HALOTHANE ENHANCES PULMONARY-ARTERY ENDOTHELIAL EICOSANOID RELEASE

To determine whether anesthetics alter endothelial eicosanoid release, cultured bovine pulmonary artery endothelial cells were studied durin g constant flow and pressure perfusion at two oxygen tensions (hypoxia , 50 +/- 2 mm Hg; normoxia, 144 +/- 5 mm Hg; mean +/- SEM) with and wi thout 1% halothane. Endothelialized microcarriers containing approxima tely 5 x 10(6) cells were loaded into cartridges and perfused (3 mL/mi n) with Krebs' solution (pH 7.4, at 37-degrees-C) equilibrated with ea ch gas mixture. Eicosanoids (6-keto prostaglandin F1alpha, thromboxane B2, and total peptidoleukotrienes [C4, D4, E4, F4]) were measured by radioimmunoassay and quantified per gram of cellular protein per minut e. Eicosanoid release did not vary over time. The 6-keto prostaglandin F1alpha release increased during hypoxia (normoxia 291 +/- 27 vs hypo xia 395 +/- 35 ng.min-1.g protein-1; P < 0.01). Halothane (H) increase d release of each eicosanoid during both normoxia and hypoxia: 6-keto prostaglandin F1alpha-normoxia 291 +/- 27 versus normoxia + H 356 +/- 32 ng.min-1.g protein-1 hypoxia 395 +/- 35 versus hypoxia + H 464 +/- 40 ng.min-1.g protein-1, P < 0.05; thromboxane B2-normoxia 19 +/- 2 ve rsus normoxia + H 26 +/- 2 ng.min-1.g protein-1, hypoxia 20 +/- 2 vers us hypoxia + H 38 +/- 5 ng.min-1.g protein-1, P < 0.001; leukotriene-n ormoxia 363 +/- 35 versus normoxia + H 489 +/- 52 ng-min-1.g protein-1 , hypoxia 329 +/- 29 versus hypoxia + H 455 +/- 39 ng.min-1.g protein- 1, P = 0.001. We conclude that alteration of endothelial eicosanoid re lease by halothane and hypoxia could modulate-pulmonary vascular tone.