ALTERATION OF VENTRICULAR-FIBRILLATION BY PROPRANOLOL AND ISOPROTERENOL DETECTED BY EPICARDIAL MAPPING WITH 506 ELECTRODES

Introduction: We hypothesized that drugs which alter ventricular refra ctoriness or excitability produce quantifiable changes in ventricular fibrillation. Methods and Results: We used a 528-channel mapping syste m to quantify the effects of the beta-antagonist, propranolol, and the beta-agonist, isoproterenol, on activation patterns in ventricular fi brillation. A plaque of 506 (22 x 23) electrodes spaced 1.12 mm apart and covering about 5% of the ventricular epicardium was sewn to the an terior right ventricle in 18 pigs (30 kg). Propranolol (0.25 to 0.4 mg /kg) increased the refractory period at a right ventricular epicardial site while isoproterenol (3 to 5 mu g/min) shortened it. Ventricular fibrillation was induced by programmed stimulation, and unipolar elect rograms were recorded from the 506 plaque electrodes for 2 seconds beg inning 1, 15, and 30 seconds after the onset of fibrillation. Active e picardial recording sites were identified from the first derivative of the unipolar potentials (dV/dt) detected at each electrode. Then, nei ghboring active sites were grouped into activation fronts by computer analysis. In six pigs the effect of repeated inductions of ventricular fibrillation was assessed by comparing ventricular fibrillation after saline with a preceding control episode of fibrillation. Each activat ion front excited 40% +/- 46% of the mapped region before blocking. No changes were observed with saline and multiple inductions of fibrilla tion. In another six pigs, ventricular fibrillation after propranolol was compared with a preceding control episode of fibrillation. Ventric ular fibrillation after propranolol exhibited a decreased activation r ate per epicardial recording site and fewer activation fronts per seco nd. There was no change in the amount of tissue excited by each activa tion front or the number of reentry cycles per activation front compar ed with control. In addition, there was no change in the maximum negat ive dV/dt detected per activation at an epicardial site. In six pigs v entricular fibrillation during isoproterenol was compared with control episodes of ventricular fibrillation before and 45 minutes after wash out of the drug. The control episodes of fibrillation were not differe nt from each other. Compared with control, ventricular fibrillation du ring isoproterenol exhibited an increased activation rate per epicardi al site, an increased amount of tissue excited by each activation fron t, and an increased maximum negative dV/dt for each activation. There nas no change in the number of activation fronts per second or the num ber of reentry cycles per activation front compared with control. Conc lusions: Quantitative analysis revealed that propranolol and isoproter enol do not have symmetrically opposite effects on ventricular fibrill ation. Propranolol decreased the number of activation fronts while iso proterenol increased the amount of tissue excited by each activation f ront. Thus, drugs that alter ventricular refractoriness or excitabilit y alter ventricular fibrillation.