Effects of thymoxamine on ouabain-induced arrhythmias in dogs

The effect of thymoxamine, a pure alpha-adrenoceptor blocking agent, on ouabain-induced arrhythmias was investigated in dogs to clarify whether thymoxamine has an arrhythmogenic or an anti-arrhythmic action. Thymoxamine. 1 mg/kg i.v., inhibited the manifestation of ventricular arrhythmias (VA) and the pressor effect produced by ouabain infusion (1 microgram/kg/min i.v.) as 5 mg/kg i.v. of phentolamine did. Low doses of these drugs did not affect the VA. Simultaneous infusion of phenylephrine (5 micrograms/kg/min i.v.) with ouabain enhanced the manifestation of VA accompanying pressor effects, which were inhibited by thymoxamine (1 mg/kg) in a parallel manner. Infusion of isoprenaline (0.2 microgram/kg min i.v.) with ouabain enhanced the manifestation of VA, but the enhancement was to a lesser extent than with phenylephrine. Thymoxamine, 1 mg/kg, did not affect the VA. The infusion of CaCl2 (20 mg/kg/min i.v.) with ouabain enhanced the manifestation of VA, which was not inhibited by thymoxamine. These results show the possibility that the protective effect of thymoxamine on the manifestation of VA may be mainly associated with inhibitions of pressor effects mediated through vascular alpha-adrenoceptors.