N-acetylcysteine protects striated muscle in a model of compartment syndrome

Background: To avoid ischemic necrosis, compartment syndrome is a surgical emergency treated with decompression once identified. A potentially lethal, oxidant-driven reperfusion injury occurs after decompression. N-acetylcysteine is an antioxidant with the potential to attenuate the reperfusion injury. Questions/purposes: We asked whether N-acetylcysteine could preserve striated muscle contractility and modify neutrophil infiltration and activation after simulated compartment syndrome release. Materials and Methods: Fifty-seven rats were randomized to control, simulated compartment syndrome, and simulated compartment syndrome plus N-acetylcysteine groups. We isolated the rodent cremaster muscle on its neurovascular pedicle and placed it in a pressure chamber. Chamber pressure was elevated above critical closing pressure for 3 hours to simulate compartment syndrome. Experiments were concluded at three times: 1 hour, 24 hours, and 7 days after decompression of compartment syndrome. We assessed twitch and tetanic contractile function and tissue myeloperoxidase activity. Ten additional rats were randomized to control and N-acetylcysteine administration after which neutrophil respiratory burst activity was assessed. Results: The simulated compartment syndrome decreased muscle contractility and increased muscle tissue myeloperoxidase activity compared with controls. Treatment with N-acetylcysteine preserved twitch and tetanic contractility. N-acetylcysteine did not alter neutrophil infiltration (myeloperoxidase activity) acutely but did reduce infiltration at 24 hours, even when given after decompression. N-acetylcysteine reduced neutrophil respiratory burst activity. Conclusion: N-acetylcysteine administration before or after simulated compartment syndrome preserved striated muscle contractility, apparently by attenuating neutrophil activation and the resultant oxidant injury. Clinical Relevance: Our data suggest a potential role for N-acetylcysteine in the attenuation of muscle injury after release of compartment syndrome and possibly in the prophylaxis of compartment syndrome.