5 mg once per day) plus placebo (n = 14) or nisoldipine (10 mg two times per day) plus placebo (n = 18) or enalapril (5 mg once per day) plus nisoldipine (10 mg two times per day) (n = 14). All patients received aspirin (325 mg) throughout the study. Data on LV EF and peak filling rate at rest and LV EF during exercise were collected during radionuclide ventriculography. In addition, the product of heart rate and systolic blood pressure (rate-pressure product) and exercise time were determined during exercise stress testing. The analyzed parameters were not significantly modified after treatment with enalapril or with nisoldipine. In contrast, the combination of enalapril and nisoldipine significantly raised LV EF at rest (from 43% +/- 3% to 48% +/- 6%, p < 0.01) and during exercise (from 45% +/- 8% to 50% +/- 9%, p < 0.01) and raised peak filling rate at rest (fraction of end-diastolic volume per second) from 1.57 +/- 0.3 to 1.67 +/- 0.3 (p < 0.05). In addition, the combined administration of the two drugs increased the rate-pressure product (values x 10(3)) (from 20.7 +/- 5 to 22.7 +/- 4, p < 0.05) and increased exercise time (from 573 +/- 173 seconds to 668 +/- 178 seconds, p < 0.05). These results show that in patients with recent anterior myocardial infarction and mild LV dysfunction, the combination of the angiotensin-converting enzyme inhibitor enalapril and the dihydropyridine nisoldipine improves resting LV systolic and diastolic function and exercise LV systolic function and exercise capacity. Topics: Adult; Angiotensin-Converting Enzyme Inhibitors; Calcium Channel Blockers; Drug Therapy, Combination; Enalapril; Exercise Test; Female; Heart Ventricles; Humans; Male; Middle Aged; Myocardial Infarction; Nisoldipine; Radionuclide Imaging; Technetium Compounds; Treatment Outcome; Ventricular Dysfunction, Left; Ventricular Function, Left | 1997 |
Association of calcium channel blocker use with increased rate of acute myocardial infarction in patients with left ventricular dysfunction.
The Studies of Left Ventricular Dysfunction (SOLVD) assessed the effect of enalapril in patients with systolic left ventricular dysfunction (LVD). We performed retrospective analyses of the association between calcium channel blocker (CCB) use and fatal and nonfatal myocardial infarction (MI) in these patients. MI occurred in 11.5% of 845 patients receiving CCBs versus 7.5% of 2551 patients not receiving CCBs in the enalapril group and in 14.4% of 874 patients receiving CCBs versus 9.3% of 2527 patients not receiving CCBs in the placebo group. By multivariate Cox regression analysis, adjusting for comorbidity, cause and severity of LVD, heart failure, and concomitant drug use, CCB use was an independent predictor of MI (relative risk [RR] 1.37, confidence interval [CI] 1.14 to 1.63). The increase in MI risk was greater among patients with a higher heart rate (RR 1.46, CI 1.14 to 1.86) and lower blood pressure (RR 1.45, CI 1.14 to 1.86). The adjusted risk ratio for all-cause mortality associated with CCB use was 1.14 (CI 1.00 to 1.28; p = 0.0454). In this analysis of patients with LVD, CCB use was associated with significantly increased risk of fatal or nonfatal MI. Topics: Angiotensin-Converting Enzyme Inhibitors; Blood Pressure; Calcium Channel Blockers; Comorbidity; Enalapril; Female; Heart Rate; Humans; Incidence; Male; Middle Aged; Myocardial Infarction; Proportional Hazards Models; Retrospective Studies; Risk Factors; Ventricular Dysfunction, Left | 1997 |
Effects of enalapril on left ventricular function and exercise performance after a first acute myocardial infarction. The EDEN Study Investigators.
To study the effects of early use of enalapril on left ventricular function and exercise capacity after a first acute myocardial infarction, 356 patients without overt signs of congestive heart failure were randomly allocated to receive placebo or enalapril between days 7 and 14 after a first myocardial infarction. The study was conducted double-blind in 40 hospitals throughout Spain.. At baseline and after 26 weeks of follow-up exercise stress tests, Doppler-echocardiograms and isotopic ventriculography were performed in study participants. At the end of follow-up, patients in the enalapril group had lower end-systolic volume compared to those in the placebo group (55 vs. 62 ml; P=0.05). No difference in exercise capacity was evident between both groups.. The present study shows that enalapril therapy administered between 7 and 14 days after a first acute myocardial infarction decreases end-systolic volume and may inhibit the remodeling process of the left ventricle. Topics: Adolescent; Adult; Aged; Angiotensin-Converting Enzyme Inhibitors; Diastole; Double-Blind Method; Echocardiography, Doppler; Enalapril; Exercise; Exercise Tolerance; Female; Follow-Up Studies; Gated Blood-Pool Imaging; Humans; Male; Middle Aged; Myocardial Infarction; Retrospective Studies; Systole; Ventricular Function, Left | 1997 |
Interaction between enalapril and aspirin on mortality after acute myocardial infarction: subgroup analysis of the Cooperative New Scandinavian Enalapril Survival Study II (CONSENSUS II)
The use of angiotensin-converting enzyme (ACE) inhibitors early after an acute myocardial infarction to reduce mortality has been studied in several trials with inconsistent results. Aspirin (ASA) has become a well-documented therapeutic adjunct in patients with coronary heart disease. Attention has recently been focused on a possible interaction between ASA and ACE inhibitors. We therefore reanalyzed data from the Cooperative New Scandinavian Enalapril Survival Study II (CONSENSUS II) to find any evidence of differential effects of the ACE inhibitor enalapril in subgroups defined by use of ASA at baseline. Logistic regression tested the multiplicative interaction. We used Rothman synergy index S, which would be equal to unity under additivity, and less than unity when suggesting antagonism, to examine the postulated interaction with departure from an additive model. Logistic regression showed that the enalapril-ASA interaction term was a significant predictor of mortality at the end of the study (p = 0.047), and was a borderline significant predictor of mortality 30 days after randomization (p = 0.085). The Rothman synergy index S was 0.66 (95% confidence interval 0.46 to 0.94) for mortality at the end of the study, and 0.68 ( 0.44 to 1.04) for 30-day mortality, indicating antagonism between enalapril and ASA with departure from an additive model. Thus, we found evidence of enalapril-ASA interaction. The effect of enalapril was less favorable among patients taking ASA than among patients not taking ASA at baseline. Topics: Aged; Angiotensin-Converting Enzyme Inhibitors; Anti-Inflammatory Agents, Non-Steroidal; Aspirin; Cause of Death; Confidence Intervals; Double-Blind Method; Drug Interactions; Enalapril; Female; Follow-Up Studies; Forecasting; Heart Failure; Humans; Logistic Models; Male; Myocardial Infarction; Placebos; Recurrence; Retrospective Studies; Scandinavian and Nordic Countries; Survival Rate; Treatment Outcome | 1997 |
Beneficial effect of enalapril on left ventricular remodelling in patients with a severe residual stenosis after acute anterior wall infarction.
The present study was designed to evaluate the effects of early angiotensin converting enzyme (ACE) inhibition on left ventricular enlargement in patients with anterior wall infarction following reperfusion therapy.. Seventy-one consecutive patients with an anterior wall myocardial infarction were randomly allocated to enalapril (n = 36) or placebo (n = 35). All patients received either thrombolytic therapy (n = 46) or underwent primary coronary angioplasty (n = 25). Medication was started within 48 h admission to hospital and continued for 48 weeks. The process of left ventricular remodelling was assessed with two-dimensional echocardiography at 3 weeks and 1 year after the acute onset, and was related to the severity of the residual stenosis of the infarct-related artery.. Baseline left ventricular ejection fraction was 39.2% +/- 8.7%. During the study period left ventricular end-diastolic volume index increased from 48.2 +/- 9.9 ml.m-2 to 54.6 +/- 12.2 ml.m-2 at 3 weeks, and to 59.4 +/- 17.0 ml.m-2 after 1 year I control patients (P < 0.001). In the enalapril-treated patients, left ventricular end-diastolic volume index increased from 50.0 +/- 16.1 to 57.7 +/- 19.3 ml.m-2 at 3 weeks, and to 61.9 +/- 22.7 ml.m-2 after 1 year (P < 0.001). Both at 3 weeks and after 1 year, no overall differences in left ventricular volumes were observed between the enalapril and the placebo group (both ns). However, patients with a residual stenosis severity of > or = 70% in the infarct-related artery (n = 43) showed significant attenuation of remodelling by enalapril (n = 22) when compared to placebo (n = 21). In patients on enalapril, left ventricular end-diastolic volume index increased from 47.0 +/- 13.0 to 53.7 +/- 17.7 ml.m-2 compared to 48.0 +/- 9.6 to 60.3 +/- 16.3 ml.m-2 in control patients (P < 0.03). Also diastolic filling parameters were significantly improved in patients with > or = 70% residual stenosis.. In patients with an anterior wall infarction and a severe residual infarct-related coronary artery stenosis following reperfusion, treatment with enalapril prevents the process of left ventricular remodelling. As left ventricular dilatation is an early process we suggest that treatment with ACE inhibition should be started as soon as possible in this group of patients. Topics: Aged; Analysis of Variance; Angiotensin-Converting Enzyme Inhibitors; Blood Pressure; Coronary Disease; Double-Blind Method; Enalapril; Female; Heart Ventricles; Humans; Hypertrophy, Left Ventricular; Male; Middle Aged; Myocardial Infarction; Myocardial Reperfusion; Myocardium; Prospective Studies; Ventricular Function, Left | 1997 |
Secondary prevention of cardiac events following myocardial infarction: effects of atenolol and enalapril. Beijing Collaborative Study Group.
To investigate the actions of beta-blocker (atenolol) and ACE inhibitor (enalapril) for the secondary prevention of the main cardiac complications after acute myocardial infarction (AMI).. 1106 cases of AMI from 7 hospitals in the Beijing area were collected and were divided randomly into three groups: control (group C), atenolol (group A), and enalapril (group E). Drugs for investigation were administered 2-4 weeks after the onset of AMI, and the subjects were followed up for a median period of 19 months. All patients were given aspirin 50 mg/day. The end points of observation were cardiac events and non-cardiac events. Cardiac events included sudden cardiac death (SCD), heart failure death, total cardiac deaths, and myocardial re-infarction.. The clinical conditions of the three groups were compatible. Sixty-six cardiac events (6.0%) occurred. Comparing with group C, the rate of SCD decreased significantly by 68% in group A after atenolol treatment for 28 months. Both atenolol and enalapril significantly increased left ventricular ejection fraction (LVEF), whereas in group C the LVEF did not change during the follow-up period. There was obvious decreasing tendency of the survival curve in group C, compared with the other two groups. Totally drugs decrease one cardiac death 0/00/month. But the rate of myocardial re-infarction was the same in the three groups. No serious side effects on blood pressure or heart rate were observed.. Both atenolol and enalapril (domestic products) are beneficial to the secondary prevention of SCD and heart failure death after AMI, but not to re-infarction. Both drugs should be continued for a prolonged period to be effective. Drugs given 2-4 weeks after acute stage are also effective, with no serious side effects. Topics: Adrenergic beta-Antagonists; Aged; Angiotensin-Converting Enzyme Inhibitors; Atenolol; Cardiac Output, Low; Death, Sudden, Cardiac; Enalapril; Follow-Up Studies; Humans; Myocardial Infarction | 1997 |
Benefit of converting enzyme inhibition on left ventricular volumes and ejection fraction in patients receiving beta-blockade after myocardial infarction. CONSENSUS II multiecho study group.
Beta-blockers reduce infarct size and improve survival after acute myocardial infarction (MI). Post-MI angiotensin-converting enzyme inhibition also improves survival and may attenuate left ventricular (LV) dilatation. We evaluated the effect of early enalapril treatment on LV volumes and ejection fraction (EF) in patients on concomitant beta-blockade after MI. Intravenous enalaprilat or placebo was administered <24 hours after MI and was continued orally for 6 months. LV volumes were assessed by echocardiography 3 +/- 2 days, 1 and 6 months after MI. Change in LV diastolic volume during the first month was attenuated with enalapril (2.7 vs placebo 6.5 ml/m2 change; p < 0.05), and significantly lower LV diastolic and systolic volumes were observed with enalapril treatment compared with placebo at 1 month (enalapril 47.21 23.9 vs placebo 53.1/29.2 ml/m2; p < 0.05) and at 6 months (enalapril 47.9/24.8 vs placebo 53.8/29.6 ml/m2; p < 0.05). EF was also significantly higher 1 month after MI in these patients (enalapril 50.4% vs placebo 46.4%; p < 0.05). Our date demonstrate that early enalapril treatment attenuates LV volume expansion and maintains lower LV volumes and higher EF in patients receiving concurrent beta-blockade after MI. A possible additive effect of combined therapy should be evaluated prospectively. Topics: Administration, Oral; Adrenergic beta-Antagonists; Aged; Angiotensin-Converting Enzyme Inhibitors; Cardiac Volume; Diastole; Dilatation, Pathologic; Double-Blind Method; Enalapril; Female; Heart Diseases; Humans; Injections, Intravenous; Male; Myocardial Infarction; Placebos; Prospective Studies; Stroke Volume; Survival Rate; Systole; Ventricular Function, Left | 1996 |
Effects of enalapril on tissue factor in patients with uncomplicated acute myocardial infarction.
In a randomized, double-blind, placebo-controlled study beginning 4 weeks after uncomplicated acute myocardial infarction, it was established that the baseline plasma tissue factor antigen level was significantly higher in patients with myocardial infarction than in control subjects, and enalapril therapy significantly reduced the elevated plasma tissue factor antigen level. This may be associated with the reduction in the risk of coronary thrombosis seen with the use of angiotensin-converting enzyme inhibitors. Topics: Angiotensin-Converting Enzyme Inhibitors; Double-Blind Method; Drug Therapy, Combination; Enalapril; Enzyme-Linked Immunosorbent Assay; Female; Humans; Male; Middle Aged; Myocardial Infarction; Peptidyl-Dipeptidase A; Thromboplastin; Time Factors | 1996 |
Prognostic significance of plasma norepinephrine in patients with asymptomatic left ventricular dysfunction. SOLVD Investigators.
Elevated plasma neurohormonal levels are associated with increased mortality rates in patients with symptomatic heart failure. A previous Studies of Left Ventricular Dysfunction (SOLVD) trial suggested that neurohumoral activation precedes the development of symptoms as demonstrated by increased neurohormonal levels in patients with asymptomatic left ventricular dysfunction. However, the significance of this early neurohumoral activation is unclear. The goals of this study were to determine the prognostic significance of the plasma concentrations of plasma norepinephrine (PNE) and atrial natriuretic peptide (ANP) and the renin activity (PRA) in patients with asymptomatic left ventricular dysfunction.. PNE and PRA were measured before randomization in 514 patients with left ventricular ejection fractions < or = 35% who did not require treatment for congestive heart failure and were enrolled in the SOLVD Prevention Trial. Plasma ANP levels were measured in a subset of 241 patients owing to study design. Using the Cox proportional hazards model that included left ventricular ejection fraction, New York Heart Association functional class, age, sex, treatment assignment to placebo or enalapril, and cause of heart failure, we examined whether these neurohormones predicted all-cause mortality, cardiovascular mortality, hospitalization for heart failure, development of heart failure, or development of ischemic events (myocardial infarction or unstable angina). PNE was the strongest predictor of clinical events in this patient population. PNE levels above the median of 393 pg/mL were associated with a relative risk of 2.59 (P = .002) for all-cause mortality, 2.55 (P = .003) for cardiovascular mortality, 2.55 (P = .005) for hospitalization for heart failure, 1.88 (P = .002) for development of heart failure, 1.92 (P = .001) for ischemic events, and 2.59 (P = .005) for myocardial infarction. PNE remained the most powerful predictor for all-cause mortality and ischemic events when the analysis included only the patients with histories of ischemic left ventricular dysfunction. The increases in other neurohormonal levels were not useful in predicting the subsequent development of clinical events.. Increased PNE levels in patients with asymptomatic left ventricular dysfunction appear to predict all-cause and cardiovascular mortalities and development of clinical events related to the onset of heart failure or acute ischemic syndromes. Thus, measurement of PNE may be a possible early marker for assessment of disease progression in patients with left ventricular dysfunction, and modulating the release or effect of PNE may lead to improved prognosis and/or a reduction in morbidity. Topics: Angina, Unstable; Angiotensin-Converting Enzyme Inhibitors; Biomarkers; Enalapril; Female; Heart Failure; Humans; Male; Middle Aged; Myocardial Infarction; Myocardial Ischemia; Norepinephrine; Placebos; Predictive Value of Tests; Prognosis; Renin; Risk Factors; Survival Rate; Ventricular Dysfunction, Left | 1996 |
Effect of enalapril initiated early after acute myocardial infarction on heart failure parameters, with reference to clinical class and echocardiographic determinants. CONSENSUS II Multi-Echo Study Group.
Although the angiotensin-converting enzyme inhibitor enalapril has recently been shown to reduce mortality and the need for hospitalization in patients with left ventricular dysfunction and congestive heart failure, this drug was found to have no significant impact on short-term mortality after acute myocardial infarction (AMI) in the CONSENSUS II trial. The effect of enalapril initiated early after AMI on clinical and echocardiographic determinants of left ventricular (LV) function was studied in a subset of patients from CONSENSUS II.. Symptoms and signs of heart failure were classified as NYHA and dyspnea classes. Echocardiography included LV end-systolic volumes (ESV) and end-diastolic volumes (EDV), as well as ejection fraction (EF), wall motion index (WMI), and mitral flow indices. In all, 428 patients were included and followed for an average of 5.1 months by serial examinations, starting 2-5 days after myocardial infarction (MI) and repeated after 1 month and at the completion of the study.. There was no beneficial effect of enalapril on clinically determined function. Changes (i.e., changes in NYHA class) in the functional status remained correlated with changes in echocardiographic determinants throughout the study in patients belonging to the placebo group: EDV index (r = 0.36, p = 0.002, ESV index (r = 0.49, p < 0.001), EF (r = -0.41, p < 0.001), and WMI (r = 0.29, p = 0.008). In a stepwise logistic regression model, the best baseline parameters to predict NYHA class at final visit in all patients were age (p = 0.014) and ESV index (p = 0.001).. Enalapril treatment for an average period of 5.1 months following MI resulted in no clinically significant beneficial effects on NYHA and dyspnea class. Changes in clinical function class were correlated with changes in echocardiographic determinants in placebo-treated patients, but not in patients given enalapril. Topics: Aged; Angiotensin-Converting Enzyme Inhibitors; Dyspnea; Echocardiography; Enalapril; Female; Humans; Logistic Models; Male; Middle Aged; Myocardial Infarction; Randomized Controlled Trials as Topic; Ventricular Function, Left | 1996 |
Ventricular late potentials and left ventricular function after early enalapril treatment in acute myocardial infarction.
Topics: Aged; Angiotensin-Converting Enzyme Inhibitors; Double-Blind Method; Electrophysiology; Enalapril; Enalaprilat; Humans; Male; Membrane Potentials; Middle Aged; Myocardial Infarction; Ventricular Function, Left | 1995 |
Effect of early enalapril therapy on left ventricular function and structure in acute myocardial infarction.
Infarct expansion starts within hours to days after transmural myocardial injury. Previous echocardiographic and left ventriculographic studies demonstrated that angiotensin-converting enzyme (ACE) inhibitor therapy limits left ventricular dilatation, particularly in patients with anterior wall acute myocardial infarction (AMI) or impaired left ventricular function. Forty-three patients with an acute Q-wave AMI were randomized within 24 hours of symptom onset to intravenous enalaprilat (1 mg) or placebo. Patients were then given corresponding oral therapy and followed for 1 month. Predrug and 1-month gated blood pool scans were obtained in 32 patients to evaluate changes in cardiac volumes and ejection fraction. Twenty-three patients underwent magnetic resonance imaging at 1 month to evaluate left ventricular infarct expansion. Blood pressure decreased at 6 hours but returned to baseline in both groups after 1 month of therapy. The change in cardiac volumes from baseline to 1 month differed between the placebo (end-diastolic volume +16 +/- 5 ml, end-systolic volume +8 +/- 6 ml), and enalapril (end-diastolic volume -8 +/- 9 ml and end-systolic volume -14 +/- 7 ml) groups (p < 0.05 vs placebo). Global and infarct zone ejection fractions improved significantly at 1 month in the enalapril group (+6 +/- 3% and 19 +/- 5%, respectively) but did not change over 1 month in the placebo group. Infarct segment length and infarct expansion index by magnetic resonance imaging were significantly less in those treated with enalapril, suggesting less infarct expansion in this group. Thus, early administration of enalaprilat to patients presenting with a first Q-wave AMI prevents cardiac dilatation and infarct expansion. Topics: Angiotensin-Converting Enzyme Inhibitors; Blood Pressure; Cardiac Volume; Cardiomegaly; Double-Blind Method; Enalapril; Female; Gated Blood-Pool Imaging; Heart Ventricles; Humans; Magnetic Resonance Imaging; Male; Middle Aged; Myocardial Infarction; Stroke Volume; Ventricular Function, Left | 1995 |
Neurohormonal changes after acute myocardial infarction. Relationships with haemodynamic indices and effects of ACE inhibition.
To determine the neurohormonal response to angiotensin-converting enzyme (ACE) inhibition after acute myocardial infarction, 36 patients presenting within 6 h of the onset of chest pain were studied in a single regional cardiology service. In this double-blind study, 13 patients were randomized to receive captopril, 12 patients received enalapril, and 11 patients received placebo, for 12 months. In patients receiving placebo, acute myocardial infarction was associated with activation of the renin-angiotensin-aldosterone and sympathetic nervous systems, and stimulation of plasma brain natriuretic peptide and atrial natriuretic peptide levels. ACE inhibition did not significantly alter circulating levels of norepinephrine, brain natriuretic peptide or atrial natriuretic peptide. Compared with placebo, enalapril induced a steep decline in plasma ACE activity, and plasma angiotensin II levels were reduced by both ACE inhibitors. Using grouped data, circulating levels of brain natriuretic peptide at the zero sampling time were significantly higher than atrial natriuretic peptide values. Brain natriuretic peptide levels at 72 h were significantly correlated with the radionuclide left ventricular ejection fraction measured 5 days and 3 months after infarction. Similar associations were observed for atrial natriuretic peptide and norepinephrine. We confirm activation of the renin-angiotensin-aldosterone and sympathetic nervous systems after acute myocardial infarction. The atrial natriuretic peptide and brain natriuretic peptide and sympathetic nervous system responses to acute myocardial infarction were not significantly modified by ACE inhibition. Brain natriuretic peptide and atrial natriuretic peptide levels were significantly correlated with the left ventricular ejection fraction measured 5 days and again 3 months after myocardial infarction, and may prove a useful prognostic index. Topics: Angiotensin-Converting Enzyme Inhibitors; Atrial Natriuretic Factor; Captopril; Creatine Kinase; Double-Blind Method; Enalapril; Female; Hemodynamics; Humans; Male; Middle Aged; Myocardial Infarction; Neurotransmitter Agents; Stroke Volume | 1995 |
Neurohormonal activation in patients with acute myocardial infarction or chronic congestive heart failure. With special reference to treatment with angiotensin converting enzyme inhibitors.
Neurohormonal activation may provide a pathophysiological link between acute myocardial infarction and chronic congestive heart failure, and modulation of neurohormonal activity may be an important therapeutic target in these conditions. Plasma neurohormones were studied in 55 patients with acute myocardial infarction. Angiotensin II, noradrenaline and ANP were elevated in the early phase but tended to normalize during the first week in patients without signs of heart failure. In patients with heart failure angiotensin II and noradrenaline remained elevated for 1 month and ANP for 4-6 months. During head-up tilt, angiotensin II and noradrenaline increased most in patients with heart failure. In patients with a first myocardial infarction there was a positive correlation between sustained neurohormonal activity and infarct size. Almost complete suppression of plasma ACE activity was achieved within 30 min in 48 patients treated with intravenous enalaprilat, initiated within 24 h from the onset of infarction. The drug was tolerated in dosages of 1.0-1.2 mg given over 1-2h. Patients with systolic blood pressure between 100 and 110 mmHg incurred a greater risk of hypotension than those with higher blood pressure at baseline. Tolerance was not worse among patients treated with intravenous diuretics, metoprolol or nitroglycerin. A total of 98 patients were randomized to treatment with enalapril or placebo, initiated within 24 h from onset of infarction and continued for 4-6 months. During treatment there were no significant differences in plasma levels of angiotensin II, aldosterone, ANP or catecholamines between groups. Echocardiographic recordings were performed in 28 patients. Among patients on placebo there was a positive correlation between plasma levels of noradrenaline at days 5-7 and the increase in left ventricular volumes during the study period, and an inverse correlation between plasma aldosterone at days 5-7 and the increase in left ventricular ejection fraction during the study. No such correlation was found among patients on enalapril. ANP levels at 1 month correlated inversely with the left ventricular ejection fraction at the same time. Plasma neurohormones were measured in 223 patients with mild or moderately severe chronic heart failure, randomized to treatment with ramipril or placebo for 3 months. There was wide variation in hormone levels. Noradrenaline and aldosterone correlated inversely with exercise duration at baseline. Noradrenaline Topics: Aged; Angiotensin-Converting Enzyme Inhibitors; Atrial Natriuretic Factor; Blood Pressure; Enalapril; Enalaprilat; Exercise; Female; Heart Failure; Hemodynamics; Humans; Male; Middle Aged; Myocardial Infarction; Neurosecretory Systems; Norepinephrine; Peptidyl-Dipeptidase A; Ramipril; Ventricular Function, Left | 1995 |
Left ventricular volumes, ejection fraction, and plasma proatrial natriuretic factor (1-98) after withdrawal of enalapril treatment initiated early after myocardial infarction. CONSENSUS II Multi-Echo Study Group.
To assess whether the reduction in left ventricular dilatation after acute myocardial infarction obtained by early administration of angiotensin converting enzyme inhibitors depends on continuous treatment.. Prospective observational and cross sectional study of withdrawal of randomised treatment with enalapril or placebo.. 106 patients on 6 months trial treatment after an acute myocardial infarction.. Left ventricular volumes and ejection fraction as assessed by echocardiography and circulating proatrial natriuretic factor (1-98) before and 4-6 weeks after withdrawal of treatment.. There were no significant changes (mean (SD)) in left ventricular systolic (0.7 (4.7) ml/m2) and diastolic (0.4 (6.6) ml/m2) volume indices, ejection fraction (-0.9 (6)%), and proatrial natriuretic factor (172 (992) pmol/l) after withdrawal of enalapril. The significantly lower left ventricular volumes observed with 6 months of enalapril therapy after acute myocardial infarction, as compared with placebo, were maintained 6 weeks after drug withdrawal.. The results show that the benefit of 6 months of enalapril treatment initiated early after myocardial infarction is maintained for at least 6 weeks after drug withdrawal, suggesting that the treatment effect on left ventricular structure is not reversed by changes in loading conditions caused by subsequent drug withdrawal. Topics: Atrial Natriuretic Factor; Cardiac Volume; Cross-Sectional Studies; Diuretics; Drug Administration Schedule; Echocardiography; Enalapril; Female; Humans; Male; Middle Aged; Myocardial Infarction; Peptide Fragments; Prospective Studies; Protein Precursors; Stroke Volume | 1995 |
Beneficial clinical effect of very early enalapril treatment in patients with acute left ventricular failure complicating myocardial infarction.
Acute myocardial infarction (AMI) leads to left ventricular dysfunction, the extent of which predicts mortality. We studied the effect of very early enalapril treatment in patients with left ventricular failure (Killip classification II-III) resulting from AMI. In a double-blind randomized trial, patients on conventional treatment were started on placebo (PL, n = 15) or 2.5 mg enalapril (EN, n = 15) twice daily as early as 24 to 30 h after AMI and were followed up over a period of 21 days. One patient died in each treatment group. There were three dropouts in the placebo group (progressive heart failure requiring antiotensin-converting enzyme inhibition) and one dropout in the enalapril group (malignant ventricular arrhythmias). Plasma atrial natriuretic peptide (ANP) and norepinephrine decreased similarly in both groups from elevated baseline concentrations. The patients with the highest baseline ANP levels died in both groups: EN: 579 fmol/ml (mean 65.3 +/- 34.4 fmol/ml), PL: 403 fmol/ml (mean 63.5 +/- 37.6 fmol/ml). Killip classification improved in 9 of 13 patients on enalapril but only in 5 of 11 patients on placebo. On echocardiography an increase in fractional shortening (FS) (3.2 +/- 7.5%, p < 0.05) was found with enalapril only. Patients on placebo required more diuretics, and plasma aldosterone increased threefold. Thus, very early enalapril treatment may help prevent left ventricular failure after AMI. Extremely high initial plasma ANP concentrations may predict an unfavorable outcome. Topics: Aged; Atrial Natriuretic Factor; Biomarkers; Double-Blind Method; Drug Administration Schedule; Echocardiography; Enalapril; Female; Heart Failure; Humans; Male; Middle Aged; Myocardial Infarction; Prognosis; Survival Rate; Ventricular Dysfunction, Left | 1995 |
Effects of early enalapril treatment on global and regional wall motion in acute myocardial infarction. CONSENSUS II Multi Echo Study Group.
Angiotensin-converting-enzyme inhibitor therapy can preserve left ventricular (LV) function and geometric features and improve survival in subsets of patients with acute myocardial infarction (AMI). We investigated the effect of enalapril treatment initiated < 24 hours after AMI on global and regional echocardiographic wall motion indexes obtained at 2 to 5 days and at 1 and 6 months in 428 consecutive patients enrolled in the randomized, placebo-controlled Cooperative New Scandinavian Enalapril Survival Study II. In anterior AMIs, the non-infarct-zone index deteriorated in the placebo group but remained unchanged in the enalapril-treated group (0.18 vs 0.02; p < or = 0.05), an effect related to attenuated LV volume expansion. No treatment effects were observed in nonanterior AMIs or in the entire unselected population. Thus in an unselected population with AMI, early enalapril treatment had no effect on LV function; yet in patients with anterior infarcts, LV function was maintained through preservation of function in the noninfarcted myocardium. Topics: Aged; Cardiac Volume; Cohort Studies; Double-Blind Method; Echocardiography; Enalapril; Female; Follow-Up Studies; Heart; Humans; Male; Myocardial Infarction; Placebos; Recurrence; Survival Rate; Ventricular Dysfunction, Left; Ventricular Function, Left | 1995 |
Platelet and leukocyte activation after myocardial infarction. Influence of enalapril.
