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Administration of Particulate Oxygen Generators Improves Skeletal Muscle Contractile Function Following Ischemia-Reperfusion Injury in the Rat Hind Limb.

Sarah E Dyer,J. Remer,Kelsey E Hannifin,Aishwarya Hombal,J. Wenke,T. Walters,G. Christ

Published 2022 in Journal of applied physiology

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 hind limb during tourniquet application. Male Lewis rats were anesthetized and underwent tourniquet application for 3 hours, 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 using in vivo contractile testing of the hind limb at 1-, 2-, and 4-weeks post-injury. By the 4 week time point, the Low Dose POGs group continued to show improved functional recovery (85% of baseline) compared to the Tourniquet-Only (48%) and High Dose POG (56%) groups. In short, the Low Dose POGs formulation appeared, at least in part, to mitigate the impact of ischemic tissue injury, thus improving contractile function following 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.

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