enalapril and Cardiomyopathy--Dilated

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

The purpose of this study was to compare outcomes (and the effect of sacubitril/valsartan) according to etiology in the PARADIGM-HF (Prospective comparison of angiotensin-receptor-neprilysin inhibitor [ARNI] with angiotensin-converting-enzyme inhibitor [ACEI] to Determine Impact on Global Mortality and morbidity in Heart Failure) trial.. Etiology of heart failure (HF) has changed over time in more developed countries and is also evolving in non-Western societies. Outcomes may vary according to etiology, as may the effects of therapy.. We examined outcomes and the effect of sacubtril/valsartan according to investigator-reported etiology in PARADIGM-HF. The outcomes analyzed were the primary composite of cardiovascular death or HF hospitalization, and components, and death from any cause. Outcomes were adjusted for known prognostic variables including N terminal pro-B type natriuretic peptide.. Among the 8,399 patients randomized, 5,036 patients (60.0%) had an ischemic etiology. Among the 3,363 patients (40.0%) with a nonischemic etiology, 1,595 (19.0% of all patients; 47% of nonischemic patients) had idiopathic dilated cardiomyopathy, 968 (11.5% of all patients; 28.8% of nonischemic patients) had a hypertensive cause, and 800 (9.5% of all patients, 23.8% of nonischemic patients) another cause (185 infective/viral, 158 alcoholic, 110 valvular, 66 diabetes, 30 drug-related, 14 peripartum-related, and 237 other). Whereas the unadjusted rates of all outcomes were highest in patients with an ischemic etiology, the adjusted hazard ratios (HRs) were not different from patients in the 2 major nonischemic etiology categories; for example, for the primary outcome, compared with ischemic (HR: 1.00), hypertensive 0.87 (95% confidence interval [CI]: 0.75 to 1.02), idiopathic 0.92 (95% CI: 0.82 to 1.04) and other 1.00 (95% CI: 0.85 to 1.17). The benefit of sacubitril/valsartan over enalapril was consistent across etiologic categories (interaction for primary outcome; p = 0.11).. Just under one-half of patients in this global trial had nonischemic HF with reduced ejection fraction, with idiopathic and hypertensive the most commonly ascribed etiologies. Adjusted outcomes were similar across etiologic categories, as was the benefit of sacubitril/valsartan over enalapril. (Efficacy and Safety of LCZ696 Compared to Enalapril on Morbidity and Mortality of Patients With Chronic Heart Failure; NCT01035255).

Topics: Aged; Aminobutyrates; Angiotensin Receptor Antagonists; Angiotensin-Converting Enzyme Inhibitors; Biphenyl Compounds; Cardiomyopathy, Alcoholic; Cardiomyopathy, Dilated; Cardiotoxicity; Cardiovascular Diseases; Cause of Death; Dangerous Behavior; Diabetic Cardiomyopathies; Drug Combinations; Enalapril; Female; Heart Failure; Heart Valve Diseases; Hospitalization; Humans; Hypertension; Infections; Male; Middle Aged; Mortality; Myocardial Ischemia; Peripartum Period; Stroke Volume; Tetrazoles; Treatment Outcome; Valsartan; Virus Diseases

Angiotensin converting enzyme (ACE) inhibition after myocardial infarction is associated with an improvement in plasma fibrinolytic parameters. The aim of the present study was to determine whether acute ACE inhibition and angiotensin II type 1 (AT1) receptor antagonism have similar effects in patients with heart failure.. Twenty patients with moderately severe chronic heart failure received enalapril 10 mg and losartan 50 mg on 2 separate occasions in a single-blind, randomized, crossover design. Plasma tissue plasminogen activator (t-PA) and plasminogen activator inhibitor type 1 (PAI-1) antigen and activity were measured at baseline and 6 hours after the dose. Acute administration of losartan but not of enalapril reduced plasma t-PA (11%; P=0.003) and PAI-1 (38%; P<0.001) antigen concentrations, which was associated with increases in t-PA (29%; P=0.03) and decreases in PAI-1 (48%; P=0.01) activity. Changes in plasma fibrinolytic parameters were more marked during losartan treatment (P<0.02), with a 3-fold greater reduction in plasma PAI-1 antigen concentrations (P<0.05).. Acute AT1 antagonism in patients with heart failure is associated with a significant improvement in plasma fibrinolytic parameters that is greater than during ACE inhibition. These beneficial effects of AT1 antagonism and ACE inhibition would therefore appear to be mediated principally through suppression of angiotensin II.

Topics: Aged; Angiotensin Receptor Antagonists; Angiotensin-Converting Enzyme Inhibitors; Antihypertensive Agents; Atrial Natriuretic Factor; Blood Pressure; Cardiomyopathy, Dilated; Cross-Over Studies; Enalapril; Female; Fibrinolysis; Heart Failure; Heart Rate; Hemodynamics; Humans; Losartan; Male; Myocardial Ischemia; Plasminogen Activator Inhibitor 1; Receptor, Angiotensin, Type 1; Receptor, Angiotensin, Type 2; Single-Blind Method; Tissue Plasminogen Activator; Ventricular Dysfunction, Left

Topics: Adrenergic beta-Antagonists; Adult; Angiotensin-Converting Enzyme Inhibitors; Cardiomyopathy, Dilated; Enalapril; Female; Humans; Male; Metoprolol; Middle Aged; Ventricular Dysfunction, Left

To test the long-term effect of enalapril maleate treatment on progression of clinical signs of heart disease in dogs with moderate or severe naturally acquired heart failure associated with chronic degenerative mitral valvular disease (mitral regurgitation [MR]) or dilated cardiomyopathy (DCM).. Prospective multicenter study.. 110 dogs enrolled at 15 locations in the United States.. All dogs enrolled in this study were maintained on their randomly allocated treatment regimen until death, treatment failure (deterioration of condition requiring additional medication), or termination of the study. All dogs entered in the study received standard heart failure treatment (furosemide with or without digoxin). Statistical analysis (log-rank test) was performed to compare the distribution of number of days in the study between dogs that received placebo tablets and dogs that received enalapril tablets.. When dogs with MR and DCM were grouped together, mean number of days until treatment failure was significantly different between those receiving enalapril and those given placebo tablets (157.5 and 77.0 days, respectively). For dogs with MR, mean number of days until treatment failure was significantly different between those receiving enalapril and placebo tablets (159.5 and 86.6 days, respectively). Mean number of days until treatment failure among dogs with DCM receiving enalapril and placebo tablets was 142.8 and 56.5, respectively.. Use of enalapril in combination with standard treatment (diuretics with or without digoxin) appears to be beneficial over an extended period, compared with standard treatment alone.

Topics: Angiotensin-Converting Enzyme Inhibitors; Animals; Cardiomyopathy, Dilated; Cardiotonic Agents; Death, Sudden, Cardiac; Digoxin; Disease Progression; Diuretics; Dog Diseases; Dogs; Double-Blind Method; Drug Therapy, Combination; Enalapril; Female; Furosemide; Heart Failure; Male; Mitral Valve Insufficiency; Prospective Studies; Uremia

In congestive heart failure (CHF), some of the effects of angiotensin-converting enzyme (ACE) inhibitors, such as an increase in exercise oxygen uptake (VO2), are mediated through prostaglandins. Angiotensin (AT1) receptor blockers apparently do not share potentiation of this biosystem. We tested whether losartan improves exercise VO2 in CHF and if the effect is the same as for enalapril. Sixteen men with CHF and 8 volunteers, all nonsmokers and not taking ACE, AT1 receptor, or cyclooxygenase inhibitors, were randomized to receive placebo, enalapril (10 mg 2 times daily), losartan (50 mg/day), each of these 2 drugs plus aspirin (325 mg/day), aspirin, or the same preparations in a reverse order, each for 3 weeks, with a 3-week washout period between treatments. Pulmonary function and VO2 were assessed at the end of each treatment. In CHF, losartan and enalapril caused a similar improvement of VO2 and exercise tolerance, which was absent in controls and was counteracted by aspirin (prostaglandin inhibition) when obtained with enalapril and not with losartan. While on enalapril, we also detected an increase in the diffusing lung capacity for carbon monoxide, which correlated with changes in VO2 and was antagonized by aspirin, suggesting the possibility that a prostaglandin-mediated functional improvement of the alveolar capillary membrane contributes to the rise in VO2. Thus, losartan is as effective as enalapril for exercise VO2 and exercise tolerance, but the mechanism seems to be dissociated from a prostaglandin biosystem activation. Losartan may represent an advancement in CHF because its efficacy on VO2 is similar to that of enalapril, but is not antagonized by aspirin.

