Minutes Of Cardiac Arrest Research Articles

Adults Are Not Just Large Kids: Caring for Adults in Pediatric Hospitals.

Adults Are Not Just Large Kids: Caring for Adults in Pediatric Hospitals.

1267: SUCCESSFUL UTILIZATION OF ECMO AND ELS IN A PEDIATRIC PATIENT WITH HYDROXYCHLOROQUINE INGESTION

Introduction: Hydroxychloroquine ingestion can present with seizures, myocardial depression, vasodilation, QRS and QTc prolongation leading to ventricular arrhythmias and cardiac arrest. Ingestions >5 g and blood concentrations >20 mg/L are associated with mortality. Plasma concentrations peak at 2-6 hours with 800–1400-hour half-life. Therapies including sodium bicarbonate, benzodiazepines, activated charcoal, and lipid infusions offer questionable benefit. Hydroxychloroquine has a large volume of distribution (>50 L/kg) and is 40-70% protein bound, so hemodialysis is not efficient for drug clearance. We describe the first case of extracorporeal liver support (ELS) (albumin dialysis) for hydroxychloroquine clearance, and the use of ECMO and ELS utilized in tandem for hydroxychloroquine ingestion. Description: A 17-year-old female presented after a 20 g intentional ingestion of hydroxychloroquine. She had ventricular tachycardia with a 15-minute cardiac arrest. She received activated charcoal, sodium bicarbonate, benzodiazepines, and lipid infusion. Due to vasodilatory shock refractory to 4 high-dose vasoactive infusions, she was cannulated to femoral-femoral venoarterial (VA) ECMO on hospital day (HD) 2. She weaned from ECMO on HD 5, but developed lower extremity ischemia necessitating a right through-the-knee amputation. To facilitate clearance of protein-bound hydroxychloroquine, ELS was initiated on HD 1. ELS was discontinued on HD 7, but resumed on HD 9 due to recurrence of vasoplegia. Hydroxychloroquine levels peaked at 52 mg/L on HD 1. Her level was 9.7 mg/L prior to discontinuation of ELS, increased to 12 mg/L after discontinuation, and decreased to < 1 mg/L on HD 15 when ELS was discontinued. She had full renal and neurologic recovery and was discharged to inpatient rehabilitation. Discussion: In cases of severe hydroxychloroquine ingestion, VA ECMO can be utilized for refractory circulatory shock and can provide hemodynamic stability to utilize other extracorporeal therapies in tandem. Based on the clinical and pharmacologic evidence in this case, ELS may provide expedited drug clearance in cases of hydroxychloroquine ingestion.

A simulation-based continuing professional development course for the first 5 minutes of cardiac arrest in the resource-limited local clinics.

Using simulation in continuing professional development (CPD) courses for local practitioners is uncommon in Korea. The aim of our study was to evaluate the responses of the local practitioners for a simulation-based short CPD course. Following the targeted needs assessment of local practitioners, we developed and implemented a 3-hour simulation-based CPD course for the first 5 minutes of cardiac arrest in the resource-limited local clinics. We evaluated the participant's responses to the course using a questionnaire. During the 3-year implementation period, 115 practitioners participated in 10 courses, and 113 (98%) responded to the questionnaire. The overall course satisfaction (10-point scale) was very positive (10 in 93 [82.3%], 9 in 19 [16.8%], and 8 in 1 [0.8%]). The level (5-point scale) of recommendation to the others was also high (5 in 103 [91.2%] and 4 in 10 [8.8%]). Many participants positively commented on the authentic practical experience of the uncommon crisis in their contexts. A simulation-based short CPD course for in-hospital cardiac arrest could provide an authentic practical experience for local practitioners working in resource-limited clinics.

