To study the antiarrhythmic effect of the newly developed alpha/beta-blocker
TJ0711, a variety of animal models of
arrhythmia were induced by CaCl2,
ouabain and
ischemia/reperfusion. Glass
microelectrode technique was used to observe action potentials of right ventricular papillary muscle of guinea pig. The onset time of
arrhythmia induced by CaCl2 was significantly prolonged by
TJ0711 at 0.75, 1.5 and 3 mg x kg(-1) doses.
TJ0711 (1.5 and 3 mg x kg(-1)) can significantly shorten the
ventricular tachycardia (VT) and
ventricular fibrillation (VF) duration, the incidence of VF and mortality were significantly reduced. On
ischemia-reperfusion-induced arrhythmic model,
TJ0711 (0.25, 0.5, 1 and 2 mg x kg(-1)) can significantly reduce the ventricular premature contraction (
PVC), VT, VF incidence, mortality,
arrhythmia score with a dose-dependent manner. At the same time, rats serum
lactate dehydrogenase (LDH) and
creatine kinase (CK) activities decreased significantly by
TJ0711 (1 and 2 mg x kg(-1)).
Ouabain could cause
arrhythmia in guinea pigs, when
TJ0711 (0.375, 0.75, 1.5 and 3 mg x kg(-1)) was given, the doses of
ouabain inducing a variety of
arrhythmia PVC, VT, VF,
cardiac arrest (CA) were significantly increased with a dose-dependent manner. In the
TJ0711 0.1-30 micromol x L(-1) concentration range, guinea pig right ventricular papillary muscle action potential RP (rest potential), APA (action potential amplitude) and V(max) (maximum velocity of depolarization) were not significantly affected. APD20, APD50 and APD90 had a shortening trend but no statistical difference with the increase of
TJ0711 concentration.
TJ0711 has antiarrhythmic effect on the sympathetic nerve excitement and myocardial cell high
calcium animal
arrhythmia model. Myocardial action potential zero phase conduction velocity and resting membrane potential were not inhibited by
TJ0711. APD20, APD50 and APD90 were shortened by
TJ0711 at high concentration. Its antiarrhythmic action mechanism may be besides the action of blocking beta1 receptor, may also have a strong selective blocking action on alpha1 receptor and reducing intracellular
calcium concentration.