The effect of esmolol on the ventricular fibrillation threshold (VFT) was determined in 11 open-chest dogs anesthetized with sodium pentobarbital. Since changes in VFT by antiarrhythmic drugs have been shown to depend on the method used to test vulnerability to fibrillation, two methods were studied. The vulnerable period was scanned with a train of pulses (100 Hz, 4 ms, 20 pulses) in nine experiments and a single pulse (10 ms) in eight experiments. Following control measurements, esmolol was administered as an intravenous bolus of 500 μg/kg followed by a continuous infusion of 300 μg/kg/min. After 15 min of infusion, the adequacy of beta-blockade was tested by the administration of 0.5 μg/kg of isoproterenol. Isoproterenol increased the heart rate by only 18 ± 2 beats/min following esmolol administration which was significantly less than the control response (79 ± 7 beats/min, p < 0.01). Although the VFT measured with the single-pulse technique did not change in response to esmolol (14.1 ± 1.1 mA vs. 14.3 ± 1.2 mA), the VFT measured with the train-of-pulses technique significantly increased (3.7 ± 0.5 mA to 14.5 ± 2.8 mA, p < 0.01). Twenty minutes after discontinuing esmolol, the VFT measurements were repeated and did not differ from control values with either technique. The increase in heart rate in response to isoproterenol also returned to control values (80 ± 6 beats/min). The results suggest that the ability of esmolol to raise VFT as measured by the train-of-pulses technique is due to beta-adrenergic blockade. The two methods may differ because of the relatively greater release of norepinephrine with the train-of-pulses technique.
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