Effects of propranolol and tetrandrine in combination on epinephrine-induced arrhythmias in rabbits

The effects of propranolol (Pro) and tetrandrine (Tet) combination on cpinephrinc-induced arrhythmias in conscious rabbits revealed that Pro (0.2 mg/kg iv), Tet (3 mg/kg iv), 1/2 Tet + 1/2Pro, and Tet+Pro postponed the onset of ventricular arrhythinias induced by epinephrine (50 vg/kg iv) from 17.7+2.3 t0 30+8.20+ 14, 44+24, 106 i- 42 s and reduced the duration of ventricular arrhythmias from 196土33 to 11.6 + 41, 134+20, 81+39, and 19+8 s, respcctively. The results obtained by decreasing the number of ventricular tachycardias by the combination of Pro with Tet were superior to those when Pro and Tet were administrated separately. The plasma levels of Pro. determined by spectrofluorometry. showed a biphasic two-compartment open model for the concentration-time curves. The protein binding rate of Pro in rabbit plasma was 63+3% determined by equilibrium dialysis at different concentrations. Tet in combination with Pro did not alter the concentration-time curves, pharmacokinetic parameters or binding rate of Pro. The results suggest that the combined effects of Pro and Tet on epinephrine-induced arrhythrr:ias in rabbits are markcdly increased. and that this may due to differences with respect to their respective pharmacodynamics and pharmacokinetics.