Effects of acute acidemia on the fetal cardiovascular defense to acute hypoxemia

Abstract

Thakor AS, Giussani DA. Effects of acute acidemia on the fetal cardiovascular defense to acute hypoxemia. Am J Physiol Regul Integr Comp Physiol 295: R90 -R99, 2009. First published October 15, 2008 doi:10.1152/ajpregu.90689.2008.-In complicated pregnancy, fetal hypoxemia rarely occurs in isolation but is often accompanied by fetal acidemia. There is growing clinical concern about the combined effects of fetal hypoxemia and fetal acidemia on neonatal outcome. However, the effects on the fetal defense responses to acute hypoxemia during fetal acidemia are not well understood. This study tested the hypothesis that fetal acidemia affects the fetal defense responses to acute hypoxemia. The hypothesis was tested by investigating, in the late-gestation sheep fetus surgically prepared for long-term recording, the in vivo effects of acute fetal acidemia on 1) the fetal cardiovascular responses to acute hypoxemia and 2) the neural and endocrine mechanisms mediating these responses. Under general anesthesia, five sheep fetuses at 0.8 gestation were instrumented with catheters and Transonic flow probes around the femoral and umbilical arteries. After 5 days, animals were subjected to an acute hypoxemia protocol during intravenous infusion of saline or treatment with acidified saline. Treatment with acidified saline reduced fetal basal pH from 7.35 Ϯ 0.01 to 7.29 Ϯ 0.01 but did not alter basal cardiovascular variables, blood glucose, or plasma concentrations of catecholamines, ACTH, and cortisol. During hypoxemia, treatment with acidified saline increased the magnitude of the fetal bradycardia and femoral vasoconstriction and concomitantly increased chemoreflex function and enhanced the increments in plasma concentrations of catecholamines, ACTH, and cortisol. Acidemia also reversed the increase in umbilical vascular conductance during hypoxemia to vasoconstriction. In conclusion, the data support our hypothesis and show that acute acidemia markedly alters fetal hemodynamic, metabolic, and endocrine responses to acute hypoxemia.

Hypoxémie, chémorécepteurs périphériques et rythme cardiaque fœtal

“…La réponse à la fois cardiovasculaire et humorale à une agression hypoxique aigüe (inhalation par la brebis d'un mélange appauvri en oxygène) est tout particulièrement augmentée dans le groupe des foetus antérieurement hypoxémiques et cette sensibilisation est associée à une élévation des concentrations plasmatiques en noradréna-line et vasopressine. L'étude menée par Thakor à Oxford [35] est plus récente : elle analyse la réponse cardiovasculaire gazométrique et hormonale à une hypoxémie aigüe chez cinq foetus de brebis en fin de gestation préalable-ment maintenus en état d'acidémie par la perfusion d'un soluté acide (pH 7,29) et compare les résultats avec ceux obtenus chez les mêmes foetus, lors d'une hypoxémie aigüe sans acidification préalable. On constate que l'acidémie est associée à une sensibilisation du chémoréflexe caractérisée par l'amplification du ralentissement et de la vasoconstriction en réponse à l'hypoxémie aigüe et que cette majoration du chémoréflexe s'accompagne d'une plus grande élévation des concentrations plasmatiques en catécholamines, ACTH et cortisol.…”

Mathematical Model of Cardiovascular and Metabolic Responses to Umbilical Cord Occlusions in Fetal Sheep

“…The sudden compression of the umbilical cord leads to fetal hypertension and fetal heart rate (FHR) decelerations, which are mediated through chemoreflex and sympathetic stimulation (Low et al 1995;Westgate et al 1999;Bennet et al 2005). Fetal oxygen delivery via the umbilical cord is interrupted and leads to hypoxemia and acute cerebral hypoxia (Mallard et al 1995;Koos et al 1995;Bishai et al 2003;Hunter et al 2003;Westgate et al 2007;Thakor and Giussani 2008). In addition, FHR reduction and oxygen deficiency also activate sympathetic and parasympathetic brainstem centers resulting in changes of afferent and threshold efferent firing rates (Frasch et al 2009a(Frasch et al , 2012.…”

Fetal stress. Focus on “Effects of acute acidemia on the fetal cardiovascular defense to acute hypoxemia” by Thakor and Giussani

“…Thakor and Giussani (17) address a fundamental component of the fetal stress response: acidemia and it role as a modulator of the hypothalamus-pituitary-adrenal (HPA) axis responsiveness to hypoxia.…”

“…Fetal hypoxia, as produced in the work by Thakor and Giussani (17), is arguably the most physiologically-relevant model of fetal stress. Any disturbance in maternal oxygen delivery to the uterus, perhaps resulting from maternal hypotension or maternal ventilatory hypoxia, will cause fetal hypoxia.…”

“…It is likely that the lessons learned from Thakor and Giussani (17) apply to the developing human fetus. Stress responsiveness of the fetus in utero is highly dependent on the blood acid-base status, itself greatly influenced by challenges to fetal homeostasis.…”