title: Ischemia-reperfusion-induced muscle damage. Protective effect of corticosteroids and antioxidants in rabbits.
abstract: We examined the potential protective effect of pretreatment with corticosteroids or antioxidants (ascorbic acid or allopurinol) in rabbits with reperfusion-induced damage to skeletal muscle after ischemia. 4 hours of limb ischemia induced by a pneumatic tourniquet, followed by reperfusion for 1 hour, caused a considerable amount of ultrastructural damage to the anterior tibialis muscles accompanied by a rise in circulating creatine kinase activity. Pretreatment of animals with depomedrone by a single 8 mg bolus injection led to a preservation of the anterior tibialis structure on both light and electron microscopy. High-dose continuous intravenous infusion with ascorbic acid (80 mg/hr) throughout the period of ischemia and reperfusion also preserved skeletal muscle structure, although allopurinol in various doses had no protective effect. These data are fully compatible with a mechanism of ischemia/reperfusion-induced injury to skeletal muscle, involving generation of oxygen radicals and neutrophil sequestration and activation. They also indicate that damage to human skeletal muscle caused by prolonged use of a tourniquet is likely to be reduced by simple pharmacological interventions.
authors.affiliation: Department of Medicine, University of Liverpool, U.K.
authors.forename: A
authors.initials: A
authors.lastname: Bushell
authors.forename: L
authors.initials: L
authors.lastname: Klenerman
authors.forename: H
authors.initials: H
authors.lastname: Davies
authors.forename: I
authors.initials: I
authors.lastname: Grierson
authors.forename: M J
authors.initials: MJ
authors.lastname: Jackson
mesh_terms: D000493:Allopurinol / Q000494:pharmacology; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology; D000963:Antimetabolites / Q000494:pharmacology; D000975:Antioxidants / Q000494:pharmacology; D001205:Ascorbic Acid / Q000494:pharmacology; D007511:Ischemia / Q000473:pathology*; D008775:Methylprednisolone / Q000031:analogs & derivatives / Q000494:pharmacology; D000077555:Methylprednisolone Acetate; D009132:Muscles / Q000098:blood supply* / Q000187:drug effects* / Q000648:ultrastructure; D011817:Rabbits; D015427:Reperfusion Injury / Q000517:prevention & control*
chemical_list: D000893:Anti-Inflammatory Agents; D000963:Antimetabolites; D000975:Antioxidants; D000077555:Methylprednisolone Acetate; D000493:Allopurinol; D001205:Ascorbic Acid; D008775:Methylprednisolone