In this double-blind placebo-controlled study with enalapril, 74 patients with acute myocardial infarction were followed at 0, 7, 30, 60 and 180 days after the event. Platelets and leukocytes were activated during the first 7 days. During the 6-month period fibrinogen, leukocytes, elastase, and B beta 30-43 remained elevated in 50, 15, 30 and 80% of the patients, respectively, but there was no detectable angiotensin converting enzyme activity in platelets. Enalapril did not modulate fibrinogen, leukocyte count or elastase, while B beta 30-43 peptide showed decreased levels, although the proportion of patients with values above the reference limit did not differ from placebo. In conclusion, in the 6-month post acute myocardial infarction period, while platelet function is activated only during the first week after acute myocardial infarction, fibrinogen and leukocyte function continue to be activated throughout the 6 months in a considerable proportion of patients. These signs may indicate an ongoing atherosclerotic process. Enalapril has no major influence on these reactivities. Topics: Adult; Aged; Aged, 80 and over; Angiotensin-Converting Enzyme Inhibitors; Coronary Artery Disease; Double-Blind Method; Enalapril; Female; Fibrin Fibrinogen Degradation Products; Fibrinogen; Follow-Up Studies; Humans; Leukocyte Count; Male; Middle Aged; Myocardial Infarction; Pancreatic Elastase; Peptide Fragments; Platelet Activation; Platelet Aggregation; Risk Factors; Survival Rate | 1995 |
The role of ACE inhibitors in preventing myocardial infarction: potential mechanisms and clinical implications.
Topics: Angiotensin-Converting Enzyme Inhibitors; Cardiomegaly; Enalapril; Humans; Hypertension; Myocardial Infarction; Myocardial Ischemia; Peptidyl-Dipeptidase A; Polymorphism, Genetic | 1995 |
[Enalapril reduces the degree of left ventricular remodeling after acute myocardial infarction and reduces the incidence of arrhythmia in ischemic disease].
The present study shows that enalapril prevents the excessive remodeling of the left ventricle after acute myocardial infarction. This randomized and double blind clinical study analysed 50 patients with an inferior myocardial infarction. The effect of enalapril was evaluated through cardiac volumes, ejection fraction, neurohormonal levels and incidence of the left ventricle disfunction after acute myocardial infarction. The patients treated with enalapril showed a significant reduction on the values of nor-epinefrine, angiotensine II, natriuretic hormone and vasopressine, four weeks after initiation of treatment. The ejection fraction and the level of the wall movement was more favourable, four weeks after infarction, in the group treated with enalapril. The incidence of congestive heart failure and arrhythmias was lower in the group treated with enalapril. So, we conclude that enalapril is a drug that prevents the excessive remodelling of the left ventricle after an acute myocardial infarction. Topics: Aged; Arrhythmias, Cardiac; Double-Blind Method; Enalapril; Female; Humans; Male; Middle Aged; Myocardial Infarction; Ventricular Function, Left | 1994 |
Quality of life on enalapril after acute myocardial infarction.
Quality of life was assessed 4-6 months after an acute myocardial infarction in a randomized double-blind study of enalapril versus placebo. Quality of life was evaluated using the Nottingham Health Profile (NHP), the Physical Symptoms Distress Index (PSDI), the Work Performance Scale (WPS) and the Life Satisfaction Index (LSI). The study comprised 36 women (aged 46-85 years, mean 68) and 96 males (aged 39-81 years, mean 62). Quality of life did not differ significantly between patients treated with enalapril versus placebo. The scores were (enalapril vs placebo, mean +/- SE): average NHP 15.4 +/- 2.3 vs 17.1 +/- 2.3; PSDI 9.5 +/- 1.0 vs 10.8 +/- 0.9; WPS 19.8 +/- 2.0 vs 19.4 +/- 1.4; LSI 24.1 +/- 1.0 vs 22.5 +/- 1.4. Men reported a better quality of life than women on most assessments, and non-smokers and ex-smokers better than smokers. Patients with moderate or severe angina pectoris had a worse quality of life measured by PSDI and NHP than patients with minimal or no angina pectoris. Patients with congestive heart failure had a higher PSDI than those without (13.6 +/- 1.7 vs 9.4 +/- 0.7, P < 0.05), while no significant differences were observed in the NHP scores. In conclusion, quality of life was similar in enalapril and placebo-treated patients after an acute myocardial infarction. However, it was reduced in patients with angina pectoris or heart failure and in those who continued smoking. Topics: Activities of Daily Living; Adult; Aged; Aged, 80 and over; Angina Pectoris; Double-Blind Method; Enalapril; Female; Follow-Up Studies; Heart Failure; Humans; Male; Middle Aged; Myocardial Infarction; Quality of Life; Sick Role; Smoking | 1994 |
Left ventricular remodelling, neurohormonal activation and early treatment with enalapril (CONSENSUS II) following myocardial infarction.
The effects of angiotensin converting enzyme (ACE) inhibitors on mortality following acute myocardial infarction (MI) has recently been studied in several clinical trials. The rationale for the use of these drugs following an injury to the myocardium is largely based on their ability to attenuate left ventricular volume expansion and modulate neurohormonal activation. Left ventricular dilatation following MI is due to complex structural changes in the infarcted myocardium as well as alterations in the non-infarcted contractile myocardium. The magnitude of this remodelling is associated with adverse prognosis. Neurohormonal systems are activated in the early phase of acute MI. Prolonged neurohormonal activation mainly occurs among patients with marked left ventricular dysfunction. The CONSENSUS II trial examined the effects on mortality of the ACE inhibitor enalapril, when initiated within 24 h from the onset of the infarct and continued for 6 months. There were 6090 patients randomly assigned to placebo (n = 3046) or enalapril (n = 3044). At the end of the trial, 598 patients had died: 286 (9.4%) in the placebo group and 312 (10.2%) in the enalapril group (P = 0.26). These results are in contrast to some other studies in which mortality was reduced by ACE inhibitor therapy post-MI. It is considered likely that the positive effects of ACE inhibitors following MI are confined mainly to patients with marked left ventricular dysfunction and prolonged neurohormonal activation. Topics: Aged; Double-Blind Method; Enalapril; Female; Humans; Hypertrophy, Left Ventricular; Male; Myocardial Infarction; Sympathetic Nervous System; Time Factors | 1994 |
Plasma endothelin determination as a prognostic indicator of 1-year mortality after acute myocardial infarction.
Plasma endothelin concentrations are increased in the acute phase of myocardial infarction and in chronic heart failure. Since endothelin may contribute to hemodynamic deterioration by potent vasoconstrictory and cardiotoxic actions, increased plasma levels may be associated with an unfavorable prognosis after myocardial infarction.. We tested the hypothesis that plasma endothelin determination in the subacute phase of myocardial infarction is related to subsequent survival and assessed whether plasma endothelin measurements provide additional prognostic information to that obtained from clinical and biochemical variables previously known to be associated with high mortality. Plasma endothelin determination was obtained from 142 patients (average age +/- SD, 67.8 +/- 10.1 years) on day 3 after documented myocardial infarction and was related to 1-year mortality. Sixteen patients died during the follow-up period. In a univariate Cox proportional-hazards model, day 3 plasma endothelin concentrations were significantly related to mortality (P < .0001). Patient age, previous treatment for systemic hypertension, presence of clinical heart failure, and plasma atrial natriuretic factor levels were all related to mortality in univariate analysis but provided no additional prognostic information to that obtained from endothelin determination in a multivariate model.. Plasma endothelin concentrations are strongly related to outcome after myocardial infarction and provide prognostic information independent of clinical and biochemical variables previously associated with a poor prognosis. Topics: Aged; Double-Blind Method; Enalapril; Endothelins; Female; Follow-Up Studies; Humans; Male; Multivariate Analysis; Myocardial Infarction; Prognosis; Proportional Hazards Models; Risk Factors; Time Factors | 1994 |
Effects of early administration of enalapril on radionuclide left ventricular ejection fraction and plasma N-terminal atrial natriuretic peptide after acute myocardial infarction.
The effects of enalapril therapy on radionuclide ejection fraction and plasma N-terminal atrial natriuretic peptide were investigated in a randomized, double-blind, placebo-controlled study of 52 patients with acute myocardial infarction. The medication was begun intravenously within 24 hours of the onset of symptoms. At discharge and the end point of 6 months, the radiographic size of the heart was significantly smaller in patients receiving (n = 28) than in those not receiving (n = 24) enalapril therapy (p < 0.03 vs < 0.01). However, left ventricular ejection fraction decreased simultaneously from 50 +/- 10% to 47 +/- 11% in patients treated with enalapril, whereas it increased from 48 +/- 13% to 50 +/- 14% in control patients (p < 0.05 for the difference of the changes). The decrease in ejection fraction was most marked in the infarct-related region of the left ventricle (p < 0.01). During the in-hospital period, plasma N-terminal atrial natriuretic peptide was decreased in patients treated with enalapril, whereas it was increased in those treated with placebo with complicated acute myocardial infarction (p < 0.05). During the following 6 months, the differences remained insignificant. Early administration of enalapril significantly attenuated heart enlargement after myocardial infarction and probably improved hemodynamics during the acute phase of complicated infarction. The decrease in ejection fraction during recovery indicates an impairment of systolic function. The decrease in infarct-related regional ejection fraction suggests that the impairment may be due to poor healing of the infarction scar. Topics: Aged; Atrial Natriuretic Factor; Double-Blind Method; Enalapril; Female; Humans; Male; Middle Aged; Myocardial Infarction; Radionuclide Ventriculography; Stroke Volume; Time Factors; Ventricular Function, Left | 1994 |
Plasma corticotrophin releasing hormone, vasopressin, ACTH and cortisol responses to acute myocardial infarction.
We assessed the magnitude and duration of the response of hypothalamic-pituitary-adrenal hormones to the stress of myocardial infarction, in the presence and absence of angiotensin converting enzyme inhibitors. In particular, we wished to analyse the interrelationships between peripheral plasma levels of corticotrophin releasing hormone (CRH), vasopressin (AVP) and adrenocorticotrophin (ACTH), and also between ACTH and cortisol, during a prolonged medical stress.. All hormones were measured within 6 hours of the onset of an acute myocardial infarction. Patients were randomly allocated to three different study groups according to a double blind procedure.. Group 1 (10 patients) received placebo treatment, Group 2 (13 patients) received a maintenance dose of captopril 25 mg three times daily, Group 3 (11 patients) received enalapril 5 mg three times daily.. Peptide hormones were measured by radioimmunoassay, and cortisol by ELISA. Reference ranges for all hormones were obtained from 40 or more volunteers from the electoral roll.. At the start of the study, mean +/- SEM plasma AVP (27.9 +/- 4.6 pmol/l) was significantly (P < 0.001) raised above the mean for the reference range (1.82 +/- 0.09 pmol/l), and 12 patients had values > 50 pmol/l. Mean plasma cortisol (960 +/- 89.6 nmol/l) was also raised above the reference range mean (554 +/- 28 nmol/l, P < 0.001), as was mean plasma CRH (4.97 +/- 0.5 pmol/l, reference mean 1.52 +/- 0.09 pmol/l, P < 0.001). By contrast, mean ACTH (3.88 +/- 0.66 pmol/l) was significantly less than the reference mean (10.7 +/- 0.7 pmol/l, P < 0.001). During the 72-hour observation period there was a highly significant fall (P < 0.001) in plasma CRH, AVP and cortisol. By contrast, plasma ACTH rose, and the change with time of ACTH was significantly different from the fall in plasma CRH, AVP or cortisol (P < 0.001 for each comparison). No significant differences in plasma CRH, AVP, ACTH or cortisol responses to placebo, captopril or enalapril were observed.. Within 6 hours of a myocardial infarction, mean plasma CRH, AVP and cortisol values were very significantly raised above mean control values, while ACTH was very significantly reduced. During the 3 days following an acute myocardial infarction, plasma CRH, AVP and cortisol fell substantially, and this pattern was not influenced by angiotensin converting enzyme inhibitors. By contrast, plasma ACTH showed a significant increase with time. This suggests that the usual relationships between CRH, AVP and ACTH, and between ACTH and cortisol are disturbed in patients admitted to hospital with myocardial infarction. Maximum levels of AVP observed in 12 patients exceeded 50 pmol/l, which may be sufficiently high to interfere with tissue perfusion. It is postulated that V1 AVP receptor antagonists may have a therapeutic application in limiting infarct size. Topics: Adrenocorticotropic Hormone; Angiotensin-Converting Enzyme Inhibitors; Arginine Vasopressin; Captopril; Corticotropin-Releasing Hormone; Double-Blind Method; Enalapril; Female; Humans; Hydrocortisone; Male; Myocardial Infarction | 1994 |
Comparison of enalapril versus captopril on left ventricular function and survival three months after acute myocardial infarction (the "PRACTICAL" study).
Left ventricular (LV) function and survival can be improved with captopril when initiated later than 24 hours after acute myocardial infarction. Animal studies suggest additional benefits may be obtained with earlier initiation of angiotensin-converting enzyme (ACE) inhibitors. The effects on LV function of captopril and enalapril initiated within 24 hours of myocardial infarction were studied. Two hundred twenty-five patients with acute myocardial infarction were enrolled within 24 hours of the onset of chest pain. They were randomized to receive either captopril 25 mg three times daily, enalapril 5 mg three times daily, or placebo. LV ejection fraction (EF) and volumes were measured by radionuclide ventriculography at baseline during treatment and at 3 months after a 3-day withdrawal from therapy. The ACE inhibitor group had a significant increase in EF (45 +/- 1 to 47 +/- 1%; p = 0.005) and significantly attenuated LV dilatation compared with results in the placebo group (175 +/- 6 to 189 +/- 7 ml in the placebo group vs 168 +/- 4 to 172 +/- 4 ml in the ACE inhibitor group; p = 0.051 for LV end-diastolic volume; and 99 +/- 6 to 108 +/- 7 ml in the placebo group vs 94 +/- 3 to 94 +/- 4 ml; p = 0.026 for LV end-systolic volume). The beneficial effects of ACE inhibitor therapy on LV function were observed irrespective of the degree of initial LV dysfunction and were comparable in both the captopril and enalapril groups.(ABSTRACT TRUNCATED AT 250 WORDS) Topics: Aged; Angiotensin II; Blood Pressure; Captopril; Cardiac Volume; Cause of Death; Double-Blind Method; Drug Tolerance; Enalapril; Female; Follow-Up Studies; Gated Blood-Pool Imaging; Humans; Male; Middle Aged; Myocardial Infarction; Placebos; Stroke Volume; Survival Rate; Ventricular Function, Left | 1994 |
The effect of early converting enzyme inhibition on neurohumoral activation in acute myocardial infarction.
The effect of early converting enzyme inhibition with enalapril on the extent of neurohumoral activation in acute myocardial infarction was evaluated in a randomized, placebo-controlled double blind fashion. Plasma levels of atrial natriuretic factor and noradrenaline on day 1, i.e. prior to randomization (n = 99), and on days 3 (n = 145) and 30 (n = 69) following myocardial infarction were determined. Enalapril did not significantly affect neurohumoral activation on day 3 (enalapril vs. placebo (mean (S.E.M.); atrial natriuretic factor: 35.3 (3.0) vs. 37.2 (2.9) pmol/l; noradrenaline: 2.82 (0.20) vs. 3.70 (1.02) nmol/l) or at 1 month (atrial natriuretic factor: 33.1 (3.0) vs. 32.4 (3.9) pmol/l; noradrenaline: 2.77 (0.25) vs. 2.82 (0.28) nmol/l). However, in myocardial infarction patients developing heart failure, a significant attenuation of the day 3 atrial natriuretic factor, but not of the noradrenaline response, was seen (atrial natriuretic factor: 47.0 (7.7) vs. 59.0 (6.4) pmol/l, P < 0.05; noradrenaline: 3.37 (0.42) vs. 6.59 (3.26) nmol/l, P = ns). In conclusion, enalapril did not significantly reduce neurohumoral activation in acute myocardial infarction, possibly because the activation in most patients is modest and confined to the early convalescent phase. However, in patients with myocardial infarction and heart failure enalapril therapy was associated with a reduction in early plasma atrial natriuretic factor levels, compatible with decreased cardiac filling pressures. Topics: Aged; Atrial Natriuretic Factor; Double-Blind Method; Enalapril; Female; Heart Failure; Humans; Male; Myocardial Infarction; Norepinephrine; Time Factors | 1993 |
Reduced mortality and morbidity with the use of angiotensin-converting enzyme inhibitors in patients with left ventricular dysfunction and congestive heart failure.
The Studies of Left Ventricular Dysfunction (SOLVD) examined the effect of an angiotensin-converting enzyme (ACE) inhibitor, enalapril on mortality and hospitalization in 6,797 patients with low ejection fraction (EF < 0.35). Patients requiring treatment for heart failure were entered to the treatment trial (n = 2,569) while those patients not receiving pharmacological treatment for heart failure were entered in the prevention trial (n = 4,228). In the treatment trial, there was a 16% (95% confidence interval [CI], 5% to 26%) reduction in mortality with the largest reduction in deaths due to progressive heart failure (22%, 95% CI, 6 to 35%). There was also a 26% (95% CI, 18 to 34%) reduction in mortality or hospitalization for worsening heart failure. In the prevention trial there was an 8% (95% CI, -8 to 21%) reduction in mortality, 12% (95% CI, -3 to 26%) reduction in cardiovascular mortality, and a 29% (95% CI, 21 to 36%) reduction in mortality or development of heart failure. In addition, there was a 20% (95% CI, 9 to 30%) reduction in mortality or hospitalization for heart failure. There were consistent effects among subgroups defined by baseline serum sodium, vasodilator use, etiology and NYHA functional class. The effect of enalapril on mortality and hospitalization for heart failure was significantly greater for patients with the lowest ejection fraction. In both trials, there were highly significant reductions in myocardial infarction (23%, 95% CI, 11 to 34%) and hospitalizations for unstable angina (20%, 95% CI, 9 to 29%). Topics: Adult; Aged; Double-Blind Method; Enalapril; Exercise Test; Female; Follow-Up Studies; Heart Failure; Hemodynamics; Humans; Male; Middle Aged; Myocardial Infarction; Renin; Stroke Volume; Survival Rate; Ventricular Function, Left | 1993 |
The use of simulation in the design of two cardiovascular survival studies.
Simulation has become practical as an everyday tool given the wide availability of high performance workstations. We argue that simulation can play an important role in determining the number of patients required in a survival study, particularly if the assumption of proportional hazards does not hold, or if the study design is complex. The argument is illustrated by two examples. The first considers the design of a post myocardial infarction survival trial in which the hazard ratio is not constant. The second provides sample size estimates for a multicentre heart failure study in which both the treatment effect and the control mortality rate vary across centres. Topics: Computer Simulation; Enalapril; Follow-Up Studies; Heart Failure; Humans; Myocardial Infarction; Survival Rate; Thrombolytic Therapy; Tissue Plasminogen Activator | 1993 |
Attenuation of left ventricular dilatation after acute myocardial infarction by early initiation of enalapril therapy. CONSENSUS II Multi-Echo Study Group.
This trial investigated the effect of enalapril, administered early, on left ventricular (LV) volumes after myocardial infarction. Four hundred twenty-eight patients included in the Cooperative New Scandinavian Enalapril Survival Study (CONSENSUS II) were examined with echocardiography within 5 days, at 1 month and at 6 months after myocardial infarction. Enalaprilat (1 mg) or placebo infusion was initiated within 24 hours after infarction, followed by oral treatment to a target dose of 20 mg/day. A significant attenuation of LV dilatation was noted at 1 month in patients treated with enalapril compared with those receiving placebo. Changes in LV end-diastolic volume indexes during the first month were (mean +/- SEM) 5.7 +/- 1.0 ml/m2 for the placebo group and 1.9 +/- 0.8 ml/m2 for the enalapril group (p < 0.02). Changes in LV end-systolic volume indexes were 3.1 +/- 0.8 and 0.5 +/- 0.6 ml/m2, respectively (p < 0.02). The between-group difference was most marked in patients with anterior wall infarction (p < 0.005). Volume changes beyond the first month were similar in both groups but the differences observed at 1 month were maintained. The larger volumes in the placebo versus enalapril group were significant or borderline significant at 1 and 6 months. Thus, enalapril treatment initiated early after myocardial infarction and continued for 6 months can attenuate LV dilatation during the first month resulting in smaller LV volumes after 1 and 6 months. Topics: Aged; Drug Administration Schedule; Enalapril; Heart Ventricles; Humans; Hypertrophy, Left Ventricular; Myocardial Infarction; Stroke Volume | 1993 |
Regional remodeling and nonuniform changes in diastolic function in patients with left ventricular dysfunction: modification by long-term enalapril treatment. The SOLVD Investigators.
The purpose of the present study was to assess the process of late regional remodeling and the changes in regional diastolic function at the base and apex of the left ventricle in patients with chronic systolic dysfunction.. Remodeling has been suggested to play an important role in the progression of left ventricular dysfunction and heart failure. However, the regional difference in the process of late remodeling and its relation to diastolic function remain unclear.. In 32 patients with previous myocardial infarction and left ventricular ejection fraction < or = 35%, left ventricular hemodynamic and angiographic data were studied before and 1 year after randomization to conventional therapy with placebo (n = 12) or enalapril, 10 mg twice daily (n = 20). Left ventricular regional wall dynamics were analyzed in the basal and apical regions by the area method.. In the placebo group, left ventricular end-diastolic and end-systolic regional areas increased significantly over time at the base but were unchanged at the apex. At the base, the diastolic left ventricular pressure-regional area relation shifted rightward and the regional stiffness constant decreased (6.9 +/- 4.3 to 5.0 +/- 3.1 x 10(-3) mm-2, p < 0.05), indicating an increase in regional distensibility. At the apex, however, the diastolic pressure-regional area relation shifted upward slightly, and the regional stiffness constant increased from 11.5 +/- 4.4 to 14.4 +/- 5.6 x 10(-3) mm-2 (p = 0.08). The regional peak filling rate was maintained at the base but decreased at the apex (1,014 +/- 436 to 762 +/- 306 mm2/s, p < 0.05); further, the changes in regional peak filling rate during follow-up were inversely related to the changes in the regional stiffness constant (r = -0.78, p < 0.001) at the apex. In contrast, in the enalapril group, end-diastolic and end-systolic regional areas significantly decreased over time both at the base and at the apex. Diastolic pressure-regional area relations shifted leftward, but the regional stiffness constant and regional peak filling rate did not change significantly either at the base or at the apex.. These findings suggest that in patients with severe systolic left ventricular dysfunction, there was a regional difference in the process of late remodeling between the base and apex of the left ventricle, which was associated with nonuniform changes in regional diastolic function in the placebo group. The data also suggest that the nonuniform progression of regional remodeling and diastolic dysfunction was prevented by long-term enalapril treatment. Topics: Cardiac Catheterization; Diastole; Enalapril; Female; Follow-Up Studies; Gated Blood-Pool Imaging; Heart Failure; Hemodynamics; Humans; Male; Middle Aged; Myocardial Infarction; Placebos; Severity of Illness Index; Systole; Time Factors; Ventricular Function, Left | 1993 |
Enalapril related changes in the fibrinolytic system in survivors of myocardial infarction.
Disturbances of the fibrinolytic system have been associated with cardiovascular disease and its risk factors. In the present study the effects of an ACE-inhibitor (enalapril) and a placebo on the fibrinolytic system have been compared. Eighty one survivors of acute myocardial infarction were randomised to treatment with enalapril or placebo. The mass concentrations and activity of tissue plasminogen activator (tPA) and plasminogen activator inhibitor (PAI-1) in plasma were measured three months after the infarction. The enalapril group had a significantly lower level of tPA antigen compared to the placebo-treated group (9.2 and 10.6 respectively). There was no difference between the two groups in any of the other fibrinolytic variables. We conclude that survivors of myocardial infarction treated with enalapril have a significantly lower concentration of tPA antigen than those treated with placebo. This may have a prognostic implication, as lower plasma concentrations of tPA antigen have been associated with better prognosis in patients with established coronary heart disease. Topics: Adolescent; Adult; Double-Blind Method; Enalapril; Enzyme-Linked Immunosorbent Assay; Female; Humans; Male; Myocardial Infarction; Plasminogen Activator Inhibitor 1; Tissue Plasminogen Activator | 1993 |
The relationship between early plasma atrial natriuretic factor levels and exercise performance after myocardial infarction.
We tested the hypothesis that early plasma atrial natriuretic factor (ANF) values are related to subsequent functional capacity in patients with acute myocardial infarction (MI). Blood for ANF determination was sampled from 90 male patients (age 66.5 +/- 9.5 (mean +/- SD) years) day 3 post MI. Exercise testing on an upright bicycle ergometer to symptomatic end-points was performed 1 and 6 months after MI in 83 and 78 patients, respectively. A weak, but significant inverse relationship between day 3 plasma ANF levels and exercise duration after MI (1 month: r = -0.27, P = 0.012; 6 months: r = -0.36, P = 0.001) was observed. In the subgroup of patients without effort-associated ischaemia, the relationship was closer (1 month; n = 38, r = -0.57, P < 0.001; t months: n = 33, r = -0.65, P < 0.001). In multivariate analysis, with ANF, patient age and peak creatine kinase MB values as covariates, the relationship remained significant. These findings suggest that in male patients subacute plasma ANF measurements are predictive of exercise capacity following acute MI. The relationship appears to be especially prominent in patients without effort-related ischaemia during exercise. Topics: Aged; Atrial Natriuretic Factor; Creatine Kinase; Double-Blind Method; Enalapril; Exercise Test; Hemodynamics; Humans; Isoenzymes; Male; Middle Aged; Myocardial Contraction; Myocardial Infarction; Radioimmunoassay; Scandinavian and Nordic Countries; Survival Rate | 1993 |
Neurohormonal effects of early treatment with enalapril after acute myocardial infarction and the impact on left ventricular remodelling.
Plasma neurohormones were sequentially analysed in 98 patients with acute myocardial infarction randomized to treatment with enalapril or placebo for 4-6 months. Plasma angiotensin converting enzyme activity was rapidly suppressed by enalapril, but unaffected by placebo (P = 0.0001). No significant differences were found in the plasma levels of angiotensin II, aldosterone, atrial natriuretic peptide, noradrenaline, adrenaline or dopamine between the two treatment groups. Among patients with infarct size above median, plasma angiotensin II increased during head-up tilt at one month in the placebo group, but not in the enalapril group. Left ventricular end-diastolic volume (LVEDV) and left ventricular end-systolic volume (LVESV) were evaluated by echocardiography in 28 patients (placebo 15, enalapril 13) and changes in left ventricular volumes between baseline and 4-6 months were calculated. Only in the placebo group was a positive correlation found between plasma levels of noradrenaline at day 5-7 and the subsequent increase in LVEDV (r = 0.78, P = 0.005) and LVESV (r = 0.75, P = 0.008). The same trend was found for angiotensin II, adrenaline and dopamine levels at days 5-7 and the subsequent increase in left ventricular volumes. In the placebo group a negative correlation was found between plasma aldosterone at days 5-7 and the subsequent increase in left ventricular ejection fraction (r = -0.77, P = 0.006) during the study period. Although circulating neurohormones were not significantly influenced by enalapril treatment, it is concluded that enalapril may influence the relationship found between sustained neurohormonal activation and left ventricular remodelling after acute myocardial infarction. Topics: Aldosterone; Angiotensin II; Atrial Natriuretic Factor; Dopamine; Double-Blind Method; Enalapril; Epinephrine; Female; Hormones; Humans; Male; Myocardial Infarction; Norepinephrine; Peptidyl-Dipeptidase A; Survival Rate; Sweden; Ventricular Function, Left | 1993 |
Effect on exercise performance of enalapril therapy initiated early after myocardial infarction. Nordic Enalapril exercise Trial.
The Nordic Enalapril Exercise Trial was a multicenter subtrial of the Cooperative New Scandinavian Enalapril Survival Study (CONSENSUS II) designed to evaluate the effect on maximal exercise performance of a 6-month period of enalapril treatment initiated early after myocardial infarction.. When begun early after myocardial infarction, converting enzyme inhibition therapy has been shown to attenuate infarct expansion and reduce left ventricular volume. Therapy has been associated with improved exercise performance.. Three hundred twenty-seven men (mean age 63.3 +/- 10.9 years) with documented acute myocardial infarction were randomized to treatment with enalapril or placebo on a double-blind basis. Intravenous enalaprilat or placebo therapy was initiated within 24 h after the onset of symptoms. Oral therapy was continued at a target dose of 20 mg/day. Patients exercised maximally at 1 month and 6 months after infarction to symptom-limited end points on a cycle ergometer with a 20 W/min incremental protocol.. The treatment and control groups were comparable in patient age, concurrent therapy and type and site of infarction. At 1 month, for all patients, mean total work performed was 34.9 +/- 20.9 kJ in the enalapril group (n = 169) versus 28.5 +/- 20.6 kJ in the placebo group (n = 158) (difference = 18.4%, p < 0.01). This between-group difference in favor of enalapril was greatest in patients > 70 years old (difference = 41.4%, p < 0.01, n = 105) and those with clinical evidence of heart failure (difference = 33.0%, p < 0.01, n = 122). At 6 months for all patients, mean total work performed was 35.4 +/- 23.8 kJ in the enalapril group versus 34.0 +/- 23.9 kJ in the placebo group (difference = 4.1%, NS).. This trial found that chronic converting enzyme inhibition initiated early after myocardial infarction was associated with significantly greater exercise capacity in men tested at 1 month. This difference was independent of type or site of infarction, patient age or the presence of clinical heart failure. The difference between the treatment and control groups was not significant at 6 months because of improvement in the placebo group. Further research is needed to elucidate the potential mechanisms involved, profile those patients most likely to profit from early therapy and establish the optimal timing and duration for intervention. Topics: Administration, Oral; Age Factors; Aged; Double-Blind Method; Enalapril; Exercise Test; Heart Failure; Hemodynamics; Humans; Infusions, Intravenous; Male; Middle Aged; Myocardial Infarction; Physical Exertion; Time Factors | 1993 |
Effects of enalapril on ventricular volumes and neurohumoral status after inferior wall myocardial infarction.
The activation of the sympathetic nervous system and the renin-angiotensin-aldosterone system and its beneficial modification with the use of angiotensin-converting enzyme inhibin after inferior wall myocardial infarction (MI) was evaluated. Fifty patients with acute inferior MI were randomly assigned to receive 5 mg per day of either enalapril or placebo after admission. Blood tests for neurohormone levels and echocardiograms were performed at initial examination and 4 weeks later. Baseline characteristics were similar in the two groups. Four weeks after randomization, patients treated with enalapril had lower end-diastolic volume (146 +/- 29 vs 167 +/- 15 ml; p = 0.04), end-systolic volume (56 +/- 18 vs 107 +/- 17 ml; p = 0.03), serum norepinephrine levels (320 +/- 93 vs 465 +/- 77 pg/ml; p < 0.01), angiotensin II levels (18 +/- 6 vs 54 +/- 11 pg/ml; p < 0.01), and atrial natriuretic polypeptide levels (106 +/- 9 vs 122 +/- 17 pg/ml; p = 0.05) than patients given placebo. The incidence of heart failure after MI was also lower in this group (4% vs 16%; p = 0.009). Results show that there is early neurohumoral activation in the course of acute inferior wall MI. Enalapril reduces neurohumoral levels and preserves ventricular volumes. These effects were associated with a reduction in the incidence of heart failure 4 weeks after MI in these patients. Topics: Aged; Aldosterone; Angiotensin II; Cardiac Volume; Double-Blind Method; Enalapril; Female; Humans; Male; Middle Aged; Myocardial Infarction; Norepinephrine; Ventricular Function, Left | 1993 |
ACE inhibitors after myocardial infarction.
Topics: Enalapril; Humans; Hypotension; Myocardial Infarction | 1993 |
Effect of enalapril on myocardial infarction and unstable angina in patients with low ejection fractions.
