The effects of hypothermia and L-arginine on skeletal muscle function in ischemia-reperfusion injury.

Abstract

Ischemia-reperfusion (I/R) injury can have detrimental effects on skeletal muscle. We have shown that vessel permeability can be minimized in a hypothermic setting and also by administering the nitric oxide synthase (NOS) stimulator, L-arginine, at physiologic temperatures. The purpose of this study was to examine and compare skeletal muscle contractility after an I/R insult during hypothermic conditions, warm conditions, and also with the administration of L-arginine at physiologic temperatures. We hypothesized that hypothermia and L-arginine administration will also demonstrate protective effects to skeletal muscle contractility. Using Sprague-Dawley rats, the extensor digitorum longus muscle was rotated on its vascular pedicle to a thermo-controlled stage. Ischemia was established using an atraumatic femoral artery tourniquet. Reperfusion was performed under control and experimental conditions including local hypothermia and intravenous L-arginine. After harvesting experimental muscles, contractility was then quantified by using a tissue bath stimulator with force transducers. Warm reperfusion resulted in marked decrease in muscle contractility compared with sham animals. Local hypothermia showed statistically significant preservation of contractility compared with the sham group. This protective effect was recapitulated by the application of NOS inducers (L-arginine) at warm conditions. These findings demonstrate that hypothermia and L-arginine are protective of skeletal muscle contractility after an I/R injury. The results presented may have profound effects on future therapeutic recommendations and suggest possible pathways for clinical intervention to modulate I/R injury, which is commonplace in orthopaedic trauma and reconstructive surgery.