15-hydroxy-11-alpha-9-alpha-(epoxymethano)prosta-5-13-dienoic-acid and Alkalosis--Respiratory

After an initial vasodilator response to alkalosis, many children with pulmonary hypertension exhibit marked pulmonary vascular reactivity despite continued alkalosis therapy. This study sought to a) identify the mediator of alkalosis-induced pulmonary vasodilation in isolated lamb lungs; b) determine whether alkalosis-induced pulmonary vasodilation decreases over time in this model; and c) determine whether alkalosis enhanced vascular reactivity to subsequent pressor stimuli.. Prospective, interventional study.. Isolated perfused lungs from 1-month-old lambs.. Hypocarbic alkalosis, hypoxia, and infusion of the thromboxane mimetic agent U46619. Pulmonary artery pressure was measured at constant flow, so a change in pressure reflects change in resistance. Hypoxic pulmonary artery pressure was compared after 20 and 100 mins of hypocarbic alkalosis or normocarbia in control and cyclooxygenase-inhibited lungs. Pulmonary artery dose responses to U46619 were then measured in control lungs. Responses to hypoxia and U46619 were also compared after 60-80 mins of hypocarbic or normocarbic normoxia. Hypocarbic alkalosis acutely reduced hypoxic pulmonary vascular resistance, and this was sustained for at least 100 mins. Cyclooxygenase inhibition blocked this vasodilation, suggesting that it was mediated by dilator prostaglandins. However, subsequent reactivity to U46619 was enhanced in hypoxic alkalotic lungs, and both hypoxia and U46619 caused significant vasoconstriction in normoxic alkalotic lungs.. Alkalosis caused sustained vasodilation when pulmonary vascular resistance was high but either failed to attenuate or enhanced vascular reactivity to subsequent pressor stimuli.

Topics: 15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid; Alkalosis, Respiratory; Animals; Cyclooxygenase Inhibitors; Hypertension, Pulmonary; Hypoxia; In Vitro Techniques; Indomethacin; Prospective Studies; Pulmonary Circulation; Random Allocation; Sheep; Time Factors; Vascular Resistance; Vasoconstrictor Agents; Vasodilation

Mechanically induced respiratory alkalosis decreases pulmonary arterial pressure in infants with persistent pulmonary hypertension of the newborn and in newborn lambs with hypoxia-induced pulmonary hypertension. Since thromboxane A2 may mediate the pulmonary hypertension in infants with Group B beta-hemolytic streptococci and Escherichia coli pneumonia, we studied the effect of respiratory alkalosis on thromboxane-induced pulmonary hypertension. A specific thromboxane A2-mimetic, U46619, was infused into six normoxic, sedated, mechanically ventilated lambs. U46619 produced pulmonary hypertension which was significantly attenuated during respiratory alkalosis. These results support the use of respiratory alkalosis to treat infants and children with pulmonary hypertension regardless of the presumed etiology.

Topics: 15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid; Alkalosis, Respiratory; Animals; Animals, Newborn; Blood Pressure; Hydrogen-Ion Concentration; Hypertension, Pulmonary; Oxygen; Prostaglandin Endoperoxides, Synthetic; Respiration, Artificial; Sheep