Adrenaline improves regional cerebral blood flow, cerebral oxygenation and cerebral metabolism during CPR in a porcine cardiac arrest model using low-flow extracorporeal support

BackgroundThe effects of adrenaline on cerebral blood vessels during cardiopulmonary resuscitation (CPR) are not well understood. We developed an extracorporeal CPR model that maintains constant low systemic blood flow while allowing adrenaline-associated effects on cerebral vasculature to be assessed at different mean arterial pressure (MAP) levels independently of the effects on systemic blood flow. MethodsAfter eight minutes of cardiac arrest, low-flow extracorporeal life support (ECLS) (30 ml/kg/min) was started in fourteen pigs. After ten minutes, continuous adrenaline administration was started to achieve MAP values of 40 (n = 7) or 60 mmHg (n = 7). Measurements included intracranial pressure (ICP), cerebral perfusion pressure (CePP), laser-Doppler-derived regional cerebral blood flow (CBF), cerebral regional oxygen saturation (rSO2), brain tissue oxygen tension (PbtO2) and extracellular cerebral metabolites assessed by cerebral microdialysis. ResultsDuring ECLS without adrenaline, regional CBF increased by only 5% (25th to 75th percentile: −3 to 14; p = 0.2642) and PbtO2 by 6% (0–15; p = 0.0073) despite a significant increase in MAP to 28 mmHg (25–30; p < 0.0001) and CePP to 10 mmHg (8–13; p < 0.0001). Accordingly, cerebral microdialysis parameters showed a profound hypoxic-ischemic pattern. Adrenaline administration significantly improved regional CBF to 29 ± 14% (p = 0.0098) and 61 ± 25% (p < 0.001) and PbtO2 to 15 ± 11% and 130 ± 82% (both p < 0.001) of baseline in the MAP 40 mmHg and MAP 60 mmHg groups, respectively. Importantly, MAP of 60 mmHg was associated with metabolic improvement. ConclusionThis study shows that adrenaline administration during constant low systemic blood flow increases CePP, regional CBF, cerebral oxygenation and cerebral metabolism.

Cyclosporine A-enhanced cardioplegia preserves mitochondrial basal respiration after ischemic arrest.

Mitochondrial permeability transition pore (mPTP) opening plays a crucial role in cell death during ischemia-reperfusion injury (IRI). Cyclosporine A (CsA) inhibits mPTP opening. This study aimed to investigate the effects of CsA treatment during cardioplegia on the mitochondrial function and cardiac IRI. Landrace pigs (52.9 ± 3.7 kg) were subjected to midline sternotomy, cardiopulmonary bypass at 34°C and 90 minutes of cardiac arrest. They received either a single shot of standard 4°C cold histidine-tryptophan-α-ketoglutarate (HTK)-Bretschneider solution (n = 11) or HTK-Bretschneider plus 1.2 mg/L CsA (histidine-tryptophan-α-ketoglutarate plus cyclosporine A (HTK/CsA); n = 11). During reperfusion global left-ventricular function was assessed and myocardial biopsies were harvested at baseline, during ischemia and 45 minutes following reperfusion. High-resolution respirometry and hydrogen peroxide production were measured. Immunohistochemical stainings for apoptosis-inducing factor and hypoxia-inducible factor-1α as well as a flow cytometry-based JC-1 mitochondrial membrane potential assay were performed. Hemodynamic parameters were comparable between both groups. The cytochrome C release (HTK: 930.3 ± 804.4 pg/mg, HTK/CsA: 699.7 ± 394.0 pg/mg, p = 0.457) as well as PGC1α content (HTK: 66.7%, HTK/CsA: 33.3%, p = 0.284) was lower in the HTK/CsA group. Respiratory measurements revealed that the oxygen flux under basal respiration was higher in the HTK/CsA group (8.2 ± 1.3 pmol·O2·s-1·mg-1·ww) than in the HTK group (3.8 ± 1.4 pmol·O2·s-1·mg-1·ww, p = 0.045). There were no significant differences regarding histological surrogates of apoptosis and necrosis. Supplementing cardioplegic solutions with CsA enhances the basal mitochondrial respiration thereby exerting a cardioprotective effect and diminishing IRI-induced damage. CsA seems to preserve mitochondrial function via non-ROS related pathways.

