Endotracheal calcineurin inhibition ameliorates injury in an experimental model of lung ischemia-reperfusion

There is a marked increase in permeability index between unmanipulated animals (normal) and vehicle-treated animals undergoing ischemia of 90 minutes followed by reperfusion of 4 hours (IR4). TAC-treated animals showed protection against increased vascular permeability at all 3 doses studied (P < .005 for all 3 groups). There was no significant difference in permeability index between the 0.2 and 0.1 mg/kg doses. TAC, Tacrolimus; I/R, ischemia-reperfusion.

Left lung tissue MPO content increased dramatically between unmanipulated animals (normal) and vehicle-treated animals undergoing 90 minutes of ischemia followed by 4 hours of reperfusion (IR4). MPO content was significantly decreased with TAC treatment (0.1 mg/kg) (P < .001).

BAL cell count increased 20-fold between unmanipulated animals (normal) and vehicle-treated animals undergoing 90 minutes of ischemia followed by 4 hours of reperfusion (IR4). Cell counts were decreased by 77% in the TAC-treated group (0.1 mg/kg) (P < .001).

A, There was a marked increase in BAL CINC content in vehicle-treated animals undergoing 90 minutes of ischemia followed by 4 hours of reperfusion (IR4) compared with unmanipulated animals (normal). TAC treatment (0.1 mg/kg) significantly decreased CINC levels in BAL fluid (P < .002). B, MIP-1α content of BAL fluid was increased in vehicle-treated animals undergoing 90 minutes of ischemia followed by 4 hours of reperfusion (IR4) compared with unmanipulated animals (normal). TAC treatment (0.1 mg/kg) decreased this by 93% (P < .001). C, TNF-α content in BAL increased in vehicle-treated animals undergoing 90 minutes of ischemia followed by 4 hours of reperfusion (IR4) compared with unmanipulated animals (normal). TAC treatment (0.1 mg/kg) decreased this by 69% (P < .03).

A, Representative EMSA for NF-κB nuclear translocation. Cold competition (cold lane); vehicle-treated animals that underwent 90 minutes of ischemia followed by 15 minutes of reperfusion (IR15 lanes); TAC-treated animals (0.1 mg/kg undergoing the same periods of I/R (TAC lanes). There is less activation of NF-κB in the TAC-treated animals than in the vehicle-treated animals. B, Relative densitometry from EMSAs for NF-κB nuclear translocation. There is a decrease in relative densitometric value with TAC treatment when compared with the vehicle-treated groups (P < .003).