digoxin and Myocardial-Ischemia

Heart failure is a major public health problem. Heart failure with preserved systolic function (HF-PSF) is a common form, which is difficult to diagnose. Results of recent studies show that HF-PSF has a poor prognosis, with an annual survival rate similar to that of heart failure with left ventricular systolic dysfunction. Despite these findings, the therapeutic management of HF-PSF is not clearly defined. We will discuss in this review of the literature the current therapeutic management of HF-PSF, including the role of precipitating factors such as hypertension, myocardial ischaemia and supraventricular arrhythmias, and the main results of epidemiological registries and randomized controlled clinical trials in this disease. Only four large therapeutic trials have assessed the impact of different classes of drugs (digoxin, angiotensin II converting enzyme inhibitors, angiotensin II receptors type I blockers and beta-blockers) on morbidity and mortality in HF-PSF. Results of these trials are disappointing. Apart from the beta-blockers, the other three classes of drugs did not show benefit on the outcome of the disease. Moreover, the results of the beta-blocker trial are controversial as a mixed population of heart failure with and without preserved systolic function was studied. Finally, the current therapeutic management of patients with HF-PSF is still based on our pathophysiological knowledge: education, low salt diet, diuretics, slowing heart rate and controlling triggering factors. Other large randomized controlled multicenter trials, which may help us in the understanding of HF-PSP and its therapeutic management, are ongoing.

Topics: Adrenergic beta-Antagonists; Adult; Aged, 80 and over; Algorithms; Angiotensin-Converting Enzyme Inhibitors; Benzopyrans; Blood Pressure; Cardiotonic Agents; Digoxin; Ethanolamines; Heart Failure; Heart Rate; Humans; Hypertension; Myocardial Ischemia; Nebivolol; Perindopril; Randomized Controlled Trials as Topic; Registries; Renal Artery Obstruction; Systole; Treatment Outcome

Ischaemic heart disease is probably the most important cause of heart failure. All patients with heart failure may benefit from treatment designed to retard progressive ventricular dysfunction and arrhythmias. Patients with heart failure due to ischaemic heart disease may also, theoretically, benefit from treatments designed to relieve ischaemia and prevent coronary occlusion and from revascularisation. However, there is little evidence to show that effective treatments, such as angiotensin converting enzyme (ACE) inhibitors and beta-blockers, exert different effects in patients with heart failure with or without coronary disease. Moreover, there is no evidence that treatment directed specifically at myocardial ischaemia, whether or not symptomatic, or coronary disease alters outcome in patients with heart failure. Some agents, such as aspirin, designed to reduce the risk of coronary occlusion appear ineffective or harmful in patients with heart failure. There is no evidence, yet, that revascularisation improves prognosis in patients with heart failure, even in patients who are demonstrated to have extensive myocardial hibernation. On current evidence, revascularisation should be reserved for the relief of angina. Large-scale, randomised controlled trials are currently underway investigating the role of specific treatments targeted at coronary syndromes in patients who have heart failure. The CHRISTMAS study is investigating the effects of carvedilol in a large cohort of patients with and without hibernating myocardium. The WATCH study is comparing the efficacy of aspirin, clopidogrel and warfarin. The HEART-UK study is assessing the effect of revascularisation on mortality in patients with heart failure and myocardial hibernation. Smaller scale studies are currently assessing the safety and efficacy of statin therapy in patients with heart failure. Only when the results of these and other studies are known will it be possible to come to firm conclusions about whether patients with heart failure and coronary disease should be treated differently from other patients with heart failure due to left ventricular systolic dysfunction.

Topics: Adrenergic beta-Antagonists; Angiotensin-Converting Enzyme Inhibitors; Calcium Channel Blockers; Cardiotonic Agents; Digoxin; Diuretics; Heart Failure; Humans; Hypolipidemic Agents; Myocardial Ischemia; Myocardial Revascularization; Nitrates; Patient Selection; Smoking Cessation; Spironolactone; Thrombolytic Therapy

