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Query: UMLS:C0018801 (heart failure)
 72,216 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

1. The present study was designed to test the hypothesis that beneficial effects of angiotensin converting enzyme (ACE)inhibitors are independent of a fall in blood pressure in rat experimental heart failure following coronary ligation. 2. The animals were assigned randomly to six groups; sham operation, controls subjected to coronary ligation (control), coronary ligation plus chronic treatment with ACE inhibitors at non- and hypotensive doses; perindopril (0.2 or 2 mg kg-1 day-1) or enalapril (2 or 20 mg kg-1 day-1) for three weeks starting one week after the ligation. 3. Systemic blood pressure was measured every week during the experiments. At the end of the treatments, cardiac function and heart weight (an index of myocardial hypertrophy) were determined. In the other animals, ACE activities in plasma and tissues including heart, kidney, lung and blood vessels were measured. 4. In the controls, cardiac ACE activity, weight of right ventricle and left ventricular end-diastolic pressure (LVEDP) were higher compared to those in the sham-operated animals four weeks after the coronary ligation. However, ACE activities were not changed in plasma, kidney, lung and aorta by ligation of the coronary artery. 5. The chronic treatment with perindopril at a dose of 0.2 mg kg-1 day-1 inhibited the increase in ACE activity in cardiac tissue and suppressed the right ventricular hypertrophy without affecting systemic haemodynamics. In contrast, enalapril at a dose of 20 mg kg-1 day-1, but not 2 mg kg-1 day-1, prevented the development of the right ventricular hypertrophy. Enalapril at 20 mg kg-1 day-1 also lowered systemic blood pressure. 6. There is no significant correlation between systemic blood pressure and right ventricular hypertrophy at the end of the treatment with perindopril (r = 0.06) or enalapril (r = 0.1).7. These findings demonstrate that perindopril, an ACE inhibitor, prevents cardiac hypertrophy without affecting systemic blood pressure in the rat with heart failure after coronary ligation, and suggest that selective augmentation of ACE activity in cardiac tissue is involved in the progression of hypertrophy in this model.
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PMID:Lack of correlation of hypotensive effects with prevention of cardiac hypertrophy by perindopril after ligation of rat coronary artery. 792 10

In heart failure, both the sympathetic nervous system and the renin angiotensin system play important pathophysiological roles, and the two systems may interact with each other, e.g., angiotensin II facilitating noradrenaline release. An abnormality in beta-adrenoceptor density (i.e., a decrease) occurs in clinical and pacing-induced heart failure. This observation together with the therapeutic effectiveness of converting-enzyme inhibitors in the management of patients with heart failure led to the current investigation. The aim was to explore the impact of chronic enalapril treatment on the status of myocardial beta-adrenoceptors in dogs paced (250 beats.min-1) to end-stage heart failure. Placebo or enalapril treatment (5 mg b.i.d.) commenced 1 week after the onset of ventricular pacing and continued until end-stage heart failure was reached. Myocardial beta-adrenoceptor density and affinity were assessed by radioligand binding with [125I]iodocyanopindolol. Left ventricular angiotensin II formation and noradrenaline concentration were measured. In addition, plasma renin activity and plasma noradrenaline levels were determined. The results showed that there was a significant increase in beta-adrenoceptor density following enalapril treatment compared with placebo in the heart-failure group. Enalapril did not change the beta-adrenoceptor density in the control animals. However, in both heart failure and control animals, enalapril caused an unexpected increase in Kd. Furthermore, in heart failure, enalapril caused a significant increase in myocardial angiotensin II formation. We conclude that enalapril prevents or reverses the myocardial beta-adrenoceptor abnormality seen in heart failure and promotes angiotensin II formation.
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PMID:Myocardial beta-adrenoceptors in pacing-induced heart failure: regulation by enalapril? 795 98

Angiotensin-converting enzyme inhibitors are proved, effective agents for the treatment of hypertension and congestive heart failure. New data suggest that angiotensin-converting enzyme inhibitors may be effective therapy for patients following acute myocardial infarction. Results from clinical trials, such as the Survival and Ventricular Enlargement trial, have demonstrated that captopril attenuates left ventricular enlargement, minimizes and/or prevents the subsequent development of overt congestive heart failure, and improves survival in patients with asymptomatic left ventricular dysfunction after myocardial infarction. Clinical reinfarctions and need for subsequent revascularization procedures were also reduced with captopril. In the Acute Infarction Ramipril Efficacy study, patients with clinically evident heart failure following acute myocardial infarction who received ramipril demonstrated a significant reduction in mortality and cardiovascular events. The mortality benefit in this study was evident within 30 days, possibly reflecting differences in patients studied (ie, population with high-risk heart failure in the Acute Infarction Ramipril Efficacy study as opposed to population with asymptomatic left ventricular dysfunction in the Survival and Ventricular Enlargement trial). Contrary results have been reported in another major postmyocardial infarction trial, the Cooperative New Scandinavian Enalapril Survival Study, which evaluated enalaprilat/enalapril maleate in unselected patients with acute myocardial infarction. This article reviews the recent trials using angiotensin-converting enzyme inhibition after myocardial infarction and will explore the reasons why angiotensin-converting enzyme inhibition seems to be beneficial in this clinical setting.
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PMID:Comparing angiotensin-converting enzyme inhibitor trial results in patients with acute myocardial infarction. 788 63

