ANTIISCHEMIC AND ANTIARRHYTHMIC ACTIVITIES OF SOME NOVEL ALINIDINE ANALOGS IN THE RAT-HEART

The antiischemic and antiarrhythmic effects of alinidine and a number of novel alinidine analogs were examined by using perfused rat-heart m odels. In the isolated working rat heart, the alinidine analog TH91:21 (10 mu M; a butyl derivative) significantly increased the postischemi c recovery of the heart in terms of both power and efficiency when com pared with the control group. In the in situ perfused heart model, thi s same compound, along with TH91:22 (10 mu M; a pentyl derivative) als o significantly reduced the severity of both ischemia- and reperfusion -induced arrhythmias in both paced and unpaced hearts. Thus this study is the first to demonstrate the potent antiarrhythmic efficacy of two novel alinidine analogs TH91:21 and TH91:22, with TH91:21 also demons trated to be a potent antiischemic agent in the isolated working rat h eart. Although the mode of action of these compounds remains unclear, results from this study suggest that it is not simply a result of brad ycardia or blockade of K-ATP channels, two actions these compounds pos sess. These compounds thus possess a novel and beneficial pharmacologi c profile worthy of further study.