No 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.

Ventricular dilatation may have important prognostic implications for the survival of patients with left ventricular (LV) dysfunction. To determine the manner and extent to which the left ventricle of the rat remodels and dilates after myocardial infarction, we obtained the passive pressure-volume relationships, chamber stiffness constants, and mass during both the early and late phases. In moderate and large infarcts as inflammation and edema developed, LV weight increased then progressively decreased as a thin scar formed, returning to normal values as a result of compensatory hypertrophy of the residual myocardium. LV dilatation occurred in all rats with infarcts but to different extents depending on infarct size and duration. In the early postinfarction phase, pressure-volume relationship was relatively unchanged in all infarct-size groups, except for significant rightward shift in low pressure range for rats with moderate and large infarcts and significant leftward shift in high pressure range for rats with small infarcts. During resolution of the inflammatory response, LV dilatation occurred in all infarct groups in relation to infarct size. As scar formation became complete, LV enlargement did not progress in rats with small infarcts but did so in rats with moderate and large infarcts. LV chamber stiffness remained within the range of normal values during the early phase in all rats with infarcts but decreased significantly during the late phase in rats with moderate and large infarcts in association with the extent of ventricular enlargement. Alterations in the volume-to-mass ratio (V/Vwt) were most marked in the late postinfarction phase, wherein both volume (increased) and mass (decreased, then increased) changed dramatically and V/Vwt progressively increased in rats with large infarcts.

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 < .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. Circulation 72, No. 2, 406-412, 1985. THE DIAGNOSIS of congestive heart failure has a grave prognosis.' 2In the Framingham Study, the 5 year mortality rate was greater than 50% for individuals newly diagnosed as having congestive heart failure.' In more recent studies, the median survival of patients with less clearly defined durations of ventricular dysfunction was often measured in months, not years.3-5 Although congestive heart failure is a syndrome that encompasses multiple etiologies, the severity of the cardiac dysfunction appears to have greater prognostic significance than does the specific cause of disease.4 The use of vasodilators, especially the angiotensin-converting enzyme inhibitors, in the treatment

To determine the effects of healed myocardial infarction on the diastolic compliance of the left ventricle, we studied 36 rats 26 days after left coronary artery ligation. Peak cardiac output and stroke volume were measured under ether anesthesia during volume loading, and peak left ventricular developed pressure was determined during occlusion of the ascending aorta. During a slow infusion of saline into the potassium-arrested left ventricle, diastolic pressure and volume were measured continuously over the pressure range -5 to 30 mm Hg. Infarct size was determined by planimetry of serial sections taken from each heart at 1-mm intervals from apex to base. In rats with healed infarcts, left ventricular volume was increased in proportion to infarct size and the diastolic pressure-volume relationship was shifted so that at pressures below 2.5 mm Hg volume was increased, resulting in an increased ventricular compliance in this low pressure range. Above this pressure, the slopes of the pressure-volume curves were similar in rats with and without infarctions. Peak cardiac output and pressure-generating capacity were impaired in proportion to infarct size. This impairment of cardiac performance correlated with the infarct size-related increase in diastolic volume, which served to offset the reduction in flow generating capacity caused by systolic dysfunction, while contributing directly to the impairment of pressure generating capacity.