For out-of-hospital cardiac arrest (OHCA) to be predicted and prevented, it is imperative the healthcare system has access to those vulnerable before the event occurs. We aimed to determine the extent of contact to the healthcare system before OHCA.. All patients in Denmark with a registered OHCA June 1, 2001-December 31, 2005 were matched on age and sex with 10 random controls from the entire Danish population. We estimated the association with OHCA by conditional logistic regression analyses, and we determined the proportion of patients in contact with the healthcare system before OHCA from hospital admissions or claimed prescriptions.. We identified 12,089 patients with an OHCA. Of these, 62% (7548) and 85% (10,312) were in contact with the healthcare system up to 30 days and 1 year before OHCA, respectively. Association with OHCA up to 30 days before the event pertained to myocardial infarction (odds ratio (OR)=6.4, 95% confidence interval (CI): 4.7-8.6)); heart failure (OR=5.1, CI: 4.1-6.3); ischemic heart disease (OR=1.9, CI: 1.6-2.4); and cardiac dysrhythmia (OR=1.8, CI: 1.4-2.2). Concomitant pharmacotherapy up to 30 days before OHCA with the strongest association was: corticosteroids (systemic) (OR=2.7, CI: 2.5-3.0), bronchial dilators (OR=2.5, CI: 2.3-2.7), anti-psychotic medication (OR=2.1, CI: 1.9-2.3), and digoxin (OR=2.1, CI: 2.0-2.3). Similar results were found for associations up to 1 year before OHCA.. Contrary to general belief, the majority of OHCA patients are in contact with the healthcare system shortly before OHCA.

Topics: Adrenal Cortex Hormones; Aged; Antipsychotic Agents; Arrhythmias, Cardiac; Bronchodilator Agents; Denmark; Digoxin; Female; Health Behavior; Heart Failure; Humans; Male; Middle Aged; Myocardial Infarction; Myocardial Ischemia; Out-of-Hospital Cardiac Arrest; Patient Admission; Regression Analysis

To evaluate the effect of an arteriolar dilator (diltiazem hydrochloride) versus a venodilator (isosorbide dinitrate) on digoxin kinetics and to estimate the efficacy and tolerability of these vasodilators when combined with digoxin for 10 days therapy in patients with congestive heart failure secondary to ischemic heart disease.. A double blind randomized cross over study was carried out to investigate the effect of an arteriolar dilator (diltiazem hydrochloride 180 mg/day orally) versus a venodilator (isosorbide dinitrate 30 mg/day orally) on digoxin kinetics (0.25 mg/day orally), after 10 days therapy in patients with heart failure due to ischemic heart disease. Also, the effect of these drugs on blood pressure, heart rate, renal functions and serum electrolytes, and their efficacy and tolerability in combination with digoxin were studied. This study was carried out in the Department of Medicine, Main Alexandria University Hospital, Alexandria, Egypt, during the period May 1999 through to May 2000.. Diltiazem caused a significant increase in digoxin maximum serum concentration without significant change in time to reach maximum concentration and the apparent volume of distribution. The total digoxin clearance was significantly reduced and the elimination half life was prolonged. Subsequently the area under time-concentration curve and the steady-state digoxin level were increased, but were still within therapeutic margin. On the other hand isosorbide dinitrate significantly increased digoxin maximum serum concentration but without change in the other digoxin pharmacokinetic parameters. Isosorbide dinitrate, but not diltiazem, caused significant reduction in supine and standing blood pressure, while both drugs did not significantly alter pulse rate, renal functions, serum sodium potassium and electrocardiographic pattern.. Patients who received diltiazem displayed a mean 51% increase in the area under the plasma concentration-time curve, 50% increase in mean steady state serum digoxin concentration, and 37% increase in peak serum digoxin concentration. While patients who received isosorbide dinitrate showed only a 15% increase in digoxin maximum serum concentration and no statistically significant change in mean steady state digoxin concentration or area under the plasma concentration-time curve. The elimination half life during the diltiazem phase was prolonged by 29% while there was no significant change with isosorbide dinitrate. Netiher diltiazem or isosorbide dinitrate significantly altered the time to reach maximum serum digoxin concentration. The addition of a vasodilator such as, diltiazem or isosorbid dinitrate to digoxin could significantly improve the symptoms and signs of heart failure compared to digoxin alone. They were well tolerated and without fear of electrolyte imbalance which potentiate digoxin toxicity.

