Partial contributions of developmental hypoxia and undernutrition to prenatal alterations in somatic growth and cardiovascular structure and function

Camm, Emily J.; Hansell, Jeremy A.; Kane, Andrew D.; Herrera, Emílio; Lewis, Cara; Wong, Samuel Yeung‐Shan; Morrell, Nicholas W.; Giussani, Dino A.

doi:10.1016/j.ajog.2010.06.046

Cited by 79 publications

(117 citation statements)

References 70 publications

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“…Our findings suggest, therefore, that the lung vasculature is protected against known IUGR-induced cardiovascular redistribution, which is apparent in chronic hypoxia (37). However, we and others have previously shown that growth restriction causes endothelial dysfunction in other vascular beds (12,57), and we speculate that endothelial dysfunctions likely exist in pulmonary vessels, even in the absence of gross changes in vasculature. We did not examine pulmonary vascular function in these lambs, so we cannot rule out that poor vascular function, such as reduced vasodilator response, may be an underlying mechanism for the decline in respiratory function observed in preterm IUGR infants.…”

Section: Discussionsupporting

confidence: 43%

Ventilation-induced lung injury is not exacerbated by growth restriction in preterm lambs

Allison

Hooper

Coia

et al. 2016

American Journal of Physiology-Lung Cellular and Molecular Phys

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Intrauterine growth restriction (IUGR) and preterm birth are frequent comorbidities and, combined, increase the risk of adverse respiratory outcomes compared with that in appropriately grown (AG) infants. Potential underlying reasons for this increased respiratory morbidity in IUGR infants compared with AG infants include altered fetal lung development, fetal lung inflammation, increased respiratory requirements, and/or increased ventilation-induced lung injury. IUGR was surgically induced in preterm fetal sheep (0.7 gestation) by ligation of a single umbilical artery. Four weeks later, preterm lambs were euthanized at delivery or delivered and ventilated for 2 h before euthanasia. Ventilator requirements, lung inflammation, early markers of lung injury, and morphological changes in lung parenchymal and vascular structure and surfactant composition were analyzed. IUGR preterm lambs weighed 30% less than AG preterm lambs, with increased brain-to-body weight ratio, indicating brain sparing. IUGR did not induce lung inflammation or injury or alter lung parenchymal and vascular structure compared with AG fetuses. IUGR and AG lambs had similar oxygenation and respiratory requirements after birth and had significant, but similar, increases in proinflammatory cytokine expression, lung injury markers, gene expression, and surfactant phosphatidylcholine species compared with unventilated controls. IUGR does not induce pulmonary structural changes in our model. Furthermore, IUGR and AG preterm lambs have similar ventilator requirements in the immediate postnatal period. This study suggests that increased morbidity and mortality in IUGR infants is not due to altered lung tissue or vascular structure, or to an altered response to early ventilation.

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Section: Discussionsupporting

confidence: 43%

Ventilation-induced lung injury is not exacerbated by growth restriction in preterm lambs

Allison

Hooper

Coia

et al. 2016

American Journal of Physiology-Lung Cellular and Molecular Phys

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“…The observed increase in relative heart weight in the IUGR rats is indicative of left-ventricular hypertrophy in these animals which is supported by the observed increase in relative PW thickness in the left ventricle. Left-ventricular hypertrophy has been described in other experimental models of IUGR as well (18)(19)(20), but this is often associated with an elevation in arterial Articles Lim et al blood pressure (19,20). Of note, left-ventricular hypertrophy in the IUGR offspring in our study appears to have developed independently of a change in blood pressure; when tail-cuff blood pressure was measured from 24 to 32 wk of age there was no difference in blood pressure between the LPD and NPD offspring.…”

Section: Altered Cardiac Growth In Offspring With Iugrmentioning

confidence: 99%

Intrauterine growth restriction coupled with hyperglycemia: effects on cardiac structure in adult rats

