Ischemia-reperfusion-induced muscle damage. Protective effect of corticosteroids and antioxidants in rabbits.
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.
Bushell
A
A
Department of Medicine, University of Liverpool, U.K.
Klenerman
L
L
Davies
H
H
Grierson
I
I
Jackson
M J
MJ
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*
D000893:Anti-Inflammatory Agents; D000963:Antimetabolites; D000975:Antioxidants; D000077555:Methylprednisolone Acetate; D000493:Allopurinol; D001205:Ascorbic Acid; D008775:Methylprednisolone