Ischaemia-reperfusion during infrainguinal bypass for critical limb ischaemia and the effects of a nitric oxide donor
Hypothesis: That infrainguinal arterial bypass procedures are associated with an ischaemia-reperfusion injury and that this may be reduced by administration of sodium nitroprusside, a nitric oxide donor. First study: 28 subjects, with critical limb ischaemia, undergoing infrainguinal bypass were randomised to receive sodium nitroprusside (0.1 μg/kg body weight/min) (n=15) or placebo (n = 13), infused into the operated limb, during the performance of the second or distal anastomosis and the infusion continued for twenty minutes after. Blood sampling and a doppler studies were performed. 9 patients undergoing varicose vein operations were also examined. The results indicated that application of the proximal clamp resulted in ischaemia and reperfusion with associated neutrophil activation. Sodium nitroprusside resulted in vasodilatation but had no effect on either parameter. Bypass patients had higher baseline neutrophil activation than the varicose vein group. Second Study: 30 further bypass patients ere randomised (treatment n = 15, placebo n = 15) with the infusion commencing at the time of the proximal anastomosis. Blood and urine sampling and doppler studies were performed. Changes in plasma antioxidant status, microalbuminuria and enzymuria occurred only in the placebo group indicating that, in addition to vasodilating the critically ischaemic limb, the nitric oxide donor may have been protective. Paradoxically, myeloperoxidase levels rose only in the treatment group but there was no evidence of increased free radical activity or permeability changes associated with this. Conclusion: Infrainguinal bypass is associated with an ischaemia-reperfusion injury which begins at the time of first clamp application. These procedures also result in a small but significant decrease in antioxidants and an increase in permeability. Sodium nitroprusside, a nitric oxide donor, administered into the operated limb appears to be protective against these changes and is an effective peripheral vasodilator.