Effects of airway management and tidal volume feedback ventilation during pediatric resuscitation in piglets with asphyxial cardiac arrest.

To compare the effect on the recovery of spontaneous circulation (ROSC) of early endotracheal intubation (ETI) versus bag-mask ventilation (BMV), and expiratory real-time tidal volume (VTe) feedback (TVF) ventilation versus without feedback or standard ventilation (SV) in a pediatric animal model of asphyxial cardiac arrest. Piglets were randomized into five groups: 1: ETI and TVF ventilation (10 ml/kg); 2: ETI and TVF (7 ml/kg); 3: ETI and SV; 4: BMV and TVF (10 ml/kg) and 5: BMV and SV. Thirty breaths-per-minute guided by metronome were given. ROSC, pCO2, pO2, EtCO2 and VTe were compared among groups. Seventy-nine piglets (11.3 ± 1.2 kg) were included. Twenty-six (32.9%) achieved ROSC. Survival was non-significantly higher in ETI (40.4%) than BMV groups (21.9%), p = 0.08. No differences in ROSC were found between TVF and SV groups (30.0% versus 34.7%, p = 0.67). ETI groups presented lower pCO2, and higher pO2, EtCO2 and VTe than BMV groups (p < 0.05). VTe was lower in TVF than in SV groups and in BMV than in ETI groups (p < 0.05). Groups 1 and 3 showed higher pO2 and lower pCO2 over time, although with hyperventilation values (pCO2 < 35 mmHg). ETI groups had non significantly higher survival rate than BMV groups. Compared to BMV groups, ETI groups achieved better oxygenation and ventilation parameters. VTe was lower in both TVF and BMV groups. Hyperventilation was observed in intubated animals with SV and with 10 ml/kg VTF.

Effect of therapeutic hypothermia on renal and myocardial function in asphyxiated (near) term neonates: A systematic review and meta-analysis.

BACKGROUND: Therapeutic hypothermia (TH) is a well-established neuroprotective therapy applied in (near) term asphyxiated infants. However, little is known regarding the effects of TH on renal and/or myocardial function. OBJECTIVES: To describe the short- and long-term effects of TH on renal and myocardial function in asphyxiated (near) term neonates. METHODS: An electronic search strategy incorporating MeSH terms and keywords was performed in October 2019 and updated in June 2020 using PubMed and Cochrane databases. Inclusion criteria consisted of a RCT or observational cohort design, intervention with TH in a setting of perinatal asphyxia and available long-term results on renal and myocardial function. We performed a meta-analysis and heterogeneity and sensitivity analyses using a random effects model. Subgroup analysis was performed on the method of cooling. RESULTS: Of the 107 studies identified on renal function, 9 were included. None of the studies investigated the effects of TH on long-term renal function after perinatal asphyxia. The nine included studies described the effect of TH on the incidence of acute kidney injury (AKI) after perinatal asphyxia. Meta-analysis showed a significant difference between the incidence of AKI in neonates treated with TH compared to the control group (RR = 0.81; 95% CI 0.67-0.98; p = 0.03). No studies were found investigating the long-term effects of TH on myocardial function after neonatal asphyxia. Possible short-term beneficial effects were presented in 4 out of 5 identified studies, as observed by significant reductions in cardiac biomarkers and less findings of myocardial dysfunction on ECG and cardiac ultrasound. CONCLUSIONS: TH in asphyxiated neonates reduces the incidence of AKI, an important risk factor for chronic kidney damage, and thus is potentially renoprotective. No studies were found on the long-term effects of TH on myocardial function. Short-term outcome studies suggest a cardioprotective effect.

The effect of high-dose intramuscular epinephrine on the recovery of spontaneous circulation in an asphyxia-induced cardiac arrest rat model.

