Pulmonary microcirculatory responses to leukotrienes B 4, C 4 and D 4 in sheep

Abstract

The pulmonary microvascular responses to leukotrienes B 4, C 4 and D 4 (total dosage of 4 μg/kg i.v.) were examined in acutely-prepared halothane anesthetized and awake sheep prepared with lung lymp fistulas. In anesthetized as well as unanesthetized sheep, LTB 4 caused a marked and transient decrease in the circulating leukocyte count. Pulmonary transvascular protein clearance (pulmonary lymph flow x lymph-to-plasma protein concentration ratio) increased transiently in awake sheep, suggesting a small increase in pulmonary vascular permeability. The mean pulmonary artery pressure (P pa ) also increased. In the acutely-prepared sheep, the LTB 4-induced pulmonary hemodynamic and lymph flow responses were damped. Leukotriene C 4 increased P pa to a greater extent in awake sheep than in anesthetized sheep, but did not significantly affect the pulmonary lymph flow rate (Q̇ lym) and lmph-to-plasma protein concentration (L/P) ration in either group. LTD 4 increased P pa and Q̇ lymp in both acute and awake sheep; Q̇ lym increased without a significant change in the L/P ratio. The LTD 4-induced rise in P pa occurred in association with an increase in plasma thromboxane B 2 (Txb 2) cocentration. The relativity small increase in Q̇ lym with LTD 4 suggests that the increase in the transvascular fluid filtration rate is the result of a rise in the pulmonary capillary hydrostatic pressure. In conclusion, LTB 4 induces a marked neutropenia, pulmonary hypertension, and may transiently increase lung vascular permeability. Both LTC 4 and LTD 4 cause a similar degree of pulmonary hypertension in awake sheep, but had different lymph flow responses which may be due to pulmonary vasoconstriction at different sites, i.e. greather pre-capillary constriction with LTC 4 because Q̇ lym did not change and greater post-capillary constriction with LTD 4 because Q̇ increased with the same rise in P pa .