Comparison of bisoprolol and carvedilol cardioprotection in a rabbit ischemia and reperfusion model.
Carvedilol, a selective alpha(1) and non-selective beta-adrenoceptor antagonist and antioxidant, has been shown to provide significant cardiac protection in animal models of myocardial ischemia. To further explore the mechanisms contributing to the efficacy of carvedilol cardioprotection, the effects of carvedilol on hemodynamic variables, infarct size and myeloperoxidase activity (an index of neutrophil accumulation) were compared with a beta(1) selective adrenoceptor antagonist, bisoprolol. Carvedilol (1 mg/kg) or bisoprolol (1 mg/kg) was given intravenously 5 min before reperfusion. In vehicle-treated rabbits, ischemia (45 min) and reperfusion (240 min) resulted in significant increases in left ventricular end diastolic pressure, large myocardial infarction (64.7+/-2.6% of area-at-risk) and a marked increase in myeloperoxidase activity (64+/-14 U/g protein in area-at-risk). Carvedilol treatment resulted in sustained reduction of the pressure-rate-index and significantly smaller infarcts (30+/-2.9, P<0.01 vs. vehicle) as well as decreased myeloperoxidase activity (26+/-11 U/g protein in area-at-risk, P<0.01 vs. vehicle). Administration of bisoprolol at 1 mg/kg resulted in a pressure-rate-index comparable to that of carvedilol and also decreased infarct size (48.4+/-2.5%, P<0.001 vs. vehicle, P<0.05 vs. carvedilol), although to a significantly lesser extent than that observed with carvedilol. Treatment with bisoprolol failed to reduce myeloperoxidase activity in the ischemic myocardial tissue. In addition, carvedilol, but not bisoprolol, markedly decreased cardiac membrane lipid peroxidation measured by thiobarbituric acid formation. Taken together, this study suggests that the superior cardioprotection of carvedilol over bisoprolol is possibly the result of carvedilol's antioxidant and anti-neutrophil effects, not its hemodynamic properties.
Gao
F
F
Department of Emergency Medicine, Jefferson Medical College, Thomas Jefferson University, 1020 Sansom Street, Philadelphia, PA 19107-5004, USA.
Chen
J
J
Lopez
B L
BL
Christopher
T A
TA
Gu
J
J
Lysko
P
P
Ruffolo
R R
RR
Ohlstein
E H
EH
Ma
X L
XL
Yue
T L
TL
D000318:Adrenergic beta-Agonists / Q000494:pharmacology; D000319:Adrenergic beta-Antagonists / Q000494:pharmacology*; D000818:Animals; D000975:Antioxidants / Q000494:pharmacology; D017298:Bisoprolol / Q000494:pharmacology*; D002227:Carbazoles / Q000494:pharmacology*; D002317:Cardiovascular Agents / Q000494:pharmacology*; D000077261:Carvedilol; D003402:Creatine Kinase / Q000097:blood / Q000187:drug effects; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D006339:Heart Rate / Q000187:drug effects; D007545:Isoproterenol / Q000494:pharmacology; D015227:Lipid Peroxidation / Q000187:drug effects; D008297:Male; D008563:Membrane Lipids / Q000378:metabolism; D017202:Myocardial Ischemia / Q000150:complications / Q000473:pathology / Q000517:prevention & control; D009206:Myocardium / Q000201:enzymology / Q000473:pathology; D009195:Peroxidase / Q000187:drug effects / Q000378:metabolism; D011412:Propanolamines / Q000494:pharmacology*; D011817:Rabbits; D015427:Reperfusion Injury / Q000503:physiopathology / Q000517:prevention & control*; D017725:Ventricular Pressure / Q000187:drug effects
D000318:Adrenergic beta-Agonists; D000319:Adrenergic beta-Antagonists; D000975:Antioxidants; D002227:Carbazoles; D002317:Cardiovascular Agents; D008563:Membrane Lipids; D011412:Propanolamines; D000077261:Carvedilol; C086740:SB 211475; D009195:Peroxidase; D003402:Creatine Kinase; D007545:Isoproterenol; D017298:Bisoprolol