Effects of gestational age and cortisol treatment on ovine fetal heart function in a novel biventricular Langendorff preparation

Fletcher, Andrew; Forhead, Alison J.; Fowden, Abigail L.; Ford, William R.; Nathanielsz, Peter W.; Giussani, Dino A.

doi:10.1113/jphysiol.2004.074161

Cited by 15 publications

(17 citation statements)

References 59 publications

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“…It was then cannulated via the aorta (<2 min from excision) and perfused through the coronary arteries at a constant pressure of 30 mmHg, as detailed by Fletcher et al. ()). A pulmonary arteriotomy was also performed.…”

Section: Methodsmentioning

confidence: 99%

Induction of controlled hypoxic pregnancy in large mammalian species

et al. 2015

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Progress in the study of pregnancy complicated by chronic hypoxia in large mammals has been held back by the inability to measure long‐term significant reductions in fetal oxygenation at values similar to those measured in human pregnancy complicated by fetal growth restriction. Here, we introduce a technique for physiological research able to maintain chronically instrumented maternal and fetal sheep for prolonged periods of gestation under significant and controlled isolated chronic hypoxia beyond levels that can be achieved by habitable high altitude. This model of chronic hypoxia permits measurement of materno‐fetal blood gases as the challenge is actually occurring. Chronic hypoxia of this magnitude and duration using this model recapitulates the significant asymmetric growth restriction, the pronounced cardiomyopathy, and the loss of endothelial function measured in offspring of high‐risk pregnancy in humans, opening a new window of therapeutic research.

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Section: Methodsmentioning

confidence: 99%

Induction of controlled hypoxic pregnancy in large mammalian species

et al. 2015

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“…While fetal cardiac reactivity to muscarinic agonists increases, it decreases to β 1 ‐adrenergic stimulation, thereby promoting cardiac vagal dominance with increased maturation (Fletcher et al . , ). Similarly, the greater increment in fetal femoral vascular resistance during acute hypoxia with advancing gestational age results, in part, from maturation of the carotid body chemoreflex and, in part, from greater plasma catecholamine, vasopressin and neuropeptide Y responses (Fletcher et al .…”

Section: Causes and Consequences Of Fetal Hypoxiamentioning

confidence: 97%

The fetal brain sparing response to hypoxia: physiological mechanisms

Giussani

2016

The Journal of Physiology

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292

342

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figure legend. The fetal brain sparing response to hypoxia. The fetal brain sparing response to acute hypoxia is triggered by a carotid chemoreflex which leads to bradycardia and an increase in peripheral vasoconstriction. The bradycardia is mediated by a dominant vagal influence on the fetal heart. The neurally triggered peripheral vasoconstriction is maintained by the release of constrictor hormones into the fetal circulation as well as a local vascular oxidant tone, determined by the interaction between NO and ROS, such as the superoxide anion (·O 2 − ). Abstract How the fetus withstands an environment of reduced oxygenation during life in the womb has been a vibrant area of research since this field was introduced by Joseph Barcroft, a century ago. Studies spanning five decades have since used the chronically instrumented fetal sheep preparation to investigate the fetal compensatory responses to hypoxia. This defence is contingent on the fetal cardiovascular system, which in late gestation adopts strategies to decrease oxygen consumption and redistribute the cardiac output away from peripheral vascular beds and towards essential circulations, such as those perfusing the brain. The introduction of simultaneous measurement of blood flow in the fetal carotid and femoral circulations by ultrasonic transducers has permitted investigation of the dynamics of the fetal brain sparing response for the first time. Now we know that major components of fetal brain sparing during acute hypoxia are triggered exclusively by a carotid chemoreflex and that they are modified by endocrine agents and the recently discovered vascular oxidant tone. The latter is determined by the interaction between nitric oxide and reactive oxygen species. The fetal brain sparing response matures as the fetus approaches term, in association with the prepartum increase in fetal plasma cortisol, and treatment of the preterm fetus with clinically relevant doses of synthetic steroids mimics this maturation. Despite intense interest into how the fetal brain sparing response may be affected by adverse intrauterine conditions, this area of research has been comparatively scant, but it is likely to take centre stage in the near future. Dino Giussani is Professor of Cardiovascular

