Effects of respiratory alkalosis on thromboxane-induced pulmonary hypertension in piglets.
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 micrograms/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 PaCO2 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 PaCO2 returned to 44 +/- 5 mm Hg.(ABSTRACT TRUNCATED AT 250 WORDS)
Redding
G J
GJ
Department of Pediatrics, University of Washington School of Medicine, Seattle 98195.
Gibson
R L
RL
Davis
C B
CB
Truog
W E
WE
D000472:Alkalosis, Respiratory / Q000150:complications*; D000818:Animals; D006439:Hemodynamics; D006976:Hypertension, Pulmonary / Q000139:chemically induced* / Q000150:complications; D011450:Prostaglandin Endoperoxides, Synthetic / Q000494:pharmacology; D011652:Pulmonary Circulation / Q000187:drug effects; D011659:Pulmonary Gas Exchange; D013552:Swine; D013928:Thromboxane A2; D013990:Tidal Volume; D014661:Vasoconstriction / Q000187:drug effects
D011450:Prostaglandin Endoperoxides, Synthetic; D013928:Thromboxane A2