Administration of particulate oxygen generators improves skeletal muscle contractile function after ischemia-reperfusion injury in the rat hindlimb.

Abstract

Extended tourniquet application, often associated with battlefield extremity trauma, can lead to severe ischemia-reperfusion (I/R) injury in skeletal muscle. Particulate oxygen generators (POGs) can be directly injected into tissue to supply oxygen to attenuate the effects of I/R injury in muscle. The goal of this study was to investigate the efficacy of a sodium percarbonate (SPO)-based POG formulation in reducing ischemic damage in a rat hindlimb during tourniquet application. Male Lewis rats were anesthetized and underwent tourniquet application for 3 h at a pressure of 300 mmHg. Shortly after tourniquet inflation, animals received intramuscular injections of either 0.2 mg/mL SPO with catalase (n = 6) or 2.0 mg/mL SPO with catalase (n = 6) directly into the tibialis anterior (TA) muscle. An additional Tourniquet-Only group (n = 12) received no intervention. Functional recovery was monitored by in vivo contractile testing of the hindlimb at 1, 2, and 4 wk after injury. By the 4 wk time point, the Low-Dose POG group continued to show improved functional recovery (85% of baseline) compared with the Tourniquet-Only (48%) and High-Dose POG (56%) groups. In short, the low-dose POG formulation appeared, at least in part, to mitigate the impact of ischemic tissue injury, thus improving contractile function after tourniquet application. Functional improvement correlated with maintenance of larger muscle fiber cross-sectional area and the presence of fewer fibers containing centrally located nuclei. As such, POGs represent a potentially attractive therapeutic solution for addressing I/R injuries associated with extremity trauma.NEW & NOTEWORTHY Skeletal muscle contraction was evaluated in the same animals at multiple time points up to 4 wk after injury, following administration of particulate oxygen generators (POGs) in a clinically relevant rat hindlimb model of tourniquet-induced ischemia. The observed POG-mediated improvement of muscle function over time confirms and extends previous studies to further document the potential clinical applications of POGs. Of particular significance in austere environments, this technology can be applied in the absence of an intact circulation.