An association between raised renin levels and myocardial infarction has been reported. We studied the effects of enalapril, an angiotensin-converting enzyme (ACE) inhibitor, on the development of myocardial infarction and unstable angina in 6797 patients with ejection fractions < or = 0.35 enrolled into the two Studies of Left Ventricular Dysfunction (SOLVD) trials. Patients were randomly assigned to placebo (n = 3401) or enalapril (n = 3396) at doses of 2.5-20 mg per day in two concurrent double-blind trials with the same protocol. Patients with heart failure entered the treatment trial (n = 2569) and those without heart failure entered the prevention trial (n = 4228). Follow-up averaged 40 months. In each trial there were significant reductions in the number of patients developing myocardial infarction (treatment trial: 158 placebo vs 127 enalapril, p < 0.02; prevention trial: 204 vs 161 p < 0.01) or unstable angina (240 vs 187 p < 0.001; 355 vs 312, p < 0.05). Combined, there were 362 placebo group patients with myocardial infarction compared with 288 in the enalapril group (risk reduction 23%, 95% CI 11-34%; p < 0.001). 595 placebo group patients developed unstable angina compared with 499 in the enalapril group (risk reduction 20%, 95% CI 9-29%, p < 0.001). There was also a reduction in cardiac deaths (711 placebo, 615 enalapril; p < 0.003), so that the reduction in the combined endpoint of deaths, myocardial infarction, and unstable angina was highly significant (20% risk reduction, 95% CI 14-26%; p < 0.0001). Enalapril treatment significantly reduced myocardial infarction, unstable angina, and cardiac mortality in patients with low ejection fractions. Topics: Angina, Unstable; Blood Pressure; Death, Sudden, Cardiac; Enalapril; Female; Heart Failure; Humans; Incidence; Male; Myocardial Infarction; Prognosis; Prospective Studies; Risk Factors; Stroke Volume; Time Factors | 1992 |
Enalapril and exercise-induced hyperkalemia. A study of patients randomized to double-blind treatment with enalapril or placebo after acute myocardial infarction.
During exercise a marked increase in plasma potassium in healthy subjects has repeatedly been demonstrated. In patients on treatment with angiotensin-converting enzyme inhibitors this may be further augmented. Therefore, the aim of present study was to evaluate the effect of enalapril on exercise-induced hyperkalemia. This was done in patients with acute myocardial infarction randomized to double-blind treatment with enalapril 10-20 mg per day (n = 7) or placebo (n = 6) within 24 h of onset of chest pain, and the results were compared with data from healthy control subjects (n = 11). Baseline plasma potassium did not differ between the three groups; i.e. 4.2, 4.0, and 4.1 mmol/l, respectively. An incremental, symptom-limited, bicycle exercise test was done one month after the myocardial infarction, and blood samples were taken for determination of plasma potassium. The exercise-induced increase in plasma potassium was not higher in the enalapril group as compared to the placebo and control groups, and there was no difference between the enalapril and placebo group, the specific values being 0.6 vs. 0.6 and 0.7 mmol/l, respectively. No difference was observed in the slope (dK/dt) between the 3 groups. In conclusion, enalapril at a dosage of 10-20 mg per day does not provoke any augmentation of the increase in plasma potassium during exercise. Topics: Adult; Aged; Bias; Creatine Kinase; Double-Blind Method; Enalapril; Exercise Test; Female; Hemodynamics; Humans; Hyperkalemia; Isoenzymes; Male; Middle Aged; Myocardial Infarction; Potassium | 1992 |
Effects of the early administration of enalapril on mortality in patients with acute myocardial infarction. Results of the Cooperative New Scandinavian Enalapril Survival Study II (CONSENSUS II)
Long-term administration of angiotensin-converting--enzyme (ACE) inhibitors has been shown to improve survival in patients with symptomatic left ventricular failure and to attenuate left ventricular dilatation in patients with myocardial infarction. We studied whether mortality could be reduced during the 6 months after an acute myocardial infarction with use of the ACE inhibitor enalapril.. At 103 Scandinavian centers patients with acute myocardial infarctions and blood pressure above 100/60 mm Hg were randomly assigned to treatment with either enalapril or placebo, in addition to conventional therapy. Therapy was initiated with an intravenous infusion of enalapril (enalaprilat) within 24 hours after the onset of chest pain, followed by administration of oral enalapril.. Of the 6090 patients enrolled, 3046 were assigned to placebo and 3044 to enalapril. The life-table mortality rates in the two groups at one and six months were not significantly different (6.3 and 10.2 percent in the placebo group vs. 7.2 and 11.0 percent in the enalapril group, P = 0.26). The relative risk of death in the enalapril group was 1.10 (95 percent confidence interval, 0.93 to 1.29). Death due to progressive heart failure occurred in 104 patients (3.4 percent) in the placebo group and 132 (4.3 percent) in the enalapril group (P = 0.06). Therapy had to be changed because of worsening heart failure in 30 percent of the placebo group and 27 percent of the enalapril group (P less than 0.006). Early hypotension (systolic pressure less than 90 mm Hg or diastolic pressure less than 50 mm Hg) occurred in 12 percent of the enalapril group and 3 percent of the placebo group (P less than 0.001).. Enalapril therapy started within 24 hours of the onset of acute myocardial infarction does not improve survival during the 180 days after infarction. Topics: Administration, Oral; Aged; Blood Pressure; Double-Blind Method; Enalapril; Female; Heart Failure; Humans; Infusions, Parenteral; Male; Myocardial Infarction; Survival Rate; Ventricular Function, Left | 1992 |
The prevention of heart failure--a new agenda.
Topics: Angiotensin-Converting Enzyme Inhibitors; Captopril; Cardiovascular Diseases; Enalapril; Follow-Up Studies; Heart Failure; Humans; Myocardial Infarction; Ventricular Function, Left | 1992 |
Effect of enalapril on plasma atrial natriuretic peptide in late recovery phase of acute myocardial infarction.
A 12 week randomised, double blind, placebo controlled study on the effect of enalapril (5-20 mg daily) on the concentration of plasma atrial natriuretic peptide level and activity of the sympathetic nervous system and renin angiotensin system was done on 27 patients who had suffered an uncomplicated acute myocardial infarction two to six months earlier. None of our patients needed drug treatment for heart failure, but their exercise capacity was markedly limited. Plasma neurohormone concentrations at baseline and after 12 weeks of treatment were also compared with those of healthy controls. Concentrations of plasma atrial natriuretic peptide concentrations remained high throughout the study in those patients on beta-blockers. Enalapril treatment had no definite effect on the concentrations of plasma atrial natriuretic peptide or other neurohormone. Topics: Aldosterone; Atrial Natriuretic Factor; Double-Blind Method; Enalapril; Epinephrine; Female; Humans; Male; Middle Aged; Myocardial Infarction; Norepinephrine; Renin | 1991 |
Effect of long-term enalapril therapy on cardiopulmonary exercise performance in men with mild heart failure and previous myocardial infarction.
Forty-one men with documented myocardial infarction greater than 6 months previously were randomized to long-term (48 weeks) therapy with placebo or enalapril on a double-blind basis. All patients were receiving concurrent therapy with digitalis and a diuretic drug for symptomatic heart failure (functional class II or III). The mean age was 64 +/- 7.3 years and no patient suffered from exertional chest pain. Patients underwent maximal cardiopulmonary exertional chest pain. Patients underwent maximal cardiopulmonary exercise testing to exhaustion on an ergometer cycle nine times over the course of 48 weeks. Gas exchange data were collected on a breath by breath basis with use of a continuous ramp protocol. In the placebo group (n = 21), the mean (+/- SD) peak oxygen consumption (VO2) at baseline was 18.8 +/- 5.2 versus 18.5 +/- 5.5 ml/kg per min at 48 weeks (-1.4%, p = NS). In the enalapril group (n = 20), the corresponding values were 18.1 +/- 3.1 versus 18.3 +/- 2.6 ml/kg per min (+2.8%, p = NS). The mean VO2 at the anaerobic threshold for the placebo group at baseline study was 13.1 +/- 3.5 versus 12.8 +/- 2.1 ml/kg per min at 48 weeks (-2.2%, p = NS). The corresponding values for the enalapril group were 11.8 +/- 2.3 versus 11.8 +/- 2.4 ml/kg per min (+1.4%, p = NS). The mean total exercise duration in the placebo group at baseline study was 589 +/- 153 versus 620 +/- 181 s at 48 weeks (+5.4%, p = NS).(ABSTRACT TRUNCATED AT 250 WORDS) Topics: Anaerobic Threshold; Double-Blind Method; Enalapril; Exercise; Exercise Test; Heart Failure; Humans; Male; Middle Aged; Myocardial Infarction; Pulmonary Gas Exchange; Renin-Angiotensin System; Time Factors | 1991 |
Effects of long-term enalapril therapy on cardiopulmonary exercise performance after myocardial infarction.
The Enalapril Postinfarction Exercise (EPIE) trial was designed to study the effect of enalapril treatment on peak and submaximal cardiopulmonary exercise performance over the course of 1 year in men after myocardial infarction with mild exercise intolerance.. One hundred sixty men with a peak VO2 less than 25 ml/kg/min and without effort angina were randomized to receive enalapril 20 mg qd or placebo on a double-blind basis. The mean age was 60.3 +/- 7.6 years. All patients received concurrent beta-blocker therapy for secondary prophylaxis. Treatment began at 21 days (group 1, n = 100) or more than 6 months after infarction (group 2, n = 60). Patients underwent exercise with real-time gas-exchange analysis nine times over the course of 48 weeks. In group 1, improvement in exercise performance occurred during the course of the trial in both groups of patients receiving placebo or enalapril. The mean peak VO2 for the placebo-treated patients in group 1 increased from 18.3 +/- 3.4 ml/kg/min by 4.9% at 48 weeks (p less than 0.05). The corresponding values for enalapril-treated patients were 18.9 +/- 3.8 ml/kg/min with a 3.7% increase (p = 0.07). Total exercise time increased in the placebo-treated patients from 645 +/- 96 seconds by 7.3% (p less than 0.01). Corresponding values for enalapril-treated patients were 674 +/- 103 seconds with a 5.4% increase (p less than 0.01). In group 2, the mean peak VO2 at baseline for the placebo-treated patients of 20.3 +/- 3.8 ml/kg/min increased by 4.4% at 48 weeks (p = NS). The corresponding values for enalapril-treated patients were 19.2 +/- 3.6 ml/kg/min with a 2.6% increase (p = NS). Total exercise time increased in the placebo-treated patients from 677 +/- 114 seconds by 0.7% (p = NS). Corresponding values for enalapril-treated patients were 659 +/- 99 seconds with a 1.1% increase (p = NS). There were no significant differences between the placebo and enalapril subgroups at any time with regard to peak VO2, exercise duration, or the VO2 at the anaerobic threshold.. This trial demonstrates that long-term converting enzyme inhibition with enalapril had no significant effect on the peak or submaximal cardiopulmonary exercise performance over the course of 1 year in men after myocardial infarction with only mildly reduced exercise capacity. Topics: Aged; Blood Pressure; Enalapril; Exercise Test; Heart; Humans; Lung; Male; Middle Aged; Myocardial Infarction; Oxygen Consumption; Physical Endurance; Physical Exertion; Prospective Studies; Pulmonary Gas Exchange; Systole; Time Factors | 1991 |
[Consensus with CONSENSUS (Cooperative North Scandinavian Enalapril Survival Study)].
Topics: Clinical Trials as Topic; Enalapril; Heart Failure; Humans; Myocardial Infarction | 1988 |
The risk-benefit equation: when to initiate treatment.
Topics: Adrenergic beta-Antagonists; Angiotensin-Converting Enzyme Inhibitors; Antihypertensive Agents; Arrhythmias, Cardiac; Benzothiadiazines; Blood Pressure; Clinical Trials as Topic; Death, Sudden; Diastole; Dipeptides; Diuretics; Double-Blind Method; Enalapril; Follow-Up Studies; Humans; Hypertension; Myocardial Infarction; Risk; Sodium Chloride Symporter Inhibitors | 1984 |
Other Studies
111 other study(ies) available for enalapril and Myocardial-Infarction
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Treatment with apoptosis inhibitor restores cognitive impairment in rats with myocardial infarction.
We previously reported that apoptosis is responsible for cognitive impairment in rats with myocardial infarction (MI). Acute administration of an apoptosis inhibitor (Z-vad) effectively reduced brain inflammation in rats with cardiac ischemia/reperfusion injury. However, the beneficial effects of Z-vad on cognitive function, brain inflammation, mitochondrial function, cell death pathways, and neurogenesis in MI rats have not been investigated. Male rats were divided into sham or MI groups (left anterior descending coronary ligation). A successful MI was determined by a reduction of ejection fraction <50 %. Then, MI rats were allocated to receive vehicle, enalapril (10 mg/kg, a positive control), and Z-vad (1 mg/kg) for 4 weeks. Cardiac function, cognitive function, and molecular analysis were investigated. MI rats exhibited cardiac dysfunction, cognitive impairment, blood brain barrier (BBB) breakdown, dendritic spine loss, which were accompanied by an upregulation of oxidative stress, mitochondrial dysfunction, and apoptosis. Chronic treatment with Z-vad attenuated cardiac dysfunction following MI to the same extent as enalapril. Z-vad successfully improved cognitive function and restored dendritic spine density in MI rats through a reduction of systemic oxidative stress and brain mitochondrial dysfunction similar to enalapril. Moreover, Z-vad provided greater efficacy than enalapril in enhancing mitophagy, neurogenesis, synaptic proteins and reducing apoptosis in hippocampus of MI rats. Nevertheless, neither Z-vad nor enalapril increased BBB tight junction protein. In conclusion, treatment with an apoptosis inhibitor reduced cognitive impairment in MI rats via reducing oxidative stress, mitochondrial dysfunction, apoptosis, and restoring dendritic spine density, together with enhancing mitophagy and neurogenesis. Topics: Animals; Apoptosis; Cognitive Dysfunction; Enalapril; Encephalitis; Male; Myocardial Infarction; Rats | 2023 |
Angiotensin-converting enzyme inhibitor treatment early after myocardial infarction attenuates acute cardiac and neuroinflammation without effect on chronic neuroinflammation.
Myocardial infarction (MI) triggers a local inflammatory response which orchestrates cardiac repair and contributes to concurrent neuroinflammation. Angiotensin-converting enzyme (ACE) inhibitor therapy not only attenuates cardiac remodeling by interfering with the neurohumoral system, but also influences acute leukocyte mobilization from hematopoietic reservoirs. Here, we seek to dissect the anti-inflammatory and anti-remodeling contributions of ACE inhibitors to the benefit of heart and brain outcomes after MI.. C57BL/6 mice underwent permanent coronary artery ligation (n = 41) or sham surgery (n = 9). Subgroups received ACE inhibitor enalapril (20 mg/kg, oral) either early (anti-inflammatory strategy; 10 days treatment beginning 3 days prior to surgery; n = 9) or delayed (anti-remodeling; continuous from 7 days post-MI; n = 16), or no therapy (n = 16). Cardiac and neuroinflammation were serially investigated using whole-body macrophage- and microglia-targeted translocator protein (TSPO) PET at 3 days, 7 days, and 8 weeks. In vivo PET signal was validated by autoradiography and histopathology.. Myocardial infarction evoked higher TSPO signal in the infarct region at 3 days and 7 days compared with sham (p < 0.001), with concurrent elevation in brain TSPO signal (+ 18%, p = 0.005). At 8 weeks after MI, remote myocardium TSPO signal was increased, consistent with mitochondrial stress, and corresponding to recurrent neuroinflammation. Early enalapril treatment lowered the acute TSPO signal in the heart and brain by 55% (p < 0.001) and 14% (p = 0.045), respectively. The acute infarct signal predicted late functional outcome (r = 0.418, p = 0.038). Delayed enalapril treatment reduced chronic myocardial TSPO signal, consistent with alleviated mitochondrial stress. Early enalapril therapy tended to lower TSPO signal in the failing myocardium at 8 weeks after MI (p = 0.090) without an effect on chronic neuroinflammation.. Whole-body TSPO PET identifies myocardial macrophage infiltration and neuroinflammation after MI, and altered cardiomyocyte mitochondrial density in chronic heart failure. Improved chronic cardiac outcome by enalapril treatment derives partially from acute anti-inflammatory activity with complementary benefits in later stages. Whereas early ACE inhibitor therapy lowers acute neuroinflammation, chronic alleviation is not achieved by early or delayed ACE inhibitor therapy, suggesting a more complex mechanism underlying recurrent neuroinflammation in ischemic heart failure. Topics: Acute Disease; Angiotensin-Converting Enzyme Inhibitors; Animals; Chronic Disease; Enalapril; Heart; Inflammation; Mice; Mice, Inbred C57BL; Myocardial Infarction; Nervous System Diseases | 2020 |
Protective effects and chemical composition of Corchorus olitorius leaf fractions against isoproterenol-induced myocardial injury through p65NFkB-dependent anti-apoptotic pathway in rats.
Background The fractions of Corchorus olitorius leaf (COLF) were evaluated against oxidative stress, inflammation and apoptosis in isoproterenol (ISO)-induced myocardial injury (MI) Wistar rats. Methods The n-hexane, dichloromethane, ethylacetate and ethanol fractions were obtained from COLF extract. Male Wistar strains were randomly grouped into 11 groups (n = 6 in each group), which comprises normal control group, MI control group, 4 fraction groups with two doses (50 and 100 mg/kg) and enalapril (10 mg/kg). The sera were obtained for biochemical studies like AOPP (advance oxidized protein product), CRP (C-reactive protein), LDH (lactate dehydrogenase), CKMB (creatine kinase-MB) and myocardial tissue obtained for GSH, p65NFkB, bax, bcl2, p53 and p65NFkB assays. Results The subcutaneous administration of ISO increased the serum level of CRP, LDH and CKMB significantly (p < 0.05) and decreased serum AOPP, tissue GSH and p65NFkB (p < 0.05) in the infarction control rats. Pretreatment with COLF and enalapril increased the tissue GSH and p65NFkB levels (p < 0.05) and significantly reduced serum CRP, AOPP, LDH and CKMB. The dichloromethane fraction (CODCM) being the most active was chosen to evaluate the anti-apoptotic effect. CODCM (50 and 100 mg/kg) and enalapril showed a significant (p < 0.05) effect through severe expression of p65NFkB, which correlates with increased bcl2 protein expression, decreased bax protein and p53 expression. Gas chromatography mass spectrometry revealed the presence of 26 compounds in CODCM. Conclusions From the present study, COLF protected the myocardial tissue against ischemic injury in rats probably via the p65NFkB-dependent anti-apoptotic pathway and attenuation of pro-inflammatory marker level. Topics: Animals; Apoptosis; Cardiotonic Agents; Corchorus; Disease Models, Animal; Dose-Response Relationship, Drug; Enalapril; Gas Chromatography-Mass Spectrometry; Isoproterenol; Male; Myocardial Infarction; Oxidative Stress; Plant Extracts; Plant Leaves; Rats; Rats, Wistar; Transcription Factor RelA | 2020 |
Brain renin-angiotensin system blockade with orally active aminopeptidase A inhibitor prevents cardiac dysfunction after myocardial infarction in mice.
Brain renin-angiotensin system (RAS) hyperactivity has been implicated in sympathetic hyperactivity and progressive left ventricular (LV) dysfunction after myocardial infarction (MI). Angiotensin III, generated by aminopeptidase A (APA), is one of the main effector peptides of the brain RAS in the control of cardiac function. We hypothesized that orally administered firibastat (previously named RB150), an APA inhibitor prodrug, would attenuate heart failure (HF) development after MI in mice, by blocking brain RAS hyperactivity. Two days after MI, adult male CD1 mice were randomized to three groups, for four to eight weeks of oral treatment with vehicle (MI + vehicle), firibastat (150 mg/kg; MI + firibastat) or the angiotensin I converting enzyme inhibitor enalapril (1 mg/kg; MI + enalapril) as a positive control. From one to four weeks post-MI, brain APA hyperactivity occurred, contributing to brain RAS hyperactivity. Firibastat treatment normalized brain APA hyperactivity, with a return to the control values measured in sham group two weeks after MI. Four and six weeks after MI, MI + firibastat mice had a significant lower LV end-diastolic pressure, LV end-systolic diameter and volume, and a higher LV ejection fraction than MI + vehicle mice. Moreover, the mRNA levels of biomarkers of HF (Myh7, Bnp and Anf) were significantly lower following firibastat treatment. For a similar infarct size, the peri-infarct area of MI + firibastat mice displayed lower levels of mRNA for Ctgf and collagen types I and III (markers of fibrosis) than MI + vehicle mice. Thus, chronic oral firibastat administration after MI in mice prevents cardiac dysfunction by normalizing brain APA hyperactivity, and attenuates cardiac hypertrophy and fibrosis. Topics: Administration, Oral; Animals; Biomarkers; Brain; Cardiomegaly; Disease Models, Animal; Enalapril; Enzyme Inhibitors; Fibrosis; Glutamyl Aminopeptidase; Heart; Heart Failure; Inflammation Mediators; Male; Mice; Myocardial Infarction; Renin-Angiotensin System; Stroke Volume | 2019 |
Is the cardioprotective effect of the ACE2 activator diminazene aceturate more potent than the ACE inhibitor enalapril on acute myocardial infarction in rats?
Myocardial infarction is a major cause of cardiac dysfunction. All components of the cardiac renin-angiotensin system (RAS) are upregulated in myocardial infarction. Angiotensin-converting enzyme (ACE) and ACE2 are key enzymes involved in synthesis of components of RAS and provide a counter-regulatory mechanism within RAS. We compared the cardioprotective effect of the ACE2 activator diminazene aceturate (DIZE) versus the ACE inhibitor enalapril on post acute myocardial infarction (AMI) ventricular dysfunction in rats. Adult male rats received subcutaneous injections of either saline (control) or isoproterenol (85 mg/kg) to induce AMI. Rats with AMI confirmed biochemically and by ECG, were either left untreated (AMI) or administered DIZE (AMI + DIZE) or enalapril (AMI + enalapril) daily for 4 weeks. DIZE caused a significant activation of cardiac ACE2 compared with enalapril. DIZE caused a significantly greater enhancement of cardiac hemodynamics. DIZE also caused greater reductions in heart-type fatty acid binding protein (H-FABP), β-myosin heavy chain (β-MYH), and in heart mass to total body mass ratio. These results indicated that activation of cardiac ACE2 by DIZE enhanced the protective axis of RAS and improved myocardial function following AMI, whereas enalapril was not sufficient to restore all cardiac parameters back to normal. Topics: Acute Disease; Angiotensin-Converting Enzyme 2; Angiotensin-Converting Enzyme Inhibitors; Animals; Cardiotonic Agents; Diminazene; Enalapril; Enzyme Activation; Heart Ventricles; Hypertrophy, Right Ventricular; Male; Myocardial Infarction; Peptidyl-Dipeptidase A; Rats; Rats, Wistar | 2019 |
Effects of dipeptidyl peptidase-4 inhibitor in insulin-resistant rats with myocardial infarction.
Adverse cardiac remodeling after myocardial infarction (MI) leads to progressive heart failure. Obese-insulin resistance increases risks of MI and heart failure. Although dipeptidyl peptidase-4 (DPP4) inhibitor is known to exert cardioprotection, its effects on adverse remodeling after MI in obese-insulin-resistant rats are unclear. We hypothesized that DPP4 inhibitor reduces adverse left ventricular (LV) remodeling and LV dysfunction in obese-insulin-resistant rats with MI. Rats were fed either normal diet (ND) or high-fat diet (HFD) for 12 weeks to induce obese-insulin resistance, followed by left anterior descending coronary artery ligation to induce MI. Then, rats in each dietary group were divided into five subgroups to receive vehicle, enalapril (10mg/kg/day), metformin (30mg/kg/day), DPP4 inhibitor vildagliptin (3mg/kg/day), or combined metformin and vildagliptin for 8 weeks. Heart rate variability (HRV), LV function, pathological and biochemical studies for LV remodeling, and cardiomyocyte apoptosis were determined. Obese-insulin-resistant rats had severe insulin resistance and LV dysfunction. HFD rats had a higher mortality rate than ND rats, and all treatments reduced the mortality rate in obese-insulin-resistant rats. Although all drugs improved insulin resistance, HRV, LV function as well as reduced cardiac hypertrophy and fibrosis, vildagliptin effectively reduced cardiomyocyte cross-sectional areas more than enalapril and was related to markedly decreased ERK1/2 phosphorylation. In ND rats with MI, metformin neither improved LV ejection fraction nor reduced cardiac fibrosis. The infarct size and transforming growth factor-β expression were not different among groups. In obese-insulin-resistant rats with chronic MI, DPP4 inhibitor vildagliptin exerts better cardioprotection than enalapril in attenuating adverse LV remodeling. Topics: Adamantane; Animals; Cardiotonic Agents; Dipeptidyl Peptidase 4; Dipeptidyl-Peptidase IV Inhibitors; Enalapril; Heart Rate; Hypoglycemic Agents; Insulin Resistance; Male; Metformin; Myocardial Infarction; Nitriles; Oxidative Stress; Pyrrolidines; Rats; Rats, Wistar; Ventricular Remodeling; Vildagliptin | 2016 |
Dipeptidyl peptidase-4 inhibitor improves cardiac function by attenuating adverse cardiac remodelling in rats with chronic myocardial infarction.
What is the central question of this study? Although cardioprotective effects of dipeptidyl peptidase-4 (DPP-4) inhibitors have been demonstrated, their cardiac effects in chronic myocardial infarction (MI) are unclear. We determined the effects of a DPP-4 inhibitor on cardiac function and remodelling in rats with chronic MI. What is the main finding and its importance? We demonstrated, for the first time, that DPP-4 inhibitor, but not metformin, exerted similar efficacy in improving cardiac function and attenuating cardiac fibrosis compared with enalapril in rats with chronic MI. These findings reveal benefits additional to the glycaemic control by the DPP-4 inhibitor in chronic MI, and it might become the new drug of choice for MI in patients with diabetes mellitus. Adverse cardiac remodelling after myocardial infarction (MI) leads to progressive heart failure. Dipeptidyl peptidase-4 (DPP-4) inhibitors are new antidiabetic drugs that exert cardioprotection. However, their role in cardiac function and remodelling in chronic MI is unclear. We hypothesized that the DPP-4 inhibitor vildagliptin reduces adverse cardiac remodelling and improves cardiac function in rats with chronic MI. These effects were also compared with enalapril and metformin. Male Wistar rats (n = 36) with chronic MI induced by ligation of the left anterior descending coronary artery were divided into six groups to receive vehicle, vildagliptin (3 mg kg(-1) day(-1) ), metformin (30 mg kg(-1) day(-1) ), enalapril (10 mg kg(-1) day(-1) ), combined metformin and enalapril or combined vildagliptin and enalapril for 8 weeks. At the end of the study, plasma malondialdehyde (MDA), heart rate variability (HRV), left ventricular (LV) function, pathological and biochemical studies of cardiac remodelling were investigated. Our study demonstrated that rats with chronic MI had increased oxidative stress levels, depressed HRV, adverse cardiac remodelling, indicated by cardiac fibrosis, and LV dysfunction. Treatment with vildagliptin or enalapril significantly decreased oxidative stress, attenuated cardiac fibrosis and improved HRV and LV function. We conclude that vildagliptin exerts similar cardioprotective effects to enalapril in attenuating oxidative stress and cardiac fibrosis and improving cardiac function in rats with chronic MI. Metformin does not provide these benefits in this model. Moreover, addition of either metformin or vildagliptin to enalapril does not provide additional benefit in a Topics: Adamantane; Angiotensin-Converting Enzyme Inhibitors; Animals; Dipeptidyl Peptidase 4; Dipeptidyl-Peptidase IV Inhibitors; Disease Models, Animal; Enalapril; Fibrosis; Heart Rate; Hypoglycemic Agents; Male; Metformin; Myocardial Infarction; Myocardium; Nitriles; Oxidative Stress; Pyrrolidines; Rats, Wistar; Recovery of Function; Signal Transduction; Time Factors; Ventricular Dysfunction, Left; Ventricular Function, Left; Ventricular Remodeling; Vildagliptin | 2015 |
Inhibition of neutrophil-dependent cytotoxicity for human endothelial cells by ACE inhibitors.
Angiotensin-converting enzyme inhibitors (ACEi) have immunomodulating properties and have been suggested to protect against endothelial injury, for example myocardial infarction and reperfusion injury. We tested whether two ACEi (captopril and enalapril), differing in a thiol group, protected human umbilical vein endothelial cells (HUVEC) from cytotoxicity induced by polymorphonuclear neutrophils (PMN) in vitro, when cells were activated by tumour necrosis factor-α (TNFα) or the arachidonate derivative lipoxin-A4 (LXA4 ), using separate cytotoxicity pathways. When (51) Cr labelled HUVEC were treated with captopril (0-500 μm) or enalapril (0-100 μm) for 2 h and then activated by TNFα (100 ng/ml) for 24 h, a significant, dose-dependent reduction of (51) Cr release was observed. Similarly, captopril reduced (51) Cr release when LXA4 (0.1 μm) was used to stimulate PMN for 4 h. Among previously defined mechanisms of significance for the cytotoxic reaction, expression of ICAM-1, but not intracellular Ca(2+) changes in PMN or PMN adherence to HUVEC, were reduced by ACEi treatment. Moreover, both ACEi inhibited HUVEC surface expression of TNFα receptor I (but not II). Thus, these ACEi, particularly captopril, interfere with PMN-induced cytotoxicity for endothelial cells by modulating pro-inflammatory surface receptors, which is a novel effect that might be explored for further therapeutic approaches. Topics: Angiotensin-Converting Enzyme Inhibitors; Captopril; Cell Adhesion; Cells, Cultured; Cytotoxicity, Immunologic; Enalapril; Human Umbilical Vein Endothelial Cells; Humans; Immunologic Factors; Immunomodulation; Intercellular Adhesion Molecule-1; Lipoxins; Myocardial Infarction; Neutrophils; Receptors, Tumor Necrosis Factor; Reperfusion Injury; Tumor Necrosis Factor-alpha | 2014 |
Impact of ACE inhibitors on mortality and morbidity in patients with AMI: Does tissue selectivity matter?
To examine the impact of tissue selectivity of angiotensin-converting enzyme (ACE) inhibitors on mortality and morbidity in patients following acute myocardial infarction (AMI).. A retrospective cohort study using a Medicaid claims database was conducted. Patients hospitalized for an AMI and subsequently filling a prescription for an ACE inhibitor were followed longitudinally for the occurrence of cardiovascular-related hospitalizations and all-cause mortality. A subanalysis was also conducted to account for switching/discontinuation of ACE inhibitor therapy. Stepwise (forward conditional) Cox-proportional hazards models were used to analyze the effect of tissue selectivity on study outcomes.. The final study sample consisted of 689 AMI and the results indicated that tissue-selective ACE inhibitors had a protective effect against hospitalization due to stroke/transient ischemic attack (TIA) (hazard ratio [HR] = 0.265; 95% confidence interval [CI] = 0.101-0.698). A similar lower rate in hospitalizations due to heart failure was observed in the group using tissue-selective ACE inhibitors; however, the results were not statistically significant (HR = 0.681; 95% CI = 0.436-1.063). A protective effect was also observed on the combined outcome of hospitalization due to any cardiovascular condition (HR = 0.712; 95% CI = 0.536-0.945). Hospitalizations due to recurrent AMI, need for coronary revascularization procedures, and mortality were not significantly different between patients using tissue-selective and non-tissue-selective ACE inhibitors. The completer subanalysis provided similar findings regarding the impact of tissue selectivity on study outcomes.. Tissue-selective ACE inhibitors may have a protective effect against hospitalization due to stroke/TIA or heart failure when compared to non-tissue-selective ACE inhibitors for patients following AMI. Topics: Adult; Angiotensin-Converting Enzyme Inhibitors; Antihypertensive Agents; Cardiovascular Diseases; Comorbidity; Enalapril; Female; Heart Failure; Humans; Lisinopril; Longitudinal Studies; Male; Middle Aged; Multivariate Analysis; Myocardial Infarction; Organ Specificity; Proportional Hazards Models; Ramipril; Retrospective Studies; Secondary Prevention; Stroke; Survival Analysis | 2011 |
Therapeutic effects of continuous infusion of brain natriuretic peptides on postmyocardial infarction ventricular remodelling in rats.
