Differential effects of chronic intermittent and chronic constant hypoxia on postnatal growth and development

Abstract

Summary. Exposure to chronic constant or intermittent hypoxia (CCH or CIH) may have different effects on growth and development in early life. In this work, we exposed postnatal day 2 (P2) CD1 mice to CCH or CIH (11% O 2 ) for 4 weeks and examined the effect of hypoxia on body and organ growth until P30. Regression analysis showed that weight increased in control, CCH and CIH cohorts with age with r 2 values of 0.99, 0.97, and 0.94, respectively. Between days 2 and 30, slopes were 0.93 AE 0.057, 0.76 AE 0.108, and 0.63 AE 0.061 (g/day, means AE SEM) for control, CIH, and CCH, respectively and significantly different from each other (P < 0.001). The slopes between P2 and P16 were 0.78 AE 0.012, 0.46 AE 0.002, and 0.47 AE 0.019 for control, CCH and CIH, respectively. From P16 to 30, slopes were 1.12 AE 0.033, 1.09 AE 0.143, and 0.82 AE 0.08 for control, CIH, and CCH, respectively with no significant difference from each other, suggesting a catch-up growth in the latter part of the hypoxic period. Slower weight gain resulted in a 12% and 23% lower body weight in CIH and CCH mice (P < 0.001) by P30. Lung/body ratios were 0.010, 0.015, 0.015 for control, CIH, and CCH at P30, respectively. The decrease in liver, kidney, and brain weight were greater in CCH than CIH. Smaller liver weight was shown to be due to a reduction in cell size and cell number. Liver in CIH and CCH mice showed a 5% and 10% reduction in cell size (P < 0.05) and a reduction of 28% in cell number (P < 0.001) at P30. In contrast, CCH and CIH heart weight was 13% and 33% greater than control at P30 (P < 0.05), respectively. This increase in the heart weight was due to an increase in the size of cardiomyocytes which showed an increase of 12% and 14% (P < 0.001) for CIH and CCH, respectively as compared to control. Brain weight was 0.48 and 0.46 g for CIH and CCH, respectively (95% and 92% of normal). We concluded that (a) CIH and CCH follow different body and organ growth patterns; (b) mostly with CCH, the liver and kidneys are reduced in size in a proportionate way to body size but heart, lung, and brain are either spared or increased in size compared to body weight; and (c) the decrease in liver is secondary mostly to a decrease in cell number.

Gestational and Early Postnatal Exposure to Simulated High Altitude Does Not Modify Postnatal Body Mass Growth Trajectory in the Rat

“…Weight of rats at the time of weaning (21 days) was 49.53 -3.28 g in those raised under normoxic conditions (NX) and 25.45 -2.12 g in those animals raised at SHA (HX) ( p < 0.0001), as expected from previously reported studies (Farahany et al, 2008;Moore et al, 2011;Chen et al, 2012;Giussani et al, 2012) that showed that chronic hypoxia slows fetal and perinatal growth. Whether these effects are due to different factors, such as neuronal development, endocrine state, and behavior patterns (Peters, 1988;Champagne et al, 2003) or merely represent the known inhibitory effect of hypoxia on body mass, as occurs during later life periods, remains as an open question.…”

Intestinal microbiota and blue baby syndrome

“…Intestinal weights and lengths and the composition of the intestinal microbiota were not reported. 68 Similar studies have been performed in rats with similar results. 69,70 Attempts to manipulate the intestinal microbiota with probiotics to improve growth in premature infants have been successful in some populations but not in others.…”

Distinct physiological strategies are used to cope with constant hypoxia and intermittent hypoxia in killifish (Fundulus heteroclitus)

“…This is starkly contrasted by the extensive literature on intermittent hypoxia in mammals, which has uncovered widespread physiological, developmental and genomic consequences that are distinct from continuous hypoxia exposure (Neubauer, 2001;Douglas et al, 2007;Farahani et al, 2008). There is evidence that exposure to repeated bouts of hypoxia compromises growth in some fish species (Atlantic salmon, Salmo salar, and southern catfish, Silurus meridionalis) but not others (spot, Leiostomus xanthurus, and killifish, Fundulus heteroclitus) (Stierhoff et al, 2003;McNatt and Rice, 2004;Burt et al, 2013;Yang et al, 2013).…”