cycloprotobuxine-a and Arrhythmias--Cardiac

Cycloprotobuxine-A (CPB-A) 1-4 mg.kg-1 iv increased the dose of ouabain required to induce ventricular arrhythmias in guinea pigs. At the equitoxic doses (1/50 LD50), CPB-A was more potent than cyclovirobuxine-D and amiodarone. Pretreatment with reserpine (5 mg.kg-1 ip), vagotomy or pithing spinal cord did not prevent the action of CPB-A, which indicate that the protective effect of CPB-A may be due to its direct action on myocardium without the involvement of nervous system. In isolated guinea pig ventricular muscles, CPB-A 3 mumol.L-1 consistently decreased the amplitude of oscillatory afterpotentials (OAP) and blocked triggered activity elicited by ouabain. At 30 mumol.L-1, CPB-A abolished the appearance of OAP. It seems that one of the mechanisms for the anti-arrhythmic action of CPB-A was a decrease in the amplitude of OAP.

Topics: Alkaloids; Amiodarone; Animals; Anti-Arrhythmia Agents; Arrhythmias, Cardiac; Blood Pressure; Electrophysiology; Female; Guinea Pigs; Heart Rate; Male; Ouabain

Cycloprotobuxine-A (CPB-A) 1-4 mg/kg (1/100-1/25 LD50) produced therapeutic and prophylactic effects which were found to be dose-dependent on experimental arrhythmias induced by BaCl2, aconitine and chloroform. Given at equitoxic doses, the anti-arrhythmic action of CPB-A was as potent as cyclovirobuxine-D (CVB-D) and amiodarone (Amio). However, its therapeutic index (LD50/ED50) was 1.8 times that of CVB-D and 1.2 times that of Amio. The most pronounced effects of CPB-A (0.3-30 mumol/L) on the electrophysiology of ventricular muscle of guinea pig were the lengthening of APD50, APD90 and ERP. This may contribute to its anti-arrhythmic action and suggests that CPB-A most likely belongs to class III anti-arrhythmic drugs (prolongation of APD). Perfused with the same concentration (3 mumol/L), CPB-A brought about more significant increases in APD50, APD90 and ERP than CVB-D and Amio did.

Topics: Action Potentials; Alkaloids; Animals; Anti-Arrhythmia Agents; Arrhythmias, Cardiac; Drugs, Chinese Herbal; Female; Guinea Pigs; Male; Mice; Rats; Rats, Inbred Strains; Ventricular Fibrillation