Topics: Angiotensin-Converting Enzyme Inhibitors; Antihypertensive Agents; Aspirin; Cardiomyopathy, Dilated; Cross-Over Studies; Cyclooxygenase Inhibitors; Double-Blind Method; Enalapril; Exercise Test; Heart Failure; Hemodynamics; Humans; Losartan; Male; Middle Aged; Myocardial Ischemia; Oxygen Consumption; Pulmonary Diffusing Capacity; Pulmonary Ventilation; Respiratory Mechanics

Anthracycline chemotherapy in cancer can cause severe, frequently fatal congestive heart failure (CHF), the first-line treatment for which is diuretics and digoxin. We have studied the use of an angiotensin-converting-enzyme (ACE) inhibitor added as a third agent.. In an observational study in hospital and as outpatients, 92 patients with advanced breast cancer were treated with epirubicin at a cumulative dose of 360 to 1000 mg/m2 (median 1000). Of 85 evaluable, nine developed life-threatening CHF at 1.5 to 13 months after ending epirubicin. Left ventricular ejection fraction (LVEF) decreased from normal to 18 to 35%. All received frusemide and digoxin, and then, after transient clinical relief, enalapril or ramipril (initially 1.25 mg orally daily, increasing to 10-15 mg after 4-6 weeks).. Eight of the nine patients deteriorated while on digoxin/diuretic. Within 3 months of starting the ACE inhibitor in these patients, LVEF had increased to normal or near normal. Only one patient died in heart failure. Follow-up ranged from 11 to 42 months (median 26). The ACE inhibitor was well-tolerated, with no first-dose hypotension, except for one patient who discontinued treatment after 6 months because of persistent cough. Two others discontinued treatment with their ACE inhibitor after 22 and 28 months because they felt well. Survival in the nine patients was similar to that of those who did not develop CHF.. Our experience suggests that treatment of anthracycline-induced CHF with an ACE inhibitor should start soon after clinical improvement on digoxin/diuretic regardless of the severity of symptoms rather than waiting for clinical deterioration.

Topics: Adult; Angiotensin-Converting Enzyme Inhibitors; Antibiotics, Antineoplastic; Breast Neoplasms; Cardiomyopathy, Dilated; Enalapril; Epirubicin; Female; Humans; Middle Aged; Prospective Studies; Ramipril; Stroke Volume; Treatment Outcome; Ventricular Function, Left

Cardiac adaptations to volume overload have been poorly investigated in heart failure. The aim of this study was to assess dynamic left ventricular responses to acute volume loading by continuous radionuclide monitoring in patients with asymptomatic to mildly symptomatic left ventricular dysfunction.. Left ventricular end-diastolic (EDV) and end-systolic (ESV) volumes, ejection fraction (EF), and peak filling rate (PFR) were monitored by a radionuclide detector (Vest) before and during volume expansion (sodium chloride, 0.9%, 0.25 mL.kg-1.min-1 for 2 hours) in 10 patients with idiopathic dilated cardiomyopathy (DCM) and mild heart failure (New York Heart Association class I or II, ejection fraction < 50%). The patients were studied off treatment and after 6 to 8 weeks of oral treatment with enalapril (5 mg/d). A control group of 11 age- and sex-matched healthy volunteers (N group) was also studied. In the N group, volume loading caused prompt and sustained increases of EDV, EF, and PFR (all P < .001), whereas ESV was progressively reduced (P < .001), and heart rate and blood pressure did not change. In contrast, in DCM, EDV showed a smaller increase than in the N group (two-way ANOVA: F = 5.98, P < .001), ESV increased (P < .001), and EF and PFR remained unchanged. After enalapril, the cardiac adaptations to volume loading were restored to normal. In particular, EDV, EF, and PFR increased (P < .001), and ESV was reduced (P < .001). In 6 additional DCM patients studied before and after 6 to 8 weeks of placebo treatment, left ventricular responses to volume loading remained unchanged.. Left ventricular dynamic adaptations to acute volume loading are compromised in patients with idiopathic DCM and mild heart failure. These impaired responses are ameliorated by treatment with enalapril.

Topics: Adult; Angiotensin-Converting Enzyme Inhibitors; Cardiac Volume; Cardiomyopathy, Dilated; Enalapril; Female; Heart Failure; Humans; Male; Middle Aged; Radionuclide Ventriculography; Ventricular Function, Left

This double-blind, randomized, long-term study investigated the effects of the angiotensin-converting enzyme inhibitor enalapril and the beta-blocker metoprolol on clinical, hemodynamic, angiographic, and neurohormonal parameters in patients with dilated cardiomyopathy and moderate cardiac functional impairment (left ventricular ejection fraction [LVEF] 35% +/- 6%). After 12 months of treatment, a 12% reduction in 24-hour heart rate was observed in both groups (p < 0.05), whereas heart rate during exercise was reduced only in the metoprolol group. Echocardiographic fractional shortening increased (enalapril: 17% +/- 6% to 21% +/- 7%; metoprolol: 21% +/- 9% to 29% +/- 7%; both p < 0.05), as did the angiographic LVEF (enalapril: 35% +/- 7% to 43% +/- 12%, p = 0.1; metoprolol: 34% +/- 7% to 44% +/- 9%, p < 0.05), whereas ventricular volume decreased. Initially, both groups were comparable in terms of all parameters investigated. After 12 months fractional shortening was greater, and the heart rate at 50 W was lower in the beta-blocker group. At the doses used, the effect of the beta-blocker on dilated cardiomyopathy with moderate functional impairment was at least as great as that of the angiotensin-converting enzyme inhibitor.

Topics: Adrenergic beta-Antagonists; Angiotensin-Converting Enzyme Inhibitors; Cardiac Catheterization; Cardiomyopathy, Dilated; Double-Blind Method; Echocardiography; Electrocardiography, Ambulatory; Enalapril; Exercise Tolerance; Female; Hemodynamics; Humans; Male; Metoprolol; Middle Aged; Prospective Studies; Time Factors; Ventricular Function

The double-blind, placebo-controlled, multinational trial Xamoterol in Severe Heart Failure randomized 290 patients treated with captopril and 217 treated with enalapril to xamoterol or placebo. At the end of the 100-day follow-up period, the cumulative probability of survival in patients with coronary artery disease or with dilated cardiomyopathy decreased in the captopril group (90.3%) when compared with the enalapril group (97.2%). The excess mortality in the captopril group could not be related to the indexes of the severity of heart failure, such as baseline exercise duration, functional class, cardiothoracic ratio, ejection fraction or dose of diuretic drugs. Furthermore, the excess in mortality was seen in all subsets of patients examined as well as across countries. Examination of the dosing regimen used, however, suggests that insufficient daily dosage of captopril or the inadequate schedule of administration, or both, might be responsible for different degrees of angiotensin-converting enzyme inhibition between the enalapril and captopril groups and hence for the difference in mortality. It is important in future clinical trials to determine to what extent complete circadian angiotensin-converting enzyme inhibition is necessary to provide the full benefit of this therapy in heart failure.

Topics: Adrenergic beta-Agonists; Adult; Aged; Aged, 80 and over; Captopril; Cardiomyopathy, Dilated; Cause of Death; Double-Blind Method; Drug Interactions; Enalapril; Female; Follow-Up Studies; Humans; Life Tables; Male; Middle Aged; Probability; Propanolamines; Xamoterol

We present preliminary data of a study comparing captopril, a short acting, with lisinopril, a long acting ACE-inhibitor in 8 of 12 projected patients with severe chronic heart failure (NYHA III-IV) and one additional risk factor (e.g. diabetes mellitus, renal failure). The 8 patients were treated in a cross over design for 12 weeks with either drug. While lisinopril improved NYHA-class in all patients, captopril reached this goal in only 3. Renal function was stable in all patients. Captopril influenced hormones (renin, aldosterone, norepinephrine, epinephrine) and microalbuminuria less than lisinopril. The number of adverse reactions was smaller in lisinopril treated patients. These preliminary data demonstrate at least an equal efficacy of lisinopril compared to captopril in high risk patients with severe chronic heart failure.