Usefulness of thrombolysis in cardiac arrest secondary to suspected or confirmed pulmonary embolism

Acute pulmonary embolism (PE) is a form of venous thromboembolism associated with significant morbidity and mortality. Massive PE, characterized by hemodynamic instability, has been reported as a common cause of cardiac arrest. Thrombolytic agents have therefore been identified as a potential rescue therapy to restore circulatory perfusion. This study describes use patterns of systemic thrombolysis in cardiac arrest and corresponding patient outcomes. A multicenter retrospective chart review was conducted to evaluate adult patients who received rescue thrombolysis during cardiac arrest for suspected or confirmed PE. A total of 27 patients were included. PE was confirmed in 4 patients (15%). Pulseless electrical activity was the initial rhythm in 21 patients (78%), with a median cardiac arrest duration of 23 minutes in patients with return of spontaneous circulation (ROSC) vs 42.5 minutes in patients without ROSC. Among the 11 patients (41%) with ROSC, two (7%) survived to hospital discharge. Notable characteristics of the two survivors included a confirmed PE, an initial presenting rhythm of pulseless electrical activity, and administration of alteplase within 5 minutes of cardiac arrest. We recommend early administration of rescue thrombolysis when there is a high clinical index of suspicion that PE is the cause of the arrest.

EFFECTIVENESS OF HYPOTHERMIC THERAPY IN PATIENTS STOP HEART POST: LITERATURE REVIEW

Cardiac arrest has become one of the most unexpected, dramatic, and life-threatening events in the world of health. The increase in the number of patients who survived after cardiac pulmonary resuscitation has increased as more cardiopulmonary resuscitation training and defibrillation equipment are becoming easier to carry to various locations, but brain damage begins within minutes of cardiac arrest with the consequence of patients having their hearts beating again. and hospitalized unable to leave the hospital or in a vegetative state. Hypothermic therapy has been used frequently in cardiac surgery for several years for neurological protection. The data-based used in making this literature review are Google Scholar and Proquest. The keywords used in the search for articles on google scholar are "Therapeutic" and "Hypothermia" and "post" and "cardiac" and "arrest" and limit the publication year of 2011-2016. While the search on Proquest "Therapeutic" and "Hypothermia" and "after" and "cardiac" and "arrest". Based on the results of the literature search on google scholar, there were 9730, Pubmed 150, and ProQuest 2460. The screening results were 7,200 but only 9 journals were relevant to the topic. Hypothermic therapy can significantly improve neurological status in post-cardiac arrest patients even after the patient has been discharged from the hospital&#x0D; Keywords:Hypothermic Therapy; Post Cardiac Arrest

H2O2-Responsive Antioxidant Nanoparticle Attenuates Whole Body Ischemia/Reperfusion-Induced Multi-Organ Damages.

Mortality and morbidity after cardiac arrest remain high due to ischemia/reperfusion (I/R) injury causing multi-organ damages, even after successful return of spontaneous circulation. We previously generated H2O2-activatable antioxidant nanoparticles formulated with copolyoxalate containing vanillyl alcohol (PVAX) to prevent I/R injury. In this study, we examined whether PVAX could effectively reduce organ damages in a rat model of whole-body ischemia/reperfusion injury (WBIR). To induce a cardiac arrest, 70µl/100 g body weight of 1 mmol/l potassium chloride was administered via the jugular venous catheter. The animals in both the vehicle and PVAX-treated groups had similar baseline blood pressure. After 5.5 minutes of cardiac arrest, animals were resuscitated via intravenous epinephrine followed by chest compressions. PVAX or vehicle was injected after the spontaneous recovery of blood pressure was noted, followed by the same dose of second injection 10 minutes later. After 24 hours, multiple organs were harvested for pathological, biochemical, molecular analyses. No significant difference on the restoration of spontaneous circulation was observed between vehicle and PVAX groups. Analysis of organs harvested 24 hours post procedure showed that whole body I/R significantly increased reactive oxygen species (ROS) generation, inflammatory markers, and apoptosis in multiple organs (heart, brain, and kidney). PVAX treatment effectively blocked ROS generation, reduced the elevation of pro-inflammatory cytokines, and decreased apoptosis in these organs. Taken together, our results suggest that PVAX has potent protective effect against WBIR induced multi-organ injury, possibly by blocking ROS-mediated cell damage.

