title: Halothane-oxidant interactions in the ex vivo perfused rabbit lung. Fluid conductance and eicosanoid production.
abstract: BACKGROUND
  The present studies were undertaken to determine the interactions between halothane and oxidative injury with respect to endothelial integrity, as measured by pulmonary capillary filtration coefficient (Kfc), and production of arachidonic acid-derived mediators, in perfused rabbit lungs challenged with the oxidant tert-butyl-hydroperoxide (t-bu-OOH).
  
  
  METHODS
  Isolated lungs were prepared from 27 New Zealand white rabbits (2-3 kg) and were perfused with Ca(2+)-free Krebs-Henseleit buffer solution. In group A (n = 9), lungs were ventilated with halothane 2.5% in carrier gas (5% CO2 in air); in group B (n = 9), with carrier gas alone; and in group C (n = 9), with carrier gas, but without injury. The lungs in the two injury groups (A and B) received four infusions of t-bu-OOH, 200 microM, over 1 min, directly into the pulmonary artery. The uninjured lungs received four infusions of vehicle (normal saline). Kfc was determined after each t-bu-OOH infusion. Concentrations of thromboxane B2 (TxB2) and 6-keto-prostaglandin F1 alpha were measured in samples of effluent perfusate obtained before and 30 s after the end of each infusion of t-bu-OOH. The wet/dry weight ratio of each pair of lungs was determined at the end of each experiment.
  
  
  RESULTS
  Kfc progressively increased after each infusion of oxidant in group A when compared with the other two groups. Lung wet/dry ratios were elevated in group A (14.3 +/- 0.7) and group B (13.2 +/- 0.2) compared with group C (12.1 +/- 1.1). TxB2 production in group A (2206 +/- 263 pg.min-1.g-1 dry lung tissue) was greater than in group B (1413 +/- 127) by the final infusion of t-bu-OOH.
  
  
  CONCLUSIONS
  Ex vivo perfused rabbit lungs ventilated with halothane exhibited, simultaneously, evidence of greater fluid conductance across the pulmonary capillary bed and production of thromboxane A2 when challenged with oxidant than did lungs ventilated with carrier gas. Both of these effects may be mediated by halothane-related enhancement of intracellular endothelial Ca2+ mobilization stimulated by intrapulmonary infusion of oxidant.
authors.affiliation: Department of Anesthesiology, University of Michigan Medical School, Ann Arbor 48109-0800.
authors.forename: J R
authors.initials: JR
authors.lastname: Shayevitz
authors.forename: K J
authors.initials: KJ
authors.lastname: Johnson
authors.forename: P R
authors.initials: PR
authors.lastname: Knight
mesh_terms: D000818:Animals; D001826:Body Fluids / Q000187:drug effects / Q000502:physiology; D002021:Buffers; D004195:Disease Models, Animal; D004347:Drug Interactions; D015777:Eicosanoids / Q000096:biosynthesis*; D011464:Epoprostenol / Q000378:metabolism; D006221:Halothane / Q000494:pharmacology*; D008168:Lung / Q000098:blood supply* / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D010545:Peroxides / Q000633:toxicity*; D011014:Pneumonia / Q000139:chemically induced / Q000378:metabolism; D011650:Pulmonary Alveoli / Q000098:blood supply / Q000187:drug effects; D011654:Pulmonary Edema / Q000139:chemically induced / Q000378:metabolism; D011817:Rabbits; D013928:Thromboxane A2 / Q000378:metabolism; D020122:tert-Butylhydroperoxide
chemical_list: D002021:Buffers; D015777:Eicosanoids; D010545:Peroxides; D013928:Thromboxane A2; D020122:tert-Butylhydroperoxide; D011464:Epoprostenol; D006221:Halothane