Previous studies have shown protective effects of brain natriuretic peptide (BNP) against the postmyocardial infarction (MI) remodelling process. The transcription factor NF-κB is known to play an important role after MI.. To investigate if NF-κB is involved in the protective effects of BNP against adverse post-MI remodelling.. Rats were randomly assigned to five groups: sham-operation; MI by coronary ligation; MI treated with chronic BNP infusion; MI treated with enalapril; MI treated with BNP+enalapril. Rats were closely monitored for survival rate analysis. Rats from each group were sacrificed on days 3, 7 and 28 postoperation.. The results showed that chronic continuous BNP infusion achieved similar effects to enalapril therapy, as evidenced by improved survival rate within the 28-day observation period compared with MI group rats; this effect was closely associated with preserved cardiac geometry and performance. The treatment combination did not offer extra benefits in terms of survival rate. Both BNP and enalapril therapy produced higher heart tissue concentrations of cyclic guanosine monophosphate and lower expression levels of inflammatory cytokines, including tumour necrosis factor-α, interleukin-1 and interleukin-6. These benefits were associated with lower phosphorylation levels of NF-κB subunits IκBα, p50 and p65. While enalapril significantly inhibited extracellular matrix remodelling via regulation of the protein expression ratio of matrix metalloproteinase/tissue inhibitor of metalloproteinase and the activity of matrix metalloproteinase, these variables were not affected by BNP, indicating that the two therapies involve different mechanisms.. Chronic BNP infusion can provide beneficial effects against adverse post-MI remodelling. Topics: Angiotensin II; Angiotensin-Converting Enzyme Inhibitors; Animals; Cardiovascular Agents; Collagen; Cyclic GMP; Disease Models, Animal; Enalapril; Hemodynamics; I-kappa B Proteins; Inflammation Mediators; Infusion Pumps, Implantable; Infusions, Intravenous; Male; Matrix Metalloproteinase 2; Matrix Metalloproteinase 9; Myocardial Infarction; Myocardium; Natriuretic Peptide, Brain; NF-kappa B p50 Subunit; NF-KappaB Inhibitor alpha; Phosphorylation; Rats; Rats, Sprague-Dawley; Time Factors; Tissue Inhibitor of Metalloproteinase-1; Transcription Factor RelA; Ventricular Function, Left; Ventricular Remodeling | 2011 |
A natural p300-specific histone acetyltransferase inhibitor, curcumin, in addition to angiotensin-converting enzyme inhibitor, exerts beneficial effects on left ventricular systolic function after myocardial infarction in rats.
A natural p300-specific histone acetyltransferase (HAT) inhibitor, curcumin, may have therapeutic potential for heart failure. However, it is unclear whether curcumin exhibits beneficial additive or synergistic effects on conventional therapy with angiotensin-converting enzyme inhibitors (ACEIs).. Rats were subjected to a sham operation or left coronary artery ligation. One week later, 34 rats with a moderate sized myocardial infarction (MI) were randomly assigned to 4 groups: solvents as control (n = 8), enalapril (an ACEI, 10 mg·kg⁻¹·day⁻¹) alone (n=8), curcumin (50 mg·kg⁻¹·day⁻¹) alone (n = 9) and enalapril plus curcumin (n = 9). Daily oral treatment was repeated and continued for 6 weeks. Echocardiographic data were similar among the 4 groups before treatment. After treatment, left ventricular (LV) fractional shortening (FS) was significantly higher in the enalapril (29.0 ± 1.9%) and curcumin (30.8 ± 1.7%) groups than in the vehicle group (19.7 ± 1.6%). Notably, LVFS further increased in the enalapril/curcumin combination group (34.4 ± 1.8%). Histologically, cardiomyocyte diameter in the non-infarct area was smaller in the enalapril/curcumin combination group than in the enalapril group. Perivascular fibrosis was significantly reduced in the enalapril/curcumin group compared with the curcumin group.. A natural non-toxic dietary compound, curcumin, combined with an ACEI exerts beneficial effects on post-MI LV systolic function in rats. Topics: Angiotensin-Converting Enzyme Inhibitors; Animals; Curcumin; E1A-Associated p300 Protein; Electrocardiography; Enalapril; Heart Failure; Histone Deacetylase Inhibitors; Male; Myocardial Infarction; Rats; Rats, Sprague-Dawley; Systole; Ventricular Function, Left | 2011 |
Angiotensin-(1-9) regulates cardiac hypertrophy in vivo and in vitro.
Angiotensin-(1-9) is present in human and rat plasma and its circulating levels increased early after myocardial infarction or in animals treated with angiotensin-converting enzyme inhibitor. However, the cardiovascular effects of this peptide are unknown.. To determine whether angiotensin-(1-9) is a novel anti-cardiac hypertrophy factor in vitro and in vivo and whether this peptide is involved in the pharmacological effects of cardiovascular drugs acting on the renin-angiotensin system.. The administration of angiotensin-(1-9) to myocardial infarcted rats by osmotic minipumps (450 ng/kg per min, n = 6) vs. vehicle (n = 8) for 2 weeks decreased plasma angiotensin II levels, inhibited angiotensin-converting enzyme activity and also prevented cardiac myocyte hypertrophy. However, cardiac myocyte hypertrophy attenuation triggered by angiotensin-(1-9) was not modified with the simultaneous administration of the angiotensin-(1-7) receptor antagonist A779 (100 ng/kg per min, n = 6). In experiments in vitro with cultured cardiac myocytes incubated with norepinephrine (10 micromol/l) or with insulin-like growth factor-1 (10 nmol/l), angiotensin-(1-9) also prevented hypertrophy. In other experimental setting, myocardial infarcted rats (n = 37) were randomized to receive either vehicle (n = 12), enalapril (10 mg/kg per day, n = 12) or angiotensin II receptor blocker candesartan (10 mg/kg per day, n = 13) for 8 weeks. Both drugs prevented left ventricle hypertrophy and increased plasma angiotensin-(1-9) levels by several folds. Angiotensin-(1-9) levels correlated negatively with different left ventricular hypertrophy markers even after adjustment for blood pressure reduction.. Angiotensin-(1-9) is an effective and a novel anti-cardiac hypertrophy agent not acting via the Mas receptor. Topics: Angiotensin I; Angiotensin II; Angiotensin II Type 1 Receptor Blockers; Angiotensin-Converting Enzyme Inhibitors; Animals; Benzimidazoles; Biphenyl Compounds; Bradykinin; Cardiomegaly; Cell Enlargement; Cells, Cultured; Enalapril; Humans; Hypertrophy, Left Ventricular; In Vitro Techniques; Insulin-Like Growth Factor I; Male; Myocardial Infarction; Myocytes, Cardiac; Norepinephrine; Peptide Fragments; Peptidyl-Dipeptidase A; Rats; Rats, Sprague-Dawley; Renin-Angiotensin System; Tetrazoles; Ventricular Function, Left | 2010 |
Angiotensin-converting enzyme inhibition prevents the release of monocytes from their splenic reservoir in mice with myocardial infarction.
Monocytes recruited to ischemic myocardium originate from a reservoir in the spleen, and the release from their splenic niche relies on angiotensin (Ang) II signaling.. Because monocytes are centrally involved in tissue repair after ischemia, we hypothesized that early angiotensin-converting enzyme (ACE) inhibitor therapy impacts healing after myocardial infarction partly via effects on monocyte traffic.. In a mouse model of permanent coronary ligation, enalapril arrested the release of monocytes from the splenic reservoir and consequently reduced their recruitment into the healing infarct by 45%, as quantified by flow cytometry of digested infarcts. Time-lapse intravital microscopy revealed that enalapril reduces monocyte motility in the spleen. In vitro migration assays and Western blotting showed that this was caused by reduced signaling through the Ang II type 1 receptor. We then studied the long-term consequences of blocked splenic monocyte release in atherosclerotic apolipoprotein (apo)E(-/-) mice, in which infarct healing is impaired because of excessive inflammation in the cardiac wound. Enalapril improved histologic healing biomarkers and reduced inflammation in infarcts measured by FMT-CT (fluorescence molecular tomography in conjunction with x-ray computed tomography) of proteolytic activity. ACE inhibition improved MRI-derived ejection fraction by 14% on day 21, despite initially comparable infarct size. In apoE(-/-) mice, ischemia/reperfusion injury resulted in larger infarct size and enhanced monocyte recruitment and was reversible by enalapril treatment. Splenectomy reproduced antiinflammatory effects of enalapril.. This study suggests that benefits of early ACE inhibition after myocardial infarction can partially be attributed to its potent antiinflammatory impact on the splenic monocyte reservoir. Topics: Angiotensin-Converting Enzyme Inhibitors; Animals; Cell Movement; Enalapril; Female; Mice; Mice, Inbred C57BL; Mice, Knockout; Mice, Transgenic; Monocytes; Myocardial Infarction; Spleen | 2010 |
[Isolated systolic hypertension].
Topics: Age Factors; Aged, 80 and over; Antihypertensive Agents; Drug Combinations; Enalapril; Female; Humans; Hypertension; Myocardial Infarction; Nitrendipine; Risk Factors; Stroke; Systole | 2009 |
Impact of telmisartan on coronary stenting in patients with acute myocardial infarction compared with enalapril.
To determine whether telmisartan reduces in-stent restenosis (ISR) after coronary angioplasty using bare metal stent (BMS) in patients with acute myocardial infarction (AMI) compared with an angiotensin converting enzyme (ACE) inhibitor.. The efficacy of inhibition of renin-angiotensin-aldosterone system in patients with AMI has been established, and the prescription of ACE inhibitor is recommended as class I indication for all AMI patients, whereas that of angiotensin II receptor blocker (ARB) as class IIa. Telmisartan is a unique ARB since it has a peroxisome proliferator-activated receptor (PPAR) gamma activating effect which is known to reduce neointimal tissue proliferation after coronary stenting.. In 64 patients, telmisartan (20-40 mg per day) was orally administered for 6 months after stenting (telmisartan group). The incidence of ISR after stenting in these patients was retrospectively compared with those in the other 60 patients administrated enalapril (2.5-5 mg per day) (enalapril group).. There were no adverse events such as death, re-infarction and emergency bypass surgery in telmisartan group during a follow-up period for 6 months. The ISR rate was lower in telmisartan group (18.8%) than in enalapril group (33.3%) (p=0.06). However, percent diameter stenosis (%DS) at follow-up in telmisartan group was significantly smaller than in enalapril group (26.7+/-18.6% vs 38.0+/-23.9%, p=0.004). Late lumen loss was also significantly smaller in telmisartan group than in enalapril group (0.97+/-0.48 mm vs 1.19+/-0.68 mm, p=0.039).. Telmisartan not only is tolerable in patients with AMI but has a potential to reduce neointimal tissue proliferation after AMI treated with coronary angioplasty using BMS compared with enalapril. Topics: Angioplasty, Balloon, Coronary; Angiotensin II Type 1 Receptor Blockers; Angiotensin-Converting Enzyme Inhibitors; Benzimidazoles; Benzoates; Coronary Restenosis; Enalapril; Female; Humans; Incidence; Japan; Male; Middle Aged; Myocardial Infarction; Retrospective Studies; Stents; Telmisartan | 2009 |
[Equivalent preparations--equivalent package inserts?].
Topics: Antihypertensive Agents; Drug Labeling; Drugs, Generic; Enalapril; Humans; Myocardial Infarction; Stroke | 2008 |
Effect of L-2286, a poly(ADP-ribose)polymerase inhibitor and enalapril on myocardial remodeling and heart failure.
Increased activation of poly(ADP-ribose) polymerase (PARP) enzyme has been implicated in the pathogenesis of acute and chronic myocardial dysfunction. We have demonstrated the protective effect of PARP inhibitors against postinfarction myocardial remodeling and heart failure. The primary aim of our recent work was to compare the effect and efficacy of a potent PARP-inhibitor (L-2286) to enalapril, a widely used angiotensin-converting enzyme (ACE) inhibitor. in experimental heart failure model. Both L-2286 and enalapril were tested in a rat model of chronic heart failure after isoproterenol-induced myocardial infarction. After a 12-week treatment period, echocardiography was performed, cardiac hypertrophy and interstitial collagen deposition were assessed, and the phosphorylation state of Akt-1/GSK-3beta pathway as well as the PKC and MAPK kinases were determined. Both PARP and ACE inhibition reduced the progression of postinfarction heart failure by attenuating cardiac hypertrophy and interstitial fibrosis. More importantly, PARP inhibition increased the activity of the prosurvival signal transduction factors (Akt-1/GSK-3beta pathway, PKCepsilon). Due to these effects, L-2286 improved the systolic left ventricular function. Enalapril treatment exerted a similar, but weaker protective effect against postinfarction myocardial remodeling and heart failure. In conclusion, we demonstrated in an experimental heart failure model that L-2286 decreased the postinfarction myocardial remodeling more effectively than enalapril treatment. Topics: Angiotensin-Converting Enzyme Inhibitors; Animals; Cardiomegaly; Disease Models, Animal; Echocardiography; Enalapril; Enzyme Inhibitors; Fibrosis; Heart Failure; Male; Myocardial Infarction; Piperidines; Poly(ADP-ribose) Polymerase Inhibitors; Quinazolines; Rats; Rats, Sprague-Dawley; Signal Transduction; Ventricular Remodeling | 2008 |
Enalapril therapy and cardiac remodelling in sickle cell disease patients.
Angiotensin-converting enzyme inhibitors (ACEi) have been successfully used for patients with cardiac dysfunction after myocardial infarction.. The aim of the present study was to investigate cardiac effects of ACEi in sickle cell disease (SCD) patients, as there are no previous reports regarding these effects.. Enalapril was administered to 9 SCD patients with microalbuminuria. Nine SCD patients without microalbuminuria, matched according to age, diagnosis and levels of haemoglobin, haematocrit and foetal haemoglobin did not receive enalapril and were followed up as the control group during the same period of study. Echocardiograms were performed before the study entry and after 36 months of follow-up.. At 36 months of follow-up, significant increases in left ventricular mass, left ventricular mass index, posterior left ventricular wall thickness in end-diastole, interventricular septal wall thickness in end-diastole, and aortic root diameter values were seen in untreated, but not in enalapril-treated patients. No major changes were seen in left ventricular systolic diameter, diastolic dimension and ejection fraction, and left atrial diameter, in both groups, along the observational period.. The results of this study suggest that enalapril prevents cardiac remodelling in SCD patients. However, a large trial concerning the response to enalapril in patients with SCD should be carried out to further clarify this issue. Topics: Adult; Anemia, Sickle Cell; Angiotensin-Converting Enzyme Inhibitors; Diastole; Echocardiography; Enalapril; Female; Follow-Up Studies; Hemodynamics; Humans; Male; Middle Aged; Myocardial Infarction; Prospective Studies; Stroke Volume; Ventricular Remodeling | 2008 |
Atrial flutter and myocardial infarction-like ECG changes as manifestations of left ventricle involvement from lung carcinoma.
Lung cancer involvement of the heart is not unusual, but in most cases is silent. Arrhythmia and electrocardiographic findings suggesting an acute myocardial infarction could be the first manifestation of myocardial infiltration by the tumour. Echocardiography could be a valuable tool to define the diagnosis in patients with lung cancer and newly diagnosed arrhythmia or ST-T wave alterations. When echocardiographics findings are not conclusive, magnetic resonance imaging (MRI) allows differentiation between tumour and myocardium. Topics: Antihypertensive Agents; Antineoplastic Combined Chemotherapy Protocols; Atrial Flutter; Carboplatin; Carcinoma, Squamous Cell; Combined Modality Therapy; Diabetes Mellitus; Docetaxel; Echocardiography; Electrocardiography; Enalapril; Fatal Outcome; Glyburide; Heart Neoplasms; Humans; Hypertension; Hypoglycemic Agents; Lung Neoplasms; Male; Middle Aged; Myocardial Infarction; Radiotherapy; Taxoids; Tomography, X-Ray Computed | 2008 |
Both enalapril and losartan attenuate sarcolemmal Na+-K+-ATPase remodeling in failing rat heart due to myocardial infarction.
To investigate the mechanisms underlying the depressed sarcolemmal (SL) Na(+)-K(+)-ATPase activity in congestive heart failure (CHF), different isoforms and gene expression of Na(+)-K(+)-ATPase were examined in the failing left ventricle (LV) at 8 weeks after myocardial infarction (MI). In view of the increased activity of renin-angiotensin system (RAS) in CHF, these parameters were also studied after 5 weeks of treatment with enalapril (10 mg x kg-1 x day-1), an angiotensin-converting enzyme inhibitor, and losartan (20 mg.kg-1.day-1), an angiotensin II type 1 receptor antagonist, starting at 3 weeks after the coronary ligation in rats. The infarcted animals showed LV dysfunction and depressed SL Na(+)-K(+)-ATPase activity. Protein content and mRNA levels for Na(+)-K(+)-ATPase alpha2 isoform were decreased whereas those for Na(+)-K(+)-ATPase alpha3 isoform were increased in the failing LV. On the other hand, no significant changes were observed in protein content or mRNA levels for Na(+)-K(+)-ATPase alpha1 and beta1 isoforms. The treatment of infarcted animals with enalapril or losartan improved LV function and attenuated the depression in Na(+)-K(+)-ATPase alpha2 isoform as well as the increase in alpha3 isoform, at both the protein and mRNA levels; however, combination therapy with enalapril and losartan did not produce any additive effects. These results provide further evidence that CHF due to MI is associated with remodeling of SL membrane and suggest that the blockade of RAS plays an important role in preventing these alterations in the failing heart. Topics: Angiotensin II Type 1 Receptor Blockers; Angiotensin-Converting Enzyme Inhibitors; Animals; Disease Models, Animal; Enalapril; Gene Expression Regulation, Enzymologic; Heart Failure; Hemodynamics; Losartan; Male; Myocardial Infarction; Myocardium; Rats; Rats, Sprague-Dawley; Renin-Angiotensin System; RNA, Messenger; Sarcolemma; Sodium-Potassium-Exchanging ATPase; Time Factors; Ventricular Dysfunction, Left; Ventricular Remodeling | 2008 |
Chronic pretreatment of ACEI reduces no-reflow in patients with acute myocardial infarction treated with primary angioplasty.
In animal models, pretreatment with angiotensin-converting enzyme inhibitor (ACEI) can reduce no-reflow. In the present study, we investigated whether pretreatment with ACEI may prevent no-reflow in patients who underwent primary coronary intervention for AMI.. A total of 259 consecutive patients who underwent primary angioplasty for a first AMI were studied. No-reflow was defined as a TIMI flow grade < 3. The no-reflow phenomenon was found in 33 of 259 patients. There were no significant differences in clinical characteristics between the patients with and without ACEI pretreatment. However, the 47 patients receiving chronic ACEI treatment before admission had lower incidence of the no-reflow than those without it (4.2 and 14.6%, p<0.05). Multivariable logistic regression analysis revealed that absence of ACEI pretreatment was a significant predictor of the no-reflow along with absence of preinfarction angina, complete occlusion of the culprit lesion, high-burden thrombus, ejection fraction on admission, number of Q-waves, absence of statin pretreatment, and anterior AMI.. Pretreatment with ACEI could preserve the microvascular integrity after acute myocardial infarction in humans. Topics: Adult; Aged; Analysis of Variance; Angioplasty, Balloon, Coronary; Angiotensin-Converting Enzyme Inhibitors; Blood Flow Velocity; Captopril; Coronary Angiography; Coronary Circulation; Electrocardiography; Enalapril; Female; Fosinopril; Humans; Logistic Models; Male; Middle Aged; Myocardial Infarction; Predictive Value of Tests; Research Design; Stroke Volume; Time Factors; Treatment Outcome | 2007 |
Angiotensin receptor blockade and angiotensin-converting-enzyme inhibition limit adverse remodeling of infarct zone collagens and global diastolic dysfunction during healing after reperfused ST-elevation myocardial infarction.
To determine whether therapy with the angiotensin II type 1 receptor blocker (ARB) candesartan and the comparator angiotensin-converting-enzyme inhibitor (ACEI) enalapril during healing after reperfused ST-elevation myocardial infarction (RSTEMI) limit adverse remodeling of infarct zone (IZ) collagens and left ventricular (LV) diastolic dysfunction, we randomized 24 dogs surviving anterior RSTEMI (90-min coronary occlusion) to placebo, candesartan, and enalapril therapy between day 2 and 42. Six other dogs were sham. We measured regional IZ and non-infarct zone (NIZ) collagens (hydroxyproline; types I/III; cross-linking), transforming growth factor-beta (TGF-beta) and topography at 6 weeks, and hemodynamics, LV diastolic and systolic function, and remodeling over 6 weeks. Compared to sham, placebo-RSTEMI differentially altered regional collagens, with more pronounced increase in TGF-beta, hydroxyproline, and type I, insoluble, and cross-linked collagens in the IZ than NIZ, and increased IZ soluble and type III collagens at 6 weeks, and induced persistent LV filling pressure elevation, diastolic and systolic dysfunction, and LV remodeling over 6 weeks. Compared to placebo-RSTEMI, candesartan and enalapril limited adverse regional collagen remodeling, with normalization of type III, soluble and insoluble collagens and decrease in pyridinoline cross-linking in the IZ at 6 weeks, and attenuation of LV filling pressure, diastolic dysfunction, and remodeling over 6 weeks. The results suggest that candesartan and enalapril during healing after RSTEMI prevent rather than worsen adverse remodeling of IZ collagens and LV diastolic dysfunction, supporting the clinical use of ARBs and ACEIs during subacute RSTEMI. Topics: Angiotensin II Type 1 Receptor Blockers; Angiotensin Receptor Antagonists; Angiotensin-Converting Enzyme Inhibitors; Animals; Benzimidazoles; Biphenyl Compounds; Collagen; Dogs; Enalapril; Hydroxyproline; Myocardial Infarction; Myocardial Reperfusion; Peptidyl-Dipeptidase A; Tetrazoles; Transforming Growth Factor beta1; Ventricular Dysfunction, Left; Ventricular Remodeling; Wound Healing | 2007 |
Effect of enalapril treatment on the sensitivity of cardiopulmonary reflexes in rats with myocardial infarction.
1. The aim of the present study was to evaluate the effect of treatment with enalapril on the sensitivity of cardiopulmonary reflexes 30 days after myocardial infarction in Wistar rats. 2. Animals were divided into four groups: (i) sham operated, receiving vehicle (SHAM); (ii) infarcted, receiving vehicle (0.9% NaCl; INF); (iii) sham operated, receiving enalapril (SHAME); and (iv) infarcted, receiving enalapril (INFE). 3. Enalapril was administered at a dose of 10 mg/kg per day. Serotonin (4-32 microg/kg, i.v.) was administered in order to activate the Bezold-Jarisch reflex, which was estimated as the percentage of reduction in heart rate. 4. The volume-sensitive cardiopulmonary reflex was induced by saline overload and evaluated as the percentage increase in sodium and volume renal excretion. At the end of the experiments, rats were killed and hearts excised to estimate the size of the infarction. The weight of the kidneys, lungs, liver and cardiac chambers as ratios of bodyweight was used to estimate the extent of hypertrophy. 5. The results showed an impairment in the sensitivity of the cardiopulmonary reflexes in the INF group compared with the SHAM and SHAME groups. We observed right ventricle and pulmonary hypertrophy, a reduction in mean and systolic arterial pressure and an increase in heart rate in INF animals. In the INFE group, nearly all the parameters were normal compared with the INF group, except for systolic arterial pressure, which was only partially improved. 6. The main finding of the present study was that treatment with enalapril normalized the sensitivity of the cardiopulmonary reflexes, which could be due, in part, to the reduction of cardiac hypertrophy. The present study provides information about the beneficial effects of the angiotensin-converting enzyme inhibitors by normalizing the cardiopulmonary reflexes involved with the regulation of volume and sodium, as well as control of arterial pressure and heart rate in infarcted animals. Topics: Angiotensin-Converting Enzyme Inhibitors; Animals; Baroreflex; Blood Pressure; Cardiomegaly; Chronic Disease; Disease Models, Animal; Enalapril; Heart Rate; Kidney; Lung; Male; Myocardial Infarction; Natriuresis; Rats; Rats, Wistar; Reflex; Sympathetic Nervous System; Urination; Water-Electrolyte Balance | 2007 |
Enalapril attenuates downregulation of Angiotensin-converting enzyme 2 in the late phase of ventricular dysfunction in myocardial infarcted rat.
The early and long-term effects of coronary artery ligation on the plasma and left ventricular angiotensin-converting enzyme (ACE and ACE2) activities, ACE and ACE2 mRNA levels, circulating angiotensin (Ang) levels [Ang I, Ang-(1-7), Ang-(1-9), and Ang II], and cardiac function were evaluated 1 and 8 weeks after experimental myocardial infarction in adult Sprague Dawley rats. Sham-operated rats were used as controls. Coronary artery ligation caused myocardial infarction, hypertrophy, and dysfunction 8 weeks after surgery. At week 1, circulating Ang II and Ang-(1-9) levels as well as left ventricular and plasma ACE and ACE2 activities increased in myocardial-infarcted rats as compared with controls. At 8 weeks post-myocardial infarction, circulating ACE activity, ACE mRNA levels, and Ang II levels remained higher, but plasma and left ventricular ACE2 activities and mRNA levels and circulating levels of Ang-(1-9) were lower than in controls. No changes in plasma Ang-(1-7) levels were observed at any time. Enalapril prevented cardiac hypertrophy and dysfunction as well as the changes in left ventricular ACE, left ventricular and plasmatic ACE2, and circulating levels of Ang II and Ang-(1-9) after 8 weeks postinfarction. Thus, the decrease in ACE2 expression and activity and circulating Ang-(1-9) levels in late ventricular dysfunction post-myocardial infarction were prevented with enalapril. These findings suggest that in this second arm of the renin-angiotensin system, ACE2 may act through Ang-(1-9), rather than Ang-(1-7), as a counterregulator of the first arm, where ACE catalyzes the formation of Ang II. Topics: Angiotensin I; Angiotensin II; Angiotensin-Converting Enzyme 2; Angiotensin-Converting Enzyme Inhibitors; Animals; Down-Regulation; Enalapril; Hemodynamics; Male; Myocardial Infarction; Peptide Fragments; Peptidyl-Dipeptidase A; Rats; Rats, Sprague-Dawley; Ventricular Dysfunction; Ventricular Function, Left | 2006 |
Inhibitory effect of candesartan cilexetil on left ventricular remodeling after myocardial infarction.
Although angiotensin-converting enzyme inhibitors (ACEIs) have been shown to reduce left ventricular remodeling after acute myocardial infarction (AMI), the effects of angiotensin receptor blockers have yet to be established. This study was conducted to examine the effects of candesartan on left ventricular remodeling after AMI. Consecutive AMI patients were assigned to a candesartan group or ACEI group after successful coronary intervention. The patients in the candesartan group (n = 77, mean age, 62.8 +/- 1.3) received candesartan and the patients in the ACEI group (n = 80, mean age, 63.3 +/- 1.2) received lisinopril, enalapril, or trandolapril. Four mg was the most frequent dose in the candesartan group at 6 months. Lisinopril, enalapril, and trandolapril were administered to 52%, 27%, and 21% of the patients in the ACEI group, respectively. No significant differences in the incidences of cardiac death, nonfatal MI, or hospitalization for heart failure (P = NS) were found between the groups. The candesartan group exhibited a somewhat higher percent increase in left ventricular ejection fraction and significantly lower percent increases in left ventricular end-diastolic volume index and left ventricular end-systolic volume index compared to the ACEI group (P < 0.05, P < 0.05, respectively). Candesartan is more effective than ACEI in preventing left ventricular remodeling after AMI. Topics: Angiotensin II Type 1 Receptor Blockers; Angiotensin-Converting Enzyme Inhibitors; Benzimidazoles; Biphenyl Compounds; Enalapril; Female; Humans; Indoles; Lisinopril; Male; Middle Aged; Myocardial Infarction; Tetrazoles; Ventricular Function, Left; Ventricular Remodeling | 2006 |
Sarcoplasmic reticulum Ca2+ transport and gene expression in congestive heart failure are modified by imidapril treatment.
This study was designed to test the hypothesis that blockade of the renin-angiotensin system improves cardiac function in congestive heart failure by preventing changes in gene expression of sarcoplasmic reticulum (SR) proteins. We employed rats with myocardial infarction (MI) to examine effects of an angiotensin-converting enzyme inhibitor, imidapril, on SR Ca(2+) transport, protein content, and gene expression. Imidapril (1 mg.kg(-1).day(-1)) was given for 4 wk starting 3 wk after coronary artery occlusion. Infarcted rats exhibited a fourfold increase in left ventricular end-diastolic pressure, whereas rates of pressure development and decay were decreased by 60 and 55%, respectively. SR Ca(2+) uptake and Ca(2+) pump ATPase, as well as Ca(2+) release and ryanodine receptor binding activities, were depressed in the failing hearts; protein content and mRNA levels for Ca(2+) pump ATPase, phospholamban, and ryanodine receptor were also decreased by approximately 55-65%. Imidapril treatment of infarcted animals improved cardiac performance and attenuated alterations in SR Ca(2+) pump and Ca(2+) release activities. Changes in protein content and mRNA levels for SR Ca(2+) pump ATPase, phospholamban, and ryanodine receptor were also prevented by imidapril treatment. Beneficial effects of imidapril on cardiac function and SR Ca(2+) transport were not only seen at different intervals of MI but were also simulated by another angiotensin-converting enzyme inhibitor, enalapril, and an ANG II receptor antagonist, losartan. These results suggest that blockade of the renin-angiotensin system may increase the abundance of mRNA for SR proteins and, thus, may prevent the depression in SR Ca(2+) transport and improve cardiac function in congestive heart failure due to MI. Topics: Animals; Antihypertensive Agents; Calcium; Calcium-Transporting ATPases; Cardiomegaly; Enalapril; Gene Expression; Heart Failure; Imidazolidines; Losartan; Male; Myocardial Infarction; Rats; Rats, Sprague-Dawley; Ryanodine Receptor Calcium Release Channel; Sarcoplasmic Reticulum; Sarcoplasmic Reticulum Calcium-Transporting ATPases; Tritium; Ventricular Pressure | 2005 |
Involvement of nitric oxide and prostaglandin pathways in the cardioprotective actions of bradykinin in rats with experimental myocardial infarction.
