Cardioprotective and antiarrhythmic effects of beta-blockers, propranolol, bisoprolol, and nipradilol in a canine model of regional ischemia.
Cardioprotective and antiarrhythmic effects of three beta-blockers with different pharmacological properties were investigated in 33 anesthetized dogs with a 2-h coronary occlusion. Dogs were divided into 4 groups and received physiological saline or one of the following drugs using a 10-min infusion at 25 min before the occlusion: saline or control (n = 12), propranolol (0.3 mg/kg, n = 7), bisoprolol (0.05 mg/kg, n = 7), and nipradilol (0.2 mg/kg, n = 7) groups. Blood pressure did not significantly differ among the 4 experimental groups throughout the entire observation period. On the contrary, the postocclusion change (fall) in heart rate from the preocclusion value was significantly (P less than 0.05-0.01) greater in the drug-treated groups than in the control group. Each of the beta-blockers effectively prevented the development of ventricular arrhythmias associated with the 2-h coronary occlusion. In terms of assessing a cardioprotective effect, the respiratory control index and rate of oxygen consumption in State III in mitochondria, and lysosomal enzyme activities (N-acetyl-beta-glucosaminidase or beta-glucuronidase) in myocardial tissues, all prepared from both ischemic and non-ischemic areas, were measured using the respective, established methods. The 2-h coronary occlusion induced a mitochondrial dysfunction and leakage of lysosomal enzymes in the control group, whereas each beta-blocker significantly (P less than 0.05-0.01) protected mitochondria against ischemia and prevented the lysosomal enzyme leakage. The results indicate that the antiarrhythmic effects of beta-blockers on ischemic myocardium are, at least in part, due to their cardioprotective action, and these effects appear to be unrelated to the ancillary pharmacological properties of these drugs.
Ogawa
T
T
Department of Internal Medicine, Faculty of Medicine, University of Nagoya, Japan.
Hieda
N
N
Sugiyama
S
S
Ito
T
T
Satake
T
T
Ozawa
T
T
D000118:Acetylglucosaminidase / Q000378:metabolism; D000319:Adrenergic beta-Antagonists / Q000494:pharmacology*; D000818:Animals; D001145:Arrhythmias, Cardiac / Q000503:physiopathology*; D017298:Bisoprolol; D003326:Coronary Circulation / Q000187:drug effects*; D003327:Coronary Disease / Q000503:physiopathology*; D004285:Dogs; D005260:Female; D005966:Glucuronidase / Q000378:metabolism; D006333:Heart Failure / Q000503:physiopathology; D006339:Heart Rate / Q000187:drug effects*; D008247:Lysosomes / Q000187:drug effects; D008297:Male; D008929:Mitochondria, Heart / Q000187:drug effects; D009200:Myocardial Contraction / Q000187:drug effects; D009203:Myocardial Infarction / Q000503:physiopathology; D011412:Propanolamines / Q000494:pharmacology*; D011433:Propranolol / Q000494:pharmacology*; D014693:Ventricular Fibrillation / Q000503:physiopathology
D000319:Adrenergic beta-Antagonists; D011412:Propanolamines; D011433:Propranolol; D005966:Glucuronidase; D000118:Acetylglucosaminidase; C036089:nipradilol; D017298:Bisoprolol