Topics: Analysis of Variance; Digoxin; Diltiazem; Double-Blind Method; Drug Interactions; Drug Therapy, Combination; Electrolytes; Enzyme Inhibitors; Female; Half-Life; Heart Failure; Hemodynamics; Humans; Isosorbide Dinitrate; Male; Middle Aged; Myocardial Ischemia; Vasodilator Agents

Congestive heart failure (CHF) is commonly associated with nonvalvular atrial fibrillation (AF), and their combination may affect treatment strategies and outcomes.. To assess the treatment strategies and 1-year clinical outcomes of antithrombotic and CHF therapies for patients with newly diagnosed AF with concomitant CHF stratified by etiology (ischemic cardiomyopathy [ICM] vs nonischemic cardiomyopathy [NICM]).. The GARFIELD-AF registry is a prospective, noninterventional registry. A total of 52 014 patients with AF were enrolled between March 2010 and August 2016. A total of 11 738 patients 18 years and older with newly diagnosed AF (≤6 weeks' duration) and at least 1 investigator-determined stroke risk factor were included. Data were analyzed from December 2017 to September 2018.. One-year follow-up rates of death, stroke/systemic embolism, and major bleeding were assessed.. Event rates per 100 person-years were estimated from the Poisson model and Cox hazard ratios (HRs) and 95% confidence intervals.. The median age of the population was 71.0 years, 22 987 of 52 013 were women (44.2%) and 31 958 of 52 014 were white (61.4%). Of 11 738 patients with CHF, 4717 (40.2%) had ICM and 7021 (59.8%) had NICM. Prescription of oral anticoagulant and antiplatelet drugs was not balanced between groups. Oral anticoagulants with or without antiplatelet drugs were used in 2753 patients with ICM (60.1%) and 5082 patients with NICM (73.7%). Antiplatelets were prescribed alone in 1576 patients with ICM (34.4%) and 1071 patients with NICM (15.5%). Compared with patients with NICM, use of angiotensin-converting enzyme inhibitors/angiotensin receptor blockers (72.6% [3439] vs 60.3% [4236]) and of β blockers (63.3% [2988] vs 53.2% [3737]) was higher in patients with ICM. Rates of all-cause and cardiovascular death per 100 patient-years were significantly higher in the ICM group (all-cause death: ICM, 10.2; 95% CI, 9.2-11.1; NICM, 7.0; 95% CI, 6.4-7.6; cardiovascular death: ICM, 5.1; 95% CI, 4.5-5.9; NICM, 2.9; 95% CI, 2.5-3.4). Stroke/systemic embolism rates tended to be higher in ICM groups compared with NICM groups (ICM, 2.0; 95% CI, 1.6-2.5; NICM, 1.5; 95% CI, 1.3-1.9). Major bleeding rates were significantly higher in the ICM group (1.1; 95% CI, 0.8-1.4) compared with the NICM group (0.7; 95% CI, 0.5-0.9).. Patients with ICM received oral anticoagulants with or without antiplatelet drugs less frequently and antiplatelets alone more frequently than patients with NICM, but they received angiotensin-converting enzyme inhibitors/angiotensin receptor blockers more often than patients with NICM. All-cause and cardiovascular death rates were higher in patients with ICM than patients with NICM.. ClinicalTrials.gov Identifier: NCT01090362.

Topics: Adrenergic beta-Antagonists; Aged; Aged, 80 and over; Angiotensin Receptor Antagonists; Angiotensin-Converting Enzyme Inhibitors; Anticoagulants; Atrial Fibrillation; Cardiomyopathies; Cardiotonic Agents; Cardiovascular Diseases; Cohort Studies; Digoxin; Female; Guideline Adherence; Heart Failure; Hemorrhage; Humans; Male; Middle Aged; Mineralocorticoid Receptor Antagonists; Mortality; Myocardial Ischemia; Platelet Aggregation Inhibitors; Practice Guidelines as Topic; Proportional Hazards Models; Registries; Sodium Potassium Chloride Symporter Inhibitors; Stroke; Stroke Volume

This study assessed sex-related differences in a large cohort of unselected patients with heart failure (HF) across the ejection fraction (EF) spectrum.. Females are under-represented in randomized clinical trials. Potential sex-related differences in HF may question the generalizability of trials.. In the Swedish Heart Failure Registry population multivariate Cox and logistic regression models were fitted to investigate differences in prognosis, prognostic predictors, and treatments across males and females.. Of 42,987 patients, 37% were females (55% with HF with preserved EF [HFpEF], 39% with HF with mid-range EF [HFmrEF], and 29% with HF with reduced EF [HFrEF]). Females were older and more symptomatic and more likely to have hypertension and kidney disease but less likely to have diabetes and ischemic heart disease. After adjustments, females were more likely to use beta-blockers and digoxin but less likely to receive HF device therapy. Crude mortality/HF hospitalization rates for HFpEF (hazard ratio [HR]: 1.16) and HFmrEF (HR: 1.14) were significantly higher in females but lower in females with HFrEF (HR: 0.95). After adjustments, the risk was significantly lower in females regardless of EF (HR: 0.80 in HFrEF, HR: 0.91 in HFmrEF, and HR: 0.93 in HFpEF). The main sex-related differences in prognostic predictors concerned diabetes in HFrEF and anemia in HFmrEF.. Males and females with HF showed different characteristics across the EF spectrum. Males reported a lower crude risk of mortality/morbidity in HFpEF and HFmrEF but higher risk of HFrEF, although after adjustments, prognosis was better in females regardless of EF. The observed sex-related differences highlight the need for an adequate representation of females in HF randomized controlled trials to improve generalizability.

