ACE-INHIBITION DECREASES POSTOPERATIVE MORTALITY IN RATS WITH LEFT-VENTRICULAR HYPERTROPHY AND MYOCARDIAL-INFARCTION

In male Sprague Dawley rats with left ventricular hypertrophy (LVH) an d hypertension induced by aortic constriction (AC) and subsequent myoc ardial infarction (MI) by occlusion of the left coronary artery the ef fects of ACE inhibition with ramipril (RA 1 mg/kg/day via the drinking water during 6 weeks) on survival as well as cardiac function and met abolism were investigated. Respective groups (sham AC; AC; AC + sham M I; normotensive animals with sham MI; MI; MI + RA) served as compariso ns. Following MI hypertensive rats with AC and LVH revealed an increas ed postoperative mortality (68%) when compared to normotensives withou t AC (28%). ACE inhibition with ramipril significantly reduced mortali ty in hypertensive rats by 26%. Untreated hypertensive animals with LV H clearly showed reduced MI size (6.2 +/- 2.3 %) in comparison with un treated normotensive animals and MI(31.0 +/- 3.3 %). In hypertensive r ats with MI which died during the study a significant increase in infa rct Size was found compared to those which survived MI. In normotensiv e animals ramipril reduced infarct size by 50%. Due to the quite small infarct size observed in hypertensive rats, ACE inhibition did not fu rther reduce MI in these animals. LVH as well as hydroxyproline/prolin e ratio was diminished by ACE inhibitor treatment. In the isolated hea rts of ramipril treated rats contractility was improved when compared to the respective untreated groups with MI. In the coronary effluent o f isolated hearts from rats with AC and MI lactate dehydrogenase and c reatine kinase activities as well as lactate levels were increased. Ra mipril treatment starting one week before MI normalized these paramete rs and in addition increased prostacyclin output. Hearts with MI from treated normotensive animals contained increased energy rich phosphate s when compared to hearts from untreated rats with MI. Conclusions: Hy pertensive rats with LVH undergoing MI experienced increased postopera tive mortality probably due to a reduced tolerance to myocardiac ische mia and occurrence of arrhythmias. In these animals ACE inhibition wit h ramipril increased survival. Both, increased survival in hypertensiv e and reduction in infarct size in normotensive rats by ACE inhibition with ramipril was accompanied by an improved myocardial metabolism.