Function and Biomechanics of Developing Cardiovascular Systems

Keller, Bradley B.

doi:10.1007/978-1-4612-0207-3_13

Cited by 13 publications

(7 citation statements)

References 82 publications

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“…To explain these effects, it has been proposed that normal blood flow is necessary for vascular remodeling. Numerous studies from avian embryos, dating back to well over a century ago, support this hypothesis because the surgical manipulation of blood flow can lead to a wide range of abnormalities in heart and vessel development (Keller, 2001;Kurz, 2000).…”

Section: Introductionmentioning

confidence: 99%

Vascular remodeling of the mouse yolk sac requires hemodynamic force

et al. 2007

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The embryonic heart and vessels are dynamic and form and remodel while functional. Much has been learned about the genetic mechanisms underlying the development of the cardiovascular system, but we are just beginning to understand how changes in heart and vessel structure are influenced by hemodynamic forces such as shear stress. Recent work has shown that vessel remodeling in the mouse yolk sac is secondarily effected when cardiac function is reduced or absent. These findings indicate that proper circulation is required for vessel remodeling, but have not defined whether the role of circulation is to provide mechanical cues, to deliver oxygen or to circulate signaling molecules. Here, we used time-lapse confocal microscopy to determine the role of fluid-derived forces in vessel remodeling in the developing murine yolk sac. Novel methods were used to characterize flows in normal embryos and in embryos with impaired contractility (Mlc2a -/-). We found abnormal plasma and erythroblast circulation in these embryos, which led us to hypothesize that the entry of erythroblasts into circulation is a key event in triggering vessel remodeling. We tested this by sequestering erythroblasts in the blood islands, thereby lowering the hematocrit and reducing shear stress, and found that vessel remodeling and the expression of eNOS (Nos3) depends on erythroblast flow. Further, we rescued remodeling defects and eNOS expression in low-hematocrit embryos by restoring the viscosity of the blood. These data show that hemodynamic force is necessary and sufficient to induce vessel remodeling in the mammalian yolk sac.

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Section: Introductionmentioning

confidence: 99%

Vascular remodeling of the mouse yolk sac requires hemodynamic force

et al. 2007

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“…The embryonic heart, the main driver of hemodynamic loads, acutely adapts passive ventricular properties and contractile function in response to altered loads (Keller, 2001; Tobita et al, 2002; Shi et al, 2013), and proceeds to undergo abnormal growth and morphogenesis that later result in cardiac defects (Harh et al, 1973; Clark et al, 1989; Hogers et al, 1997; Sedmera et al, 1999; Tobita and Keller, 2000). Studies have shown that mechanical stresses and strains in the myocardium regulate ventricular growth and remodeling, and trigger endothelial cell organization and signaling (Fisher et al, 2001; Hove et al, 2003; Van Der Heiden et al, 2006), as well as changes in geometry and passive properties to offset the effects of altered wall stresses and/or strain (Omens, 1998).…”

Section: Introductionmentioning

confidence: 99%

Congenital heart malformations induced by hemodynamic altering surgical interventions

Midgett

Rugonyi

2014

Front. Physiol.

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Embryonic heart formation results from a dynamic interplay between genetic and environmental factors. Blood flow during early embryonic stages plays a critical role in heart development, as interactions between flow and cardiac tissues generate biomechanical forces that modulate cardiac growth and remodeling. Normal hemodynamic conditions are essential for proper cardiac development, while altered blood flow induced by surgical manipulations in animal models result in heart defects similar to those seen in humans with congenital heart disease. This review compares the altered hemodynamics, changes in tissue properties, and cardiac defects reported after common surgical interventions that alter hemodynamics in the early chick embryo, and shows that interventions produce a wide spectrum of cardiac defects. Vitelline vein ligation and left atrial ligation decrease blood pressure and flow; and outflow tract banding increases blood pressure and flow velocities. These three surgical interventions result in many of the same cardiac defects, which indicate that the altered hemodynamics interfere with common looping, septation and valve formation processes that occur after intervention and that shape the four-chambered heart. While many similar defects develop after the interventions, the varying degrees of hemodynamic load alteration among the three interventions also result in varying incidence and severity of cardiac defects, indicating that the hemodynamic modulation of cardiac developmental processes is strongly dependent on hemodynamic load.

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“…The period of primary cardiovascular (CV) morphogenesis is also the time of greatest vulnerability to epigenetic events 1 . During this critical developmental window the fetal CV system is the first functioning organ to transport oxygen and nutrients between the uteroplacental and fetoplacental circulations 2 . A broad range of developmental errors can occur during this time and the investigation of CV morphogenesis and adaptation reveals significant epigenetic plasticity, supporting the important role of epigenetic events on developmental fate 3 .…”

Section: Introductionmentioning

confidence: 99%

Maternal hypoxia and caffeine exposure depress fetal cardiovascular function during primary organogenesis

Momoi

Tinney

Keller

et al. 2012

J of Obstet and Gynaecol

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Aims Hypoxia is known to influence cardiovascular (CV) function, in part, through adenosine receptor activation. We have shown in a mouse model that during primary cardiac morphogenesis, acute maternal hypoxia negatively affects fetal heart rate, and recurrent maternal caffeine exposure reduces fetal cardiac output (CO) and down-regulates fetal adenosine A2A receptor gene expression. In the present study, we investigated whether maternal caffeine dosing exacerbates the fetal CV response to acute maternal hypoxia during the primary morphogenesis period. Methods Gestational day 11.5 pregnant mice were exposed to hypoxia (45 second duration followed by 10 minutes of recovery and repeated 3 times) while simultaneously monitoring maternal and fetal CO using high-resolution echocardiography. Results Following maternal hypoxia exposure, maternal CO transiently decreased and then returned to pre-hypoxia baseline values. In contrast to a uniform maternal cardiac response to each exposure to hypoxia, the fetal CO recovery time to the baseline decreased, and CO rebounded above baseline following the 2nd and 3rd episodes of maternal hypoxia. Maternal caffeine treatment inhibited the fetal CO recovery to maternal hypoxia by lengthening the time to CO recovery and eliminating the CO rebound post-recovery. Selective treatment with an adenosine A2A receptor antagonist, but not an adenosine A1 receptor antagonist, reproduced the altered fetal CO response to maternal hypoxia created by caffeine exposure. Conclusions Results suggest an additive negative effect of maternal caffeine on the fetal CV response to acute maternal hypoxia, potentially mediated via adenosine A2A receptor inhibition during primary cardiovascular morphogenesis.

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Function and Biomechanics of Developing Cardiovascular Systems

Cited by 13 publications

References 82 publications

Vascular remodeling of the mouse yolk sac requires hemodynamic force

Vascular remodeling of the mouse yolk sac requires hemodynamic force

Congenital heart malformations induced by hemodynamic altering surgical interventions

Maternal hypoxia and caffeine exposure depress fetal cardiovascular function during primary organogenesis

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