Protective effect of preconditioning and adenosine pretreatment in experimental skeletal muscle reperfusion injury.
BACKGROUND
Prolonged ischaemia followed by reperfusion (I/R) of skeletal muscle results in significant tissue injury. Ischaemic preconditioning (IPC), achieved by repeated brief periods of I/R before prolonged ischaemia or adenosine pretreatment, can prevent I/R injury in cardiac muscle. The aim of this study was to ascertain in a rodent model if damage to skeletal muscle due to global hindlimb tourniquet-induced I/R could be similarly attenuated.


METHODS
Anaesthetized rats were randomized (n = 6-10 per group) to five groups: sham-operated controls; I/R (4 h of ischaemia, 2 h of reperfusion); IPC (three cycles of 10 min of ischaemia/10 min of reperfusion) alone; IPC immediately preceding I/R; or adenosine 1000 microg/kg immediately before I/R. At the end of reperfusion, biopsies were taken from the left gastrocnemius muscle for measurement of myeloperoxidase (MPO) and reduced glutathione (GSH). Before ischaemia and at the end of reperfusion, blood samples were taken for measurement of nitric oxide metabolites, tumour necrosis factor (TNF) alpha and macrophage inflammatory protein (MIP) 2.


RESULTS
IPC before I/R resulted in lower levels of MPO (P < 0.001) and TNF-alpha (P = 0.004), and higher levels of GSH (P < 0.001) and nitric oxide metabolites (P = 0.002) than I/R alone. Adenosine had effects comparable to IPC pretreatment (P < 0.001 for MPO, P = 0.002 for GSH, P = 0.02 for nitric oxide metabolites and P = 0.001 for TNF-alpha). There was no difference in the blood pressure or the MIP-2 concentration among the groups.


CONCLUSIONS
IPC or pretreatment with adenosine ameliorates the I/R injury of skeletal muscle.
Division of Surgery, Anaesthetics and Intensive Care, Imperial College School of Medicine, Hammersmith Hospital, London. UK.
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Papanastasiou
S E
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Estdale
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Homer-Vanniasinkam
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Mathie
D000241:Adenosine / Q000627:therapeutic use*; D000818:Animals; D001794:Blood Pressure; D002317:Cardiovascular Agents / Q000627:therapeutic use*; D054426:Chemokine CXCL2; D005978:Glutathione / Q000378:metabolism; D019194:Ischemic Preconditioning / Q000379:methods*; D008297:Male; D015846:Monokines / Q000378:metabolism; D018482:Muscle, Skeletal / Q000098:blood supply* / Q000293:injuries; D009569:Nitric Oxide / Q000378:metabolism; D009195:Peroxidase / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D015427:Reperfusion Injury / Q000517:prevention & control*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
D002317:Cardiovascular Agents; D054426:Chemokine CXCL2; D015846:Monokines; D014409:Tumor Necrosis Factor-alpha; D009569:Nitric Oxide; D009195:Peroxidase; D005978:Glutathione; D000241:Adenosine