Improving newborn respiratory outcomes with a sustained inflation: a systematic narrative review of factors regulating outcome in animal and clinical studies

Respiratory support is critically important for survival of newborns who fail to breathe spontaneously at birth. Although there is no internationally accepted definition of a sustained inflation (SI), it has commonly been defined as a positive pressure inflation designed to establish functional residual capacity and applied over a longer time period than normally used in standard respiratory support (SRS). Outcomes vary distinctly between studies and to date there has been no comprehensive investigation of differences in SI approach and study outcome in both pre-clinical and clinical studies. A systematic literature search was performed and, after screening, identified 17 animal studies and 17 clinical studies evaluating use of a SI in newborns compared to SRS during neonatal resuscitation. Study demographics including gestational age, SI parameters (length, repetitions, pressure, method of delivery) and study outcomes were compared. Animal studies provide mechanistic understanding of a SI on the physiology underpinning the cardiorespiratory transition at birth. In clinical studies, there is considerable difference in study quality, delivery of SIs (number, pressure, length) and timing of primary outcome evaluation which limits direct comparison between studies. The largest difference is method of delivery, where the role of a SI has been observed in intubated animals, as the inflation pressure is directly applied to the lung, bypassing the obstructed upper airway in an apnoeic state. This highlights a potential limitation in clinical use of a SI applied non-invasively. Further research is required to identify if a SI may have greater benefits in subpopulations of newborns.Developmen

Elektrochemische Potentiale während Hochfrequenz-Katheterablation von Herzrhythmusstörungen : In vitro und in vivo Experimente und erste klinische Erfahrungen

Einleitung: Die temperaturkontrollierte Katheterablation besitzt eine Reihe von Limitationen wie u.a. moderate Korrelation mit der Gewebetemperatur und Läsionsentwicklung. Ziel der vorliegenden Arbeit war es, ein Steuerungsparameter zu entwickeln, der die Qualität des Elektrodenkontaktes mit dem Gewebe und das Wachstum der Koagulationsnekrose direkt anhand zellulärer bzw. biologischer Prozesse des Zielgewebes wiedergibt. Material und Methodik: Endomyokard-Präparate frisch geschlachteter Rinder wurden in einem Tankbad mit physiologischer Kochsalzlösung für die in vitro Experimente verwandt, wo bei das elektrochemische Potential (eP) wie bei allen Untersuchungen zwischen der distalen und der proximalen Elektrode abgeleitet wurde. Tierexperimente wurden bei 8 intubiert, beatmeten Schweinen durchgeführt, wobei der experimentelle Aufbau adäquat zu den Bedingungen in vitro- elektrochemisches Potential zwischen distaler und proximaler Elektrode - war. Die ersten klinischen Untersuchungen wurden an 50 konsekutiven Patienten (m/w 29:21; 49,7 ± 9,8 Jahre), die zur elektiven Katheter-Ablation von supraventrikulären Tachykardien AVNRT bzw. WPW-Syndrom eingewiesen wurden, durchgeführt. Der meßtechnische Aufbau war unverändert zu den in vitro bzw. Tierexperimenten. Ergebnisse: Der Nachweis von eP gelang sowohl invitro, tierexperimentell als auch im klinischen Teil der Arbeit. Ferner konnte eine hohe Korrelation des elektrochemischen Potentials mit dem bisher üblichen Parameter \u27Temperatur\u27 errechnet werden (r=0,87). Eine ebenfalls hohe Korrelation wurde zwischen der Läsionsentwicklung und den eP festgestellt: r=0,85; p<0,001. Auch bei den \u27Routine-Kateterablationen\u27 konnte die Messung der eP bei Patienten durchgeführt werden. Ferner konnte mittels eP-gesteuerter Energieabgabe die Durchführbarkeit einer Katheterablation mit dem Parameters \u27eP\u27 gezeigt werden. Diskussion: Der Ursprung des eP liegt in der Läsionsentwicklung durch Erhitzung des myokardialen Gewebes. Die elektromotorische Kraftquelle des eP ist die Diffusion von freien Radikalen und intrazellulären Elektrolyten aus der Koagulationsläsion. Die eP stellt einen zusätzlichen Parameter neben der Temperatur und Impedanz - mit besserer Korrelation zur Läsion- dar. Die Steuerung der HF-Strom-Energieabgabe durch die eP ist möglich und erlaubt den Einsatz thermosensorfreier Elektroden. Potentiell klinische Anwendungen stellen die gekühlte Ablation sowie der Einsatz von multipolaren Ablationskathetern dar.Introduction: Temperature controlled radiofrequency catheter ablation (TRF) is widely introduced in current clinical practice with several limitations as the moderate correlation between catheter tip temperature (CTT) and lesion size (LS), and the increase in stiffness of multielectrode thermosensor catheters for the creation of linear lesions. Thermal injury of subendocardial tissue leads to a release of electrolytes and free radicals from the intracellular site creating a change in potential (dP) between distal and proximal catheter tip electrode. The aim of the doctorate was to verify the detection of ablation-induced release of electrolytes and free radicals and the possibility to control energy delivery in ablation by measuring dP. Energieabgabe die Durchführbarkeit einer Katheterablation mit dem Parameters \u27eP\u27 gezeigt werden. Methods and Results: In vitro tests at constant flow condition were performed in a 10 l bath of physiological saline solution and cattle blood. Endomyocardial preparations of fresh cattle hearts were used. Closed-loop temperature-controlled and closed-loop dP-controlled ablations were performed. In vivo animal investigations were performed in anesthetized and ventilated pigs. The existence of the dP was established in the tank model and was confirmed in the animal investigations. Good correlations were found between dP and CTT (r=0.87) and between maximum dP and induced LS (r=0.85). A high correlation (r=0.85, p<0.001) was found between dP and lesion volume. During routinely catheter ablation in 50 patients with supraventicular tachycardia dP-measurement was performed. Energieabgabe die Durchführbarkeit einer Katheterablation mit dem Parameters \u27eP\u27 gezeigt werden. Conclusions: Control of energy delivery during RF-ablation by the measurement of dP is feasible. In comparison to TRF, ablation steered by dP-measurement revealed superior correlation to induced LS. During irrigated catheter ablation, dP measurement is the only tool for energy control. To our knowledge, this is the first report on this novel method of ablation control