Out-of-Hospital Cardiopulmonary Resuscitation

With an incidence of 50 - 70 resuscitations attempted per 100000 inhabitants and year Out-of-hospital cardiac arrest (OHCA) is one of the leading causes of death in adults in the developed world. Thus, cardiac arrest is a common emergency situation attended by emergency medical services (EMS). Due to the pathophysiology it is one of the most time-critical emergencies: after 3 - 5 minutes of cardiac arrest without resuscitation efforts the likelihood of neurological impairments is significantly increased once the patient survives the initial event. Therefore, the immediate start of basic life support (BLS) with high quality chest compressions is paramount. Advanced life support comprises defibrillation, if indicated, airway management, the application of selected drugs and the treatment of reversible causes. After return of spontaneous circulation (ROSC) a structured post-resuscitation care in EMS and in dedicated hospitals is essential to achieve the best neurological outcome for the patient. The universal resuscitation algorithm has to be adapted for special circumstances of OHCA (e. g. a traumatic cause, cardiac arrest in pregnancy, …).

Challenges of Cardiopulmonary Resuscitation during Pregnancy

AbstractCardiac arrest, though rare, is the most feared complication in the pregnant woman as it involves two lives. Most arrests occur because of conditions that result from the pregnancy itself or from preexisting medical conditions exacerbated by the pregnancy. Prompt resuscitative efforts are crucial for favorable outcomes for the mother and fetus. The basic principles of resuscitation during pregnancy such as airway, breathing, and circulation are similar to the resuscitation in a cardiopulmonary arrest in any patient; however, certain modifications are necessary to account for the physiologic changes that occur during the pregnancy. Cardiopulmonary resuscitation (CPR) of the parturient should include uterine tilt or displacement to relieve the compression of the inferior vena cava and aorta by the gravid uterus, intubation using rapid sequence intubation with cricoid pressure, and timely perimortem cesarean section (PMCS). Ideally, the PMCS must be performed within 5 minutes of cardiac arrest if the pregnant woman does not have a return of spontaneous circulation, and resuscitation is deemed unsuccessful. The PMCS is performed if the gestational age is at least 20 weeks or the gravid uterus is evident. A high-quality CPR and multispecialty team approach, consisting of obstetricians, cardiologists, anesthesiologists, neonatologists, and nursing staff, is essential for survival.

Abstract 328: Hemodynamic Comparison of Zucker Diabetic Fatty Rats to Their Lean Littermates After Asphyxial Cardiac Arrest

Patients with metabolic syndrome are at higher risk for cardiac arrest (CA), and also have worse neurologic outcome after CA related to their comorbidities (e.g., Type 2 Diabetes Mellitus [T2DM]). Using Zucker Diabetic Fatty (ZDF) rats as a new and relevant model with common comorbidities for CA and cardiopulmonary resuscitation (CPR), we hypothesized that T2DM is associated with a lower chance for return of spontaneous circulation (ROSC) and/or a worse outcome regarding heart function after asphyxial CA compared to their lean littermates. Two groups of rats (8 ZDF, 7 lean) were monitored for 37±2 weeks. The rats were anesthetized and intubated; heart rate was monitored by subcutaneous ECG needles. Femoral artery and vein were cannulated for continuous blood pressure measurement and delivery of fluids and medications, respectively. Before ventilation was stopped to initiate asphyxial CA, rocuronium was given. After 8 minutes of CA, ventilation was re-initiated with FiO 2 1.0, epinephrine and sodium-bicarbonate were administered, and pneumatic chest compression were started with 200 compressions per minute. Chest compressions were stopped when a systolic blood pressure of 120 mmHg was achieved. During 4 hours of observation, vital parameters were closely monitored, blood gases were measured, and ejection fraction (EF %) was assessed with ultrasound. Data are mean ± SD. Statistics: Unpaired student’s t-test (two-tailed), α.05. At baseline, ZDF rats showed significantly higher blood glucose levels (504±52 vs 174±14 mg/dl) compared to their lean littermates. All ZDF and lean rats achieved ROSC, and measurements taken directly after ROSC and after the first hour showed no relevant differences. After four hours, there was no difference in heart rate between ZDF and lean rats. However, diabetic rats had a significantly higher mean arterial blood pressure (142±24vs. 107±19 mmHg) and ejection fraction (42±16%vs 20±8%) compared to their lean littermates. The hypothesis that ROSC-rate in diabetic rats would be lower could not be proven. Conversely, the ZDF rats showed a significantly higher blood pressure related to an increased EF%. Further analysis in this study will focus on the impact of T2DM on cardiac and neurological ischemia-reperfusion injury.

