A Porcine Model of Neonatal Hypoxia-Asphyxia to Study Resuscitation Techniques in Newborn Infants

Two to three million newborn infants worldwide need extensive cardiopulmonary resuscitation (CPR), and approximately one million of these infants die annually worldwide. Therefore, resuscitation techniques require further refinement to provide better outcomes. To investigate the effectiveness of various interventions and to understand the pathophysiology and pharmacology of neonatal CPR, it is important to have animal models that reliably reproduce features observed in neonates who require resuscitation. Herein, we describe an experimental animal model in newborn piglets that simulates neonatal asphyxia and enables us to examine resuscitation interventions, reoxygenation, and recovery processes. The newborn piglet has several advantages including similar development to a human fetus at 36–38 week’s gestation, and comparable body systems and body size, allowing for surgical instrumentation, monitoring, and collection of biological samples. Furthermore, using this model of neonatal asphyxia, we are also able to describe an increasingly important clinical situation in the laboratory setting—pulseless electrical activity (PEA). Since the integration of electrocardiogram into the neonatal resuscitation guidelines, there has been an increased awareness of PEA in newborn infants. The animal model we describe can therefore serve as a valuable tool to bridge the knowledge gap and improve the outcome of asphyxiated newborns in the delivery room

Respiratory Function During Chest Compressions

Chest compression (CC) is an infrequent event (0.08%) in newborns delivered at near-term and term gestation, and occurs at a higher frequency (10%) in preterm deliveries. In addition, outcome studies of deliveries requiring resuscitation or chest compression have reported high rates of mortality and neurodevelopmental impairment in surviving children. A respiratory function monitor (RFM) can help guide a resuscitator during cardiopulmonary resuscitation (CPR) in a neonate and help assess the quality and efficacy of chest compression. Utilizing a non-invasive respiratory function monitor during chest compression may decrease high mortality rates in addition to having many distinct advantages, which will benefit both the newborn and the resuscitators. There are several different ways that a respiratory function monitor can assist a resuscitator during chest compression; these include confirming and ensuring adequate lung ventilation, analyzing the efficacy and quality of chest compression and exhaled CO2 monitoring

Early Gnathostome Phylogeny Revisited: Multiple Method Consensus

This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.A series of recent studies recovered consistent phylogenetic scenarios of jawed vertebrates, such as the paraphyly of placoderms with respect to crown gnathostomes, and antiarchs as the sister group of all other jawed vertebrates. However, some of the hylogenetic relationships within the group have remained controversial, such as the positions of Entelognathus, ptyctodontids, and the Guiyu-lineage that comprises Guiyu, Psarolepis and Achoania. The revision of the dataset in a recent study reveals a modified phylogenetic hypothesis, which shows that some of these phylogenetic conflicts were sourced from a few inadvertent miscodings. The interrelationships of early gnathostomes are addressed based on a combined new dataset with 103 taxa and 335 characters, which is the most comprehensive morphological dataset constructed to date. This dataset is investigated in a phylogenetic context using maximum parsimony (MP), Bayesian inference (BI) and maximum likelihood (ML) approaches in an attempt to explore the consensus and incongruence between the hypotheses of early gnathostome interrelationships recovered from different methods. Our findings consistently corroborate the paraphyly of placoderms, all `acanthodians' as a paraphyletic stem group of chondrichthyans, Entelognathus as a stem gnathostome, and the Guiyu-lineage as stem sarcopterygians. The incongruence using different methods is less significant than the consensus, and mainly relates to the positions of the placoderm Wuttagoonaspis, the stem chondrichthyan Ramirosuarezia, and the stem osteichthyan LophosteusÐthe taxa that are either poorly known or highly specialized in character complement. Given that the different performances of each phylogenetic approach, our study provides an empirical case that the multiple phylogenetic analyses of morphological data are mutually complementary rather than redundant

Dissecting the Shared Genetic Architecture of Suicide Attempt, Psychiatric Disorders, and Known Risk Factors

