Synergistic interaction of alpha 1- and beta-adrenoceptor agonists on induction arrhythmias during halothane anesthesia in dogs

The authors investigated the role of alpha 1- and beta-adrenoceptors on the induction of arrhythmias during halothane anesthesia in the dog. The arrhythmogenic doses (ADs) of various combinations of alpha 1- and beta-adrenoceptor agonists were determined in dogs (N = 105) during halothane anesthesia. Isoproterenol (ISP) and phenylephrine (PHE) administered separately failed to induce arrhythmias in doses up to 4 micrograms/kg and 200 micrograms/kg, respectively. The interaction between ISP and PHE in inducing arrhythmias showed typical hyperbolic isoboles. At a systolic pressure of 140 mmHg, the AD of ISP in the presence of PHE was significantly lower than that in the presence of angiotensin II (ANG II). At a systolic pressure of 150, 160, 170, or 180 mmHg, there was no significant difference between the AD of ISP in the presence of PHE and that in the presence of ANG II. Increasing heart rate by electrical pacing did not replace ISP in the arrhythmogenic interaction between ISP and PHE. The results indicate that both alpha 1- and beta-adrenoceptor agonists are important for producing arrhythmias during halothane anesthesia, and that these agonists synergistically interact on the heart by different mechanisms.