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

Angiotensin-converting enzyme (ACE) inhibitors are widely used for treatment of heart failure after myocardial infarction (MI). The beneficial effects consist of a combination of hemodynamic effects and interference with cardiac structural alterations. These effects are believed to depend on inhibition of angiotensin II (AII) formation and thus diminished angiotensin receptor stimulation. We administered the angiotensin II-1 (AT-1) receptor antagonist losartan during and after completion of the repair phase of an MI to investigate involvement of the AT-1 receptor in the above described effects of captopril. MI reduced cardiac output (CO) (sham 94 +/- 4 ml/min, MI 78 +/- 5 ml/min) and maximal CO (sham 154 +/- 4, MI 107 +/- 5 ml/min, respectively). Losartan (15 mg/kg/day) resulted in a rightward shift of the AII pressor dose-response curve by a factor of 32-40. Neither CO nor COVL,max was affected by losartan treatment in either phase (late treatment CO = 78 +/- 5, COVL,max = 118 +/- 9 ml/min). Although early treatment with losartan reduced cardiac hypertrophy measured as heart weight, DNA synthesis was reduced only slightly. In contrast, collagen deposition was inhibited completely. The results suggest that the effects of captopril in rats after MI are not dependent on AT-1 receptor-mediated mechanisms.
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PMID:Angiotensin II receptor blockade after myocardial infarction in rats: effects on hemodynamics, myocardial DNA synthesis, and interstitial collagen content. 128 Jul 40

Angiotensin-converting enzyme (ACE) inhibitors are established in the treatment of hypertension and heart failure; both conditions are complicated by resistance to insulin-mediated glucose disposal. The defect in essential hypertension is both tissue and pathway specific, i.e., confined to nonoxidative (glycogen synthetic) routes of intracellular glucose utilization in skeletal muscle, whereas heart failure and non-insulin-dependent diabetes mellitus (NIDDM) are associated with more widespread abnormalities of carbohydrate and lipid metabolism. Thus, the mechanisms of the insulin resistance in hypertension, NIDDM, and heart failure are fundamentally different, so metabolic responses to drug therapy may not be the same in all insulin-resistant states. There have been conflicting reports about the effects of ACE inhibitors on insulin sensitivity and glycemic control. A number of studies, both with captopril and with enalapril, have shown small increases in insulin sensitivity, and there is evidence that this is due to enhanced glucose uptake into skeletal muscle. The interpretation of these studies, however, is often compromised by poor trial design, lack of full placebo data, various indirect measurements of insulin sensitivity, and heterogeneous patient populations in whom the biochemical mechanisms of insulin resistance (and drug responses) may not be the same. Overall, there probably is a modest class effect of ACE inhibitors that enhances insulin-mediated glucose disposal; the mechanism of this effect is likely to be a combination of increased muscle blood flow, local renin-angiotensin system blockade, and elevated kinin levels.
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PMID:Angiotensin-converting enzyme inhibitors and insulin sensitivity: metabolic effects in hypertension, diabetes, and heart failure. 128 42

Insulin resistance and hyperinsulinemia is now recognized in non-insulin-dependent diabetes, essential hypertension, obesity, atherosclerotic heart disease, dyslipidemia, heart failure, and in heavy smokers. Several mechanisms have been proposed to explain hyperinsulinemia, insulin resistance and its relationship to hypertension; reduced sodium excretion, activation of the sympathetic nervous system, increased activity of the sodium/hydrogen pump, and stimulation of cellular growth. Some of the nonpharmacological methods to control hyperinsulinemia are of benefit in the management of hypertension, most notably weight loss, exercise program, and reduced salt intake. High-fiber and reduced-protein diets also reduce hyperinsulinemia. Thiazide diuretics can result in insulin resistance, and insulin secretion may be inhibited, possibly associated with concomitant hypokalemia. beta-Blockers result in some reduction of glucose tolerance and mask some of the features of hypoglycemia. Angiotensin-converting enzyme (ACE) inhibitors and alpha-receptor blockers do not effect insulin resistance; probably the same is true for calcium antagonists. Although the effect on risk factors should not be discounted, it is the effect of treatment on hard end points, cerebrovascular accidents, myocardial infarction, or death that is most important. Evidence in hypertension is at present restricted to diuretics and beta-blocking drugs.
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PMID:Hypertension and insulin resistance. 128 47