Bradykinin is a potent endothelium-dependent vasodilator in the coronary vascular bed. Endothelial mediators released by bradykinin include nitric oxide, prostacyclin and as yet unidentified endothelium-derived hyperpolarising factors. We wished to determine the involvement of nitric oxide and prostaglandin pathways in the cardioprotective actions mediated by bradykinin via the combined inhibition of ACE and aminopeptidase P (APP) in an in vivo rat model of acute ischemia (30 min) and reperfusion (4h). Myocardial infarct size was measured by using the staining agent 2,3,5-triphenyl tetrazolium chloride (TTC). Lipid peroxide levels in serum and in heart tissue were estimated spectrophotometrically. A lead II electrocardiogram was monitored at various intervals throughout the experiment. Infarct size reduction obtained with the combined inhibition of enalapril and apstatin, lisinopril and apstatin was blocked partially but significantly with the prior administration of L-NAME (Nomega-nitro-L-arginine methyl ester) or aspirin, suggesting the involvement of both nitric oxide and prostaglandin pathways in the cardioprotective actions mediated by bradykinin. Topics: Animals; Aspirin; Bradykinin; Disease Models, Animal; Drug Therapy, Combination; Enalapril; Female; Heart Rate; Injections, Intravenous; Lisinopril; Male; Malondialdehyde; Myocardial Infarction; Myocardial Reperfusion Injury; Myocardium; NG-Nitroarginine Methyl Ester; Peptides; Rats; Rats, Sprague-Dawley; Staining and Labeling; Tetrazolium Salts | 2004 |
The problem of underdosing of angiotensin-converting enzyme inhibitors is markedly overrated: results from a study of patients discharged from hospital after an acute myocardial infarction.
The use of angiotensin-converting enzyme (ACE) inhibitors has increased markedly during the last decade. It has been claimed that doses of ACE inhibitors prescribed in clinical practice are considerably lower than the target doses used in randomized clinical trials. The aim of the study was to investigate dosing of ACE inhibitors in patients discharged from the hospital after an acute myocardial infarction (AMI) and, furthermore, to compare these doses with the doses actually reached in clinical trials.. From 16 hospitals, we drew a sample of patients who were discharged alive with the diagnosis of AMI during a 3-month period in 1999/2000. From medical records, physicians in each hospital obtained the observed rate of cardiovascular drugs at discharge, including type and doses of ACE inhibitors. The clinicians' main indication for ACE inhibitor use was also reported. Outcome variables, including deaths and drug utilization with dosing after 6 months, were collected.. Of a total of 767 patients discharged alive, 274 patients received an ACE inhibitor. The daily mean doses of the four ACE inhibitors used in the study were as follows: captopril 69.8+/-36.9 mg (n=44), enalapril 13.6+/-8.1 mg (n=75), lisinopril 11.0+/-7.2 mg (n=114), and ramipril 8.4+/-4.5 mg (n=38). The doses were unchanged after 6 months except for captopril, which showed a rise in mean daily dose to 84.4+/-36.7 mg. Ramipril compared most favorably with clinical trial medications, while captopril deviated most. The indication of hypertension was associated with slightly higher doses than the indication of secondary prevention.. AMI patients were discharged from the hospital with ACE inhibitor doses fairly close to the ones achieved in clinical trials showing survival benefits for ACE inhibitors. A distinction should be made between target doses and doses actually obtained in clinical trials. Topics: Acute Disease; Aged; Angiotensin-Converting Enzyme Inhibitors; Captopril; Dose-Response Relationship, Drug; Drug Administration Schedule; Drug Utilization; Enalapril; Evaluation Studies as Topic; Female; Hospitalization; Humans; Lisinopril; Male; Myocardial Infarction; Patient Discharge; Pharmacoepidemiology; Ramipril; Randomized Controlled Trials as Topic | 2004 |
Effects of differential blockade of the renin-angiotensin system in postinfarcted rats.
The present study compared short-term effects of the AT(1)-receptor antagonist, irbesartan with the angiotensin-converting enzyme (ACE) inhibitor, enalapril on systemic haemodynamics and cardiac remodelling in post-myocardia-infarcted (MI) rats. MI Sprague-Dawley rats were orally treated for 4 weeks with irbesartan (50 mg/kg/day) or enalapril (10 mg/kg/day). Then, cardiac and systemic haemodynamics were measured. Compared with the sham-operated group, left ventricular end-diastolic pressure (LVEDP), diastolic pressure (LVDP), heart weight to body weight ratio were all significantly increased in the MI group while the LV contractility (dP/dt) and pulsatile arterial pressure were significantly reduced. Both drugs reduced the elevated LVEDP and LVDP and prevented cardiac hypertrophy. Furthermore, irbesartan attenuated the right shift of the pressure-volume curves, prevented postinfarction-induced increase in urinary cyclic guanosine monophosphate and reduced urinary aldosterone excretion. Although both drugs were able to prevent further cardiac hypertrophy and improved cardiac filling pressure, only irbesartan limited LV dilatation. These data indicate that blockade of the renin-angiotensin system at the level of AT1 receptors may have a better cardioprotective benefit than reducing angiotensin II levels by ACE inhibition. Topics: Aldosterone; Angiotensin II Type 1 Receptor Blockers; Angiotensin-Converting Enzyme Inhibitors; Animals; Biphenyl Compounds; Cyclic GMP; Enalapril; Hemodynamics; Irbesartan; Male; Myocardial Infarction; Rats; Rats, Sprague-Dawley; Tetrazoles; Ventricular Remodeling | 2004 |
Changes in skeletal muscle SR Ca2+ pump in congestive heart failure due to myocardial infarction are prevented by angiotensin II blockade.
In order to understand the mechanisms of exercise intolerance and muscle fatigue, which are commonly observed in congestive heart failure, we studied sarcoplasmic reticulum (SR) Ca(2+)-transport in the hind-leg skeletal muscle of rats subjected to myocardial infarction (MI). Sham-operated animals were used for comparison. On one hand, the maximal velocities (Vmax) for both SR Ca(2+)-uptake and Ca(2+)-stimulated ATPase activities in skeletal muscle of rats at 8 weeks of MI were higher than those of controls. On the other hand, the Vmax values for both SR Ca(2+)-uptake and Ca(2+)-stimulated ATPase activities were decreased significantly at 16 weeks of MI when compared with controls. These alterations in Ca(2+)-transport activities were not associated with any change in the affinity (1/Ka) of the SR Ca(2+)-pump for Ca2+. Furthermore, the stimulation of SR Ca(2+)-stimulated ATPase activity by cyclic AMP-dependent protein kinase was not altered at 8 or 16 weeks of MI when compared with the respective control values. Treatment of 3-week infarcted animals with angiotensin-converting enzyme (ACE) inhibitors such as captopril, imidapril, and enalapril or an angiotensin receptor (AT1R) antagonist, losartan, for a period of 13 weeks not only attenuated changes in left ventricular function but also prevented defects in SR Ca(2+)-pump in skeletal muscle. These results indicate that the skeletal muscle SR Ca(2+)-transport is altered in a biphasic manner in heart failure due to MI. It is suggested that the initial increase in SR Ca(2+)-pump activity in skeletal muscle may be compensatory whereas the depression at late stages of MI may play a role in exercise intolerance and muscle fatigue in congestive heart failure. Furthermore, the improvements in the skeletal muscle SR Ca(2+)-transport by ACE inhibitors may be due to the decreased activity of renin-angiotensin system in congestive heart failure. Topics: Angiotensin II; Angiotensin II Type 1 Receptor Blockers; Angiotensin-Converting Enzyme Inhibitors; Animals; Apoptosis; Calcium; Calcium-Transporting ATPases; Captopril; Cyclic AMP-Dependent Protein Kinases; Enalapril; Heart Failure; Imidazolidines; Losartan; Male; Muscle, Skeletal; Muscular Atrophy; Myocardial Infarction; Rats; Rats, Sprague-Dawley; Sarcoplasmic Reticulum; Time Factors | 2004 |
Modification of myosin protein and gene expression in failing hearts due to myocardial infarction by enalapril or losartan.
The effects of enalapril, an angiotensin converting enzyme (ACE) inhibitor, and losartan, an angiotensin II receptor type I antagonist, were investigated on alterations in myofibrillar ATPase activity as well as myosin heavy chain (MHC) content and gene expression in failing hearts following myocardial infarction (MI). Three weeks after ligation of the left coronary artery, rats were treated with or without enalapril (10 mg/kg/day), and/or losartan (20 mg/kg/day) for 5 weeks. The infarcted animals exhibited an increase in left ventricle (LV) end diastolic pressure and depressed rates of LV pressure development as well as pressure decay. LV myofibrillar Ca2+ -stimulated ATPase activity was decreased in the infarcted hearts compared with controls, MHC alpha-isoform content was significantly decreased whereas that of MHC beta-isoform was markedly increased. The level of MHC alpha-isoform mRNA was decreased whereas that of MHC beta-isoform was increased in the viable infarcted LV. Treatment of animal with enalapril, losartan, or combination of enalapril and losartan partially prevented the MI induced changes in LV function, myofibrillar Ca2+ -stimulated ATPase activity, MHC protein expression and MHC gene expression. The results suggest that the beneficial effects of the renin-angiotensin system blockade in heart failure are associated with partial prevention of myofibrillar remodeling. Topics: Adenosine Triphosphatases; Angiotensin-Converting Enzyme Inhibitors; Animals; Antihypertensive Agents; Blotting, Northern; Calcium; Diastole; Enalapril; Gene Expression Regulation; Immunoblotting; Losartan; Magnesium; Male; Myocardial Infarction; Myocardium; Myosin Heavy Chains; Myosins; Protein Isoforms; Rats; Rats, Sprague-Dawley; RNA; RNA, Messenger; Time Factors; Ventricular Function, Left | 2004 |
Changes in beta-adrenoceptors in heart failure due to myocardial infarction are attenuated by blockade of renin-angiotensin system.
Earlier studies have revealed an improvement of cardiac function in animals with congestive heart failure (CHF) due to myocardial infarction (MI) by treatment with angiotensin converting enzyme (ACE) inhibitors. Since heart failure is also associated with attenuated responses to catecholamines, we examined the effects of imidapril, an ACE inhibitor, on the beta-adrenoceptor (beta-AR) signal transduction in the failing heart. Heart failure in rats was induced by occluding the coronary artery, and 3 weeks later the animals were treated with g/(kg x day) (orally) imidapril for 4 weeks. The animals were assessed for their left ventricular function and inotropic responses to isoproterenol. Cardiomyocytes and crude membranes were isolated from the non-ischemic viable left ventricle and examined for the intracellular concentration of Ca2+ [Ca2+]i and beta-ARs as well as adenylyl cyclase (AC) activity, respectively. Animals with heart failure exhibited depressions in ventricular function and positive inotropic response to isoproterenol as well as isoproterenol-induced increase in [Ca2+]i in cardiomyocytes; these changes were attenuated by imidapril treatment. Both beta1-AR receptor density and isoproterenol-stimulated AC activity were decreased in the failing heart and these alterations were prevented by imidapril treatment. Alterations in cardiac function, positive inotropic effect of isoproterenol, beta1-AR density and isoproterenol-stimulated AC activity in the failing heart were also attenuated by treatment with another ACE inhibitor, enalapril and an angiotensin II receptor antagonist, losartan. The results indicate that imidapril not only attenuates cardiac dysfunction but also prevents changes in beta-AR signal transduction in CHF due to MI. These beneficial effects are similar to those of enalapril or losartan and thus appear to be due to blockade of the renin-angiotensin system. Topics: Adenylyl Cyclases; Angiotensin-Converting Enzyme Inhibitors; Animals; Disease Models, Animal; Enalapril; Heart Failure; Imidazolidines; Isoproterenol; Kinetics; Losartan; Male; Myocardial Infarction; Myocardium; Rats; Rats, Sprague-Dawley; Receptors, Adrenergic, beta; Renin-Angiotensin System; Signal Transduction | 2004 |
Effects of angiotensin II receptor blockade versus angiotensin-converting-enzyme inhibition on ventricular remodelling following myocardial infarction in the mouse.
Left ventricular (LV) remodelling following myocardial infarction (MI) is associated with increased morbidity and mortality. Previous data suggest that angiotensin II (Ang II) plays a central role in the molecular events contributing to LV remodelling. We explored the effects of angiotensin-converting-enzyme (ACE) inhibition versus Ang II (AT(1)) receptor blockade on LV remodelling in mice post-MI. Mice underwent sham procedure or left coronary artery ligation, and received placebo, the AT(1) receptor antagonist, losartan or the ACE inhibitor, enalapril. At 6 weeks, echocardiography and haemodynamic studies were performed. Infarct size and interstitial collagen content were determined. Expression of genes encoding atrial natriuretic peptide (ANP), collagen type I, AT(1a) and AT(1b) receptors were measured. The placebo MI group showed increased LV end-diastolic diameter, LV end-systolic diameter with depressed fractional shortening ( P <0.01 versus shams), increased LV mass and volume (both P <0.01 versus shams). The placebo MI group also exhibited increased non-infarct zone collagen content ( P <0.01), ANP ( P <0.01) and collagen type 1 ( P <0.01) gene expression, with a non-significant rise in AT(1a) receptor gene expression. Neither losartan or enalapril prevented LV dilation or improved fractional shortening. Both similarly lowered systolic blood pressure ( P <0.01 for each versus placebo). Losartan and enalapril inhibited LV hypertrophy ( P <0.01), and decreased ANP ( P <0.01) and collagen type 1 gene expression ( P <0.05). Levels of AT(1a) receptor gene expression were higher than shams ( P <0.05 for both), but similar to placebo. AT(1b) receptor gene expression was much lower than that for AT(1a) receptor and similar in all groups. Thus, in this model, AT(1) receptor antagonism and ACE inhibition have equivalent inhibitory effects on myocardial hypertrophy and fibrosis. These results serve as an important basis for planned investigations to evaluate the anti-remodelling effects of these agents on mice in which genetic manipulations are used to disrupt components of the Ang II signalling system. Topics: Angiotensin Receptor Antagonists; Angiotensin-Converting Enzyme Inhibitors; Animals; Collagen; Enalapril; Gene Expression Regulation; Hemodynamics; Losartan; Male; Mice; Mice, Inbred C57BL; Myocardial Infarction; Receptors, Angiotensin; Reverse Transcriptase Polymerase Chain Reaction; Ultrasonography; Ventricular Remodeling | 2003 |
ST-segment resolution and late (6-month) left ventricular remodeling after acute myocardial infarction.
Topics: Aged; Antihypertensive Agents; Coronary Circulation; Electrocardiography; Enalapril; Female; Humans; Losartan; Male; Microcirculation; Middle Aged; Myocardial Infarction; Myocardial Reperfusion; Predictive Value of Tests; Prognosis; Prospective Studies; Radionuclide Ventriculography; Severity of Illness Index; Single-Blind Method; Stroke Volume; Time Factors; Treatment Outcome; Ventricular Remodeling | 2003 |
Effects of angiotensin-converting enzyme inhibitor therapy on QT dispersion post acute myocardial infarction.
The aim of this study was to determine the effect of an angiotensin-converting enzyme inhibitor (ACEI), initiated within 24 hours of an acute myocardial infarction (AMI), on the QT dispersion (QTd). ACEIs have proven beneficial in improving left ventricular remodeling, following an AMI while contributing to a reduction in sudden cardiac death (SCD). A prolonged QTd is a marker of electrical instability predisposing to ventricular arrhythmias and SCD. No one has looked at the effects on the QTd of ACEI therapy initiated within 24 hours of an AMI. The study included 239 consecutive patients who presented with an AMI between January 1, 1998 and December 31, 1998. A total of 105 patients had never been treated with an ACEI, and 51 patients were started on enalapril within 24 hours of presentation. Patient demographics were similar in both groups. All patients were treated with aspirin and beta-blocker therapy. A baseline QTd was determined and recalculated on days 3-4 and 6-7 following the AMI. There was no significant difference in the baseline QTd, heart rate, QTc(min), and QTc(max) between the two groups. On days 3-4 the QTd in the treatment group (A) was 39.2 +/- 19.4 ms, as opposed to 84.4 +/- 31.2 ms in the control group (B) (P = 1.0E-06). This reduction in QTd was accounted for by a significant difference in the QTc(max). The QTd shortened in both groups on days 6-7 with a QTd of 30.0 +/- 17.5 in group A and a QTd of 54.1 +/- 26.3 in group B (P = 1.0E-05). There was a significant difference in ejection fraction (EF) between the two groups with the ACEI treated group exhibiting a lower EF, (0.403 (A), 0.494 (B), P < 0.043). The mean dose of enalapril was 6.45 mg daily in the treatment group. ACEIs have been previously shown to reduce the QTd after two months of therapy following an AMI. This study shows that the beneficial effects of ACEI occur early following administration of the drug. The authors speculate that the reduction in SCD conferred by ACEI therapy may be attributed to its effect on reducing the degree of ventricular dispersion of repolarization following a myocardial infarction. Topics: Aged; Angiotensin-Converting Enzyme Inhibitors; Case-Control Studies; Death, Sudden, Cardiac; Electrocardiography; Enalapril; Female; Heart Rate; Humans; Male; Myocardial Infarction; Retrospective Studies; Time Factors; Treatment Outcome | 2003 |
[Drug therapy of coronary heart disease--are therapeutic guidelines being paid attention to?].
Drug therapy of coronary heart disease (CHD) is a life-long treatment. With every change from in-patient to out-patient care and back, changes in medication may occur. If a drug is chosen which provides no proven long-term benefit in terms of reduced morbidity and mortality, the expected therapeutic benefit may be missed. We investigated in 224 patients admitted to the medical departments of two hospitals (one with a specialized Cardiology Unit, one with a General Internal Medicine Unit) the prescriptions for CHD by the general practitioner before admittance into the hospital, the prescriptions recommended at the time of discharge, and the prescriptions made by the general practitioner three months after discharge. Of the drug classes with proven effects on morbidity and mortality (acetylsalicylic acid, beta-blockers, statins, ACE inhibitors), none had sufficiently high prescription rates. Prescription rates at discharge were 30% for beta-blockers and statins, 70% for acetylsalicylic acid, and 60% for ACE inhibitors. Only in patients with acute myocardial infarction were the prescription rates for these drug classes higher at this time point. The presence of contraindications was not of prime importance for the low prescription rates, as even in patients without contraindications prescription rates were not significantly higher than in the total patient cohort. Out of the patients with hypercholesterolemia, one third of those treated in the Cardiology Department and two thirds of those treated in the General Internal Medicine Department were not given any lipid-lowering medication. Prescription rates for those drug classes that provide symptomatic relief but have little impact on mortality rates (calcium channel blockers, nitrates) were high in both hospitals. The present study shows that evidence-based guidelines for the drug treatment of coronary heart disease are not adequately put into practice. Topics: Adrenergic beta-Antagonists; Aged; Analysis of Variance; Angiotensin-Converting Enzyme Inhibitors; Calcium Channel Blockers; Captopril; Coronary Disease; Drug Prescriptions; Enalapril; Evidence-Based Medicine; Female; Guideline Adherence; Humans; Hypolipidemic Agents; Inpatients; Male; Middle Aged; Myocardial Infarction; Nitrates; Outpatients; Platelet Aggregation Inhibitors; Practice Guidelines as Topic | 2003 |
[Cardiac rehabilitation in a HIV-patient treated with protease inhibitors].
We report a case of a 38-years-old HIV-positive patient, undergoing in the last 18 months therapy with three antiretroviral drugs including a protease inhibitor (nelfinavir). The patient was admitted in our Department with acute anterior myocardial infarction and was submitted to PTCA on the left anterior descending coronary artery. The patient, a 30 cigarettes/day smoker, with family history of hypertension and high levels of trygliceride and cholesterol, was subsequently admitted to our Cardiac Rehabilitation Unit. Cardiac Rehabilitation Program was composed of cycle aerobic training 4 times/week, dietary education, psychologic support and therapy with pravastatin, aspirin, nitrate, enalapril, and carvedilol. At the end of the 8 week Rehabilitation Program we observed a normalization of cholesterol and trygliceride levels and an improvement of cardiac functional capacity and mental health. Topics: Adult; Aspirin; Carbazoles; Carvedilol; Cholesterol; Coronary Angiography; Diet Therapy; Drug Therapy, Combination; Enalapril; Exercise Therapy; HIV Infections; Humans; Male; Myocardial Infarction; Nitrates; Pravastatin; Propanolamines; Protease Inhibitors; Treatment Outcome; Triglycerides | 2003 |
Interleukin-6 and tumor necrosis factor alpha in relation to myocardial infarct size and collagen formation.
Interleukin-6 (IL-6) and tumor necrosis factor alpha (TNF-alpha) levels increase after acute myocardial infarction (AMI) in humans. Experimental data suggest that these cytokines regulate the initiation of scar formation after AMI. We investigated the interrelationships of IL-6 and TNF-alpha, tissue injury, infarct size, cardiac function, and collagen formation in humans.. Serum and plasma samples were taken on 93 patients receiving thrombolytic treatment for their first AMI. Collagen formation was evaluated by measuring concentrations of serum aminoterminal propeptide of type III procollagen (PIIINP).. IL-6 levels increased by 44% (P<.001) and peaked at 24 hours. Peak IL-6 levels correlated positively with area under the curve of creatine kinase MB mass (r=.31, P<.01), peak troponin T level (r=.34, P<.005), and PIIINP measured at discharge (r=.46, P<.001). There were no changes in TNF-alpha levels, and patients with left ventricular dysfunction (EF<40%) had similar TNF-alpha levels as those with preserved left ventricular function.. IL-6 may regulate collagen formation and thus remodeling of the left ventricle after AMI. In addition, TNF-alpha measurement is useless in the assessment of infarct size or left ventricular function during the immediate post-infarction period. Topics: Angiotensin-Converting Enzyme Inhibitors; Area Under Curve; Arrhythmias, Cardiac; Biomarkers; C-Reactive Protein; Collagen; Creatine Kinase; Creatine Kinase, MB Form; Electrocardiography; Enalapril; Female; Finland; Humans; Interleukin-6; Isoenzymes; Male; Myocardial Infarction; Peptide Fragments; Procollagen; Quinapril; Severity of Illness Index; Statistics as Topic; Stroke Volume; Tetrahydroisoquinolines; Time Factors; Treatment Outcome; Trinitrotoluene; Tumor Necrosis Factor-alpha; Ventricular Dysfunction, Left | 2003 |
Infarct size limiting effect of apstatin alone and in combination with enalapril, lisinopril and ramipril in rats with experimental myocardial infarction.
Bradykinin is a potent vasoactive peptide that is known to elicit a number of biological responses. A number of peptidases have been identified to possess kininase activity, the inhibition of which increases the availability and effectiveness of kinins. We wished to determine the cardioprotective actions of an aminopeptidase P inhibitor, apstatin alone and in combination with enalapril/lisinopril/ramipril in an in vivo rat model of acute ischemia (30 min) and reperfusion (4 h). Myocardial infarction was produced by occlusion of the left anterior descending coronary artery for 30 min followed by 4 h of reperfusion. Infarct size was measured by using the staining agent 2,3,5-triphenyl tetrazolium chloride (TTC). Lipid peroxide levels in serum and in heart tissue were estimated spectrophotometrically. A lead II electrocardiogram was monitored at various intervals throughout the experiment. Infarct size was reduced to a greater extent with apstatin and with combined inhibition it was further reduced. Infarct size reduction obtained with the combined inhibition came to normal with the prior administration of B2 bradykinin antagonist HOE140 suggests the involvement of bradykinin in the cardioprotective actions of apstatin. Topics: Angiotensin-Converting Enzyme Inhibitors; Animals; Bradykinin; Bradykinin Receptor Antagonists; Drug Therapy, Combination; Enalapril; Female; Heart Rate; Lipid Peroxides; Lisinopril; Male; Malondialdehyde; Myocardial Infarction; Myocardial Reperfusion Injury; Myocardium; Peptides; Ramipril; Rats; Rats, Sprague-Dawley; Time Factors | 2003 |
Two better than one.
Topics: Adult; Aged; Angiotensin-Converting Enzyme Inhibitors; Animals; Class Ib Phosphatidylinositol 3-Kinase; Cognition Disorders; Contraindications; Drug Therapy, Combination; Enalapril; Eplerenone; Fibrinolytic Agents; Heart Failure; Humans; Hypertension; Hypertrophy, Left Ventricular; Isoenzymes; Mice; Mice, Knockout; Middle Aged; Mineralocorticoid Receptor Antagonists; Myocardial Infarction; Myocardial Reperfusion; Phosphatidylinositol 3-Kinases; Phosphoinositide-3 Kinase Inhibitors; Receptors, Adrenergic, beta; Spironolactone | 2003 |
Cell transplantation to prevent heart failure: a comparison of cell types.
Autologous cell transplantation may restore viable muscle after a myocardial infarction. We compared the effect of three cell types or an angiotensin-converting enzyme (ACE) inhibitor on preservation of ventricular function after cardiac injury.. A uniform transmural myocardial scar was created in adult rats by cryoinjury. Three weeks later the rats were randomly assigned to one of four blinded treatments: transplantation with 5 x 10(6) aortic smooth muscle cells (SMC, n = 12), ventricular heart cells (VHC, n = 13), skeletal muscle cells (SKC, n = 13) or culture medium alone (control, n = 11). The ACE inhibitor group (n = 8) received enalapril (1.0 mg/kg per day), also beginning 3 weeks after cryoinjury. Five and 12 weeks after transplantation, left ventricle (LV) function was assessed in a Langendorff apparatus, and histologic and immunohistological evaluation of the LV scars was performed.. At 5 weeks, greater scar elastin content and better LV function was noted with cell transplantation or ACE inhibitor therapy compared with control rats (p < 0.05). Twelve weeks after transplantation, cell-transplanted rats still had greater elastin content and better LV function than control rats, although elastin content and LV function had declined in ACE inhibitor-treated animals to levels below those observed in control rats (p < 0.05).. Transplantation of SMC, VHC, and SKC preserved ventricular function equivalent to the effects of an ACE inhibitor. Muscle cell transplantation, but not ACE inhibitor therapy, continues to be effective later after cryoinjury. No differences were detected between the muscle cells. Topics: Angiotensin-Converting Enzyme Inhibitors; Animals; Aorta; Cardiac Output, Low; Cell Transplantation; Cells, Cultured; Cicatrix; Cryopreservation; Elastin; Enalapril; Heart Injuries; Heart Ventricles; Immunohistochemistry; Muscle, Skeletal; Muscle, Smooth, Vascular; Myocardial Infarction; Myocardium; Rats; Rats, Inbred Lew; Ventricular Function, Left | 2003 |
Partial prevention of changes in SR gene expression in congestive heart failure due to myocardial infarction by enalapril or losartan.
Although activation of the renin-angiotensin system (RAS) is known to produce ventricular remodeling and congestive heart failure (CHF), its role in inducing changes in the sarcoplasmic reticulum (SR) protein and gene expression in CHF is not fully understood. In this study, CHF was induced in rats by ligation of the left coronary artery for 3 weeks and then the animals were treated orally with or without an angiotensin converting enzyme inhibitor, enalapril (10 mg/kg/day) or an angiotensin II receptor antagonist, losartan (20 mg/kg/day) for 4 weeks. Sham-operated animals were used as control. The animals were hemodynamically assessed and protein content as well as gene expression of SR Ca(2+)-release channel (ryanodine receptor, RYR), Ca(2+)-pump ATPase (SERCA2), phospholamban (PLB) and calsequestrin (CQS) were determined in the left ventricle (LV). The infarcted animals showed cardiac hypertrophy, lung congestion, depression in LV +dP/dt and -dP/dt, as well as increase in LV end diastolic pressure. Both protein content and mRNA levels for RYR, SERCA2 and PLB were decreased without any changes in CQS in the failing heart. These alterations in LV function as well as SR protein and gene expression in CHF were partially prevented by treatment with enalapril or losartan. The results suggest that partial improvement in LV function by enalapril and losartan treatments may be due to partial prevention of changes in SR protein and gene expression in CHF and that these effects may be due to blockade of the RAS. Topics: Administration, Oral; Animals; Antihypertensive Agents; Blotting, Northern; Blotting, Western; Calcium; Calcium-Binding Proteins; Calcium-Transporting ATPases; Calsequestrin; Cicatrix; Enalapril; Gene Expression Regulation; Heart Failure; Heart Ventricles; Losartan; Male; Myocardial Infarction; Rats; Rats, Sprague-Dawley; RNA; RNA, Messenger; Sarcoplasmic Reticulum; Sarcoplasmic Reticulum Calcium-Transporting ATPases; Time Factors | 2003 |
Studies on the involvement of bradykinin using enalapril and 2-mercaptoethanol in ischemia-reperfusion induced myocardial infarction in albino rats.
The effects of bradykinin were evaluated using the ACE inhibitor enalapril and the APP inhibitor, 2-mercaptoethanol alone and in combination in rats with experimental myocardial infarction. Myocardial infarction was produced by occlusion of the left anterior descending coronary artery for 30 min followed by 4 h of reperfusion. Infarct size was measured by the TTC stain method. Lipid peroxide levels in serum and heart tissue were estimated by the methods developed by Yagi and Ohkawa et al., respectively. A lead II electrocardiogram was monitored throughout the experiment. With the combined inhibition of both the enzymes ACE and APP, a better cardioprotection was observed when compared to individual inhibition of the enzymes, suggesting the involvement of bradykinin during experimental myocardial infarction. Topics: Angiotensin-Converting Enzyme Inhibitors; Animals; Antihypertensive Agents; Bradykinin; Coronary Vessels; Electrocardiography; Enalapril; Female; Heart Rate; Lipid Peroxides; Male; Mercaptoethanol; Myocardial Infarction; Myocardial Reperfusion Injury; Myocardium; Necrosis; Rats; Rats, Sprague-Dawley | 2003 |
Role of AT2 receptors in the cardioprotective effect of AT1 antagonists in mice.
Angiotensin II (Ang II) acts mainly on two receptor subtypes: AT1 and AT2. Most of the known biological actions of Ang II are mediated by AT1 receptors; however, the role of AT2 receptors remains unclear. We tested the hypothesis that the cardioprotective effects of AT1 receptor antagonists (AT1-ant) after myocardial infarction (MI) are partially mediated by activation of AT2 receptors; thus in AT2 receptor gene knockout mice (AT2-/Y), the effect of AT1-ant will be diminished or absent. MI was induced by ligating the left anterior descending coronary artery. Four weeks later, AT2-/Y and their wild-type littermates (AT2+/Y) were started on vehicle, AT1-ant (valsartan, 50 mg/kg per day), or ACE inhibitor (enalapril, 20 mg/kg per day) for 20 weeks. Basal blood pressure and cardiac function as well as remodeling after MI did not differ between AT2+/Y and AT2-/Y. AT1-ant increased ejection fraction and cardiac output and decreased left ventricular diastolic dimension, myocyte cross-sectional area, and interstitial collagen deposition in AT2+/Y, and these effects were significantly diminished in AT2-/Y. ACE inhibitors improved cardiac function and remodeling similarly in both strains. We concluded that (1) activation of AT2 during AT1 blockade plays an important role in the therapeutic effect of AT1-ant and (2) the AT2 receptor may not play an important role in regulation of cardiac function, either under basal conditions after MI remodeling or in the therapeutic effect of ACE inhibitors. Topics: Angiotensin Receptor Antagonists; Angiotensin-Converting Enzyme Inhibitors; Animals; Blood Pressure; Cardiotonic Agents; Collagen; Enalapril; Heart Rate; Hemodynamics; Male; Mice; Mice, Inbred C57BL; Mice, Knockout; Myocardial Infarction; Myocardium; Receptor, Angiotensin, Type 1; Receptor, Angiotensin, Type 2; Receptors, Angiotensin; Renin; Survival Analysis; Tetrazoles; Valine; Valsartan; Ventricular Remodeling | 2002 |
Effects of the angiotensin-converting enzyme inhibitor enalapril on sympathetic neuronal function and beta-adrenergic desensitization in heart failure after myocardial infarction in rats.
