Fetal Ventricular Interactions and Wall Mechanics During Ductus Arteriosus Occlusion in a Sheep Model

Hashima, Jason; Rogers, Vanessa J.C.; Langley, Stephen M.; Ashraf, Muhammed; Sahn, David J.; Ohtonen, Pasi; Davis, Lowell E.; Hohimer, A. Roger; Räsänen, Juha

doi:10.1016/j.ultrasmedbio.2014.11.002

Cited by 10 publications

(15 citation statements)

References 29 publications

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“…It is obvious that there was a slight increase in FO volume blood flow, because LV stroke volume was maintained during the occlusion. No change in FO volume blood flow was noted (Hashima et al, 2015). Although the Frank-Starling mechanism is functional in the fetal heart (Kirkpatrick, Pitlick, Naliboff, & Friedman, 1976), the fetal ventricles seem to operate near the plateau of their function curves and have limited capacity to respond to volume loading by increasing stroke volume (Reller et al, 1987;Thornburg & Morton, 1983.…”

Section: Resultsmentioning

confidence: 97%

“…During prolonged DA occlusion in near-term fetal sheep, RVCO and CCO decreased, while LVCO increased (Hashima et al, 2015). Interestingly, an increase in LVCO was attributable to increased pulmonary volume blood flow while FO volume blood flow did not change (Hashima et al, 2015). This suggests that at near-term gestation the fetal pulmonary circulation is an important regulator of LVCO, whereas FO blood flow might be at or near its maximal capacity.…”

Section: Introductionmentioning

confidence: 90%

“…However, changes in ventricular loading conditions can lead to redistribution of CCO between the two ventricles and disturb the RV dominance, because RVCO is particularly sensitive to increased afterload (Reller, Morton, Reid, & Thornburg, 1987; Thornburg & Morton, 1983). During prolonged DA occlusion in near-term fetal sheep, RVCO and CCO decreased, while LVCO increased (Hashima et al, 2015). Interestingly, an increase in LVCO was attributable to increased pulmonary volume blood flow while FO volume blood flow did not change (Hashima et al, 2015).…”

Section: Introductionmentioning

confidence: 99%

“…In physiological conditions in near-term fetal sheep, ∼70% of combined cardiac output (CCO) is ejected by the right ventricle (RVCO), and almost 90% of RVCO is directed through the ductus arteriosus (DA) towards the lower body and placenta, and the rest to the pulmonary circulation (Anderson, Bissonnette, Faber, & Thornburg, 1981;Rudolph, 1985). During prolonged DA occlusion in near-term fetal sheep, RVCO and CCO decreased, while LVCO increased (Hashima et al, 2015). However, changes in ventricular loading conditions can lead to redistribution of CCO between the two ventricles and disturb the RV dominance, because RVCO is particularly sensitive to increased afterload (Reller, Morton, Reid, & Thornburg, 1987; Thornburg & Morton, 1983).…”

Section: Introductionmentioning

confidence: 99%

“…Given that the fetal pulmonary circulation is under acquired vasoconstriction at near-term gestation (Lewis, Heymann, & Rudolph, 1976), blood flow across the foramen ovale (FO) accounts for 34% of CCO and 85% of LV output (LVCO) (Anderson et al, 1981). Interestingly, an increase in LVCO was attributable to increased pulmonary volume blood flow while FO volume blood flow did not change (Hashima et al, 2015). During prolonged DA occlusion in near-term fetal sheep, RVCO and CCO decreased, while LVCO increased (Hashima et al, 2015).…”

Section: Introductionmentioning

confidence: 99%

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Foramen ovale blood flow and cardiac function after main pulmonary artery occlusion in fetal sheep

