The Effect of Melatonin on Hemodynamics, Blood Flow, and Myocardial Infarct Size in a Rabbit Model of Ischemia-Reperfusion

Abstract

Background: Melatonin, a hormone, has gained popularity and is being used by millions for a variety of indications. There are few data on its safety or its effects on hemodynamics and coronary blood flow. Also, studies have confirmed that melatonin is a potent antioxidant. Therefore, it may be capable of scavenging free radicals during the reperfusion phase after a heart attack. This study evaluates the safety of melatonin with regard to its cardiovascular effects and tests the hypothesis that melatonin might be protective in the setting of ischemia-reperfusion and reduce myocardial infarct size. Methods and Results: Anesthetized rabbits were treated with melatonin (n = 8, 10 mg/kg, intravenously) 10 minutes before coronary artery occlusion (CAO) and again 15 minutes before reperfusion. Control rabbits received vehicle (n = 8). All rabbits underwent 30 min utes of occlusion and 3 hour reperfusion. Both before and during CAO, melatonin did not alter heart rate compared with control (185 ± 7 beats/min v 181 ± 7 before; and 179 ± 5 v 181 ± 9 during, respectively, P = NS) or blood pressure (70 ± 4 mmHg v 66 ± 6 before and 59 ± 4 v 58 ± 5 during, respectively, P = NS). Regional myocardial blood flow (RMBF) was similar before CAO in the melatonin group (1.18 ± 0.17 mL/min/g) versus the control group (1.15 ± 0.10 mL/min/g). Infarct size, expressed as a fraction of ischemic risk zone, was simi lar in the melatonin (0.29 ± 0.03) and control groups (0.29 ± 0.06, P = NS). At a higher dose of 50 mg/kg in treated (n = 7) versus control (n = 7) rabbits, melatonin treatment did not alter heart rate (204 ± 14 in melatonin group v 181 ± 5 in controls, P = NS) or blood pressure (80 ± 11 in melatonin v 66 ± 7 in controls, P = NS) when compared with control. Melatonin at this dose also did not affect infarct size, 0.38 ± 0.06, when compared with con trol, 0.34 ± 0.07, P = NS. Conclusion: Melatonin's effects on hemodynamics and coronary blood flow were neutral, and it did not exacerbate myocardial ischemia or necrosis in this model. Melatonin appears to be a safe drug with no apparent effects on the cardiovascular system in this model.