Topics: Angiotensin-Converting Enzyme Inhibitors; Captopril; Cardiomyopathy, Dilated; Coronary Disease; Enalapril; Female; Heart Failure; Hemodynamics; Humans; Kidney Function Tests; Lisinopril; Male; Middle Aged

The haemodynamic changes that follow a meal can mimic the response to a vasodilator drug. To avoid overestimating the beneficial effects of treatment in uncontrolled studies, measurements of haemodynamic function are usually performed with patients in the fasting postabsorptive state. But such recordings are not representative of the resting patient during daily life. In this double blind placebo controlled study the short term haemodynamic effects of enalapril were assessed during 12 hours in 19 patients with moderate heart failure caused by dilated cardiomyopathy. The patients ate lunch and dinner and were studied in the absorptive and postabsorptive phases. In the placebo group systemic vascular resistance, mean arterial pressure, and the rate-pressure product fell significantly (5-16%) after lunch. Four hours after lunch the haemodynamic function had returned to baseline--that is the postabsorptive state. Enalapril, accentuated the haemodynamic effects during the absorptive state producing a larger post-prandial fall in mean arterial blood pressure and rate-pressure product and changes in the absorptive phase were maintained into the post-absorptive phase. Pulmonary wedge pressure fell significantly after treatment with enalapril. These overall changes during the study period indicated that enalapril reduced the preload and afterload on the heart--over and above the reduction produced by eating. These findings suggest that the effects of enalapril given at rest to patients with moderate heart failure unload the heart and enhance the reduction of afterload induced by meals.

Topics: Adult; Cardiomyopathy, Dilated; Double-Blind Method; Eating; Enalapril; Female; Hemodynamics; Humans; Male; Middle Aged; Randomized Controlled Trials as Topic; Time Factors

The long-term effect of enalapril (group 1) and captopril (group 2) on clinical symptomatology and left ventricular function was evaluated in 29 patients with severe congestive heart failure (13 ischemic and 12 dilated cardiomyopathy, four valvular heart disease). During the 6-month observation period, five patients died (two on enalapril and three on captopril therapy = 6-month mortality rate 18%). Nine patients showed no beneficial effect of enalapril or captopril on clinical and hemodynamic findings (= nonresponders). The initial findings on these nine patients were, however, not significantly different from the clinical and hemodynamic findings on the patients who improved. Enalapril had to be discontinued in two patients because of side effects (progressive renal failure and gastrointestinal symptoms, respectively). A total of 22 patients completed the study, 11 treated with enalapril (mean dosage 25 +/- 10 mg/day) and 11 treated with captopril (mean dosage 77 +/- 26 mg/day). After 6 months there was a significant improvement according to the New York Heart Association (NYHA) classification, from 2.4 to 1.9 in group 1 (p less than 0.01) and from 2.7 to 1.9 in group 2 (p less than 0.001). The cardio-thoracic ratio (chest x-ray) decreased significantly from 0.59 to 0.56 (p less than 0.001) in group 1 and from 0.56 to 0.53 (p less than 0.001) in group 2. Physical working capacity (bicycle ergometry) showed a significant increase in both groups from 61% to 81% in group 1 (p less than 0.01) and from 66% to 83% in group 2 (p less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Blood Pressure; Captopril; Cardiac Output; Cardiomyopathy, Dilated; Coronary Disease; Enalapril; Female; Heart Failure; Heart Rate; Humans; Male; Middle Aged; Randomized Controlled Trials as Topic

The study objective was to evaluate the effect of bilateral sympathectomy on ventricular remodeling and function in a rat model of dilated cardiomyopathy induced by doxorubicin.. Dilated cardiomyopathy was induced in male Wistar rats by weekly intraperitoneal injection of doxorubicin (2 mg/kg) for 9 weeks. Animals were divided into 4 groups: dilated cardiomyopathy; bilateral sympathectomy, submitted on day 15 of the protocol to bilateral sympathectomy; angiotensin-converting enzyme inhibitor, treated with enalapril through day 15 until the end of the experimental protocol; and sham, nonsubmitted through doxorubicin protocol, with weekly intraperitoneal injections of saline solution (0.9%). The left ventricular function was assessed, and the heart was collected for posterior analyses.. Bilateral sympathectomy was effective in preventing remodeling and left ventricular dysfunction in a rat model of dilated cardiomyopathy induced by doxorubicin.

Topics: Angiotensin-Converting Enzyme Inhibitors; Animals; Cardiomyopathy, Dilated; Disease Models, Animal; Doxorubicin; Enalapril; Humans; Male; Rats; Rats, Wistar; Sympathectomy; Ventricular Dysfunction, Left; Ventricular Remodeling

The combination of an angiotensin-converting enzyme inhibitor (ACEI) with an aldosterone receptor antagonist can increase serum potassium and magnesium and lower serum sodium concentrations. The objective of this study was to retrospectively determine whether an ACEI and spironolactone can be co-administered to Doberman pinschers with occult dilated cardiomyopathy without serious adverse influences on serum electrolyte concentrations. Between 2001 and 2007, 26 client-owned Doberman pinschers were given enalapril, spironolactone, and carvedilol and followed for at least 6 months. Most dogs had been prescribed mexiletine for ventricular tachyarrhythmia suppression. Dogs were treated with pimobendan when congestive heart failure was imminent. Baseline and follow-up (3-10 visits) color-flow Doppler echocardiograms, serum urea nitrogen (SUN), creatinine, sodium, potassium, and magnesium concentration data were tabulated. Compared to baseline data, there were no significant changes in serum sodium or serum creatinine concentrations. Serum magnesium (P = 0.003), serum potassium (P = 0.0001), and SUN (P = 0.0001) concentrations increased significantly with time. Although the combination of ACEI and spironolactone was associated with significant increases in magnesium, potassium, and SUN concentrations, these changes were of no apparent clinical relevance. At the dosages used in this study, this combination of drugs appears safe.

Topics: Angiotensin-Converting Enzyme Inhibitors; Animals; Cardiomyopathy, Dilated; Cohort Studies; Dog Diseases; Dogs; Drug Combinations; Electrolytes; Enalapril; Female; Male; Mineralocorticoid Receptor Antagonists; Retrospective Studies; Species Specificity; Spironolactone

To assess the role of the renin-angiotensin (RAS) and adrenergic systems in the development and progression of dilated cardiomyopathy in the Syrian cardiomyopathic hamster (SCH), echocardiographic parameters were evaluated in 6-month-old animals after 5 months of treatment with enalapril (25 mg/kg/day) plus losartan (10 mg/kg/day), or with carvedilol (1 mg/kg/day). Cardiac output indexes (COI) increased by 53% after RAS blockade and by 20% after beta-blockade in SCH. Moreover, LVEDV and LVESV decreased 30% and 62%, respectively (P < .05) during RAS blockade, whereas ejection fraction (EF) increased by 48%. By contrast, carvedilol reduced LVESV by only 28% (P < .05) and increased EF by only 15% (P < .05). These results suggest that RAS activation plays a critical role in the development of cardiac dysfunction in SCH and that suppression of RAS may be more effective than beta-blockade in retarding the development of cardiomyopathy in SCH. Owing to timing (pre-heart failure stage) and to the single dose protocol, the implications of this study for human subjects remain to be clarified.

Topics: Adrenergic beta-Antagonists; Angiotensin II Type 1 Receptor Blockers; Angiotensin-Converting Enzyme Inhibitors; Animals; Blood Pressure; Carbazoles; Cardiac Output; Cardiomyopathy, Dilated; Carvedilol; Cricetinae; Disease Models, Animal; Disease Progression; Enalapril; Losartan; Male; Mesocricetus; Propanolamines; Renin-Angiotensin System; Stroke Volume; Time Factors; Ultrasonography; Ventricular Function, Left

Cardiomyopathic Syrian hamsters (Bio TO-2 dilated strain) constitute an animal model of congestive heart failure, which progressively develops an alteration of cardiac function leading to decreased arterial blood pressure and musculo-cutaneous blood flow associated with a complex process of cardiac remodeling including left ventricle dilation, wall thinning, and greater collagen density. The protocols described in this unit are designed to assess the pharmacological effects of new therapeutic strategies on cardiac and systemic hemodynamics, morphometry (body and target organs weight), cardiac remodeling (left ventricle dilation and collagen density), and survival in this model of dilated cardiomyopathy. Examples of results obtained with enalapril, an angiotensin I converting enzyme inhibitor, are provided for illustrative purposes.

