Protection against acute porcine lung ischemia/reperfusion injury by systemic preconditioning via hind limb ischemia

Abstract

Previous work on various organs and tissues has shown that ischemic preconditioning protects against reperfusion injury in these organs and also against secondary effects in the lung. In contrast, the purpose of this study was to investigate the effects of preconditioning in a remote organ (hind limb ischemia) on an ischemia/reperfusion (I/R) treatment of the lung itself. A porcine model of in situ left lung ischemia (90 min) and reperfusion (5 h) was used. Systemic preconditioning was induced by clamping the left common femoral artery (3 x 5 min). Lung injury was assessed in terms of pulmonary vascular resistance, pulmonary artery pressure, pulmonary venous and arterial pO(2), and tissue macrophage counts. The zymosan-stimulated release of reactive oxygen species (ROS) in whole blood was determined by a chemiluminometric procedure. Inflammatory cytokines (interleukin-1beta and interleukin-6) were measured in arterial plasma as indicators of a systemic inflammatory reaction. Preconditioning by hind limb ischemia completely prevented the I/R-induced functional impairment of the lung, the pulmonary hypertension and the reduced oxygenation capacity. The plasma levels of interleukin-1beta and the macrophage counts in preconditioned animals were reduced to control values, whereas the levels of interleukin-6 and the release of ROS were not affected by preconditioning. In conclusion, systemic preconditioning by repeated hind limb ischemia protects against acute I/R injury of the lung but not against all indices of reperfusion-associated systemic inflammation.