BACKGROUND: Obtaining vascular access can be challenging during resuscitation following cardiac arrest, and it is particularly difficult and time-consuming in paediatric patients. We aimed to compare the efficacy of high-dose intramuscular (IM) versus intravascular (IV) epinephrine administration with regard to the return of spontaneous circulation (ROSC) in an asphyxia-induced cardiac arrest rat model. METHODS: Forty-five male Sprague-Dawley rats were used for these experiments. Cardiac arrest was induced by asphyxia, and defined as a decline in mean arterial pressure (MAP) to 20 mmHg. After asphyxia-induced cardiac arrest, the rats were randomly allocated into one of 3 groups (control saline group, IV epinephrine group, and IM epinephrine group). After 540 s of cardiac arrest, cardiopulmonary resuscitation was performed, and IV saline (0.01 cc/kg), IV (0.01 mg/kg, 1:100,000) epinephrine or IM (0.05 mg/kg, 1:100,000) epinephrine was administered. ROSC was defined as the achievement of an MAP above 40 mmHg for more than 1 minute. Rates of ROSC, haemodynamics, and arterial blood gas analysis were serially observed. RESULTS: The ROSC rate (61.5%) of the IM epinephrine group was less than that in the IV epinephrine group (100%) but was higher than that of the control saline group (15.4%) (log-rank test). There were no differences in MAP between the two groups, but HR in the IM epinephrine group (beta coefficient = 1.02) decreased to a lesser extent than that in the IV epinephrine group with time. CONCLUSIONS: IM epinephrine induced better ROSC rates compared to the control saline group in asphyxia-induced cardiac arrest, but not compared to IV epinephrine. The IM route of epinephrine administration may be a promising option in an asphyxia-induced cardiac arrest.

Compression asphyxia and other clinicopathological findings from the Hillsborough Stadium disaster.

Ninety-six people died following a crowd crush at the Hillsborough Football Stadium, Sheffield, UK in 1989. The cause of death in nearly all cases was compression asphyxia. The clinical and pathological features of deaths encountered in crowds are discussed with a particular focus on the Hillsborough disaster.

A physiologically validated rat model of term birth asphyxia with seizure generation after, not during, brain hypoxia.

OBJECTIVE: Birth asphyxia (BA) is often associated with seizures that may exacerbate the ensuing hypoxic-ischemic encephalopathy. In rodent models of BA, exposure to hypoxia is used to evoke seizures, that commence already during the insult. This is in stark contrast to clinical BA, in which seizures are typically seen upon recovery. Here, we introduce a term-equivalent rat model of BA, in which seizures are triggered after exposure to asphyxia. METHODS: Postnatal day 11-12 male rat pups were exposed to steady asphyxia (15 min; air containing 5% O2  + 20% CO2 ) or to intermittent asphyxia (30 min; three 5 + 5-min cycles of 9% and 5% O2 at 20% CO2 ). Cortical activity and electrographic seizures were recorded in freely behaving animals. Simultaneous electrode measurements of intracortical pH, Po2 , and local field potentials (LFPs) were made under urethane anesthesia. RESULTS: Both protocols decreased blood pH to <7.0 and brain pH from 7.3 to 6.7 and led to a fall in base excess by 20 mmol·L-1 . Electrographic seizures with convulsions spanning the entire Racine scale were triggered after intermittent but not steady asphyxia. In the presence of 20% CO2 , brain Po2 was only transiently affected by 9% ambient O2 but fell below detection level during the steps to 5% O2 , and LFP activity was nearly abolished. Post-asphyxia seizures were strongly suppressed when brain pH recovery was slowed down by 5% CO2 . SIGNIFICANCE: The rate of brain pH recovery has a strong influence on post-asphyxia seizure propensity. The recurring hypoxic episodes during intermittent asphyxia promote neuronal excitability, which leads to seizures only after the suppressing effect of the hypercapnic acidosis is relieved. The present rodent model of BA is to our best knowledge the first one in which, consistent with clinical BA, behavioral and electrographic seizures are triggered after and not during the BA-mimicking insult.

Magnesium Sulfate Attenuates Lethality and Oxidative Damage Induced by Different Models of Hypoxia in Mice.

Mg2+ is an important cation in our body. It is an essential cofactor for many enzymes. Despite many works, nothing is known about the protective effects of MgSO4 against hypoxia-induced lethality and oxidative damage in brain mitochondria. In this study, antihypoxic and antioxidative activities of MgSO4 were evaluated by three experimental models of induced hypoxia (asphyctic, haemic, and circulatory) in mice. Mitochondria protective effects of MgSO4 were evaluated in mouse brain after induction of different models of hypoxia. Antihypoxic activity was especially pronounced in asphyctic hypoxia, where MgSO4 at dose 600 mg/kg showed the same activity as phenytoin, which used as a positive control (P < 0.001). In the haemic model, MgSO4 at all used doses significantly prolonged latency of death. In circulatory hypoxia, MgSO4 (600 mg/kg) doubles the survival time. MgSO4 significantly decreased lipid peroxidation and protein carbonyl and improved mitochondrial function and glutathione content in brain mitochondria compared to the control groups. The results obtained in this study showed that MgSO4 administration has protective effects against lethality induced by different models of hypoxia and improves brain mitochondria oxidative damage.

