Effects of tacrolimus on mechanical and humoral determinants of brain death-induced lung injury

Abstract

The mechanisms of brain death (BD)-induced lung injury is due to mechanical and humoral perturbations. Brain death was induced by slow intracranial blood infusion in anesthetized pigs after randomization to placebo (n = 9) or to tacrolimus (n = 8 ; 0.1 mg/Kg/J) to inhibit the expression of pro-inflammatory mediators. Pulmonary artery pressure (PAP), wedged PAP (PAWP), pulmonary vascular resistance (PVR) and effective pulmonary capillary pressure (PCP) were measured 2, 4 and 6 hours after Cushing reflex. Lung tissue was sampled to determine gene expressions of cytokinesand pathologically score lung injury. Intracranial hypertension caused a transient increase in blood pressure followed, after brain death was diagnosed, by persistent increases in PAP, PCP and the venous component of PVR, while PAWP did not change. Arterial PO2/fraction of inspired O2 (PaO2/FiO2) decreased. Brain death was associated with an accumulation of neutrophils in lung tissue together with increased pro-inflammatory interleukin (IL)-6/IL-10 ratio. Blood expressions of IL-6 and IL-1β were also increased. Blood expressions of IL-6 and IL-1β were also increased. Tacrolimus pre-treatment was associated with a blunting of increased PCP and PVR venous component, which returned to baseline 6 hours after BD, and partially corrected lung tissue biological perturbations. PaO2/FiO2 and lung injury score were prevented. In conclusion, increase in pulmonary capillary pressure with pulmonary venous resistance, associated with lung inflammatory process were partially prevented by tacrolimus BD-induced lung injury pig model.