Topics: Adrenergic beta-Antagonists; Age Distribution; Aged; Aged, 80 and over; Cardiac Resynchronization Therapy; Cardiotonic Agents; Diabetes Mellitus; Digoxin; Female; Heart Failure; Hospitalization; Humans; Hypertension; Kidney Diseases; Logistic Models; Male; Middle Aged; Mortality; Myocardial Ischemia; Phenotype; Prognosis; Proportional Hazards Models; Registries; Severity of Illness Index; Sex Factors; Stroke Volume; Sweden

Topics: Aged; Aged, 80 and over; Anti-Arrhythmia Agents; Arrhythmias, Cardiac; Coronary Disease; Diagnosis, Differential; Digoxin; Electrocardiography; Female; Humans; Myocardial Ischemia; Signal Processing, Computer-Assisted

We assessed, in patients with a first hospitalization for heart failure (HF), the temporal relationship of the incidence of cardiovascular events, all-cause mortality, and cardiovascular drug treatment.. Data were obtained from the PHARMO Record Linkage System, a population-based registry of pharmacy records linked with hospital discharge records in The Netherlands. Patients were selected based on a first hospital discharge diagnosis of documented HF. Two time-periods were compared: 1998-2002 and 2003-07. In each time-period, we analysed all prescribed cardiovascular medications, all-cause mortality, and cardiovascular events (rehospitalization for HF and ischaemic events) within the first year after hospitalization, and the occurrence of ischaemic events separately (myocardial infarction and ischaemic stroke). Cox-regression analysis was performed to calculate hazard ratios (HR) with 95% confidence intervals (CI). We identified 8276 patients in 1998-2002 and 9548 patients from 2003-07. There was an increase in almost all cardiovascular medication prescriptions in the second period: in particular, beta-blocker prescriptions rose from 36% in 1998-2002 to 55% in 2003-07. In the first year after hospitalization, there was no difference in all-cause mortality or any cardiovascular event (HR 1.00, 95%CI: 0.95-1.05), as a composite endpoint or when analysed separately. The incidence of ischaemic events decreased from 2.7 to 1.9% in the first and second time-period, respectively (HR 0.74, 95%CI: 0.61-0.90).. Prescription of cardiovascular medications in patients with a first hospitalization for HF has increased in recent years, particularly for beta-blockers, and the incidence of ischaemic events may have decreased. There was no decrease in all-cause mortality or cardiovascular events.

Topics: Adrenergic beta-Antagonists; Aged; Aged, 80 and over; Angina Pectoris; Angiotensin-Converting Enzyme Inhibitors; Cardiotonic Agents; Digoxin; Diuretics; Female; Heart Failure; Hospitalization; Humans; Male; Myocardial Infarction; Myocardial Ischemia; Practice Patterns, Physicians'; Prognosis; Spironolactone; Stroke

Endogenous ouabain-like factor (OLF) has been detected in mammalian plasma, adrenal gland, and hypothalamus. We investigate whether cardiac tissue may also produce OLF. HPLC chromatographic separation of cardiac extracts showed that RIA-determined OLF activity coincided with the elution profile of exogenous ouabain and with the ability to inhibit 86Rb uptake in human erythrocytes. OLF activity was remarkably higher in excised hearts (3.94 +/- 0.84 pmol/g wet weight by RIA) than in rat blood (0.05 +/- 0.02 pmol/ml). Similar values were obtained in perfused working hearts, without significant changes over time from 5 to 30 minutes of aerobic perfusion. Significant OLF release in the perfusion buffer was also observed (0.54 +/- 0.05 pmoles over 30 minutes). In hearts subjected to 15 minutes of aerobic perfusion followed by 15 minutes of global myocardial ischemia OLF concentration was remarkably increased (8.59 +/- 1.13 versus 4.58 +/- 0.57 pmol/g wet weight by RIA, P < 0.01; an increase after ischemia was confirmed by the assay of 86Rb uptake). Our findings suggest that the rat heart is able to produce OLF, and that its concentration increases during ischemia. Myocardial OLF might modulate the Na/K-ATPase, producing relevant effects on ionic homeostasis and/or gene transcription.

