enalaprilat-anhydrous and Cardiomyopathy--Hypertrophic

Left ventricular (LV) diastolic function and coronary flow are impaired in hypertrophic obstructive cardiomyopathy (HOCM). This study was designed to evaluate the impact of cardiac and circulatory ACE inhibition on such derangements.. Twenty patients with HOCM underwent cardiac ACE inhibition with intracoronary (IC) enalaprilat (0.05 mg/min infused into the left anterior descending coronary artery for 15 minutes) followed by circulatory ACE inhibition with 25 mg sublingual (SL) captopril. Contrast ventriculography, pressure, and coronary flow measurements were performed at baseline, after IC enalaprilat infusion, and 45 minutes after SL captopril. Heart rate was not affected by the respective interventions (75+/-11 versus 76+/-13 versus 75+/-10 bpm; P=NS), whereas mean aortic pressure dropped slightly after IC enalaprilat and significantly after SL captopril (90+/-8 versus 85+/-10 versus 74+/-9 mm Hg; P<.05). Compared with baseline, IC enalaprilat resulted in a decrease in LV end-diastolic pressure (17.6+/-5.9 versus 14.4+/-4.9 mm Hg; P<.05), time constant of isovolumic LV pressure relaxation (tauG) (69+/-9 versus 52+/-10 ms; P<.05), and outflow gradient (45.2+/-6.9 versus 24.4+/-3.7 mm Hg; P<.05) and in an increase in coronary blood flow (107+/-10 versus 127+/-12 mL/min; P<.05) and coronary flow reserve (2.2+/-0.4 versus 2.6+/-0.3; P<.05). After SL captopril, tauG was prolonged (60+/-13 ms; P<.05 versus IC enalaprilat), and LV outflow gradient, coronary blood flow, and coronary flow reserve values returned to baseline (45.5+/-5.3 mm Hg, 107+/-12 mL/min, and 2.2+/-0.5, respectively; P=NS versus baseline).. Activation of the cardiac renin-angiotensin system contributes to LV diastolic dysfunction as well as to the decreased coronary blood flow and coronary flow reserve in HOCM. Cardiac ACE inhibition restores and circulatory ACE inhibition aggravates the above derangements.

Topics: Adult; Analysis of Variance; Angiotensin-Converting Enzyme Inhibitors; Captopril; Cardiomyopathy, Hypertrophic; Coronary Circulation; Diastole; Echocardiography; Enalaprilat; Female; Heart; Hemodynamics; Humans; Infusions, Parenteral; Male; Middle Aged; Prospective Studies; Ventricular Dysfunction, Left

Hearts with compensatory pressure-overload hypertrophy show an increased intracardiac activation of angiotensin II that may contribute to ischemic diastolic dysfunction. We studied whether pressure-overload hypertrophy in response to aortic banding would result in exaggerated diastolic dysfunction during low-flow ischemia and whether the specific inhibition of the cardiac angiotensin converting enzyme by enalaprilat would modify systolic and diastolic function during ischemia and reperfusion in either hypertrophied or nonhypertrophied hearts. Isolated, red blood cell-perfused isovolumic nonhypertrophied and hypertrophied rat hearts were subjected to enalaprilat (2.5 x 10(-7) M final concentration) infusion during 20 minutes of baseline perfusion and during 30 minutes of low-flow ischemia and 30 minutes of reperfusion. Coronary flow per gram was similar in nonhypertrophied and hypertrophied hearts during baseline perfusion, ischemia, and reperfusion. At baseline, left ventricular developed pressure was higher in hypertrophied than nonhypertrophied hearts in untreated groups (224 +/- 8 versus 150 +/- 9 mm Hg; p less than 0.01) and in enalaprilat-treated groups (223 +/- 9 versus 145 +/- 8 mm Hg; p less than 0.01). During low-flow ischemia, left ventricular developed pressure was depressed but similar in all groups. All groups showed deterioration of diastolic function; however, left ventricular end-diastolic pressure increased to a significantly higher level in untreated hypertrophied than in nonhypertrophied hearts (65 +/- 7 versus 33 +/- 3 mm Hg; p less than 0.001). Enalaprilat had no effect in nonhypertrophied hearts, but it significantly attenuated the greater increase in left ventricular end-diastolic pressure in hypertrophied hearts treated with enalaprilat compared with no drug (65 +/- 7 versus 50 +/- 5 mm Hg; p less than 0.01). The beneficial effect could not be explained by differences in coronary blood flow per gram left ventricular weight, glycolytic flux as reported by lactate production, myocardial water content, oxygen consumption, and tissue levels of glycogen and high energy phosphate compounds. During reperfusion, all hearts showed a partial recovery of developed pressure to 70-74% of initial values. No effect of enalaprilat could be detected during reperfusion on systolic and diastolic function or restoration of tissue levels of high energy compounds. In conclusion, our experiments show that hypertrophied red blood cell-perfused hearts mani

Topics: Angiotensin-Converting Enzyme Inhibitors; Animals; Cardiomyopathy, Hypertrophic; Coronary Circulation; Diastole; Enalaprilat; Heart Ventricles; Hemodynamics; In Vitro Techniques; Ischemia; Male; Myocardial Reperfusion; Myocardium; Oxygen Consumption; Perfusion; Rats; Rats, Inbred Strains