Effects of drugs on excitation and conduction abnormalities in various stages of myocardial ischemia in experimental animals

Abstract

Many drugs are being developed for treatment of ventricular arrhythmias (VA) in myocardial infarction. However, the characters of excitation and conduction abnormalities change during the period of ischemia. Thus, these abnormalities should be clarified and the most effective drug should be chosen for the treatment of VA. In acutely ischemic myocardium of experimental animals, an alternation of ST-T comlex in ECG is observed, which is sssociated with VA. The causes of these VA are large injury currents as well as delayed conduction. The VA are prevented by the pretreatment of calcium antagonists, but not by class I antiarrhythmic drugs. In one day-old infarction, serious VA appeared, which are caused by abnormal automaticity in Purkinje fibers. These VA are inhibited by class I drugs. In one week-old infarction, VA are caused by reentry mechanism, which is prevented by the class I drugs. In one to three months-old infarction, reentry is hardly produced by premature stimulation. In these infarction, abnormal automaticity appeared in the border of non-infarcted and infarcted area, and the automaticity sometimes caused VA. Hypertension and diabetes mellitus enhance the abnormal automaticity. Hyperthyroidism enhances ischemia-reperfusion induced VA, which may be caused by enhanced abnormal automaticity. However, mechanisms of VA in old infarction and in other heart diseases should be further investigated, and effects of drugs on these VA remain to be clarified.