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Biomedical subjects

A Cohen-Solal

Publications and source records attributed to A Cohen-Solal.

At least 91 records · Page 5Linked to original sources

[Role of digitalis glycosides in the treatment of cardiac failure].

While no doubt has ever been cast on the usefulness of digitalis in cardiac failure with atrial fibrillation and a fast ventricular rate, they are periodically brought into question regarding chronic cardiac failure in sinus rhythm. While they have not been supplanted by new positive inotropic agents, they are in competition with converting enzyme inhibitors. Recent therapeutic trials have shown that digitalis preparations, alone or in association with converting enzyme inhibitors, have beneficial effects on symptoms and exercise duration in patients with symptomatic impaired left ventricular systolic function. While the effects of digitalis preparations on mortality remain unknown, a large North American study should soon provide an answer to this question.

Chronic Disease↗

Endopeptidase from rat liver membranes, which generates miniglucagon from glucagon.

An endopeptidase activity that cleaves glucagon, producing miniglucagon or glucagon (19-29), a Ca2+ pump inhibitory peptide, was isolated from rat liver membranes. The purified enzyme has a molecular mass of approximately 100 kDa and a pH optimum of approximately 8. It is inhibited by both sulfhydryl-blocking reagents and metal-chelating reagents and activated by thiol compounds. The partial N-terminal amino acid sequence of the 100-kDa protein does not correspond to any known protein. An antiserum was raised against a synthetic octapeptide corresponding to the N-terminal sequence. Immunoblot analysis of crude liver membranes revealed a single band at 100 kDa. Immunoreactivity was found in liver, pancreas, and heart, which are glucagon and miniglucagon target tissues, and in gastric mucosa and kidney. Low levels were detected in spleen, whereas immunoreactivity was undetectable in skeletal muscle and intestinal mucosa. The endopeptidase activity was inhibited by insulin, glucagon-like peptide-1, and glucagon-like peptide-1 (7-36) amide, whereas other peptides that contain dibasic sites had no effect on its activity, indicating that the endopeptidase does not display strict selectivity toward basic doublets.

Amino Acid Sequence↗

Cardiopulmonary response during exercise of a beta 1-selective beta-blocker (atenolol) and a calcium-channel blocker (diltiazem) in untrained subjects with hypertension.

The effects of beta-blockers and calcium-channel blockers on cardiopulmonary response during exercise are not well characterized. Sixteen sedentary patients with essential hypertension underwent a randomized, double-blind, cross-over study comparing atenolol and diltiazem sustained-release 300 mg, each administered during 6 weeks, after a 15-day run-in placebo period. Neither atenolol nor diltiazem significantly affected maximal exercise duration, maximal oxygen uptake, ventilatory threshold, or any of the ventilatory parameters during exercise. With atenolol, the maximal oxygen pulse was significantly increased and compensated for the decrease in heart rate during exercise. Atenolol and diltiazem do not limit maximal exercise tolerance in untrained hypertensive subjects, but the circulatory profile is more preserved with diltiazem.

Adult↗

[Effects of aging on left ventricle-arterial coupling in man].

Twenty-five normotensive men without any cardiac or arterial pathology, aged 22 to 68 years, 12 less than 45 year old, 13 over 45 years, underwent cardiac catheterisation and angiography. The following parameters were calculated: 1) a global index of arterial function (Ea) and its determining factors (Ea = LVESP/SV where LEVSP = left ventricular end systolic pressure and SV = left ventricular stroke volume); Ea = (HR x SVR) + Ea' where HR = heart rate, SVR = total systemic vascular resistance and Ea' = (LVESP - MAP/SV) (MAP = mean arterial pressure); 2) an index of global left ventricular pump function: ELV (ELV = LVESP/LVESV, where LVEDV = left ventricular end systolic volume; 3) an index of LV-arterial coupling: the Ea/ELV ratio. With aging, both Ea (by increase in SVR) and Ea' and ELV increased significantly. Ea/ELV (inverse of the ejection fraction-1) increased with age but ELV less than Ea. Ea/ELV was significantly higher in patients over 45 years of age but the correlation between ejection fraction and age was not statistically significant (p = 0.10). These results suggest that with aging, the improvement in LV pump function approximately corresponds to the degradation in arterial transport function: the left ventricular-arterial coupling as assessed by the Ea/ELV ratio (and therefore the ejection fraction) is maintained in the majority of cases.

