Effects of bunazosin and propranolol on ventricular arrhythmias in dogs with hypokalemia

Abstract

The arrhythmogenic mechanism in dogs with hypokalemia was investigated in relation to the effects of an alpha 1-blocking agent and a beta-blocking agent. Hypokalemia was induced by inserting an ion-exchange resin into the colon. In the hypokalemia group, nine out of 17 dogs with arrhythmia ratios of over 10% (that is the percentage of the number of ventricular ectopic beats divided by the total number of heart beats during 5 min, after 10 micrograms/kg of epinephrine injection) were observed. In the control group (n = 13), which maintained normal serum K+ levels, only one dog showed an arrhythmia ratio of over 10%. Dogs with lower serum K+ levels showed higher arrhythmia ratios. The Ca2+ content of heart mitochondria, considered to be a reflection of intracellular Ca2+ concentration, was 24.4 +/- 5.7 nmoles/mg protein in the control group 5 min after epinephrine injection, while that of the hypokalemia group was increased to 35.0 +/- 13.4. A good reciprocal correlation between the concentration of serum K+ just before epinephrine injection and mitochondrial Ca2+ content was observed in the hypokalemia group (r = -0.79), while in the control group, no correlation was observed. Clear correlation between mitochondrial Ca2+ content and the arrhythmia ratio was also observed in the propranolol group. Pretreatment with bunazosin, an alpha 1-"blocker," effectively prevented the increase in mitochondrial Ca2+ content, and reduced the arrhythmia ratio. On the other hand, pretreatment with propranolol, a beta-"blocker," did not affect the mitochondrial Ca2+ content and the arrhythmia ratio.(ABSTRACT TRUNCATED AT 250 WORDS)