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J Thorac Cardiovasc Surg 1997;114:236-242
© 1997 Mosby, Inc.

CARDIOPULMONARY BYPASS, MYOCARDIAL MANAGEMENT, AND SUPPORT TECHNIQUES

INTRAVENOUS CO-INFUSION OF ADENOSINE AND NOREPINEPHRINE PRECONDITIONS THE HEART WITHOUT ADVERSE HEMODYNAMIC EFFECTS

Supported in part by grants from the National Institutes of Health: Heart, Lung, and Blood Institute grants HL-20648 and HL-50688.

Received for publication Dec. 16, 1996 Revisions requested Feb. 14, 1997; revisions received March 11, 1997 Accepted for publication March 13, 1997. Address for reprints: Michael V. Cohen, MD, Department of Physiology, MSB 3050, University of South Alabama, College of Medicine, Mobile, AL 36688.

Abstract

Objective: A simple intervention is needed that could protect the heart against infarction during limited-access coronary artery bypass grafting. Adenosine and norepinephrine can precondition the heart with resulting protection, but adverse hemodynamic effects prevent clinical application. Because heart rate, blood pressure, and contractility effects of these two drugs are diametrically opposite, a mixture might be beneficial. Methods:  A superficial branch of the left coronary artery of rabbits was surrounded with a suture. Infarction was produced in all hearts by a 30-minute coronary artery occlusion. Infarct size after reperfusion was measured and is presented as a percentage of the risk zone. The effect of 5-minute intravenous co-infusion of adenosine (20 mg/kg) and norepinephrine (0.1 mg/kg) 15 minutes before ischemia was examined. In addition, the protective effect of three sequential intravenous bolus injections of adenosine at either 0.2 or 0.4 mg/kg was evaluated. Results:  Thirty minutes of regional ischemia caused infarction of 40% ± 4% of the risk zone. The combination of adenosine and norepinephrine caused no change in blood pressure but rather protected the heart, with infarction of only 9% ± 2% of the risk zone (p = 0.0001 vs control). Adenosine-norepinephrine co-infusion still protected the heart when the interval between infusion and ischemia was extended to 60 minutes, but it did not protect with a 120-minute interval. Intravenous bolus injections of adenosine resulted in cardiac slowing and marked hypotension. Boluses of 0.2 mg/kg resulted in a minimal, but significant, reduction in infarct size, whereas the higher dose provided no protection. Conclusion: Adenosine-norepinephrine co-infusion provides a feasible and safe parenteral method for preconditioning the heart. J Thorac Cardiovasc Surg 1997;114:236-42

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