ENDOTHELIAL DAMAGE DUE TO ISCHEMIA AND REPERFUSION IS PREVENTED WITH SIN-1

Background: Acute ischemia followed by reperfusion results in direct e ndothelial damage characterized by cell swelling, increased permeabili ty and loss of acetylcholine-mediated vasorelaxation. Ischemia followe d by reperfusion in a New Zealand white rabbit hindlimb has been shown to result in loss of acetylcholine-induced relaxation of superficial femoral arteries. This loss of relaxation in response to acetylcholine is a reflection of the decreased nitric oxide availability that occur s with reperfusion injury. The purpose of this investigation was to ev aluate the effect of SIN-1, a direct nitric oxide donor, on this endot helial injury. Methods: New Zealand white rabbits underwent complete i schemia of the right hindlimb for 3 h followed by 2 h of reperfusion, Aliquots of 20 ml of either 0.88-mM SIN-1 or normal saline was infused via a lateral branch of the right common iliac artery during the firs t 20 min of reperfusion, Sham vessels were subjected to the S-h operat ive intervention to control for anesthetic effect. Control vessels wer e harvested from rabbits not exposed to ischemia or reperfusion, Super ficial femoral artery rings were evaluated in vitro for endothelial ce ll-mediated relaxation, Rings were contracted with potassium chloride and norepinephrine and then exposed to standardized incremental doses of acetylcholine to measure percent relaxation, Artery sections were s ent for hematoxylin and eosin staining. Results: No significant differ ences were seen in contraction caused by either potassium chloride or norepinephrine in all four experimental groups. Saline infused vessel rings relaxed a mean of 8.42 +/- 2.39% and 49.57 +/- 8.65% in response to acetylcholine doses of 3 x 10(-8) M and 1 x 10(-7) M, respectively . In contrast, SIN-1 infused vessels relaxed a mean of 57.82 +/- 2.65% and 100.23 +/- 1.53% to the same doses of acetylcholine. Control and sham arteries showed a similar relaxation response as compared with SI N-1 infused vessels. Differences in relaxation when comparing saline i nfused vessels with SIN-1 infused, sham and control arteries, were sig nificantly different at each dose of acetylcholine from 3 x 10(-8) M t o 1 x 10(-7) M (P < 0.05, ANOVA). Histologic examination of the vessel s revealed no morphologic differences among the experimental groups, A ll vessels were structurally normal with an intact endothelium, Conclu sion: In this model of rabbit hindlimb ischemia, preservation of endot helial cell-mediated vasorelaxation occurs with administration of intr a-arterial SIN-1 during reperfusion. This preservation of endothelial function cannot be explained by histologic changes in the arterial wal l or attributed to altered arterial contractility in response to potas sium chloride or norepinephrine. (C) 1998 The International Society fo r Cardiovascular Surgery. Published by Elsevier Science Ltd. All right s reserved.