Angiotensin-converting enzyme (ACE) inhibitors act by lowering the level of angiotensin II. The therapeutic benefits of these drugs and their potential side-effects therefore result from suppression of the physiological effects of angiotensin II. It is rational to prescribe an ACE inhibitor when the renin-angiotensin system is activated, as in renin-dependent essential hypertension, malignant hypertension and hypertension associated with heart failure. The beneficial effects of ACE inhibitor must be weighed against the special risks of renovascular hypertension: risk of renal artery thrombosis in case of unilateral stenosis and risk of renal failure if the stenosis is bilateral or affects a solitary kidney. In some situations the renin-angiotensin system is not directly involved in hypertension but may play a local haemodynamic role, as in some cases of primary or diabetic nephropathy. In such case the ACE inhibitors are thought to exert a protective effect. ACE inhibitors were reputed to be less effective in the elderly than in younger patients, but we now know that they can be prescribed with equal success in both instances to reduce peripheral resistance and improve regional blood flow as well as arterial compliance. Finally, ACE inhibitors can be prescribed, albeit with limited effectiveness, when the renin-angiotensin system is not activated, as in low renin hypertension and idiopathic hyperaldosteronism due to adrenal hyperplasia. They are ineffective in case of Conn's adenoma and contra-indicated in pregnant women.
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PMID:[For which hypertensive patient should angiotensin-converting enzyme inhibitor be prescribed or forbidden?]. 129 38

Angiotensin-converting enzyme (ACE) inhibitors were introduced in the treatment of heart failure in 1982. They improve the life comfort of the patients and their capacity for exercise in both moderate and severe heart failure. In moderate heart failure, their effectiveness on exercise performance is about the same as that of digitalis compounds and classical vasodilators, and superior to that of diuretics. The superiority of ACE inhibitors lies in that they improve the prognosis of heart failure, as has been demonstrated in the severe and moderate forms of the disease and, quite recently, in asymptomatic left ventricular dysfunction following myocardial infarction. Their beneficial effects on mortality undoubtedly result from their favourable action on the neurohormonal systems which are activated early in the course of heart failure. Extending the indications of these drugs to asymptomatic patients raises questions concerning optimal dosage, date of initiation and duration of treatment and possible class effect.
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PMID:[Converting enzyme inhibitors and aims of the objectives of the treatment of cardiac failure]. 129 40

Catecholamines have been found to be powerful indicators of prognosis in patients with congestive heart failure. However, it is uncertain whether catecholamines are a marker for decreased cardiac performance or part of the pathologic process. Catecholamines, exogenously derived beta-adrenergic stimulants, and drugs that amplify sympathetic responsiveness produce early hemodynamic benefits, but do not appear to provide long-term improvement in terms of symptoms or exercise tolerance, whereas blockade of the beta-adrenoceptor appears to have little early benefit but may improve long-term prognosis. This suggests that in the long term, increased catecholamine levels may be deleterious. Angiotensin-converting enzyme (ACE) inhibitors can modulate circulating catecholamines, and the persistence and degree of ACE inhibition may be important not only in reducing catecholamines, but possibly also in reducing mortality in heart failure. It appears that ACE inhibitors definitely reduce mortality in congestive heart failure. It remains to be documented whether the persistence and degree of ACE inhibition is a factor in this effect, and, thus, comparison of short- with long-acting ACE inhibitors and study of the dosage of ACE inhibitors are of importance. The extent to which modulation of the sympathetic nervous system by ACE inhibitors is an important mechanism in their effect in reducing mortality remains to be established.
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PMID:Angiotensin-converting enzyme inhibition, the sympathetic nervous system, and congestive heart failure. The Australian Zestril (Lisinopril) Study Group. 132 66

