Calcitonin gene-related peptide enhances the recovery of contractile function in stunned myocardium

Introduction: Calcitonin gene-related peptide, a potent vasodilating inotropic agent, increases coronary artery perfusion when administered exogenously and reduces ischemic injury in nonmyocardial tissue. However, it is unclear whether this agent improves recovery of myocardial performance after reversible myocardial ischemia. Methods: Nine dogs underwent complete occlusion of the left anterior descending coronary artery for 15 minutes and were monitored during 24 hours of reperfusion. Calcitonin gene-related peptide (0.07 mu g . kg(-1) . min(-1)), nitroglycerin (65 mu g . kg(-1) . min(-1)), or saline solution placebo was infused intravenously during initial reperfusion. Ischemia/reperfusion was repeated in concurrent 24-hour periods until all animals received infusions in random order. Micromanometry and sonomicrometry determined left ventricular pressure and myocardial segment length. Myocardial performance, based on the linear relationship between stroke work and end-diastolic segment length, was estimated with the preload recruitable work area. Results were analyzed as percent control and compared statistically with the use of repeated measures analysis of variance. Results: Recovery of myocardial performance was augmented during reperfusion with calcitonin gene-related peptide infusion relative to placebo (P = .005; mean preload recruitable work area +/- SE after calcitonin gene-related peptide infusion, 2484 +/- 705 mm Hg at 90 minutes of reperfusion versus 1473 +/- 300 mm Hg for placebo. Recovery of performance after nitroglycerin infusion was similar to recovery after placebo. Conclusions: Calcitonin gene-related peptide infusion improves recovery of contractile function in stunned myocardium. Unlike inotropic agents that impair recovery from reversible ischemia, calcitonin gene-related peptide may confer cardioprotective effects on ischemic myocardium.