Cardiac Output Monitoring in Preterm Infants

McGovern, Matthew; Miletin, Jan

doi:10.3389/fped.2018.00084

Cited by 21 publications

(18 citation statements)

References 107 publications

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“…Cutting the umbilical cord eliminates the low-resistance placental flow and stimulates peripheral and central chemoreceptors, which combined with other factors (thermal, neuroendocrine, and mechanical stimuli), contributes to the onset and maintenance of neonatal respiratory efforts. A subsequent increase in SVR and reduction in right heart preload results [6], with the SVR continuing to increase due to cold stress and catecholamine surges [76]. Initiation of breathing stimulates a series of events that are responsible for the shift from fetal to postnatal circulatory patterns.…”

Section: Neonatal Structural Adaptations: Neonatal Circulation and Momentioning

confidence: 99%

The Transitional Heart: From Early Embryonic and Fetal Development to Neonatal Life

Tan

Lewandowski²

2019

Fetal Diagn Ther

173

123

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Formation of the human heart involves complex biological signals, interactions, specification of myocardial progenitor cells, and heart tube looping. To facilitate survival in the hypoxemic intrauterine environment, the fetus possesses structural, physiological, and functional cardiovascular adaptations that are fundamentally different from the neonate. At birth, upon separation from the placental circulation, the neonatal cardiovascular system takes over responsibility of vital processes for survival. The transition from the fetal to neonatal circulation is considered to be a period of intricate physiological, anatomical, and biochemical changes in the cardiovascular system. With a successful cardiopulmonary transition to the extrauterine environment, the fetal shunts are functionally modified or eliminated, enabling independent life. Investigations using medical imaging tools such as ultrasound and magnetic resonance imaging have helped to define normal and abnormal patterns of cardiac remodeling both in utero and ex utero. This has not only allowed for a better understanding of how congenital cardiac malforma-tions alter the hemodynamic transition to the extrauterine environment but also how other more common complications during pregnancy including intrauterine growth restriction, preeclampsia, and preterm delivery adversely affect offspring cardiac remodeling during this early transitional period. This review article describes key cardiac progenitors involved in embryonic heart development; the cellular, physiological, and anatomical changes during the transition from fetal to neonatal circulation; as well as the unique impact that different pregnancy complications have on cardiac remodeling.

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Section: Neonatal Structural Adaptations: Neonatal Circulation and Momentioning

confidence: 99%

The Transitional Heart: From Early Embryonic and Fetal Development to Neonatal Life

Tan

Lewandowski²

2019

Fetal Diagn Ther

173

123

View full text Add to dashboard Cite

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“…Maintenance of cardiac output is a key predictor of sepsis survival in infants and children and an important therapeutic target. [51][52][53] Additionally, we found that M3 was able to increase left ventricular end diastolic diameter, a characteristic that has also been associated with increased survival. [54,55] As such, we postulated that the myocardial dysfunction in sepsis was due, in part, to eCIRP.…”

Section: Discussionmentioning

confidence: 51%

Targeting the eCIRP/TREM-1 Interaction with a Small Molecule Inhibitor Improves Cardiac Dysfunction in Neonatal Sepsis

Denning

Aziz

et al. 2020

Preprint

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Background: Neonatal sepsis and the associated myocardial dysfunction remain a leading cause of infant mortality. Extracellular cold-inducible RNA-binding protein (eCIRP) acts as a ligand of triggering receptor expressed on myeloid cells-1 (TREM-1). M3 is a small CIRP-derived peptide that inhibits the eCIRP/TREM-1 interaction. We hypothesize that the eCIRP/TREM-1 interaction in cardiomyocytes contributes to sepsis-induced cardiac dysfunction in neonatal sepsis, while M3 is cardioprotective. Methods: Serum was collected from neonates in the Neonatal Intensive Care Unit (NICU). 5-7-day old C57BL/6 mouse pups were used in this study. Primary murine neonatal cardiomyocytes were stimulated with recombinant murine (rm) CIRP with M3. TREM-1 mRNA and supernatant cytokine levels were assayed. Mitochondrial oxidative stress, ROS, and membrane potential were assayed. Neonatal mice were injected with rmCIRP and speckle-tracking echocardiography was conducted to measure cardiac strain. Sepsis was induced by i.p. cecal slurry. Mouse pups were treated with M3 or vehicle. After 16 h, echocardiography was performed followed by euthanasia for tissue analysis. A 7-day survival study was conducted. Results: Serum CIRP levels were elevated in septic human neonates. rmCIRP stimulation of cardiomyocytes increased TREM-1 gene expression. Stimulation of cardiomyocytes with rmCIRP upregulated TNF-α and IL-6 in the supernatants, while this upregulation was inhibited by M3. Stimulation of cardiomyocytes with rmCIRP resulted in a reduction in mitochondrial membrane potential (MMP) while M3 treatment returned MMP to near baseline. rmCIRP caused mitochondrial calcium overload; this was inhibited by M3. rmCIRP injection impaired longitudinal and radial cardiac strain. Sepsis resulted in cardiac dysfunction with a reduction in cardiac output and left ventricular end diastolic diameter. Both were improved by M3 treatment. Treatment with M3 attenuated serum, cardiac, and pulmonary levels of pro-inflammatory cytokines compared to vehicle-treated septic neonates. M3 dramatically increased sepsis survival. Conclusions: Inhibition of eCIRP/TREM-1 interaction with M3 is cardioprotective, decreases inflammation, and improves survival in neonatal sepsis. Trial registration: Retrospectively registered.