Angiotensin-converting enzyme (ACE) inhibitors have been shown to prolong life expectancy in patients with congestive heart failure. In order to determine the relative contributions of the different factors involved in this beneficial effect, we investigated in an experimental model of postinfarction cardiac insufficiency in the rat over a 9-12-month period (1) the kinetics of the development of the hemodynamic, biologic, and morphologic alterations that accompany heart failure, and (2) the kinetics of the effects of a new, long-acting ACE inhibitor, trandolapril. Following induction of infarction, systolic blood pressure, left ventricular dP/dt, and end-diastolic pressure were immediately decreased, decreased, and increased, respectively, and these modifications persisted throughout the study. Cardiac index, on the other hand, was only initially and transiently decreased. Cardiac remodeling (left ventricular dilation, myocardial hypertrophy, and fibrosis) occurred as early as 7 days after infarction and worsened throughout the study. Plasma atrial natriuretic factor (ANF) and urinary cyclic guanosine monophosphate (cGMP) were also increased. In this model, a 1-year oral treatment with trandolapril resulted in early hemodynamic and biologic beneficial effects (reductions in pre- and afterload, increase in cardiac index, and decrease in plasma ANF), and in a delayed reversal of the infarction-induced cardiac morphologic alterations. Hence, the trandolapril-induced increase in survival rate is due initially to the drug's hemodynamic effects and over the long-term to both its hemodynamic and cardiac morphologic (limitation of remodeling) effects.
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PMID:Beneficial effects of trandolapril on experimentally induced congestive heart failure in rats. 141 25

Despite extensive clinical experience the role of digoxin is still not well defined. In patients with atrial fibrillation digoxin is beneficial for ventricular rate control. For patients in sinus rhythm and heart failure the situation is less clear. Digoxin has a narrow therapeutic:toxic ratio and concentrations are affected by a number of drugs. Also, digoxin has undesirable effects such as increasing peripheral resistance and myocardial demands, and causing arrhythmias. There is a paucity of data from well-designed trials. The trials that are available are generally small with limitations in design and these show variation in patient benefit. More convincing evidence is required showing that digoxin improves symptoms or exercise capacity. Furthermore, no trial has had sufficient power to evaluate mortality. Pooled analysis of the effects of other inotropic drugs shows an excess mortality and there is a possibility that digoxin may increase mortality after myocardial infarction (MI). Angiotensin-converting enzyme (ACE) inhibitors should be used first as they are safer, do not require blood level monitoring, modify progression of disease, relieve symptoms, improve exercise tolerance and reduce mortality. Caution should be exercised in using digoxin until large mortality trials are completed showing either benefit or harm. Until then digoxin should be considered a third-line therapy.
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PMID:Heart failure: to digitalise or not? The view against. 144 52

Congestive heart failure has emerged as an important public health problem world wide. It is the single most common cause for hospitalization of patients over the age of 65 years in the United States. The past decade has witnessed the completion of a number of clinical trials which have been helpful in formulating treatment strategies for patients with chronic congestive heart failure. Angiotensin-converting enzyme inhibitors have emerged as distinctly useful pharmacologic therapy for this condition, and digitalis and diuretics are still widely used. New clinical trials are being planned and conducted to further refine our knowledge of treatment. Future studies are likely to be focused on understanding how myocardial damage begins and progresses to end-stage heart failure, and how early therapy may prevent the advanced stages of the disease.
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PMID:Heart failure in 1991. 167 34

Death during and following myocardial infarction can arise from a number of different causes. Some of them, such as early ventricular fibrillation and cardiac rupture, seem unrelated to infarct size. However, deaths occurring later during the course of infarction do seem to be related to the extent of myocardial damage and to such phenomena as infarct extension and expansion, and the mechanisms involved include cardiac failure and shock, and late arrhythmias. Preventive measures must be directed at the various mechanisms involved. Thrombolytic drugs, by limiting infarct size, prevent death from several causes, whereas beta-blockers seem mainly to operate by preventing early rupture, reinfarction, and late ventricular fibrillation. Aspirin prevents reinfarction. Angiotensin-converting enzyme (ACE) inhibitors may prove to have a beneficial role in the early phase by unloading the heart and later by preventing infarct expansion and subsequent cardiac failure.
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PMID:Why do patients die after myocardial infarction? 172 50


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