Selective type III phosphodiesterase inhibition prevents elevated compartment pressure after ischemia reperfusion injury

Background: A new synthetic cyclic adenosine monophosphate phosphodiesteras e inhibitor, cilostazol, has been shown to inhibit platelet aggregation and act synergistically with endogenous prostaglandin I,to enhance smooth-musc le cell vasodilitation. The effect of cilostazol in ischemia/reperfusion in jury-induced compartment syndrome was investigated, Methods: Sixteen rabbits underwent femoral artery occlusion after ligation of branches from the terminal aorta to the femoral artery, After 7 hours of ischemia, reperfusion was established with heparinized polyethylene shunts , Experimental animals (n = 8) received cilostazol (3.0 mg/kg) and control animals (n = 8) received normal saline as an intravenous infusion 10 minute s before shunt placement. During reperfusion, anterior compartment pressure was continuously monitored in the left lower extremity, and femoral artery blood flow was measured by laser Doppler fluorometry, To quantitate skelet al muscle oxidative metabolism and viability, triphenyltetrazolium chloride (TTC) reduction (micrograms of TTC per milligram of protein) of tibialis a nterior muscle from the right lower extremity was measured at femoral arter y occlusion, 7 hours of ischemia, and 2 hours of reperfusion, To assess tis sue edema, dry/wet weight ratios were also determined at these intervals. D ata were expressed as means +/- SE. Comparisons within groups were performe d by analysis of variance, and comparisons between groups with two-tailed u npaired t tests. Results: At 2 hours of reperfusion, the difference between controls and cil ostazol-treated animals was extremely significant (p = 0.0008), Preischemia and 2-hour reperfusion TTC and dry/wet weight ratios were not significantl y different within or between experimental groups, nor was femoral artery b lood flow during reperfusion, Conclusion: Cilostazol inhibits the increase in compartment pressure centra l to the development of the compartment syndrome, The mechanism appears to be independent of altered tissue permeability or oxidative metabolism.