MEXILETINE AND LIDOCAINE REDUCE POSTISCHEMIC FUNCTIONAL AND BIOCHEMICAL DYSFUNCTION OF PERFUSED HEARTS

The present study was undertaken to determine whether class Ib antiarr hythmic agents, mexiletine and lidocaine, exert beneficial effects on ischemia/reperfusion-induced cardiac contractile dysfunction. Isolated rat hearts were subjected to 35-min global ischemia, followed by 60-m in reperfusion and the functional and metabolic alterations were exami ned with and without mexiletine or lidocaine treatment. Ischemia/reper fusion resulted in a lack of recovery of contractile function, a susta ined rise in left ventricular end-diastolic pressure and increased cor onary perfusion pressure of the perfused heart during reperfusion. Con tractile dysfunction was associated with increases in tissue Na+ and C a2+ levels, decreases in K+ and Mg2+ levels, and release of creatine k inase and purine nucleosides and bases (ATP metabolites) from the hear t. Treatment of the perfused heart with either 10-100 mu M of either m exiletine or lidocaine during pre-ischemia resulted in an enhancement of post-ischemic contractile recovery, a suppression of changes in tis sue Na+, K+, Ca2+ and Mg2+ contents and an attenuation of the release of creatine kinase and ATP metabolites in an almost concentration-depe ndent manner. Tissue sodium accumulation was observed at the end of is chemia, which was also attenuated by pretreatment with these agents. T he prevention of Na+ overload and accompanying Ca2+ overload in cardia c cells may be the mechanism underlying the improvement of post-ischem ic contractile function of perfused hearts by these agents.