The ‘funny’ side of sepsis

Barbuti, Andrea; DiFrancesco, Dario

doi:10.1113/jphysiol.2014.271171

Cited by 3 publications

(5 citation statements)

References 7 publications

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“…Reduction of certain HRV measures during systemic inflammation is strongly correlated with an unfavourable prognosis. (14) Our findings provide the first evidence that iHRV originates in fetal life and that chronic fetal hypoxia significantly alters it. The relationship between nonlinear measures of fHRV and LVEDP suggests that such fHRV measures may reflect fetal myocardial function.…”

Section: Discussionmentioning

confidence: 52%

First evidence that intrinsic fetal heart rate variability exists and is affected by hypoxic pregnancy

Frasch

Herry

Niu

et al. 2018

Preprint

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Heart rate variability (HRV) is an important indicator of health and disease, yet its physiological origins are poorly understood. The contribution of intrinsic and extrinsic sources to HRV is not known. In a near-term fetal sheep model, we aimed to identify fetal HRV measures reflecting intrinsic contributions to HRV. Ex vivo Langendorff preparation was used to record intrinsic HRV in animals who were normoxic or hypoxic in vivo. We identify the intrinsic HRV in isolated hearts from fetal sheep in late gestation and how it is affected by chronic fetal hypoxia. Significance StatementHeart rate variability (HRV) is an important indicator of health and disease, yet its physiological origins are poorly understood. Both, the heart, intrinsically, and extrinsic systems, such as the brain, are hypothesized to contribute to HRV. In a near-term fetal sheep model of human development, we identified fetal HRV components reflecting intrinsic contributions to HRV. In addition, we show that these intrinsic HRV components carry memory of chronic oxygen deprivation the fetus experienced during the last third of gestation.peer-reviewed) is the author/funder. All rights reserved. No reuse allowed without permission.The copyright holder for this preprint (which was not . http://dx.doi.org/10.1101/242107 doi: bioRxiv preprint first posted online Jan. 22, 2018; 3 IntroductionFetal heart rate (FHR) monitoring is widely used clinically during labour, although its ability to identify fetuses at risk of severe metabolic acidosis is poor.(1) It is established that normal FHR variability (fHRV) represents a complex, nonlinear integration of the sympathetic and parasympathetic nervous system activities. Fetal body and breathing movements, baroreflex and circadian processes also influence HRV.(2,3,4-6) There is also some evidence that intrinsic pacemaker rhythms of the sino-atrial node affect HRV in critically ill adults. (7) However, whether intrinsic HRV (iHRV) exists in the fetal period and whether this is affected by chronic fetal hypoxia has never been tested. Here, we show iHRV in isolated hearts from fetal sheep in late gestation. We also show that chronic fetal hypoxia has significant effects on iHRV.

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Section: Discussionmentioning

confidence: 52%

First evidence that intrinsic fetal heart rate variability exists and is affected by hypoxic pregnancy

Frasch

Herry

Niu

et al. 2018

Preprint

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“…In a model of a spontaneously active sinoatrial cell, endotoxin-induced I f impairment reduced the responsiveness of the model cell to fluctuations of autonomic input, thereby reducing heart rate variability between 38% and 62% 36. This endotoxin effect is not mediated by any of the intracellular modulatory pathways affecting HCN channels, but is instead due to a direct interaction with the channel 60–62. In addition to this direct inhibitory effect of endotoxin on I f , endotoxin in human atrial cardiomyocytes also sensitizes I f to beta-adrenergic stimulation, thereby increasing heart rate 36.…”

Section: Ivabradine – Mode Of Action and Pharmacologymentioning

confidence: 98%

Advances in the management of heart failure: the role of ivabradine

Müller‐Werdan

Stöckl

Werdan

2016

VHRM

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A high resting heart rate (≥70–75 b.p.m.) is a risk factor for patients with heart failure (HF) with reduced ejection fraction (EF), probably in the sense of accelerated atherosclerosis, with an increased morbidity and mortality. Beta-blockers not only reduce heart rate but also have negative inotropic and blood pressure-lowering effects, and therefore, in many patients, they cannot be given in the recommended dose. Ivabradine specifically inhibits the pacemaker current (funny current, If) of the sinoatrial node cells, resulting in therapeutic heart rate lowering without any negative inotropic and blood pressure-lowering effect. According to the European Society of Cardiology guidelines, ivabradine should be considered to reduce the risk of HF hospitalization and cardiovascular death in symptomatic patients with a reduced left ventricular EF ≤35% and sinus rhythm ≥70 b.p.m. despite treatment with an evidence-based dose of beta-blocker or a dose below the recommended dose (recommendation class “IIa” = weight of evidence/opinion is in favor of usefulness/efficacy: “should be considered”; level of evidence “B” = data derived from a single randomized clinical trial or large nonrandomized studies). Using a heart rate cutoff of ≥ 75 b.p.m., as licensed by the European Medicines Agency, treatment with ivabradine 5–7.5 mg b.i.d. reduces cardiovascular mortality by 17%, HF mortality by 39% and HF hospitalization rate by 30%. A high resting heart rate is not only a risk factor in HF with reduced EF but also at least a risk marker in HF with preserved EF, in acute HF and also in special forms of HF. In this review, we discuss the proven role of ivabradine in the validated indication “HF with reduced EF” together with interesting preliminary findings, and the potential role of ivabradine in further, specific forms of HF.

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“…[24] LPS released from Gram-negative bacteria during severe sepsis reduces both native If and HCN2-or HCN4-mediated currents and shifts their activation to more negative potentials. [25] The LPS effect is not mediated by any of the intracellular modulatory pathways affecting HCN channels, but is instead due to a direct interaction with the channel. which may impair normal rate control and decrease the cardiac safety factor, making the system more prone to life-threatening perturbations (Fig.…”

Section: ) How Is Cps Impacted By Developmental Hypoxia and Infection?mentioning

confidence: 99%

“…[24] LPS released from Gram-negative bacteria during severe sepsis reduces both native If and HCN2-or HCN4-mediated currents and shifts their activation to more negative potentials. [25] The LPS effect is not mediated by any of the intracellular modulatory pathways affecting HCN channels, but is instead due to a direct interaction with the channel. [22] Klöckner et al have shown that alterations of the HCN current require the integrity of the LPS molecule, since neither the proinflammatory lipid A alone nor the O-chain polysaccharidic region alone were effective.…”

Section: ) How Is Cps Impacted By Developmental Hypoxia and Infection?mentioning

confidence: 99%

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Impact of Chronic Fetal Hypoxia and Inflammation on Cardiac Pacemaker Cell Development

Frasch

Giussani

2020

Cells

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Chronic fetal hypoxia and infection are examples of adverse conditions during complicated pregnancy, which impact cardiac myogenesis and increase the lifetime risk of heart disease.However, the effects that chronic hypoxic or inflammatory environments exert on cardiac pacemaker cells are poorly understood. Here, we review the current evidence and novel avenues of bench-to-bed research in this field of perinatal cardiogenesis as well as its translational significance for early detection of future risk for cardiovascular disease.

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The ‘funny’ side of sepsis

Cited by 3 publications

References 7 publications

First evidence that intrinsic fetal heart rate variability exists and is affected by hypoxic pregnancy

First evidence that intrinsic fetal heart rate variability exists and is affected by hypoxic pregnancy

Advances in the management of heart failure: the role of ivabradine

Impact of Chronic Fetal Hypoxia and Inflammation on Cardiac Pacemaker Cell Development

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