title: Hepatic cryoablation-induced acute lung injury: pulmonary hemodynamic and permeability effects in a sheep model.
abstract: OBJECTIVE
  Hepatic cryoablation of 30% to 35% or more of liver parenchyma in a sheep model results in eicosanoid and nuclear factor-kappaB (NF-kappaB)-mediated changes in pulmonary hemodynamics and lung permeability.
  
  
  METHODS
  Laboratory.
  
  
  METHODS
  At initial thoracotomy, catheters were placed in the main pulmonary artery, left atrium, right carotid artery, and efferent duct of the caudal mediastinal lymph node for subsequent monitoring in adult sheep. After a 1- to 2-week period of recovery, animals underwent laparotomy and left-lobe cryoablation (approximately 35% by volume) with subsequent awake monitoring and on postoperative days 1 to 3.
  
  
  METHODS
  Cryoablation-induced lung permeability and hemodynamic changes were compared with baseline values in sheep that underwent instrumentation. Similarly handled sheep underwent resection of a similar volume of hepatic parenchyma or had pulmonary artery pressure increases induced by mechanical left atrial obstruction. Activation of NF-kappaB was assessed with electrophoretic mobility shift assay, and serum thromboxane levels were measured with mass spectroscopy.
  
  
  RESULTS
  Cryoablation resulted in acutely increased mean pulmonary (20 to 35 cm water) and systemic pressures, which returned to baseline at 24 hours with no change in cardiac output. Serum thromboxane levels increased 30 minutes after cryoablation (9-fold) and returned to baseline at 24 hours. Activation of NF-kappaB was present in liver and lung tissue by 30 minutes after cryoablation. Lung lymph-plasma protein clearance markedly exceeded the expected increase from pulmonary pressures alone, and increased lymph-plasma protein ratio persisted after pulmonary artery pressures normalized. Similar 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-kappaB-mediated inflammatory mechanisms. These data show that cryosurgery causes pathophysiological changes similar to those observed with endotoxin and other systemic inflammatory stimuli.
authors.affiliation: Division of Hepatobiliary Surgery, Vanderbilt University Medical Center, Nashville, Tenn. 37232-4753, USA. will.chapman@surgery.mc.vanderbilt.edu
authors.forename: W C
authors.initials: WC
authors.lastname: Chapman
authors.forename: J P
authors.initials: JP
authors.lastname: Debelak
authors.forename: T S
authors.initials: TS
authors.lastname: Blackwell
authors.forename: K A
authors.initials: KA
authors.lastname: Gainer
authors.forename: J W
authors.initials: JW
authors.lastname: Christman
authors.forename: C W
authors.initials: CW
authors.lastname: Pinson
authors.forename: K L
authors.initials: KL
authors.lastname: Brigham
authors.forename: R E
authors.initials: RE
authors.lastname: Parker
mesh_terms: D000818:Animals; D001798:Blood Proteins / Q000378:metabolism; D002199:Capillary Permeability / Q000502:physiology; D003452:Cryosurgery / Q000009:adverse effects*; D008099:Liver / Q000601:surgery*; D008196:Lymph / Q000502:physiology; D016328:NF-kappa B / Q000378:metabolism; D011651:Pulmonary Artery / Q000502:physiology; D011652:Pulmonary Circulation / Q000502:physiology; D012128:Respiratory Distress Syndrome / Q000209:etiology*; D012756:Sheep; D013931:Thromboxanes / Q000097:blood
chemical_list: D001798:Blood Proteins; D016328:NF-kappa B; D013931:Thromboxanes