Pravastatin attenuates tourniquet-induced skeletal muscle ischemia reperfusion injury.
BACKGROUND
Revascularization of a limb following prolonged ischemia results in substantial skeletal muscle injury. Statins play a well-understood role in the treatment of hypercholesterolemia but are also known to have anti-inflammatory properties. The purpose of this study was to examine the effects of pravastatin pre-treatment in the setting of skeletal muscle ischemia reperfusion injury (IRI).


METHODS
Adult male Sprague Dawley rats (n = 27) were randomized into 3 groups: control group, I/R group, IR group pre-treated with pravastatin. Bilateral hind-limb ischemia was induced by rubber band application proximal to the level of the greater trochanters for 2.5 h. Treatment groups received normal saline in equal volumes prior to tourniquet release. Following 12 h reperfusion, the tibialis anterior muscle was dissected and muscle function assessed electrophysiologically by electrical field stimulation. The animals were then killed and skeletal muscle harvested for evaluation.


RESULTS
We found that pre-treatment with pravastatin reduces the tissue oxidative damage and edema associated with skeletal muscle reperfusion injury. Skeletal muscle injury, measured by edema, leucosequestration and electrical properties were significantly lower with pravastatin pre-treatment compared to the non-treated group.


CONCLUSIONS
We feel that pravastatin pre-treatment may be a potential therapeutic intervention for skeletal muscle ischemia reperfusion injury in the clinical setting.
Department of Orthopaedics and Academic Surgery, Cork University Hospital, Wilton, Cork, Ireland. dillonjp@o2.ie
John P
JP
Dillon
Alan J
AJ
Laing
John R S
JR
Chandler
Jiang H
JH
Wang
Anthony
A
McGuinness
Henry P
HP
Redmond
D000284:Administration, Oral; D000818:Animals; D000924:Anticholesteremic Agents / Q000008:administration & dosage / Q000494:pharmacology*; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000008:administration & dosage / Q000494:pharmacology*; D008297:Male; D018482:Muscle, Skeletal / Q000098:blood supply / Q000187:drug effects* / Q000503:physiopathology; D017035:Pravastatin / Q000008:administration & dosage / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D015427:Reperfusion Injury / Q000209:etiology / Q000517:prevention & control*; D014111:Tourniquets / Q000009:adverse effects*
D000924:Anticholesteremic Agents; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D017035:Pravastatin