Combined treatment with ramipril and metoprolol prevents changes in the creatine kinase isoenzyme system and improves hemodynamic function in rat hearts after myocardial infarction

Beneficial effects of monotherapy with ACE inhibitors or beta-blockers on h emodynamic function after myocardial infarction are well known. Until now t he effects of combined treatment on cardiac function and energy metabolism have been poorly described. This study examines the effects of combined ram ipril and metoprolol treatment on the creatine kinase (CK) system and hemod ynamic function in rats after infarction. Wistar rats with experimental inf arction were randomized for treatment with ramipril (R), metoprolol (M), co mbined treatment (MR), or placebo (P). Sham-operated (SO) animals served as controls. After 6 weeks, we assayed for CK isoenzymes and performed hemody namic measurements. In P versus SO, left ventricular systolic pressures (dp /dt(max) and dp/dt(min)) diminished, whereas left ventricular end-diastolic pressure (LVEDP) increased. Decreased total CK activity and mitochondrial CK isoenzyme, increased CK-MB, and increased CK-BB isoenzymes were measured in P versus SO. With infarct size less than or equal to 45%, mitochondrial CK increased in M and R versus P. Combined treatment had an additional enh ancing effect on mitochondrial CK isoenzyme level versus M. and R, decrease d LVEDP versus P, as well as increased dp/dt(max) and dp/dt(min) versus R. These results provide evidence of an interaction between normalization of e nergy metabolism and improvement in cardiac function due to a combination o f ACE inhibition and beta blockade after myocardial infarction.