Abstract 338: Impact of No-Flow Time on the Coagulopathy of Prolonged Cardiac Arrest

Introduction: Prolonged cardiac arrest (CA) eligible for ECPR has pathologic features that are more pronounced than CA durations in which ROSC is typically achieved. One such feature is consumptive coagulopathy resulting in microvascular thrombosis and no-reflow. In this study we examined the impact of no-flow time on CA coagulopathy during prolong CPR in swine Hypothesis: No-flow time amplifies the coagulopathy of prolonged cardiac arrest. Methods: Animals were anesthetized and instrumented for hemodynamic monitoring. After 4 or 8 min of untreated ventricular fibrillation (groups CA-4 and CA-8, n=5/group), goal-directed CPR was initiated and continued for a total arrest time of 45 minutes. Viscoelastic properties of clot formation and fibrinolysis were measured by TEG in whole blood at baseline and at the end of resuscitation protocol. Rate of fibrin activation (Angle alpha), Maximum amplitude (MA), Time to MA (TMA), and reduction of clot after 30 min (CL30) were measured to describe coagulation status. Results: TEG showed reduction in clot strength after the CPR protocol. For groups CA-4 and CA-8, Alpha declined from 71(4) to 55(7) and from 68(5) to 51(9) deg, MA reduced from 75(2) to 58(7) and from 73(3) to 53(11) mm and TMA prolonged from 21(2) to 27(4) and from 20(4) to 25(2) min. CL30 increased from 95(2) to 97(2) and from 96(2) to 100(1) % (all p&lt;0.05). Clot lysis was more reduced in CA-8 (p&lt;0.05) but other parameters did not significantly vary between groups. Overall, platelets declined from 328(86) to 138(81) thousands/mm3 while hematocrit increased (all p&lt;0.01). Conclusion: In this clinically relevant model of prolonged CA with consumptive coagulopathy, the reduction of clot formation and clot strength after 45 minutes of CA and CPR was not significantly different with 4 and 8 min no-flow time. However, clot lysis was more reduced after 8-min no-flow. Further studies are needed to determine the impact of no-flow time on CA coagulopathy at the microvascular level.

RNA Sequencing Reveals the Suitability of Cardiac Death Livers for Transplantation.

Background Organ transplantation is considered the best treatment for end-stage organ failure. However, the lack of available organs for transplantation and the increasing number of patients waiting for transplants are primary issues facing the transplant community. Thus, developing strategies to increase the number of donors, especially for liver transplantation, has become a priority. The use of organs acquired from donors who suffered cardiac related deaths has increased the pool of potential liver donors. However, donation after cardiac death (DCD) livers increases the risk of primary graft dysfunction. Methods In the current study, we conducted transcriptome sequencing using livers from a DCD rat to assess the short-term feasibility and functional efficacy of DCD livers. RNA sequencing (RNAseq) data showed that the liver transcriptome varied greatly in rat livers subjected to 15 minutes of cardiac arrest. Results The livers used in the current study had a significant loss of normal function before transplantation. Functional and network analyses consistently indicated that transcription and translation processes were inhibited after approximately 15 minutes of cardiac arrest. Moreover, the transcriptomic sequencing data provides significant insight for identifying functional genes and testing additional biological questions in DCD liver transplantation in future studies.

Reperfusion Activates AP-1 and Heat Shock Response in Donor Kidney Parenchyma after Warm Ischemia.

