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 (nϭ40), 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 ␤-blockers attenuated (PϽ0.01) or tended to attenuate the increase in LV end-diastolic diameters caused by CS. With similar blood pressure and heart rate lowering by 3 ␤-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 ␤ blockade on ischemic cardiac dysfunction seem to depend on the different properties of the ␤-blockers and the doses used. Among the ␤-blockers tested, carvedilol provided potent cardioprotection for compromised ischemic but viable myocardium rather than for infarcted myocardium.

Is overall blockade superior to selective blockade of adrenergic receptor subtypes in suppressing left ventricular remodeling in spontaneously hypertensive rats?

“…6 As the purpose of this study was to compare the efficacy of different AR antagonists in suppressing LV remodeling secondary to hypertension, the prerequisite for a chosen drug is to lower blood pressure to a normal level. The drug doses were determined by referring to previous studies on animal models of LV remodeling [7][8][9][10] and by a preliminary study in which the drug doses were increased gradually from a low dose until the systolic blood pressure (SBP) in each drug-treated group reached the level of SBP as that of WKY rats. Our preliminary results showed that bisoprolol, propranolol and carvedilol at a dose of 2 mg kg À1 per day, 6 mg kg À1 per day and 6 mg/kg/day, respectively, were effective in normalizing SBP in SHR and thus, these doses were finally chosen for comparing the therapeutic effects of bisoprolol, propranolol and carvedilol in suppressing LV remodeling in SHR.…”

The Effects of Nebivolol on Apoptosis in a Rat Infarct Model

“…38 In contrast, Yaoita et al explain the attenuation of LV remodeling with propranolol and metoprolol by reduction of heart rate and systolic blood pressure. 41 Furthermore, Zhu et al have showed that in a rat model ischemia/reperfusion injury, metoprolol produced cardioprotection via hemodynamic effects. 42 More recently, Omerovic et al suggest that metoprolol attenuates post-infarct structural remodeling, without concomitant improvement in myocardial energy metabolism and function in rats with chronic congestive heart failure, 43 but authors could not completely explain which effect is responsible from this improvement.…”

Electrophysiological Effects of Carvedilol on Rabbit Heart Pacemaker Cells

“…18) Since supraventricular tachyarrhythmias leading to atrial fibrillation can affect cardiac function, carvedilol's effect on I K and I Ca observed in our study, at least in part, may be responsible for the good prognosis in various clinical trials. Of course, carvedilol has a number of ancillary activities, including antioxidant, anti-inflammatory, and antiapoptotic properties in addition to the well-known properties, [2][3]5) and hence, some unknown antiarrhythmic activities might exist. Further studies will be required to elucidate these points.…”

“…In addition to its nonselective β-adrenergic blocking effect, it also has α 1 adrenergic blocking actions, 1) antioxidant properties, 2,3) Ca 2+ blocking effects, 4) and inhibitory effects on cardiac remodeling and myocyte apoptosis. [5][6][7] Recently, this agent has attracted increasing attention among cardiologists following positive outcomes in various clinical trials.…”