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N-ACETYL CYSTEINE PRE AND POST TREATMENT PREVENTS COMPARTMENT SYNDROME INDUCED SKELETAL MUSCLE INJUR



Abstract

Purpose: Compartment syndrome (CS) is a unique form of skeletal muscle ischaemia. N-acetyl cysteine (NAC) is an anti-oxidant with beneficial microcirculatory effects. We aim to assess the effect of NAC administration on CS induced muscle injury.

Methods: Sprague-Dawley rats (n=6/group) were randomised into Control, CS and CS pre-treated with NAC (0.5g/kg i.p. 1 hr prior to induction) groups. In a post-treatment group NAC was administered upon muscle decompression. Cremasteric muscle was placed in a pressure chamber in which pressure was maintained at diastolic minus 10 mm Hg for 3 hours inducing CS, muscle was then returned to the abdominal cavity. At 24 hours and 7 days post CS contractile function was assessed by electrical stimulation. Myeloperoxidase (MPO) activity were assessed at24-hours.

Results: CS injury reduced twitch (50.4 ± 7.7 vs 108.5 ± 11.5, p< 0.001; 28.1 ± 5.5 vs. 154.7 ± 14.1, p< 0.01) and tetanic contraction (225.7 ± 21.6 vs 455.3 ± 23.3, p< 0.001; 59.7 ± 12.1 vs 362.9 ± 37.2, p< 0.01) compared with control at 24hrs and 7 days respectively. NAC pre-treatment reduced CS injury at 24 hours preserving twitch (134.3 ± 10.4 , p< 0.01 vs CS) and tetanic (408.3 ± 34.3, p< 0.01 vs CS) contraction. NAC administration reduced neutrophil infiltration (MPO) at 24 hours (24.6 ± 5.4 vs 24.6 ± 5.4, p< 0.01). NAC protection was maintained at 7 days preserving twitch (118.2 ± 22.9 vs 28.1 ± 5.5, p< 0.01) and tetanic contraction (256.3 ± 37 vs 59.7 ± 12.1, p< 0.01). Administration of NAC at decompression also preserved muscle twitch (402.4 ± 52; p< 0.01 versus CS) and tetanic (402.4 ± 52; p< 0.01 versus CS) contraction, reducing neutrophil infiltration (24.6 ± 5.4 units/g; p< 0.01).

Conclusions: |NAC provides extended protection to skeletal muscle against compartment syndrome induced injury by both direct reducing neutrophil mediated tissue toxicity and by reducing neutrophil recruitment to the site of injury.

Correspondence should be addressed to Cynthia Vezina, Communications Manager, COA, 4150-360 Ste. Catherine St. West, Westmount, QC H3Z 2Y5, Canada