In a tertiary referral centre 63 patients underwent 67 treatment periods with enalapril. The median age was 5.4 months. All children had signs of heart failure: congestive cardiac failure with breathlessness at rest was present in 88%. Haemodynamic groups were left-to-right shunt (n = 15), impaired ventricular function (n = 14), after cardiac surgery (n = 23), valvar regurgitation (n = 12), and hypertension (n = 3). Serial clinical, radiological, and laboratory data were used to judge outcome. The mean (SD) maximal dose was 0.30 (0.21) mg/kg/day. Thirty nine (58%) patients improved, 20 (30%) showed no improvement, and eight (12%) had side effects requiring discontinuation of enalapril. Renal failure in eight patients was related to young age, low weight, and left-to-right shunt group. Three patients died in congestive heart failure with renal failure. Enalapril was clinically safe and effective for children with cardiac failure secondary to ventricular impairment, valvar regurgitation, or after cardiac surgery. Renal failure was a problem in young infants with left-to-right shunts.
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PMID:Efficacy and dosage of enalapril in congenital and acquired heart disease. 811 5

The effect of early converting enzyme inhibition with enalapril on the extent of neurohumoral activation in acute myocardial infarction was evaluated in a randomized, placebo-controlled double blind fashion. Plasma levels of atrial natriuretic factor and noradrenaline on day 1, i.e. prior to randomization (n = 99), and on days 3 (n = 145) and 30 (n = 69) following myocardial infarction were determined. Enalapril did not significantly affect neurohumoral activation on day 3 (enalapril vs. placebo (mean (S.E.M.); atrial natriuretic factor: 35.3 (3.0) vs. 37.2 (2.9) pmol/l; noradrenaline: 2.82 (0.20) vs. 3.70 (1.02) nmol/l) or at 1 month (atrial natriuretic factor: 33.1 (3.0) vs. 32.4 (3.9) pmol/l; noradrenaline: 2.77 (0.25) vs. 2.82 (0.28) nmol/l). However, in myocardial infarction patients developing heart failure, a significant attenuation of the day 3 atrial natriuretic factor, but not of the noradrenaline response, was seen (atrial natriuretic factor: 47.0 (7.7) vs. 59.0 (6.4) pmol/l, P < 0.05; noradrenaline: 3.37 (0.42) vs. 6.59 (3.26) nmol/l, P = ns). In conclusion, enalapril did not significantly reduce neurohumoral activation in acute myocardial infarction, possibly because the activation in most patients is modest and confined to the early convalescent phase. However, in patients with myocardial infarction and heart failure enalapril therapy was associated with a reduction in early plasma atrial natriuretic factor levels, compatible with decreased cardiac filling pressures.
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PMID:The effect of early converting enzyme inhibition on neurohumoral activation in acute myocardial infarction. 811 4

New information suggests that heart failure treatment strategies should change. Indeed, angiotensin-converting enzyme (ACE) inhibitors now should be considered first-line therapy in some instances. It is important, therefore, to review results of recently completed mortality end-point trials of ACE inhibitors in patients with congestive heart failure and asymptomatic left ventricular dysfunction. In the Treatment Trial of Studies of Left Ventricular Dysfunction (SOLVD), addition of enalapril to baseline therapy significantly improved prognosis in patients with mild to moderate heart failure. These results extend the findings of the Cooperative North Scandinavian Enalapril Survival Study (CONSENSUS), and indicate that ACE inhibition is beneficial to patients with all grades of overt congestive heart failure. In the Prevention Trial of SOLVD, and the Survival and Ventricular Enlargement Study (SAVE), therapy with enalapril or captopril improved prognosis among patients with, generally, asymptomatic left ventricular dysfunction. In particular, the risk of development of overt heart failure was reduced. Importantly, a marked anti-ischaemic effect of ACE inhibition was identified in both the SOLVD and SAVE trials. Clinical data amassed in nearly 9000 patients identify a substantial role for ACE inhibition in patients with all grades of symptomatic heart failure as well as in those with asymptomatic left ventricular dysfunction (such as often follows a myocardial infarction). Data support early intervention with ACE inhibitor therapy alone in asymptomatic cardiac failure and triple combination therapy (ACE inhibitor, diuretic, digoxin) in patients with symptomatic congestive heart failure.
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PMID:Angiotensin-converting enzyme inhibitors in heart failure: new strategies justified by recent clinical trials. 818 69