Lantto

Erkinaro

Haapsamo

et al. 2019

Experimental Physiology

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New Findings What is the central question of this study?At near‐term gestation, foramen ovale blood flow accounts for a significant proportion of fetal left ventricular output. Can the foramen ovale increase its volume blood flow when right ventricular afterload is increased by main pulmonary artery occlusion? What is the main finding and its importance?Foramen ovale volume blood flow increased during main pulmonary artery occlusion. However, this increase was attributable to an increase in fetal heart rate, because left ventricular stroke volume remained unchanged. These findings suggest that the foramen ovale has a limited capacity to increase its volume blood flow. Abstract The foramen ovale (FO) accounts for the majority of fetal left ventricular (LV) output. Increased right ventricular afterload can cause a redistribution of combined cardiac output between the ventricles. To understand the capability of the FO to increase its volume blood flow and thus LV output, we mechanically occluded the main pulmonary artery in seven chronically instrumented near‐term sheep fetuses. We hypothesized that FO volume blood flow and LV output would increase during main pulmonary artery occlusion. Fetal cardiac function and haemodynamics were assessed by pulsed and tissue Doppler at baseline, 15 and 60 min after occlusion of the main pulmonary artery and 15 min after occlusion was released. Fetal ascending aorta and central venous pressures and blood gas values were monitored. Main pulmonary artery occlusion initially increased fetal heart rate (P < 0.05) from [mean (SD)] 158 (7) to 188 (23) beats min−1 and LV cardiac output (P < 0.0001) from 629 (198) to 776 (283) ml min−1. Combined cardiac output fell (P < 0.0001) from 1524 (341) to 720 (273) ml min−1. During main pulmonary artery occlusion, FO volume blood flow increased (P < 0.001) from 507 (181) to 776 (283) ml min−1. This increase was related to fetal tachycardia, because LV stroke volume did not change. Fetal ascending aortic blood pressure remained stable. Central venous pressure was higher (P < 0.05) during the occlusion than after it was released. During the occlusion, fetal pH decreased and PnormalCO2 increased. Left ventricular systolic dysfunction developed while LV diastolic function was preserved. Right ventricular systolic and diastolic function deteriorated after the occlusion. In conclusion, the FO has a limited capacity to increase its volume blood flow at near‐term gestation.

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Section: Resultsmentioning

confidence: 97%

Section: Introductionmentioning

confidence: 90%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

Foramen ovale blood flow and cardiac function after main pulmonary artery occlusion in fetal sheep

Lantto

Erkinaro

Haapsamo

et al. 2019

Experimental Physiology

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Learn from Your Elders: Developmental Biology Lessons to Guide Maturation of Stem Cell-Derived Cardiomyocytes

2019

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Human pluripotent stem cells (hPSCs) offer a multifaceted platform to study cardiac developmental biology, understand disease mechanisms, and develop novel therapies. Remarkable progress over the last two decades has led to methods to obtain highly pure hPSC-derived cardiomyocytes (hPSC-CMs) with reasonable ease and scalability. Nevertheless, a major bottleneck for the translational application of hPSC-CMs is their immature phenotype, resembling that of early fetal cardiomyocytes. Overall, bona fide maturation of hPSC-CMs represents one of the most significant goals facing the field today. Developmental biology studies have been pivotal in understanding the mechanisms to differentiate hPSC-CMs. Similarly, evaluation of developmental cues such as electrical and mechanical activities or neurohormonal and metabolic stimulations revealed the importance of these pathways in cardiomyocyte physiological maturation. Those signals cooperate and dictate the size and the performance of the developing heart. Likewise, this orchestra of stimuli is important in promoting hPSC-CM maturation, as demonstrated by current in vitro maturation approaches. Different shades of adult-like phenotype are achieved by prolonging the time in culture, electromechanical stimulation, patterned substrates, microRNA manipulation, neurohormonal or metabolic stimulation, and generation of human-engineered heart tissue (hEHT). However, mirroring this extremely dynamic environment is challenging, and reproducibility and scalability of these approaches represent the major obstacles for an efficient production of mature hPSC-CMs. For this reason, understanding the pattern behind the mechanisms elicited during the late gestational and early postnatal stages not only will provide new insights into postnatal development but also potentially offer new scalable and efficient approaches to mature hPSC-CMs.

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Fetal programming as a predictor of adult health or disease: the need to reevaluate fetal heart function

et al. 2017

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Epidemiologic and experimental evidence suggests that adverse stimuli during critical periods in utero permanently alters organ structure and function and may have persistent consequences for the long-term health of the offspring. Fetal hypoxia, maternal malnutrition, or ventricular overloading are among the major adverse conditions that can compromise cardiovascular development in early life. With the heart as a central organ in fetal adaptive mechanisms, a deeper understanding of the fetal cardiovascular physiology and of the echocardiographic tools to assess both normal and stressed pregnancies would give precious information on fetal well-being and hopefully may help in early identification of special risk groups for cardiovascular diseases later in life. Assessment of cardiac function in the fetus represents an additional challenge when comparing to children and adults, requiring advanced training and a critical approach to properly acquire and interpret functional parameters. This review summarizes the basic fetal cardiovascular physiology and the main differences from the mature postnatal circulation, provides an overview of the particularities of echocardiographic evaluation in the fetus, and finally proposes an integrated view of in utero programming of cardiovascular diseases later in life, highlighting priorities for future clinical research.

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Fetal Ventricular Interactions and Wall Mechanics During Ductus Arteriosus Occlusion in a Sheep Model

Cited by 10 publications

References 29 publications

Foramen ovale blood flow and cardiac function after main pulmonary artery occlusion in fetal sheep

Foramen ovale blood flow and cardiac function after main pulmonary artery occlusion in fetal sheep

Learn from Your Elders: Developmental Biology Lessons to Guide Maturation of Stem Cell-Derived Cardiomyocytes

Fetal programming as a predictor of adult health or disease: the need to reevaluate fetal heart function

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