High-Frequency Ultrasound Assessment of the Murine Heart From Embryo Through to Juvenile

Corrigan, Niamh; Brazil, Derek P.; Auliffe, Fionnuala Mc

doi:10.1177/1933719109348923

Cited by 39 publications

(59 citation statements)

References 24 publications

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“…1C). In contrast, myocardial performance index, a combined measure of systolic and diastolic function (25), was unaltered by genotype (see Table S1 for myocardial performance index and a breakdown of each of the cardiac components assessed by ultrasound).…”

Section: Significancementioning

confidence: 93%

“…Thus, there was an interaction between gestational age and genotype for both umbilical vein blood velocity and RI. Heart function matures between E14.5 and E17.5, and as the fetal heart becomes more compliant, left ventricle (LV) filling becomes more dependent on passive filling (the E wave) and less dependent on LV filling due to active contraction of the atria (the A wave) (25); this clearly occurs in both Hsd11b2 +/+ and Hsd11b2 +/− fetuses but did not occur in Hsd11b2 −/− fetal hearts (Fig. 1C).…”

Section: Significancementioning

confidence: 99%

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Pravastatin ameliorates placental vascular defects, fetal growth, and cardiac function in a model of glucocorticoid excess

Wyrwoll

Noble

Thomson

et al. 2016

Proc. Natl. Acad. Sci. U.S.A.

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Fetoplacental glucocorticoid overexposure is a significant mechanism underlying fetal growth restriction and the programming of adverse health outcomes in the adult. Placental glucocorticoid inactivation by 11β-hydroxysteroid dehydrogenase type 2 (11β-HSD2) plays a key role. We previously discovered that Hsd11b2 −/− mice, lacking 11β-HSD2, show marked underdevelopment of the placental vasculature. We now explore the consequences for fetal cardiovascular development and whether this is reversible. We studied Hsd11b2 +/+ , Hsd11b2 +/− , and Hsd11b2 −/− littermates from heterozygous (Hsd11b +/− ) matings at embryonic day (E)14.5 and E17.5, where all three genotypes were present to control for maternal effects. Using high-resolution ultrasound, we found that umbilical vein blood velocity in Hsd11b2 −/− fetuses did not undergo the normal gestational increase seen in Hsd11b2 +/+ littermates. Similarly, the resistance index in the umbilical artery did not show the normal gestational decline. Surprisingly, given that 11β-HSD2 absence is predicted to initiate early maturation, the E/A wave ratio was reduced at E17.5 in Hsd11b2 −/− fetuses, suggesting impaired cardiac function. Pravastatin administration from E6.5, which increases placental vascular endothelial growth factor A and, thus, vascularization, increased placental fetal capillary volume, ameliorated the aberrant umbilical cord velocity, normalized fetal weight, and improved the cardiac function of Hsd11b2 −/− fetuses. This improved cardiac function occurred despite persisting indications of increased glucocorticoid exposure in the Hsd11b2 −/− fetal heart. Thus, the pravastatin-induced enhancement of fetal capillaries within the placenta and the resultant hemodynamic changes correspond with restored fetal cardiac function. Statins may represent a useful therapeutic approach to intrauterine growth retardation due to placental vascular hypofunction.placenta | 11β-HSD2 | glucocorticoids | fetal heart | developmental programming

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Section: Significancementioning

confidence: 93%

Section: Significancementioning

confidence: 99%

Pravastatin ameliorates placental vascular defects, fetal growth, and cardiac function in a model of glucocorticoid excess

Wyrwoll

Noble

Thomson

et al. 2016

Proc. Natl. Acad. Sci. U.S.A.

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“…Both systolic and diastolic function improve in late gestation (Harada et al 1997, Corrigan et al 2010, reflecting the improved contractility and relaxation properties of the cardiomyocytes. The ventricle walls progressively thicken (Webb et al 1996, Christoffels et al 2000, driven predominantly by cardiomyocyte hyperplasia (Oparil et al 1984).…”

Section: Late Gestation Cardiac Maturationmentioning

confidence: 99%

Glucocorticoids and foetal heart maturation; implications for prematurity and foetal programming

Rog-Zielinska¹,

Richardson²,

Denvir³

et al. 2013

Journal of Molecular Endocrinology

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Glucocorticoids are steroid hormones, essential in mammals to prepare for life after birth. Blood levels of glucocorticoids (cortisol in most mammals including humans; corticosterone in rats and mice) rise dramatically shortly before birth. This is mimicked clinically in the routine administration of synthetic glucocorticoids to pregnant women threatened by a preterm birth or to preterm infants to improve neonatal survival. Whilst effects on lung are well documented and essential for postnatal survival, those on heart are less well known. In this study, we review recent evidence for a crucial role of glucocorticoids in late gestational heart maturation. Either insufficient or excessive glucocorticoid exposure before birth may alter the normal glucocorticoid-regulated trajectory of heart maturation with potential life-long consequences.

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“…In the case of the mouse heart, the beating rate increases during pre-and postnatal development; the heart rate of the fetal mouse reaches 200 on the 16th fetal day (7), is about 320 on the day of birth, and reaches the adult level of about 700 at 2 weeks after birth (1,8). Various changes in the excitation-contraction mechanisms that enable rapid contraction and relaxation should be taking place in the developing mouse cardiomyocyte to adjust to the large increase in heart rate.…”

Section: Introductionmentioning

confidence: 99%

Developmental Changes in Excitation–Contraction Mechanisms of the Mouse Ventricular Myocardium as Revealed by Functional and Confocal Imaging Analyses

et al. 2013

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Abstract. Developmental changes in excitation-contraction mechanisms were examined in the ventricular myocardium from fetal, neonatal, and 1-, 2-, and 4-week-old mice. In isolated tissue, the negative inotropic effect of nifedipine decreased, while that of ryanodine increased with age. Action potential duration decreased with age, especially during the late fetal period. In ventricular cardiomyocytes, fluorescence imaging revealed that the sarcoplasmic reticulum increases progressively during pre-and postnatal development. t-Tubules were absent in the fetus and neonate, were observed only in the subsarcolemmal region at 1 week after birth, and were present throughout the cytoplasm at 2 and 4 weeks after birth. The amplitude of Ca 2+ transients, as well as its ryanodine-sensitive component, increased with age. In the neonate and 1-week-old mice, Ca 2+ at the cell center showed slower rise than the subsarcolemmal region, but in 2-and 4-week-old mice, Ca 2+ increased simultaneously across the entire width of the cell. These results suggest that in the mouse ventricular myocardium, the shortening of the action potential during the late fetal period and the development of t-tubule-sarcoplasmic reticulum coupling during the second postnatal week largely contribute to the developmental increase in the dependence of contraction on sarcoplasmic reticulum function.

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High-Frequency Ultrasound Assessment of the Murine Heart From Embryo Through to Juvenile

Abstract: The ultrasound biomicroscope allows for noninvasive in-depth assessment of cardiac function of embryos and pups. Detailed physiological and functional cardiac function readouts can be obtained, which is invaluable for comparison to mouse models of disease.

Cited by 39 publications

References 24 publications

Pravastatin ameliorates placental vascular defects, fetal growth, and cardiac function in a model of glucocorticoid excess

Pravastatin ameliorates placental vascular defects, fetal growth, and cardiac function in a model of glucocorticoid excess

Glucocorticoids and foetal heart maturation; implications for prematurity and foetal programming

Developmental Changes in Excitation–Contraction Mechanisms of the Mouse Ventricular Myocardium as Revealed by Functional and Confocal Imaging Analyses

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