Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:3.4.15.1 (ACE)
 18,300 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The aims of treatment of chronic heart failure are to improve the symptoms and the quality of life, reduce mortality and prevent left ventricular dysfunction. Before the first symptom occurs, neurohormonal activation takes place (increased catecholamines and atrial natriuretic peptide levels). Diuretics improve symptoms and are irreplaceable for the elimination of salt and water overload. Loop diuretics are used more often than the thiazides. Their deleterious effects on electrolyte balance are well known. The fact that they activate the renin angiotensin system is a more recent acquisition; the increase in plasma renin activity is a poor prognostic factor. Diuretics potentialize the vasodilator effect of angiotensin converting enzyme inhibitors which inhibit the neurohumoral activation induced by the diuretics. This therapeutic association is very logical, effective and allows reduction in the dosage of the diuretic. To date, there are no large scale controlled studies of the effects of diuretics on mortality. Spironolactone corrects hypokalaemia and hypomagnesaemia induced by loop diuretics. Moreover, it has been shown experimentally in renovascular hypertension and in hyperaldosteronism, that this molecule can prevent myocardial fibrosis, a factor which leads to ventricular dysfunction. The RALES study will analyse the effect of associating spironolactone to diuretic and ACE inhibitor therapy on the mortality of patients in NYHA classes III-IV. The value of digitalis in heart failure patients with sinus rhythm is a classical controversy. Digitalis has a positive inotropic effect (inhibition of NaK-dependent ATPase). More recently, a favourable neurohormonal effect has been reported; digitalis decreases the activation of the sympathetic and renin-angiotensin systems.(ABSTRACT TRUNCATED AT 250 WORDS)
Arch Mal Coeur Vaiss 1995 Apr
PMID:[Classic treatment of chronic heart insufficiency. What if new?]. 748 8

New agents for treating chronic heart failure include angiotensin converting enzyme (ACE) inhibitors, betablockers and phosphodiesterase inhibitors. The ACE inhibitors represent the major therapeutic advance of the 1980-1990 decade. This is the most effective class of drugs on survival, whatever the stage of heart failure and it shows the evolution towards symptoms in asymptomatic patients. Studies currently under way are evaluating the dose-effect relationship of ACE inhibitors. Betablockers improve the quality of life and physical performance but a benefit on mortality has not been shown in two recent trials. Phosphodiesterase inhibitors improve quality of life and physical performance at the price of an increase in mortality. Therefore, they are not indicated in the treatment of heart failure. However, new molecules such as vesnarininone or pimobendan are under trial. Finally, in the next few years, the introduction of antagonists to Angiotensin II receptors is eagerly awaited.
Arch Mal Coeur Vaiss 1995 Apr
PMID:[Treatment of chronic heart failure: current views]. 748 9

The history of the treatment of heart failure may be divided into three stages, the consequences of different conceptions of the physiopathology of the disease, with diuretics to counteract salt and water retention, vasodilators to improve conditions of cardiac load, angiotensin converting enzyme inhibitors to limit the effect of neurotumoral and sympathetic activation. There are two main reasons for using calcium antagonist in heart failure, the first being arterial vasodilatation leading to improve systolic function and the second being the beneficial effect on ventricular relaxation. However, their use has been controversial because of the results obtained with the first generation of these drugs. New molecules derived from dihydropyridine have been developed. Clinical trials with these second generation calcium antagonists are analysed.
Arch Mal Coeur Vaiss 1995 Apr
PMID:[Calcium antagonists and treatment of chronic heart failure]. 748 13

There have been many therapeutic trials to determine the efficacy of given drugs prescribed after myocardial infarction. This may be explained by the very number of families of drugs which may intervene during the evolution of coronary artery disease. A common mistake is to think that the results of therapeutic trials can be automatically applied in clinical practice. In order for the demonstrated effect of a product to lead to its automatic prescription, there must be confirmation that the importance of the expected benefits does not depend on the type of infarction. This is probably the case for aspirin and the reduction of cholesterol levels which seem to be effective irrespective of the characteristics of the initial infarction. On the other hand, the efficacy or dangers of anti-ischaemic drugs, angiotensin converting enzyme inhibitors or antiarrhythmics, is very dependent on the impact of the infarct on left ventricular function. The prescription of drugs after myocardial infarction depends on individual parameters which lead to the adaptation of consensus recommendations to each particular case.
Arch Mal Coeur Vaiss 1995 Aug
PMID:[Medical treatment after myocardial infarct: reflex prescription or thoughtful prescription]. 750 17

