Hepatic cryoablation-induced acute lung injury - Pulmonary hemodynamic andpermeability effects in a sheep model

Hypothesis: Hepatic cryoablation of 30% to 35% or more of liver parenchyma in a sheep model results in eicosanoid and nuclear factor-kappa B (NF-kappa B)-mediated changes in pulmonary hemodynamics and lung permeability. Setting: Laboratory. Interventions: At initial thoracotomy, catheters were placed in the main pu lmonary artery, left atrium, right carotid artery, and efferent duct of the caudal mediastinal lymph node for subsequent monitoring in adult sheep. Af ter a 1- to 2-week period of recovery, animals underwent laparotomy and lef t-lobe cryoablation (approximately 35% by volume) with subsequent awake mon itoring and on postoperative days 1 to 3. Main Outcome Measures: Cryoablation-induced lung permeability and hemodynam ic changes were compared with baseline values in sheep that underwent instr umentation. Similarly handled sheep underwent resection of a similar volume of hepatic parenchyma or had pulmonary artery pressure increases induced b y mechanical left atrial obstruction. Activation of NF-kappa B was assessed with electrophoretic mobility shift assay, and serum thromboxane Results: Cryoablation resulted in acutely increased mean pulmonary (20 to 3 5 cm water) and systemic pressures, which returned to baseline at 24 hours with no change in cardiac output. Serum thromboxane levels increased 30 min utes after cryoablation (9-fold) and returned to baseline at 24 hours. Acti vation of NF-kappa B was present in liver and lung tissue by 30 minutes aft er cryoablation. Lung lymph-plasma protein clearance markedly exceeded the expected increase from pulmonary pressures alone, and increased lymph-plasm a pro rein ra tio persisted after pulmonary artery pressures normalized. Si milar changes were not associated with 35% hepatic resection. Conclusions: This study demonstrates that 35% hepatic cryoablation results in an acute but transient increase in pulmonary artery pressure that may be mediated by increased thromboxane levels. Increases in pulmonary capillary permeability are not accounted for by pressure changes alone, and may be a result of NF-kappa B-mediated inflammatory mechanisms. These data show tha t cryosurgery causes pathophysiological changes similar to those observed w ith endotoxin and other systemic inflammatory stimuli.