One of the beneficial effects of angiotensin-converting enzyme (ACE) inhibitors in the treatment of heart failure may derive from sympathoinhibition and the prevention of beta-adrenergic desensitization. However, the roles of these properties in the overall effects of ACE inhibitor are not clear. We studied the effects of chronic enalapril treatment (20 mg/L in drinking water for 12 weeks) on left ventricular (LV) function, cardiac norepinephrine (NE), sympathetic neuronal function assessed by 131I-metaiodobenzylguanidine (MIBG), beta-receptors, and isometric contraction of papillary muscle in rats with myocardial infarction (MI) induced by coronary artery ligation. Decreased LV function in the MI rats was associated with reduced cardiac NE content and MIBG uptake, and severely blunted responses of non-infarcted papillary muscle to isoproterenol, forskolin, and calcium. Enalapril attenuated LV remodeling in association with a reduction of the ventricular loading condition and restored baseline developed tension of non-infarcted papillary muscle to the level of sham-operated rats. However, enalapril did not improve cardiac NE content, MIBG uptake, or inotropic responsiveness to beta-agonists. These results suggest that the major effect of the ACE inhibitor enalapril in the treatment of heart failure is not due to sympathoinhibition or restoration of beta-adrenergic pathway in this model of heart failure. Topics: Angiotensin-Converting Enzyme Inhibitors; Animals; Enalapril; Heart Failure; Hemodynamics; Male; Myocardial Contraction; Myocardial Infarction; Myocardium; Norepinephrine; Papillary Muscles; Rats; Rats, Wistar; Receptors, Adrenergic, beta; Sympathetic Nervous System; Ventricular Function, Left; Ventricular Remodeling | 2002 |
Comparison of the effects of losartan, enalapril and their combination in the prevention of left ventricular remodeling after acute myocardial infarction in the rat.
To compare the effects of losartan, enalapril and their combination in the prevention of left ventricular remodeling (LVRM) after acute myocardial infarction (AMI) in the rat.. AMI model was induced in female SD rats by ligating left coronary artery. Forty-eight hours after the procedure, 83 surviving rats were randomized into one of the following 4 groups : 1) AMI control group (n = 19), 2) losartan group (n = 22, 3 mg x kg(-1) x d(-1)), 3) enalapril group (n = 20, 1 mg x kg(-1) x d(-1)), 4) losartan-enalapril combinative group (n = 22, 3 and 1 mg x kg(-1) x d(-1) respectively). 5) Sham-operated group (n = 10) and 6) normal rats group (n = 10) were selected randomly to serve as non-infarction controls. Losartan and enalapril were delivered by direct gastric gavage. After 4 weeks of medical therapy, hemodynamic studies were performed in each group, then the rat hearts were fixed with 10% formalin and pathologic analysis on them was performed. Complete experimental data was obtained in 56 rats, comprising 1) AMI controls (n = 11), 2) losartan group (n = 10), 3) enalapril group (n = 10), 4) the combination of losartan and enalapril group (n = 11), 5) sham-operated group (n = 6) and 6) normal controls (n = 8).. There were no significant differences among the 4 AMI groups in MI size (41.7% to approximately 43.4%, all P > 0.05). Compared with sham group, the left ventricular (LV) end diastolic pressure (LVEDP), volume (LVV), long and short axis length (L and D), as well as LV absolute and relative weight (LVAW and LVRW) in AMI group were all significantly increased (P < 0.05 to approximately 0.001); whereas the maximum left ventricular pressure rising and dropping rates (+/- dp/dt) and their corrected values by LV systolic pressure (+/- dp/dt/LVSP) were significantly reduced (all P < 0.001), indicating LVRM occurred and LV systolic and diastolic function impaired after AMI. Compared with AMI group, LVEDP, LVV, LVAW and LVRW were all significantly decreased (P < 0.05 to approximately 0.001); while +/- dp/dt/LVSP were significantly enhanced in all 3 treatment groups (P < 0.05 to approximately 0.001) except -dp/dt/LVSP in losartan group (P > 0.05). There were no significant differences in the above indices among the 3 treatment groups (all P > 0.05).. Both losartan and enalapril can prevent from LVRM after AMI in the rat and improve LV function with equivalent effects. There seems no additive effect when the 2 drugs are used in combination. Topics: Animals; Antihypertensive Agents; Drug Synergism; Enalapril; Female; Losartan; Myocardial Infarction; Random Allocation; Rats; Rats, Sprague-Dawley; Ventricular Function, Left; Ventricular Remodeling | 2002 |
[Blood pressure control must be effective until the next tablet. Infarct is most frequent in the morning].
Topics: Antihypertensive Agents; Blood Pressure; Cerebral Infarction; Circadian Rhythm; Delayed-Action Preparations; Enalapril; Half-Life; Humans; Hypertension; Myocardial Infarction | 2002 |
Comparison of three doses of enalapril in preventing left ventricular remodeling after acute myocardial infarction in the rat.
To compare the effects of high, middle and low doses of enalapril in preventing left ventricular remodeling (LVRM) after acute myocardial infarction (AMI) in rats, especially evaluating the efficacy of low dose enalapril.. AMI was induced by ligating the left coronary artery in 149 female SD rats. 48 hours after the procedure, the 97 surviving rats were randomized to one of the following four groups: (1) AMI controls (n = 24), (2) high-dose (10 mg x kg(-1) x d(-1), n = 25), (3) middle-dose (1 mg x kg(-1) x d(-1), n = 23), and (4) low-dose (0.1 mg x kg(-1) x d(-1), n = 25) enalapril groups. In addition, sham-operated (n = 13) and normal rats (n = 10) were randomly selected to serve as non-infarction controls. Enalapril was delivered by direct gastric gavage. After 4 weeks of therapy, hemodynamic studies were performed, then the rat hearts were fixed with 10% formalin and pathology analysis was performed. Exclusive of the dead rats and those with MI size < 35% or > 55%, complete experimental data were obtained from 67 rats, which were comprised of (1) AMI controls (n = 13), (2) high-dose enalapril (n = 13), (3) middle-dose enalapril (n = 12), (4) low-dose enalapril (n = 12), (5) sham-operated (n = 8) and (6) normal (n = 9) groups.. There were no significant differences among the four AMI groups in infarction size (all P > 0.05). Compared with the sham-operated group, the left ventricular (LV) end diastolic pressure (LVEDP), volume (LVV), absolute and relative weight (LVAW, LVRW) in AMI group were all significantly increased (all P < 0.001), while maximum LV pressure rising and dropping rates (+/- dp/dt) and their corrected values by LV systolic pressure (+/- dp/dt/LVSP) were all significantly reduced in the AMI control group (P < 0.01 - 0.001), indicating LVRM occurred and LV systolic and diastolic functions were impaired. Compared with the AMI group, LVEDP, LVV, LVAW and LVRW were all significantly decreased in the three enalapril groups (control P < 0.001), with the reduction of LVEDP, LVV and LVAW being more significant in high-dose than in low-dose enalapril groups (all P < 0.05), and the +/- dp/dt/LVSP were significantly increased only in the high and middle-dose enalapril groups (P < 0.01).. High, middle and low doses of enalapril were all effective in preventing LVRM after AMI in the rat, with low dose enalapril being effective and high dose superior. As for LV functional improvement, only high and middle-dose enalapril were effective. Topics: Angiotensin-Converting Enzyme Inhibitors; Animals; Dose-Response Relationship, Drug; Enalapril; Female; Myocardial Infarction; Rats; Rats, Sprague-Dawley; Ventricular Remodeling | 2002 |
Vascular remodeling during healing after myocardial infarction in the dog model: effects of reperfusion, amlodipine and enalapril.
We sought to determine whether reperfusion and the calcium channel blocker amlodipine or the angiotensin-converting enzyme inhibitor enalapril, during healing over six weeks after myocardial infarction (MI), limit structural vascular remodeling in the noninfarct zone (NIZ).. The effect of reperfusion and amlodipine or enalapril on structural vascular remodeling during healing of MI has not been determined.. We randomly assigned 54 dogs to reperfused or nonreperfused MI, followed by twice-daily doses of oral placebo, amlodipine (5 mg) or enalapril (5 mg) for six weeks and three days off treatment, or to three matching sham groups. We measured in vivo hemodynamic data and left ventricular (LV) function and remodeling (by echocardiography) over the six weeks, as well as ex vivo structural vascular, ventricular and collagen remodeling in the hearts after six weeks.. Compared with placebo and sham groups, both amlodipine and enalapril with or without reperfusion produced LV unloading and limited structural LV remodeling and dysfunction over six weeks in vivo, and also decreased the NIZ resistance vessel media/lumen area ratio at six weeks ex vivo. In addition, amlodipine, but not enalapril, preserved infarct scar collagen and increased the border zone collagen volume fraction and perivascular fibrosis, as well as NIZ resistance vessel media thickness. Enalapril, but not amlodipine, decreased transforming growth factor-beta in the border zone and NIZ.. The results indicate that therapy with amlodipine and enalapril during healing after reperfused MI limits structural vascular remodeling in the NIZ, probably by different mechanisms. Topics: Amlodipine; Angiotensin-Converting Enzyme Inhibitors; Animals; Biomarkers; Calcium Channel Blockers; Collagen; Coronary Vessels; Disease Models, Animal; Dogs; Echocardiography; Enalapril; Hydroxyproline; In Vitro Techniques; Myocardial Infarction; Myocardial Reperfusion; Transforming Growth Factor beta; Ventricular Remodeling | 2002 |
Effects of long-term enalapril and losartan therapy of heart failure on cardiovascular aldosterone.
Plasma aldosterone escape is found during long-term ACE inhibitor therapy of chronic heart failure. Evidence for aldosterone production in cardiovascular tissues raised the question of whether aldosterone escape occurs or not in these tissues. Rats with infarction-induced chronic heart failure were treated with enalapril (20 mg/kg/d) and losartan (15 mg/kg/d) for 20 weeks. Untreated chronic heart failure and sham-operated rats were used as positive and normal controls, respectively. Ex vivo mesenteric artery and heart perfusion, high performance liquid chromatography, and RIA for aldosterone were performed. Chronic heart failure due to myocardial infarction was associated with tissue-specific activation of cardiovascular aldosterone synthesis. In the mesenteric artery, enalapril significantly inhibited aldosterone production compared to untreated, chronic heart failure rats, and losartan lowered aldosterone production to that of sham rats. In myocardium, enalapril failed to significantly inhibit aldosterone production, and losartan significantly inhibited aldosterone production compared to untreated, chronic heart failure rats. These results provide the first evidence that long-term ACE inhibition therapy induces aldosterone escape in myocardium but not in mesenteric artery of chronic heart failure. The angiotensin II subtype 1 receptor blocker losartan tranquilized aldosterone levels in the cardiovascular tissues of chronic heart failure rats. Topics: Aldosterone; Angiotensin II; Angiotensin-Converting Enzyme Inhibitors; Animals; Cardiac Output, Low; Cardiomegaly; Cardiovascular System; Chronic Disease; Enalapril; Losartan; Male; Mesenteric Arteries; Myocardial Infarction; Rats; Rats, Wistar | 2002 |
Beneficial effects of therapy on the progression of structural remodeling during healing after reperfused and nonreperfused myocardial infarction: different effects on different parameters.
Structural left ventricular remodeling after myocardial infarction is a complex process with several pathophysiologic descriptors that can be modified by pharmacotherapy. However, the possibility that different classes of antiremodeling agents might exert different effects on different remodeling parameters after reperfused and nonreperfused myocardial infarction has not been systematically studied.. We measured detailed left ventricular remodeling parameters in vivo (echocardiograms) repeatedly over 6 weeks and ex vivo (planimetry) at 6 weeks after myocardial infarction in 36 dogs randomized (factorial design) after reperfused or nonreperfused myocardial infarction to 6 weeks of twice daily oral therapy with the calcium channel blocker amlodipine (5 mg), the angiotensin-converting enzyme inhibitor enalapril (5 mg) or placebo, and 18 matching sham or control animals. Compared to placebo and control groups over 6 weeks, both agents reduced left ventricular loading and limited overall remodeling in both reperfused and nonreperfused groups, but there were pertinent differences. Enalapril limited the increase in left ventricular asynergy in the reperfused group. Both enalapril and amlodipine limited infarct zone thinning in the nonreperfused groups but increased infarct zone thinning in the reperfused groups, despite preserved infarct zone collagen with amlodipine. Enalapril decreased left ventricular diastolic volume and mass more than amlodipine in the reperfused group and increased left ventricular ejection fraction in the nonreperfused group. Both agents limited regional and global shape deformation in reperfused and non-reperfused groups. Diastolic wall stress in the infarct zone decreased with amlodipine, and increased with enalapril and reperfusion.. Different antiremodeling therapies may exert different effects on different remodeling parameters during healing after reperfused myocardial infarction. Significant interactions occur during reperfusion. More than one variable may be needed for the comprehensive assessment of the antiremodeling efficacy of different therapies. Topics: Amlodipine; Angiotensin-Converting Enzyme Inhibitors; Animals; Calcium Channel Blockers; Cardiac Volume; Cicatrix; Collagen; Disease Models, Animal; Dogs; Enalapril; Heart; Hemodynamics; Myocardial Infarction; Myocardial Reperfusion; Myocardium; Organ Size; Time Factors; Ventricular Remodeling; Wound Healing | 2002 |
[ACE inhibition in patients with myocardial infarct and ventricular dysfunction: inappropriate application of therapy standards in patient samples].
Several reports indicate the benefit of ACE inhibitors for patients with left ventricular systolic dysfunction after acute myocardial infarction (MI). We sought to determine the implementation of the treatment guidelines in patient samples from the general population. Furthermore we aimed to identify patient characteristics associated with the use of ACE inhibitors. Screening of two MI-registries allowed the identification of 226 MI patients with left ventricular dysfunction. Patients were considered to be eligible for ACE inhibitor therapy when a EF < or = 40% was documented in the patient records of cardiac rehabilitation clinics (REG-MI, n = 147) or detected by standardised echocardiography (KORA, n = 78). On average 5.5 years following MI, a standardised questionnaire and a detailed medical history was obtained. Specifically, information was collected regarding current medication and potential contraindications for ACE inhibitors. MI patients with LV dysfunction received ACE inhibitors in 62% (REG-MI) and 45% (KORA). The doses prescribed were substantially smaller than target doses used in the large-scale studies (REG-MI: 40 +/- 4%, KORA: 23 +/- 3%, % of target doses). Only 13% (REG-MI) and 3% (KORA) received more than 50% of the target dosage. Additionally, actual doses of the most frequently used ACE inhibitors were significantly different (captopril: 23 +/- 2%, enalapril: 42 +/- 5% of target doses). The likelihood of receiving ACE inhibitors was significantly higher in patients with written recommendation for such medication (odds ratio 6.02, confidence interval 1.93-20.16) and in patients visiting cardiologists (odds ratio 3.69, confidence interval 1.26-11.07) as revealed by multivariate analysis of the REG-MI database. Despite national and international guidance, a large proportion of MI patients with left ventricular dysfunction is not receiving ACE inhibitors, and when used, the doses prescribed are markedly smaller than target doses used in clinical trials that established the utility of these drugs. Medical care by cardiologists and written recommendation of ACE inhibition in patient records were independent predictors of a more appropriate prescription of ACE inhibitors. Topics: Aged; Angiotensin-Converting Enzyme Inhibitors; Antihypertensive Agents; Captopril; Clinical Trials as Topic; Confidence Intervals; Echocardiography; Enalapril; Female; Follow-Up Studies; Humans; Male; Middle Aged; Myocardial Infarction; Odds Ratio; Practice Guidelines as Topic; Ramipril; Registries; Sampling Studies; Surveys and Questionnaires; Time Factors; Ventricular Dysfunction, Left | 2001 |
What are 'tissue ACE inhibitors,' and should they be used instead of other ACE inhibitors?
Topics: Angiotensin-Converting Enzyme Inhibitors; Antihypertensive Agents; Captopril; Cardiovascular Diseases; Clinical Trials as Topic; Enalapril; Heart Failure; Humans; Indoles; Isoquinolines; Myocardial Infarction; Perindopril; Prodrugs; Quinapril; Ramipril; Stroke; Stroke Volume; Tetrahydroisoquinolines; Treatment Outcome; Ventricular Dysfunction, Left | 2001 |
Improved survival with simendan after experimental myocardial infarction in rats.
This study compared the effects of simendan, a calcium sensitizer, with those of milrinone and enalapril on survival of rats with healed myocardial infarction. Seven days after ligation-induced myocardial infarction, the rats were randomized to control, milrinone, enalapril, or simendan groups. All compounds were administered via the drinking water for 312 days, at which time there was 80% mortality in the control group--the study's primary endpoint. The infarct sizes were similar across all groups. At endpoint, the mortality rates were: 63% (milrinone), 56% (enalapril) and 53% (simendan); the risk reductions were 25% (P = 0.04 vs. control) and 28% (P = 0.02 vs. control) with enalapril and simendan, respectively. Milrinone had no statistically significant effect on the survival rate. These findings suggest that, like enalapril, simendan improved survival in rats with healed myocardial infarction. Topics: Animals; Antihypertensive Agents; Cardiotonic Agents; Enalapril; Hydrazones; Male; Milrinone; Myocardial Infarction; Pyridazines; Rats; Rats, Wistar; Simendan | 2001 |
Late coronary artery reperfusion has additive beneficial effects on infarct expansion when combined with early angiotensin converting enzyme inhibitor therapy post myocardial infarction.
Individually, late coronary artery reperfusion and early angiotensin converting enzyme (ACE) inhibitor therapy prevent infarct expansion post myocardial infarction (MI).. To examine the effect of late reperfusion on infarct expansion when added to early ACE inhibitor therapy post MI.. Rats were randomized into two groups: Reperfusion group: rats underwent coronary artery occlusion followed by reperfusion 2 hours after MI, a time too late to reduce infarct size. A control group: rats underwent permanent coronary artery occlusion followed by a sham operation 2 hours after MI. All rats received enalapril (2.0 +/- 0.2 mg/kg) daily in drinking water, started immediately after the second operation. Rats were sacrificed 2 weeks after coronary occlusion. Hearts were arrested and fixed at a constant pressure, then sectioned and photographed for morphometric analysis.. Infarct size was similar in the reperfusion and control groups (23 +/- 2 vs 26 +/- 2%, p = NS). Septal thickness was also similar in both groups (1.8 +/- 0.1 vs 1.8 +/- 0.1 mm, p = NS). There was a trend towards thicker infarcts in the reperfusion group compared to the control group (0.84 +/- 0.06 vs 0.72 +/- 0.05 mm, p = 0.1). Compared to early ACE inhibition alone, late reperfusion combined with early ACE inhibition limited infarct expansion (expansion index, 1.13 +/- 0.12 vs 1.44 +/- 0.14, p < 0.05), prevented left ventricular (LV) dilation (LV volume, 0.30 +/- 0.02 vs 0.39 +/- 0.03 ml, p < 0.01) and prevented LV hypertrophy (LV weight, 0.71 +/- 0.18 vs 0.77 +/- 0.20 gm, p < 0.05).. Late coronary artery reperfusion prevents infarct expansion, LV dilation and hypertrophy even when added to early ACE inhibitor therapy post MI. This suggests that late reperfusion may be beneficial in patients with acute MI treated with early ACE inhibitor therapy. Topics: Angiotensin-Converting Enzyme Inhibitors; Animals; Combined Modality Therapy; Enalapril; Female; Heart Ventricles; Hypertrophy, Left Ventricular; Myocardial Infarction; Myocardial Reperfusion; Rats; Rats, Sprague-Dawley; Tissue Fixation | 2001 |
Relationship between transcardiac extraction of aldosterone and left ventricular remodeling in patients with first acute myocardial infarction: extracting aldosterone through the heart promotes ventricular remodeling after acute myocardial infarction.
The purpose of this study was to evaluate whether plasma aldosterone (ALD) is extracted or produced through the heart in patients with acute myocardial infarction (AMI) and to determine the relationship between transcardiac extraction of plasma ALD and left ventricular (LV) remodeling.. Although we demonstrated that circulating ALD was extracted through the failing heart and that transcardiac extraction of ALD correlated with LV end-diastolic volume index (LVEDVI) in patients with congestive heart failure, the existence and increase of ALD synthase in the hearts of infarct rats were reported, suggesting cardiac production of ALD in patients with AMI.. We measured plasma ALD in the aortic root (Ao) and coronary sinus (CS) in 57 consecutive patients who received successful revascularization and enalapril, with first AMI at acute phase and after one month. We also measured plasma procollagen type III aminoterminal peptide (PIIINP) in the CS.. Plasma ALD was significantly lower in the CS than it was in the Ao at the acute phase (84.7 +/- 6.3 pg/ml vs. 105.5 +/- 8.0 pg/ml, p < 0.0001). Significant positive correlations exist between the transcardiac gradient of ALD at the acute phase and the LVEDVI at one month. Moreover, the transcardiac gradient of plasma ALD at the acute phase has a significant correlation with plasma PIIINP, a biochemical marker of fibrosis, after one month. Stepwise multivariate analysis showed that transcardiac extraction of plasma ALD at the acute phase had an independent and significant positive relationship with a large LVEDVI after one month.. These results indicate that plasma ALD is extracted through the heart in patients with AMI at the acute phase and that the extracted ALD plays an important role in modulating post-infarct LV remodeling. Topics: Acute Disease; Aged; Aldosterone; Angioplasty, Balloon, Coronary; Angiotensin-Converting Enzyme Inhibitors; Aorta; Biomarkers; Coronary Vessels; Cytochrome P-450 CYP11B2; Disease Progression; Enalapril; Female; Fibrosis; Heart Failure; Humans; Male; Middle Aged; Mineralocorticoid Receptor Antagonists; Multivariate Analysis; Myocardial Infarction; Peptide Fragments; Procollagen; Prospective Studies; Severity of Illness Index; Stroke Volume; Time Factors; Veins; Ventricular Remodeling | 2001 |
Additional effects of endothelin receptor blockade and angiotensin converting enzyme inhibition in rats with chronic heart failure.
To evaluate the acute effects of tezosentan, a new dual parenteral endothelin receptor antagonist, on hemodynamics in a rat model of chronic heart failure (CHF), and further investigated if the combination of tezosentan with the angiotensin converting enzyme (ACE) inhibitor, enalapril, had additive hemodynamic effect.. Hemodynamics was measured in rats with CHF, induced by ligation of the left coronary artery.. At 3 to 5 weeks after myocardial infarction, rats developed CHF. This was evidenced by a marked increase in left ventricular end-diastolic pressure (LVEDP) with mean values of 23 to 26 mmHg, by a 30 % to 40 % reduction in left ventricular dp/dt(max) and by a more than 10 % decrease in mean arterial pressure (MAP) as compared to sham-operated rats. In CHF rats, acute intravenous administration of either tezosentan (10 mg . kg) or enalapril (1 mg . kg) markedly decreased MAP and LVEDP, without affecting heart rate or dp/dtmax. Tezosentan had additive effects on MAP and LVEDP when given with enalapril compared with tezosentan (P < 0.05) or enalapril (P < 0.05) alone. There were no significant changes in heart rate and dp/dtmax with the combination treatment compared with tezosentan- or enalapril-treated CHF rats.. Acute intravenous tezosentan improves cardiac hemodynamics and decreases LVEDP and afterload (MAP) without changes in heart rate and cardiac contractility dp/dtmax) in CHF rats. These favorable effects of tezosentan are similar to those of enalapril. Furthermore, the benefits of tezosentan are apparent in addition to ACE inhibition. Thus, tezosentan could be a useful therapeutic agent in the acute treatment of heart failure. Topics: Angiotensin-Converting Enzyme Inhibitors; Animals; Blood Pressure; Drug Synergism; Enalapril; Endothelin Receptor Antagonists; Heart Failure; Heart Rate; Hemodynamics; Male; Myocardial Infarction; Pyridines; Rats; Rats, Wistar; Tetrazoles | 2001 |
Kallikrein-kinin system activation and its interactions with other plasma haemostatic components in the coronary artery disease.
Concentrations of kininogens, prekallikrein, fibrinogen and antigens of protease inhibitors as well as kininase, fibrinolytic and antipapain activities were estimated in blood plasma (or serum) of patients with coronary artery disease (CAD) before and after the exercise test. The study was conducted on 44 subjects with chronic, stable CAD and 54 myocardial infarction patients (15 treated with streptokinase and 39 subjected to primary percutaneous transluminal coronary angioplasty, PTCA). The patients were divided into two subgroups: treated and untreated with angiotensin I-converting enzyme inhibitor (ACE-I), enalapril. Activation of the fibrinolytic system and the prekallikrein during the exercise test was demonstrated. No significant kininogen consumption was observed. A decrease in kininase activity was found. The results suggest the possibilities of endothelial cells contribution to plasminogen activation in CAD patients. Kininogen and kallikrein directly, or through the released kinins, may participate in regulation of endothelial cell hemostatic functions. Conversion of plasminogen to plasmin may undergo under the influence of kallikrein. The bradykinin induces the tissue plasminogen activator (t-PA) secretion, which depends also on the increased blood flow during the exercise test. Topics: Adult; Aged; Angioplasty, Balloon, Coronary; Angiotensin-Converting Enzyme Inhibitors; Case-Control Studies; Coronary Artery Disease; Enalapril; Exercise Test; Female; Hemostasis; Humans; Kallikrein-Kinin System; Male; Middle Aged; Myocardial Infarction | 2001 |
Differential effects of long-term renin-angiotensin system blockade on limitation of infarct size in cholesterol-fed rabbits.
We evaluated the effects of chronic inhibition of angiotensin-converting enzyme (ACE) or receptor blockade of angiotensin II type I on the size of myocardial infarcts induced by coronary occlusion-reperfusion in rabbits fed a high-cholesterol or normal diet for 10 weeks. In treated rabbits, myocardial infarction occurred 24 h after the last dose of enalapril or L-158809, an angiotensin II type I receptor antagonist, because of the drugs' waning effects on hemodynamic parameters. The size of the infarct was significantly larger in cholesterol-fed rabbits than in rabbits fed a normal diet. This augmentation of infarct size in cholesterol-fed rabbits was reversed by long-term treatment with enalapril, but not L-158809. The favorable effects of enalapril treatment disappeared after pretreatment with the bradykinin B(2) receptor blocker HOE 140. Long-term enalapril or L-158809 administration did not reduce the size of the infarct in rabbits fed a normal diet. ACE activity in ischemic myocardium significantly exceeded that in nonischemic myocardium and was further increased in cholesterol-fed rabbits, but was significantly reduced by long-term enalapril, but not L-158809. Moreover, treatment with enalapril, but not L-158809, restored acetylcholine-induced endothelium-dependent relaxation of aortic rings from cholesterol-fed rabbits. These results demonstrate that long-term ACE inhibition, but not angiotensin II type I receptor blockade, effectively reduces the size of myocardial infarcts in cholesterol-fed rabbits. The favorable effects of enalapril treatment may involve primarily a bradykinin B(2) receptor-mediated pathway. Topics: Analysis of Variance; Animals; Cholesterol, Dietary; Disease Models, Animal; Enalapril; Endothelium, Vascular; Hemodynamics; Imidazoles; Male; Myocardial Infarction; Myocardial Reperfusion; Probability; Rabbits; Reference Values; Renin-Angiotensin System; Survival Rate; Tetrazoles | 2000 |
Early angiotensin converting enzyme inhibitor therapy enhances the benefits of late coronary artery reperfusion on infarct expansion.
Individually, both late reperfusion and early angiotensin converting enzyme (ACE) inhibitor treatment prevent infarct expansion after acute myocardial infarction.. To examine the effect and mechanism of early post-myocardial infarction ACE inhibitor treatment, when used in combination with late coronary artery reperfusion, on infarct expansion.. Sprague-Dawley rats underwent 8 h of coronary occlusion followed by permanent reperfusion. The treatment group received enalapril, started 1 h after coronary occlusion and continued for 13 days. A control group received placebo. Two weeks after acute myocardial infarction, hemodynamic, morphometric and histologic analyses were performed.. Hemodynamic parameters were similar in both groups (P = NS). Infarct size was similar in the ACE inhibitor and placebo treatment groups (44 +/- 4% compared with 39 +/- 4%, P = NS). Septal thickness was also similar in the two groups (2.8 +/- 0.3 mm compared with 2.7 +/- 0.3 mm, P = NS). The ACE inhibitor-treated group had thicker infarcts than those in the placebo-treated group (0.93 +/- 0.07 mm compared with 0.76 +/- 0.04 mm, P < 0.05) and these infarcts were less expanded (expansion index 1.17 +/- 0.12 compared with 1.57 +/- 0.12, P < 0.05). ACE inhibitor treatment was associated with hypertrophy of viable myocytes within the scar compared with placebo treatment (cell diameter 11.1 +/- 0.5 microns compared with 8.9 +/- 0.4 microns, P < 0.01).. Early post-myocardial infarction ACE inhibitor treatment enhances the benefits of late coronary reperfusion on infarct expansion. The benefits may be related to hypertrophy of still-viable myocytes within the infarcted zone. Topics: Angiotensin-Converting Enzyme Inhibitors; Animals; Disease Models, Animal; Enalapril; Female; Hemodynamics; Myocardial Infarction; Myocardial Reperfusion; Myocardium; Necrosis; Probability; Random Allocation; Rats; Rats, Sprague-Dawley; Reference Values; Survival Rate; Time Factors; Treatment Outcome | 2000 |
Opposite effects of amlodipine and enalapril on infarct collagen and remodelling during healing after reperfused myocardial infarction.