Topics: Angiotensin-Converting Enzyme Inhibitors; Animals; Cardiomyopathy, Dilated; Cricetinae; Disease Models, Animal; Drug Evaluation, Preclinical; Drug-Related Side Effects and Adverse Reactions; Enalapril; Heart Failure; Hemodynamics; Male; Mesocricetus; Organ Size; Random Allocation; Survival Analysis; Ventricular Remodeling

In congestive heart failure, enalapril (E), metoprolol (M), and spironolactone (S) improve survival. Their direct effects on cardiac remodeling, when administered in combination, remain to be assessed.. One hundred and five cardiomyopathic hamsters were divided into 5 groups (control, E, E-M, E-S, E-M-S) and treated from 150 to 240 days of age (E: 3 mg/kg, M: 1 mg/kg, S: 20 mg/kg). Cardiac and systemic hemodynamics, and cardiac remodeling were investigated. There was no difference between groups on blood pressure. Compared with C, both S-treated groups significantly increased cardiac index (E-S: +49%; E-M-S: +46%). Compared with C, E significantly decreased left ventricular (LV) cavity area (-10%). Compared with E, all combinations significantly decreased LV cavity area (E-M: -13%, E-S: -22%, E-M-S: -19%) and right ventricular (RV) collagen density (E-M: -18%, E-S: -30%, E-M-S: -34%), and the tri-therapy significantly decreased LV collagen density (-18%). Compared with bi-therapies, the tri-therapy significantly decreased LV (-19% vs. E-M, -16% vs. E-S) and RV (-20% vs. E-M) collagen densities.. At subdepressor doses, both bi-therapies induced similar effects on myocardial remodeling, enhancing the effects of E on LV cavity area and reducing RV collagen density. Compared with bi-therapies, the tri-therapy induced additional effects on LV and RV collagen densities.

Topics: Adrenergic beta-Antagonists; Angiotensin-Converting Enzyme Inhibitors; Animals; Cardiomyopathy, Dilated; Cardiovascular System; Cricetinae; Drug Therapy, Combination; Enalapril; Liver; Lung; Male; Metoprolol; Mineralocorticoid Receptor Antagonists; Myocardium; Spironolactone; Ventricular Remodeling

Nitric oxide (NO) production is known to be impaired in heart failure. A new compound (NCX 899), a NO-releasing derivative of enalapril was characterized, and its actions were evaluated in Bio 14.6 cardiomyopathic (CM) hamsters with heart failure. The hamsters were randomized to oral treatment for 4 weeks with vehicle (n=11), NCX 899 (NCX, 25 mg/kg, n=10), or enalapril (25 mg/kg, n=10). In the vehicle group, fractional shortening by echocardiography decreased (-23.6+/-2.0%) and LV end-diastolic dimension) increased (+10.9+/-1.0%), whereas fractional shortening increased (+17.5+/-4.4%) in NCX and was unchanged in the enalapril group (both P<0.01 vs. vehicle). End-diastolic dimension decreased only in NCX. LV contractility (LVdP/dt max and Emax) was significantly greater in NCX than in enalapril or vehicle, while relaxation (Tau) was shortened in both NCX and enalapril vs. vehicle. ACE activity was inhibited equally by NCX and enalapril in the CM hamster, and plasma nitrate levels were increased only in NCX (P<0.05 vs. enalapril and vehicle). In aortic strips endothelium-independent relaxation occurred only with NCX. The superior effects of NO-releasing enalapril (NCX) vs. enalapril alone to enhance vascular effects, increase LV contractility and prevent unfavorable remodeling and are consistent with vascular delivery of exogenous NO. NCX 899 may hold promise for the future treatment of heart failure.

Topics: Angiotensin-Converting Enzyme Inhibitors; Animals; Aorta; Cardiomyopathy, Dilated; Cricetinae; Cytoskeletal Proteins; Disease Models, Animal; Disease Progression; Drug Evaluation, Preclinical; Enalapril; Endothelium, Vascular; Enzyme Inhibitors; Heart Failure; Hemodynamics; Male; Membrane Glycoproteins; Mesocricetus; Myocardial Contraction; Nitrates; Nitric Oxide; Nitric Oxide Donors; Nitrites; Oxadiazoles; Quinoxalines; Rabbits; Sarcoglycans; Ultrasonography; Vasoconstriction; Ventricular Remodeling

The cardioprotective properties of angiotensin-converting enzyme (ACE) inhibitors, quinapril and enalapril were studied in a rat model of heart failure. Seventy-five rats were divided into five groups and administered quinapril or enalapril at 2 and 20 mg/kg/day (groups Q2, Q20, E2 and E20) or vehicle alone (group V, all groups n = 15). Although both ACE inhibitors improved survival rate and ventricular function in a dose-dependent manner, the left ventricular end-diastolic pressure and expression level of transforming growth factor-beta1 mRNA were the lowest in group Q20. These results suggest that quinapril may confer greater protection than enalapril against injury from the renin-angiotensin system in heart failure.

Topics: Angiotensin II; Angiotensin II Type 1 Receptor Blockers; Angiotensin-Converting Enzyme Inhibitors; Animals; Blood Pressure; Cardiomyopathy, Dilated; Collagen Type III; Disease Models, Animal; Dose-Response Relationship, Drug; Enalapril; Fibrosis; Male; Myocardium; Quinapril; Rats; Rats, Inbred Lew; RNA, Messenger; Survival Rate; Tetrahydroisoquinolines; Transforming Growth Factor beta; Transforming Growth Factor beta1; Ventricular Function, Left; Ventricular Pressure

Chronic angiotensin I-converting enzyme inhibition can be associated with aldosterone escape. We investigated the effects of enalapril, spironolactone, and their combination on hemodynamics and cardiac remodeling in cardiomyopathic hamsters to determine whether these drugs could exert additive effects. Cardiomyopathic hamsters, Bio TO-2 dilated strain, were orally treated with enalapril (20 mg. kg. day ) and/or spironolactone (20 mg. kg. day ) according to a 2 x 2 factorial design from 120 days of age. Animals were investigated at 180 (10 animals per group) and 240 (16 animals per group) days of age. Compared with corresponding untreated groups, enalapril significantly decreased mean blood pressure (-18%); enalapril and spironolactone significantly increased cardiac output (+28%, +11%) and femoral blood flow (+10%, +12%) and significantly decreased systemic (-38%, -17%) and femoral (-26%, -13%) vascular resistances. Enalapril and spironolactone significantly decreased left ventricle cavity area (-21%, -26%) and left (-34%, -47%) and right (-37%, -48%) ventricle collagen density. Spironolactone significantly increased left ventricle wall thickness (+4%). There were significant enalapril x spironolactone interactions for most variables (compared with control group, +52%, +36%, +45% for cardiac output; +26%, +28%, +26% for femoral blood flow; -50%, -30%, -45% for systemic vascular resistance; -33%, -20%, -35% for femoral vascular resistance; -27%, -31%, -40% for left ventricle cavity area; and -46%, -58%, -60% for left and -39%, -50%, -66% for right ventricle collagen density in enalapril, spironolactone, and enalapril + spironolactone groups, respectively). In cardiomyopathic hamsters, enalapril and spironolactone in combination did not improve hemodynamics more than enalapril alone but induced stronger effects than each drug alone on cardiac remodeling.

