Abstract
Purpose: This study was designed to determine whether indomethacin, a potent anti-inflammatory agent, reduces muscle damage secondary to elevated ICP.
Method: 16 adult Wistar rats were randomized to 4 groups. In group 1 (control), no intervention occurred. Group 2 (indo) rats were administered indomethacin (12mg/kg) with no elevation of ICP. Group 3 (CS) rats had elevated ICP (30–40mmHg × 45 minutes) using saline injection. Group 4 rats (CS/indo) had elevated ICP and indomethacin administration. After 45 minutes, hindlimb fasciotomy was performed. The extensor digitorum longus muscle was reflected onto an intravital microscope. Capillary perfusion was measured by comparing the number of continuously perfused capillaries to intermittent and non perfused capillaries. Inflammation was determined using the number of activated (rolling and adherent) white blood cells. Muscle cell damage was measured using differential fluorescent staining. Perfusion, inflammation, and muscle damage were compared in all 4 groups using a one-way ANOVA (p< 0.05).
Results: Perfusion: Indomethacin treatment (CS/indo) increased the proportion of intermittently perfused capillaries (39.1 ± 2.2 vs 30.3 ± 2.7) and decreased nonperfused capillaries (38.4 ± 1.8 vs 50.1 ±2.5) compared to CS (p=0.0002). Control and indo groups demonstrated more continuously perfused capillaries compared to CS or CS/indo groups (p0.05).
Conclusion: Treatment of elevated ICP with indomethacin improved microvascular perfusion and reduced cell damage. The protective mechanism of indomethacin is unknown, but may be related to an anti-oxidative and vasodilatory effect. Treatment of elevated intracompartmental pressure with indomethacin dramatically reduces muscle damage and may have important future clinical benefit. Further research is required to determine the mechanism of action.
Correspondence should be addressed to Meghan Corbeil, Meetings Coordinator Email: meghan@canorth.org
