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J Thorac Cardiovasc Surg 1995;110:1054-1062
© 1995 Mosby, Inc.

CARDIOPULMONARY BYPASS, MYOCARDIAL MANAGEMENT, AND SUPPORT TECHNIQUES

SIMULTANEOUS MANIPULATION OF THE NITRIC OXIDE AND PROSTANOID PATHWAYS REDUCES MYOCARDIAL REPERFUSION INJURY

Oakland, Calif.

Supported in part by a grant from the East-Bay Neonatology Foundation

Received for publication Dec. 9, 1994. Accepted for publication March 15, 1995. Address for reprints: William M. DeCampli, MD, PhD, Division of Cardiothoracic Surgery, Children'sHospital Oakland, 747 52nd St., Oakland, CA 94609

Abstract

The effects of aspirin and L-arginine (biological precursor of nitric oxide) on the production of hydroxyl radicals, cyclic guanosine monophosphate levels, vascular tone, and the recovery of the ischemic myocardium were investigated in isolated rat hearts subjected to ischemia and reperfusion. After 30 minutes of perfusion, hearts were arrested with St. Thomas' Hospital cardioplegic solution, global ischemia was induced at 37° C for 45 minutes, and the hearts were then reperfused at 37° C for 30 minutes. The percent change in recovery of pulse pressure and maximal change of this pressure with time were better in the group perfused with Krebs-Henseleit solution containing aspirin plus L-arginine (17%±23%, p = 0.001, and 10%±25%, p = 0.002, respectively) compared with these values in the control group perfused with Krebs-Henseleit solution alone (-7%±14% and -11%±16%, respectively). Coronary vascular resistance before and after ischemia were lower in the aspirin plus L-arginine group (0.19±0.03 dynes sec/cm ⁵, p = 0.001, and 0.23±0.04 dynes sec/cm ⁵, p = 0.0, respectively) compared with those of the control group (0.24±0.02 and 0.28±0.07 dynes sec/cm ⁵, respectively). Cyclicguanosine monophosphate levels increased from 22.5±6 pmol/100 mg of tissue in the control group to 37.1±8.9 pmol/100 mg (p = 0.002) in the aspirin plus L-arginine group. Adding N-nitro-L-arginine methyl ester to the perfusion medium caused a deterioration in pulse pressure and maximal change of this pressure with time, a decrease in cyclic guanosine monophosphate, and a rise in coronary vascular resistance. The addition of L-arginine to the solution in the Krebs-Henseleit solution plus aspirin group increased the production of hydroxyl radicals from 0.32±0.18 nmol/gm per 3 minutes to 0.75±0.33 nmol/gm per 3 minutes (p = 0.03). Despite the association of nitric oxide with increased hydroxyl radical production, it appears that nitric oxide has an overall beneficial effect on the recovery of the ischemic myocardium. The synergism between aspirin and arginine may be caused in part by the scavenging of hydroxyl radicals. Alternatively, by inhibiting the prostaglandin pathway, aspirin may reduce the generation of superoxide anion, a free radical that inactivates nitric oxide. The prolonged half-life of nitric oxide may explain the increased levels of cyclic guanosine monophosphate seen in the group perfused with Krebs-Henseleit solution plus aspirin plus L-arginine. Aspirin and L-arginine, both readily available, may be useful adjuncts to clinical cardioplegia strategy. (J THORAC CARDIOVASC SURG 1995;110:1054-62)

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