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

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 oxi de with endothelial injury may occur during two phases: cardioplegic i schemia and reperfusion (aortic declamping). This study tested the hyp othesis that inhibition of endogenously released nitric oxide in heart s subjected to regional ischemia, cardioplegic arrest, and reperfusion (1) restricts endogenous cardioprotection and permits neutrophil-medi ated damage and (2) expresses damage during the reperfusion phase, L-N itro-arginine was used to block basal nitric oxide production. In 22 a nesthetized 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 a n 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 cardioplegi c 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%, re spectively), 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 activi ty in the area at risk was elevated comparably in groups 2 and 3 (grou p 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), sugge sting polymorphonuclear neutrophil accumulation occurs primarily durin g reperfusion. Polymorphonuclear neutrophil adherence in ischemic-repe rfused left anterior descending artery segments was comparably greater in group 2 (L-nitro-arginine as an additive to blood cardioplegic sol ution and at reperfusion: 195 +/- 21 polymorphonuclear neutrophils/mm( 2) of artery, p < 0.05 vs group 1) and group 3 (L-nitro-arginine only at reperfusion: 224 +/- 20 polymorphonuclear neutrophils/mm(2) of arte ry, p < 0.05 vs group 1) relative to that in group 1 (108 +/- 19 polym orphonuclear neutrophils/mm(2) of artery). There was no significant ad herence to nonischemic circumflex; arteries. We conclude that blockade of endogenous nitric oxide augments postischemic injury mediated by p olymorphonuclear neutrophils, and this damage is expressed primarily d uring the reperfusion phase.