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

Cardiac hypertrophy is characterized by marked abnormalities in the contraction/relaxation pattern of the heart. For example, delayed relaxation is a prominent feature, impairing ventricular filling and coronary flow. In intact heart preparations the relative contribution of fibrosis and of the myocardial cell itself to these abnormalities cannot be correctly assessed. Biochemical studies on the mechanisms of impaired contraction and relaxation and hypertensive heart failure are hampered by the fact that 75% of all heart cells are non-myocytes. We therefore established the model of the isolated calcium-tolerant, adult rat cardiomyocyte as a new approach to the investigation of these problems. Contractility was measured using a videomicroscope system with high time resolution (1 ms). Angiotensin II induced a marked relaxation delay in the cardiomyocyte from normotensive rats and showed a moderate positive inotropic effect, whereas isoproterenol had a strong positive inotropic effect but accelerated relaxation. Therefore, angiotensin II is capable of inducing a relaxation delay even in the absence of coronary ischaemia or hypertension. These first results show that the isolated cardiomyocyte model may be a useful approach to investigating the mechanisms of hypertensive heart disease.
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PMID:Isolated myocardial cells: a new tool for the investigation of hypertensive heart disease. 214 54

Challenge to a new therapeutic principle to treat heart failure is to ameliorate or eliminate symptoms, decelerate progression of the disease and reduce mortality. However, to begin, one would request improvement of objective hemodynamic parameters. Angiotensin converting enzyme (ACE) inhibitors may have acute and chronic, global and regional effects. ACE inhibitors acutely and chronically reduce pre- and afterload without reflex tachycardia. They lower myocardial oxygen consumption and improve the relation of coronary blood flow to myocardial oxygen consumption. Cerebral and renal blood flow generally are beneficially influenced if the blood pressure is not lowered too much. Left ventricular dilatation following extensive myocardial infarction which is prognostically unfavourable, may be retarded or prevented by ACE-inhibitors. It is not yet clear whether mortality may thus be reduced as in patients with severe heart failure. Large multicenter studies currently address this question. It is unclear as well whether the effects of ACE-inhibitors are exclusively due to a reduction of circulating angiotensin II. Most likely, interference is of major importance with local renin-angiotensin systems, other hormone systems and the central and peripheral nervous system.
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PMID:[Modification of hemodynamics by angiotensin converting enzyme inhibitors in heart failure]. 219 16

Stimulation of the renin angiotensin system, catecholamines and antidiuretic hormone causes prominent vasoconstriction in severe heart failure. Angiotensin converting enzyme inhibitors reverse these effects, and thus ameliorate cardiac function and reduce mortality in severe heart failure. Angiotensin II is an important regulator of renal function in diseases with renal hypoperfusion, and treatment with angiotensin converting enzyme inhibitors may cause a serious decrease in glomerular filtration and hyperkalemia. Asymptomatic heart failure, acute heart failure and acute myocardial infarction are areas where angiotensin converting enzyme inhibitors may prove beneficial in the future.
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PMID:[Treatment of heart failure with angiotensin converting enzyme inhibitors]. 221 71

Angiotensin converting enzyme inhibitors are now firmly established in the treatment of patients with chronic heart failure (CHF). Their beneficial acute and chronic hemodynamic effects are not associated with reflex tachycardia or drug tolerance. Angiotensin converting enzyme inhibitors produce symptomatic improvement and improve exercise capacity in all grades of heart failure. They also improve the prognosis of patients with severe heart failure. Quinapril is a recently introduced, nonsulfhydryl ACE inhibitor, whose intermediate half-life makes it well-suited for the treatment of patients with CHF. The acute and chronic hemodynamic effects of quinapril are similar to those of other ACE inhibitors. In a large, multicenter, randomized, placebo-controlled study of 225 patients with mild to moderate CHF, 10 to 40 mg/day quinapril significantly improved clinical status and exercise capacity in a dose-related manner. The incidence of side effects did not differ significantly from that of placebo. The initial studies with quinapril are promising and warrant further clinical investigation of this compound.
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PMID:Quinapril in chronic heart failure. 226 Nov 47

Angiotensin converting enzyme (ACE) inhibitors are a novel class of antihypertensive and anticongestive heart failure agents with wide patient and physician acceptability. By blocking the formation of angiotensin II in blood and tissue, all ACE inhibitors significantly lower systemic vascular resistance, lower blood pressure, and improve cardiac function, while maintaining or enhancing perfusion of vital organs: kidneys, brain, and heart. Captopril is the first oral ACE inhibitor with an active sulfhydryl group. Enalapril and lisinopril are potent nonsulfhydryl inhibitors of ACE characterized by weak chelating properties. The side effects of skin rashes, pruritus, taste abnormalities, oral ulcers, pemphigus, and blood dyscrasias have been considered to be strongly characteristic of penicillaminelike drugs, including the sulfhydryl ACE inhibitors. The class effects of cough, angio-edema, hyperkalemia, nonoliguric functional renal insufficiency, and hypotension can occur with equal frequency with all ACE inhibitors. It is unclear whether the many yet investigational ACE inhibitors would have distinct advantages over captopril, enalapril, lisinopril, and enalaprilat. This paper reviews the comparative structure and clinical pharmacology of the three commercially available but chemically different oral ACE inhibitors.
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PMID:Angiotensin converting enzyme inhibitors: comparative structure, pharmacokinetics, and pharmacodynamics. 228 12