Prion protein interacts with bace1 and differentially regulates its activity towards wild type and swedish mutant amyloid precursor protein

In Alzheimer disease amyloid-β (Aβ) peptides derived from the amyloid precursor protein (APP) accumulate in the brain. Cleavage of APP by the β-secretase BACE1 is the rate-limiting step in the production of Aβ. We have reported previously that the cellular prion protein (PrP(C)) inhibited the action of BACE1 toward human wild type APP (APP(WT)) in cellular models and that the levels of endogenous murine Aβ were significantly increased in PrP(C)-null mouse brain. Here we investigated the molecular and cellular mechanisms underlying this observation. PrP(C) interacted directly with the prodomain of the immature Golgi-localized form of BACE1. This interaction decreased BACE1 at the cell surface and in endosomes where it preferentially cleaves APP(WT) but increased it in the Golgi where it preferentially cleaves APP with the Swedish mutation (APP(Swe)). In transgenic mice expressing human APP with the Swedish and Indiana familial mutations (APP(Swe,Ind)), PrP(C) deletion had no influence on APP proteolytic processing, Aβ plaque deposition, or levels of soluble Aβ or Aβ oligomers. In cells, although PrP(C) inhibited the action of BACE1 on APP(WT), it did not inhibit BACE1 activity toward APP(Swe). The differential subcellular location of the BACE1 cleavage of APP(Swe) relative to APP(WT) provides an explanation for the failure of PrP(C) deletion to affect Aβ accumulation in APP(Swe,Ind) mice. Thus, although PrP(C) exerts no control on cleavage of APP(Swe) by BACE1, it has a profound influence on the cleavage of APP(WT), suggesting that PrP(C) may be a key protective player against sporadic Alzheimer disease

The effect of breathing on ductus arteriosus blood flow directly after birth

Research into fetal development and medicin

Ductal flow ratio as a measure of transition in preterm infants after birth: a pilot study

