Remote lung injury after experimental intestinal ischemia-reperfusion in horses

Abstract

Ischemia followed by reperfusion leads to release of toxic molecules into the circulation, and these molecules may cause injury in remote organs such as the lung. Horses commonly suffer from episodes of intestinal ischemia-reperfusion (IR) due to intestinal twisting/strangulation followed by repair. Because there is no evidence of lung injury associated with IR in horses, we designed a study to characterize the intestinal IR-associated lung inflammation and determine the effect of lidocaine on lung inflammation in IR horses. Lung tissues were collected from non-anesthetized (n=4) and anesthetized (n=4) control horses and horses (n=12) after 70 minutes of ischemia followed by 60 minutes of reperfusion. Horses in IR groups received Lactated Ringer’s Solution (LRS; n=6) or lidocaine (n=6) intravenously. Control lungs had normal histology but lungs from IR horses showed moderate accumulation of neutrophils in blood vessels and airways. We found increased staining for TLR4, IL-8, TLR9, and von Willebrand factor (vWF) along with aggregates of vWFpositive platelets in lung vessels of IR horses compared to the controls. Lung TNFα was significantly increased in IR horses compared to the control horses (P<0.05). Neutrophil numbers, but not MPO concentrations, were significantly lower, while macrophage numbers were higher in the IR group receiving lidocaine compared to the LRS horses (P<0.05). We conclude that intestinal IR leads to remote lung injury characterized by recruitment of inflammatory cells and expression of inflammatory molecules in horses, and lidocaine may ameliorate lung inflammation following intestinal IR.