Effects of Bunazosin, a Selective α1-Blocking Agent, and Propranolol Used Alone and in Combination on Canine Ventricular Refractoriness and its Dispersion During Myocardial Ischemia

The individual and combined effects of bunazosin, a selective aradrenergic blocking agent, and propranolol on ventricular refractoriness and its dispersion were assessed in 33 chloralose-anesthetized, sympathec-tomized, and vagotomized dogs 2–3 h after occlusion of the obtuse marginal branches of the circumflex artery. The refractory period was measured in eight sites of the ischemic zone, two sites of the border zone, and two sites of the normal zone with S1-S2 extrastimulus methods. In group 1 dogs (n = 9), coronary artery ligation significantly shortened refractoriness in the ischemic zone (p = 0.023–0.001 in each site). Intravenous (i.v.) administration of a low dose of bunazosin at 0.1 mg/kg significantly blunted the shortening of refractoriness in the ischemic zone (p = 0.026–0.002 in each site), although the values did not reach those observed in the nonischemic zones (both the border and normal zones), where refractoriness remained unchanged. In group 2 dogs (n = 11), a higher dose of i.v. bunazosin, 0.5 mg/kg, significantly blunted the shortening of the refractory period within the ischemic zone (from 149 ± 14 to 175 ± 8 ms; mean ± SD, p < 0.001) and reached the levels of the nonischemic zones (border zone 175 ± 15 ms, normal zone 170 ± 14 ms), resulting in a dispersion reduction in refractoriness between the ischemic and nonischemic zones. This dispersion tended to increase again with i.v. administration of 0.2 mg/kg propranolol (ischemic vs. border zone p = 0.034; ischemic vs. normal zone p = 0.089). In group 3 animals (n = 13), i.v. administration of 0.2 mg/kg propranolol significantly blunted the shortening of the refractory period in the ischemic zone (from 148 ± 17 ms to 171 ± 20 ms, p < 0.001). However, it also prolonged the refractory period in the nonischemic zone (ischemic vs. border zone p = 0.009; ischemic vs. normal zone p = 0.011), resulting in an increased difference between refractoriness in the ischemic and nonischemic zones. This difference remained unchanged with addition of i.v. administration of 0.5 mg/kg bunazosin. These results indicate that an α1-blocking agent may be superior to a β-blocking agent and to a combination of the two agents in reducing dispersion of ventricular refractoriness between ischemic and nonischemic zones after coronary artery occlusion.