Adult↗

[Functional coupling of the left ventriculo-arterial system and aging in man].

In a haemodynamic and angiographic study at rest conducted in 25 men aged from 22 to 68 years who had no more than another risk factor for arterial disease and showed no evidence of cardiac or arterial disease several parameters were measured or calculated. Firstly, a global index of arterial system function (Ea) and its various factors: Ea = ESP/SV [ESP: left ventricular end-systolic pressure; SV: systolic volume]; Ea = (HR x TSR)+Ea' [HR: heart rate/min; TSR: total systemic resistance] where Ea' = (ESP - AoP/SV) [AoP: mean aortic pressure]. Secondly, the parameters concerning the left ventricle were the mass (m) and the m/EDV ratio [EDV: end-diastolic volume] and indices of the left ventricular systolic and diastolic functions, such as ELV = ESP/ESV [ESV: end-systolic volume], kp: the volumic distensibility module of the left ventricular chamber; relations EF - o ES [EF: ejection fraction; o ES: end-systolic constraint], and kp - m/EDV as indice of left ventricular muscle distensibility. In parallel with the subjects' age, Ea increased by joint augmentation of TSR and Ea' while m, m/EDV, ELV and kp also significantly increased. The inotropic quality of the left ventricular muscle and its intrinsic distensibility were found to be decreased in a few subjects aged over 45. Ea/ELV (reverse of ejection fraction -1) tended to increase (ELV relatively less than Ea), but this increase was not significant (P = 0.10). These results show that in the ageing man the improvement observed in the ejection fraction of the left ventricular pump corresponds roughly to the degradation of the arterial system transfer function, and the arterial system-left ventricle coupling, evaluated by the Ea/ELV ratio, is maintained (better in fact than in arterial hypertension and heart failure). This improvement is achieved by increases of m and, chiefly, m/EDV which compensate for both the increase of Ea and the relative decline of left ventricular muscle contractile quality. There is a disorder of the left ventricular pump diastolic function which is due to geometric changes in the chamber and to changes in the intrinsic distensibility of the left ventricular muscle.

Adult↗

A patency-oriented strategy for early management of acute myocardial infarction using emergency coronary angiography and selective coronary angioplasty.

From June 1988 to March 1991, an unselected cohort of 150 consecutive patients with acute myocardial infarction (AMI) (less than 6 hours) was managed according to a strategy designed to ensure early patency of the infarct-related artery in the maximum number of patients. The following procedures were used: (1) intravenous thrombolysis, which was the usual treatment (n = 103), followed in 98 cases by emergency coronary angiography 90 minutes after the beginning of thrombolysis. This identified 31 thrombolysis failures (32%) and led to 19 rescue angioplasties (18 successes). All patients were then scheduled for predischarge angiography. (2) Direct angioplasty, which was performed in 40 patients because of contraindications to thrombolysis (n = 23), cardiogenic shock (n = 3), diagnostic doubt (n = 7) or "ideal" conditions for direct angioplasty (n = 7). Success (defined as Thrombolysis in Myocardial Infarction [TIMI] flow greater than 1, with a residual stenosis less than 50% in the infarct-related artery) was achieved in 36 of 40 patients (90%). (3) The 7 remaining patients were given conventional medical treatment because of advanced age, contraindications to thrombolysis and angioplasty, or spontaneous reperfusion (confirmed by emergency angiography). In all, emergency angioplasty was performed in the acute phase in 39% of the 150 patients in this nonselected cohort.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

[Acute hemodynamic effects of SIN-1 and isosorbide dinitrate in stable left ventricular failure: a comparative double-blind, cross-over study].

