Hypoxia Disturbs Fetal Hemodynamics and Growth

Abstract

Low-birth-weight babies have an increased risk of cardiovascular disease (CVD) in later life. The authors hypothesize that fetal hypoxia alters the structure and function of the developing cardiovascular system resulting in CVD. They investigated the effects of chronic hypoxia on cardiac performance, hemodynamic control, and growth during the second half of embryonic chick development. Three stages of hemodynamic adaptations were identified in hypoxic chick embryos. At embryonic day 13 (E13), heart rate and blood pressure were higher in hypoxic embryos. At E17, this was followed by sympathetic hyperinnervation of peripheral arteries, resulting in increased vasoconstriction during a chemoreflex. This was accompanied by dilatation of the left ventricle and a 50% reduction in cardiac contractility. E19 hypoxic embryos had a 33% higher baseline vascular tone, but failed to maintain blood pressure during acute stress, indicating cardiac failure. Reduced body, heart, and liver weights followed the hemodynamic changes. Chronic hypoxia induces dilated cardiomyopathy and sympathetic hyperinnervation of the peripheral vasculature leading to aberrant fetal hemodynamics and fetal growth restriction. This study identifies that alterations in fetal hemodynamic regulation are in the causal pathway between disturbances in fetal environment, restricted fetal growth and CVD, and establishes fetal hypoxia as a novel risk factor for cardiovascular disease.

Atmospheric oxygen level affects growth trajectory, cardiopulmonary allometry and metabolic rate in the American alligator (Alligator mississippiensis)

“…Altimiras, 2005; Giussani et al, 2007;Tintu et al, 2007). Although we did not measure embryonic metabolic rates, we did observe smaller yolk-free body mass and greater remnant yolk sac mass in hypoxic hatchlings.…”

“…A developing trend in liver hypotrophy was observed in embryonic alligators at different times of egg incubation and at different levels of chronic hypoxia [15% and 10% O 2 (Crossley and Altimiras, 2005)]. Similarly, chicken embryos in chronic hypoxia (15% O 2 ) exhibit a reduction in liver growth in late development (Tintu et al, 2007). Because the liver is the major metabolic centre of the vertebrate body, its small size may be a reflection of the reduced growth rate (or a functional constraint on the growth rate) of hypoxic hatchlings.…”

Trends in the use of preconditioning to hypoxia for early prevention of future life diseases

“…Intrauterine growth restriction/retardation may be caused by hypoxic hypoxia (19), preeclampsia (20), or maternal psychological stress (21). Low weight/ height at birth may be caused by hypoxic hypoxia (22) or preeclampsia (20). Therefore, all considered abnormalities of early growth are tightly related to some types of hypoxia.…”

Epigenetic Programming of Cardiovascular Disease by Perinatal Hypoxia and Fetal Growth Restriction

“…Interestingly, the follow-up of the chickens gestated under hypoxia has shown important insights into the pathophysiological mechanisms that impair the cardiovascular function. For instance, Tintu et al showed that developmental hypoxia induces cardiomyopathy associated with left ventricular dilatation, reduced ventricular wall mass, and increased apoptosis [25]. These responses were coupled with pump dysfunction, decreased ejection fractions, and diastolic dysfunction, which persisted in adulthood.…”