title: Poloxamer 188 failed to prevent exercise-induced membrane breakdown in mdx skeletal muscle fibers.
abstract: We sought to determine the effectiveness of poloxamer 188 (P188) in protecting dystrophin-deficient, mdx skeletal muscle fiber membrane against exercise-induced breaches. mdx mice were treated with either P188 or placebo via intraperitoneal injections and run on a treadmill for 60-90 min. Membrane breakdown was quantified in cross-sections of rectus femoris muscle pretreated with Evans blue dye (in vivo). The mean % dye-penetrated muscle in the P188 and placebo groups was not significantly different in each of three trials. These results contrast with a recent report of P188 being highly effective in protecting the stretch- and dobutamine-stressed mdx heart muscle. The most likely explanations for the disparity are: (1) the exercise stress we used was beyond the protective range of P188, (2) P188 delivery and serum concentration were sub-optimal, or (3) the mdx skeletal myopathy and cardiomyopathy have fundamentally different responses to treatment.
authors.affiliation: Department of Neurology, The University of Cincinnati, 4010 Medical Science Building, Cincinnati, OH 45267-0525, USA. john.quinlan@uc.edu
authors.forename: John G
authors.initials: JG
authors.lastname: Quinlan
authors.forename: Brenda L
authors.initials: BL
authors.lastname: Wong
authors.forename: Richard T
authors.initials: RT
authors.lastname: Niemeier
authors.forename: Alexandra S
authors.initials: AS
authors.lastname: McCullough
authors.forename: Linda
authors.initials: L
authors.lastname: Levin
authors.forename: Martin
authors.initials: M
authors.lastname: Emanuele
mesh_terms: D000818:Animals; D009202:Cardiomyopathies / Q000188:drug therapy / Q000378:metabolism / Q000503:physiopathology; D002463:Cell Membrane Permeability / Q000187:drug effects* / Q000502:physiology; D004396:Coloring Agents; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004333:Drug Administration Routes; D017079:Exercise Tolerance / Q000187:drug effects / Q000502:physiology; D005260:Female; D007274:Injections, Intraperitoneal; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018101:Mice, Inbred mdx; D009119:Muscle Contraction / Q000187:drug effects / Q000502:physiology; D018485:Muscle Fibers, Skeletal / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D018482:Muscle, Skeletal / Q000187:drug effects* / Q000378:metabolism / Q000503:physiopathology; D020388:Muscular Dystrophy, Duchenne / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology; D010805:Physical Conditioning, Animal / Q000502:physiology; D020442:Poloxamer / Q000494:pharmacology* / Q000627:therapeutic use; D012508:Sarcolemma / Q000187:drug effects* / Q000378:metabolism; D013501:Surface-Active Agents / Q000494:pharmacology / Q000627:therapeutic use; D017211:Treatment Failure
chemical_list: D004396:Coloring Agents; D013501:Surface-Active Agents; D020442:Poloxamer