Adrenomedullin infusion during ischemia/reperfusion attenuates left ventricular remodeling and myocardial fibrosis in rats

Recent studies have demonstrated that the activation of protein kinase Akt attenuates myocardial ischemia/reperfusion injury. However, it remains unknown whether adrenomedullin (AM), which is also a potent Akt activator, has cardioprotective effects after ischemia/reperfusion. In the present study, Sprague-Dawley rats were exposed to a 30-min period of ischemia induced by ligation of the left coronary artery followed by 24-h reperfusion. They were randomized to receive intravenous administration of AM (0.05 mug/kg/min) or saline for 60 min after coronary ligation. We examined the hemodynamics and myocardial apoptosis 24 h after ischemia/reperfusion. Echocardiographic measurements were performed 4 weeks after ischemia/repertusion. Myocardial infarct size was also measured histologically. AM significantly reduced left ventricular (LV) end-diastolic pressure (17+/-2 to 8+/-2 mmHg, p<0.05) and the number of apoptotic nuclei in myocytes (387+/-39 to 147+/-72 per field, p<0.05). AM significantly increased LV dP/dt(max) (4,803+/-228 to 5,672+/-199 mmHg/s, p<0.05). AM significantly increased LV fractional shortening (23+/-2 vs. 28+/-2%, p<0.05), and significantly reduced LV diastolic dimension (7.4 0.1 to 6.9 0.1 mm, p<0.05) and myocardial infarct size (33+/-2 to 20+/-2%, p<0.01) 4 weeks after ischemia/reperfusion. In conclusion, AM infusion during ischemia/reperfusion attenuated the development of LV remodeling and myocardial fibrosis in rats. Based on these results, the cardioprotective effects of AM may be attributed at least partly to its anti-apoptotic effect.