title: 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).
  
  
  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 beta-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 beta-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 beta blockade on ischemic cardiac dysfunction seem to depend on the different properties of the beta-blockers and the doses used. Among the beta-blockers tested, carvedilol provided potent cardioprotection for compromised ischemic but viable myocardium rather than for infarcted myocardium.
authors.affiliation: First Department of Internal Medicine, Fukushima Medical University, Fukushima, Japan.
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Yaoita
authors.forename: Atsushi
authors.initials: A
authors.lastname: Sakabe
authors.forename: Kazuhira
authors.initials: K
authors.lastname: Maehara
authors.forename: Yukio
authors.initials: Y
authors.lastname: Maruyama
mesh_terms: D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology; D000319:Adrenergic beta-Antagonists / Q000494:pharmacology; D000818:Animals; D001205:Ascorbic Acid / Q000097:blood; D002227:Carbazoles / Q000494:pharmacology*; D006328:Cardiac Catheterization; D000077261:Carvedilol; D003327:Coronary Disease / Q000503:physiopathology*; D023921:Coronary Stenosis / Q000503:physiopathology*; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004452:Echocardiography; D006439:Hemodynamics / Q000187:drug effects; D008297:Male; D008790:Metoprolol / Q000494:pharmacology*; D009638:Norepinephrine / Q000097:blood; D011412:Propanolamines / Q000494:pharmacology*; D011433:Propranolol / Q000494:pharmacology*; D011799:Quinazolines / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D012720:Severity of Illness Index; D013318:Stroke Volume / Q000187:drug effects; D015996:Survival Rate; D017392:Thiobarbituric Acid Reactive Substances / Q000032:analysis; D016277:Ventricular Function, Left / Q000187:drug effects; D020257:Ventricular Remodeling / Q000187:drug effects*
chemical_list: D000317:Adrenergic alpha-Antagonists; D000319:Adrenergic beta-Antagonists; D002227:Carbazoles; D011412:Propanolamines; D011799:Quinazolines; D017392:Thiobarbituric Acid Reactive Substances; D000077261:Carvedilol; C018176:bunazosin; D011433:Propranolol; D008790:Metoprolol; D001205:Ascorbic Acid; D009638:Norepinephrine