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

ACE inhibitors (ACEIs) have now been shown to improve symptoms and survival in patients with mild, moderate and severe chronic heart failure. Their mechanism of action is thought to be a combination of RAAS suppression and augmentation of bradykinin and prostaglandins. Although ACE inhibitors improve hemodynamics post myocardial infarction, we do not yet have consistent data on their effects on symptoms or survival in these particular patients. One other potential benefit is their effects on reperfusion injury and free radicals. As yet only minor differences have been found to exist between different ACEIs but increasing attention is now being focussed in this direction.
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PMID:The clinical pharmacology of angiotensin converting enzyme inhibitors in chronic heart failure. 164 5

Experimental myocardial infarction is a model of cardiac overload due to amputation of part of the cardiac muscle. The development of cardiac failure depends on the size of the infarct and the time factor. This model of overload is associated with changes of the phenotype of the remaining healthy muscle and with peripheral vascular modifications partially dependent of the activation of pressor and/or deactivation of dilator systems. These changes are proportional to the size of the infarction at a given time after induction of the model. The degree of right ventricular hypertrophy and the decrease in blood pressure reflect the severity of infarction and the deterioration of the remaining myocardial function, affecting the haemodynamics both before and after the left ventricle. The increases in the 1/3 forms of isomyosins, the amount of subendocardial collagen, the biosynthesis, stocking and secretion of ANF are related to the infarct size and degree of overload. Similarly, the concentration of cyclic GMP is proportional to the infarct size. These parameters reflect ventricular overload, the increase of stress and energy deprivation of the remaining healthy muscle. The activation of peripheral pressor systems is also dependent on the infarct size reflects the effect of cardiac pump dysfunction on the kidney, liver, brain and endothelium. Large infarcts are associated with increased circulating renin and renal concentrations, with a decrease in angiotensinogen levels related to its consumption by the renin and to reduced hepatic synthesis and also with increased secretion and biosynthesis of vasopressin by the hypothalamus. In this model, Perindopril is beneficial by decreasing the cardiac load. It reduces the blood pressure, causes regression of bi-auricular and right ventricular hypertrophy. Changes in myosin isoenzyme configuration regress and subendocardial fibrosis and ANF concentrations are normalised. The effects of ACE inhibitors in this context, though very beneficial, are limited by the impossibility of normalising cardiac load and stress when the initial amputation of cardiac contractile mass exceeds 40%.
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PMID:[Experimental myocardial infarction in the rat. Effect of perindopril]. 166 27

'Primary cardioprotection' has, arguably, already been shown with thiazide diuretics and probably with beta-blockers. The proven safety and efficacy of these established drugs override any theoretical or experimental considerations in favour of ACE inhibitors. It is unfortunate that, as yet, the number of hypotheses generated in support of ACE inhibitors has not been matched by large scale clinical trials employing these drugs. The first report of the clinical use of an ACE inhibitor was in 1984; it is high time comparative studies with conventional, and proven, agents were undertaken. With regard to 'secondary cardioprotection', there is overwhelming evidence in favour of the use of beta-blockers in patients with myocardial ischaemia. Indeed, we would argue that ACE inhibitors should be used with caution in such patients to avoid impairment of coronary infusion. In the patient with acute myocardial infarction, intravenous nitrates are cheap, easy to use, safe and seem to be effective (in preventing early remodelling and reducing mortality). In the subacute phase, beta-blockers improve prognosis and, according to the currently available evidence in humans, nitrates are as effective as captopril in altering late remodelling; as in the acute situation, nitrates are cheaper, simpler to use and have a track record of long-term safety. ACE inhibitors improve symptoms, exercise capacity and prognosis in chronic heart failure. In this condition, they have been a major therapeutic advance and, on the available evidence, are to be initially preferred to other vasodilators though they should be given in addition to diuretics.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Unique cardioprotective potential of angiotensin converting enzyme inhibitors: a hypothesis still to be tested on humans. 166 67

