Origin of acetyl strophanthidin-induced ventricular arrhythmias.
To examine the origin of digitalis-induced ventricular tachycardia (VT), acetyl strophanthidin (AS) (25 mug/min) was perfused into a limited zone of myocardium in intact anesthetized dogs through a catheter placed fluoroscopically in the left anterior descending artery without ischemia. A second catheter in the great cardiac vein sampled venous effluent from this region. His and left bundle branch depolarizations were recorded and bipolar intramural electrograms from endocardial and epicardial sites within the anterior descending region were obtained. No conduction alterations preceded arrhythmia. Cardiac venous K+ rose from 3.3 +/- to 4.4 +/- 0.2 meq/liter (P less than 0.001), indicating egress from the perfused zone. 10 animals (Group 1) were sacrificed 2 min after onset of VT while 11 (Group 2) continued until fibrillation (4-14 min). All showed normal (endocardial leads to epicardial) transmural depolarization during sinus rhythm, but 10/21 demonstrated reversal, usually late during VT, including 8/11 in Group 2. Epicardial activation preceded fascicular activation and QRS. Recordings from the border and circumflex regions in 10 additional dogs (Group 3) demonstrated activation reversal only in the border zone. Myocardial K+ was reduced (mean 63 +/- 1 mueq/g) and Na+ increased (mean 41 +/- 2 mueq/g) in the perfused zone (nonperfused circumflex area K+ 72 +/- 1, Na+ 33 +/- 1 mueq/g, P less than 0.001 for both); changes were similar in inner and outer ventricular wall. In related experiments, subepicardial injections of AS induced activation reversal within the immediate area, similar to recordings during coronary infusion. Reversed transmural activation with early epicardial depolarization suggest VT arises within myocardium; electrolyte gradients between adjacent regions may be causative.
D000818:Animals; D004285:Dogs; D004562:Electrocardiography; D006321:Heart / Q000187:drug effects; D006329:Heart Conduction System / Q000187:drug effects* / Q000503:physiopathology; D008297:Male; D011690:Purkinje Fibers / Q000502:physiology; D013327:Strophanthidin / Q000031:analogs & derivatives* / Q000494:pharmacology; D013610:Tachycardia / Q000139:chemically induced* / Q000503:physiopathology; D014882:Water-Electrolyte Balance
D013327:Strophanthidin