et al. 2012

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Results Growth TrajectoriesBody weight. The offspring born to pregnant rats that were fed a low-protein diet (LPD) to induce IUGR are referred to here as "LPD offspring. " Offspring born to rats that had a normal-protein diet (NPD) are referred to as "NPD offspring. " At 3 d of age, the LPD offspring had body weights (BWTs) of 4.44 ± 0.13 g which were 24% lower than the weights of NPD offspring (5.74 ± 0.16 g) (P < 0.001). At 32 wk of age, the BWTs of the LPD offspring remained significantly lower than those of the NPD offspring (10% lower, P value relating to maternal diet (P D ) < 0.0001) (Figure 1a). When type 1 diabetes was induced, the increasing levels of blood glucose reduced (P value relating to hyperglycemic treatment (P T ) < 0.0001) the BWTs in LPD offspring as well as in NPD offspring. The maintenance of blood glucose levels at a mildly hyperglycemic level attenuated the effects of hyperglycemia on BWT in NPD offspring ( Figure 1a); however, the LPD offspring with mild hyperglycemia remained significantly smaller than the LPD control offspring. Articles IUGR combined with hyperglycemiaHeart weight. There was no significant difference in absolute heart weight in LPD offspring as compared with NPD offspring (1.95 ± 0.07 and 1.98 ± 0.04, respectively). However, when heart weights were adjusted to BWTs, LPD offspring exhibited significantly higher (P D = 0.05) relative heart weights as compared with NPD offspring at 32 wk of age (Figure 1b). The induction of hyperglycemia led to a marked increase (P T = 0.0002) in absolute heart weight in both LPD and NPD offspring. Furthermore, relative heart weight was also higher in all groups with hyperglycemia (P T < 0.0001), with moderately hyperglycemic LPD offspring exhibiting the highest heart weight relative to BWT (Figure 1b). Blood PressureBlood pressure remained constant throughout the measurement period, from 24 to 32 wk of age, in both LPD and NPD offspring (Figure 2a). There was no significant effect of hyperglycemia on blood pressure over the experimental period (Figure 2a). Echocardiographic AnalysesHeart rate. Heart rate was not affected by maternal protein restriction or the induction of hyperglycemia in either LPD or NPD offspring at 32 wk of age (Figure 2b).End-diastolic internal diameter of the left ventricle. Maternal protein restriction during pregnancy and lactation led to a significant reduction (P D < 0.0001) in the end-diastolic internal diameter of the left ventricle (LVIDd) of LPD offspring as compared with control NPD offspring (Figure 3a). There was a marked increase in the LVIDd in response to the induction of hyperglycemia (P T = 0.0008). However, the response to hyperglycemia was not significantly different between LPD and NPD offspring (P D×T = 0.2). Post hoc analyses demonstrated a significant increase (P < 0.05) in the LVIDd in LPD offspring with moderate hyperglycemia as compared with LPD control offspring; however, the LVIDd was normalized when blood glucose levels were reduced to mildly hyperglycemic levels.When the LVIDd was ad...

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“…Multiple stimuli have been identified as being capable of inducing fetal programming in animal models, including malnourishment, exposure to hypoxia, cocaine, nicotine, or glucocorticoid during the pregnancy (2,14,25,32,37,48,50). Recent animal studies have demonstrated that fetal hypoxia is linked to early changes in the developing cardiovascular system (6,37,39). In fact, physiological hypoxia is a normal part of fetal life for all vertebrates, and it plays an active role in vasculogenesis, angiogenesis, hematopoeisis, and chondrogenesis during the fetal development (39).…”

mentioning

confidence: 99%

Maternal hypoxia alters matrix metalloproteinase expression patterns and causes cardiac remodeling in fetal and neonatal rats

Tong

Qin

et al. 2011

American Journal of Physiology-Heart and Circulatory Physiology

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Tong W, Xue Q, Li Y, Zhang L. Maternal hypoxia alters matrix metalloproteinase expression patterns and causes cardiac remodeling in fetal and neonatal rats. Am J Physiol Heart Circ Physiol 301: H2113-H2121, 2011. First published August 19, 2011 doi:10.1152/ajpheart.00356.2011.-Fetal hypoxia leads to progressive cardiac remodeling in rat offspring. The present study tested the hypothesis that maternal hypoxia results in reprogramming of matrix metalloproteinase (MMP) expression patterns and fibrillar collagen matrix in the developing heart. Pregnant rats were treated with normoxia or hypoxia (10.5% O2) from day 15 to 21 of gestation. Hearts were isolated from 21-day fetuses (E21) and postnatal day 7 pups (PD7). Maternal hypoxia caused a decrease in the body weight of both E21 and PD7. The heart-to-body weight ratio was increased in E21 but not in PD7. Left ventricular myocardium wall thickness and cardiomyocyte proliferation were significantly decreased in both fetal and neonatal hearts. Hypoxia had no effect on fibrillar collagen content in the fetal heart, but significantly increased the collagen content in the neonatal heart. Western blotting revealed that maternal hypoxia significantly increased collagen I, but not collagen III, levels in the neonatal heart. Maternal hypoxia decreased MMP-1 but increased MMP-13 and membrane type (MT)1-MMP in the fetal heart. In the neonatal heart, MMP-1 and MMP-13 were significantly increased. Active MMP-2 and MMP-9 levels and activities were not altered in either fetal or neonatal hearts. Hypoxia significantly increased tissue inhibitors of metalloproteinase (TIMP)-3 and TIMP-4 in both fetal and neonatal hearts. In contrast, TIMP-1 and TIMP-2 were not affected. The results demonstrate that in utero hypoxia reprograms the expression patterns of MMPs and TIMPs and causes cardiac tissue remodeling with the increased collagen deposition in the developing heart.

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Partial contributions of developmental hypoxia and undernutrition to prenatal alterations in somatic growth and cardiovascular structure and function

Cited by 79 publications

References 70 publications

Ventilation-induced lung injury is not exacerbated by growth restriction in preterm lambs

Ventilation-induced lung injury is not exacerbated by growth restriction in preterm lambs

Intrauterine growth restriction coupled with hyperglycemia: effects on cardiac structure in adult rats

Maternal hypoxia alters matrix metalloproteinase expression patterns and causes cardiac remodeling in fetal and neonatal rats

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