Reduction in digitalis-associated postinfarction mortality with nadolol in conscious dogs.
Previously, we have demonstrated an increased incidence of lethal ischemic arrhythmias in postinfarction dogs with clinically observable serum digoxin concentrations, and a significant reduction in digitalis-related lethal ischemic arrhythmias after subacute left stellectomy. In the present study, the protective actions of acute beta-adrenoceptor blockade with nadolol, 1.0 mg/kg administered intravenously immediately preceding the induction of posterolateral myocardial ischemia, were assessed in conscious dogs with recent, small anterior myocardial infarctions pretreated with digoxin, 0.0125 mg/kg/day intravenously, for 5 to 7 consecutive days (total n = 11). A cohort of postinfarction dogs pretreated with digoxin alone served as a control group (total n = 26). Pre vs postdigoxin electrophysiologic testing indicated reductions in myocardial refractoriness in ventricular noninfarct and infarct zones in both treatment groups, whereas the administration of nadolol tended to reverse the reductions in ventricular refractoriness. Arrhythmia-related deaths in response to posterolateral myocardial ischemia were reduced from 12 of 20 (60%) in the digoxin control group to 2 of 10 (20%) in the digoxin + nadolol group (p = 0.039). Serum digoxin concentrations (1.29 +/- 0.14 ng/ml vs 1.39 +/- 0.24 ng/ml), underlying anterior myocardial infarct size (6.9 +/- 1.5% vs 4.6 +/- 0.9% of left ventricle), and developing posterolateral myocardial infarct size (22.8 +/- 2.5% vs 17.5 +/- 3.6% of left ventricle) did not differ significantly between the digoxin and digoxin + nadolol groups. Acute beta-adrenoceptor blockade with nadolol appears to reduce digitalis-mediated ischemic postinfarction mortality, possibly because of a salutary increase in ventricular refractoriness.
Lynch
J J
JJ
Department of Pharmacology, University of Michigan Medical School, Ann Arbor 48109-0010.
Kitzen
J M
JM
Hoff
P T
PT
Lucchesi
B R
BR
D000818:Animals; D001145:Arrhythmias, Cardiac / Q000188:drug therapy* / Q000503:physiopathology; D002304:Cardiac Pacing, Artificial; D004070:Digitalis; D004077:Digoxin / Q000008:administration & dosage* / Q000097:blood; D004285:Dogs; D004334:Drug Administration Schedule; D004558:Electric Stimulation; D004562:Electrocardiography; D004594:Electrophysiology; D009203:Myocardial Infarction / Q000188:drug therapy* / Q000503:physiopathology; D009248:Nadolol / Q000008:administration & dosage* / Q000097:blood; D010946:Plants, Medicinal; D010947:Plants, Toxic
D009248:Nadolol; D004077:Digoxin