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J Thorac Cardiovasc Surg 1997;113:399-409
© 1997 Mosby, Inc.

CARDIOPULMONARY BYPASS, MYOCARDIAL MANAGEMENT, AND SUPPORT TECHNIQUES

BASAL NITRIC OXIDE EXPRESSES ENDOGENOUS CARDIOPROTECTION DURING REPERFUSION BY INHIBITION OF NEUTROPHIL-MEDIATED DAMAGE AFTER SURGICAL REVASCULARIZATION

Supported in part by grant HL46179 from the National Heart, Lung, and Blood Institute of the National Institutes of Health.

Received for publication May 6, 1996 revisions requested June 26, 1996; revisions received Sept. 10, 1996 accepted for publication Sept. 12, 1996. Address for reprints: Jakob Vinten-Johansen, PhD, The Cardiothoracic Research Laboratory, Department of Cardiothoracic Surgery, Carlyle Fraser Heart Center of Emory University, 550 W. Peachtree St. NE, Atlanta, GA 30365-2225.

Abstract

Ischemia-reperfusion damages endothelium and impairs basal production of nitric oxide. Basally released nitric oxide is cardioprotective by its inhibition of neutrophil activities. Loss of endogenous nitric oxide with endothelial injury may occur during two phases: cardioplegic ischemia and reperfusion (aortic declamping). This study tested the hypothesis that inhibition of endogenously released nitric oxide in hearts subjected to regional ischemia, cardioplegic arrest, and reperfusion (1) restricts endogenous cardioprotection and permits neutrophil-mediated damage and (2) expresses damage during the reperfusion phase. L-Nitro-arginine was used to block basal nitric oxide production. In 22 anesthetized dogs, the left anterior descending artery was ligated for 90 minutes followed by 1 hour of arrest with cold multidose (every 20 minutes) blood cardioplegia. Dogs were divided into three groups: the first group received standard unsupplemented blood cardioplegia (group 1, n = 8), in the second group L-nitro-arginine was administered as an additive to blood cardioplegic solution (1 mmol) and as an infusion during reperfusion (34 mg/kg) (group 2, n = 7), and in the third group L-nitro-arginine was administered only at reperfusion (group 3, n = 7). The ligature was released during the second infusion of cardioplegic solution. Infarct size (triphenyltetrazolium chloride) was increased in group 3 (L-nitro-arginine only at reperfusion) compared with that in group 1 (standard blood cardioplegia) (49% ± 6% vs 34% ± 2%, respectively), but was not further extended in group 2 (L-nitro-arginine as an additive to blood cardioplegic solution and at reperfusion) (56% ± 3%, p > 0.05 vs group 3), which suggests primarily a reperfusion process. Polymorphonuclear neutrophil–specific myeloperoxidase activity in the area at risk was elevated comparably in groups 2 and 3 (group 2: 2.9 ± 0.5 units/gm tissue, p = 0.06 vs group 1; group 3: 3.9 ± 1.0 units/gm tissue, p < 0.05 vs group 1) compared with that in the standard blood cardioplegia group (1.7 ± 0.3 units/gm tissue), suggesting polymorphonuclear neutrophil accumulation occurs primarily during reperfusion. Polymorphonuclear neutrophil adherence in ischemic-reperfused left anterior descending artery segments was comparably greater in group 2 (L-nitro-arginine as an additive to blood cardioplegic solution and at reperfusion: 195 ± 21 polymorphonuclear neutrophils/mm² of artery, p < 0.05 vs group 1) and group 3 (L-nitro-arginine only at reperfusion: 224 ± 20 polymorphonuclear neutrophils/mm² of artery, p < 0.05 vs group 1) relative to that in group 1(108 ± 19 polymorphonuclear neutrophils/mm² of artery). There was no significant adherence to nonischemic circumflex arteries. We conclude that blockade of endogenous nitric oxide augments postischemic injury mediated by polymorphonuclear neutrophils, and this damage is expressed primarily during the reperfusion phase.

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