Reproducible and uniform cardiac ischemia: effects of antiarrhythmic drugs.
The in vivo response of cardiac tissue to ischemia is inherently nonuniform, and as a result the drug effects in the latter are subject to great variability. We therefore designed a preparation that could reproducibly respond to uniform ischemia: Langendorff-perfused rabbit hearts in which ischemia was induced by stopping the perfusion. In this preparation therapeutic concentrations of antiarrhythmic drugs have no-to-moderate effects on conduction and excitability of perfused tissue, while markedly depressing these parameters in ischemic tissue. This selectivity for depression of ischemic tissue increases as the ischemia progresses. Antiarrhythmic drugs can in this way markedly attenuate the abnormal electrical activity of the ischemic tissue (responsible for arrhythmias) while minimally affecting this activity in normal tissue.
D000818:Animals; D000889:Anti-Arrhythmia Agents / Q000494:pharmacology* / Q000627:therapeutic use; D003327:Coronary Disease / Q000188:drug therapy / Q000503:physiopathology*; D004305:Dose-Response Relationship, Drug; D004553:Electric Conductivity; D004562:Electrocardiography; D009200:Myocardial Contraction / Q000187:drug effects*; D011817:Rabbits; D013997:Time Factors
D000889:Anti-Arrhythmia Agents