Dietary Inflammatory Index during Pregnancy and the Risk of Intrapartum Fetal Asphyxia: The Japan Environment and Children's Study.

We aimed to examine the impact of a daily pro-inflammatory diet during pregnancy on intrapartum fetal acidemia using a large birth cohort study in Japan. We used data on singleton pregnancies in the Japan Environment and Children's Study (JECS) involving births from 2011 to 2014 through vaginal delivery to calculate the maternal dietary inflammatory index (DII). Participants were categorized according to DII quintiles. A multiple logistic regression model was used to estimate the risk of a pro-inflammatory diet on fetal umbilical artery pH. In total, 56,490 participants were eligible for this study. Multiple regression analysis showed that nulliparous women who had undergone vaginal delivery and were consuming a pro-inflammatory diet had an increased risk of pH < 7.10 (adjusted odds ratio [aOR]: 1.64, 95% confidence interval [CI]: 1.12-2.39). Among these women, the risk of pH < 7.10 was not affected by the duration of labor (aOR: 1.64, 95% CI: 1.11-2.42). In conclusion, following a pro-inflammatory diet during pregnancy is a risk factor for fetal acidosis among nulliparous women undergoing vaginal delivery. A high DII diet during pregnancy may modify the intrapartum fetal heart rate pattern via intrauterine inflammation.

Excess cerebral oxygen delivery follows return of spontaneous circulation in near-term asphyxiated lambs.

Hypoxic-ischaemia renders the neonatal brain susceptible to early secondary injury from oxidative stress and impaired autoregulation. We aimed to describe cerebral oxygen kinetics and haemodynamics immediately following return of spontaneous circulation (ROSC) and evaluate non-invasive parameters to facilitate bedside monitoring. Near-term sheep fetuses [139 ± 2 (SD) days gestation, n = 16] were instrumented to measure carotid artery (CA) flow, pressure, right brachial arterial and jugular venous saturation (SaO2 and SvO2, respectively). Cerebral oxygenation (crSO2) was measured using near-infrared spectroscopy (NIRS). Following induction of severe asphyxia, lambs received cardiopulmonary resuscitation using 100% oxygen until ROSC, with oxygen subsequently weaned according to saturation nomograms as per current guidelines. We found that oxygen consumption did not rise following ROSC, but oxygen delivery was markedly elevated until 15 min after ROSC. CrSO2 and heart rate each correlated with oxygen delivery. SaO2 remained > 90% and was less useful for identifying trends in oxygen delivery. CrSO2 correlated inversely with cerebral fractional oxygen extraction. In conclusion, ROSC from perinatal asphyxia is characterised by excess oxygen delivery that is driven by rapid increases in cerebrovascular pressure, flow, and oxygen saturation, and may be monitored non-invasively. Further work to describe and limit injury mediated by oxygen toxicity following ROSC is warranted.

Restraint physiology: A review of the literature.

Law-enforcement often uses forensic restraints to control individuals and often these individuals are placed in positions and with various amounts of weight used to hold them in place. There has been a moderate amount of research performed on humans in this field of study to assess the physiologic impact of the positions and weight on ventilatory and cardiovascular parameters. This review discusses the scientific medical literature on the use of restraints and restraint position including the use of weight force and aggregates the findings in specific physiologic areas, such as impact on blood pressure, heart rate, and ventilatory parameters.

Late Pregnancy Vitamin D Deficiency is Associated with Doubled Odds of Birth Asphyxia and Emergency Caesarean Section: A Prospective Cohort Study.