Topics: Angiotensin-Converting Enzyme Inhibitors; Animals; Body Weight; Cardiomyopathy, Dilated; Cricetinae; Drug Therapy, Combination; Enalapril; Hemodynamics; Mineralocorticoid Receptor Antagonists; Organ Size; Spironolactone; Ventricular Remodeling

Topics: Aged; Angiotensin-Converting Enzyme Inhibitors; Blood Flow Velocity; Cardiomyopathy, Dilated; Chronic Disease; Dose-Response Relationship, Drug; Enalapril; Endothelium, Vascular; Exercise Tolerance; Female; Heart Failure; Humans; Male; Middle Aged; Muscle, Smooth, Vascular; Myocardial Ischemia; Oxygen Consumption; Pulmonary Wedge Pressure; Severity of Illness Index; Stroke Volume; Treatment Outcome; Vasodilation

Topics: Animals; Cardiomyopathy, Dilated; Cat Diseases; Cats; Diagnosis, Differential; Digoxin; Enalapril; Furosemide; Heart Failure; Male; Nitroglycerin; Oxygen Inhalation Therapy; Radiography; Ultrasonography

Angiotensin-converting enzyme inhibitors have been shown to reduce morbidity and mortality in patients with heart failure. The angiotensin type-1 blocking and cardioprotective properties of perindopril and enalapril were studied in a rat model of dilated cardiomyopathy after autoimmune myocarditis. Enalapril at 20 mg/kg showed the same angiotensin type-1 blocking action as perindopril at 2 mg/kg in rats with heart failure. Twenty-eight days after immunization, surviving Lewis rats (90/120 = 75%) were divided into six groups and administered perindopril at 0.02, 0.2 and 2 mg/kg per day (Groups P0.02, P0.2 and P2), enalapril at 2 and 20 mg/kg per day (Groups E2 and E20) or vehicle alone (Group V, all groups n = 15). After oral administration for 1 month, four of 15 (27%) rats in Group V, and two (13%) in Groups P0.02 and E2 died. None of the animals in Groups P0.2, P2 and E20, or normal rats (Group N) died. Although both angiotensin-converting enzyme inhibitors improved ventricular function in a dose-dependent manner, the left ventricular end-diastolic pressure and area of myocardial fibrosis were lower, and +/- dP/dt was higher in Group P2 (4.9 +/- 0.6 mmHg, 7.5 +/- 1.4% and +2651 +/- 254/-2622 +/- 189 mmHg/s, respectively) than in Group V (16.7 +/- 1.3, 36 +/- 2.6 and +2659 +/- 176/-2516 +/- 205, respectively) and Group E20 (7.5 +/- 2.5, 15.6 +/- 2.0 and +2018 +/- 110/-2097 +/- 102, respectively). Although the expression levels of transforming growth factor-beta1 and collagen-III mRNA in Group V (36.3 +/- 5.7 and 157.6 +/- 12.7%) were significantly higher than those in Group N (19.6 +/- 3.0 and 65.2 +/- 1.5%, both p < 0.01), they were reduced in Group P2 (21.4 +/- 5.9 and 75.2 +/- 9.3%, both p < 0.01). These results suggest that although enalapril can block increases in blood pressure caused by circulating angiotensin type-1, perindopril at 2 mg/kg may confer greater protection than enalapril at 20 mg/kg against injury from the renin-angiotensin system in heart failure.

Topics: Administration, Oral; Angiotensin I; Animals; Cardiomyopathy, Dilated; Collagen Type III; Disease Models, Animal; Dose-Response Relationship, Drug; Enalapril; Endomyocardial Fibrosis; Gene Expression; Heart Failure; Hemodynamics; Hypertension; Infusions, Intravenous; Male; Pericardial Effusion; Perindopril; Rats; Rats, Inbred Lew; RNA, Messenger; Survival Rate; Time Factors; Transforming Growth Factor beta; Transforming Growth Factor beta1; Ventricular Dysfunction, Left; Ventricular Pressure

The efficacy of ACE inhibitors (ACEIs) in the treatment of chronic heart failures is well documented. However, ACEIs may provide incomplete blockade of the renin-angiotensin system (RAS) because of the alternative pathways for angiotensin II (All) production. We hypothesized that more complete blockade of RAS by adding an AT1 receptor blocker (ARB) may have greater potential to decrease mortality associated with heart failure and improve cardiac function than monotherapy with ACEIs. The objective of this study was to evaluate the effect of combined therapy on cardiac functions and survival in cardiomyopathic hamsters. Male cardiomyopathic hamsters (BIO TO2) were administered either placebo (group C), enalapril (30 mg/kg/day) (group E), or enalapril (30 mg/kg/day) + valsartan (500 mg/ kg/day) (group EV), starting at the age of 6 weeks. Kaplan-Meier analysis was performed to assess the differences in survival. Cardiac functions were evaluated by echocardiogram and cardiac catheterization. Group EV showed significant increases in fractional shortening, LV dP/dTmax, and deceleration time, and showed significant decreases in left ventricular diastolic dimension, LV dP/dTmin, and early diastolic mitral velocity/atrial systolic velocity. Treatment with enalapril resulted in longer survival compared with placebo. Moreover, life expectancy (median probability of survival: 433 days) increased significantly in group EV compared with group E (P<0.05) as well as group C (P<0.001). It is concluded that combined therapy improved cardiac function and survival compared to placebo or enalapril monotherapy.

Topics: Angiotensin I; Angiotensin Receptor Antagonists; Angiotensin-Converting Enzyme Inhibitors; Animals; Cardiomyopathy, Dilated; Cell Count; Chronic Disease; Cricetinae; Drug Therapy, Combination; Echocardiography, Doppler; Enalapril; Fibrosis; Hemodynamics; Male; Myocytes, Cardiac; Random Allocation; Receptors, Angiotensin; Renin-Angiotensin System

Seventeen cases of severe hyponatremia induced by angiotensin-converting enzyme (ACE) inhibitor therapy have been reported in the literature. The mechanism of severe hyponatremia induced by ACE inhibitor is not clear. A 60-year-old white man with a history of idiopathic dilated cardiomyopathy was treated with enalapril, 20 mg daily, that had been started 2 weeks before heart transplantation. The serum sodium level was 138 mmol/L before initiation of enalapril therapy and 127 mmol/L just before cardiac surgery. In the post-heart transplantation period, enalapril therapy was withdrawn for the perianesthesia period, and the serum sodium level increased from 127 to 140 mmol/L. One month later, viral myocarditis developed in the patient and enalapril was reintroduced at 20 mg daily. Two weeks later, natremia decreased. Enalapril was discontinued. Three days later the serum sodium level rose to 140 mmol/L. Severe symptomatic hyponatremia induced by the syndrome of inappropriate secretion of antidiuretic hormone should be considered a rare but possible complication associated with ACE inhibitor therapy.

Topics: Angiotensin-Converting Enzyme Inhibitors; Cardiomyopathy, Dilated; Enalapril; Heart Transplantation; Humans; Hyponatremia; Inappropriate ADH Syndrome; Male; Middle Aged; Sodium

Eighteen patients with heart failure were studied to clarify whether angiotensin-converting enzyme inhibitor treatment improves excess ventilation during exercise. Treatment with angiotensin-converting enzyme inhibitors had a beneficial effect on excess ventilation during exercise, without significant improvement in exercise capacity in patients with moderate congestive heart failure.

Topics: Angiotensin-Converting Enzyme Inhibitors; Cardiomyopathy, Dilated; Enalapril; Exercise Test; Exercise Tolerance; Heart Failure; Humans; Imidazoles; Imidazolidines; Middle Aged; Pulmonary Ventilation; Time Factors

Severe digoxin toxicosis in a 13-year-old mixed-breed dog with dilated cardiomyopathy was successfully treated with i.v. administration of ovine digoxin-specific IgG Fab fragments. Management of this dog following treatment with Fab fragments was complicated by hypomagnesemia and loss of the positive inotropic effect of digoxin.

Topics: Animals; Anti-Arrhythmia Agents; Antihypertensive Agents; Blood Cell Count; Blood Chemical Analysis; Cardiomyopathy, Dilated; Cardiotonic Agents; Digoxin; Dog Diseases; Dogs; Electrocardiography; Enalapril; Female; Immunoglobulin Fab Fragments; Isoproterenol; Magnesium Deficiency; Magnesium Sulfate

The relationship between the myocardial uptake of iodine-123 metaiodobenzylguanidine (123I-MIBG) and heart rate variability parameters has not been determined. This study determined the relationship between the change in myocardial uptake of 123I-MIBG and improvement in left ventricular function after treatment, to determine the usefulness of 123I-MIBG imaging to assess the effect of therapy on heart failure due to dilated cardiomyopathy (DCM). 123I-MIBG imaging and power spectral analysis of heart rate variability were performed before and after treatment in 17 patients with heart failure due to DCM. The following parameters were compared before and after treatment: New York Heart Association (NYHA) functional class, radiographic cardiothoracic ratio (CTR), blood pressure, echocardiographic data [left ventricular end-systolic (LVDs) and end-diastolic (LVDd) diameters, left ventricular ejection fraction (LVEF)], plasma concentrations of norepinephrine and epinephrine, heart rate variability power spectral analysis data [mean low frequency (MLF) and high frequency power (MHF)] and the myocardium to mediastinum activity ratio (MYO/M) obtained in early and late images, and washout rate calculated by anterior planar imaging of 123I-MIBG. The NYHA functional class, LVEF, LVDs, CTR, MLF and MHF improved after treatment. Early MYO/M and late MYO/M improved after treatment. The rate of increase in late MYO/M was positively correlated with the rate of improvement of LVEF after treatment. Furthermore, the late MYO/M was negatively correlated with MLF. Washout rate revealed no correlation with hemodynamic parameters. These findings suggest that late MYO/M is more useful than washout rate to assess the effect of treatment on heart failure due to DCM. Furthermore, the 123I-MIBG imaging and heart rate variability parameters are useful to assess the autonomic tone in DCM with heart failure.

