Microcirculation of the Newborn

Appropriate regulation of microvascular blood flow in the neonate is crucial for cardiorespiratory stability and survival in the period immediately following birth. Inappropriate microvascular dilatation in the first few days of extrauterine life is associated with poor outcomes in preterm neonates. Male very preterm neonates (≤28 weeks completed gestation) have significantly higher flows than females of the same gestational age. This is of clinical importance as preterm males are twice as likely to die as females. Very little is known about the mechanisms underlying microvascular tone regulation in the perinatal period. Previous studies suggest a role for the gasotransmitters nitric oxide and carbon monoxide; however, differences in levels of these molecules do not account for all the variation observed, suggesting another player. In this chapter, the role of the third gasotransmitter—hydrogen sulphide—as a potential mediator of microvascular (dys)function in the preterm is explored

Interactions of the Gasotransmitters Contribute to Microvascular Tone (Dys)regulation in the Preterm Neonate

Background & Aims Hydrogen sulphide (H2S), nitric oxide (NO), and carbon monoxide (CO) are involved in transitional microvascular tone dysregulation in the preterm infant; however there is conflicting evidence on the interaction of these gasotransmitters, and their overall contribution to the microcirculation in newborns is not known. The aim of this study was to measure the levels of all 3 gasotransmitters, characterise their interrelationships and elucidate their combined effects on microvascular blood flow. Methods 90 preterm neonates were studied at 24h postnatal age. Microvascular studies were performed by laser Doppler. Arterial COHb levels (a measure of CO) were determined through co-oximetry. NO was measured as nitrate and nitrite in urine. H2S was measured as thiosulphate by liquid chromatography. Relationships between levels of the gasotransmitters and microvascular blood flow were assessed through partial correlation controlling for the influence of gestational age. Structural equation modelling was used to examine the combination of these effects on microvascular blood flow and derive a theoretical model of their interactions. Results No relationship was observed between NO and CO (p = 0.18, r = 0.18). A positive relationship between NO and H2S (p = 0.008, r = 0.28) and an inverse relationship between CO and H2S (p = 0.01, r = -0.33) exists. Structural equation modelling was used to examine the combination of these effects on microvascular blood flow. The model with the best fit is presented. Conclusions The relationships between NO and H2S, and CO and H2S may be of importance in the preterm newborn, particularly as NO levels in males are associated with higher H2S levels and higher microvascular blood flow and CO in females appears to convey protection against vascular dysregulation. Here we present a theoretical model of these interactions and their overall effects on microvascular flow in the preterm newborn, upon which future mechanistic studies may be based.The authors would like to acknowledge the parents of the neonates enrolled in the 2CANS study for their participation, the staff of the Kaleidoscope Neonatal Intensive Care Unit at the John Hunter Children’s Hospital, and Kimberly-Clark Australia for providing the diapers used in this stud

Magnesium sulfate has sex-specific, dose-dependent vasodilator effects on preterm placental vessels

Background Women at risk of preterm delivery receive magnesium sulfate (MgSO 4 ) in the pre-delivery phase to reduce their child\u27s risk of neurodevelopmental complications associated with preterm birth. However, the mechanisms underpinning its placental vascular role remain uncertain. Methods The aim of this study was to examine MgSO 4 action on vascular tone in male and female human placental vessels from term and preterm deliveries. Vessels were obtained from placental biopsy following birth at term (37-41 weeks) or preterm gestation (gestation). The vessels were mounted on a pressure myograph, pre-constricted with synthetic endoperoxide prostaglandin PGH 2 (U46619) (0.1-100 μmol/l), and percentage of relaxation was calculated following incubation with bradykinin. Experiments were carried out in the presence of MgSO 4 (0.2 mmol/l), N Ψ -nitro-L-arginine methyl ester (L-NAME) (0.1 mmol/l), indomethacin (10 μmol/l), Ca 2+ -activated K + channel blocker TRAM-34 (1 μM) and apamin (3 μM) to assess mechanisms of vascular function. Vascular [calcium ions (Ca 2+ )] was analysed using a colorimetric calcium assay. Results Vasodilation in vessels from preterm males was significantly blunted in the presence of MgSO 4 when compared to preterm female and term male and female vessels. Overall, MgSO 4 was observed to differentially modulate placental vascular tone and vascular calcium concentrations in a sex-specific manner. Conclusions As MgSO 4 regulates human placental blood flow via specific pathways, foetal sex-specific MgSO 4 treatment regimes may be necessary. In an era of increasing awareness of individualised medicine, sex-specific effects may be of importance when developing strategies to optimise care in high-risk patients

