The cardioprotective effects of a new
antiarrhythmic drug,
TYB-3823 [1-(2,6-dimethylphenyl)-dimethylaminoguanidine hydrochloride] were examined in the working hearts of rats and compared with those of
lidocaine. Before
ischemia,
TYB-3823 at 5 x 10(-5) M produced a slight negative inotropic effect, resulting in a decrease in aortic flow and cardiac output. However, at lower concentrations (10(-6) and 10(-5) M), the
drug had no significant effect on the functional cardiac parameters before
ischemia.
Lidocaine at such concentrations also had no effect. Global
ischemia for 15 min decreased cardiac function rapidly which only recovered partially, with a delay, after reperfusion in the control hearts. Treatment with
TYB-3823 accelerated the time course of recovery during reperfusion markedly, significantly improving functional cardiac parameters. However,
lidocaine had little effect on recovery of function. Reperfusion-induced
arrhythmia was equipotently inhibited by
TYB-3823 and
lidocaine. Leakage of cytosolic
enzymes (
lactate dehydrogenase,
creatine phosphokinase and alpha-hydroxybutylic
dehydrogenase) during reperfusion was inhibited more effectively by
TYB-3823 than
lidocaine. Light microscopic and electron microscopic examinations revealed that treatment with
TYB-3823 protected against the histological damage induced by
ischemia, such as hyaline degeneration of myocardium, absence of cross-striation and swelling of mitochondria. These results suggest that, unlike
lidocaine,
TYB-3823 causes a novel cardioprotective effect through unknown mechanisms in addition to its antiarrhythmic action.