DIFFERING EFFECTS OF ACUTE AND PROLONGED ALKALOSIS ON HYPOXIC PULMONARY VASOCONSTRICTION

Animal studies and clinical pediatric practice have shown that acute a lkalosis attenuates hypoxic pulmonary vasoconstriction (HPV). However, increased intracellular pH appears to enhance pulmonary vasoreactivit y. We therefore hypothesized that prolonged alkalosis augments HPV. Th is study compares the effects of acute and prolonged alkalosis on HPV in isolated perfused lungs of 1-month-old lambs (n = 5) and the hypoxi c responses of 300- to 500-mu m diameter segments of pulmonary arterie s (n = 7) from mature cats at control pH and after 30 min of alkalosis . In isolated lamb lungs, normocarbic (5% CO2) hypoxia (4% O-2) increa sed the total pressure gradient (Delta P-T) by 6.0 +/- 2.7 (SEM) mm Hg (p less than or equal to 0.05). Acute hypocarbia (3% CO2) increased t he perfusate pH to similar to 7.52 and significantly decreased the hyp oxic Delta P-T to normocarbic, normoxic (28% O-2) levels. Subsequent e xposure to normoxia (while maintaining alkalosis) further decreased De lta P-T. However, re-exposure to hypoxia after 60 min of normoxic alka losis significantly increased Delta P-T by 11.6 +/- 1.6 mm Hg (p less than or equal to 0.05) to a level similar to that seen during normocar bic hypoxia. The increased hypoxic reactivity (i.e., change in pressur e between normoxia and hypoxia) during prolonged alkalosis was due to enhanced HPV of the small vessels within the middle segment of the pul monary circuit, as defined by an inflow-outflow occlusion technique (p less than or equal to 0.05). The occlusion data also suggested that m ost of this increase occurred in small arteries. Moreover, the hypoxic response of isolated small arteries from the cat was increased almost threefold (p less than or equal to 0.05). While extrapolation to the clinical situation from in vitro animal studies must be done cautiousl y, the enhanced HPV seen after 30 to 60 min of normoxic alkalosis in t hese studies suggests the need for further evaluation of the consequen ces of prolonged alkalosis therapy in the management of pulmonary hype rtension in neonates and children.