Effect of beta receptor blockade on the initiation and perpetuation of ouabain-induced ventricular tachyarrhythmia.

The role of the cardiac beta receptor in the genesis and perpetuation of ouabain-induced ventricular tachyarrhythmias (VT) was investigated in the chloralose (20 mg/kg)-urethane (200 mg/kg) anesthetized dog. This was achieved by determining: 1) the effect of oxprenolol (0.3 mg/kg), a potent beta receptor blocking agent possessing no significant direct membrane effects on the myocardium, on the dose of ouabain necessary to cause VT (i.e., the toxic dose); and 2) whether oxprenolol had antirrhythmic efficacy against preexisting VT. The toxic dose was determined by giving a bolus injection of ouabain (similar to 36 mug/kg) plus a subsequent ouabain infusion (similar to 0.40 mug/kg min-minus 1) until VT occurred. VT was defined as at least one-third of the ventricular beats being of ectopic ventricular origin. The existence of an effective beta receptor blockade was verified by showing that 0.75 mug/kg of isoproterenol (an ED50 dose) injected intravenously had no detectable cardiovascular effects. The results were: 1) oxprenolol (0.3 mg/kg) did not alter the toxic dose significantly (P greater than .5 for both paired and group comparisons) [63.9 plus or minus 2.3 (S.E.) mug/kg vs. 64.4 plus or minus 2.9 (S.E.) mug/kg]; and 2) attempts to convert VT to sinus rhythm with oxprenolol (0.3 mg/kg) failed in 20 of 21 trials. Oxprenolol (1.0 mg/kg) effected only a temporary [10.6 plus or minus 6.4 (S.D.) minutes] reversion to sinus rhythm in 10 of 21 attempts. These results indicate that an activation of the cardiac beta receptor is not prerequisite for either the initiation or the perpetuation of ouabain-induced ventricular tachyarrhythmia in this particular model. The results cannot provide support for the notion that an increase in cardiac sympathetic nerve activity is a principal factor in VT in the dog. However, the results are consistent with the hypothesis that the direct membrane actions of ouabain are a principal cause of ouabain-induced ventricular tachyarrhythmia.