Intrauterine growth restriction improves cerebral O₂ utilization during hypercapnic hypoxia in newborn piglets

Abstract

Data are scant regarding the capacity of cerebrovascular regulation during asphyxia for prevention of brain oxygen deficit in intrauterine growth-restricted (IUGR) newborns. We tested the hypothesis that IUGR improves the ability of neonates to withstand critical periods of severe asphyxia by optimizing brain oxygen supply. Studies were conducted to examine the effects of IUGR on cerebral blood flow (CBF) regulation and oxygen consumption (cerebral metabolic rate for oxygen, CMRO 2 ) at different stages of asphyxia (hypercapnic hypoxaemia) in comparison to pure hypoxia (normocapnic hypoxaemia). We used 1-day-old anaesthetized and ventilated piglets. Animals were divided into normal weight (NW) piglets (n = 47; aged 11-26 h, body weight 1481 ± 121 g) and IUGR piglets (n = 48; aged 13-28 h, body weight 806 ± 42 g) according to their birth weight. Different stages of hypoxaemia were induced for 1 h by appropriate lowering of the inspired fraction of oxygen (moderate hypoxia: P a,O 2 = 31-34 mmHg; severe hypoxia: P a,O 2 = 20-22 mmHg). Fourteen NW and 16 IUGR piglets received additionally 9% CO 2 in the breathing gas, so that a P a,CO 2 of 74-80 mmHg resulted (hypoxia/hypercapnia groups). Eight NW and nine IUGR animals served as untreated controls. Furthermore, affinity of haemoglobin for oxygen was measured under hypoxic and asphyxic conditions. During asphyxia cerebral oxygen extraction was markedly increased in IUGR animals (P < 0.05). This resulted in a significantly diminished CMRO 2 -related increase of CBF at gradually reduced arterial oxygen content (P < 0.05). Therefore, an enhanced effectivity in oxygen availability appeared in newborn IUGR piglets under graded asphyxia by improved cerebral oxygen utilization (P < 0.05). This was not supported by related O 2 affinity of haemoglobin. Thus, IUGR newborns are more capable to ensure brain O 2 demand during asphyxia (hypercapnic hypoxia) than NW neonates.

Zika Virus Causes Persistent Infection in Porcine Conceptuses and may Impair Health in Offspring

“…A recent increase in the use of pigs as models in neuroscience, cognition, and neurobehavioral studies is due to the close similarity in brain development, growth and anatomy to humans ( Dickerson and Dobbing, 1966 ; Gieling et al, 2011 ; Glauser, 1966 ; Lind et al, 2007 ; Lunney, 2007 ; Thibault and Margulies, 1998 ). Porcine models for translational research of schizophrenia ( Lind et al, 2005 ; Lind et al, 2004 ), antipsychotic interventions ( van der Staay et al, 2009 ), epilepsy ( Marchi et al, 2007 ), intrauterine growth restriction ( Bauer et al, 2007 , Burke et al, 2006 , Ferenc et al, 2014 , Gonzalez-Bulnes et al, 2016 ), learning ( Andersen et al, 2016 ), and social interactions ( Kanitz et al, 2016 ) have been also developed. Pigs are multiparous animals with the same or larger litters than in mice and the length of gestation in pigs, 114 days, closely approximates gestation in humans.…”

The effect of prenatal nicotine on expression of nicotine receptor subunits in the fetal brain

“…We have demonstrated that the longer fetal exposure to nicotine, the severer of restriction of fetal body growth. Fetal growth restriction in human (Regnault et al, 2007), and in large and small animals (Bauer et al, 2007), can be caused by multiple mechanisms, including in utero hypoxia (Viswanathan et al, 2007). It has been shown that maternal nicotine administration decreases fetal blood PO 2 in animals including rats (Socol et al, 1982;Mao et al, 2007).…”

Brain-Sparing in Intrauterine Growth Restriction: Considerations for the Neonatologist

“…Due to vascular structural and functional changes, their autoregulation may be further compromised and IUGR neonates may thus be even less equipped than their AGA peers to cope with hypo- and hypertensive circumstances. In contrast, Bauer et al [67,68] found that low-birth-weight piglets exhibited a more adequate autoregulatory response to haemorrhagic hypotension and also higher brain oxygen extraction during hypercapnic hypoxia than their AGA peers. These results suggest that chronic intrauterine hypoxia may in fact stimulate the maturation of protective mechanisms to ensure adequate brain oxygenation and perfusion.…”

“…In contrast, animal work by Bauer et al [67,68] has suggested that exposure to chronic (mild) intrauterine hypoxia may actually improve autoregulation and cerebral oxygen extraction, allowing the IUGR brain to better withstand the effects of hypotension and HSPDA . It could also be argued that postnatal persistence of increased CBF may reduce the impact of systemic hypotension or ductal steal on the cerebral circulation.…”