Poloxamer-188 Reduces Muscular Edema After Tourniquet-Induced Ischemia-Reperfusion Injury in Rats

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 tourniquetinduced 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.

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Document Details

Document Type
Technical Report
Publication Date
May 01, 2011
Accession Number
ADA618970

Entities

People

  • Janet L. Roe
  • Michael A. Dubick
  • Robert J Christy
  • Thomas J. Walters
  • Vincent J. Mase Jr.

Organizations

  • United States Army Institute of Surgical Research

Tags

DTIC Thesaurus Topics

  • Blood
  • Cell Membrane
  • Cells
  • Chemical Synthesis
  • Chemistry
  • Combat Injuries
  • Hydrophilic Properties
  • Ischemia
  • Laboratory Animals
  • Medical Personnel
  • Oxidative Stress
  • Patient Care
  • Physical Chemistry
  • Skeletal Muscle
  • United States
  • United States Government
  • Vascular Diseases

Fields of Study

  • Medicine

Readers

  • Cardiovascular Physiology
  • Toxicology/Environmental Toxicology
  • Trauma Surgery or Emergency Medicine.

Technology Areas

  • Microelectronics
  • Microelectronics - Microelectromechanical Systems