Utilization of kidneys from extended criteria donors leads to an increase in average warm ischemia time (WIT), which is associated with larger degrees of ischemia-reperfusion injury (IRI). Kidney resuscitation by extracorporeal perfusion in situ allows up to 60 minutes of asystole after the circulatory death. Molecular studies of kidney grafts from human donors with critically expanded WIT are warranted. Transcriptomes of two human kidneys from two different donors were profiled after 35-45 minutes of WIT and after 120 minutes of normothermic perfusion and compared. Baseline gene expression patterns in ischemic grafts display substantial intrinsic differences. IRI does not lead to substantial change in overall transcription landscape but activates a highly connected protein network with hubs centered on Jun/Fos/ATF transcription factors and HSP1A/HSPA5 heat shock proteins. This response is regulated by positive feedback. IRI networks are enriched in soluble proteins and biofluids assayable substances, thus, indicating feasibility of the longitudinal, minimally invasive assessment in vivo. Mapping of IRI related molecules in ischemic and reperfused kidneys provides a rationale for possible organ conditioning during machine assisted ex vivo normothermic perfusion. A study of natural diversity of the transcriptional landscapes in presumably normal, transplantation-suitable human organs is warranted.

Abstract WP253: CaMKII Inhibition Protects Against Purkinje Cell Damage Following Global Cerebral Ischemia

Introduction: Ischemic damage triggers glutamate excitotoxicity, resulting in neuronal cell death. Previous research has demonstrated that NMDA receptor activity triggers downstream calcium-dependent signaling pathways, specifically Ca2+/calmodulin-dependent protein kinase II (CaMKII). We hypothesize that Death Associated Protein Kinase I (DAPKI) and receptor interacting protein (RIP) are downstream of CaMKII, contributing to necroptosis. Focal and global ischemia studies have shown that inhibiting CaMKII is protective against hippocampal damage, but there is little known about cerebellar cell death mechanisms. The aim of this study is to examine the neuroprotective potential of inhibiting CaMKII in Purkinje cells using a global ischemia model. Methods: C57BL/6 male adult mice were subjected to 8 minutes of cardiac arrest and cardiopulmonary resuscitation (CA/CPR). Mice were randomized to tat-CN19o or control peptide (tat-SCR), administered 30 minutes after CA/CPR, and cerebellar injury analyzed 7 days after CA/CPR. Western blot analysis of cerebellar homogenates performed 6 hrs after CA/CPR. Phosphorylated and total CAMKII, DAPKI, and total RIP was quantified. Statistical analyses were performed using 1-WAY ANOVA, with P&lt;0.05 considered significant. Results: Analysis of Purkinje cell death revealed injury at 7 days after CA/CPR that was prevented with tat-CN19o at doses of 0.1 and 1 mg/kg. We observed an increase in T286-P of CAMKII at 6 hours after CA/CPR, concurrent with increased DAPK1 activity (reduced phosphorylation) and increased RIP expression. Administration of tat-CN19o prevented CA/CPR-induced changes in DAPK1 and RIP, while having no effect on CAMKII. Conclusions: Autonomous activity of CAMKII is increased by ischemia in the cerebellum, which contributes to cell death. Neuroprotection with tat-CN19o occurred at doses 10-fold higher than that needed for protection in the hippocampus (Deng, Cell Reports, 2017). Importantly, we have identified signaling pathways downstream of CAMKII that may contribute to Purkinje cell death, DAPK1 and RIP. In summary, our findings indicate that inhibition of autonomous CaMKII activity is a promising therapeutic approach.

Influence of argon on temperature modulation and neurological outcome in hypothermia treated rats following cardiac arrest

Aim of the studyCombining xenon and mild therapeutic hypothermia (MTH) after cardiac arrest (CA) confers a degree of protection that is greater than either of the two interventions alone. However, xenon is very costly which might preclude a widespread use. We investigated whether the inexpensive gas argon would enhance hypothermia induced neurologic recovery in a similar manner. MethodsFollowing nine minutes of CA and three minutes of cardiopulmonary resuscitation 21 male Sprague-Dawley rats were randomized to receive MTH (33°C for 6h), MTH plus argon (70% for 1h), or no treatment. A first day condition score assessed behaviour, motor activity and overall condition. A neurological deficit score (NDS) was calculated daily for seven days following the experiment before the animals were killed and the brains harvested for histopathological analysis. ResultsAll animals survived. Animals that received MTH alone showed best overall neurologic function. Strikingly, this effect was abolished in the argon-augmented MTH group, where animals showed worse neurologic outcome being significant in the first day condition score and on day one to three and five in the NDS in comparison to MTH treated rats. Results were reflected by the neurohistopathological analysis. ConclusionOur study demonstrates that argon augmented MTH does not improve functional recovery after CA in rats, but may even worsen neurologic function in this model.

