Antifibrillatory actions of d,l-nadolol in a conscious canine model of sudden coronary death.
The role of beta-adrenergic receptor blockade in preventing ventricular fibrillation in a conscious canine model of sudden coronary death was examined using d,l-nadolol and the non-beta-adrenergic receptor blocking isomer, d-nadolol. On day 4, after a temporary 90-min occlusion of the left anterior descending coronary artery, an anodal current of 150 microA was applied to the intimal surface of the left circumflex coronary artery. Occlusive or nonocclusive thrombosis of the artery was accompanied by ST-segment changes. In saline-treated animals (n = 15), ST-segment changes were followed by sinus tachycardia and QT-segment prolongation, with development of ventricular premature beats. Ventricular fibrillation developed in 14 animals (93%). Pretreatment with 1 (n = 9) or 8 mg/kg d,l-nadolol (n = 13) did not alter the development of left circumflex coronary artery thrombosis and ischemic ST-segment changes, but decreased the incidence of ventricular fibrillation and increased survival at 24 h (56% and 63%, respectively) (p less than 0.01 versus saline). d,l-Nadolol also attenuated the sinus tachycardia and QT-interval prolongation accompanying acute ischemia. d-Nadolol (1 mg/kg), the non-beta-adrenergic receptor blocking isomer, failed to prevent development of ST-segment changes. Sinus tachycardia and QT-interval prolongation were not prevented, and ventricular fibrillation developed in all eight animals (100%). In animals without previously induced anterior myocardial ischemic injury (n = 10), left circumflex coronary artery thrombosis failed to produce sinus tachycardia and QT-interval prolongation and was associated with a lower incidence of ventricular fibrillation (20%, p less than 0.005).(ABSTRACT TRUNCATED AT 250 WORDS)
D000319:Adrenergic beta-Antagonists / Q000627:therapeutic use*; D000818:Animals; D000959:Antihypertensive Agents / Q000627:therapeutic use*; D004285:Dogs; D004558:Electric Stimulation; D006339:Heart Rate; D007536:Isomerism; D008297:Male; D009203:Myocardial Infarction / Q000473:pathology; D009248:Nadolol; D011412:Propanolamines / Q000627:therapeutic use*; D014693:Ventricular Fibrillation / Q000188:drug therapy / Q000503:physiopathology*
D000319:Adrenergic beta-Antagonists; D000959:Antihypertensive Agents; D011412:Propanolamines; D009248:Nadolol