Augmentation of hypoxic pulmonary vasoconstriction in isolated rabbit lungs with phosphoenolpyruvate

BACKGROUND: Phosphoenolpyruvate (PEP) is a glycolytic substrate which can be metabolized to pyruvate with concomitant formation of ATP. We examined the effects of PEP on hypoxic pulmonary vasoconstriction (HPV). METHODS: Isolated rabbit lungs (n = 6) were reperfused at a flow rate of 40 ml x kg(-1) body weight x min(-1) with a mixture of the physiological salt solution and autologous blood. They were ventilated with a mixture of 21% O2, 5% CO2, and balance N2. The HPV response was induced by reduction of inspired O2 concentration from 21 to 3% for 5 min and was evaluated by an increase of the pulmonary arterial pressure (PAP) with inhalation of nitric oxide (NO) at concentration of 0, 10, 20 ppm in random order. Next, PEP with the final concentration of 10 mM was added to the reservoir. After 30-min equilibration, the above protocol of hypoxic stimulations was repeated. RESULTS: PEP did not alter the basal PAP, but augmented the HPV response. Without and with PEP, inhaled NO depressed the HPV response in a dose-related manner and the half inhibition values (ED50) were 9.4 +/- 2.2, 14.9 +/- 10.3 ppm (mean +/- SD), respectively. CONCLUSIONS: The combination of intravenous PEP and inhaled NO may improve PaO2 without increasing PAP in acute respiratory failure.