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 (K(fc)), 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 Ca2+-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 μM, over 1 min, directly into the pulmonary artery. The uninjured lungs received four infusions of vehicle (normal saline). K(fc) was determined after each t- bu-OOH infusion. Concentrations of thromboxane B2 (TxB2) and 6-keto- prostaglandin F(1α) 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: K(fc) 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.
- Anesthetics, volatile: halothane
- Lung metabolism
- Prostaglandins: 6- keto-prostaglandin F(1α); thromboxane B
- Respiratory distress syndrome, adult
- Species: rabbit
ASJC Scopus subject areas
- Anesthesiology and Pain Medicine