Cardioprotective effects of hydrolyzed bopindolol against contractile dysfunction produced by coronary stenosis and reperfusion in dogs.
The effects of the active metabolite (18-502) of bopindolol, which is a new nonselective beta-adrenoceptor antagonist, were studied on the ischemic changes in myocardial segment shortening, cardiac lactate metabolism and S-T segment of subendocardial electrocardiogram during coronary stenosis and on their recoveries after reperfusion in anesthetized dogs, and were compared with those of propranolol at a dose exhibiting a comparable degree of beta 1-blocking activity. In the presence of coronary stenosis, intravenous administration of 18-502 (5 micrograms/kg) and propranolol (0.2 mg/kg), but not saline, produced significant improvements of regional myocardial dysfunction, lactate production and S-T segment elevations in the ischemic myocardium, which were associated with significant decreases in heart rate and cardiac contractility. After release of the stenosis, administration of 18-502, but not propranolol, resulted in a significantly accelerated recovery of the ischemic segment function as compared with the control group. In rat heart homogenates, 18-502 inhibited the lipid peroxidation approximately 4 times more potently than propranolol. These data show that 18-502 exerts favorable effects during myocardial ischemia produced by coronary stenosis and that it has a cardioprotective action against the contractile dysfunction following reperfusion.
Department of Pharmacology, School of Medicine, University of the Ryukyus, Okinawa, Japan.
K
K
Noguchi
Y
Y
Aniya
Y
Y
Ojiri
T
T
Chibana
T
T
Matsuzaki
N
N
Shiroma
K F
KF
Fong
M
M
Uza
M
M
Sakanashi
D000319:Adrenergic beta-Antagonists / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D003326:Coronary Circulation / Q000187:drug effects; D003327:Coronary Disease / Q000188:drug therapy*; D004195:Disease Models, Animal; D004285:Dogs; D004562:Electrocardiography / Q000187:drug effects; D005260:Female; D006321:Heart / Q000187:drug effects; D006339:Heart Rate / Q000187:drug effects; D006868:Hydrolysis; D066298:In Vitro Techniques; D007275:Injections, Intravenous; D007773:Lactates / Q000378:metabolism; D019344:Lactic Acid; D015227:Lipid Peroxidation / Q000187:drug effects; D008297:Male; D009200:Myocardial Contraction / Q000187:drug effects; D015428:Myocardial Reperfusion Injury / Q000188:drug therapy*; D009206:Myocardium / Q000378:metabolism; D010869:Pindolol / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use; D011433:Propranolol / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use; D051381:Rats; D017207:Rats, Sprague-Dawley
D000319:Adrenergic beta-Antagonists; D007773:Lactates; C038186:4-(2-hydroxy-3-tert-butylaminopropoxy)-2-methylindole; D019344:Lactic Acid; D011433:Propranolol; D010869:Pindolol