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.
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PMID:[Enalapril in treatment of severe heart failure in patients with dilated cardiomyopathy]. 819 Jun 55

In 1987 the Cooperative North Scandinavian Enalapril Survival Study (CONSENSUS) was published, which was a milestone for the treatment of patients with heart failure. The study showed a highly significant reduction in mortality in patients with severe heart failure treated with enalapril in comparison to placebo in combination with conventional treatment for heart failure, including the use of other vasodilators. The improvement in survival was exclusively due to a reduction of progression of pump failure. The incidence of sudden cardiac death was not affected. In 1991 2 studies were published in which patients with mild and moderate heart failure were included. The Second Vasodilator-Heart Failure Trial (V-HeFT II) compared the efficacy of enalapril with the effects of a vasodilator therapy consisting of the combination of hydralazine and isosorbide dinitrate. The study showed a highly significant reduction in mortality in the group of patients on the angiotensin-converting enzyme (ACE) inhibitor. In contrast to CONSENSUS, the benefit on survival was due to a reduction of sudden cardiac death. The second study was the Studies of Left Ventricular Dysfunction (SOLVD) treatment arm trial, which compared enalapril and placebo in combination with standard therapy in symptomatic patients with mild-to-moderate heart failure. The SOLVD treatment trial showed a highly significant improvement in survival on enalapril in comparison with placebo. ACE inhibition resulted in a borderline significant reduction of fatal myocardial infarctions, suggesting an impact of ACE inhibition on the pathogenesis of coronary artery disease. The data available show a clear indication for the treatment of symptomatic patients with mild and moderate-to-severe heart failure with ACE inhibitors as a first-line therapy.
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PMID:Lessons from recent randomized controlled trials for the management of congestive heart failure. 832 66

Angiotensin-converting enzyme (ACE) inhibitors, in conjunction with diuretic agents, have an established role in the management of moderate and severe heart failure due to left ventricular dysfunction. ACE inhibitor improves prognosis, symptoms and exercise performance. There have been some promising studies and one of the most widely quoted is the Cooperative North Scandinavian Enalapril Survival Study (CONSENSUS I), which demonstrated a 36% reduction in mortality with the ACE inhibitor, enalapril, versus placebo in patients with advanced heart failure. Over the last few years, we have received important information that seems to tell us that ACE inhibitors must be utilized if we hope to reduce mortality. An important topic is study the action of ACE inhibitors in improving prognosis, and the mechanism of the action.
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PMID:[Effect of angiotensin-converting enzyme inhibitors in congestive heart failure]. 833 96

Angiotensin-converting enzyme (ACE) inhibitors improve survival in heart failure and delay progression to clinical heart failure in patients with left ventricular dysfunction after myocardial infarction. Increasing numbers of older patients are being considered for such treatment. However, there are reports of excessive and prolonged decreases in blood pressure (BP) after the first dose of some ACE inhibitors. We have studied the hemodynamics, pharmacokinetics, and neurohumoral responses to the first dose of oral captopril 6.25 mg, enalapril 2.5 mg, perindopril 2.0 mg, intravenous enalaprilat 1.5 mg, and perindoprilat 1.0 mg, compared with oral or intravenous placebo in 6 parallel groups of 12 elderly patients each with moderate-to-severe (New York Heart Association classes II-IV) heart failure. Oral dosing with active drugs led to different temporal responses. After captopril, there was an early short-lived decrease in BP. Enalapril led to a later long-lasting decrease, but perindopril was not different from placebo. Intravenous enalaprilat and intravenous perindoprilat each lowered BP to a similar extent. The doses of drugs used appeared to be comparable because plasma ACE inhibition was similar following perindopril or enalapril and also comparing perindoprilat and enalaprilat. These studies indicate that oral ACE inhibitors have different profiles of acute BP changes after the first dose. The explanation is not clear, but could include physicochemical differences in the interaction between prodrug ester and diacid metabolites leading to differences in tissue distribution and local enzyme inhibition.
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PMID:Blood pressure response to the first dose of angiotensin-converting enzyme inhibitors in congestive heart failure. 839 82


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