RNase alleviates neurological dysfunction in mice undergoing cardiac arrest and cardiopulmonary resuscitation.

Cardiac arrest (CA) is one of the leading lethal factors. Despite cardiopulmonary resuscitation (CPR) procedure has been consecutively improved and lots of new strategies have been developed, neurological outcome of the patients experienced CPR is still disappointing. Ribonuclease (RNase) has been demonstrated to have neuroprotective effects in acute stroke and postoperative cognitive impairment, possibly through acting against endogenous RNA that released from damaged tissue. However, the role of RNase in post-cardiac arrest cerebral injury is unknown. In the present study, we investigated the role of RNase in neurological outcome of mice undergoing 5 minutes of CA and followed by CPR. RNase or the same dosage of normal saline was administrated. We found that RNase administration could: 1) improve neurologic score on day 1 and day 3 after CA/CPR performance; 2) improve memory and learning ability on day 3 after training in contextual fear-conditioning test; 3) reduce extracellular RNA (exRNA) level in plasma and hippocampus tissue, and hippocampal cytokines mRNA production on day 3 after CA/CPR procedure; 4) attenuate autophagy levels in hippocampus tissue on day 3 after CA/CPR procedure. In conclusion, RNase could improve neurological function by reducing inflammation response and autophagy in mice undergoing CA/CPR.

Degree and mechanism of brain injury during cardiac arrest and resuscitation

Objective To investigate the degree and the mechanism of brain damage induced by cardiac arrest and resuscitation in rats. Methods A total of 16 male Sprague Dawley rats were randomly divided into the sham group and cardiac arrest/cardiopulmonary resuscitation (CA/CPR) group. The model of cardiac arrest induced by asphyxia was established and CPR was performed. Serum protein neuron specific enolase (NSE) and S100β was detected by enzyme linked immunosorbent assay (ELISA). The levels of B cell lymphoma/leukemia-2 associated X protein (bax), B cell lymphoma/leukemia-2 (bcl-2), Caspase-3 protein were measured by Western boltting. Neuronal apoptosis was examined by TdT-mediated dUTP nick end labeling (TUNEL) method and morphological changes of rat brain were observed. Results S100β levels in CA/CPR group were (4.488±0.762), (6.003±0.718) and (5.913±1.817) ng/ml at 0, 3, 6 h after resuscitation respectively, statistically higher than in sham group (P=0.010, 0.000, 0.038). The levels of NSE were (15.628±3.750) ng/ml in CA/CPR group and (9.376±2.865) ng/ml in the sham group at 6 h after resuscitation, with the difference being statistically significant (P=0.038). Serum proteins NSE and S100β were on a rise, and there was significant difference in the S100β protein levels at 0, 3 h was statistically significant (P=0.031, 0.012). As compared with sham group [for bax, (0.326±0.041); for Caspase-3, (0.394±0.038); for bcl-2, (0.212±0.039)], the bax [(0.731±0.018)], and Caspase-3 (0.445±0.028) protein levels were increased, and bcl-2 [(0.125±0.036)] levels were reduced in CA/CPR group with the difference being statistically significant (P=0.000, 0.001, 0.003). The changes in brain tissue morphology were more obvious in CA/CPR group than in sham group. The apoptosis rate of neurons in CA/CPR group was (29.72±6.29)%, higher than that in sham group (P=0.000). Conclusion Five minutes of cardiac arrest in rats causes significant damage to brain tissue, and the damager gradually aggravates over time, whith may be related to the triggering of apoptosis. Key words: Cardiac arrest; Cardiopulmonary resuscitation; Brain injury; Apoptosis; Rat

Hemodynamics and gas exchange during chest compressions in neonatal resuscitation.

