Showing papers by "Marc A. Pfeffer published in 1985"

Influence of chronic captopril therapy on the infarcted left ventricle of the rat.

Abstract: To determine whether the relationship between infarct size and ventricular performance, volume, and compliance could be altered favorably, captopril was administered to rats for 3 months following coronary artery ligation. Baseline left and right ventricular and systemic arterial pressures and aortic blood flow, and maximal stroke volume and cardiac indices attained during a volume loading, were measured. Passive pressure-volume relations of the left ventricle were determined, and the slopes of segments of this relation were analyzed to characterize ventricular chamber stiffness. In untreated rats, left ventricular end-diastolic pressure progressively rose (from 5-28 mm Hg) as a function of infarct size, whereas, in captopril-treated rats, filling pressure remained within normal limits (5 +/- 1 mm Hg) in all but those with extensive infarcts. Chronic captopril therapy reduced baseline mean arterial pressure and total peripheral resistance, yet maintained cardiac and stroke outputs in rats both with and without infarcts. In untreated rats, maximal pumping ability progressively declined with increasing infarct size, whereas, in captopril-treated rats, peak stroke volume index remained within normal limits in all but those with extensive infarcts. The in vitro left ventricular volumes of captopril-treated rats were significantly less than those of untreated rats. The maintenance of forward output from a lesser dilated left ventricle yielded an index of ejection fraction for treated rats with moderate and large infarcts that was significantly elevated compared with that of untreated rats with infarcts of comparable size. Left ventricular chamber stiffness, which fell as infarct size increased in untreated rats, was normalized by chronic captopril therapy. Thus, captopril attenuated the left ventricular remodeling (dilation) and deterioration in performance that were observed in rats with chronic myocardial infarction.

Survival after an experimental myocardial infarction: beneficial effects of long-term therapy with captopril.

Abstract: Although vasodilator therapy has been shown to improve functional capacity in patients with congestive heart failure, there is no evidence that such therapy can prolong survival. Coronary artery ligation in the rat was used to produce a wide range of myocardial infarct sizes and a resultant spectrum of left ventricular dysfunction. To determine the relationship between size of myocardial infarction and long-term survival and to test the hypothesis that long-term therapy with captopril could improve survival after myocardial infarction, 302 rats were randomly assigned to either placebo or captopril therapy 14 days after coronary artery ligation. The animals were kept in a laminar flow unit and followed daily for a 1 year period or until spontaneous death. Size of myocardial infarction was determined by planimetry of serial histologic sections of the left ventricle. One year survival in placebo-treated rats decreased markedly in direct relation to increasing size of infarction (from 71% in noninfarcted rats to only 8% in rats with large infarcts). Long-term captopril therapy prolonged the survival of rats with infarcts (p less than .02). The most marked improvement in survival was noted in the animals with infarcts of moderate size, in which 1 year survival was 21% in the placebo-treated rats and 48% in the captopril-treated rats. Thus, in this experimental preparation of myocardial infarction and left ventricular dysfunction, survival was inversely related to size of infarction. Long-term therapy with captopril, which we had previously shown to improve left ventricular function and lessen dilatation in the chronic phase of infarction, also had a pronounced effect on prolonging survival in this preparation of chronic infarction.

Left ventricular hypertrophy and pressure generating capacity in aging genetically hypertensive rats.

Abstract: Alterations in the relationship between the degree of left ventricular hypertrophy and the maximum pressure generating capacity were assessed in two models of genetic hypertension in rats. Both the spontaneously hypertensive rat (SHR) and the Dahl salt-sensitive (DS) rat developed systemic hypertension and progressive increases in left ventricular mass. In the DS rat, the magnitude of the hypertension and ventricular hypertrophy produced was in direct relation to the level of dietary sodium intake. At 6 months of age, the pressure generating capacity of all hypertensive rats was directly related to the left ventricular weight/body weight ratio. With the moderate level of hypertrophy observed in the 12-month-old SHRs and DS rats on a low salt diet, the correlation between left ventricular weight and augmented pressure generating capacity during isovolumic contractions was maintained. With the more severe degrees of left ventricular hypertrophy observed in 18- and 24-month-old SHRs and 12-month-old DS rats on a moderate salt diet, the further addition of ventricular mass was no longer associated with a proportional augmentation in maximal pressure development. These studies suggest that in genetic hypertension in rats, both the magnitude and duration of the hypertension are important determinants of the degree of hypertrophy and the functional status of the ventricle.

Mechanism of the negative inotropic action of leukotrienes C4 and D4 on isolated rat heart.

Abstract: Leukotrienes C4 and D4 (LTC4 and LTD4), possible mediators of cardiac dysfunction during inflammatory injury, may depress cardiac function by reducing coronary flow or by exerting a negative effect directly on the myocardium. We used an isovolumic rat heart preparation perfused at constant pressure and measured left ventricular developed pressure (mmHg), coronary flow (ml·min−1), oxygen extraction, and myocardial oxygen consumption and delivery (μmol O2·l gramme dry weight l−1·min−1) during infusion of five doses of angiotensin II, LTC4, LTD4 (∼10 to ∼300 pmol·min−1). and noradrenaline (400 to 2000 pmol·min−1), or perfusion with medium which contained calcium at half-concentration. LTC4 and LTD4 were equipotent with angiotensin. At low effective doses, increased oxygen extraction offset the decrease in oxygen delivery, maintaining a stable level of oxygen consumption and left ventricular developed pressure. At the highest doses, angiotensin, LTC4 and LTD4 reduced coronary flow from 21 to 15, 21 to 13, and 21 to 13 ml·min−1, respectively. And, despite greater oxygen extraction of 59%, 58% and 65% for angiotensin, LTC4 and LTD4, left ventricular developed pressure fell from a baseline of 120 mmHg to 113, 106 and 92, respectively. In contrast, low calcium perfusion reduced left ventricular developed pressure (126 to 92) and oxygen extraction (46 to 30%) without changing coronary flow or oxygen delivery. These results suggest that LTC4 and LTD4 are potent coronary vasoconstricting agents which depress cardiac function by limiting oxygen delivery.