Background: Cardiovascular changes during the transition from intra- to extrauterine life, alters the pressure gradient across the ductus arteriosus (DA). DA flow ratio (R-L/L-R) has been suggested to reflect the infant's transitional status and could potentially predict neonatal outcomes after preterm birth.Aim: Determine whether DA flow ratio correlates with oxygenation parameters in preterm infants at 1 h after birth.Methods: Echocardiography was performed in preterm infants born < 32 weeks gestational age (GA), as part of an ancillary study. DA flow was measured at 1 h after birth. DA flow ratio was correlated with FiO(2), SpO(2), and SpO(2)/FiO(2) (SF) ratio. The DA flow ratio of infants receiving physiological-based cord clamping (PBCC) or time-based cord clamping (TBCC) were compared.Results: Measurements from 16 infants were analysed (median [IQR] GA 29 [27-30] weeks; birthweight 1,176 [951-1,409] grams). R-L DA shunting was 16 [17-27] ml/kg/min and L-R was 110 [81-124] ml/kg/min. The DA flow ratio was 0.18 [0.11-0.28], SpO(2) 94 [93-96]%, FiO(2) was 23 [21-28]% and SF ratio 4.1 [3.3-4.5]. There was a moderate correlation between DA flow ratio and SpO(2) [correlation coefficient (CC) -0.415; p = 0.110], FiO(2) (CC 0.384; p = 0.142) and SF ratio (CC -0.356; p = 0.175). There were no differences in DA flow measurements between infants where PBBC or TBCC was performed.Conclusion: In this pilot study we observed a non-significant positive correlation between DA flow ratio at 1 h after birth and oxygenation parameters in preterm infants.Developmen

Clinical aspects of incorporating cord clamping into stabilisation of preterm infants

Fetal to neonatal transition is characterised by major pulmonary and haemodynamic changes occurring in a short period of time. In the international neonatal resuscitation guidelines, comprehensive recommendations are available on supporting pulmonary transition and delaying clamping of the cord in preterm infants. Recent experimental studies demonstrated that the pulmonary and haemodynamic transition are intimately linked, could influence each other and that the timing of umbilical cord clamping should be incorporated into the respiratory stabilisation. We reviewed the current knowledge on how to incorporate cord clamping into stabilisation of preterm infants and the physiological-based cord clamping (PBCC) approach, with the infant's transitional status as key determinant of timing of cord clamping. This approach could result in optimal timing of cord clamping and has the potential to reduce major morbidities and mortality in preterm infants

Repetitive versus standard tactile stimulation of preterm infants at birth - A randomized controlled trial

Development and application of statistical models for medical scientific researc

High variability in nurses' tactile stimulation methods in response to apnoea of prematurity: a neonatal manikin study

Aim: Neonatal intensive care unit (NICU) nurses provide tactile stimulation to terminate apnoea in preterm infants, but guidelines recommending specific methods are lacking. In this study, we evaluated current methods of tactile stimulation performed by NICU nurses.Methods: Nurses were asked to demonstrate and explain their methods of tactile stimulation on a manikin, using an apnoea scenario. All nurses demonstrated their methods three times in succession, with the manikin positioned either prone, supine or lateral. Finally, the nurses were asked how they decided on the methods of tactile stimulation used. The stimulation methods were logged in chronological order by describing both the technique and the location. The nurses' explanations were transcribed and categorised.Results: In total, 47 nurses demonstrated their methods of stimulation on the manikin. Overall, 57 different combinations of technique and location were identified. While most nurses (40/47, 85%) indicated they learned how to stimulate during their training, 15/40 (38%) of them had adjusted their methods over time. The remaining 7/47 (15%) stated that their stimulation methods were self-developed.Conclusion: Tactile stimulation performed by NICU nurses to terminate apnoea was highly variable in both technique and location, and these methods were based on either prior training or intuition.Developmen

Transitional circulation and hemodynamic monitoring in newborn infants

Transitional circulation is normally transient after birth but can vary markedly between infants. It is actually in a state of transition between fetal (in utero) and neonatal (postnatal) circulation. In the absence of definitive clinical trials, information from applied physiological studies can be used to facilitate clinical decision making in the presence of hemodynamic compromise. This review summarizes the peculiar physiological features of the circulation as it transitions from one phenotype into another in term and preterm infants. The common causes of hemodynamic compromise during transition, intact umbilical cord resuscitation, and advanced hemodynamic monitoring are discussed.Developmen