EFFECTS OF AN EARLY TREATMENT WITH LISINOPRIL AND ISOSORBIDE-5-MONONITRATE ON HEMODYNAMICS AND LATE VENTRICULAR REMODELING IN RATS WITH 9-WEEK MYOCARDIAL-INFARCTION

This study was undertaken tb assess whether the converting enzyme inhi bitor lisinopril, and the long-acting nitrate, isosorbide- 5-mononitra te, affect left ventricle dysfunction and anatomical remodelling in ra ts with myocardial infarction. Lisinopril, isosorbide-5-mononitrate or vehicle were given to rats (n = 10-14 per group) immediately after co ronary artery occlusion (by an intravenous bolus) and then for nine we eks (in drinking water). At the end of the study, left ventricular pre ssures were measured, the heart arrested in diastole, and infarct size , left ventricular chamber volume and wall thicknesses measured. Lisin opril significantly lowered systemic blood pressure and left ventricul ar systolic pressure in rats with small (< 15% scarred tissue of the l eft ventricle) and large (> 15%) infarcts; the weight of the left vent ricle (including the septum) was reduced by 24% and 28% in animals wit h small and large infarcts, respectively. Lisinopril lowered left vent ricular end-diastolic pressure (by 33% and 39%) and chamber volume (by 4% and 34%) in rats with small and large infarcts, respectively, comp ared with controls (NS). The combined anatomical and hemodynamic chang es led to a reduction of the circumferential wall stress by 20% and 44 % in lisinopril-treated rats with small and large infarcts, respective ly (NS). No significant changes were seen in the nitrate-treated heart s compared with controls. Lisinopril, given early after myocardial inf arction and continued for nine weeks, significantly affected cardiac h emodynamics and ventricular weights in rats with infarcts of different sizes. Dilatation of the left ventricle was not affected significantl y, most because of the reduction in thickness of the spared left ventr icular myocardium. This explains, at least in part, previous reports o n the lack of efficacy of early treatment of infarction with convertin g enzyme inhibitors. The absence of detectable changes with the nitrat e seems to be dependent upon the lack of a consistent hemodynamic effe ct of this compound.