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

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

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

KEY POINTS: We introduce a technique to test whether intrinsic fetal heart rate variability (iFHRV) exists and we show the utility of the technique by testing the hypothesis that iFHRV is affected by chronic fetal hypoxia, one of the most common adverse outcomes of human pregnancy complicated by fetal growth restriction. Using an established late gestation ovine model of fetal development under chronic hypoxic conditions, we identify iFHRV in isolated fetal hearts and show that it is markedly affected by hypoxic pregnancy. Therefore, the isolated fetal heart has intrinsic variability and carries a memory of adverse intrauterine conditions experienced during the last third of pregnancy. ABSTRACT: Fetal heart rate variability (FHRV) emerges from influences of the autonomic nervous system, fetal body and breathing movements, and from baroreflex and circadian processes. We tested whether intrinsic heart rate variability (iHRV), devoid of any external influences, exists in the fetal period and whether it is affected by chronic fetal hypoxia. Chronically catheterized ewes carrying male singleton fetuses were exposed to normoxia (n = 6) or hypoxia (10% inspired O2 , n = 9) for the last third of gestation (105-138 days of gestation (dG); term ∼145 dG) in isobaric chambers. At 138 dG, isolated hearts were studied using a Langendorff preparation. We calculated basal intrinsic FHRV (iFHRV) indices reflecting iFHRV's variability, predictability, temporal symmetry, fractality and chaotic behaviour, from the systolic peaks within 15 min segments in each heart. Significance was assumed at P < 0.05. Hearts of fetuses isolated from hypoxic pregnancy showed approximately 4-fold increases in the Grid transformation as well as the AND similarity index (sgridAND) and a 4-fold reduction in the scale-dependent Lyapunov exponent slope. We also detected a 2-fold reduction in the Recurrence quantification analysis, percentage of laminarity (pL) and recurrences, maximum and average diagonal line (dlmax, dlmean) and the Multiscale time irreversibility asymmetry index. The iHRV measures dlmax, dlmean, pL and sgridAND correlated with left ventricular end-diastolic pressure across both groups (average R2  = 0.38 ± 0.03). This is the first evidence that iHRV originates in fetal life and that chronic fetal hypoxia significantly alters it. Isolated fetal hearts from hypoxic pregnancy exhibit a time scale-dependent higher complexity in iFHRV.British Heart Foundatio

Étude des altérations du contrôle cardiorespiratoire chez des modèles ovins de pathologies néonatales

Introduction : L'implication des RGO dans les événements cardiorespiratoires des prématurés reste controversée. Bien que quelques études réalisées sur des animaux nouveau-nés à terme ou adultes aient montré que la stimulation des récepteurs œsophagiens entraine des réflexes cardiorespiratoires inhibiteurs, l’impact d’une naissance prématurée sur ces derniers demeure inconnu. L’article 1 vise à tester l’hypothèse selon laquelle la naissance prématurée augmente l'inhibition cardiorespiratoire lors d’une stimulation oesophagienne. Le sepsis néonatal est à l’origine d’une mortalité substantielle, en partie en raison de ses conséquences sur le contrôle cardiorespiratoire. Les réponses au sepsis néonatal sont variables et peuvent expliquer un faible diagnostic pendant la phase initiale de l'infection. L'implication du sepsis néonatal sur le contrôle cardiorespiratoire reste mal connue. L’article 2 vise à comprendre davantage le lien entre l’inflammation accompagnant un sepsis néonatal et les altérations cardiaques et respiratoires. Méthodes : Article 1. Huit agneaux nés à terme et dix agneaux nés 14 jours prématurément ont été étudiés. Une polysomnographie a été réalisée pour suivre en continu l’ECG, la respiration, la pression artérielle systémique, les stades de conscience et la saturation en O2. Cinq stimulations de l'œsophage supérieur et/ou inférieur, incluant l'inflation rapide par ballonnet et/ou l'injection d’HCl, ont été effectuées dans un ordre aléatoire. Article 2. Deux polysomnographies de six heures ont été réalisées sur deux jours consécutifs chez huit agneaux. La première a été effectuée suivant une injection IV de solution saline, et la deuxième après une injection IV de 2,5 μg/kg de lipopolysaccharides (LPS). La température, les gaz du sang artériel, les stades de conscience, l'activité locomotrice, les fréquences respiratoire et cardiaque (FR et FC), la variabilité cardiaque et respiratoire (VFC et VFR), la pression artérielle systémique, les apnées et les ralentissements cardiaques ont été évalués. Résultats : Les stimulations œsophagiennes induisent des réflexes cardiorespiratoires inhibiteurs (apnées, bradycardies, désaturations en oxygène) qui sont amplifiés par la naissance prématurée. L'inhibition cardiorespiratoire la plus importante est observée suite à une stimulation simultanée de l'œsophage inférieur et supérieur. L’injection de LPS induit des altérations cliniques (augmentation biphasique de la température et diminution de la mobilité et de l’éveil agité) et cardiorespiratoires (augmentation de la FR et de la FC et diminution de la VFC et de la VFR) en plus d’une inflammation du tronc cérébral. Conclusion : La stimulation œsophagienne entraine une augmentation des événements cardiorespiratoires chez les agneaux prématurés, probablement en raison de l'immaturité globale du système nerveux. L'injection de LPS entraine une inflammation systémique mimant un sepsis bactérien chez les agneaux avec de multiples conséquences, y compris des altérations cardiorespiratoires

Activation of the pro-resolving receptor Fpr2 attenuates inflammatory microglial activation

