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 (TM3; 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 PCO2 (PaCO2) and [H+]. Blood for the determination of plasma strong ion difference ([SID]), albumin ([Alb]), as well as serum progesterone ([P-4]) and 17 beta-estradiol ([E-2]) concentrations was also obtained at rest. Wakefulness and central chemoreflex drives to breathe, [P-4] and [E-2], ventilation and VCO2 increased, whereas PaCO2 and the central chemoreflex ventilatory recruitment threshold for PCO2 (VRTCO2) decreased from PP to TM3 (all p < 0.01). The reductions in PaCO2 were not related to the increases in [P-4] and [E-2]. The alkalinizing effects of reductions in PaCO2 and [Alb] were partly offset by the acidifying effects of a reduced [SID], such that arterial [H+] was still reduced in TM3 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, VCO2 and cerebral blood flow account for the reductions in PaCO2, [H+] and VRTCO2. 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. (C) 2008 Elsevier B.V. All rights reserved.