OBJECTIVES: The aim of this prospective cohort study was to investigate the associations between maternal vitamin D status in late pregnancy and emergency caesarean section (EMCS) and birth asphyxia, in a population based sample of women in Sweden. METHODS: Pregnant women were recruited at the antenatal care in Sweden and 1832 women were included after exclusion of miscarriages, terminated pregnancies and missing data on vitamin D status. Mode of delivery was retrieved from medical records. EMCS was defined as caesarean section after onset of labour. Birth asphyxia was defined as either 5 min Apgar score < 7 or arterial umbilical cord pH < 7.1. Serum was sampled in the third trimester of pregnancy (T3) and 25-hydroxyvitamin D (25OHD) was analysed by liquid chromatography tandem mass spectrometry. Vitamin D deficiency was defined as 25OHD < 30 nmol/L, and associations were studied using logistic regression analysis and expressed as adjusted odds ratios (AOR). RESULTS: In total, 141 (7.7%) women had an EMCS and 58 (3.2%) children were born with birth asphyxia. Vitamin D deficiency was only associated with higher odds of EMCS in women without epidural anaesthesia (AOR = 2.01, p = 0.044). Vitamin D deficiency was also associated with higher odds of birth asphyxia (AOR = 2.22, p = 0.044). CONCLUSIONS FOR PRACTICE: In this Swedish prospective population-based cohort study, vitamin D deficiency in late pregnancy was associated with doubled odds of birth asphyxia and with EMCS in deliveries not aided by epidural anaesthesia. Prevention of vitamin D deficiency among pregnant women may reduce the incidence of EMCS and birth asphyxia. The mechanism behind the findings require further investigation.

Effect of ventilation rate on recovery after cardiac arrest in a pediatric animal model.

AIMS: To assess the impact of two different respiratory rates in hemodynamic, perfusion and ventilation parameters in a pediatric animal model of cardiac arrest (CA). METHODS: An experimental randomized controlled trial was carried out in 50 piglets under asphyxial CA. After ROSC, they were randomized into two groups: 20 and 30 respirations per minute (rpm). Hemodynamic, perfusion and ventilation parameters were measured 10 minutes after asphyxia, just before ROSC and at 5, 15, 30 and 60 minutes after ROSC. Independent medians test, Kruskal-Wallis test and χ2 test, were used to compare continuous and categorical variables, respectively. Spearman's Rho was used to assess correlation between continuous variables. A p-value <0.05 was considered significant. RESULTS: Arterial partial pressure of carbon dioxide (PaCO2) was significantly lower in the 30 rpm group after 15 minutes (41 vs. 54.5 mmHg, p <0.01), 30 minutes (39.5 vs. 51 mmHg, p < 0.01) and 60 minutes (36.5 vs. 48 mmHg, p = 0.02) of ROSC. The percentage of normoventilated subjects (PaCO2 30-50 mmHg) was significantly higher in the 30 rpm group throughout the experiment. pH normalization occurred faster in the 30 rpm group with significant differences at 60 minutes (7.40 vs. 7.34, p = 0.02). Lactic acid levels were high immediately after ROSC in both groups, but were significantly lower in the 20 rpm group at 30 (3.7 vs. 4.7 p = 0.04) and 60 minutes (2.6 vs. 3.6 p = 0.03). CONCLUSIONS: This animal model of asphyxial CA shows that a respiratory rate of 30 rpm is more effective to reach normoventilation than 20 rpm in piglets after ROSC. This ventilation strategy seems to be safe, as it does not cause hyperventilation and does not affect hemodynamics or cerebral tissue perfusion.

Positional Asphyxia in Opioid-Related Deaths: Is It Being Overlooked?

The contribution of positional asphyxia in opioid-related deaths is currently unknown. Diagnostic criteria for positional asphyxia include finding the decedent in a position that does not allow for adequate respiration and an inability to extricate themselves from the position due to various conditions. Our primary objective was to assess whether positional asphyxia and the resulting airway compromise were a contributing factor to death due to the toxic effects of opioids. We evaluated 225 deaths where the death scene investigation contained adequate information to evaluate for positional asphyxia and performed a Pearson chi-square test to determine if the proportion of deaths found in an airway compromising position was higher when opioid(s) caused the death. The proportion of decedents found in a potential airway compromising position was greater when the death was related to opioid use (p < 0.0001). Further, narrowing the dataset to decedents who were definitely in an airway compromising position [Yes (24.49%) vs. No (11.02%)] showed a statistically significant association between positional asphyxia and deaths related to opioid use (p = 0.0021). Carefully documenting the position in which the decedent was initially found may be a significant factor in accurate reporting and in harm reduction efforts to decrease the opioid mortality rate.

