Glycine preserves function and decreases necrosis in skeletal muscle undergoing ischemia and reperfusion injury

Background. Glycine (GLY) is a neutral amino acid that has been shown to be cytoprotective in the kidneys of dogs and rabbits undergoing ischemia-repe rfusion injury. To investigate whether GLY exhibits a protective effect on skeletal muscle subjected to ischemia and reperfusion injury, we used a wel l-described gracilis muscle model in canines. Methods. Twelve adult mongrel dogs were subjected to 6 hours of ischemia in 1 randomly selected side. The dogs were randomized into 2 groups: group 1 (6 animals) underwent 15 minutes of perfusion with 2.2% GLY, and group (6 a nimals) underwent 15 minutes of perfusion with normal saline solution (NS) only. Both groups had normothermic reperfusion for 1 hour along with the co rresponding perfusate. Muscle biopsy specimens were taken, frozen in liquid nitrogen, and stored ata -70 degreesC. Muscle injury was evaluated at 48 h ours by measuring weight gain (edema), maximal contractile force, and perce nt of muscle necrosis. Adenosine triphosphate (ATP) and phosphocreatine (Pc r) (an energy store for ATP synthesis) levels were determined by suing high performance liquid chromatography. Results. IN group 1, the average weight gain was 57% +/- 11.27% while in ro up 2 it was 100% +/- 12.48%. Maximal muscle contractile force was 712.5 +/- 68 g for group 1 and 511 +/- 27.91 g for group 2. The amount of muscle nec rosis was 30 +/- 3.7% in group 1, as opposed to 63 +/- 10% in group 2. The ATP content was 0.07 +/- 0.03 nmol/mg wet tissue weight (post-ischemia with NS) and 0.21 +/- 0.08 nmol/mg wet tissue weight (post-ischemia with GLY). Pcr content was 0.19 +/- 0.04 mu mol/mg wet tissue weight (post-ischemia wi th NS) and 0.27 +/- 0.04 mu mol/mg wet tissue (post-ischemia and infused wi th GLY) (P<.05). Conclusions. These data show that GLY preserves muscle function, decreases edema and the amount of muscle necrosis and preserves energy stores in this canine model. Because GLY can be safely given systematically in human bein gs in higher concentrations than that given in our model, as it is given in parenteral nutrition, its mechanism of action should be further investigat ed for its potential use in the clinical setting of ischemia and reperfusio n injury.