The myocardial scar, left behind by an infarct, makes up a potential substrate for complex ventricular arrhythmias due to the presence in such tissue of electrical inhomogeneity, altered refractoriness, and abnormal conduction properties, which facilitate the induction of reentrant arrhythmias and the release of abnormal automatic responses of the partially repolarised cells. The mechanism(s) by which complex ventricular arrhythmias is/are transformed into malignant arrhythmias has/have not yet been definitely proven. The observation that coronary revascularization - in patients with ischaemic heart disease surviving out of hospital cardiac arrest - improves the prognosis, indicates that transient ischaemic attacks might be the trigger of malignant ventricular arrhythmias in patients with prior myocardial infarction. Patients with large infarct scars (heart failure) have an increased incidence of complex ventricular arrhythmias, death, and ischaemic events. Antiarrhythmic medical intervention does not improve the prognosis in these patients. Intervention with ACE-inhibitors reduces the prevalence of complex ventricular arrhythmias, the incidence of death, and reinfarction, but not arrhythmic death, indicating that residual ischaemia might be the major risk variable in patients with heart failure. Ischaemia is one of several risk markers for transient supraventricular arrhythmias in patients recovering from an acute myocardial infarction (AMI). In addition, anti-ischaemic intervention in patients recovering from AMI suppresses residual myocardial ischaemia and thereby reduces major events.
Arch Mal Coeur Vaiss 1995 Sep
PMID:[Post-infarction, myocardial ischemia: clinical importance and risk factor]. 750 21

Acute infectious myocarditis in childhood has a very poor initial outcome, but the long-term outlook is relatively good for the survivors. This retrospective study was based on cases of acute myocarditis admitted to two hospital departments with different modes of recruitment. Firstly, a polyvalent paediatric intensive care unit where 12 children (mean age 12 months) were admitted during the acute phase of myocarditis. The initial symptoms were non-specific and misleading, the diagnosis being established at autopsy in 9 cases. Only 4 children presented with typical cardiac failure. The clinical signs were hepatomegaly, sinus tachycardia, cardiomegaly, ECG ST-T wave changes and biological signs of multiple organ failure. Left ventricular function was very poor with a fractional shortening of only 17%. The causal agent was usually viral. The clinical course was marked by a high early mortality (11/26, 42%) within 23 hours of hospital admission. Secondly, a paediatric cardiology unit where 81 children (mean age 15 months) were followed up after acute infectious myocarditis. Thirteen cases were taken from our first series and were included for long-term follow-up; 76.5% had premonitory signs of infection and 71% were in cardiac failure, Classes III or IV, during the hospital admission. The causal agent was identified in 30 cases (37%) and was usually a virus (22 cases). Treatment was classical (association of digitalis, diuretics, angiotensin converting enzyme inhibitors, anticoagulants and beta-sympathomimetics when necessary).(ABSTRACT TRUNCATED AT 250 WORDS)
Arch Mal Coeur Vaiss 1995 May
PMID:[Acute infectious myocarditis in children. Apropos of 2 series from Lyon]. 764 88

The raised mean arterial pressure observed in hypertension increases the stress on the walls of large arteries by increasing the mechanical forces to which they are submitted. Cardiac and arterial wall hypertrophy seem to be adaptive mechanisms tending to reduce the stress in each musculo-elastic unit of the cardiovascular system. However, this adaptation only partially explains the development of cardiovascular hypertrophy. Cardiovascular changes are sometimes observed before the increase in blood pressure, as in normotensive children of hypertensive parents. Moreover, a dissociation has been shown between the antihypertensive effects of different antihypertensive agents. For the same reduction in mean arterial pressure, some drugs are associated with a greater regression in these changes than others. At present, it is acknowledged that other factors than mean arterial pressure may cause these changes. For example, the pulse pressure is a major factor, independent of mean arterial pressure, in developing cardiovascular hypertrophy. The activation of hormonal systems, especially the angiotensin converting enzyme system, influences cardiovascular structure. Therefore, hyperactivity of the renin-angiotensin system may stimulate the growth factor responsible for cardiac and arterial hypertrophy.
Arch Mal Coeur Vaiss 1995 Feb
PMID:[Relation between cardiac hypertrophy and changes in the large arterial trunks. Role of the renin-angiotensin system]. 764 6