The acute hemodynamic effects of intravenous SIN-1 (1 mg) and sublingual isosorbide dinitrate (5 mg) were investigated in 12 patients (8 men and 4 women) between 38 and 80 years of age and suffering from stable chronic left ventricular failure (NYHA Classes III-IV) secondary to ischemic myocardiopathy (n = 5), hypertensive disease (n = 2) or idiopathic disorder (n = 5) corresponding to the following hemodynamic inclusion criteria: stable condition, cardiac index > or = 2 l/min/m2, mean capillary pressure > or = 18 mmHg and < or = 28 mmHg. Previous treatments were continued with the exception of vasodilators and diuretics which were stopped 24 hours earlier. The hemodynamic data from this cross-over, double-blind double-dummy trial were collected for two 60-hour periods separated by a washout period of 120 minutes. Simultaneously, venous samples were taken for the assay of plasma levels of SIN-1. The heart rate, cardiac output, pulmonary artery resistance and blood pressure were not affected by either SIN-1 or isosorbide dinitrate. An obvious reduction (> 15% of the basal value) in the mean capillary pressure, pulmonary artery pressure and mean right atrial pressure was observed in 10 subjects after SIN-1 and in 7 patients isosorbide dinitrate. A statistically non-significant trend towards a more marked effect (number of patients responding and maximum amplitude of pressure reduction) which occurred more rapidly and lasted longer was observed after SIN-1. Analysis of the relationship between the pharmacodynamics and pharmacokinetics of SIN-1 suggests that an active metabolites is involved. No adverse effects were reported.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

[How to evaluate the hemodynamic risk after myocardial infarction?].

The hemodynamic prognosis of myocardial infarction is determined, at medium and long term, by the function of the left ventricle. This is related to the infarct size, the dilatation and geometry of the ventricle secondary to left ventricular remodeling which often follows infarction. In addition to clinical criteria, the hemodynamic parameters which are essential for patient evaluation are the ejection fraction (by radionuclide or conventional ventriculography), rapidly progressive ventricular dilatation (by repeated echocardiography) and circulatory reserve from the exercise stress test data.

Angiocardiography↗

[Prevention of postinfarction cardiac insufficiency: role of angiotensin converting enzyme inhibitors].

Cardiac failure remains a serious complication of myocardial infarction. In addition to therapeutic interventions to limit the infarct size, it would seem possible to influence the progressive changes in geometry and size of the left ventricle, known as remodeling. Experimental and clinical studies have shown beneficial effects of angiotensin converting enzyme inhibitors and the SAVE trial evaluated the prognostic consequences of this therapy, reporting a significant reduction in mortality after 10 months' treatment. Many questions remain which require further research in this field, mainly concerning the optimal time of introduction the treatment, the importance of the chemical molecule used, the most appropriate dosage and the influence of associated drug therapy. ACE inhibitors are now part of the therapeutic arsenal of myocardial infarction but their prescription should be strictly reserved for the population concerned by these trials, that is to say patients with a recent, extensive infarct with left ventricular dysfunction but without clinical signs of cardiac failure.

Angiotensin-Converting Enzyme Inhibitors↗

[Negativity of the exercise thallium test despite tight stenosis of the common trunk of the left coronary artery].

The authors report a case of severe angina linked to subocclusive ostial stenosis of the common trunk of the left coronary, characterised by the contrast between a very positive stress test on the basis of clinical and electrocardiographic parameters and a negative Thallium stress test. The occasion is taken to review the sensitivity of Thallium stress testing in lesions of the common trunk.

Constriction, Pathologic↗

Ventilatory threshold during exercise in patients with mild to moderate chronic heart failure: determination, relation with lactate threshold and reproducibility.