The importance of the dopaminergic system in heart failure is unknown and the therapeutic potential of orally active compounds stimulating dopaminergic receptors has yet to be established. Despite similar acute haemodynamic changes in heart failure and despite a comparable profile of receptor stimulation, oral levodopa (the prodrug of dopamine) and oral ibopamine (the prodrug of epinine) produce opposite effects on plasma norepinephrine and have different pharmacokinetics. Placebo-controlled studies indicate a beneficial effect of ibopamine on exercise tolerance in patients with heart failure, whereas invasive evaluation of left ventricular function indicate that at the doses used in these trials, ibopamine does not act as a positive inotropic drug but rather as a vasodilator. This suggests that DA1 and DA2 receptor stimulation may be beneficial in heart failure. Further studies are, however, needed to specify the exact role of this therapeutic approach in comparison with other agents, such as ACE inhibitors, also able to modulate neuro-humoral activation in heart failure.
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PMID:Dopaminergic drugs in the management of chronic heart failure. 168 Jun 85

In addition to the underlying pathophysiological processes that cause myocarditis and dilated cardiomyopathy, structural, biochemical, neurohormonal and haemodynamic influences and interrelations promote progression of the heart failure syndrome. Independent of their symptomatic benefits, diuretics, digitalis, ACE inhibitors, PDE inhibitors and dopamine agonists exert specific influences on factors that retard or accelerate progression of congestive heart failure (CHF). Important factors that indicate or promote progression of CHF are discussed here, with special emphasis on therapeutic options. Interference with baroreceptor function (digitalis, ACE inhibitors), the RAA system (ACE inhibitors), the sympathetic nerve system (dopamine agonists, ACE inhibitors, digitalis) can potentially retard progression of CHF, while other therapeutic options, such as PDE inhibitors and diuretics, might accelerate progression of left ventricular dysfunction and CHF.
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PMID:Therapeutic alternatives in dilated cardiomyopathy--a review of current options. 168 Jun 88

The three approaches (physiopathological, epidemiological and pharmacological) to the management of hypertension should converge to provide a personalized prescription of the most appropriate treatment to prevent and/or cure the cardiovascular complications of hypertension: hypertensive left ventricular hypertrophy and the risks directly related to it (haemodynamic, arrhythmic, ischaemic) may be corrected by certain antihypertensive agents (methyldopa, ACE inhibitors, some calcium antagonists) although there is no proof as yet of the benefits of this intervention (which could suppress the adaptation to the increased wall stress of the left ventricle); malignant hypertension and its cardiovascular complications have almost disappeared with modern antihypertensive therapy. Cardiac failure can be effectively prevented and cured when exclusively related to hypertension. When diastolic pressures are lowered by 8-10 mmHg cerebrovascular risk is reduced by a half and coronary risk by a quarter. Cardiovascular mortality related to hypertension is thus reduced by 20% and total mortality is thereby significantly decreased; the large scale clinical trials which provided these data were performed in the years 1965-1985 with diuretic therapy relayed by (or compared with) betablockers from 1980 onwards. These two families remain the drugs of reference in the prevention and treatment of the cardiovascular complications of hypertension. Personalized description of antihypertensive therapy should take into account the degree of risk and previous cardiovascular complications of the hypertensive patient: betablockers eventually associated with calcium antagonists are to be preferred in cases of hypertension with coronary artery disease and/or arrhythmias, severe hypertension and hypertension complicated by cardiac failure are good indications for ACE inhibitors without prejudicing other therapeutic options necessary in certain contexts, in particular aspirin therapy in patients with previous transient ischemic cerebral attacks.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:[Treatment of hypertension and cardiovascular complications]. 168 21

