Long-term effects of carvedilol on left ventricular function, remodeling, and expression of cardiac cytokines after large myocardial infarction in the rat.
Carvedilol (20 mg/kg, bid) or vehicle was given to rats surviving a myocardial infarction (MI) 24 h (n = 409). In rats with large MI, carvedilol partially preserved left ventricular (LV) function and intrinsic myocardial contractility and reactivity to beta-adrenergic stimulation. Carvedilol led to scar thickening, increased LV hypertrophy, and decreased cardiac fibrosis but did not prevent LV dilatation. Carvedilol reduced cardiac expression of interleukin-1beta but did not prevent cardiac fetal gene re-expression or modify cardiac oxidative stress. Despite these beneficial effects, carvedilol decreased survival (38.8%, versus vehicle, 50.6%) due to excessive early mortality. Thus, post-MI carvedilol has many beneficial effects, however, in this study it increased post-MI mortality, perhaps due to excessive hypotension.
Sia
Ying Tung
YT
Department of Medicine, Montreal Heart Institute, Montreal, Quebec, Canada.
Parker
Thomas G
TG
Tsoporis
James N
JN
Liu
Peter
P
Adam
Albert
A
Rouleau
Jean L
JL
D000319:Adrenergic beta-Antagonists / Q000494:pharmacology*; D000818:Animals; D002227:Carbazoles / Q000494:pharmacology*; D000077261:Carvedilol; D016207:Cytokines / Q000187:drug effects* / Q000378:metabolism; D005355:Fibrosis; D008401:Gas Chromatography-Mass Spectrometry; D006439:Hemodynamics / Q000187:drug effects; D066298:In Vitro Techniques; D008297:Male; D009200:Myocardial Contraction / Q000187:drug effects; D009203:Myocardial Infarction / Q000378:metabolism* / Q000401:mortality / Q000503:physiopathology*; D009206:Myocardium / Q000473:pathology; D023282:Nuclease Protection Assays; D018384:Oxidative Stress / Q000187:drug effects; D010210:Papillary Muscles / Q000187:drug effects; D011412:Propanolamines / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D016277:Ventricular Function, Left / Q000187:drug effects*; D020257:Ventricular Remodeling / Q000187:drug effects*
D000319:Adrenergic beta-Antagonists; D002227:Carbazoles; D016207:Cytokines; D011412:Propanolamines; D000077261:Carvedilol