Detection of the ventilatory threshold during exercise has been proposed in order to assess exercise tolerance in patients with chronic heart failure. The relation between the different methods of detecting the ventilatory threshold and the lactate threshold, however, and their reproducibility, have not really been assessed. Forty-three patients with chronic heart failure underwent an exercise test with respiratory gas analysis. A lactate threshold could be determined in 36 patients and a ventilatory threshold in 27 to 38 patients, depending on the method of determination of the ventilatory threshold. The greatest number of determinations (38) and the best correlation coefficient with the lactate threshold (r = 0.87 and 0.88, respectively) were obtained with the method of the ventilatory equivalent for oxygen and by averaging the different methods of determination. Reproducibility of the ventilatory threshold was only moderately good (r = 0.83) and less satisfactory than that of the peak oxygen uptake (r = 0.97). We conclude that unless the way of detecting the ventilatory threshold is improved in patients with chronic heart failure, the peak oxygen uptake will remain more reproducible.

Adult↗

Multicentre study of the determination of peak oxygen uptake and ventilatory threshold during bicycle exercise in chronic heart failure. Comparison of graphical methods, interobserver variability and influence of the exercise protocol. The VO2 French Study Group.

Assessment of the ventilatory threshold (VT) has been proposed to assess exercise tolerance more objectively, particularly in clinical trials, but reproducibility, interobserver variability and feasibility of the graphical methods for determination of VT have not been properly studied in patients with chronic heart failure (CHF). Fifty-one patients with mild to moderate CHF (mean peak oxygen uptake (VO2): 20.5 ml.min-1.kg-1) were assessed during two consecutive bicycle exercise tests within 8 days. Two graded exercise protocols were compared with stages of 30 W every 3 min (22 patients) or 10 W/min (29 patients). VT was determined separately by five trained physicians using five different graphical methods. The 'crossing method' (first crossing of the VCO2 and VO2 curves) yielded the highest rate of determination (88%) but tended to overestimate the mean VT. The VE method (disproportionate increase of ventilation relative to VO2) produced the best interobserver agreement (coefficient of variation = 78%). Peak VO2 was very highly reproducible in both exercise protocols (relative difference 2-test 1/test 1 = -0.32% for the 30 W 3 min protocol; +2.18% for the 10 W.min-1 protocol). The reproducibility of VT was slightly lower regardless of the graphical method used to determine it (relative differences varied from -3.3% to +7.3%). Therefore, peak VO2 appears more suitable than VT for assessment of exercise tolerance in CHF.

Adult↗

[Left ventricular remodeling and ischemic heart diseases. Therapeutic possibilities].

Left ventricular modeling after myocardial infarction may be modified in three ways: firstly, by limiting the infarct size; secondly, by administering ACE inhibitors: these drugs limit infarct expansion and ventricular dilatation. They reduce the prevalence of secondary left ventricular failure and, in the animal, improve the prognosis. Glyceryl trinitrate also appears to be effective. The third therapeutic option is maintaining the patency of the artery responsible for the infarction, which has a beneficial effect on ventricular remodeling. The respective therapeutic indications of these three options are still a matter of discussion.

Adrenergic beta-Antagonists↗

[Ventricular "remodeling" after myocardial infarction].

Cardiac failure is the principal medium-term complication of myocardial infarction. Changes in left ventricular geometry are observed after infarction, called ventricular remodeling, which, though compensatory initially, cause ventricular failure in the long-term. Experimental and clinical studies suggest that early treatment by coronary recanalisation, trinitrin and angiotensin converting enzyme inhibitors may prevent or limit the expansion and left ventricular dilatation after infarction, so improving ventricular function, and, at least in the animal, reduce mortality. Large scale trials with converting enzyme inhibitors are currently under way to determine the effects of this new therapeutic option. It would seem possible at present, independently of any reduction in the size of the infarction, to reduce or delay left ventricular dysfunction by interfering with the natural process of dilatation and ventricular modeling after infarction.

Angiotensin-Converting Enzyme Inhibitors↗