Early assessment of skeletal muscle damage after ischaemia-reperfusion injury using Tc-99m-glucarate

Purpose: After acute arterial obstruction of the lower extremity, muscle da mage is the critical determinant for clinical outcome. The extent of muscle damage and limb viability are currently assessed by clinical examination, which is inaccurate. Tc-99m-pyrophosphate (PYP) has been applied for imagin g ischaemia-reperfusion damage. More recently, a new imaging agent, Tc-99m- glucarate (GLUC), was introduced for delineating early myocardial infarctio n after ischaemia-reperfusion. The aim of this study was to determine if GL UC could delineate early skeletal muscle damage after ischaemia-reperfusion . Both tracers were used in a novel murine model of hindlimb ischaemia-repe rfusion. Methods: In anaesthetised mice, ischaemia of one hindlimb was maintained fo r 2, 3 and 4 h using a tourniquet, followed by a reperfusion period of 1 h. Additionally, reperfusion periods of 3, 24 and 96 h were studied after 3 h of ischaemia. PYP or GLUC was injected 45 min before end of reperfusion. C oncentrations of both agents were determined in blood, reperfused and contr alateral muscle. Reperfused-to-contralateral muscle ratios were calculated. In separate experiments, muscle biopsies were obtained for histologic exam ination. Results: Ischaemia and reperfusion damage was demonstrated histologically. Using scintigraphy GLUC depicted reperfusion significantly better than PVP. After 2, 3 and 4 h of ischaemia, the reperfused-to-contralateral ratios fo r GLUC were 10.7 +/- 0.9, 8.9 +/- 0.9 and 8.6 +/- 1,1, as compared to 4.5 /- 0.7, 4.9 +/- 0.4 and 4.5 +/- 0.4 for PYP (P < 0.05 at all points). For l onger periods of reperfusion, the ratios for GLUC decreased to similar leve ls as observed for PYP. Conclusion: The present study indicates that GLUC is a specific early marke r of myocyte necrosis after ischaemia-reperfusion. GLUC may become an usefu l agent for clinical, early, non-invasive monitoring of skeletal muscle dam age after ischaemia-reperfusion. (C) 2000 The International Society for Car diovascular Surgery. Published by Elsevier Science Ltd. All rights reserved .