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“…Recent work in our laboratory using a Langendorff preparation showed greater sensitivity to muscarinic agonists but less sensitivity to ␤-adrenergic agonists in isolated hearts from full-term than from younger fetal sheep (21). Thus reciprocal changes in cardiac sensitivity to vagal and humoral sympathetic stimulation provide a mechanism contributing to persistence of bradycardia during acute hypoxemia in the ovine fetus at full term.…”

Section: Fhr Response To Hypoxemiamentioning

confidence: 98%

Development of the ovine fetal cardiovascular defense to hypoxemia towards full term

Fletcher¹,

Gardner²,

Edwards³

et al. 2006

American Journal of Physiology-Heart and Circulatory Physiology

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. Development of the ovine fetal cardiovascular defense to hypoxemia towards full term. Am J Physiol Heart Circ Physiol 291: H3023-H3034, 2006. First published July 21, 2006 doi:10.1152/ajpheart.00504.2006.-We tested the hypothesis that fetal cardiovascular responses to hypoxemia change close to full term in relation to the prepartum increase in fetal basal cortisol and investigated, in vivo, the neural and endocrine mechanisms underlying these changes. Fetal heart rate and peripheral hemodynamic responses to 1 h of hypoxemia were studied in 25 chronically instrumented sheep within three narrow gestational age ranges: 125-130 (n ϭ 13), 135-140 (n ϭ 6), and Ͼ140 (n ϭ 6) days (full term ϳ145 days). Chemoreflex function and plasma concentrations of vasoconstrictor hormones were measured. Reductions in fetal arterial PO2 during hypoxemia were similar at all ages. At 125-130 days, hypoxemia elicited transient bradycardia, femoral vasoconstriction, and increases in plasma concentrations of catecholamines, neuropeptide Y (NPY), AVP, ACTH, and cortisol. Close to full term, in association with the prepartum increase in fetal basal cortisol, there was a developmental increase in the magnitude and persistence of fetal bradycardia and in the magnitude of the femoral constrictor response to hypoxemia. The mechanisms mediating these changes close to full term included increases in the gain of chemoreflex function and in the magnitudes of the fetal NPY and AVP responses to hypoxemia. Data combined irrespective of gestational age revealed significant correlations between fetal basal cortisol and fetal bradycardia, femoral resistance, chemoreflex function, and plasma AVP concentrations. The data show that the fetal cardiovascular defense to hypoxemia changes in pattern and magnitude just before full term because of alterations in the gain of the neural and endocrine mechanisms mediating them, in parallel with the prepartum increase in fetal basal cortisol.fetus; prepartum cortisol surge; glucocorticoid IN ALL MAMMALIAN SPECIES studied to date, fetal basal cortisol concentration increases immediately before full term (23). In the ovine fetus, this increase in plasma cortisol begins in the last 15 days of gestation, at ϳ130 days (full term ϳ145 days) (3, 43), and increases most dramatically within the last 5 days before delivery, between 140 and 145 days. The prepartum cortisol surge is known to be an important factor in the developmental maturation of fetal tissues and physiological systems in preparation for the transition to neonatal life (23). For example, the prepartum maturation of basal cardiovascular function in the fetus is influenced by cortisol. The developmental increase in ovine fetal mean arterial blood pressure (FBP) and fall in fetal heart rate (FHR) are prevented by fetal adrenalectomy and restored to normal by cortisol replacement (63). Similarly, the prepartum cortisol surge has been associated with developmental changes in the basal activity of many fetal endocrine vasoconstrictor mechanisms, such as the norad...

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Effects of gestational age and cortisol treatment on ovine fetal heart function in a novel biventricular Langendorff preparation

Cited by 15 publications

References 59 publications

Induction of controlled hypoxic pregnancy in large mammalian species

Induction of controlled hypoxic pregnancy in large mammalian species

The fetal brain sparing response to hypoxia: physiological mechanisms

Development of the ovine fetal cardiovascular defense to hypoxemia towards full term

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