To compare the effects of the calcium channel blocker amlodipine versus the angiotensin-converting enzyme inhibitor enalapril with or without reperfusion on infarct collagen and remodelling during healing after anterior myocardial infarction (MI).. In vivo left ventricular (LV) remodelling and function (by quantitative echocardiography) and hemodynamics were measured over six weeks in dogs that were randomized 24 h after reperfusion (2 h after anterior MI) or no reperfusion to oral amlodipine (5 mg bid, n=6), enalapril (5 mg bid, n=6), placebo (bid, n=6) or sham surgery (n=6) for six weeks. Ex vivo infarct size, infarct collagen (hydroxyproline), collagen volume fraction and LV topography were measured at six weeks.. Compared with placebo controls without reperfusion over six weeks in vivo, enalapril or amlodipine with or without reperfusion produced LV unloading and preserved volumes, shape and function, but enalapril limited LV hypertrophy more than amlodipine. However, compared with no reperfusion, amlodipine preserved infarct wall thickness and shape while enalapril decreased infarct wall thickness and increased the shape index. Ex vivo at six weeks, scar size as a percentage of risk was similar in the MI groups. Importantly, enalapril decreased infarct collagen already lowered by reperfusion, while amlodipine preserved infarct collagen after reperfusion and increased collagen volume fraction in spared myocardium.. Preservation of infarct collagen limits infarct remodelling during healing after reperfused MI and preserves LV shape. Amlodipine and enalapril exert opposite effects on infarct collagen and remodelling after reperfused MI. Topics: Amlodipine; Analysis of Variance; Angiotensin-Converting Enzyme Inhibitors; Animals; Calcium Channel Blockers; Collagen; Dogs; Enalapril; Female; Male; Myocardial Infarction; Myocardial Reperfusion; Random Allocation; Ventricular Remodeling; Wound Healing | 2000 |
Additional follow-up from the ABCD trial in patients with type 2 diabetes and hypertension.
Topics: Angiotensin-Converting Enzyme Inhibitors; Calcium Channel Blockers; Cardiovascular Diseases; Diabetes Mellitus, Type 2; Enalapril; Follow-Up Studies; Heart Failure; Humans; Hypertension; Myocardial Infarction; Nisoldipine | 2000 |
Changes in cardiac ANG II postmyocardial infarction in rats: effects of nephrectomy and ACE inhibitors.
We evaluated in rats the time course of changes in cardiac versus plasma ANG I and II postmyocardial infarction (MI) and the effects of nephrectomy and angiotensin-converting enzyme (ACE) inhibitors on the early changes post-MI. Acute coronary artery ligation was induced in conscious rats using the two-stage model, and plasma and cardiac tissue were obtained shortly (6 h, 1 and 3 days) and chronically (1, 4, and 8-9 wk) after MI. In an additional group of rats, bilateral nephrectomy was performed 18 h before the coronary artery ligation, and samples were obtained at 6 h post-MI. Furthermore, in two additional groups of rats, treatment with enalapril and quinapril was started 3 days before the ligation, and samples were obtained at 1 or 3 days post-MI. In these groups of rats, plasma and left ventricular (LV) (infarct and infarct free) ANG I and II were measured by RIA after separation on HPLC. In control rats, plasma ANG I and II showed a clear increase at 6 h post-MI but subsequently only minor increases were observed. In contrast, LV ANG II showed major increases at 6 h and 1 day post-MI, which had returned to normal by 3 days in the infarct-free LV and after 1(-2) wk in the infarct LV. LV ANG I showed a more gradual increase and remained elevated in the infarct up to 8-9 wk. Nephrectomy preceding the MI lowered ANG I and II in plasma but enhanced their increases in the heart at 6 h post-MI. Both ACE inhibitors decreased plasma ANG II associated with large increases in plasma ANG I. They also inhibited the increases in LV ANG II in both the infarct and infarct-free LV at 1 and 3 days post-MI with however no significant increase in LV ANG I. In conclusion, induction of a MI in conscious rats leads to rapid and marked, but only short-lived, increases in cardiac tissue ANG II in both the infarct and infarct-free parts of the LV. Pretreatment with ACE inhibitors, but not nephrectomy, blocks this increase. Local production appears to play a major role in the increases in cardiac ANG II post-MI. Topics: Angiotensin I; Angiotensin II; Angiotensin-Converting Enzyme Inhibitors; Animals; Enalapril; Heart Ventricles; Isoquinolines; Male; Myocardial Infarction; Myocardium; Nephrectomy; Quinapril; Rats; Rats, Wistar; Renin; Tetrahydroisoquinolines | 1999 |
Enalapril improves arterial elastic properties in rats with myocardial infarction.
Systemic arterial elastic properties, important determinants of left ventricular function and coronary blood flow, are compromised in myocardial infarction (MI). The cardiac effect of angiotensin-converting enzyme inhibitors (ACEIs) has been extensively studied, whereas their arterial effect has been poorly reported in MI. The aim of this work was to study the effect of prolonged ACEI enalapril treatment on systemic arterial structure and elastic properties in rats with MI. One week after the induction of an MI, 40 male Wistar rats received either no treatment (n = 20) or ACEI enalapril (2 mg/kg; n = 20) for 17 weeks. At the end of the treatment period, blood pressure, cardiac output, total peripheral resistance, systemic arterial compliance, characteristic impedance, and left ventricular power were measured in anesthetized rats. Then the rats were killed for infarct-size determination and aortic histomorphometric study. Infarct size, heart, and left and right ventricular weights were similar in the ACEI-treated and untreated infarcted rats. Prolonged ACEI enalapril treatment reduced blood pressure by 17% (p < 0.001), total peripheral resistance by 22% (p < 0.01), and characteristic impedance by 26% (p < 0.03), and increased systemic arterial compliance by 35% (p < 0.01), in comparison with untreated infarcted rats. Enalapril reduced aortic media wall thickness by 9% (p < 0.02) and increased elastin content by 22% (p < 0.03) and elastin-to-collagen content ratio by 42% (p < 0.01). Enalapril did not affect cardiac output and left ventricular power. Smooth muscle cell nuclei number and size and collagen content of aortic wall were similar in the ACEI-treated and untreated infarcted rats. These results indicate that long-term treatment with ACEI enalapril improves arterial elastic properties through structural modifications of arterial wall in rats with MI. This vascular effect may contribute to improve the left ventricular function and the coronary perfusion of infarcted myocardium, and added to the cardiac effect, may explain the prevention of left ventricular remodeling observed with ACEI in this model. Topics: Anesthesia; Angiotensin-Converting Enzyme Inhibitors; Animals; Arteries; Body Weight; Enalapril; Hemodynamics; Male; Myocardial Infarction; Organ Size; Rats; Rats, Wistar; Time Factors | 1999 |
[Early application of angiotensin converting enzyme inhibitors in acute myocardial infarction].
Inhibitors of angiotensin converting enzyme (ACE) were tried in patients early after myocardial infarction (MI) irrespective of the severity of circulation insufficiency. Monopril was used in 23 patients in the dose 7.6 mg/day. Ednit was given to 21 patients in the dose 5.3 mg/day. Control groups included 19 and 21 patients, respectively. All the patients underwent treadmill test and echocardiography on MI day 1 and 13-14. ACE inhibitors provide better exercise tolerance and favourable course of MI even in the absence of marked manifestations of cardiac failure though left ventricular ejection changed insignificantly. They may also prevent myocardial ischemia. The difference between monopril and ednit effects was insignificant. Topics: Angiotensin-Converting Enzyme Inhibitors; Coronary Care Units; Echocardiography; Enalapril; Exercise Test; Follow-Up Studies; Fosinopril; Humans; Male; Middle Aged; Myocardial Contraction; Myocardial Infarction; Stroke Volume; Time Factors; Treatment Outcome | 1999 |
Statistical methods for analyzing repeated measures.
Repeated measurements arise frequently in biomedical research. In many situations, the scientific question of interest concerns finding differences in the measurements between groups. This question is frequently addressed by using analysis of variance-type methods that fail to incorporate information regarding the repeated sampling design of the experiment. In this paper, we provide an introduction to nonstatisticians of two approaches for analyzing such data. The procedures can be performed by using available software. These methods are illustrated on data from a preclinical study conducted by ZymoGenetics. Topics: Angiotensin-Converting Enzyme Inhibitors; Animals; Blood Pressure; Data Interpretation, Statistical; Dobutamine; Dose-Response Relationship, Drug; Enalapril; Male; Models, Statistical; Myocardial Infarction; Rats; Rats, Sprague-Dawley; Statistics as Topic; Ventricular Function, Left | 1999 |
Calcium-channel blockers for hypertension--uncertainty continues.
Topics: Angiotensin-Converting Enzyme Inhibitors; Calcium Channel Blockers; Cardiovascular Diseases; Diabetes Mellitus, Type 2; Enalapril; Humans; Hypertension; Myocardial Infarction; Nisoldipine | 1998 |
Divergent effects of angiotensin-converting enzyme inhibition and angiotensin II-receptor antagonism on myocardial cellular proliferation and collagen deposition after myocardial infarction in rats.
There is mechanistic rationale to suggest differential effects of angiotensin-converting enzyme (ACE) inhibition and angiotensin II type 1 (AT1)-receptor antagonism on ventricular remodeling after myocardial infarction (MI). We compared the effects of ACE inhibition, AT1-receptor antagonism, and their combination on post-MI ventricular remodeling in rats. We induced MI in 62 rats, which then received one of four treatments: (a) placebo; (b) the ACE inhibitor, enalapril; (c) the AT1-receptor antagonist, losartan; and (d) enalapril and losartan in combination. Two weeks after MI, we examined: (a) heart weight (HW)/body weight (BW) ratio; (b) nonmyocyte cellular proliferation in the noninfarct zone by using proliferating cell nuclear antigen staining; and (c) collagen content within the noninfarct zone. Placebo-treated, infarcted rats developed significant increases in HW/BW ratio (p < 0.001), left ventricular (LV) volume (p < 0.01), nonmyocyte cellular proliferation (p < 0.04), and collagen content (p < 0.01) compared with noninfarcted controls. Enalapril, losartan, and combination therapy limited the increase in HW/BW ratio (all p values <0.01 vs. placebo). Enalapril inhibited nonmyocyte proliferation (p < 0.01 vs. placebo), whereas losartan had a smaller effect (p = NS vs. placebo; p < 0.03 vs. enalapril); combined treatment also reduced nonmyocyte cellular proliferation but did not reach statistical significance (p = 0.08 vs. placebo). Enalapril and combination treatment significantly diminished collagen content (both p values <0.01 vs. placebo), whereas losartan did not. Thus, ACE inhibition and AT1-receptor antagonism equally limited myocardial hypertrophy after MI in rats, but ACE inhibition more effectively prevented nonmyocyte cellular proliferation and collagen deposition in the noninfarcted myocardium. Combination therapy was no more effective than was ACE inhibition alone. These data suggest that the myocyte hypertrophic response after MI is strongly influenced by activation of the AT1 receptor, whereas nonmyocyte cellular proliferation and collagen deposition result, in part, from mechanisms separate from AT1-receptor activation. Topics: Angiotensin Receptor Antagonists; Angiotensin-Converting Enzyme Inhibitors; Animals; Antihypertensive Agents; Cell Division; Collagen; Enalapril; Losartan; Male; Myocardial Infarction; Myocardium; Rats; Rats, Sprague-Dawley | 1998 |
Harmful effect of enalapril on left ventricular remodelling in patients without a severe residual stenosis after acute anterior wall infarction?
Topics: Angioplasty, Balloon, Coronary; Angiotensin-Converting Enzyme Inhibitors; Combined Modality Therapy; Enalapril; Humans; Myocardial Infarction; Recurrence; Stroke Volume; Thrombolytic Therapy; Ventricular Function, Left | 1998 |
Nisoldipine and myocardial infarction.
Topics: Angiotensin-Converting Enzyme Inhibitors; Calcium Channel Blockers; Diabetes Mellitus, Type 2; Enalapril; Humans; Hypertension; Insulin; Myocardial Infarction; Nisoldipine | 1998 |
Nisoldipine and myocardial infarction.
Topics: Angiotensin-Converting Enzyme Inhibitors; Calcium Channel Blockers; Diabetes Mellitus, Type 2; Enalapril; Humans; Hypertension; Myocardial Infarction; Nisoldipine | 1998 |
Nisoldipine and myocardial infarction.
Topics: Albuminuria; Angiotensin-Converting Enzyme Inhibitors; Calcium Channel Blockers; Diabetes Mellitus, Type 2; Enalapril; Humans; Hypertension; Myocardial Infarction; Nisoldipine | 1998 |
Early angiotensin converting enzyme inhibitor therapy after experimental myocardial infarction prevents left ventricular dilation by reducing infarct expansion: a possible mechanism of clinical benefits.
To examine the effects of early angiotensin-converting enzyme (ACE) inhibitor therapy after myocardial infarction on infarct expansion in an experimental rat model.. ACE inhibitor therapy within 24 h of acute myocardial infarction (AMI) reduces mortality by unknown mechanism(s).. Rats underwent permanent coronary artery occlusion. A treated group received enalapril (1.9+/-0.2 mg/kg) daily in drinking water beginning 2 h after coronary artery occlusion, a time too late to reduce infarct size. Rats were sacrificed 2 days or 2 weeks after myocardial infarction. Hearts were arrested and fixed at a constant pressure, then sectioned and photographed for morphometric analysis.. Infarcts in the control group expanded between 2 days and 2 weeks after myocardial infarction (expansion index 0.7+/-0.1 versus 2.5+/-0.4, P< 0.05). However, infarct expansion remained unchanged in the enalapril group between 2 days and 2 weeks after myocardial infarction (expansion index 0.8+/-0.1 versus 1.3+/-0.1, NS). Two weeks after myocardial infarction, the enalapril group had fewer expanded infarcts than the control group (expansion index 1.3+/-0.1 versus 2.5+/-0.4, P< 0.05). While left ventricular volume increased in the control group between 2 days and 2 weeks after myocardial infarction (0.17+/-0.01 ml versus 0.36+/-0.03 ml, P< 0.05), it remained constant in the enalapril group (0.22+/-0.02 ml versus 0.25+/-0.03 ml, NS). Two weeks after myocardial infarction, the left ventricles were larger in the control group than in the enalapril group (0.36+/-0.03 ml versus 0.25+/-0.03 ml, P< 0.05).. Treatment with enalapril initiated 2 h after AMI prevented left ventricular dilation by limiting infarct expansion. This may explain the mechanism by which ACE inhibitor therapy started within 24 h of an AMI improves survival 5-6 weeks after infarction. Topics: Angiotensin-Converting Enzyme Inhibitors; Animals; Enalapril; Female; Hypertrophy, Left Ventricular; Myocardial Infarction; Random Allocation; Rats; Rats, Sprague-Dawley; Time Factors; Ventricular Remodeling | 1998 |
Pharmacological profile of valsartan, a non-peptide angiotensin II type 1 receptor antagonist. 4th communication: improvement of heart failure of rats with myocardial infarction by valasartan.
The hemodynamic effects of valsartan ((S)-N-valeryl-N-¿[2'-(1H-tetrazol-5-yl)bipheneoyl-4-yl]meth yl¿valine, CAS 137862-53-4, CGP 48933), a new angiotensin II type 1 receptor antagonist, on rats with myocardial infarction induced by coronary artery ligation was examined. Four weeks after ligation, mean blood pressure, left ventricular pressure and cardiac output decreased, while left ventricular end-diastolic pressure increased in control rats. Left ventricular end-diastolic pressure significantly decreased in rats treated with valsartan at 30 mg/kg/d p.o. for 4 weeks. Total systemic resistance remarkably decreased in those with enalapril 3 mg/kg/d p.o. and valsartan 30 mg/kg/d p.o. Valsartan and enalaprilat did not affect cardiac functions of isolated intact rat hearts before and after ischemia in Langendorff apparatus. In addition to hemodynamic effects observed in vivo, valsartan at 30 mg/kg p.o. significantly inhibited left ventricular hypertrophy. Valsartan would thus appear to be clinically useful for treating heart failure following myocardial infarction. Topics: Angiotensin Receptor Antagonists; Animals; Antihypertensive Agents; Blood Pressure; Body Weight; Cardiomegaly; Enalapril; Male; Myocardial Infarction; Myocardial Ischemia; Myocardial Reperfusion Injury; Organ Size; Rats; Receptor, Angiotensin, Type 1; Receptor, Angiotensin, Type 2; Tetrazoles; Valine; Valsartan; Vascular Resistance; Ventricular Function, Left | 1997 |
Effect of angiotensin-converting enzyme inhibition on infarct collagen deposition and remodelling during healing after transmural canine myocardial infarction.
Angiotensin-converting enzyme (ACE) inhibition for six weeks after myocardial infarction (MI) lowers the collagen content of infarct scars in dogs. However, temporal changes in collagen content of the infarct zone (IZ) with ACE inhibition during healing over six weeks after MI and their possible relation to IZ remodelling have not been determined.. IZ collagen (hydroxyproline) was measured over six to seven weeks in dogs treated with captopril (50 mg bid), enalapril (2.5 mg bid) or placebo, beginning on the second day following transmural anterior MI (or sham). In vivo changes in IZ and global left ventricular (LV) remodelling, mass and function (echocardiograms) and hemodynamics among six-week survivors were also measured.. Compared with placebo, both inhibitors decreased IZ collagen (P < 0.001) over the seven weeks. Among the six-week survivors, both inhibitors lowered IZ collagen (P < or = 0.001) and increased the collagen type I:III ratio. However, preload was lower, increase in diastolic volume and mass were less and systolic function improved. Although the doses of captopril (but no enalapril) decreased afterload, inhibition of IZ collagen was less, IZ bulging and global LV dilation were less and systolic function was better with captopril than with enalapril. In all three MI groups, deaths over the seven weeks correlated with greater infarct size, LV volume and dysfunction and lower IZ collagen.. ACE inhibition suppresses the temporal increase in IZ collagen and attenuates IZ expansion, thinning and bulging, and LV enlargement and aneurysm formation during healing after MI. Topics: Angiotensin-Converting Enzyme Inhibitors; Animals; Captopril; Collagen; Dogs; Enalapril; Heart Ventricles; Hydroxyproline; Hypertrophy, Left Ventricular; Myocardial Infarction; Ultrasonography | 1997 |
The time course of left ventricular remodeling after acute myocardial infarction.
Topics: Angiotensin-Converting Enzyme Inhibitors; Enalapril; Humans; Hypertrophy, Left Ventricular; Multicenter Studies as Topic; Myocardial Infarction; Scandinavian and Nordic Countries; Time Factors; Ventricular Dysfunction, Left; Ventricular Function, Left | 1997 |
Effects of amlodipine versus enalapril on left ventricular remodelling after reperfused anterior myocardial canine infarction.
To compare the effects of the calcium channel blocker amlodipine with those of the angiotensin-converting enzyme (ACE) inhibitor enalapril on left ventricular (LV) remodelling and dysfunction during healing after reperfused anterior myocardial infarction (MI). ACE inhibitors and reperfusion are known to limit LV remodelling after MI. However, the effects of ACE inhibitors and calcium channel blockers on LV remodelling after reperfused MI have not been compared.. Changes in LV topography and function (quantitative echocardiograms) and hemodynamics were measured over six weeks in dogs that were randomized 24 h after reperfusion, done after 2 h of anterior MI, to oral amlodipine (5 mg bid; n = 7), enalapril (5 mg bid; n = 6) or no drug (controls; n = 6) for six weeks. Postmortem LV topography was measured at six weeks.. Scar sizes after six weeks were similar in the three groups. Both enalapril and amlodipine reduced the rate pressure product, but decreases in mean arterial and left atrial pressures were more sustained over six weeks with enalapril. Compared with controls over six weeks, both enalapril and amlodipine preserved LV volumes, global ejection fraction, regional function and infarct segment length, but enalapril blocked the increase in non-infarct wall thickness, attenuated the infarct wall thickness, preserved shape and decreased global LV mass more than amlodipine. Sham-operated dogs (n = 3) showed no significant structural changes.. Both enalapril and amlodipine preserve LV volumes and function during healing after reperfused MI, but enalapril more effectively limits hypertrophy, attenuates infarct wall thickness and preserves shape. Topics: Amlodipine; Angiotensin-Converting Enzyme Inhibitors; Animals; Calcium Channel Blockers; Disease Models, Animal; Dogs; Drug Evaluation; Enalapril; Heart; Myocardial Infarction; Myocardial Reperfusion; Postoperative Care; Wound Healing | 1997 |
ACE inhibition and left ventricular remodelling.
Topics: Angiotensin-Converting Enzyme Inhibitors; Coronary Disease; Enalapril; Humans; Myocardial Infarction; Ventricular Function, Left | 1997 |
Allopurinol and enalapril. Drug induced anaphylactic coronary spasm and acute myocardial infarction.
Topics: Allopurinol; Anaphylaxis; Coronary Vasospasm; Drug Interactions; Emergencies; Enalapril; Humans; Male; Middle Aged; Myocardial Infarction | 1995 |
Effect of captopril and enalapril on left ventricular geometry, function and collagen during healing after anterior and inferior myocardial infarction in a dog model.
This study compared the effects of captopril and enalapril on left ventricular geometry, function and mass and on scar collagen and topography during healing after anterior and inferior myocardial infarction in a canine model.. The beneficial effect of prolonged angiotensin-converting enzyme inhibitor therapy on remodeling during healing after myocardial infarction might be greater in anterior than inferior infarcts and more effective with captopril than enalapril therapy.. The effects of 6 weeks of therapy with captopril (50 mg twice a day), enalapril (2.5 mg twice a day) or placebo on in vivo variables of left ventricular remodeling, function and mass (by echocardiography), hemodynamic function, postmortem topography (by planimetry) and collagen (hydroxyproline levels) were studied in 36 instrumented dogs randomized to receive therapy 48 h after left anterior descending or left circumflex coronary artery occlusion.. Compared with placebo therapy, both captopril and enalapril decreased infarct expansion and thinning, progressive ventricular dilation, ventricular mass and asynergy and infarct collagen levels in anterior and inferior infarcts. Despite similar small scar sizes, the effects on remodeling and dysfunction were greater in anterior than inferior infarcts. In addition, captopril produced greater attenuation of infarct expansion and ventricular enlargement, greater improvement in volume ejection fraction and less decrease in infarct collagen levels than enalapril.. On balance, captopril and enalapril attenuated left ventricular remodeling and preserved function in small anterior and inferior infarcts despite differences in the effects of the drugs on individual remodeling variables. Further studies will be needed to determine whether inhibition of infarct collagen might be harmful, or differences between captopril and enalapril therapy important, in large transmural infarctions. Topics: Animals; Captopril; Collagen; Dogs; Echocardiography; Electrocardiography; Enalapril; Hemodynamics; Hypertrophy, Left Ventricular; Myocardial Infarction; Systole; Time Factors; Ventricular Function, Left | 1995 |
Effect of enalapril on ventricular remodeling and function during healing after anterior myocardial infarction in the dog.
Ventricular remodeling after myocardial infarction involves changes in ventricular size, shape, structure, and matrix that impact on function. Prolonged angiotensin-converting enzyme inhibition after infarction with captopril reduces ventricular enlargement and improves clinical outcome, but whether enalapril produces similar benefits is controversial.. The effect of enalapril during healing between 1 day and 6 weeks after myocardial infarction on in vivo changes in ventricular size, shape, mass, and function (asynergy, or akinesis and dyskinesis, and ejection fraction), as determined by serial two-dimensional echocardiography, hemodynamics, postmortem topography (planimetered short- and long-axis ventricular contours), and collagen content (determined by levels of hydroxyproline, a marker for collagen), was measured in 25 instrumented dogs. The dogs were randomized 1 day after left anterior descending coronary artery ligation to a control group (no treatment) and a group receiving oral enalapril (2.5 mg BID). Compared with no treatment, enalapril produced a sustained lowering of left atrial pressure but no difference in heart rate and mean blood pressure over the 6 weeks. Also compared with no treatment, enalapril modified in vivo remodeling parameters between 1 day and 6 weeks, with less elongation of the asynergy-containing segment, a lower expansion index (ratio of endocardial lengths of infarct to non-infarct-containing segments demarcated by papillary muscle landmarks), less scar wall thinning, a lower thinning ratio (ratio of average thickness of infarcted wall to average thickness of the normal wall), smaller ventricular volume, less regional bulging and aneurysm frequency, prevention of the increase in ventricular mass, less total extent of asynergy, and higher volume ejection fraction. At postmortem examination, scar mass was similar in the two groups, but topographic maps with enalapril revealed less infarct bulging, flatter infarct scars, and less noninfarct wall thickness. In addition, postmortem collagen content was similar in noninfarct zones of the two groups but lower in infarct zones of the dogs given enalapril.. Prolonged enalapril therapy, in a dose that did not lower blood pressure, during healing after anterior infarction produced prolonged reduction of left ventricular preload in dogs. This diastolic unloading was associated with limitation of remodeling parameters (infarct expansion and thinning, progressive ventricular dilation and hypertrophy, and regional bulging), less total asynergy, and improved left ventricular ejection fraction. Although angiotensin-converting enzyme inhibition was associated with lower collagen content in the infarct area and altered scar topography, these effects did not impact negatively on overall remodeling and function. Topics: Aldosterone; Animals; Collagen; Dogs; Enalapril; Female; Hemodynamics; Male; Myocardial Infarction; Renin; Ventricular Function | 1995 |
Effect of a calcium-sensitizing positive inotropic agent MCI-154 and its combined use with enalapril on postischemic contractile dysfunction of dog hearts.
We wished to elucidate the effects of the calcium-sensitizing positive inotropic agent MCI-154 and its combined use with an angiotensin-converting enzyme (ACE) inhibitor enalapril on postischemic contractile dysfunction. Anesthetized dogs underwent a 30-min occlusion of the left anterior descending coronary artery (LAD) followed by 2 h of reperfusion. Regional myocardial segment shortening in the ischemic LAD area was assessed by sonomicrometry. Myocardial segment shortening decreased in response to the LAD occlusion and remained decreased during 2-h reperfusion. The intravenous infusion of MCI-154 (0.1 or 0.3 micrograms/kg/min) initiated 10 min after occlusion and throughout reperfusion significantly improved the recovery of segment shortening. The alleviation of the postischemic contractile dysfunction by MCI-154 was augmented when the animals were treated with a bous injection of enalapril (0.3 mg/kg) 15 min before ischemia followed by an infusion of the drug (0.003 mg/kg/min). The pretreatment with enalapril alone (0.3 mg/kg plus 0.003 mg/kg/min or 1 mg/kg plus 0.01 mg/kg/min) did not alleviate the postichemic dysfunction, however, although it decreased systemic blood pressure (BP). Ischemic bed size, myocardial necrosis (by triphenyltetrazolium chloride staining), and collateral blood flow (by colored microspheres) were similar in all experimental groups. These results indicate that MCI-154 improves the postischemic contractile function of dog heart, whereas enalapril fails to improve it. ACE inhibitors may also augment the efficacy of cardiotonics on postischemic dysfunction. Topics: Angiotensin-Converting Enzyme Inhibitors; Animals; Blood Pressure; Calcium; Cardiotonic Agents; Coronary Circulation; Disease Models, Animal; Dogs; Dose-Response Relationship, Drug; Enalapril; Female; Infusions, Intravenous; Male; Myocardial Contraction; Myocardial Infarction; Myocardial Ischemia; Pyridazines | 1995 |
Effects of long-term therapy with ACE inhibitors, captopril, enalapril and trandolapril, on myocardial energy metabolism in rats with heart failure following myocardial infarction.
Although pharmacological therapy with angiotensin converting enzyme (ACE) inhibitors has proved to be effective in patients with heart failure (HF), the experimental basis of this effect has not yet been addressed. In the present study, animals with HF were treated with an oral administration of 10 mg/kg/day captopril, 10 mg/kg/day enalapril and 3 mg/kg/day trandolapril from the 2nd to 12th week after the operation. HF was induced by permanent occlusion of the left coronary artery of the rat at 2 mm from its origin. Treatment of the HF rats with the ACE inhibitors enhanced the decrease in mean arterial blood pressure, attenuated the rise in left ventricular end-diastolic pressure, an indirect marker of preload, and diminished the reduction in cardiac output and stroke volume indices of the HF animal. Treatment also reversed the reduction in ATP, creatine phosphate, creatine and the mitochondrial oxygen consumption rate of the viable left and right ventricles of the HF animal. The improvement of the cardiac output index and high-energy phosphate levels of the HF rat by the ACE inhibitors was associated with the recovery of the mitochondrial oxygen consumption rate. In sham-operated animals, treatment with the ACE inhibitors reduced mean arterial pressure and left ventricular systolic pressure, but not metabolic variables concerning myocardial energy metabolism. The present results provide evidence that ACE inhibitor therapy improves cardiac function and myocardial energy metabolism of experimental animals with chronic heart failure. The mechanism underlying the benefit of long-term treatment with ACE inhibitors is probably attributable to recovery or preservation of the mitochondrial function and reduction in preload. Topics: Adenine Nucleotides; Angiotensin-Converting Enzyme Inhibitors; Animals; Captopril; Enalapril; Energy Metabolism; Heart Failure; Hemodynamics; Indoles; Lactates; Male; Mitochondria, Heart; Myocardial Infarction; Myocardium; Organ Size; Oxygen Consumption; Phosphocreatine; Rats; Rats, Wistar | 1995 |
Effects of enalapril on T and B cell function in rats after myocardial infarction.
The cellular mechanisms following myocardial infarction remain poorly characterized. It is believed that an inflammatory and immunologic process may be involved and that the beneficial effects of enalapril on remodeling may, in part, work through an immune mechanism. To characterize the effect of enalapril on immune alterations in the late phase of ventricular remodeling after myocardial infarction, rats underwent left coronary artery ligation followed by 6 weeks of either enalapril or placebo treatment. Infarct sizes, heart weights, and volumes were compared. Peripheral and splenic leukocyte and lymphocyte subsets, along with T cell blastogenesis, were quantified in enalapril treated rats 6 weeks after coronary ligation and compared to untreated control rats. Additionally, antibody production to a de novo antigen, keyhole limpet hemocyanin, was assessed with and without treatment. Average infarct size was equivalent among enalapril-treated myocardial infarction rats and untreated infarct rats. There was, however, less left and right ventricular hypertrophy in the enalapril treated group. Enalapril completely prevented the 42% increase in white blood count, the 88% increase in neutrophils, and the 28% increase in lymphocyte count seen in untreated infarct rats. Both untreated and enalapril treated rats tended toward a decrease in T helper:suppressor ratio. All rats treated with enalapril, however, had a significant increase in the T helper:suppressor ratio versus untreated control rats (F = 3.6, P = .018). Blastogenesis was markedly increased in T cells from infarcted animals. This was mitigated by treatment with enalapril. Additionally, immunoglobulin G antibody production was significantly lessened in rats treated with enalapril. The results of this study suggest that alterations in immunoregulatory cell type and function occurs following myocardial infarction. The beneficial effects of the angiotensin-converting enzyme inhibitor enalapril may be, in part, due to its mitigating effects on immune cell release and activation following myocardial infarction. Topics: Angiotensin-Converting Enzyme Inhibitors; Animals; B-Lymphocytes; Enalapril; Fluorescent Antibody Technique; Male; Myocardial Infarction; Rats; Rats, Sprague-Dawley; T-Lymphocytes | 1995 |
[Echocardiographic evaluation of left ventricular function in patients after myocardial infarction treated with enalapril].