Videomicroscopy as a tool for investigation of the microcirculation in the newborn

The perinatal period remains a time of significant risk of death or disability. Increasing evidence suggests that this depends on microcirculatory behavior. Sidestream dark-field orthogonal polarized light videomicroscopy (OPS) has emerged as a useful assessment of adult microcirculation but the values derived are not delineated for the newborn. We aimed to define these parameters in well term newborn infants. Demographic details were collected prospectively on 42 healthy term neonates (n = 20 females, n = 22 males). OPS videomicroscopy (Microscan) was used to view ear conch skin microcirculation at 6, 24, and 72 h of age. Stored video was analyzed by a masked observer using proprietary software. There were no significant differences between the sexes for any structural parameters at any time point. There was a significant increase over time in small vessel perfusion in female infants only (P = 0.009). A number of 6- and 72-h measurements were significantly correlated, but differed from the 24-h values. These observations confirm the utility of the ear conch for neonatal microvascular videomicroscopy. They provide a baseline for studies into the use of OPS videomicroscopy in infants. The changes observed are comparable with previous studies of term infants using these and other microvascular techniques. It is recommended that studies for examining the mature neonatal microvascular structure be delayed until 72 h of life, but studies of the physiology of cardiovascular transition should include the 24-h time point after delivery

Estimating particulate matter (PM) concentrations from a meteorological index for data-scarce regions : a pilot study

In regions where air quality data are scarce or access thereto is limited, a comprehensive understanding of air pollution is hindered by a lack of emission data and ambient air pollution measurements. Therefore, in this pilot study, we assess the feasibility of estimating particulate matter (PM) mass concentrations from a meteorological index. Measured PM concentrations from air quality monitoring stations (2013–2016) situated in and around South African air pollution priority areas were analysed. Simulated meteorological parameters were used to calculate the newly-developed Air Dispersion Potential (ADP) index, which describes the meteorological potential for pollution dispersion in the atmosphere. For most conditions, there exists weak (r = 0.1–0.29) to moderate (r = 0.30–0.49) correlations between the ADP index and PM classes. At the three stations with adequate data availability, it was found that the ADP index was relatively successful in predicting conditions of high PM concentrations. An investigation of the effect of meteorological conditions on the diurnal variation of PM concentrations led to both the quantification of this effect, and the realization that at these diverse sites, up to 29% of variation in hourly PM concentrations can be explained by variations in meteorology. The application of the index in this way can play an important role in air quality management by quantifying the impacts of meteorological drivers on PM peaks.SASOL through the Laboratory for Atmospheric Studies (LAS) at the University of Pretoria.https://www.elsevier.com/locate/apr2020-09-01hj2019Geography, Geoinformatics and Meteorolog

Early microvascular changes in the preterm neonate: a comparative study of the human and guinea pig

Dysfunction of the transition from fetal to neonatal circulatory systems may be a major contributor to poor outcome following preterm birth. Evidence exists in the human for both a period of low flow between 5 and 11 h and a later period of increased flow, suggesting a hypoperfusion-reperfusion cycle over the first 24 h following birth. Little is known about the regulation of peripheral blood flow during this time. The aim of this study was to conduct a comparative study between the human and guinea pig to characterize peripheral microvascular behavior during circulatory transition. Very preterm (≤28 weeks GA), preterm (29-36 weeks GA), and term (≥37 weeks GA) human neonates underwent laser Doppler analysis of skin microvascular blood flow at 6 and 24 h from birth. Guinea pig neonates were delivered prematurely (62 day GA) or at term (68-71 day GA) and laser Doppler analysis of skin microvascular blood flow was assessed every 2 h from birth. In human preterm neonates, there is a period of high microvascular flow at 24 h after birth. No period of low flow was observed at 6 h. In preterm animals, microvascular flow increased after birth, reaching a peak at 10 h postnatal age. Blood flow then steadily decreased, returning to delivery levels by 24 h. Preterm birth was associated with higher baseline microvascular flow throughout the study period in both human and guinea pig neonates. The findings do not support a hypoperfusion-reperfusion cycle in the microcirculation during circulatory transition. The guinea pig model of preterm birth will allow further investigation of the mechanisms underlying microvascular function and dysfunction during the initial extrauterine period

Nitrous oxide improves cardiovascular, respiratory, and thermal stability during prolonged isoflurane anesthesia in juvenile guinea pigs