Topics: Animals; Cardenolides; Chromatography, High Pressure Liquid; Digoxin; Male; Myocardial Ischemia; Myocardium; Radioimmunoassay; Rats; Rats, Wistar; Saponins; Sodium-Potassium-Exchanging ATPase

Cardiotonic agents may differentially alter indices of the cytosolic [Ca2+]/left ventricular pressure (LVP) relationship when given before and after ischemia. We measured and calculated systolic-diastolic [Ca2+], systolic-diastolic LVP, velocity ratios (VRs) d[Ca2+]/dtmax to dLVP/dtmax (VRmax), d[Ca2+]/dtmin to dLVP/dtmin (VRmin), and area ratio (AR, area Ca2+]/area LVP per beat) before and after 30 min global ischemia in guinea pig hearts.. Hearts were perfused with levosimendan, dobutamine, dopamine, or digoxin. Ca2+ transients were recorded by indo-1 fluorescence via a fiber optic probe placed on the LV free wall. [Ca2+]/LVP loops were acquired by plotting LVP time as a function of [Ca2+] at multiple time points during the cardiac cycle.. Ischemia reperfusion increased [Ca2+] and decreased contractility and relaxation and produced a flatter and broader [Ca2+]/LVP loop. All drugs shifted the [Ca2+]/LVP loop rightward and upward when given before and after ischemia. Dobutamine increased [Ca2+] and contractility more than other drugs. Digoxin increased [Ca2+] the least but increased contractility similar to dopamine and levosimendan. Before ischemia dopamine and digoxin both decreased VRmax and VRmin, whereas dobutamine increased VRmin, but not VRmax, and levosimendan had no effect on VR. VRmax and VRmin were markedly elevated after ischemia, but again decreased with dopamine and digoxin; dobutamine again increased VRmin, but not VRmax, and levosimendan decreased both VRmax and VRmin. Before ischemia dopamine and digoxin both decreased AR, dobutamine increased AR, and levosimendan had no effect; after ischemia AR was markedly elevated but dopamine and digoxin decreased AR, dobutamine increased AR, and levosimendan decreased AR.. Although each drug enhanced contractility and relaxation both before and after ischemia by increasing cytosolic [Ca2+] and Ca2+ flux, dopamine and digoxin improved, and dobutamine worsened responsiveness to Ca2+, i.e., velocity ratio and area ratio, whereas levosimendan had no net effect before ischemia but improved responsiveness after ischemia.

Topics: Animals; Calcium; Cardiotonic Agents; Cytosol; Digoxin; Dopamine; Guinea Pigs; Hydrazones; Myocardial Ischemia; Perfusion; Pyridazines; Random Allocation; Simendan; Ventricular Pressure

The effect of digoxin on electrocardiogram (ECG) at rest and during exercise, and on QRS amplitude variability (variance ECG) was studied in 20 healthy, middle-aged men and women. Exercise test and variance ECG were performed before and after pretreatment with digoxin orally. Plots of ST-segment level vergus heart rate (HR) were constructed from the rest and exercise ECG recordings. Thus obtained ST/HR loops were compared with loops from 10 male patients with angiographically verified ischemic heart disease (IHD). Pretreatment with digoxin caused a significant (P <.001) ST depression in precordial leads, which was similar in men and women and returned promptly to the isoelectric level after exercise resulting in a counterclockwise rotation of the ST/HR loop. In IHD patients, the exercise-induced ST-segment depression was significantly more pronounced (P <.01) and the ST-segment recovery slower, resulting in clockwise rotated ST/HR loops. The results of variance ECG were not influenced by digoxin. The digoxin-induced ST-reaction during exercise mimics exercise-induced ischemic ST-reaction in patients with IHD, but can still be discerned by the analysis of ST/HR loops.