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“…Treatment of septic mouse pups with M3 resulted in an improvement in CO. Maintenance of cardiac output is a key predictor of sepsis survival in infants and children and an important therapeutic target (Weiss 2020;Davis 2017;McGovern and Miletin 2018). Additionally, we found that M3 was able to increase left ventricular end diastolic diameter, a characteristic that has also been associated with increased survival (Huang et al 2013;Furian 2012).…”

Section: Global Longitudinal and Radial Strain Declines Following Expmentioning

confidence: 60%

Targeting the eCIRP/TREM-1 interaction with a small molecule inhibitor improves cardiac dysfunction in neonatal sepsis

Denning

Aziz

et al. 2020

Mol Med

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Background Neonatal sepsis and the associated myocardial dysfunction remain a leading cause of infant mortality. Extracellular cold-inducible RNA-binding protein (eCIRP) acts as a ligand of triggering receptor expressed on myeloid cells-1 (TREM-1). M3 is a small CIRP-derived peptide that inhibits the eCIRP/TREM-1 interaction. We hypothesize that the eCIRP/TREM-1 interaction in cardiomyocytes contributes to sepsis-induced cardiac dysfunction in neonatal sepsis, while M3 is cardioprotective. Methods Serum was collected from neonates in the Neonatal Intensive Care Unit (NICU). 5–7-day old C57BL/6 mouse pups were used in this study. Primary murine neonatal cardiomyocytes were stimulated with recombinant murine (rm) CIRP with M3. TREM-1 mRNA and supernatant cytokine levels were assayed. Mitochondrial oxidative stress, ROS, and membrane potential were assayed. Neonatal mice were injected with rmCIRP and speckle-tracking echocardiography was conducted to measure cardiac strain. Sepsis was induced by i.p. cecal slurry. Mouse pups were treated with M3 or vehicle. After 16 h, echocardiography was performed followed by euthanasia for tissue analysis. A 7-day survival study was conducted. Results Serum eCIRP levels were elevated in septic human neonates. rmCIRP stimulation of cardiomyocytes increased TREM-1 gene expression. Stimulation of cardiomyocytes with rmCIRP upregulated TNF-α and IL-6 in the supernatants, while this upregulation was inhibited by M3. Stimulation of cardiomyocytes with rmCIRP resulted in a reduction in mitochondrial membrane potential (MMP) while M3 treatment returned MMP to near baseline. rmCIRP caused mitochondrial calcium overload; this was inhibited by M3. rmCIRP injection impaired longitudinal and radial cardiac strain. Sepsis resulted in cardiac dysfunction with a reduction in cardiac output and left ventricular end diastolic diameter. Both were improved by M3 treatment. Treatment with M3 attenuated serum, cardiac, and pulmonary levels of pro-inflammatory cytokines compared to vehicle-treated septic neonates. M3 dramatically increased sepsis survival. Conclusions Inhibition of eCIRP/TREM-1 interaction with M3 is cardioprotective, decreases inflammation, and improves survival in neonatal sepsis. Trial registration Retrospectively registered.

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Cardiac Output Monitoring in Preterm Infants

Cited by 21 publications

References 107 publications

The Transitional Heart: From Early Embryonic and Fetal Development to Neonatal Life

The Transitional Heart: From Early Embryonic and Fetal Development to Neonatal Life

Targeting the eCIRP/TREM-1 Interaction with a Small Molecule Inhibitor Improves Cardiac Dysfunction in Neonatal Sepsis

Targeting the eCIRP/TREM-1 interaction with a small molecule inhibitor improves cardiac dysfunction in neonatal sepsis

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