Heightened affective response to perturbation of respiratory but not pain signals in eating, mood, and anxiety disorders.

Several studies have recently suggested that an abnormal processing of respiratory interoceptive and nociceptive (painful) stimuli may contribute to eating disorder (ED) pathophysiology. Mood and anxiety disorders (MA) are also characterized by abnormal respiratory symptoms, and show substantial comorbidity with ED. However, no studies have examined both respiratory and pain processing simultaneously within ED and MA. The present study systematically evaluated responses to perturbations of respiratory and nociceptive signals across the levels of physiology, behavior, and symptom report in a transdiagnostic ED sample (n = 51) that was individually matched to MA individuals (n = 51) and healthy comparisons (HC; n = 51). Participants underwent an inspiratory breath-holding challenge as a probe of respiratory interoception and a cold pressor challenge as a probe of pain processing. We expected both clinical groups to report greater stress and fear in response to respiratory and nociceptive perturbation than HCs, in the absence of differential physiological and behavioral responses. During breath-holding, both the ED and MA groups reported significantly more stress, feelings of suffocation, and suffocation fear than HC, with the ED group reporting the most severe symptoms. Moreover, anxiety sensitivity was related to suffocation fear only in the ED group. The heightened affective responses in the current study occurred in the absence of group differences in behavioral (breath hold duration, cold pressor duration) and physiological (end-tidal carbon dioxide, end-tidal oxygen, heart rate, skin conductance) responses. Against our expectations, there were no group differences in the response to cold pain stimulation. A matched-subgroup analysis focusing on individuals with anorexia nervosa (n = 30) produced similar results. These findings underscore the presence of abnormal respiratory interoception in MA and suggest that hyperreactivity to respiratory signals may be a potentially overlooked clinical feature of ED.

Stearic acid methyl ester affords neuroprotection and improves functional outcomes after cardiac arrest.

Cardiac arrest causes neuronal damage and functional impairments that can result in learning/memory dysfunction after ischemia. We previously identified a saturated fatty acid (stearic acid methyl ester, SAME) that was released from the superior cervical ganglion (sympathetic ganglion). The function of stearic acid methyl ester is currently unknown. Here, we show that SAME can inhibit the detrimental effects of global cerebral ischemia (i.e. cardiac arrest). Treatment with SAME in the presence of asphyxial cardiac arrest (ACA) revived learning and working memory deficits. Similarly, SAME-treated hippocampal slices after oxygen-glucose deprivation inhibited neuronal cell death. Moreover, SAME afforded neuroprotection against ACA in the CA1 region of the hippocampus, reduced ionized calcium-binding adapter molecule 1 expression and inflammatory cytokines/chemokines, with restoration in mitochondria respiration. Altogether, we describe a unique and uncharted role of saturated fatty acids in the brain that may have important implications against cerebral ischemia.

Synergistic Effects of Moderate Therapeutic Hypothermia and Levosimendan on Cardiac Function and Survival After Asphyxia-Induced Cardiac Arrest in Rats.

Background This study investigated whether levosimendan, an inotropic calcium sensitizer, when combined with moderate therapeutic hypothermia, may exert synergistic benefits on post-cardiac arrest myocardial dysfunction and improve outcomes. Methods and Results After 9.5-minute asphyxia-induced cardiac arrest and resuscitation, 48 rats were randomized equally into 4 groups following return of spontaneous circulation (ROSC), including normothermia, hypothermia, normothermia-levosimendan, and hypothermia-levosimendan groups. For the normothermia group, the target temperature was 37°C while for the hypothermia group, the target temperature was 32°C, both of which were to be maintained for 4 hours after ROSC. Levosimendan was administered after ROSC with a loading dose of 10 µg/kg and then infused at 0.1 µg/kg per min for 4 hours. In the hypothermia-levosimendan group, left ventricular systolic function and cardiac output increased significantly, whereas the heart rate and systemic vascular resistance decreased significantly compared with the normothermia group. Also, the concentrations of interleukin 1ß at 4 hours post-ROSC and the production of NO between 1 hour and 4 hours post-ROSC were reduced significantly in the hypothermia-levosimendan group compared with the normothermia group. The 72-hour post-ROSC survival and neurological recovery were also significantly better in the hypothermia-levosimendan group compared with the normothermia group (survival, 100% versus 50%, χ2 test, P=0.006). Conclusions Compared with normothermia, only combined moderate therapeutic hypothermia and levosimendan treatment could consistently improve post-cardiac arrest myocardial dysfunction and decrease the release of pro-inflammatory molecules, thereby improving survival and neurological outcomes. These findings suggest synergistic benefits between moderate therapeutic hypothermia and levosimendan.

