Effects of Alpha Adrenergic Stimulation and Blockade on Early Afterdepolarizations Induced by Cesium in Canine Cardiac Purkinje Fibers

Abstract

Alpha Adrenergic Stimulation and EADs. The effects of alpha adrenergic stimulation and three alpha adrenoceptor blockers on early afterdepolarizations (EADs) were examined in canine card diac Purkinje fibers. In the first group of 18 preparations, EADs were induced by superfusion with 7.5 mM cesium (Cs) dissolved in low potassium (2.7 mM KCl) Tyrode's solution. During alpha adrenoceptor stimulation (norepinephrine 1 μM and propranolol 1 μM) to enhance EADs, the effects of phentotamine and two new alpha 1 adrenoceptor antagonists, benoxathian and WB 4101 (1, 3, and 10 μM), were examined. WB 4101 (1 μM) suppressed EADs in all six preparations. Benoxathian required 3 μM in five preparations and 10 μM in one to suppress EADs. Phentolamine (10 μM) suppressed EADs in two of six preparations. In the second group of 21 preparations, the effects on cesium‐induced EADs of the three alpha adrenoceptor hlockers (10 μM) were examined without alpha adrenoceptor stimulation. WB 4101 (10 μM) suppressed EADs in seven of seven preparations, while benoxathian (10 μM) suppressed EADs in five of seven. Phentolamine (10 μM) enhanced EADs in six of seven preparations. In the third group of 24 Purkinje fibers, the direct effects (without alpha adrenoceptor stimulation) of these three antagonists on the characteristics of normal Purkinje fiber action potentials superfused with normal Tyrode's solution were examined. Phentolamine (1, 3, and 10 μM, n = 8) prolonged action potential duration at 90% repolarization (APD90) by 5.3%± 1.3%, 10.0%± 1.8%, and 14.3%± 2.7%, respectively. Benoxathian (n = 8) and WB 4101 (n = 8) shortened APD90 equally: 6.8%± 1.1% vs 7.7%± 1.3% at 1 μM, 13.6%± 1.0% vs 14.5%± 1.6% at 3 μM, and 21.1%± 1.2% vs 20.8%± 2.1% at 10 μM, respectively. We conclude that in cesium treated Purkinje fibers: (1) Alpha adrenoceptor stimulation enhanced EADs; (2) Phentolamine was least effective in suppressing EADs, probably because of a direct effect that prolonged MM)90,: and (3) Although benoxathian and WB 4101 had similar etTects on APD90, WB 4101 was more effective in suppressing EADs at lower concentrations than henoxathian.