Poster number: P-T099 Theme: Neurodegenerative disorders & ageing Activation of the pro-resolving receptor Fpr2 reverses inflammatory microglial activation Authors: Edward S Wickstead - Life Science & Technology University of Westminster/Queen Mary University of London Inflammation is a major contributor to many neurodegenerative disease (Heneka et al. 2015). Microglia, as the resident immune cells of the brain and spinal cord, provide the first line of immunological defence, but can become deleterious when chronically activated, triggering extensive neuronal damage (Cunningham, 2013). Dampening or even reversing this activation may provide neuronal protection against chronic inflammatory damage. The aim of this study was to determine whether lipopolysaccharide (LPS)-induced inflammation could be abrogated through activation of the receptor Fpr2, known to play an important role in peripheral inflammatory resolution. Immortalised murine microglia (BV2 cell line) were stimulated with LPS (50ng/ml) for 1 hour prior to the treatment with one of two Fpr2 ligands, either Cpd43 or Quin-C1 (both 100nM), and production of nitric oxide (NO), tumour necrosis factor alpha (TNFα) and interleukin-10 (IL-10) were monitored after 24h and 48h. Treatment with either Fpr2 ligand significantly suppressed LPS-induced production of NO or TNFα after both 24h and 48h exposure, moreover Fpr2 ligand treatment significantly enhanced production of IL-10 48h post-LPS treatment. As we have previously shown Fpr2 to be coupled to a number of intracellular signaling pathways (Cooray et al. 2013), we investigated potential signaling responses. Western blot analysis revealed no activation of ERK1/2, but identified a rapid and potent activation of p38 MAP kinase in BV2 microglia following stimulation with Fpr2 ligands. Together, these data indicate the possibility of exploiting immunomodulatory strategies for the treatment of neurological diseases, and highlight in particular the important potential of resolution mechanisms as novel therapeutic targets in neuroinflammation. References Cooray SN et al. (2013). Proc Natl Acad Sci U S A 110: 18232-7. Cunningham C (2013). Glia 61: 71-90. Heneka MT et al. (2015). Lancet Neurol 14: 388-40

Libro de actas. XXXV Congreso Anual de la Sociedad Española de Ingeniería Biomédica

596 p.CASEIB2017 vuelve a ser el foro de referencia a nivel nacional para el intercambio científico de conocimiento, experiencias y promoción de la I D i en Ingeniería Biomédica. Un punto de encuentro de científicos, profesionales de la industria, ingenieros biomédicos y profesionales clínicos interesados en las últimas novedades en investigación, educación y aplicación industrial y clínica de la ingeniería biomédica. En la presente edición, más de 160 trabajos de alto nivel científico serán presentados en áreas relevantes de la ingeniería biomédica, tales como: procesado de señal e imagen, instrumentación biomédica, telemedicina, modelado de sistemas biomédicos, sistemas inteligentes y sensores, robótica, planificación y simulación quirúrgica, biofotónica y biomateriales. Cabe destacar las sesiones dedicadas a la competición por el Premio José María Ferrero Corral, y la sesión de competición de alumnos de Grado en Ingeniería biomédica, que persiguen fomentar la participación de jóvenes estudiantes e investigadores

XXIV congreso anual de la sociedad española de ingeniería biomédica (CASEIB2016)

En la presente edición, más de 150 trabajos de alto nivel científico van a ser presentados en 18 sesiones paralelas y 3 sesiones de póster, que se centrarán en áreas relevantes de la Ingeniería Biomédica. Entre las sesiones paralelas se pueden destacar la sesión plenaria Premio José María Ferrero Corral y la sesión de Competición de alumnos de Grado en Ingeniería Biomédica, con la participación de 16 alumnos de los Grados en Ingeniería Biomédica a nivel nacional. El programa científico se complementa con dos ponencias invitadas de científicos reconocidos internacionalmente, dos mesas redondas con una importante participación de sociedades científicas médicas y de profesionales de la industria de tecnología médica, y dos actos sociales que permitirán a los participantes acercarse a la historia y cultura valenciana. Por primera vez, en colaboración con FENIN, seJane Campos, R. (2017). XXIV congreso anual de la sociedad española de ingeniería biomédica (CASEIB2016). Editorial Universitat Politècnica de València. http://hdl.handle.net/10251/79277EDITORIA

Regularity of Fetal HRV changes in an In-vivo Sheep Model of Labor

Labor exposes the fetus to repetitive transient hypoxic stress. We assessed whether such events modify the regularity of the fetal inter-beat interval series (fRR), using an in-vivo near-term sheep model, by means of entropy measures. Umbilical cord occlusions (UCO), from partial to complete, were applied to 7 near-term pregnant sheep. Fetal blood samples were collected at intervals of 20 minutes, to quantify pH, lactate and base deficit (\u201cbiomarkers\u201d). Fetal ECG recordings were collected with implanted electrodes and used to derive the fRR series. Sample entropy (SampEn), permutation entropy (PE) and conditional PE(cPE) were estimated for fRR patterns of various lengths m, in each 2.5 minutes-long cycle of occlusion and successive recovery. Entropies' changes in time, during the course of the experiment, and their relation with the simultaneous values of the biomarkers were evaluated with Spearman's rank-order correlations. Entropy values decreased during the experimental protocol (rs= 120.62 for SampEn at m = 1, rs= 120.27 for PE at m = 5 and rs= 120.30 for cPE at m = 4; p < 0.05). Correlations with biomarkers were found to be moderate for SampEn (0.49 < |rs| < 0.62; p < 0.05) and weak to moderate for PE and cPE (0.31 < |rs| < 0.54; p < 0.05). Repetitive UCOs changed the regularity of fRR, suggesting a pronounced modulation as first line adaptive response