Topics: Administration, Oral; Aged; Carotid Arteries; Digoxin; Echocardiography; Electrocardiography; Exercise; Exercise Test; Female; Humans; Male; Middle Aged; Myocardial Ischemia; Rest

The aim of the present study was to describe patients considered to have had heart failure (HF), or were being treated for HF, in a defined area in primary health care, e.g. diagnostic procedures, aetiologic diseases and management, and to evaluate whether there is a difference between the genders.. Descriptive retrospective investigation.. Atvidaberg community situated in southeast Sweden, 12 400 inhabitants.. 256 patients treated for symptomatic HF.. Prevalence, aetiology, diagnostic procedures and management of HF and differences between the genders.. The diagnosis of HF was based on an objective evaluation of cardiac function in only 31% of the patients. Ischaemic heart disease (IHD) was the predominant associated disease, followed by hypertension. Therapy included diuretics (84%), angiotensin converting enzyme (ACE) inhibitors (56%) and digoxin (40%). Only 52% had optimal doses of ACE inhibitors. Women had a significantly higher mean age and their diagnoses were based on an objective diagnostic test (echocardiography) in only 20%. Women were prescribed ACE inhibitors to a lesser extent (43%) than men (64%) and with a lower optimal dose (44% versus 56% in men).. There is still room for improvement in the management of HF in primary health care, especially in women, where the diagnosis is not generally based on an objective evaluation of cardiac function and where the treatment to a lesser extent than in men includes ACE inhibitors.

Topics: Adult; Age Distribution; Aged; Aged, 80 and over; Angiotensin-Converting Enzyme Inhibitors; Cardiac Output, Low; Digoxin; Diuretics; Electrocardiography; Female; Humans; Hypertension; Male; Middle Aged; Myocardial Ischemia; Primary Health Care; Retrospective Studies; Sex Distribution; Sweden; Women's Health

Topics: Adult; Angiotensin-Converting Enzyme Inhibitors; Anti-Arrhythmia Agents; Cardiomyopathy, Dilated; Cardiotonic Agents; Coronary Disease; Digoxin; Diuretics; Heart Defects, Congenital; Heart Failure; Hemodynamics; Humans; Hypertension; Myocardial Ischemia; Phosphodiesterase Inhibitors; Vasodilator Agents

In patients with heart failure, therapy with "maximally tolerated" oral doses of diuretics, vasodilators, and digitalis results in a significant increase in the distance walked during the 6-minute walking test, compared with conventional therapy at "standard" doses, indicating an improvement in exercise tolerance. The 6-minute walk test is a simple, inexpensive, and well-tolerated test to measure changes in exercise tolerance induced by pharmacologic interventions, even on a short-term basis.

Topics: Administration, Oral; Adult; Aged; Cardiomyopathy, Dilated; Cardiotonic Agents; Digoxin; Diuretics; Dose-Response Relationship, Drug; Drug Administration Schedule; Echocardiography; Electrocardiography; Exercise Test; Heart Failure; Humans; Male; Middle Aged; Myocardial Ischemia; Treatment Outcome; Vasodilator Agents; Walking

This study attempted to identify which group of cardiac patients is most at risk when dental extractions are performed under a local anesthetic with a vasopressor.. Forty cardiac patients who had dental extractions under local anesthesia were connected to a Holter monitor for 24 hours, starting an hour before the procedure. The electrocardiogram was analyzed for the number of premature beats, ST depression, and cardiac rhythm. A mean rate was calculated for the first 2 hours after injection of the local anesthetic and for the subsequent 22 hours. The preoperative electrocardiogram was compared with the electrocardiogram performed 1 week before treatment.. Electrocardiographic changes were observed in 15 patients (37.5%), and all occurred during the first 2 hours after injection of the local anesthetic. Of the 15 patients, eight were being treated with digoxin.. Cardiac patients being treated with digoxin had more electrocardiographic changes after administration of a local anesthetic than other cardiac patients. When the local anesthetic contained a vasopressor, there was a greater incidence of tachycardia but less arrhythmia or ST depression.