PurposeCurrent knowledge about pulmonary/systemic hemodynamics and gas exchange during neonatal resuscitation in a model of transitioning fetal circulation with fetal shunts and fluid-filled alveoli is limited. Using a fetal lamb asphyxia model, we sought to determine whether hemodynamic or gas-exchange parameters predicted successful return of spontaneous circulation (ROSC).MethodsThe umbilical cord was occluded in 22 lambs to induce asphyxial cardiac arrest. Following five minutes of asystole, resuscitation as per AHA-Neonatal Resuscitation Program guidelines was initiated. Hemodynamic parameters and serial arterial blood gases were assessed during resuscitation.ResultsROSC occurred in 18 lambs (82%) at a median (IQR) time of 120 (105–180) seconds. There were no differences in hemodynamic parameters at baseline and at any given time point during resuscitation between the lambs that achieved ROSC and those that did not. Blood gases at arrest prior to resuscitation were comparable between groups. However, lambs that achieved ROSC had lower PaO2, higher PaCO2, and lower lactate during resuscitation. Increase in diastolic blood pressures induced by epinephrine in lambs that achieved ROSC (11 ±4 mmHg) did not differ from those that were not resuscitated (10 ±6 mmHg). Low diastolic blood pressures were adequate to achieve ROSC.ConclusionsHemodynamic parameters in a neonatal lamb asphyxia model with transitioning circulation did not predict success of ROSC. Lactic acidosis, higher PaO2 and lower PaCO2 observed in the lambs that did not achieve ROSC may represent a state of inadequate tissue perfusion and/or mitochondrial dysfunction.

Abstract 024: Public Access Defibrillation State Law Assessment: Do Current Laws Align With Best Available Evidence?

I. Introduction: Cardiac arrest (CA) is a leading cause of death in the U.S. An estimated 70-90% of people experiencing out-of-hospital CA die before reaching the hospital. Applying cardiopulmonary resuscitation (CPR) and using an automated external defibrillator (AED) within minutes of CA can dramatically raise survival rates. Public Access Defibrillation (PAD) laws can facilitate rapid AED application by lay bystanders. This study assesses whether existing state laws align with best available evidence for PAD implementation to assist decision makers in strengthening existing PAD policies. II. Methods: Two analysts applied CDC’s Quality and Impact of Component (QuIC) Evidence Assessment to appraise the strength of evidence bases for 9 PAD program “policy components,” defined as discrete requirements, provisions, or other elements within a public health policy. Analysts utilized subject matter experts (SME), PubMed, and grey literature to collect evidence and identify 9 policy components. Analysts independently coded evidence across 8 dimensions of evidence quality and public health impact. Resulting scores were used to rank the policy component evidence bases into 3 categories; best, promising or emerging. To identify policy components found in state law, two legal researchers reviewed PAD peer-reviewed and grey literature and analyzed 10 states’ laws using Westlaw. The results were used to construct variables for a legal dataset. Researchers coded and categorized the components in statutes and regulations for all 50 states and Washington, D.C, in effect as of December 31, 2015. Researchers conducted descriptive analysis of the legal dataset and examined correlations with the QuIC policy component results. III. Results: Fifty jurisdictions had PAD laws in effect as of December 31, 2015, authorizing at least one of the 9 evidence-informed PAD policy components (maximum: 8; median: 6). The QuIC assessment categorized 3 components “best”, 4 “promising” and 2 “emerging.” The most common components found in law were PAD use training (best), EMS coordination (best) and lay bystander limited liability (emerging). No state authorized all 9 components. However, 3 states authorized 8 components and 12 states authorized all 3 best components. Two states authorized only lay bystander limited liability (emerging). IV. Implications: There is strong evidence of potential public health impact for targeted AED placement, user training, and EMS PAD coordination, yet two thirds of states have not enacted all three policy components. The Institute of Medicine recommends developing policy strategies and addressing legal barriers to bystander CPR and defibrillation to improve CA outcomes. Studies directly evaluating the role of PAD law in cardiac arrest response and associated health outcomes are needed to determine the best policy approaches to meet state needs and contexts.