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

Publisher Website
Google Scholar
Abstract
1. 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 (1) 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 (2) 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. 2. 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. 3. 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. 4. 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. 5. Stability of pulmonary vascular tone at F1o2 0.4 and at F1o2 0.1 and reproducibility of the hypoxic pressor response was ascertained in an additional group of five dogs with CI kept constant and MPAP measurements every 6 min during four consecutive periods of 30 min (i.e. maximum time needed to generate a MPAP/CI plot) alternately at F1o2 0.4 and at F1o2 0.1. 6. These results suggest that pulmonary vascular reactivity to hypoxia is regulated by balanced actions of vasoconstricting leukotrienes and vasodilating prostaglandins in anaesthetized dogs. They also indicate a vasodilating effect of FPL 57231 on systemic vessels.