Topics: Adult; Aged; Aged, 80 and over; Anesthesia, Dental; Anesthetics, Local; Arrhythmias, Cardiac; Contraindications; Dental Care for Chronically Ill; Digoxin; Drug Interactions; Electrocardiography, Ambulatory; Epinephrine; Female; Heart Diseases; Humans; Lidocaine; Male; Middle Aged; Myocardial Ischemia; Tooth Extraction; Vasoconstrictor Agents

The inhibition of sarcolemmal Na+,K+-ATPase activity is closely related to ischemic myocardial cell injury. However, the involvement of this enzyme in preconditioning has not been determined.. We assessed the effect of ischemia on sarcolemmal Na+,K+-ATPase activity. Control and preconditioned rabbits were subjected to 0, 10, 20, 30, and 60 minutes of coronary occlusion. Ten to 60 minutes of ischemia reduced Na+,K+-ATPase activity, whereas preconditioning preserved the activity of this enzyme only during the first 20 minutes of ischemia. To determine whether the preservation of Na+,K+-ATPase activity in the early phase of ischemia contributed to limiting the infarct size, additional rabbits underwent 30 minutes of occlusion followed by 3 hours of reperfusion with or without pretreatment with digoxin, an inhibitor of Na+,K+-ATPase. Infarct size in animals pretreated with digoxin in the absence of preconditioning did not differ from that in controls. It was markedly reduced by preconditioning, whereas digoxin reduced the infarct size-limiting effect. Moreover, preconditioning increased sarcolemmal Na+-Ca2+ exchange activity in rabbits subjected to 20 minutes of ischemia, whereas digoxin diminished this increase.. Preconditioning preserves the ischemia-induced reduction in sarcolemmal Na+,K+-ATPase activity in the early phase of ischemia in rabbit hearts. Inhibition of Na+,K+-ATPase activity reduces the infarct size-limiting effect of preconditioning with a loss of increased Na+-Ca2+ exchange activity, implying that this preservation is responsible for the cardioprotective effect of preconditioning.

Topics: Animals; Digoxin; Enzyme Inhibitors; Hemodynamics; Ischemic Preconditioning, Myocardial; Myocardial Infarction; Myocardial Ischemia; Rabbits; Sarcoplasmic Reticulum; Sodium-Potassium-Exchanging ATPase

To elucidate the issues such as excitation-contraction coupling and myocardial ischemia, it is necessary to measure intracellular free Ca2+ concentration and mechanical function of hearts perfused via the normal arterial circulation. For this purpose, we simultaneously measured Ca(2+)-dependent indo-1 fluorescence and left ventricular (LV) pressure on a beat-to-beat basis in Langendorff guinea-pig hearts, and investigated the changes in Ca2+ transient and LV function during inotropic stimulation and myocardial ischemia. The indo-1 fluoresence ratio and LV developed pressure increased the perfusate [Ca2+] increased from 1.6 to 3.2 mmol/L, and there was a good correlation between Ca2+ transient and LV contractility. Digoxin (10(-6) mol/L) and milrinone (10(-5) mol/L) increased LV contractility with a concomitant increase in Ca2+ transient, and the relative increase of Ca2+ transient produced by milrinone was much more than that by digoxin. The reduction of coronary perfusion pressure from 80 to 40 mm Hg decreased LV contractility with an increase in indo-1 fluorescence ratio. These results suggest that Ca2+ responsiveness of contractile apparatus declines during inotropic stimulation by milrinone and during myocardial ischemia. Thus, this experimental technique is useful to investigate the interrelation of Ca2- regulation and LV function during a variety of pharmacological and physiologic perturbations.

Topics: Animals; Calcium; Cardiotonic Agents; Digoxin; Fluorescent Dyes; Guinea Pigs; Indoles; Male; Milrinone; Myocardial Contraction; Myocardial Ischemia; Pyridones; Spectrometry, Fluorescence; Ventricular Function, Left

We investigated the effects of EMD-53998 and digoxin on Ca2+ transients and left ventricular (LV) function in indo 1-loaded Langendorff guinea pig hearts. EMD-53998 (10(-9) to 10(-5) M) and digoxin (10(-10) to 10(-6) M) increased +dP/dt and Ca2+ transients in normal hearts. The relative increase in Ca2+ transients by EMD-53998 was similar to digoxin. At 10(-5) M, EMD-53998 increased LV end-diastolic pressure. Low-flow ischemia decreased +dP/dt by 50%, while indo 1 ratio increased by 10-25%. EMD-53998 (10(-9) to 10(-6) M) effectively restored the depressed +dP/dt with little effect on indo 1 ratio, but at 10(-5) M, it markedly elevated LV end-diastolic pressure and the beneficial effect on contractile dysfunction disappeared. Digoxin (10(-10) to 10(-7) M) failed to improve LV function, but at 10(-6) M, it restored contractile dysfunction with a large increase in indo 1 ratio. The relation between indo 1 ratio and +dP/dt clearly showed that EMD-53998 restored contractile dysfunction by Ca2+ sensitization. These findings suggest that Ca2+ sensitization by EMD-53998 is an advantageous approach for ischemic contractile failure but impairs diastolic function.

