Influence of cyclo-oxygenase inhibition and of leukotriene receptor blockade on pulmonary vascular pressure/cardiac index relationships in hyperoxic and in hypoxic dogs

Abstract

Overall mean pulmonary arterial pressure (MPAP)/cardiac index (CI) relationships were investigated in 13 pentobarbital anaesthetized dogs ventilated consecutively with a fraction of inspired O2 (F1O2) of 0.4 and with a F1O2 of 0.1. This sequence of alternated F1O2 0.4 and F1O2 0.1 was repeated in the dogs with a strong pulmonary pressor response to hypoxia (more than 20% increase in pulmonary vascular resistance) (n = 6) under a continuous infusion of the leukotriene receptor blocker FPL 57231 (2 mg min-1 kg-1), and in the dogs with a weak pressor response to hypoxia (n = 7) after cyclo-oxygenase inhibition by acetylsalicylic acid (1 g intravenously). Five-point MPAP/CI plots were constructed by opening a femoral arteriovenous fistula or by stepwise inflations of an inferior vena cava balloon catheter. The MPAP/CI plots were rectilinear in all experimental conditions. In responders, hypoxia was associated with an increase in MPAP over the entire range of CI studied (1-5 litres min-1 m-2). Infusion of FLP 57231 abolished the vasoconstricting effect of hypoxia. In non-responders, MPAP was not affected by hypoxia over the entire range of CI. After acetylsalicylic acid administration, hypoxia resulted in a significant rise in MPAP from 2 to 5 litres min-1 m-2. Infusion of FLP 57231 decreased mean systemic arterial pressure at both F1O2 0.4 and F1O2 0.1, while acetylsalicylic acid had no effect on systemic haemodynamics.(ABSTRACT TRUNCATED AT 250 WORDS)