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

Heart Institute of Good Samaritan Hospital, and the Division of Cardiology, University of Southern California, Los Angeles, California

Sharon L. Hale

Heart Institute of Good Samaritan Hospital, and the Division of Cardiology, University of Southern California, Los Angeles, California

Robert A. Kloner

Heart Institute of Good Samaritan Hospital, and the Division of Cardiology, University of Southern California, Los Angeles, California

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.

Key Words: myocardial infarction • antioxidants • free radical scavenger • drug.

Journal of Cardiovascular Pharmacology and Therapeutics, Vol. 3, No. 2, 153-159 (1998)
DOI: 10.1177/107424849800300208


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