In renal hypertensive rats with pressure overload left ventricular hypertrophy the angiotensin converting enzyme inhibitor ramipril, given in a high blood pressure lowering dose as well as in a low, non-antihypertensive dose, prevented and regressed left ventricular hypertrophy. These beneficial effects were abolished by coadministration of the specific bradykinin receptor antagonist (HOE 140) in the prevention--but not in the regression studies. Vascular function of rats with pressure overload left ventricular hypertrophy was impaired, whereas treated animals showed a reversal to normal. The angiotensin II subtype AT1 receptor antagonist, losartan, was barely active in the prevention, however markedly active in the regression of left ventricular hypertrophy. From these experimental studies in rats with pressure overload left ventricular hypertrophy and vascular dysfunction we conclude that inhibition of bradykinin degradation induced by ramipril may contribute to the antihypertrophic action during the prevention phase, whereas attenuation of angiotensin II formation may be more important during the regression period. In another model, the spontaneously hypertensive rat (SHR and stroke prone SHR)--a non-renal hypertensive model--cardiac left ventricular hypertrophy could be reduced by chronic high-dose ramipril treatment in prevention and regression studies, whereas the low dose regimen only reduced left ventricular hypertrophy in the regression experiments. In addition, both doses improved the myocardial capillary supply to the heart leading to improved function and metabolism. In comparison, vascular hypertrophy of the mesenteric artery could only be prevented by early-onset high dose treatment with the angiotensin converting enzyme inhibitor but not once hypertrophy has been established.(ABSTRACT TRUNCATED AT 250 WORDS)
Arch Mal Coeur Vaiss 1995 Feb
PMID:Experimental evidence for effects of ramipril on cardiac and vascular hypertrophy beyond blood pressure reduction. 764 9

The role of the angiotensin converting enzyme (ACE) in the regulation of local synthesis of angiotensin II has not been clearly defined. The authors investigated the local factors which might orientate the effects of ACE inhibitors to particular organs in the Wistar rat. The in vivo study of the effects of low doses of ramipril on the myocardium showed that cardiac ACE was significantly inhibited by the non-antihypertensive dose of 0.01 mg/kg whereas the inhibition only occurred from doses higher than 0.1 mg/kg in the other tissues studied. In the kidney: the affinity of 3H-ramiprilate for the brush borders of the proximal tubular cells was increased by high concentrations of chloride ions as observed in the renal parenchyma, the presence of esterases makes local activation of ramipril (diester) into ramiprilate (active diacid) possible, prolonged treatment with ramipril leads to a lowering of the concentration of ACE in the brush border of the proximal tubular cells, verified after the elimination of the ACE inhibitor fixed on the tissue. These data indicate that the myocardium and the kidney could be privileged targets of the action of ramipril.
Arch Mal Coeur Vaiss 1995 Feb
PMID:[Ramipril and cardiac and renal angiotensin converting enzyme]. 764 11

Left ventricular hypertrophy is frequent in hypertension although there is no close correlation between the level of blood pressure and the cardiac mass. The HYCAR study has shown a dissociation in the reversibility of left ventricular hypertrophy: ramipril at doses of 1.25 or 5 mg per day reduces left ventricular mass independently of its effects on the blood pressure. Nevertheless, it remains to be shown by a prospective study that the reduction of the blood pressure and the cardiac mass have additional benefits in the prevention of coronary artery disease in hypertensive subjects. In the meantime, two points resume the objectives of treatment of hypertension with respect to left ventricular hypertrophy and coronary risk. Firstly, prevention of left ventricular hypertrophy is better than its cure. Early prevention is based on accurate measurement and interpretation of the blood pressure according to international recommendations. Prevention necessitates good control of the blood pressure and it would appear to be particularly effective in patients who respond well to angiotensin converting enzyme inhibitors. Secondly, when left ventricular hypertrophy is present, it is possible to reduce the left ventricular mass: however, it remains to be seen whether this is accompanied by a normalisation of structure and function. This requires control of the blood pressure using either an angiotensin converting enzyme inhibitor in good responders to this family of drugs or another type of antihypertensive agent. In the latter case, the association of a low dose of ramipril may be envisaged when left ventricular hypertrophy persists despite good control of the blood pressure. This hypothesis requires testing with an appropriate prospective therapeutic trial.
Arch Mal Coeur Vaiss 1995 Feb
PMID:[Is reversal of left ventricular hypertrophy a priority in patients with hypertension?]. 764 12


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