Topics: 3-Iodobenzylguanidine; Angiotensin-Converting Enzyme Inhibitors; Cardiomyopathy, Dilated; Cardiotonic Agents; Digoxin; Diuretics; Enalapril; Female; Furosemide; Heart Failure; Heart Rate; Humans; Male; Middle Aged; Radionuclide Imaging; Radiopharmaceuticals; Ventricular Function, Left

This study aimed at determining risk factors for perioperative mortality for patients undergoing partial left ventriculectomy. Fourteen patients with end-stage congestive heart failure underwent partial ventriculectomy at our institution from February, 1995 to October, 1997. Mean age was 48+/-11 years, symptoms duration 44+/-34 months, New York Heart Association symptoms score 4+/-0, systolic blood pressure 97.69+/-20.06 mmHg, diastolic blood pressure 65.38+/-13.91 mmHg, heart rate 91+/-15 beats/min, furosemide daily dose 121.66+/-96.65 mg and captopril daily dose 68.75+/-76.76 mg. Seven (50%) patients needed inotropic support for hemodynamic stabilization. On echocardiography, left ventricular diastolic dimension was 81.71+/-11.92 mm. Left ventricular ejection fraction determined by radionuclide ventriculography or echocardiography was 16.71+/-5.13. At heart catheterization, mean right atrial pressure was 12.50+/-7.72 mmHg, mean pulmonary capillary wedge pressure 23.60+/-7.79 mmHg, and mean pulmonary artery pressure 34.10+/-12.81 mmHg. Twelve patients had idiopathic dilated cardiomyopathy and two patients had a globally dilated heart with single vessel coronary artery disease. Aneurysmectomy, mitral valve surgery or coronary artery bypass surgery were not performed in any patient. Four (28%) patients died: three in the operating theatre and one from low output syndrome 2 days after surgery. The proportion of patients operated on with cardiogenic shock was four (100%) in nonsurvivors and 0% in survivors (P=0.001). Inotropic support was necessary in three (30%) survivors and in four (100%) nonsurvivors (P=0.06). Thus, preoperative hemodynamic instability may be associated with perioperative mortality after partial left ventriculectomy.

Topics: Adult; Angiotensin-Converting Enzyme Inhibitors; Captopril; Cardiac Surgical Procedures; Cardiomyopathy, Dilated; Diuretics; Echocardiography; Electrocardiography; Enalapril; Female; Furosemide; Heart Failure; Heart Ventricles; Hemodynamics; Humans; Male; Middle Aged; Perioperative Care; Postoperative Complications; Preoperative Care; Risk Factors; Shock, Cardiogenic

Anthracycline chemotherapy of cancer can cause severe, frequently fatal congestive heart failure (CHF), the first line treatment for which is diuretics and digoxin. We have studied the use of an ACE-inhibitor added as a third agent. Of 85 patients evaluable for cardiotoxicity after treatment with a median of 1000 mg/m2 of epirubicin for metastatic breast cancer, nine developed CHF at 1.5 to 13 months after therapy. Left ventricular ejection fraction decreased from normal to 18 to 35%. All patients received digitalo-diuretic therapy and after a transient clinical relief enalapril or ramipril increasing from 1.25 mg orally daily to 10-15 mg after 4-6 weeks. Eight of the nine patients deteriorated while on digitalo-diuretic therapy. Within three months of starting the ACE-inhibitor in these patients, LVEF increased to normal or near normal. Only one patient died in heart failure. Follow-up ranged from 11-42 months (median 26) and survival in the nine patients was similar to that of those who did not develop CHF. We suggest that treatment of anthracycline-induced CHF with an ACE-inhibitor should start within one to two weeks after digitalo-diuretic therapy regardless of the severity of symptoms rather than waiting for clinical deterioration.

Topics: Administration, Oral; Adult; Aged; Angiotensin-Converting Enzyme Inhibitors; Antibiotics, Antineoplastic; Antineoplastic Agents; Breast Neoplasms; Cardiomyopathy, Dilated; Enalapril; Epirubicin; Female; Humans; Middle Aged

A 58-year-old man with idiopathic dilated cardiomyopathy was treated with incremental administration of a beta-blocker (metoprolol) and an angiotensin converting enzyme inhibitor (enarapril). The left ventricular end-diastolic dimension and ejection fraction improved in 8 months from 83.3 mm and 17.3% to 46 mm and 69%, respectively. The washout ratio and heart-to-mediastinum ratio depicted on the delayed image for iodine-123 metaiodobenzylguanidine 123I-MIBG) uptake improved from 61.7% and 1.34 to 23.1% and 1.85, respectively, in association with improvement of left ventricular indices. Successive endomyocardial biopsy specimens disclosed reduction of the degrees of vacuolation, staining irregularity, and deformity of myocyte cytoplasm and nucleus compared to the findings before therapy. In this patient with dilated cardiomyopathy 123I-MIBG scintigraphy was useful for the evaluation of the effects of therapy. We conclude that it may be informative in the estimation of the histopathological abnormalities of the myocardium.

Topics: 3-Iodobenzylguanidine; Adrenergic beta-Antagonists; Angiotensin-Converting Enzyme Inhibitors; Biopsy; Cardiomyopathy, Dilated; Enalapril; Endocardium; Humans; Iodine Radioisotopes; Iodobenzenes; Male; Metoprolol; Middle Aged; Myocardium; Radionuclide Imaging; Stroke Volume; Ventricular Function, Left

The onset and the mechanisms leading to Na+ retention in incipient congestive heart failure (CHF) have not been systematically investigated. To investigate renal Na+ handling in the early or mild stages of CHF, Na+ balance and renal clearances were assessed in 10 asymptomatic patients with idiopathic or ischemic dilated cardiomyopathy and mild heart failure (HF) off treatment (left ventricular ejection fraction, 29.7+/-2%) and in 10 matched normal subjects during a diet containing 100 mmol/d of NaCl and after 8 days of high salt intake (250 mmol/d). Six patients were studied again after 6 weeks of treatment with enalapril (5 mg/d P.O.). At the end of the high salt diet, in patients with mild HF the cumulative Na+ balance exceeded by 110 mmol that of normal subjects (F=3.86, P<.001). During high salt intake, renal plasma flow and glomerular filtration rate were similarly increased in both normal subjects and mild HF patients. In spite of comparable increases of filtered Na+ in the two groups, fractional excretion of Na+, fractional clearance of free water, and fractional excretion of K+ (indexes of distal delivery of Na+) increased in normal subjects and were reduced in patients with mild HF. During enalapril treatment, in the mild HF patients the cumulative Na+ balance was restored to normal; furthermore, enalapril significantly attenuated the abnormalities in the distal delivery of Na+. Our results indicate that a defective adaptation of Na+ reabsorption in the proximal nephron is associated with Na+ retention in response to increased salt intake in the early or mild stages of HF. These abnormalities of renal Na+ handling are largely reversed by enalapril.