Anesthesia is frequently used to facilitate physiological monitoring during interventional animal studies. However, its use may induce cardiovascular (central and peripheral), respiratory, and thermoregulatory depression, confounding results in anesthetized animals. Despite the wide utility of guinea pigs as a translational platform, anesthetic protocols remain unstandardized for extended physiological studies in this species. Therefore, optimizing an anesthetic protocol that balances stable anesthesia with intact cardiorespiratory and metabolic function is crucial. To achieve this, 12 age and sex-matched juvenile Dunkin Hartley guinea pigs underwent extended anesthesia (≤150 min) with either (a) isoflurane (ISO: 1.5%), or (b) isoflurane + N2O (ISO+ N2O: 0.8% +70%), in this randomized cross-over designed study. Cardiovascular (HR, SBP, peripheral microvascular blood flow), respiratory (respiratory rate, SpO2), and thermal (Tre and Tsk) measures were recorded continuously throughout anesthesia. Blood gas measures pre- and post- anesthesia were performed. Incorporation of 70% N2O allowed for significant reductions in isoflurane (to 0.8%) while maintaining an effective anesthetic depth for prolonged noninvasive physiological examination in guinea pigs. ISO+N2O maintained heart rate, peripheral blood flow, respiratory rate, and thermoregulatory function at levels closest to those of conscious animals, especially in females; however, it did not fully rescue anesthesia-induced hypotension. These results suggest that for studies requiring prolonged physiological examination (≤150 min) in guinea pigs, 0.8% isoflurane with a 70% N2O adjuvant provides adequate anesthesia, while minimizing associated cardiorespiratory depression. The preservation of cardiorespiratory status is most marked throughout the first hour of anesthesia

Outcomes of 23- and 24-weeks gestation infants in Wellington, New Zealand: A single centre experience

Optimal perinatal care of infants born less than 24 weeks gestation remains contentious due to uncertainty about the long-term neurodevelopment of resuscitated infants. Our aim was to determine the short-term mortality and major morbidity outcomes from a cohort of inborn infants born at 23 and 24 weeks gestation and to assess if these parameters differed significantly between infants born at 23 vs. 24 weeks gestation. We report survival rates at 2-year follow-up of 22/38 (58%) at 23 weeks gestation and 36/60 (60%) at 24 weeks gestation. Neuroanatomical injury at the time of discharge (IVH ≥ Grade 3 and/or PVL) occurred in in 3/23 (13%) and 1/40 (3%) of surviving 23 and 24 weeks gestation infants respectively. Rates of disability at 2 years corrected postnatal age were not different between infants born at 23 and 24 weeks gestation. We show evidence that with maximal perinatal care in a tertiary setting it is possible to achieve comparable rates of survival free of significant neuroanatomical injury or severe disability at age 2 in infants born at 23-week and 24-weeks gestation

A novel whole-body thermal stress test for monitoring cardiovascular responses in guinea pigs

Cardiovascular disease is a leading cause of morbidity and mortality worldwide. Stress tests are frequently employed to expose early signs of cardiovascular dysfunction or disease and can be employed, for example, in the context of preterm birth. We aimed to establish a safe and effective thermal stress test to examine cardiovascular function. Guinea pigs were anaesthetized using a 0.8% isoflurane, 70% N2O mix. ECG, non-invasive blood pressure, laser Doppler flowmetry, respiratory rate, and an array of skin and rectal thermistors were applied. A physiologically relevant heating and a cooling thermal stress test was developed. Upper and lower thermal limits for core body temperature were set at 41.5 OC and 34 OC, for the safe recovery of animals. This protocol therefore presents a viable thermal stress test for use in guinea pig models of health and disease that facilitates exploration of whole-system cardiovascular function

Effortful control and parenting: Associations with HPA axis reactivity in early childhood

While activation of the hypothalamic-pituitary-adrenal (HPA) axis is an adaptive response to stress, excessive HPA axis reactivity may be an important marker of childhood vulnerability to psychopathology. Parenting, including parent affect during parent-child interactions, may play an important role in shaping the developing HPA system; however, the association of parent affect may be moderated by child factors, especially children\u27s emerging self-regulatory skills. We therefore tested the relationship between parent affectivity and 160 preschoolers\u27 cortisol reactivity during a laboratory visit, examining children\u27s effortful control (EC) as a moderator. Greater parent negative affectivity was related to greater initial and increasing cortisol over time, but only when children were low in EC. Higher parent positive affectivity was related to a higher baseline cortisol for children with low EC and lower baseline cortisol for children with high EC. Results indicate that children\u27s EC moderates the extent to which parent affect shapes stress reactive systems in early childhood. © 2013 Blackwell Publishing Ltd