Physiological mechanisms of hyperventilation during human pregnancy

This study examined the role of pregnancy-induced changes in wakefulness (or non-chemoreflex) and central chemoreflex drives to breathe, acid-base balance and female sex hormones in the hyperventilation of human pregnancy. Thirty-five healthy women were studied in the third trimester (TM 3 ; 36.3±1.0 weeks gestation; mean±S.D.) and again 20.2±7.8 weeks post-partum (PP). An iso-oxic hyperoxic rebreathing procedure was used to evaluate wakefulness and central chemoreflex drives to breathe. At rest, arterialized venous blood was obtained for the estimation of arterial PCO 2 (PaCO 2 ) and [H + ]. Blood for the determination of plasma strong ion difference ([SID]), albumin ([Alb]), as well as serum progesterone ([P 4 ]) and 17β-estradiol ([E 2 ]) concentrations was also obtained at rest. Wakefulness and central chemoreflex drives to breathe, [P 4 ] and [E 2 ], ventilation and VCO 2 increased, whereas PaCO 2 and the central chemoreflex ventilatory recruitment threshold for PCO 2 (VRTCO 2 ) decreased from PP to TM 3 (all p < 0.01). The reductions in PaCO 2 were not related to the increases in [P 4 ] and [E 2 ]. The alkalinizing effects of reductions in PaCO 2 and [Alb] were partly offset by the acidifying effects of a reduced [SID], such that arterial [H + ] was still reduced in TM 3 vs. PP (all p < 0.001). A mathematical model of ventilatory control demonstrated that pregnancy-induced changes in wakefulness and central chemoreflex drives to breathe, acid-base balance, VCO 3 and cerebral blood flow account for the reductions in PaCO 2 , [H + ] and VRTCO 2 . This is the first study to demonstrate that the hyperventilation and attendant hypocapnia/alkalosis of human pregnancy results from a complex interaction of pregnancy-induced changes in wakefulness and central chemoreflex drives to breathe, acid-base balance, metabolic rate and cerebral blood flow.