Showing papers by "Marc A. Pfeffer published in 1982"

Regression of left ventricular hypertrophy and prevention of left ventricular dysfunction by captopril in the spontaneously hypertensive rat

Abstract: To determine whether chronic antihypertensive therapy prevents the progression of cardiac hypertrophy and the deterioration in cardiac performance observed in spontaneously hypertensive rats (SHR) with long-term hypertension, 14-month-old female SHR and normotensive American Wistar rats (NWR) were treated for 10 months with an inhibitor of angiotensin I-converting enzyme, captopril (2 g/liter of drinking water). Captopril reduced the marked left ventricular hypertrophy of 24-month-old SHR (untreated, 4.37 +/- 0.2 mg/g of body weight; treated, 3.01 +/- 0.1 mg/g; P less than 0.02) to levels observed in 6-month-old SHR. Treatment prevented the reductions in baseline and maximal aortic blood flows that occurred in SHR between ages 12 and 24 months yet had no effect on the blood flows of NWR. The diminished maximal stroke volume of untreated SHR was ejected from a significantly increased left ventricular end-diastolic volume, so that the ejection-fraction index was markedly reduced (24-month-old untreated NWR, 84 +/- 3%; untreated SHR, 56 +/- 5%; P less than 0.001). Therapy restores this index in SHR to normal (77 +/- 4%). The relationship between ejection-fraction index, and afterload was also normal in treated SHR. Thus, chronic therapy with captopril produced a marked regression of cardiac hypertrophy and prevented the deterioration of cardiac performance in SHR with long-standing hypertension.

Favorable effects of therapy on cardiac performance in spontaneously hypertensive rats.

Abstract: To determine whether chronic antihypertensive therapy reduces cardiac mass and improves performance in spontaneously hypertensive rats (SHR) with marked left ventricular hypertrophy and evidence of cardiac dysfunction, 12-mo-old male and female SHR and age- and sex-matched normotensive rats (NORM) were treated for 6 mo with either tap water or tap water containing hydralazine or guanethidine. Cardiac performance was assessed by the peak stroke volume and cardiac indices attained during volume loading and by the maximum left ventricular pressure developed during an aortic occlusion. Passive diastolic pressure-volume curves were obtained in the potassium-arrested heart. Treatment prevented the progression of left ventricular hypertrophy in SHR and the marked deterioration in peak pumping ability observed in untreated male SHR and the modest impairment observed in female SHR. The peak developed pressure of both the male and female treated SHR was reduced toward that of NORM and was associated with a reduction in the left ventricular mass-to-volume ratio toward that of NORM. Thus chronic therapy with either hydralazine or guanethidine reduced cardiac mass and prevented the deterioration in cardiac pumping performance observed in SHR with sustained hypertension and marked cardiac hypertrophy.

Effects of hypertension on cardiac performance in rats with myocardial infarction.

Abstract: To determine the effects of hypertension and myocardial infarction on cardiac performance, hemodynamic studies were performed on etheranesthetized, female spontaneously hypertensive rats and on two strains of normotensive rats, Wistar-Kyoto and American Wistar, 26 days after coronary arterial ligation. Baseline measurements of ventricular and arterial pressures and cardiac output (electromagnetic flowmeter) were obtained. Peak cardiac pumping and pressure-generating capacities were determined during a volume load and aortic occlusion, respectively. Infarct size was determined by planimetry. There was a progressive reduction in mean arterial pressure in relation to infarct size in both hypertensive and normotensive rats, but this reduction was twice as great in spontaneously hypertensive rats as in the normotensive rats, such that the arterial pressure of hypertensive rats with a moderate or large infarction decreased to within the “normotensive range.” However, spontaneously hypertensive rats still maintained significantly higher arterial pressures than did normotensive rats at comparable infarct sizes. There was also a progressive reduction in the peak pressure developed during an afterload stress, and this reduction was greater in hypertensive rats than in normotensive rats with a large infarct. Maximal flow-generating capacity was similarly altered in rats with infarction: Peak stroke volume index varied inversely with infarct size and the reduction in this index was significantly greater in spontaneously hypertensive rats than in normotensive rats with a large infarct. Moreover, peak stroke work index was reduced to a greater extent in spontaneously hypertensive rats than in both normotensive strains of rats at any infarct size. Thus, after myocardial infarction, greater reductions in both pressure and flow-generating capacities occurred in hypertensive rats than in normotensive rats.

Alterations in the Electrocardiogram of Spontaneously Hypertensive Rats by Chronic Antihypertensive Therapy With Captopril

Abstract: To determine whether the electrocardiogram (ECG) could detect a reduction in ventricular mass with chronic antihypertensive therapy, ECGs were obtained in two year old female normotensive (NR) and spontaneously hypertensive rats (SHR) following nine months of treatment with captopril or water. The ECG of untreated SHR was considerably different than that of age- and sex-matched NR. The notable differences were the increased voltage, left axis deviation, a delay in the intrinsicoid deflection, and the increased frequency of left atrial abnormalities. Chronic captopril therapy produced a substantial reduction in left ventricular mass in the SHR (NR, 0.63 +/- 0.01; SHR, 1.08 +/- 0.03; captopril SHR, 0.80 +/- 0.04 g). The ECG reflected this regression of left ventricular hypertrophy since the voltage and axis of the treated SHR were no longer different than those of NR. Thus, the ECG may be effective in evaluating the regression of cardiac hypertrophy in response to chronic therapy in experimental hypertension.