Alteration of ventricular fibrillation by propranolol and isoproterenol detected by epicardial mapping with 506 electrodes.
We hypothesized that drugs which alter ventricular refractoriness or excitability produce quantifiable changes in ventricular fibrillation.
Methods and results
We used a 528-channel mapping system to quantify the effects of the beta-antagonist, propranolol, and the beta-agonist, isoproterenol, on activation patterns in ventricular fibrillation. 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 anterior 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 micrograms/min) shortened it. Ventricular fibrillation was induced by programmed stimulation, and unipolar electrograms were recorded from the 506 plaque electrodes for 2 seconds beginning 1, 15, and 30 seconds after the onset of fibrillation. Active epicardial recording sites were identified from the first derivative of the unipolar potentials (dV/dt) detected at each electrode. Then, neighboring 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 activation front excited 40% +/- 46% of the mapped region before blocking. No changes were observed with saline and multiple inductions of fibrillation. In another six pigs, ventricular fibrillation after propranolol was compared with a preceding control episode of fibrillation. Ventricular fibrillation after propranolol exhibited a decreased activation rate per epicardial recording site and fewer activation fronts per second. There was no change in the amount of tissue excited by each activation front or the number of reentry cycles per activation front compared with control. In addition, there was no change in the maximum negative dV/dt detected per activation at an epicardial site. In six pigs ventricular fibrillation during isoproterenol was compared with control episodes of ventricular fibrillation before and 45 minutes after washout of the drug. The control episodes of fibrillation were not different from each other. Compared with control, ventricular fibrillation during isoproterenol exhibited an increased activation rate per epicardial site, an increased amount of tissue excited by each activation front, and an increased maximum negative dV/dt for each activation. There was no change in the number of activation fronts per second or the number of reentry cycles per activation front compared with control.
Quantitative analysis revealed that propranolol and isoproterenol do not have symmetrically opposite effects on ventricular fibrillation. Propranolol decreased the number of activation fronts while isoproterenol increased the amount of tissue excited by each activation front. Thus, drugs that alter ventricular refractoriness or excitability alter ventricular fibrillation.
Hillsley, RE; Bollacker, KD; Simpson, EV; Rollins, DL; Yarger, MD; Wolf, PD; Smith, WM; Ideker, RE
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