Effects of delayed intraventricular TLR7 agonist administration on long-term neurological outcome following asphyxia in the preterm fetal sheep.

In the preterm brain, accumulating evidence suggests toll-like receptors (TLRs) are key mediators of the downstream inflammatory pathways triggered by hypoxia-ischemia (HI), which have the potential to exacerbate or ameliorate injury. Recently we demonstrated that central acute administration of the TLR7 agonist Gardiquimod (GDQ) confers neuroprotection in the preterm fetal sheep at 3 days post-asphyxial recovery. However, it is unknown whether GDQ can afford long-term protection. To address this, we examined the long-term effects of GDQ. Briefly, fetal sheep (0.7 gestation) received sham asphyxia or asphyxia induced by umbilical cord occlusion, and were studied for 7 days recovery. Intracerebroventricular (ICV) infusion of GDQ (total dose 3.34 mg) or vehicle was performed from 1-4 hours after asphyxia. GDQ was associated with a robust increase in concentration of tumor necrosis factor-(TNF)-α in the fetal plasma, and interleukin-(IL)-10 in both the fetal plasma and cerebrospinal fluid. GDQ did not significantly change the number of total and immature/mature oligodendrocytes within the periventricular and intragyral white matter. No changes were observed in astroglial and microglial numbers and proliferating cells in both white matter regions. GDQ increased neuronal survival in the CA4 region of the hippocampus, but was associated with exacerbated neuronal injury within the caudate nucleus. In conclusion, our data suggest delayed acute ICV administration of GDQ after severe HI in the developing brain may not support long-term neuroprotection.

High-Dose Melatonin and Ethanol Excipient Combined with Therapeutic Hypothermia in a Newborn Piglet Asphyxia Model.

With the current practice of therapeutic hypothermia for neonatal encephalopathy, disability rates and the severity spectrum of cerebral palsy are reduced. Nevertheless, safe and effective adjunct therapies are needed to optimize outcomes. This study's objective was to assess if 18 mg/kg melatonin given rapidly over 2 h at 1 h after hypoxia-ischemia with cooling from 1-13 h was safe, achieved therapeutic levels within 3 h and augmented hypothermic neuroprotection. Following hypoxia-ischemia, 20 newborn piglets were randomized to: (i) Cooling 1-13 h (HT; n = 6); (ii) HT+ 2.5% ethanol vehicle (HT+V; n = 7); (iii) HT + Melatonin (HT+M; n = 7). Intensive care was maintained for 48 h; aEEG was acquired throughout, brain MRS acquired at 24 and 48 h and cell death (TUNEL) evaluated at 48 h. There were no differences for insult severity. Core temperature was higher in HT group for first hour after HI. Comparing HT+M to HT, aEEG scores recovered more quickly by 19 h (p < 0.05); comparing HT+V to HT, aEEG recovered from 31 h (p < 0.05). Brain phosphocreatine/inorganic phosphate and NTP/exchangeable phosphate were higher at 48 h in HT+M versus HT (p = 0.036, p = 0.049 respectively). Including both 24 h and 48 h measurements, the rise in Lactate/N-acetyl aspartate was reduced in white (p = 0.030) and grey matter (p = 0.038) after HI. Reduced overall TUNEL positive cells were observed in HT+M (47.1 cells/mm2) compared to HT (123.8 cells/mm2) (p = 0.0003) and HT+V (97.5 cells/mm2) compared to HT (p = 0.012). Localized protection was seen in white matter for HT+M versus HT (p = 0.036) and internal capsule for HT+M compared to HT (p = 0.001) and HT+V versus HT (p = 0.006). Therapeutic melatonin levels (15-30mg/l) were achieved at 2 h and were neuroprotective following HI, but ethanol vehicle was partially protective.