Background Suicide is a leading cause of death worldwide, and nonfatal suicide attempts, which occur far more frequently, are a major source of disability and social and economic burden. Both have substantial genetic etiology, which is partially shared and partially distinct from that of related psychiatric disorders. Methods We conducted a genome-wide association study (GWAS) of 29,782 suicide attempt (SA) cases and 519,961 controls in the International Suicide Genetics Consortium (ISGC). The GWAS of SA was conditioned on psychiatric disorders using GWAS summary statistics via multitrait-based conditional and joint analysis, to remove genetic effects on SA mediated by psychiatric disorders. We investigated the shared and divergent genetic architectures of SA, psychiatric disorders, and other known risk factors. Results Two loci reached genome-wide significance for SA: the major histocompatibility complex and an intergenic locus on chromosome 7, the latter of which remained associated with SA after conditioning on psychiatric disorders and replicated in an independent cohort from the Million Veteran Program. This locus has been implicated in risk-taking behavior, smoking, and insomnia. SA showed strong genetic correlation with psychiatric disorders, particularly major depression, and also with smoking, pain, risk-taking behavior, sleep disturbances, lower educational attainment, reproductive traits, lower socioeconomic status, and poorer general health. After conditioning on psychiatric disorders, the genetic correlations between SA and psychiatric disorders decreased, whereas those with nonpsychiatric traits remained largely unchanged. Conclusions Our results identify a risk locus that contributes more strongly to SA than other phenotypes and suggest a shared underlying biology between SA and known risk factors that is not mediated by psychiatric disorders.Peer reviewe

Search for Gravitational Waves from Intermediate Mass Binary Black Holes

We present the results of a weakly modeled burst search for gravitational waves from mergers of non-spinning intermediate mass black holes (IMBH) in the total mass range 100--450 solar masses and with the component mass ratios between 1:1 and 4:1. The search was conducted on data collected by the LIGO and Virgo detectors between November of 2005 and October of 2007. No plausible signals were observed by the search which constrains the astrophysical rates of the IMBH mergers as a function of the component masses. In the most efficiently detected bin centered on 88+88 solar masses, for non-spinning sources, the rate density upper limit is 0.13 per Mpc^3 per Myr at the 90% confidence level.Comment: 13 pages, 4 figures: data for plots and archived public version at https://dcc.ligo.org/cgi-bin/DocDB/ShowDocument?docid=62326, see also the public announcement at http://www.ligo.org/science/Publication-S5IMBH

Ventilation Strategies during Neonatal Cardiopulmonary Resuscitation

Approximately, 10–20% of newborns require breathing assistance at birth, which remains the cornerstone of neonatal resuscitation. Fortunately, the need for chest compression (CC) or medications in the delivery room (DR) is rare. About 0.1% of term infants and up to 15% of preterm infants receive these interventions, this will result in approximately one million newborn deaths annually worldwide. In addition, CC or medications (epinephrine) are more frequent in the preterm population (~15%) due to birth asphyxia. A recent study reported that only 6 per 10,000 infants received epinephrine in the DR. Further, the study reported that infants receiving epinephrine during resuscitation had a high incidence of mortality (41%) and short-term neurologic morbidity (57% hypoxic-ischemic encephalopathy and seizures). A recent review of newborns who received prolonged CC and epinephrine but had no signs of life at 10 min following birth noted 83% mortality, with 93% of survivors suffering moderate-to-severe disability. The poor prognosis associated with receiving CC alone or with medications in the DR raises questions as to whether improved cardiopulmonary resuscitation methods specifically tailored to the newborn could improve outcomes

A Randomized, Controlled Animal Study: 21% or 100% Oxygen during Cardiopulmonary Resuscitation in Asphyxiated Infant Piglets

