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Showing papers by "Marc A. Pfeffer published in 1987"


Journal Article
TL;DR: It is hypothesized that this remodeling of the infarcted left ventricle was a response to an increase in both systolic and diastolic wall stresses and that captopril, by reducing wall stress, would attenuate the process, and that the potential exists for the attenuation of progressive ventricular enlargement and improved survival of patients recovering from a myocardial infarction.
Abstract: Increased ventricular volume is one of the most powerful predictors of reduced survival in patients with heart disease. Despite its well-documented prognostic significance, the magnitude of the progression of ventricular dilatation from the acute to the chronic phase of myocardial infarction has only recently been appreciated. In an experimental preparation of myocardial infarction in rats, left ventricular cavitary volume increased progressively even after histologic resolution of the infarct region. We hypothesized that this remodeling of the infarcted left ventricle was a response to an increase in both systolic and diastolic wall stresses and that captopril, by reducing wall stress, would attenuate the process. For comparably sized infarcts, the captopril-treated rats had smaller ventricular volumes at common distending pressures, yet they had maintained or improved cardiac output. Most importantly, long-term captopril therapy also prolonged the survival of these rats with experimental myocardial infarction. The implication of these animal studies is that the potential exists for the attenuation of progressive ventricular enlargement and improvement of survival of patients recovering from a myocardial infarction. At the present time, no information is available in patients as to the therapeutic potential of interrupting this insidious process of ventricular dilatation in order to improve survival. Clinical trials are required to determine whether salutary benefits similar to those observed in animals can be provided to patients recovering from a myocardial infarction.

155 citations


Journal Article
TL;DR: In rats given captopril until death or for a period of up to 1 year, survival was significantly prolonged, particularly in those rats with moderate-sized infarcts, and therefore the ejection fraction index was significantly increased.
Abstract: To determine whether the hemodynamic profile of chronic heart failure secondary to myocardial infarction could be altered, captopril was administered to female Wistar rats 3 weeks after coronary artery ligation and continued for 3 months. Captopril reduced left ventricular mass, prevented the increase in right ventricular mass observed with increasing infarct size, lessened the increase in left ventricular end-diastolic pressure, and reduced mean arterial pressure and total peripheral resistance, whereas cardiac output and heart rate were maintained. The end-diastolic volume of treated rats with moderate infarcts was significantly less than that of untreated rats, and therefore the ejection fraction index was significantly increased. In rats given captopril until death or for a period of up to 1 year, survival was significantly prolonged, particularly in those rats with moderate-sized infarcts.

111 citations


Journal ArticleDOI
TL;DR: The pharmacokinetics of a single oral dose of buspirone (20 mg) were determined in 12 patients with cirrhosis and 12 normal subjects and on the kinetic evidence busPirone should be used with caution in liver disease.
Abstract: The pharmacokinetics of a single oral dose of buspirone (20 mg) were determined in 12 patients with cirrhosis and 12 normal subjects. The mean AUC of buspirone was 55 +/- 38 s.d. ng ml-1 h in cirrhotics and 3.5 +/- 2.4 s.d. ng ml-1 h in normals. The time until maximum concentration (tmax) attained was similar in the two groups (0.6 vs 0.7 h), but mean maximum concentration Cmax was higher in patients (18.8 +/- 16.3 s.d. ng ml-1) than in normals (1.2 +/- 0.8 s.d. ng ml-1). Mean elimination half-life of buspirone was greater in cirrhotics, but this difference was marginally significant statistically (cirrhotics, 6.1 +/- 3.5 s.d. h, normals 3.2 +/- 1.5 s.d. h, P = 0.05). Eight of 12 patients and seven of 12 normal subjects had a second peak in the plasma concentrations of buspirone. In patients this occurred at 10.8 +/- 7.4 s.d. h after the dose, and its mean concentration was 3.1 +/- 6.6 ng ml-1. In normal subjects the second peak occurred at 4.3 +/- 2.1 h after the dose and its mean concentration was 0.5 +/- 0.3 ng ml-1. On the kinetic evidence buspirone should be used with caution in liver disease.

15 citations





Journal Article
TL;DR: After combined administration of both drugs, the effect of the H1-blocker proved to be significantly increased and the possible mode of action and the consequences for anti-allergic therapy are discussed.
Abstract: The antipruritic effect of modern H1- and H2-receptor blockers in chronic urticaria, that had been clinically proved, was experimentally studied by means of the histamine weal test. The H2-antihistamine preparation ranidine alone did not clearly reduce weals or erythemas induced by histamine when compared with a placebo. As expected, both parameters were markedly reduced by the H1-antihistamine preparation terfenadine. After combined administration of both drugs, the effect of the H1-blocker proved to be significantly increased. We discuss the possible mode of action and the consequences for anti-allergic therapy.

3 citations