Inhibition of PAR-2 Attenuates Neuroinflammation and Improves Short-Term Neurocognitive Functions Via ERK1/2 Signaling Following Asphyxia-Induced Cardiac Arrest in Rats.

OBJECTIVE: Global cerebral ischemia-induced neuroinflammation causes neurofunctional impairment following cardiac arrest. Previous studies have demonstrated that the activation of protease-activated receptor-2 (PAR-2) contributes to neuroinflammation. In the present study, we aimed to determine the potential treatment effect of PAR-2 inhibition against neuroinflammation in the setting of asphyxial CA (ACA) in rats. METHODS: A total of 116 adult, male Sprague-Dawley rats were randomly divided into Sham (n = 18) and ACA (n = 98) groups. Time course, short-term outcome, and mechanism studies were conducted. All drugs were delivered intranasally. The effect of PAR-2 inhibitor FSLLRY-NH2 on neurocognitive functions was assessed by neurologic deficit score, number of seizures, and T-maze test, while hippocampal neuronal degeneration was evaluated by Fluoro-Jade C staining after ACA. Western blotting was performed for the mechanism study at 24 h following ACA. Selective PAR-2 agonist (AC55541) and ERK1/2 inhibitor (PD98059) were used for intervention. RESULTS: Inhibition of PAR-2 decreased neuroinflammation, reduced the number of degenerating hippocampal neurons and improved neurocognitive functions following ACA. PAR-2 activator alone exerted opposite effects to PAR-2 inhibitor. PAR-2 mediated the augmented brain levels of proinflammatory cytokines by promoting the phosphorylation of ERK1/2. CONCLUSIONS: PAR-2 inhibition diminished neuroinflammation and thereby reduced hippocampal neuronal degeneration and neurocognitive impairment following ACA. This effect was at least partly mediated via the PAR-2/ERK1/2 signaling.

A possible cause of Sudden Infant Death Syndrome.

It is suggested that an orienting response to loud sound causes apnea, which, in already asphyxic infants, triggers a maximal secondary chemoreceptor response, with massive vagal stimulation of the heart, which causes heart arrest.

Inhaling Hydrogen Ameliorates Early Postresuscitation EEG Characteristics in an Asphyxial Cardiac Arrest Rat Model.

BACKGROUND: Electroencephalography (EEG) is commonly used to assess the neurological prognosis of comatose patients after cardiac arrest (CA). However, the early prognostic accuracy of EEG may be affected by postresuscitation interventions. Recent animal studies found that hydrogen inhalation after CA greatly improved neurological outcomes by selectively neutralizing highly reactive oxidants, but the effect of hydrogen inhalation on EEG recovery and its prognostication value are still unclear. The present study investigated the effects of hydrogen inhalation on early postresuscitation EEG characteristics in an asphyxial CA rat model. METHODS: Cardiopulmonary resuscitation was initiated after 5 min of untreated CA in 40 adult female Sprague-Dawley rats. Animals were randomized for ventilation with 98% oxygen plus 2% hydrogen (H2) or 98% oxygen plus 2% nitrogen (Ctrl) under normothermia for 1 h. EEG characteristics were continuously recorded for 4 h, and the relationships between quantitative EEG characteristics and 96 h neurological outcomes were investigated. RESULTS: No differences in baseline and resuscitation data were observed between groups, but the survival rate was significantly higher in the H2 group than in the Ctrl group (90% vs. 40%, P < 0.01). Compared to the Ctrl group, the H2 group showed a shorter burst onset time (21.85 [20.00-23.38] vs. 25.70 [22.48-30.05], P < 0.01) and time to normal trace (169.83 [161.63-208.55] vs. 208.39 [186.29-248.80], P < 0.01). Additionally, the burst suppression ratio (0.66 ± 0.09 vs. 0.52 ± 0.17, P < 0.01) and weighted-permutation entropy (0.47 ± 0.16 vs. 0.34 ± 0.13, P < 0.01) were markedly higher in the H2 group. The areas under the receiver operating characteristic curves for the 4 EEG characteristics in predicting survival were 0.82, 0.84, 0.88, and 0.83, respectively. CONCLUSIONS: In this asphyxial CA rat model, the improved postresuscitation EEG characteristics for animals treated with hydrogen are correlated with the better 96 h neurological outcome and predicted survival.