[Vasodilator effects of bradykinin on the resistive circulation of the forearm of coronary patients]. / Effet vasodilatateur de la bradykinine au niveau de la circulation résistive de l'avant-bras de patients coronariens.

This study was undertaken to determine the vascular effects of bradykinin and its modes of action on the resistive circulation of the forearms of coronary patients and healthy volunteers. Two groups were studied: Group I comprising 8 coronary patients with normal left ventricular function and Group II with 8 healthy volunteers. The method of measurement of forearm blood flow was occlusive venous plethysmography with a mercury strain gauge. The vasodilatory response of the two groups to local arterial perfusion of acetylcholine (40 and 80 micrograms/min), bradykinin (10, 30, 100 pmoles/min), then the association of L-Ng-monomethyl-L-arginine (L-NMMA) at 8 microG/min, an inhibitor of the synthesis of nitric oxide, with acetylcholine and bradykinin. Five subjects of the control group received oral aspirin (250 mg/day) for one week before the study. Acetylcholine and bradykinin increased forearm flow in a dose-dependent manner but the increase was significantly less in coronary patients than in the healthy volunteers (p < 0.05). The L-NMMA inhibited the vasodilatory response to acetylcholine by about 40% in the two groups but had no significant effect on the vasodilatation induced by bradykinin. Aspirin had no effect on the vasodilatation induced by acetylcholine or bradykinin. These data show that the vasodilatory response to bradykinin is decreased in coronary patients and suggest that nitric oxide is not the second main messenger of bradykinin in the resistive circulation of the forearm.

Molsidomine improves flow-dependent vasodilation in brachial arteries of patients with coronary artery disease.

Flow-mediated vasodilation (FMD) of human blood vessels is essential to adaptation and regulation of peripheral blood flow, and is mediated by endogenously produced nitric oxide. Endothelial function is impaired in many pathologic states, especially in coronary heart disease. We questioned in this study whether exogenous nitric oxide (NO) would restore endothelial dysfunction in peripheral arteries of patients with coronary artery disease (CAD). In a randomized double-blinded case-control assay, we used computerized A-mode ultrasonography to measure diastolic diameters of the brachial artery before and after hyperemia in two groups of 10 patients with CAD. Each group received orally either placebo or 12 mg molsidomine a day for 48 h. In the molsidomine group, FMD was improved with a 60% increase after the first intake of molsidomine, and the same trend was observed after the last intake, although less pronounced. Significant increase in diastolic diameter was observed after the last molsidomine intake, but not after the first one. Thus molsidomine has an early positive effect on FMD in addition to a delayed vasodilator effect. Improvement of endothelial dysfunction by molsidomine in patients with CAD may uncover new therapeutic perceptive in the use of nitrovasodilators.

[Indications for antiplatelet medications]. / Indications des médicaments antiplaquettaires.

Platelet active drugs are part of the antithrombotics. Their biological effect is not assessed in current practice. Their clinical efficacy has been firmly established in randomised controlled trials. Aspirin has been the most widely tested drug and is effective in various forms of coronary artery disease and in the secondary prevention after a first ischaemic stroke; in these settings, aspirin reduces the incidence of myocardial infarction, stroke and cardiac death; aspirin has been tested in various daily doses from 30 to 1300 mg: best evidence has been gathered for dosages between 75 and 300 mg; good clinical practice is to use the lowest effective dose. Ticlopidine and clopidogrel have been shown to be superior to aspirin in 2 trials where the incidence of myocardial infarction has been lowered by the new drugs; nevertheless the superiority is apparent only in patients with lower limb atherosclerosis and after stroke. The combination of dipyridamole and aspirin has been proven to be superior to aspirin in the secondary prevention of stroke in one trial contrasting with the other trials performed with other combinations of those two drugs. Glycoprotein GP IIb/IIIa antagonists have been tested in coronary angioplasty and in acute coronary syndromes and only in short intravenous administration; these drugs reduce the incidence of myocardial infarction without any effect on 6-month mortality.

Improvement of bradykinin endothelium-mediated vasodilation of forearm resistance circulation by quinaprilat in patients with coronary artery disease with or without left ventricular dysfunction.

Angiotensin-converting enzyme (ACE) inhibition potentiates bradykinin and acetylcholine endothelium-mediated vasodilation. Three groups were studied. Group I (n = 10) was the reference group; group II was composed of nine patients with coronary artery disease; and group III of seven patients with coronary artery disease and left ventricular dysfunction. Forearm blood flow was measured with plethysmography. Acetylcholine and bradykinin were administered in a random order in the brachial artery at infusion rates of 40 and 80 microg/min and 10, 30, 100 pmol/min, respectively. Then quinaprilat was infused alone at the rate of 50 microg/min and then coinfused with acetylcholine and bradykinin. Five of the reference subjects were pretreated with acetylsalicylate. Acetylcholine and bradykinin increased forearm blood flow in a dose-dependent manner in the three groups. However, the vasodilator responses to both agents were significantly lower in the two groups of patients than in the reference group. Quinaprilat significantly enhanced the vasodilator response to acetylcholine only in subjects of the reference group, whereas it enhanced the vasodilator response to each dose of bradykinin, both in subjects of the reference group and in patients. Pretreatment with aspirin did not change the vasodilator responses in any group. In healthy persons, quinaprilat had no effect on its own on forearm blood flow but enhanced the response to bradykinin and even acetylcholine. In patients with coronary disease, short-term administration of quinaprilat was able to improve the impaired response to bradykinin. The response to acetylcholine, however, could not be significantly enhanced in contrast to that in healthy subjects.

