Oxygen radical system in chronic infarcted rat heart: The effect of combined beta blockade and ACE inhibition

In vitro experiments suggest that beta blockade and angiotensin-converting enzyme (ACE) inhibition may protect the failing heart by reduction of myoca rdial oxidative stress. To test this hypothesis in an in vivo model, the be ta blocker metoprolol (350 mg) and the ACE inhibitor ramipril (I mg) were , given either alone or in combination to rats (per kilogram body weight per day) for 6 weeks after myocardial infarction. Left ventricular end-diastoli c pressure (LVEDP), contractile function of papillary muscles, enzymatic an tioxidative defense (indicated by the activities of the superoxide dismutas e isoenzymes and glutathione peroxidase), and the extent of lipid peroxidat ion were studied, placebo-treated rats showed cardiac hypertrophy. increase d LVEDP, lower rates of contraction and relaxation, as well as a deficit in the myocardial antioxidative defense associated with increased lipid perox ide levels, when compared with sham-operated animals. Combined beta blockad e and ACE inhibition improved the antioxidative defense, reduced hypertroph y and LVEDP, and enhanced rates of contraction. Thus prolonged beta blockad e and ACE inhibition after infarction may decrease myocardial oxidative str ess and thereby could be beneficial in heart failure.