Ischemic preconditioning before lower limb ischemia--reperfusion protects against acute lung injury.

Abstract

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.

CONCLUSION:

Lower limb IPC protects against systemic inflammation and acute lung injury in lower limb I/R injury.

• Authors: Denis W Harkin, Aires A B Barros D'Sa, Kevin McCallion, Margaret Hoper, F Charles Campbell
• Journal: Journal of vascular surgery (J Vasc Surg) Vol. 35 Issue 6 Pg. 1264-73 (Jun 2002) ISSN: 0741-5214 [Print] United States
• PMID: 12042740 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Interleukin-6
• Tumor Necrosis Factor-alpha

Topics

• Animals
• Hindlimb (blood supply)
• Interleukin-6 (blood)
• Ischemic Preconditioning
• Male
• Pulmonary Gas Exchange
• Reperfusion Injury (prevention & control)
• Respiratory Distress Syndrome (prevention & control)
• Swine
• Tumor Necrosis Factor-alpha (analysis)