MORTALITY FOLLOWING LOWER-LIMB ISCHEMIA-REPERFUSION - A SYSTEMIC INFLAMMATORY RESPONSE

Restoration of blood flow to an acutely ischemic lower limb may parado xically result in systemic complications and unexpected mortality. It has been suggested that lower limb ischemia reperfusion alters gut per meability. In this study, using a rat model, we determined the effect of acute lower limb ischemia-reperfusion on mortality rate, bowel morp hology, and circulating concentrations of endotoxin and the proinflamm atory cytokine interleukin-6. Survival rate was compared in two groups of adult Wister rats: (1) control group (n = 10); and (2) animals sub jected to 3 hours of bilateral hind limb ischemia followed by reperfus ion (n = 10). Both groups were observed under standard conditions for 4 days. In a second experiment three groups of animals were studied: ( I) control (n = 12); (II) 3 hours of bilateral hind limb ischemia alon e (n = 12); and (III) 3 hours of bilateral hind limb ischemia followed by 2 hours of reperfusion (n = 12). Animals subjected to bilateral hi nd limb ischemia followed by reperfusion had a significantly higher mo rtality rate (70%) than controls (0%) (p < 0.005), Morphometric assess ment of the small bowel showed a significant decrease in mean mucosal thickness in the ischemia-reperfusion group compared with that in the group of controls and the ischemia-alone group (p < 0.05). Bilateral h ind limb ischemia followed by reperfusion was associated with signific antly increased plasma concentrations of endotoxin (p < 0.05) and inte rleukin-6 (p < 0.0001) compared with that of controls and ischemia alo ne, These results indicate that reperfusion of the acutely ischemic lo ,ver limb is accompanied by structural changes in the gut mucosa assoc iated with increased systemic endotoxin concentrations and cytokine ac tivation. Mortality following reperfusion of the acutely ischemic limb may be related to a systemic inflammatory response triggered by endot oxin of gut origin.