The studies were carried out in 30 patients (24 men and six women) aged 40-56 years, mean age 51 years after myocardial infarction in whom enalapril in doses 5-10 mg daily, mean dose 8,5 mg daily was added to drugs used as yet. This drug was administered for six weeks. The patients had myocardial infarction 6-18 months before their inclusion to the studies. In all patients two-dimensional echocardiographic and Doppler examinations were performed twice: before and after the treatment with enalapril. Left ventricular contractility disturbances and the following parameters were analysed: maximal early diastolic filling rate (EDF), maximal late diastolic filling rate (LDF), EDF/LDF ratio and early diastolic deceleration time (dec. EDF) and early diastolic slope (EF sl.). Enalapril administered in patients after myocardial infarction caused an increase of ejection fraction and increase of the contractility of left ventricular muscle segments not involved by necrosis. It exerted, however, no effect on the changes of contractility index. After the treatment with enalapril the maximal late diastolic filling rate (LDF) was significantly decreased while early diastolic deceleration slope (EF sl.) was significantly increased. The observed influence of enalapril on the left ventricular filling profile may suggest an improvement of left ventricular diastolic function. Topics: Adult; Enalapril; Female; Humans; Male; Middle Aged; Myocardial Infarction; Ultrasonography; Ventricular Function, Left | 1994 |
[The role of ACE inhibitors in heart failure. Lessons of CONSENSUS, SOLVD and V-HeFTII].
Heart failure is today one of the most serious health problems of modern industrialized societies. The increase in the mean age of the population is an additional factor which favours a high incidence of episodes of heart failure. Age is also a relevant factor in mortality linked with heart failure. On this basis more emphasis has been given by researchers and physicians to improve a preventive and therapeutic approach to heart failure. For many years the pharmacological treatment of heart failure patients was based on the increase in inotropism through the digitalis and on the reduction in sodium-water retention through diuretics, while less importance was given to the improvement of the afterload. We have had knowledge of vasodilatory drugs in chronic heart failure for at least 20 years but only 10 years ago with the Vasodilator-Heart Failure Trial (V-HeFTI), it was proved that the combination of hydralazine and nitrates in addition to the conventional treatment, improved the survival of patients affected by moderate-severe heart failure. With the advent of the ACE-inhibitors, in the '80s, the first studies concerning the role of such drugs in heart failure were carried out. In the Cooperative North Scandinavian Enalapril Survival Study (CONSENSUS I) it was proved for the first time that an ACE-inhibitor (enalapril), added to the conventional heart failure therapy, improved the survival of patients with severe congestive heart failure (NYHA class IV). The result was so extraordinary that the study was interrupted for ethical reasons. However, it has raised a considerable interest in the study of the ACE-inhibitors in heart failure and now it has been proved that such drugs are a milestone in a correct pharmacological approach to heart failure. Topics: Adult; Aged; Aged, 80 and over; Angina Pectoris; Angiotensin-Converting Enzyme Inhibitors; Clinical Trials as Topic; Clinical Trials, Phase I as Topic; Digoxin; Drug Therapy, Combination; Enalapril; Felodipine; Follow-Up Studies; Heart Failure; Humans; Middle Aged; Multicenter Studies as Topic; Myocardial Infarction; Randomized Controlled Trials as Topic; Time Factors; Vasodilator Agents; Ventricular Dysfunction | 1994 |
[The clinical and hemodynamic effects of enalapril and its influence on the peri-infarct area in patients with an acute myocardial infarct].
Topics: Adult; Aged; Aged, 80 and over; Drug Evaluation; Enalapril; Female; Heart; Heart Failure; Hemodynamics; Humans; Male; Middle Aged; Myocardial Infarction; Nitroglycerin | 1994 |
Comparative effects of chronic angiotensin-converting enzyme inhibition and angiotensin II type 1 receptor blockade on cardiac remodeling after myocardial infarction in the rat.
After myocardial infarction, the noninfarcted left ventricle develops reactive hypertrophy associated with a depressed coronary flow reserve, myocardial interstitial fibrosis, and reduced capillary density. The present study investigated the comparative cardiac effects of chronic angiotensin-converting enzyme (ACE) inhibition and selective angiotensin II type 1 receptor (AT1) blockade in the rat model of myocardial infarction and failure.. Seven days after coronary ligation (MI), rats were randomized to enalapril (n = 8; 500 micrograms.kg-1.d-1), losartan (n = 9; 3 mg.kg-1.d-1), or placebo (n = 8) and treated for 6 weeks. Sham-operated rats (n = 10) served as controls. Coronary blood flow was measured with radiolabeled microspheres during baseline and maximal coronary dilation induced by dipyridamole (2 mg.kg-1.min-1 over 10 minutes). Right and left ventricular (LV) weight was increased in infarcted rats compared with sham-operated animals and enalapril- and losartan-treated MI rats. Minimal LV and right ventricular coronary vascular resistance was increased in MI rats but normalized with enalapril and losartan (LV:sham, 8.9; MI-placebo, 12.7; MI-enalapril, 9.2; MI-losartan, 8.8 mm Hg.mL-1.min-1.g-1, all P < .05 versus MI-placebo). Interstitial fibrosis determined from perfusion-fixed hearts was increased in infarcted rats but reduced by both enalapril and losartan. Myocardial capillary density improved with enalapril and losartan. In separate groups treated as above, plasma and tissue ACE activity was determined and demonstrated significantly higher ACE activity in noninfarcted LV tissue of MI-placebo rats compared with sham (0.64 vs 0.27 nmol.mg protein-1.min-1, P < .05). Enalapril and losartan reduced LV ACE activity (0.39 and 0.29 nmol.mg protein-1.min-1, P < .05 versus MI-placebo).. The present study demonstrates that both chronic ACE inhibition and AT1 receptor blockade (1) reduces cardiac hypertrophy, (2) restores minimal coronary vascular resistance in postinfarction reactive hypertrophy, and (3) attenuates the development of myocardial interstitial fibrosis in the noninfarcted LV. These results suggest that inhibition of generation of angiotensin II and AT1 receptor blockade are equally effective in preventing important features of ventricular remodeling after myocardial infarction. Topics: Angiotensin II; Angiotensin Receptor Antagonists; Animals; Biphenyl Compounds; Coronary Circulation; Enalapril; Hypertrophy, Left Ventricular; Imidazoles; Losartan; Male; Myocardial Infarction; Myocardium; Rats; Rats, Sprague-Dawley; Tetrazoles; Time Factors | 1994 |
[ACE inhibitors in cardiac insufficiency and myocardial infarct. What happens after myocardial infarct?].
Topics: Angiotensin-Converting Enzyme Inhibitors; Echocardiography; Enalapril; Heart Failure; Humans; Myocardial Infarction | 1994 |
Comparison of angiotensin converting enzyme and renin inhibition in rats following myocardial infarction.
Renal and systemic hemodynamics were studied in rats 1 month after induction of myocardial infarction by ligation of the left coronary artery. The mean arterial pressure, heart rate, and cardiac index were not different from controls, but there were striking elevations in heart weight (p < 0.001), left ventricular end diastolic pressure (p < 0.002), and renal vascular resistance (p < 0.01). Renal blood flow and the percent of cardiac output perfusing the kidneys were reduced by 18% (p < 0.01) and 14% (p < 0.01), respectively. Acute angiotensin inhibition was studied at a dose of the converting enzyme inhibitor, enalapril, or the renin inhibitor, CP71362, that lowered the mean arterial pressure by 15 mm Hg in normal rats. In normal rats, enalapril and CP71362 were without effect on renal blood flow (RBF), renal vascular resistance (RR), and RBF as a percent of cardiac output. However, in rats with myocardial infarction, enalapril and CP71362 increased the RBF and RBF as a percent of cardiac output and lowered the RR to levels similar to normal controls (p < 0.02). Enalapril and CP71362 were equally effective in reducing the left ventricular end-diastolic pressure and total peripheral resistance in rats with myocardial infarction. These data demonstrate significant intrarenal vasoconstriction following myocardial infarction in the absence of detectable changes in mean arterial pressure or cardiac index. Converting enzyme inhibition or renin inhibition had similar beneficial effects on cardiorenal function, suggesting that both classes of compounds act by a similar mechanism to improve renal hemodynamics in congestive heart failure. Topics: Angiotensin-Converting Enzyme Inhibitors; Animals; Blood Pressure; Cardiac Output; Coronary Circulation; Coronary Vessels; Enalapril; Heart Rate; Male; Microspheres; Myocardial Infarction; Oligopeptides; Rats; Rats, Sprague-Dawley; Renal Circulation; Renin | 1993 |
Time course of spirapril-induced structural and functional changes after myocardial infarction in rats followed with magnetic resonance imaging.
Structural alterations after myocardial infarction (MI) in rats are usually examined only after death of the experimental animal. Magnetic resonance imaging (MRI) allows repeated and noninvasive measurements of important structural [left ventricular (LV) mass, LV wall thickness, LV chamber radius] as well as function [LV end-systolic and LV end-diastolic volume, stroke volume (SV), ejection fraction (EF)] parameters for a prolonged period. We describe our experience in a series of experiments in rats. Three weeks after MI, infarct size (IS) was determined by MRI and the rats were divided into two groups with equal IS. Three weeks later, treatment with the angiotensin-converting enzyme (ACE) inhibitor spirapril (10 mg/kg in food) or placebo was started. In both groups, the first MRI scan taken before the treatment showed moderately dilated left ventricles and signs of impaired LV function, i.e., an increase in LV end-systolic and end-diastolic volume and decreased EF. After 3-week treatment, no significant differences with respect to heart structure and function were detected as compared with those of untreated animals. Prolonged treatment for 10 weeks with spirapril resulted in significant reduction of LV dilatation, LV mass, and LV end-systolic and end-diastolic volume, which was accompanied by improved EF. Hemodynamic examinations after treatment for 6 months showed, in contrast to control animals, no increase in right ventricular systolic pressure in animals receiving spirapril. Furthermore, histologic examination of perfusion-fixed hearts at the end of the study demonstrated more pronounced LV dilatation in control animals, thus confirming the in vivo MRI data. Delayed treatment with spirapril proved to have beneficial effects on structure and function of infarcted hearts within 10 weeks. Spirapril limited LV dilatation, reduced LV weight and LV end-systolic and end-diastolic volumes, and improved EF. Topics: Angiotensin-Converting Enzyme Inhibitors; Animals; Blood Pressure; Body Weight; Enalapril; Hemodynamics; Image Processing, Computer-Assisted; Magnetic Resonance Imaging; Male; Myocardial Infarction; Peptidyl-Dipeptidase A; Perfusion; Rats; Rats, Wistar; Stroke Volume; Ventricular Function, Left | 1993 |
Effect of enalapril on congestive heart failure treated with diuretics in elderly patients with prior myocardial infarction and normal left ventricular ejection fraction.
Topics: Aged; Aged, 80 and over; Echocardiography, Doppler; Enalapril; Exercise Test; Female; Furosemide; Heart Failure; Humans; Male; Myocardial Infarction; Stroke Volume; Ventricular Function, Left | 1993 |
Myocardial infarction and heart failure. The common ground.
Topics: Captopril; Cardiac Output, Low; Enalapril; Humans; Myocardial Infarction | 1993 |
ACE inhibitors after myocardial infarction.
Topics: Enalapril; Humans; Myocardial Infarction; Vascular Patency | 1993 |
ACE inhibitors after myocardial infarction.
Topics: Aged; Contraindications; Enalapril; Humans; Hypotension; Myocardial Infarction | 1993 |
Propionyl-L-carnitine limits chronic ventricular dilation after myocardial infarction in rats.
To determine whether propionyl-L-carnitine (PLC) administration ameliorates ventricular remodeling after myocardial infarction, we performed coronary occlusion in rats and examined the long-term effects of the drug 19-24 wk after surgery. In view of the well-established role of angiotensin-converting enzyme (ACE) inhibitors in the reduction of ventricular dilation after infarction, the therapeutic impact of oral PLC (60 mg/kg) was compared with that of enalapril (1 mg/kg). Infarct size measured planimetrically was found to be comparable in untreated, PLC-treated, and enalapril-treated rats, averaging 40-46% of the left ventricular free wall. Heart weight was increased 14, 16, and 11% with no treatment, with PLC, and with enalapril, respectively. The relationship between left ventricular filling pressure and chamber volume demonstrated that PLC and enalapril significantly prevented the expansion in cavitary size after infarction. These protective influences were observed throughout the range of filling pressures measured, from 0 to 30 mmHg. At a uniform reference point of filling pressure of 4 mmHg, untreated infarcted hearts showed an expansion in ventricular volume of 2.17-fold (P < 0.0001). Corresponding increases in this parameter after PLC and enalapril were 36 and 43%, respectively, both not statistically significant. Moreover, PLC was capable of reducing the alterations in myocardial compliance associated with myocardial infarction. In conclusion, PLC reduces the magnitude of decompensated eccentric hypertrophy produced by myocardial infarction in a manner similar to that found with ACE inhibition. Topics: Administration, Oral; Animals; Blood Pressure; Carnitine; Enalapril; Hypertrophy, Left Ventricular; Male; Myocardial Infarction; Myocardium; Rats; Ventricular Function, Left | 1993 |
[Hemodynamic effects of enalapril in patients with non-complicated acute myocardial infarct].
To evaluate the hemodynamic effects of the first oral administration of enalapril maleate, a long-acting ACE-inhibitor, in the early phase of an acute uncomplicated myocardial infarction, we studied 15 patients, in Killip class I or II, within 72 hours from the onset of symptoms. Hemodynamic measurements were obtained by a triple lumen 7 F Swan-Ganz catheter, inserted into the pulmonary artery, under control conditions and 2, 4, 6, 8 and 12 hours after 10 mg (15 patients) and 20 mg (11 patients) of the drug. Ten milligrams of enalapril reduced systolic and mean arterial blood pressure (from 118 +/- 17 to 111 +/- 18 mmHg, p < .05, and from 92 +/- 12 to 83 +/- 12 mmHg, p < .01, respectively), with a maximum effect after 4 hours from administration. Heart rate and vascular resistances showed an insignificant trend toward reduction, and no changes were observed in left ventricular systolic work index, right and left ventricular filling pressures or cardiac index. Hemodynamic changes induced by 20 mg of the drug, in a smaller group of patients, had a similar trend, which did not reach a statistical significance. In conclusion, in patients with acute uncomplicated myocardial infarction, a single oral dose of enalapril maleate is safe and well tolerated, does not induce severe hypotension, and produces potentially beneficial changes in hemodynamics. Topics: Administration, Oral; Adult; Aged; Blood Pressure; Enalapril; Female; Heart Rate; Humans; Male; Middle Aged; Myocardial Infarction; Vascular Resistance | 1992 |
Monitoring clinical trials with a conditional probability stopping rule.
Conditional probability procedures offer a flexible means of performing sequential analysis of clinical trials. Since these procedures are not based on repeated significance test, the number and schedule of the interim analyses is less important than with group sequential procedures. Their main disadvantage is that the magnitude of their effect on the significance level is difficult to assess. This paper describes a conditional probability procedure which attempts to maintain the overall significance level by balancing the probabilities of false early rejection and false early acceptance. Monte Carlo sampling results suggest that this procedure can achieve a large reduction in expected sample size without greatly affecting either the significance level or power of the trial. Topics: Binomial Distribution; Clinical Trials as Topic; Enalapril; Humans; Monte Carlo Method; Myocardial Infarction; Probability; Sampling Studies | 1992 |
Converting enzyme inhibition after experimental myocardial infarction in rats: comparative study between spirapril and zofenopril.
The aim was to compare the effects of two novel angiotensin converting enzyme (ACE) inhibitors, spirapril and zofenopril, on cardiac remodelling in rats with congestive heart failure after myocardial infarction. Spirapril contains no sulphydryl group, whereas zofenopril is a sulphydryl containing ACE inhibitor.. Experimental myocardial infarction was induced by ligation of the left coronary artery. Sham operated animals served as controls. Treatment with spirapril (2-2.5 mg.kg-1.d-1) or zofenopril (12-15 mg.kg-1.d-1) added to the drinking water was started immediately after myocardial infarction or sham operation and continued for six weeks. After the treatment period, all rats were killed. The heart was rapidly removed and perfused as described by Langendorff. Heart rate and left ventricular pressure were measured both at baseline and during stimulation with isoprenaline (6 nM). Heart and lung weights were determined.. Normotensive male Wistar rats (220-240 g) were used.. Experimental myocardial infarction considerably increased left ventricular cavity volume. Chronic treatment with either spirapril or zofenopril significantly attenuated this increase in volume. In infarcted rats, the increase in total heart and lung weight was also significantly reduced by chronic treatment with spirapril and zofenopril, indicating that these compounds reduce cardiac mass and pulmonary congestion in congestive heart failure due to myocardial infarction. There were no significant differences between treatment with spirapril and zofenopril. In the isolated and perfused rat heart, myocardial infarction significantly decreased both heart rate and left ventricular pressure. Converting enzyme inhibition only affected heart rate. Heart rate was significantly higher in infarcted animals treated with spirapril and zofenopril than in untreated infarcted animals.. Both spirapril and zofenopril attenuated ventricular enlargement and cardiac hypertrophy in rats with congestive heart failure after myocardial infarction when treatment was started in the acute phase of myocardial infarction. No additional role could be attributed to the sulphydryl moiety of zofenopril. It is also suggested that these two ACE inhibitors modify cardiac sympathetic activity in rats with congestive heart failure, but more studies are needed to confirm these findings. Topics: Angiotensin-Converting Enzyme Inhibitors; Animals; Captopril; Disease Models, Animal; Enalapril; Heart; Heart Rate; Isoproterenol; Male; Myocardial Infarction; Myocardium; Rats; Rats, Inbred Strains | 1991 |
Incidence of sudden cardiac death associated with coronary artery occlusion in dogs with hypertension and left ventricular hypertrophy is reduced by chronic beta-adrenergic blockade.
Because beta-adrenergic blockade has as one of its many effects altered electrophysiological abnormalities after dogs with left ventricular hypertrophy have been subjected to coronary occlusion, we tested the hypothesis that metoprolol (200-400 mg/day) would reduce mortality rates in dogs with one-kidney, one clip left ventricular hypertrophy while a similar reduction in arterial pressure with enalapril (20-40 mg/day) would not. Dogs with left ventricular hypertrophy were given metoprolol or enalapril for 5-7 days before a 3-hour coronary occlusion. Infarct size and risk area were measured with triphenyltetrazolium chloride stain and barium angiography, respectively. For control (n = 15), left ventricular hypertrophy (n = 17), left ventricular hypertrophy plus metoprolol (n = 12), and left ventricular hypertrophy plus enalapril (n = 15) groups, mean arterial pressure, ratio of infarct size to risk area, and dogs experiencing sudden death were 110 +/- 4, 142 +/- 4, 121 +/- 7, and 120 +/- 3 mm Hg; 44 +/- 5%, 65 +/- 5%, 44 +/- 7%, and 30 +/- 4%; and 27%, 65%, 17%, and 53%, respectively. Thus, the excessive increase in early mortality occurring when dogs with hypertension and left ventricular hypertrophy undergo coronary occlusion is interrupted with beta-blockade, possibly via electrophysiological effects rather than by changes in arterial pressure or infarct size. Topics: Adrenergic beta-Antagonists; Animals; Cardiomegaly; Coronary Circulation; Coronary Disease; Death, Sudden; Dogs; Enalapril; Female; Heart Ventricles; Hemodynamics; Hypertension; Male; Metoprolol; Myocardial Infarction; Risk Factors | 1990 |
Beneficial hemodynamic effects of milrinone and enalapril in conscious rats with healed myocardial infarction.
Milrinone and enalapril, which inhibit PDE-III and ACE, respectively, are able to prolong survival of myocardially infarcted (MI) rats. This study sought to identify oral hemodynamic effects of these agents which could underlie such efficacy in this heart failure model. Four weeks after ligation of the left main coronary artery, basal left ventricular (LV) systolic pressure and dP/dtmax, heart rate and mean blood pressure of the MI rats were significantly less than that of sham-operated controls, and LV end-diastolic pressure (LVEDP) was markedly elevated. Milrinone, at 2.0 mg/kg, reduced LVEDP and renal blood flow of these 4-week MI rats by an average of 39 and 18%, respectively (P less than 0.05) within 1 h. At 4.0 mg/kg, it reduced LVEDP by 46% and raised heart rate by 16% (P less than 0.05). Enalapril (1.0 mg/kg) increased small intestine blood flow of these compromised rats by 16% (P less than 0.05), and tended to reduce LVEDP (-28%) within 1.5 h. Treatment with milrinone (2.0 mg/kg) plus enalapril (1.0 mg/kg) promoted LV dP/dtmax, coronary blood flow, and heart rate by 48, 40 and 13%, and reduced LVEDP by 40% (P less than 0.05 for all effects). Thus these agents can reduce LVEDP and redistribute cardiac output of MI rats. Furthermore, the combination of enalapril and milrinone can restore LVEDP and LV dP/dtmax of MI rats to near normal and promote coronary blood flow without compromising cardiac output or renal blood flow. Such effects, it timely or sustained, may prolong survival. Topics: Administration, Oral; Animals; Blood Pressure; Enalapril; Heart Rate; Hemodynamics; Male; Milrinone; Myocardial Infarction; Organ Size; Pyridones; Rats; Rats, Inbred Strains; Vascular Resistance | 1989 |
Cardiac hypertrophy and salt status in chronic myocardial infarction in the rat: effects of enalapril versus salt restriction.
The effects of salt restriction and the ACE inhibitor enalapril were compared in a model of chronic myocardial infarction in the rat. Total exchangeable sodium was measured by an isotopic dilution technique to quantitate the effects of the low salt diet and ACE inhibitor on body sodium and extracellular fluid. Rats with infarction developed a marked increase in cardiac weight (4.29 +/- 0.18 mg/g body weight) compared with control rats (3.64 +/- 0.08 mg/g, p less than 0.01). There was hypertrophy of both left and right ventricles. Salt restricted rats with infarction developed identical cardiomegaly (4.30 +/- 0.11 mg/g), although total exchangeable body sodium fell by 10% (p less than 0.001). In contrast, rats with infarction receiving enalapril developed significantly less cardiomegaly (3.97 +/- 0.10 mg/g) while body sodium remained unchanged. Rats with infarction had a significant increase in lung weight which was not changed by salt restriction but which was abolished by enalapril. These results suggest that salt restriction does not prevent the progression of cardiomegaly in chronic left heart failure. In contrast our results confirm the ability of ACE inhibitors to prevent progressive cardiomegaly and left heart failure without affecting long-term changes in sodium balance. Topics: Animals; Cardiomegaly; Diet, Sodium-Restricted; Enalapril; Female; Myocardial Infarction; Organ Size; Rats; Rats, Inbred Strains; Sodium | 1988 |
Beneficial effects of milrinone and enalapril on long-term survival of rats with healed myocardial infarction.
The long-term survival of rats with healed myocardial infarction and congestive heart failure treated with milrinone, enalapril and the combination of milrinone plus enalapril, was documented. Seven days after sham or coronary ligation, 200 rats (99 sham and 101 myocardial infarcted) were randomized based on electrocardiographic criteria to receive tap water, milrinone (20-40 mg/l drinking water), enalapril (17-25 mg/l) or the combination of milrinone plus enalapril (20-40 mg/17-25 mg per l). The date of spontaneous death was recorded and heart weights and myocardial infarct size (by planimetry) were determined. Long-term enalapril therapy prolonged survival with a median 50% survival (MS50) of 233 days compared to 203 days in the tap water group. Milrinone therapy also prolonged survival with a MS50 of 297 days. The combination therapy prolonged survival with a MS50 of 277 days. In general, there were three times as many rats alive in the treatment groups at the end of one year compared to untreated control groups. Cardiac hypertrophy was evident in all myocardial infarcted groups and heart weights were significantly reduced by all treatments. The average myocardial infarct sizes and the distribution of infarct sizes were not different between groups (36.8-43% of left ventricle). This study demonstrates that long-term therapy with enalapril and milrinone prolongs survival in rats with healed myocardial infarctions. The prolongation of survival was comparable in the milrinone plus enalapril groups, indicating that there was no synergy with these two agents with survival as the end point. Topics: Animals; Body Weight; Cardiomegaly; Cardiotonic Agents; Electrocardiography; Enalapril; Heart Failure; Male; Milrinone; Myocardial Infarction; Organ Size; Pyridones; Rats; Rats, Inbred Strains | 1988 |
Increased survival in rats with congestive heart failure treated with enalapril.
Vasodilating drugs such as angiotensin converting enzyme (ACE) inhibitors may extend life expectancy in patients with congestive heart failure (CHF). The purpose of this study was to evaluate whether long-term therapy (365 days) with enalapril (ENAL, an ACE inhibitor), would prolong life in rats with a healed myocardial infarction (MI), an experimental model with hemodynamic characteristics of CHF. Seven days after sham or coronary ligation, when the healing phase of MI was well underway, 132 rats (75 sham, 57 MI) were randomized to receive either enalapril in the drinking water (17-25 mg/L, approximately 1.0 mg/kg/day) or tap water. The date of spontaneous death was recorded, and heart weight and MI size (by planimetry) were determined. Serum ENAL, total ACE concentration, and angiotensin and methoxamine pressor responses were quantified in 12 survivors. Long-term enalapril prolonged survival (p = 0.014) with a median 50% survival of 164 (164-165) days, compared to 84 (64-104) days in rats receiving tap water. There were twice as many MI rats alive at the end of one year on angiotensin converting enzyme inhibition (ACEI) therapy as compared to the untreated group. The average MI size (39-40%) was not different between groups, and there was a significant inverse correlation between date of death and MI size (r = 0.7-0.8) in both treatment groups. Cardiac hypertrophy was evident in all MI rats. Serum ENAL levels, after one year, were at the clinically relevant concentration (2.3 ng/ml) and total serum ACE (inhibitor removed) doubled to 4,300 nmol/h/ml.(ABSTRACT TRUNCATED AT 250 WORDS) Topics: Animals; Enalapril; Heart Failure; Male; Myocardial Infarction; Peptidyl-Dipeptidase A; Rats; Rats, Inbred Strains | 1987 |
Acute effects of hydralazine and enalapril on contractile function of postischemic "stunned" myocardium.
Topics: Animals; Dogs; Enalapril; Hemodynamics; Hydralazine; Myocardial Contraction; Myocardial Infarction; Time Factors | 1987 |
Protective effects of captopril and enalapril on myocardial ischemia and reperfusion damage of rat.
The protective effect of angiotensin-converting enzyme inhibitors (ACEI) on myocardial ischemia and reperfusion damage was estimated in rat hearts, both in vivo and in vitro. Enalapril 2.5 mg/kg ip pretreatment at 24 and 5 h before coronary occlusion, significantly blunted the rise of CPK (445 +/- 151 vs 649 +/- 244 mu/ml, P less than 0.05) and improved electrocardiogram (ECG) 8 h after coronary occlusion. In global ischemia and reperfusion ex vivo, enalapril improved contractility (0.9 +/- 0.2 vs 0.3 +/- 0.3 g, P less than 0.05) and coronary flow (15.6 +/- 3.3 vs 11.9 +/- 3.1 ml/min/g, P less than 0.05), shortened significantly the duration of reperfusion arrhythmia (3.1 +/- 2.7 vs 9.7 +/- 8.1 min, P less than 0.05). In Langendorffs heart, captopril remarkably preserved force of contraction (2.1 +/- 0.4 vs 1.4 +/- 0.4 g, P less than 0.01) and coronary flow (2.7 +/- 0.5 vs 3.6 +/- 0.9 ml/min/g, P less than 0.05) in segmental infarction deteriorated by angiotensin I. Captopril 10(-5) M infusion reduced the release of CPK (435 +/- 112 vs 640 +/- 123 mu/min coronary flow, P less than 0.05). This action was almost completely abolished by pretreating and infusing with indomethacin. As a positive control, prostacyclin 5 X 10(-7) M infusion further reduced the release of CPK to 330 +/- 77 mu/min. It is concluded that angiotensin-converting enzyme inhibitor can protect both myocardial ischemia and reperfusion damage in rat hearts. The mechanism of protection was ascribed to reduced production of angiotensin II by ACE inhibition and increased prostacyclin release in the myocardium. Topics: Angiotensin I; Animals; Captopril; Coronary Circulation; Coronary Disease; Enalapril; Epoprostenol; Female; In Vitro Techniques; Male; Myocardial Contraction; Myocardial Infarction; Rats | 1987 |
Beneficial effects of enalapril on reperfusion arrhythmia and segmental contraction in anesthetized dogs.
Topics: Animals; Dogs; Enalapril; Female; Hemodynamics; Male; Myocardial Contraction; Myocardial Infarction; Perfusion; Ventricular Fibrillation | 1987 |
Converting enzyme inhibitors (captopril, enalapril, perindopril) prevent early-post infarction ventricular fibrillation in the anaesthetized rat.
The angiotensin-converting enzyme inhibitors, captopril, enalapril and perindopril, exert antiarrhythmic effects on early post-infarction arrhythmias in anaesthetized rats. These studies support the hypothesis that converting enzyme inhibitors could have a "cardioprotective" effect, but the doses used are probably "high" in relation to those therapeutically applicable to man. Topics: Anesthesia; Angiotensin-Converting Enzyme Inhibitors; Animals; Captopril; Enalapril; Indoles; Male; Myocardial Infarction; Perindopril; Rats; Rats, Inbred Strains; Ventricular Fibrillation | 1987 |
The use of angiotensin converting enzyme inhibitors in elderly patients with hypertension.
Topics: Aged; Angiotensin-Converting Enzyme Inhibitors; Captopril; Drug Interactions; Enalapril; Hemodynamics; Humans; Hypertension; Myocardial Infarction | 1987 |
[Drug-induced intrahepatic cholestasis caused by flecainide acetate and enalapril].
Topics: Aged; Cholestasis, Intrahepatic; Drug Therapy, Combination; Enalapril; Female; Flecainide; Heart Failure; Humans; Hypertension; Male; Middle Aged; Myocardial Infarction; Tachycardia | 1987 |
Acute and subacute hemodynamic effects of enalaprilat, milrinone and combination therapy in rats with chronic left ventricular dysfunction.
A model of congestive heart failure (CHF) was produced in rats approximately 76 days following surgical occlusion of the left coronary artery. In rats with healed myocardial infarction (MI size = 45% LV), hemodynamic variables were predictably elevated (LVEDP greater than 20 mm Hg) or depressed LV dP/dtmax (5200 mm Hg/sec). The hemodynamic response (MAP, HR, LVEDP, and dP/dtmax) to intravenous infusion of Mil (54 to 347 micrograms/kg) was measured on two occasions, separated by a 7-12 day period of oral treatment (2 mg/kg/day). Enalaprilat was tested in a similar design with the infusion phase (70 micrograms/kg, total dose) separated by oral enalapril (Enal), 1 mg/kg/day. The hemodynamic response to Mil was also examined in rats treated with the ACE inhibitor. At low doses, Mil modestly elevated HR (+17 beats/min) and dose-dependently increased (P less than 0.05) LV contractility by approximately 25%. Higher doses of Mil reduced preload (LVEDP) and afterload (MAP). Oral Mil produced little hemodynamic improvement except modest elevation (+9%) in LV contractility. There was no evidence of tachyphylaxis to i.v. Mil. In contrast, enalaprilat reduced MAP and preload without altering HR or contractility, effects observed after oral treatment. In the presence of the ACE inhibitor, Mil's hemodynamic actions were not enhanced. These experiments demonstrate that ACE inhibition improves ventricular performance by reducing preload and afterload. In this model, Mil improves performance by a direct inotropic mechanism as well as a reduction in afterload. Topics: Animals; Antihypertensive Agents; Drug Therapy, Combination; Enalapril; Enalaprilat; Heart Failure; Hemodynamics; Milrinone; Myocardial Contraction; Myocardial Infarction; Pyridones; Rats; Vasodilator Agents | 1987 |