46. INDOMETHACIN: SHEDDING NEW LIGHT ON COMPARTMENT SYNDROME

Abstract

Purpose: Indomethacin may preserve tissue viability in compartment syndrome. The mechanism of improved tissue viability is unclear, but the anti-inflammatory effects may alter the relative contribution of tissue necrosis versus apoptosis to cellular injury. Existing studies have only considered indomethacin administration prior to induction of compartment syndrome. The purpose of this study was to determine the effect of timing of indomethacin administration on muscle damage in compartment syndrome, and to assess apoptosis as a cause of tissue demise.

Method: Twenty-four Wistar rats were randomized to elevated intracompartmental pressure (EICP) for either 45 or 90 minutes (30mm Hg). In the 45 min group, indomethacin was withheld (group 1), given prior to induction of EICP (group 2) or given 15 min prior to fasciotomy (group 3). In the 90 min group, indomethacin was withheld (group 4) or provided 30 or 60 minutes prior to fasciotomy (groups 5 and 6). Intravital microscopy and histochemical staining assessed capillary perfusion, cell damage and inflammatory activation within EDL muscle. Apoptosis was assessed using ELISA staining for caspase-3. Groups were compared with one-way ANOVA (p< 0.05).

Results: Perfusion improved in indomethacin-treated groups. Nonperfused capillaries decreased from group 1 (50.1±2.5), to groups 2 (38.4±1.8) and 3 (14.13±1.73)(p< 0.0001). Similarly, groups 5 and 6 had 25% fewer non-perfused capillaries compared to group 4 (p< 0.0001). Tissue viability improved in indo-methacin-treated groups. Groups 2 and 3 showed fewer damaged cells (1±0.5% and 8.7±2%) compared to group 1 (20±14%)(p< 0.0001). Groups 5 and 6 showed decreased cell damage (13±1% and 11±1%) compared to group 4 (18±1%) (p< 0.01). Apoptotic activity was present in compartment syndrome. At 30 minutes there were elevated caspase levels in EICP groups (0.47±0.08) compared to controls (0.19±0.02). However, indomethacin treated groups did not differ from controls with regards to caspase levels (p> 0.05).

Conclusion: Indomethacin decreased cell damage and improved perfusion in compartment syndrome. The benefits of indomethacin were partially time dependent; some improvement in tissue viability occurred regardless of timing of administration. Although apoptosis was common in compartment syndrome, the protective effect of indomethacin does not appear to be related to apoptosis.