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J Thorac Cardiovasc Surg 1995;110:1047-1053
© 1995 Mosby, Inc.

CARDIOPULMONARY BYPASS, MYOCARDIAL MANAGEMENT, AND SUPPORT TECHNIQUES

CONSTITUTIVE NITRIC OXIDE RELEASE IS IMPAIRED AFTER ISCHEMIA AND REPERFUSION

Farmington, Conn., and Springfield, Mass.

Supported by grants HL 22559-14 and HL 34360-07 from the National Institutes of Health.

Received for publication Dec. 14, 1994. Accepted for publication March 24, 1995. Address for reprints: Daniel T. Engelman, MD, 7 Lincoln Ave., West Hartford, CT 06117.

Abstract

Myocardial ischemia and reperfusion may result in endothelial dysfunction and reduced release of nitric oxide. With the use of an amperometric sensor, the first direct measurements of constitutive nitric oxide release from a beating heart were measured from the coronary effluent of isolated working rat hearts subjected to ischemia and reperfusion. Rats, six to eight per group, were randomly studied as follows: control (no pretreatment) and pretreatment with the nitric oxide donor L–arginine (3 mmol/L), its enantiomer D–arginine (3 mmol/L), nitric oxide inhibitor N–nitro–L–arginine methyl ester (100µmol/L), and combined N–nitro–L–arginine methyl ester/L–arginine. Isolated hearts were pretreated for 10 minutes before 30 minutes of global ischemia and 30 minutes of reperfusion. A nonischemic control group (n = 4) was continuously perfused with oxygenated unsupplemented buffer. After ischemia/reperfusion, hearts supplemented with L–arginine recovered significantly (p <0.05) increased developed pressure, first derivative of the aortic pressure (dP/dt_max), and aortic flow compared with all other hearts that underwent ischemia/reperfusion. In addition, nitric oxide release was significantly (p <0.05) increased during reperfusion in the L–arginine group. During reperfusion, the recovery of aortic flow correlated with nitric oxide release (r = 0.81, p <0.0001). We conclude that after ischemia/reperfusion, endothelial dysfunction results in decreased nitric oxide release, which can be ameliorated with L–arginine pretreatment. The direct cytoprotective properties of nitric oxide may contribute to improved functional recovery in hearts pretreated with L–arginine. Augmentation of the L–arginine/nitric oxide pathway may provide a new approach for improved recovery after cardiovascular operations. (J THORAC CARDIOVASC SURG 1995;110:1047-53)

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