Results of uncontrolled studies suggest that the duration of action of an ACE inhibitor may be an important determinant of renal impairment when using these agents to treat patients with heart failure. To determine whether there is experimental evidence for this hypothesis, we compared the effects of intermittent (captopril, 25 mg i.v. bolus twice daily) and continuous (captopril. 25 mg bolus, then 50 mg/day by constant infusion) ACE inhibition in an ovine model where heart failure was induced by rapid left ventricular pacing (LVP). Six sheep underwent three 4-day periods of LVP with intermittent, continuous, or no treatment (control) given in random order from the onset of LVP. Despite evidence that intermittent captopril administration allowed significant recovery of serum ACE activity (4.6 +/- 1.2 vs. 1.1 +/- 0.5 pmol/L before and after captopril bolus on day 4, p less than 0.001) and restitution of arterial pressure between successive boluses (48 +/- 7 vs. 41 +/- 4 mm Hg, p less than 0.01), there was no difference in the renal effects of intermittent and continuous ACE inhibition (creatinine clearance was 44 +/- 14 and 47 +/- 8 ml/min on day 4 of the intermittent and continuous phase, respectively). Nevertheless, there was a significant correlation between the decline in arterial pressure and fall in creatinine clearance induced by ACE inhibition (r = 0.65, p less than 0.05), with evidence that drug accumulation may potentiate hypotension and renal impairment should arterial pressure be reduced below the threshold for renal autoregulation.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Renal effects of ACE inhibition in ovine heart failure: a comparison of intermittent and continuous ACE inhibition. 170 5

Treatment of patients with heart failure due to major ventricular systolic dysfunction should aim not only at symptomatic but also at prognostic improvement. If correction of the underlying problem is not possible, treatment should slow down the progression of cardiac failure and eliminate triggers for sudden cardiac death due to electromechanical dissociation or arrhythmias. In every patient with chronic congestive heart failure screening for myocardial ischemia and complete revascularization is mandatory, if possible. In patients with coronary artery disease and diminished systolic function, beta-blockade may improve prognosis by reducing ischemic events and sudden cardiac death. The incidence of life-threatening arrhythmias in patients with heart failure may be reduced by eliminating facilitating factors like electrolyte disturbances, altered autonomic tone and raised intracardiac pressure rather than by antiarrhythmic medical treatment itself. One of the most important prognostic aspects in treatment is the interference with the development of the cardiomyopathy of overload, uniformly observed in chronic congestive heart failure. Modification of mechanical and neuroendocrine stimuli may postpone myocardial hypertrophy and interstitial hyperplasia as a consequence of altered gene expression. Early treatment with ACE inhibitors and in certain patients with betablockers are the most promising strategies to delay the progression of the disease. In contrast, positive inotropic drugs, including digitalis and phosphodiesterase inhibitors, do not improve prognosis. Calcium antagonists should also be used with restriction, as Verapamil and Diltiazem, but also Nifedipine may adversely affect the outcome in congestive heart failure patients.
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PMID:[Prognostic aspects in the treatment of chronic heart insufficiency]. 173

We conclude from our studies and data from the literature that ACE inhibitors belong to the proper basic therapy of cardiac failure because of their marked influence on progression and death by pump failure. The therapeutic gain per 100 patients treated for one year exceeds that of other medications used commonly for secondary prophylaxis.
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PMID:[The effect of captopril on the progression of heart insufficiency]. 173 1

In severe chronic heart failure, myocardial beta-adrenoceptors are downregulated and G-proteins inhibiting adenylate cyclase activity are augmented. Because of these biochemical changes, all positive inotropic drugs that need cAMP for their contractile effects lose their efficacy. Among the positive inotropic drugs used today for treatment of heart failure, only cardiac glycosides remain effective without development of tolerance as long as enough contractile myocardium is left. Controlled studies with phosphodiesterase III inhibitors (milrinone and enoximone) have revealed an unfavorable prognosis in these patients in comparison to placebo. Thus, these drugs are not indicated in chronic heart failure. In higher classes of chronic heart failure, therapy should always be a combination of diuretics, digitalis, and ACE-inhibitors.
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PMID:[Positive inotropic substances--therapeutic perspectives]. 179 36


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