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

被引:61
作者
Farahani, Reza [2 ,3 ,4 ]
Kanaan, Amjad [1 ,4 ]
Gavrialov, Orit [1 ,4 ]
Brunnert, Steven [5 ]
Douglas, Robert M. [1 ,4 ]
Morcillo, Patrick [4 ]
Haddad, Gabriel G. [1 ,4 ,6 ]
机构
[1] Univ Calif San Diego, Dept Pediat, La Jolla, CA 92093 USA
[2] New York Med Coll, Dept Pediat, Valhalla, NY 10595 USA
[3] New York Med Coll, Dept Cell Biol & Anat, Valhalla, NY 10595 USA
[4] Albert Einstein Coll Med, Dept Pediat, Bronx, NY 10467 USA
[5] Albert Einstein Coll Med, Dept Pathol, Bronx, NY 10467 USA
[6] Rady Childrens Hosp, San Diego, CA USA
关键词
hypoxia; postnatal; growth; development; organ; weight; cell size;
D O I
10.1002/ppul.20729
中图分类号
R72 [儿科学];
学科分类号
100202 ;
摘要
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 +/- 0.057, 0.76 +/- 0.108, and 0.63 +/- 0.061 (g/day, means 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 +/- 0.012, 0.46 +/- 0.002, and 0.47 +/- 0.019 for control, CCH and CIH, respectively. From P16 to 30, slopes were 1.12 +/- 0.033, 1.09 +/- 0.143, and 0.82 +/- 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 I 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.
引用
收藏
页码:20 / 28
页数:9
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