ACE inhibition decreases postoperative mortality in rats with left ventricular hypertrophy and myocardial infarction.
In male Sprague Dawley rats with left ventricular hypertrophy (LVH) and hypertension induced by aortic constriction (AC) and subsequent myocardial infarction (MI) by occlusion of the left coronary artery the effects 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 metabolism were investigated. Respective groups (sham AC; AC; AC + sham MI; normotensive animals with sham MI; MI; MI + RA) served as comparisons. Following MI hypertensive rats with AC and LVH revealed an increased postoperative mortality (68%) when compared to normotensives without AC (28%). ACE inhibition with ramipril significantly reduced mortality in hypertensive rats by 26%. Untreated hypertensive animals with LVH clearly showed reduced MI size (6.2 +/- 2.3%) in comparison with untreated normotensive animals and MI (31.0 +/- 3.3%). In hypertensive rats with MI which died during the study a significant increase in infarct size was found compared to those which survived MI. In normotensive animals ramipril reduced infarct size by 50%. Due to the quite small infarct size observed in hypertensive rats, ACE inhibition did not further reduce MI in these animals. LVH as well as hydroxyproline/proline ratio was diminished by ACE inhibitor treatment. In the isolated hearts of ramipril treated rats contractility was improved when compared to the respective untreated groups with MI. In the coronary effluent of isolated hearts from rats with AC and MI lactate dehydrogenase and creatine kinase activities as well as lactate levels were increased. Ramipril treatment starting one week before MI normalized these parameters and in addition increased prostacyclin output. Hearts with MI from treated normotensive animals contained increased energy rich phosphates when compared to hearts from untreated rats with MI.


CONCLUSIONS
Hypertensive rats with LVH undergoing MI experience increased postoperative mortality probably due to a reduced tolerance to myocardial ischemia and occurrence of arrhythmias. In these animals ACE inhibition with ramipril increased survival. Both, increased survival in hypertensive and reduction in infarct size in normotensive rats by ACE inhibition with ramipril was accompanied by an improved myocardial metabolism.
Linz
W
W
Hoechst-Marion-Roussel, TD Cardiovascular Agents, Frankfurt/Main, Germany.
Wiemer
G
G
Schmidts
H L
HL
Ulmer
W
W
Ruppert
D
D
Schölkens
B A
BA
D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology*; D000818:Animals; D001011:Aorta; D001794:Blood Pressure; D003251:Constriction, Pathologic; D003331:Coronary Vessels; D006321:Heart / Q000503:physiopathology; D006973:Hypertension / Q000150:complications; D017379:Hypertrophy, Left Ventricular / Q000378:metabolism / Q000401:mortality* / Q000503:physiopathology; D008297:Male; D009203:Myocardial Infarction / Q000378:metabolism / Q000401:mortality* / Q000503:physiopathology; D009206:Myocardium / Q000378:metabolism; D011184:Postoperative Period; D017257:Ramipril / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012016:Reference Values; D016019:Survival Analysis
D000806:Angiotensin-Converting Enzyme Inhibitors; D017257:Ramipril