Effects of respiratory alkalosis on thromboxane-induced pulmonary hypertension in piglets

Abstract

Acute hypoxic pulmonary vasoconstriction is attenuated by respiratory alkalosis. It is unknown if alkalosis similarly reduces pulmonary vasoconstriction produced by thromboxane A2. Respiratory alkalosis does not always attenuate persistent pulmonary hypertension in newborns, some of whom have elevated serum thrombox­ane B2 levels. We hypothesized that alkalosis attenuates thromboxane-induced pulmonary vasoconstriction less than it does hypoxic pulmonary vasoconstriction in infants. Hemodynamic responses to respiratory alkalosis during pulmonary vasoconstriction produced in random order by breathing 12% inspired oxygen and by infusing 0.1 Mg/kg/ min of the thromboxane-mimetic U46,619 were compared in eight 2-wk-old piglets. Hypoxia increased mean pulmo­nary artery pressure from 12 ± 3 to 29 ± 2 mm Hg and pulmonary vascular resistance (PVR) from 11 ± 4 to 25 ± 8 mmHg/L/min; U46,619 increased pulmonary artery pres­sure from 16 ± 5 to 37 ± 6 mm Hg and PVR from 14 + 5 to 51 ± 17 mm Hg/liter/min. U46,619 also decreased cardiac output accounting in part for the greater increase in PVR compared to hypoxia-induced vasoconstriction. Respiratory alkalosis decreased PVR to 14 ± 6 mm Hg/ liter/min during exposure to hypoxia and to 28 ± 9 mm Hg/liter/min during infusion of U46,619. In six additional piglets with U46,619-induced pulmonary vasoconstriction, the effects of lung stretch and hypocapnic alkalosis were separated by doubling tidal volume and then adding in­spired CO2 to return PaCCh to prehyperventilation levels. Respiratory alkalosis decreased PVR from 52 ± 36 to 35 ± 21 mm Hg/liter/min. Despite the increased tidal volume, PVR increased to 53 ± 35 Hg/liter/min when PaCOz returned to 44 ± 5 mm Hg. Respiratory alkalosis rather than lung stretch reduces thromboxane-induced and hy­poxia-induced pulmonary vasoconstriction by equal pro­portions. © 1988 International Pediatrics Research Foundation, Inc.