LACK OF NITRIC-OXIDE CONTRIBUTES TO VASOSPASM DURING ISCHEMIA REPERFUSION INJURY/

Vasospasm can be a complication after free tissue transfer and replant operations. Recent studies suggest that vasospasm may be due to endot helium dysfunction, resulting in impairment of nitric oxide production . The present experiment was designed to investigate acute responses o f the microcirculation of skeletal muscle to local interarterial infus ion of sodium nitroprusside (a direct donor of nitric oxide and thus a n endothelium-independent vasodilator) or acetylcholine chloride (whic h stimulates endothelium release of endogenous nitric oxide) during re perfusion after 4 hours of warm ischemia. Male Sprague-Dawley rats, ea ch weighing 100 to 120 gm, were anesthetized with sodium pentobarbiton e and were surgically prepared with vascular isolated and denervated c remaster muscles that were subjected to 4 hours warm ischemia and 2 ho urs of reperfusion. Sodium nitroprusside (10(-3) M), acetylcholine chl oride (10(-4) M), or normal saline (eight rats for each group) were ad ministered by local infusion (0.1 ml/hour) through the femoral artery into the natural blood flow of the cremaster. The arterial tree in the cremaster was observed and arteriole diameters (A1-A4) were measured using intravital microscopy. The number of arteriole branches having t emporary stoppage of flow were counted in each cremaster. The results from this study show that local infusion of sodium nitroprusside, but not acetylcholine chloride, prevents ischemia/reperfusion vasoconstric tion in A3 and A4 arterioles and thus improves microvascular blood flo w. Generalized vasoconstriction caused by topically applied norepineph rine (10(-6) M) to sham ischemia cremasters could be completely revers ed by the local infusion of 10(-4) M acetylcholine chloride. These res ults indicate that vasospasm after ischemia/reperfusion may be related to temporary endothelial cell dysfunction, resulting in the inability to produce sufficient nitric oxide during early reperfusion. Vascular smooth muscle, however, is responsive to locally administered sodium nitroprusside infusion (which is thought to provide exogenous nitric o xide).