Mitiglinide, a novel oral hypoglycemic agent, preserves the cardioprotective effect of ischemic preconditioning in isolated perfused rat hearts

Diabetic patients often have manifestation of coronary heart disease. As a consequence, therapeutic strategies for diabetes should pay more attention to hypoglycemic agents which do not have adverse effects on myocardium. Mitiglinide is considered to have little or no impact on the cardioprotective effect of ischemic preconditioning (IP) because of its high selectivity for blocking sulfonylurea receptor1 (SUR1). However, glibenclamide, a nonselective SUR blocker, attenuates this beneficial effect. In the present study, we tested the hypothesis that mitiglinide preserves the protective action of IP evaluated by ischemia/reperfusion ventricular tachyarrhythmia (rVT) in isolated perfused rat hearts. After initial perfusion, the hearts were assigned to one of the following groups: 1) non-IP with control perfusion buffer (non-IP group); 2) IP with control perfusion buffer (IP-C group); 3) IP with perfusion buffer containing glibenclamide (IP-G group); and 4) IP with perfusion buffer containing mitiglinide (IP-M group). The protocol for the non-IP group consisted of 21 minutes of aerobic perfusion before 10 minutes of ischemia. In the other 3 groups (IP groups), there were 3 cycles of 2-minute ischemia followed by 5 minutes of reperfusion before 10 minutes of ischemia. The IP-C group had a significantly shorter rVT duration than the non-IP group (4.4 +/- 1.8 minutes versus 14.3 +/- 2.5 minutes; P < 0.05). rVT duration was the shortest in the IP-M group (3.9 +/- 1.0 minutes), but among the longest in the IP-G group (14.0 +/- 2.6 minutes). In conclusion, mitiglinide preserved the cardioprotective effect of IP, however, glibenclamide abolished this beneficial effect. Therefore, mitiglinide may offer a long-term benefit for myocardial ischemia in diabetic patients.