Background: During pediatric cardiopulmonary resuscitation (CPR), resuscitation guidelines recommend 100% oxygen (O2); however, the most effective O2 concentration for infants unknown. Aim: We aimed to determine if 21% O2 during CPR with either chest compression (CC) during sustained inflation (SI) (CC + SI) or continuous chest compression with asynchronized ventilation (CCaV) will reduce time to return of spontaneous circulation (ROSC) compared to 100% O2 in infant piglets with asphyxia-induced cardiac arrest. Methods: Piglets (20–23 days of age, weighing 6.2–10.2 kg) were anesthetized, intubated, instrumented, and exposed to asphyxia. Cardiac arrest was defined as mean arterial blood pressure < 25 mmHg with bradycardia. After cardiac arrest, piglets were randomized to CC + SI or CCaV with either 21% or 100% O2 or the sham. Heart rate, arterial blood pressure, carotid blood flow, and respiratory parameters were continuously recorded. Main results: Baseline parameters, duration, and degree of asphyxiation were not different. Median (interquartile range) time to ROSC was 107 (90–440) and 140 (105–200) s with CC + SI 21% and 100% O2, and 600 (50–600) and 600 (95–600) s with CCaV 21% and 100% O2 (p = 0.27). Overall, six (86%) and six (86%) piglets with CC + SI 21% and 100% O2, and three (43%) and three (43%) piglets achieved ROSC with CCaV 21% and 100% O2 (p = 0.13). Conclusions: In infant piglets resuscitated with CC + SI, time to ROSC reduced and survival improved compared to CCaV. The use of 21% O2 had similar time to ROSC, short-term survival, and hemodynamic recovery compared to 100% oxygen. Clinical studies comparing 21% with 100% O2 during infant CPR are warranted

Four Different Finger Positions and Their Effects on Hemodynamic Changes during Chest Compression in Asphyxiated Neonatal Piglets

Background: The Neonatal Life Support Consensus on Science With Treatment Recommendations states that chest compressions (CC) be performed preferably with the 2-thumb encircling technique. The aim of this study was to compare the hemodynamic effects of four different finger positions during CC in a piglet model of neonatal asphyxia. Methods: Seven asphyxiated post-transitional piglets were randomized to CC with 2-thumb-, 2-finger-, knocking-fingers-, and over-the-head 2-thumb-techniques for one minute at each technique. CC superimposed with sustained inflations were performed manually. Results: Seven newborn piglets (age 0–4 days, weight 2.0–2.1 kg) were included in the study. The mean (SD) slope rise of carotid blood flow was significantly higher with the 2-thumb-technique and over-the-head 2-thumb-technique (118 (45) mL/min/s and 121 (46) mL/min/s, respectively) compared to the 2-finger-technique and knocking-finger-technique (75 (48) mL/min/s and 71 (67) mL/min/s, respectively) (p min (as an expression of left ventricular function) was significantly lower with the 2-thumb-technique, with −1052 (369) mmHg/s, compared to −568 (229) mmHg/s and −578(180) mmHg/s (both p = 0.012) with the 2-finger-technique and knocking-finger-technique, respectively. Conclusion: The 2-thumb-technique and the over-the-head 2-thumb-technique resulted in improved slope rises of carotid blood flow and dp/dtmin during chest compression

Chest Compression Rates of 90/min versus 180/min during Neonatal Cardiopulmonary Resuscitation: A Randomized Controlled Animal Trial

Background: To compare chest compression (CC) rates of 90/min with 180/min and their effect on the time to return of spontaneous circulation (ROSC), survival, hemodynamic, and respiratory parameters. We hypothesized that asphyxiated newborn piglets that received CC at 180/min vs. 90/min during cardiopulmonary resuscitation would have a shorter time to ROSC. Methods: Newborn piglets (n = 7/group) were anesthetized, intubated, instrumented and exposed to 45 min normocapnic hypoxia followed by asphyxia and cardiac arrest. Piglets were randomly allocated to a CC rate of 180/min or 90/min. CC was performed using an automated chest compression machine using CC superimposed with sustained inflation. Hemodynamic and respiratory parameters and applied compression force were continuously measured. Results: The mean (SD) time to ROSC was 91 (34) and 256 (97) s for CC rates of 180/min and 90/min, respectively (p = 0.08). The number of piglets that achieved ROSC was 7 (100%) and 5 (71%) with 180/min and 90/min CC rates, respectively (p = 0.46). Hemodynamic parameters (i.e., diastolic and mean blood pressure, carotid blood flow, stroke volume, end-diastolic volume, left ventricular contractile function) and respiratory parameters (i.e., minute ventilation, peak inflation and peak expiration flow) were all improved with a CC rate of 180/min. Conclusion: Time to ROSC and hemodynamic and respiratory parameters were not statistical significant different between CC rates of 90/min and 180/min. Higher CC rates during neonatal resuscitation warrant further investigation