[Physiopathological basis of the treatment of heart failure]. / Bases physiopathologiques du traitement de l'insuffisance cardiaque.

Therapeutic advances have changed the mode of presentation of cardiac failure over the last decades: the main cause, nowadays, is myocardial ischaemia. The modern treatment of cardiac failure is based on relatively simple physiopathological mechanisms which take into account the different aspects of cardiac physiology: a pump, a muscle, a coronary circulation supplying oxygen to the myocardium, an automatic contraction. The concept of vasodilatation and the blocking of vasoconstrictive systems introduced during the 70s is the basis of modern treatment of cardiac failure which involves angiotensin converting enzyme inhibitors and, increasingly, betablockers. In the near future, with earlier treatment of cardiac failure, the stimulation of vasodilator systems could become a new therapeutic strategy. Early detection of ischaemia and its complications with the aim of limiting the loss of cardiac myocytes is a priority for slowing the progression of cardiac failure. The prevention of cardiac failure also depends on educating cardiologists to treat rapidly the factors predisposing to or prolonging episodes of even mild cardiac failure.

[Therapeutic strategy of the management of acute heart failure]. / Stratégie thérapeutique de la prise en charge de l'insuffisance cardiaque aiguë.

Acute cardiac failure should be approached clinically and paraclinically as an emergency and precipitation is not always what is required. Consequently, strict clinical and paraclinical strategy leads to decisive action to improve the prognosis. The authors describe the principles of management of acute cardiac failure. The different stages which are carried out simultaneously in clinical practice are discussed: physiopathological basis, clinical and paraclinical investigations, symptomatic and aetiological treatment. The description and indications of circulatory assistance are considered. This constitutes a major therapeutic advance of the last decade and has changed the treatment of the most severe clinical forms of acute cardiac failure.

Relation between impairment in nitric oxide pathway and clinical status in patients with congestive heart failure.

A dissociation between basal and stimulated release of nitric oxide (NO) has been found in the peripheral vasculature of patients with congestive heart failure. To explore basal and stimulated NO-mediated vasodilation in patients with heart failure of varying severity, three groups of subjects were studied: group 1, eight normal subjects; group 2, six patients with moderate heart failure; and group 3, eight patients with severe heart failure. Forearm blood flow (FBF) was measured by plethysmography in response to local brachial infusion of acetylcholine, N(G)-monomethyl-L-arginine (L-NMMA), sodium nitroprusside (SNP), and noradrenaline (NA). The vasodilating response to acetylcholine was markedly impaired in patients with severe heart failure compared with the other groups, with FBF increasing by 59 +/- 19% in group 3 vs. 220 +/- 64% in group 2 (p < 0.05) and 586 +/- 168% in group 1 (p < 0.01) at 80 microg/min acetylcholine. As compared with controls, vasodilation to SNP was impaired in group 3 but unchanged in group 2. NA caused similar vasoconstrictor response in the three groups, whereas vasoconstriction to L-NMMA was less marked in group 3. These results show that vasodilator responses to both acetylcholine and SNP are impaired in patients with heart failure and that this impairment is related to the clinical severity of heart failure.

[Acute heart failure]. / Insuffisance cardiaque aiguë.

Acute cardiac failure is the principal complication of all forms of heart disease. The goal of therapy is to improve the quality and length of life, and to prevent progression of the syndrome. Although improvement in survival with medical therapy has been obtained at each stage of heart failure, quality of life has been more difficult to assess and regression of the disease is most apparent before severe symptomatic heart failure develops. Decisive recent progresses have been the development of cardiac transplantation and of assisted circulation techniques, and the generalisation of reperfusion therapies at the acute stage of myocardial infarction.

[Arrhythmogenic right ventricle: dysplasia or cardiomyopathy? Value of left ventricle ejection fraction]. / Le ventricule droit arythmogène: dysplasie ou cardiomyopathie? Valeur de la fraction d'éjection du ventricule gauche.

The left ventricular ejection fraction (LVEF) of 76 patients suffering from arrhythmogenic dysplasia or cardiomyopathy of the right ventricle (ventricular tachycardia associated with structural abnormalities of the right ventricle) demonstrated two subgroups situated above and below 45%. Values of LVEF less than 45% were similar to those of a control population of 6 cases of idiopathic dilated cardiomyopathy with ventricular tachycardia of left ventricular origin (p = 0.2). These patients also have the same unfavourable long-term prognosis. Histological data obtained from four cases belonging to the group of patients with dysplasia or cardiomyopathy of the right ventricle with a low ejection fraction demonstrated the presence of signs of myocarditis involving both ventricles. This suggests that these patients may suffer from an infectious phenomenon superimposed on a specific histological substrate, which may lead to deterioration of their myocardial function. These results are in line with those of the literature. The term arrhythmogenic cardiomyopathy of the right ventricle should therefore be reserved to the subgroup of patients with an LVEF less than 45%. Finally, arrhythmogenic cardiomyopathy of the right ventricle appears to be a complication of dysplasia following the development of a myocarditic phenomenon. This may explain the wide range of clinical forms observed in patients with ventricular tachycardia of right ventricular origin associated with structural abnormalities of the right ventricle.