Ischemic preconditioning before lower limb ischemia--reperfusion protects against acute lung injury.
OBJECTIVE
Prolonged limb ischemia followed by reperfusion (I/R) is associated with a systemic inflammatory response syndrome and remote acute lung injury. Ischemic preconditioning (IPC), achieved with repeated brief periods of I/R before the prolonged ischemic period, has been shown to protect skeletal muscle against ischemic injury. The aim of this study was to ascertain whether IPC of the limb before I/R injury also attenuates systemic inflammation and acute lung injury in a fully resuscitated porcine model of hind limb I/R.


METHODS
This prospective, randomized, controlled, experimental animal study was performed in a university-based animal research facility with 18 male Landrace pigs that weighed from 30 to 35 kg. Anesthetized ventilated swine were randomized (n = 6 per group) to three groups: sham-operated control group, I/R group (2 hours of bilateral hind limb ischemia and 2.5 hours of reperfusion), and IPC group (three cycles of 5 minutes of ischemia/5 minutes of reperfusion immediately preceding I/R). Plasma was separated and stored at -70 degrees C for later determination of plasma tumor necrosis factor-alpha and interleukin-6 with bioassay as markers of systemic inflammation. Circulating phagocytic cell priming was assessed with a whole blood chemiluminescence assay. Lung tissue wet-to-dry weight ratio and myeloperoxidase concentration were markers of edema and neutrophil sequestration, respectively. The alveolar-arterial oxygen gradient and pulmonary artery pressure were indices of lung function.


RESULTS
In a porcine model, bilateral hind limb (I/R) injury significantly increased plasma interleukin-6 concentrations, circulating phagocytic cell priming, and pulmonary leukosequestration, edema, and impaired gas exchange. Conversely, pigs treated with IPC before the onset of the ischemic period had significantly reduced interleukin-6 levels, circulating phagocytic cell priming, and experienced significantly less pulmonary edema, leukosequestration, and respiratory failure.


CONCLUSIONS
Lower limb IPC protects against systemic inflammation and acute lung injury in lower limb I/R injury.
Harkin
Denis W
DW
Vascular Surgical Unit, The Royal Victoria Hospital, Institute of Clinical Sciences, The Queen's University of Belfast, Grosvenor Road, Belfast, Northern Ireland BT12 6BJ, UK. D.W.Harkin@qub.ac.uk
Barros D'Sa
Aires A B
AA
McCallion
Kevin
K
Hoper
Margaret
M
Campbell
F Charles
FC
D000818:Animals; D006614:Hindlimb / Q000098:blood supply*; D015850:Interleukin-6 / Q000097:blood; D019194:Ischemic Preconditioning; D008297:Male; D011659:Pulmonary Gas Exchange; D015427:Reperfusion Injury / Q000517:prevention & control*; D012128:Respiratory Distress Syndrome / Q000517:prevention & control*; D013552:Swine; D014409:Tumor Necrosis Factor-alpha / Q000032:analysis
D015850:Interleukin-6; D014409:Tumor Necrosis Factor-alpha