Abstract
Purpose:
After acute arterial obstruction of the lower extremity, muscle damage 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 imaging ischaemia-reperfusion damage. More recently, a new imaging agent, Tc-99m-glucarate (GLUC), was introduced for delineating early myocardial infarction after ischaemia-reperfusion. The aim of this study was to determine if GLUC could delineate early skeletal muscle damage after ischaemia-reperfusion. Both tracers were used in a novel murine model of hindlimb ischaemia-reperfusion.
Methods:
In anaesthetised mice, ischaemia of one hindlimb was maintained for 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. Concentrations of both agents were determined in blood, reperfused and contralateral muscle. Reperfused-to-contralateral muscle ratios were calculated. In separate experiments, muscle biopsies were obtained for histologic examination.
Results:
Ischaemia and reperfusion damage was demonstrated histologically. Using scintigraphy GLUC depicted reperfusion significantly better than PYP. After 2, 3 and 4 h of ischaemia, the reperfused-to-contralateral ratios for 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 longer periods of reperfusion, the ratios for GLUC decreased to similar levels as observed for PYP.
Conclusion:
The present study indicates that GLUC is a specific early marker of myocyte necrosis after ischaemia-reperfusion. GLUC may become an useful agent for clinical, early, non-invasive monitoring of skeletal muscle damage after ischaemia-reperfusion.
Get full access to this article
View all access options for this article.