Topics: Animals; Blood Pressure; Calcium; Cardiotonic Agents; Digoxin; Guinea Pigs; Heart; Male; Myocardial Ischemia; Myocardium; Quinolines; Reference Values; Thiadiazines; Ventricular Function, Left

The effect of digoxin therapy on the survival of heart failure patients in sinus rhythm was assessed using a retrospective case control study. Patients with an acute exacerbation of chronic heart failure secondary to ischemic heart disease were selected. All were in sinus rhythm and all were treated with digoxin. Case-matched controls were identified for all digoxin-treated patients. Long-term survival was ascertained for all 18 digoxin-treated patients and 18 controls who formed the study population. The relative risk of death was 6.4 for digoxin-treated patients (95% confidence interval 0-36) during the period of hospitalization. Te increased risk of death among digoxin-treated patients persisted up to 1 year following discharge from hospital. The results raise further concern regarding the safety of digoxin therapy in managing heart failure exacerbation, when the patients are in sinus rhythm.

Topics: Administration, Oral; Aged; Cardiotonic Agents; Case-Control Studies; Digoxin; Diuretics; Drug Therapy, Combination; Female; Follow-Up Studies; Furosemide; Heart Failure; Heart Rate; Humans; Male; Middle Aged; Myocardial Ischemia; Retrospective Studies; Survival Rate

Topics: Aged; Aged, 80 and over; Digoxin; Drug Overdose; Female; Heart Failure; Humans; Immunoglobulin Fab Fragments; Kidney Failure, Chronic; Male; Middle Aged; Myocardial Ischemia; Suicide, Attempted; Ultrafiltration

The aim was to study whether a circulating sodium pump inhibitor (endogenous digoxin-like factor) contributes to the genesis of early ventricular arrhythmias in acute myocardial ischaemia in rats.. Effects of digoxin antibody (260 micrograms.kg-1) on the incidence of ventricular arrhythmias, plasma digoxin-like immunoreactivity (DELFIA immunoassay), Na+, K+, and Mg2+ ions, and activity of the ouabain sensitive Na+, K(+)-pump in different regions of myocardium have been studied in propranolol naive and propranolol pretreated rats exposed to acute coronary artery ligation. Adult male Wistar rats were divided into six experimental groups: (1) saline pretreated controls; (2) saline pretreated coronary artery ligated rats; (3) coronary artery ligated rats pretreated with 260 micrograms.kg-1 digoxin antibody; (4) propranolol pretreated controls; (5) propranolol pretreated rats with acute myocardial ischaemia; (6) rats with acute myocardial ischaemia pretreated with both propranolol and digoxin antibody.. Acute myocardial ischaemia in saline pretreated rats was associated with a twofold increase of plasma digoxin-like immunoreactivity and ventricular arrhythmias, but did not lead to changes in myocardial Na+, K(+)-pump activity. Pretreatment of coronary artery ligated rats with digoxin antibody reduced the total duration of ventricular tachycardia and ventricular fibrillation during a 15 minute postligation period from 201 (SEM 34) to 46(18) seconds (p < 0.002) but did not alter activity of the myocardial Na+, K(+)-pump. In rats pretreated with propranolol, acute myocardial ischaemia was associated with a twofold inhibition of the Na+, K(+)-pump in left atrial and left ventricular myocardium, and with a 69% increase in plasma K+ concentration. Administration of digoxin antibody to propranolol pretreated coronary artery ligated rats in parallel with the antiarrhythmic effect prevented the increase in plasma K+ concentration and inhibition of Na+, K(+)-pump in the left atrial, but not the left ventricular myocardium.. A circulating digoxin-like factor contributes to the pathogenesis of myocardial ischaemia induced ventricular arrhythmias. As propranolol pretreatment of coronary artery ligated rats inhibited the Na, K(+)-pump in myocardium, the inhibitory effect of endogenous digoxin-like factor on Na+, K(+)-ATPase was probably masked in propranolol naive animals by the stimulatory action of catecholamines on Na+, K(+)-ATPase described previously.

Topics: Acute Disease; Animals; Antibodies; Arrhythmias, Cardiac; Blood Proteins; Cardenolides; Digoxin; Male; Myocardial Ischemia; Myocardium; Rats; Rats, Wistar; Saponins; Sodium-Potassium-Exchanging ATPase