Topics: Adult; Angiotensin-Converting Enzyme Inhibitors; Body Fluids; Cardiomyopathy, Dilated; Diet, Sodium-Restricted; Enalapril; Female; Heart Failure; Hemodynamics; Humans; Kidney; Male; Middle Aged; Sodium

The effect of enalapril on cerebral blood flow (CBF) was studied in 11 patients with chronic heart failure (NYHA II or III, dilated cardiomyopathy in 6 and old myocardial infarction in 5). CBF was evaluated by analyzing the Patlak-Plot curve obtained from radionuclide angiography with technetium-99m hexamethylpropylene amine oxime (99mTC-HM-PAO). Cardiac index (CI) and stroke volume (SV) were simultaneously measured by impedance cardiography. These measurements were performed before and at four weeks after daily administration of 5 mg enalapril. The stroke volume, cardiac index, and heart rate were not significantly changed after four weeks of enalapril administration. However, CBF was increased by 6.5% from 36.72 +/- 4.66 to 39.13 +/- 5.65 mL/100g/min (P < 0.05). These results suggest that enalapril increased cerebral blood flow, which was not related to increased cardiac output in congestive heart failure. Patlak-Plot analysis of radionuclide angiography using 99mTC-HM-PAO may be available for quantitative assessment of brain perfusion.

Topics: Aged; Angiotensin-Converting Enzyme Inhibitors; Blood Flow Velocity; Cardiac Output; Cardiomyopathy, Dilated; Cerebrovascular Circulation; Chronic Disease; Enalapril; Female; Heart Failure; Heart Rate; Humans; Male; Middle Aged; Organotechnetium Compounds; Oximes; Radionuclide Angiography; Stroke Volume; Technetium Tc 99m Exametazime

Administration of angiotensin converting enzyme (ACE) inhibitors to patients with congestive heart failure (CHF) is associated to a decrease in the abnormal vasoconstrictor neurohormonal activity. This contributes to the sustained benefits of these drugs on symptoms and survival of patients with CHF. There is little information, however, regarding the effects of ACE inhibition on vasodilator and natriuretic hormones.. To evaluate the chronic effects of enalapril, in addition to digitalis and diuretics in patients with chronic cardiac failure.. Nine patients with an idiopathic dilated cardiomyopathy (8 male, aged 48 to 76 years old) under treatment with digitalis and diuretics, received enalapril 20 mg bid during eight weeks. Before and after this treatment period resting left ventricular ejection fraction, functional class, plasma levels of atrial natriuretic factor and bradykinins (BK) and urinary excretion of kalikreins (BK) and prostaglandin E2 (PGE2) were measured.. After enalapril therapy, there was a significant increase in maximal O2 consumption (14.8 +/- 1.2 to 18.6 +/- 1.5 ml/kg/min, p < 0.05) and radionuclide LV ejection fraction (27.4 +/- 1.1 to 31.4 +/- 0.9% p < 0.05). This was associated with a significant decrease in plasma ANP levels (559 +/- 158 to 178 +/- 54.8 pg/ml) and UK (391 +/- 112 to 243 +/- 92 Cu/24 h).. The decrease in ANP levels, which is a well known marker of prognosis in CHF, could contribute to explain the sustained clinical benefits observed with ACE inhibitors in patients with CHF.

Topics: Aged; Angiotensin-Converting Enzyme Inhibitors; Atrial Natriuretic Factor; Bradykinin; Cardiac Output, Low; Cardiomyopathy, Dilated; Chronic Disease; Dinoprostone; Enalapril; Female; Humans; Kallikreins; Male; Middle Aged; Oxygen Consumption; Stroke Volume; Vasodilator Agents

An American Cocker Spaniel with low plasma taurine concentration (< 2 nmol/mL) was presented with dyspnoea associated with pulmonary oedema and a left ventricular shortening fraction of 9%. Emergency therapy with furosemide, dobutamine, nitroglycerine and oxygen supplementation led to a good response. Chronic therapy was started with enalapril, furosemide, digoxin and taurine. Improvement in all echocardiographic indices were noted over a 22 week follow-up, most notably an increase in left ventricular shortening fraction to 20%, a decrease of E-point septal separation from 14 mm to 7 mm and marked left ventricular remodelling. This degree of improvement in myocardial function may represent a direct link between dilated cardiomyopathy in the American Cocker Spaniel and plasma taurine deficiency. Alternatively, this response may reflect a breed-related cardiomyopathy with a natural history and therapeutic response not commonly seen in the more common large breed cardiomyopathy presentations.

Topics: Animals; Antihypertensive Agents; Breeding; Cardiomyopathy, Dilated; Cardiotonic Agents; Digoxin; Diuretics; Dobutamine; Dog Diseases; Dogs; Dyspnea; Echocardiography; Enalapril; Female; Furosemide; Heart; Heart Ventricles; Nitroglycerin; Pulmonary Edema; Taurine; Vasodilator Agents

Topics: Adult; Angioedema; Cardiomyopathy, Dilated; Enalapril; Humans; Hypertension; Male; Tongue Diseases

The study group included 30 middle-aged patients (mean = 47.0 +/- 0.6 years) with chronic heart failure (NYHA class III and IV) in the course of primary dilated cardiomyopathy and ischemic heart disease. Enalapril in a dose of 5-10 mg/day was added to previous therapy with digitalis and diuretics. The patients were submitted for noninvasive cardiac and biochemical studies initially and at 3 months. Twenty-four patients completed the planned therapy. In 5 patients the drug had been withdrawn due to hypotension, and one patient died on the fourteenth day of observation because of heart failure worsening. After enalapril therapy 18 patients improved in NYHA functional classes. All patients showed left ventricular improvement based upon left ventricular systolic time intervals, 18 patients showed reduced peripheral vascular resistance, and in 9 patients echocardiography revealed a significant improvement of EF, CI and mVCF. Renal function also improved based upon the decrease in urea and uric acid.

Topics: Adult; Cardiomyopathy, Dilated; Enalapril; Female; Follow-Up Studies; Heart Failure; Humans; Male; Middle Aged; Treatment Outcome

Topics: Cardiomyopathy, Dilated; Carnitine; Digitalis Glycosides; Enalapril; Humans; Male; Middle Aged

Ten patients with severe (NYHAIII) heart failure were compared with 10 age-matched healthy subjects in terms of oxygen uptake and minute ventilation at rest and during exercise and calf and forearm blood flow measured by venous occlusion plethysmography at rest and after a standardized exercise test. Patients performed a symptom-limited treadmill exercise test and were then treated with enalapril for 5 weeks; the various measurements were repeated at weekly intervals. Oxygen consumption (VO2) at rest was similar in the patients and controls. During exercise, patients VO2 tended to be lower at each workload, but this was not affected by enalapril treatment. Minute ventilation was higher at rest and at each exercise stage in the patients than in the control subjects, and this was significantly reduced by enalapril treatment. Compared with the controls (2.94 +/- 0.10 and 2.93 +/- 0.20 ml.100 ml-1.min-1) forearm and calf blood flow measured by venous occlusion plethysmography was reduced at rest in the patients (1.34 +/- 0.18 and 1.24 +/- 0.11 ml.100 ml-1.min-1). but was significantly increased by enalapril treatment (1.73 +/- 0.15 and 1.60 +/- 0.16 ml.100 ml-1.min-1). Submaximal leg exercise to a fixed VO2 showed attenuation of the normal vasoconstriction in the forearm and vasodilatation of the calf; enalapril treatment changed these responses significantly towards normal but a marked abnormality of flow pattern persisted.

Topics: Aged; Arm; Cardiomyopathy, Dilated; Enalapril; Exercise Test; Exercise Tolerance; Humans; Leg; Male; Middle Aged; Muscles; Myocardial Ischemia; Oxygen Consumption; Regional Blood Flow; Respiration

Outcome in 81 pediatric patients with dilated cardiomyopathy was reviewed to assess whether treatment with angiotensin-converting enzyme (ACE) inhibitors affected survival. Age at onset was 3.6 +/- 0.6 years. Twenty-seven children (group 1) were treated with ACE inhibitors. Conventional therapy was used in the remaining 54 patients (group 2). There were no significant differences between the two groups in age at onset, left ventricular shortening fraction, left ventricular end-diastolic pressure, or mean pulmonary artery pressure. Patients treated with ACE inhibitors had a significantly better survival during the first year (p < 0.05) with continuation of this trend throughout the second year (p = 0.06). Beyond 2 years there was a tendency toward better survival in ACE inhibitor-treated patients, but the differences were no longer significant (p = 0.14). These data, along with observations in adult patients with chronic cardiac failure, indicate that converting enzyme inhibitors have a beneficial effect on prolonging survival of infants and children with severe left ventricular dysfunction from dilated cardiomyopathy.

