CONSTITUTIVE NITRIC-OXIDE RELEASE IS IMPAIRED AFTER ISCHEMIA AND REPERFUSION

Myocardial ischemia and reperfusion may result in endothelial dysfunct ion and reduced release of nitric oxide. With the use of an amperometr ic 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: contro l (no pretreatment) and pretreatment with the nitric oxide donor L-arg inine (3 mmol/L), its enantiomer D-arginine (3 mmol/L), nitric oxide i nhibitor N omega-nitro-L-arginine methyl ester (100 mu mol/L), and com bined N omega-nitro-L-arginine methyl ester/L-arginine. Isolated heart s 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 is chemia/reperfusion, hearts supplemented with L-arginine recovered sign ificantly (p < 0.05) increased developed pressure, first derivative of the aortic pressure (dP/dt(max)), and aortic flow compared with all o ther hearts that underwent ischemia/reperfusion, In addition, nitric o xide release was significantly (p < 0.05) increased during reperfusion in the L-arginine group, During reperfusion, the recovery of aortic f low correlated with nitric oxide release (r = 0.81, p < 0.0001), We co nclude that after ischemia/reperfusion, endothelial dysfunction result s in decreased nitric oxide release, which can be ameliorated with L-a rginine pretreatment. The direct cytoprotective properties of nitric o xide may contribute to improved functional recovery in hearts pretreat ed with L-arginine, Augmentation of the L-arginine/nitric oxide pathwa y may provide a new approach for improved recovery after cardiovascula r operations.