Different Effects of Carvedilol, Metoprolol, and Propranolol on Left Ventricular Remodeling After Coronary Stenosis or After Permanent Coronary Occlusion in Rats

Abstract

Background — Although carvedilol attenuates left ventricular (LV) remodeling in coronary occlusion-reperfusion, it is not known whether it attenuates ischemic LV remodeling because of coronary stenosis (CS) or permanent coronary occlusion (CO). Methods and Results — We administered a vehicle, carvedilol, propranolol (2, 10, and 30 mg/kg per day, each), metoprolol (6, 30, and 90 mg/kg per day), or bunazosin (0.2 and 1 mg/kg per day), orally for 12 weeks to a total of 608 rats with CS or CO. In these groups and the sham (n=40), we assessed LV function by echocardiography, CS severity, myocardial blood flow and coronary flow reserve, serum ascorbyl free radical, and vitamin C. Both CS and CO increased LV end-diastolic and end-systolic diameters and decreased ejection fraction. The 4 agents failed to attenuate LV remodeling caused by CO. In contrast, the 3 β-blockers attenuated ( P <0.01) or tended to attenuate the increase in LV end-diastolic diameters caused by CS. With similar blood pressure and heart rate lowering by 3 β-blockers, carvedilol additionally attenuated the increase in end-systolic diameters and improved ejection fraction. The CS reduced myocardial blood flow and coronary flow reserve, which was reversed by carvedilol without modifying the CS severity. Among the 4 agents, only carvedilol decreased ascorbyl free radical and increased vitamin C. Conclusions — The effects of β blockade on ischemic cardiac dysfunction seem to depend on the different properties of the β-blockers and the doses used. Among the β-blockers tested, carvedilol provided potent cardioprotection for compromised ischemic but viable myocardium rather than for infarcted myocardium.