Topics: Angiotensin-Converting Enzyme Inhibitors; Captopril; Cardiomyopathy, Dilated; Child, Preschool; Enalapril; Female; Humans; Life Tables; Male; Retrospective Studies; Survival Analysis; Time Factors

The purpose of the study was to evaluate the effect of enalapril on the frequency of ventricular premature beats in patients with congestive heart failure. The study group consisted of 30 patients with a mean age of 47 +/- 0.6 years with chronic congestive heart failure (NYHA classes III and IV) due to primary dilated cardiomyopathy and cardiomyopathy in the course of ischaemic heart disease. Initial therapy with digitalis and diuretics was supplemented with enalapril at a dose of 5-20 mg daily. Initially and at three months after enalapril, the following parameters were evaluated: NYHA functional class, the presence of premature ventricular beats in 24-hour ECG recording and left ventricular function by echocardiography. The scheduled therapy was completed by 23 patients; in 5 patients, the intake was discontinued because of hypotension, one patient died after 14 days due to worsening heart failure, and one patient was submitted for pacemaker implantation. Clinical improvement manifesting itself by a shift to lower NYHA classes was found in 20 patients. A reduced number of premature ventricular beats was observed in 52% of the patients. Termination of cardiac arrhythmias, especially of complex beats, was parallel to the circulatory improvement.

Topics: Adult; Cardiac Complexes, Premature; Cardiac Output; Cardiomyopathy, Dilated; Coronary Disease; Echocardiography; Electrocardiography, Ambulatory; Enalapril; Female; Heart Failure; Hemodynamics; Humans; Male; Middle Aged

In a longitudinal study comprising a total of 18 patients, the paradoxical time course of hANP plasma levels, i.e. the reproducibility of the low levels previously reported in cases of extreme cardiac insufficiency after administration of amiodarone, was investigated over a period of 9 months. At the same time, the effect of the degree of cardiac insufficiency and arrhythmia on the secretion of hANP was observed. The patients had been admitted to hospital because of the diagnoses "cardiac insufficiency secondary to cardiomyopathy" or "Grade IVb arrhythmia according to Lown's classification". During in-patient treatment, antiarrhythmic therapy was commenced in all patients. Clinical examinations and determinations of humoral parameters during therapy showed a substantial number of patients, who exhibited no increase in hANP levels despite massive cardiac decompensation. As far as drug therapy of patients with severe arrhythmias secondary to congestive (dilated) cardiomyopathy is concerned, amiodarone has proved to be the drug of choice in combination with digitalis, ACE inhibitors and diuretics. There is a close correlation between the degree of cardiac insufficiency and plasma hANP levels.

Topics: Aged; Aldosterone; Amiodarone; Arginine Vasopressin; Arrhythmias, Cardiac; Atrial Natriuretic Factor; Captopril; Cardiomyopathy, Dilated; Drug Therapy, Combination; Electrocardiography, Ambulatory; Enalapril; Female; Heart Failure; Hemodynamics; Humans; Longitudinal Studies; Male; Middle Aged

The deranged autonomic control of heart rate was studied in 34 patients with heart failure (New York Heart Association [NYHA] functional class II to III) by examining the carotid sinus baroreflex. The carotid sinus baroreceptors were stimulated by graded suction. The slope of the regression line between increases in cycle length and the degree of neck suction was taken as an index of baroreflex sensitivity. The reflex response is mediated by a selective increase of vagal efferent activity. Baroreflex sensitivity therefore represents a measure of vagal reactivity. Using multiple regression analysis, baroreflex sensitivity (BS) correlated positively to stroke volume index (SVI) and inversely to plasma renin activity (PRA) and to age: BS = 0.47 SVI - 0.38 PRA - 0.23 age + constant (r = 0.74; p less than 0.0005). In addition to digitalis and diuretics, angiotensin-converting enzyme (ACE) inhibitors (captopril or enalapril) were given to 16 patients for a mean of 17 +/- 3 days. The patients with hemodynamic improvement (group A) exhibited improved baroreflex sensitivity (1.4 +/- 0.4 to 3.6 +/- 1.2 msec/mm Hg; p less than 0.01). Baroreflex sensitivity remained unchanged (3.1 +/- 0.8 to 2.4 +/- 1.0 msec/mm Hg; n.s.) in the patients without hemodynamic improvement (group B). The increase in reflex sensitivity did not correlate with hemodynamic alterations. Baroreflex sensitivity during ACE inhibition (BSD) was only related to the baseline baroreflex sensitivity (BSB): BSD = 2.8 BSB - 0.46 (r = 0.84; p less than 0.005). In patients with heart failure, reflex bradycardia decreases with age and with PRA and increases with stroke volume. Chronic therapy with ACE inhibitors enhances vagal reactivity in patients with hemodynamic improvement.

Topics: Adult; Aged; Angiotensin-Converting Enzyme Inhibitors; Captopril; Cardiomyopathy, Dilated; Carotid Sinus; Coronary Disease; Enalapril; Female; Humans; Male; Middle Aged; Pressoreceptors; Reflex; Vagus Nerve

There is substantial evidence that the failing heart is in an energy-depleted state. The imbalance between myocardial oxygen supply and demand might be the cause for adaptive metabolic changes seen in patients with severe chronic heart failure. By analyzing the lactate dehydrogenase (LDH) isoenzyme pattern, an increase of LDH5 and a decrease of LDH1 was seen in myocardium from patients with chronic heart failure. Additionally, the concentration of the adenosine diphosphate (ADP)/adenosine triphosphate (ATP) carrier was significantly elevated. After treatment with the angiotensin-converting enzyme inhibitor enalapril in 33 patients with chronic heart failure, LDH1 increased from 38.7 +/- 6.7 to 42.3 +/- 5.5 (p less than 0.005), paralleled by a decrease in LDH5 from 20.8 +/- 7.0 to 15.8 +/- 4.7 (p less than 0.001). The ADP/ATP carrier concentration also decreased significantly within the normal range. There was a good correlation between the hemodynamic data and the LDH isoenzyme pattern. The shift of the LDH isoenzyme pattern and the decrease of the ADP/ATP concentration can be taken as an indication for an improvement of the myocardial energy balance in chronic heart failure with angiotensin-converting enzyme inhibitor therapy.

Topics: Adenosine Diphosphate; Adenosine Triphosphate; Blood Pressure; Cardiac Output; Cardiomyopathy, Dilated; Enalapril; Energy Metabolism; Female; Heart Failure; Humans; Isoenzymes; L-Lactate Dehydrogenase; Middle Aged; Myocardium; Oxygen Consumption

Angiotensin II elicits contractile responses in the coronary arteries and myocardial tissue, which suggests that blockade of the renin-angiotensin system by specific agents should lead to both coronary vasodilation and an alteration of left ventricular inotropism. The present work was designed to delineate--independently from its systemic effects--the intrinsic actions of an angiotensin converting-enzyme inhibitor on the coronary circulation and left ventricular function. To minimize peripheral effects, a bilateral intracoronary infusion of enalaprilat (0.05 mg.min-1, 1 ml.min-1 in each coronary artery) was performed in 16 patients with dilated cardiomyopathy. All patients had normal coronary arteriograms. In 12 patients (group I) the intracoronary infusion of enalaprilat resulted in minimal peripheral changes, with a 5% reduction in the mean aortic pressure (p less than .05) and no significant alteration in indexes of preload, i.e., left ventricular end-diastolic pressure and volume, or of afterload, i.e., left ventricular end-systolic stress and systemic resistances. Myocardial oxygen consumption was also unaffected by the intracoronary infusion of enalaprilat. Coronary vasodilation was demonstrated by a significant elevation of coronary sinus blood flow (+19%, from 181 +/- 73 to 214 +/- 79 ml.min-1, p less than .001) and a reduction of coronary resistance (-18%, from 0.51 +/- 0.17 to 0.41 +/- 0.15 mm Hg.ml-1.min, p less than .001), with a parallel increase in coronary sinus oxygen content and pressure (both p less than .05). Oxygen extraction by the myocardium was reduced (p less than .01).(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Adult; Cardiac Catheterization; Cardiomyopathy, Dilated; Coronary Circulation; Coronary Vessels; Enalapril; Enalaprilat; Female; Heart Ventricles; Hemodynamics; Humans; Infusions, Intravenous; Male; Middle Aged; Myocardial Contraction; Oxygen Consumption