Poloxamer-188 reduces muscular edema after tourniquet-induced ischemia-reperfusion injury in rats

J Trauma. 2011 May;70(5):1192-7. doi: 10.1097/TA.0b013e318217879a.

Abstract

Background: Skeletal muscle injury can result in significant edema, which can in turn lead to the development of acute extremity compartment syndrome (CS). Poloxamer-188 (P-188), a multiblock copolymer surfactant, has been shown to decrease edema by sealing damaged membranes in a number of tissues after a variety of injury modalities. The objective is to determine whether the administration of P-188 significantly reduces skeletal muscle edema associated with ischemia/reperfusion injury (I-R).

Methods: Male Sprague-Dawley rats underwent 180 minutes of tourniquet-induced ischemia. Five minutes before tourniquet release, rats received either a bolus of (1) P-188 (150 mg/kg; P-188 group) or (2) vehicle (Vehicle group) via a jugular catheter (n=10 per group). After 240 minutes reperfusion, both groups received a second bolus of either P-188 (P-188) or vehicle (Vehicle) via a tail vein catheter. Sixteen hours later, rats were killed; muscle weights were determined, infarct size (2,3,5-triphenyltetrazolium chloride method), and blinded histologic analysis (hematoxylin and eosin) were performed on the gastrocnemius and tibialis anterior muscles, as well as indices of antioxidant status.

Results: P-188 resulted in significantly less edema (wet weight) and reduced an index of lipid peroxidation compared with Vehicle (p<0.05). Wet:dry weight ratios were less in the P-188 group (indicating less edema). Muscle viability as indicated by 2,3,5-triphenyltetrazolium chloride staining or routine histology did not reveal statistically significant differences between groups.

Conclusion: P-188 significantly reduced ischemia-reperfusion-related muscle edema and lipid peroxidation but did not impact muscle viability. Excess edema can lead to acute extremity CS, which is associated with significant morbidity and mortality. P-188 may provide a potential adjunctive treatment for the reduction of CS.

Publication types

  • Comparative Study
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Animals
  • Disease Models, Animal
  • Edema / drug therapy*
  • Edema / etiology
  • Edema / physiopathology
  • Lipid Peroxidation / drug effects
  • Male
  • Muscular Diseases / drug therapy*
  • Muscular Diseases / etiology
  • Muscular Diseases / metabolism
  • Poloxamer / therapeutic use*
  • Rats
  • Rats, Sprague-Dawley
  • Reperfusion Injury / complications*
  • Reperfusion Injury / metabolism
  • Surface-Active Agents / therapeutic use
  • Tourniquets / adverse effects
  • Treatment Outcome

Substances

  • Surface-Active Agents
  • Poloxamer