Angiotensin converting enzyme inhibitors can be recommended in the treatment of severe cardiac failure (New York Heart Association Functional Class III or VI) where they are probably superior to other vasodilators. Their use should be considered when routine therapy with diuretics and digoxin has failed to ameliorate symptoms. Whether they can be recommended also for mild heart failure and whether the benefits outweigh any risks associated with long-term blockade of the renin-angiotensin system are questions that remain to be answered. Their use in hypertension and early in acute myocardial infarction might prevent the development of heart failure, but appropriate studies in man are awaited.
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PMID:Inhibition of the renin-angiotensin system in the treatment of heart failure: why, when, and where. 241 22

Neuroendocrine activation in acute myocardial infarction (AMI) may have important physiological consequences for myocardial perfusion and function. We measured plasma angiotensin II in 60 patients with AMI within 6 hours of pain and on days 1-3 and day 10. On admission, AII was normal at 9.9 + 1.3 pmol/l (normal range 2-12 pmol/l). At day 3, AII rose markedly to 77.5 + 25.0 in those with heart failure (group 1, n = 13); but AII also rose in uncomplicated patients (group 2, n = 47) to 27.8 + 4.0 (p less than 0.001). At day 10, levels of AII remained high, especially in group 1 (50.5 + 22.2 vs 6.1 + 1.5, p less than 0.005). Thus neuroendocrine activation, present early in AMI, is seen in both uncomplicated infarcts and in those developing heart failure. Angiotensin II mediated vasoconstriction perhaps enhanced by catecholamines could have deleterious effects on myocardial function and perfusion, and indicates the potential for angiotensin-converting enzyme inhibitors in early AMI.
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PMID:Neuroendocrine activation in acute myocardial infarction. 244 Nov 95

Activation of the renin-angiotensin system in acute myocardial infarction may have important haemodynamic consequences. The effects of captopril were assessed in nine patients with acute left ventricular failure complicating myocardial infarction. Plasma angiotensin II was elevated at 16.8 (3.6) pmol/l (mean [SE]) including high levels in three of four patients in the absence of any previous therapy, including diuretics. Repeated low doses of captopril were administered to reduce pulmonary capillary wedge pressure less than 14 mm Hg or to a maximum total dose of 25 mg. Right atrial pressure fell from 12.4 (0.9) to 9.4 (0.7) mm Hg p less than 0.001, pulmonary arterial pressure from 32.7 (3) to 26.4 (2.2) p = 0.01, and pulmonary capillary wedge pressure from 25.7 (2.9) to 19.9 (2.2) p = 0.01. Despite a fall in systemic vascular resistance from 1,540 (110) to 1,330 (76) dyn/s/cm5, and mean arterial pressure from 84.8 (3.9) to 76.7 (2.7) p = 0.001, changes in cardiac output were small: 3.8 (0.3) to 4.2 (0.3) NS. Angiotensin II fell in all patients even after only 3.125 mg to a mean of 3.6 (1.0). These improvements occurred whether basal angiotensin II was elevated or normal, and in the presence or absence of diuretic therapy. At 24 hours, seven patients received captopril in the maximum titrated dose of the previous day. Haemodynamic changes at one hour were of similar magnitude to those during incremental dosing. These results suggest that reduction of angiotensin II exerts beneficial haemodynamic effects in heart failure complicating acute myocardial infarction.
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PMID:Haemodynamic effects of captopril in acute left ventricular failure complicating myocardial infarction. 244 Nov 96

Angiotensin II appears to have important actions in modulating sympathetic nerve activity; conversely, sympathetic stimulation alters renin release. Drugs that inhibit angiotensin II formation would be expected then not only to offset the direct vasoconstricting and aldosterone releasing actions of this peptide but also to reduce sympathetic nerve activity. Hypertension and cardiac failure are two major conditions in which converting enzyme inhibitors have found important therapeutic roles; both are considered to be associated with increased activity of the renin-angiotensin-aldosterone and sympathetic nervous systems. However, in spite of considerable experimental evidence for a sympatholytic action of converting enzyme inhibitors, direct proof has been difficult to obtain in humans. In part, this results from the lack of any satisfactory way of assessing sympathetic activity in the clinical situation. Nevertheless, our failure to understand the pathophysiology of disease and the precise mechanism of action of drugs has not precluded exploiting the salutatory effects of inhibition of converting enzyme.
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PMID:The sympathetic nervous system and converting enzyme inhibition. 247 95

Relaxation delay is an important feature of hypertensive heart disease which impairs diastolic coronary flow and ventricular filling and therefore contributes to heart failure. We investigated the hypothesis that impaired relaxation is a property of the myocardium, rather than the consequence of ischaemia or interstitial fibrosis. A new videomicroscope system was used to define the contraction-relaxation cycle of isolated cardiac myocytes from spontaneously hypertensive rats (SHR) and normotensive control (Wistar-Kyoto, WKY) rats. The SHR cells showed a marked relaxation delay. Angiotensin II (Ang II) increased the contraction maximum by about 35% in WKY rats and induced a relaxation delay. In SHR Ang II greatly potentiated this relaxation delay. Our results demonstrate that impairment of relaxation is a property of the single cardiomyocyte. Angiotensin II induces a relaxation delay that is independent of blood pressure. The combination of hypertrophy and high levels of Ang II potentiates relaxation impairment and may therefore contribute to hypertensive left ventricular failure.
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PMID:Impaired relaxation of the hypertrophied myocardium is potentiated by angiotensin II. 253


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