Asystolic Cardiac Arrest Research Articles

Comparison of various vasopressin doses to epinephrine during cardiopulmonary resuscitation in asphyxiated neonatal piglets

BackgroundCurrent neonatal resuscitation guidelines recommend epinephrine for cardiac arrest. Vasopressin might be an alternative during asphyxial cardiac arrest. We aimed to compare vasopressin and epinephrine on incidence and time to return of spontaneous circulation (ROSC) in asphyxiated newborn piglets.Design/methodsNewborn piglets (n = 8/group) were anesthetized, intubated, instrumented, and exposed to 30 min of normocapnic hypoxia, followed by asphyxia and asystolic cardiac arrest. Piglets were randomized to 0.2, 0.4, or 0.8IU/kg vasopressin, or 0.02 mg/kg epinephrine. Hemodynamic parameters were continuously measured.ResultsMedian (IQR) time to ROSC was 172(103–418)s, 157(100–413)s, 122(93–289)s, and 276(117–480)s for 0.2, 0.4, 0.8IU/kg vasopressin, and 0.02 mg/kg epinephrine groups, respectively (p = 0.59). The number of piglets that achieved ROSC was 6(75%), 6(75%), 7(88%), and 5(63%) for 0.2, 0.4, 0.8IU/kg vasopressin, and 0.02 mg/kg epinephrine, respectively (p = 0.94). The epinephrine group had a 60% (3/5) rate of post-ROSC survival compared to 83% (5/6), 83% (5/6), and 57% (4/7) in the 0.2, 0.4, and 0.8IU/kg vasopressin groups, respectively (p = 0.61).ConclusionTime to and incidence of ROSC were not different between all vasopressin dosages and epinephrine. However, non-significantly lower time to ROSC and higher post-ROSC survival in vasopressin groups warrant further investigation.ImpactTime to and incidence of ROSC were not statistically different between all vasopressin dosages and epinephrine.Non-significantly lower time to ROSC and higher post-ROSC survival in vasopressin-treated piglets.Overall poorer hemodynamic recovery following ROSC in epinephrine piglets compared to vasopressin groups.Human neonatal clinical trials examining the efficacy of vasopressin during asphyxial cardiac arrest will begin recruitment soon.

Abstract 392: TAT-PHLPP9c and TAT-PIF Administration During CPR Synergistically Improves Cardiac Arrest Survival

Introduction: We have demonstrated that a novel fast-acting peptide TAT-PHLPP9c improves survival in both mouse and swine models of cardiac arrest. The protective effect is mediately by activation of Akt via inhibiting phosphatase PHLPP. We have designed another peptide TAT-PIF to activate Akt by promoting the active conformation of PDK1 via binding to PDK1 Interacting Fragment (PIF). Hypothesis: We hypothesize that TAT-PHLPP9c and TAT-PIF synergistically enhance Akt activation and improve cardiac arrest survival when administered intravenously during CPR. Methods: Cardiomyocytes were treated with TAT-PHLPP9c (10uM), or TAT-PIF (10uM) or in combination. Akt phosphorylation (p-Akt) at both Thr308 and Ser473 sites were assessed by Western blot. In C57BL/6 retired female mice (n=24), a 12-min asystolic cardiac arrest was induced with KCl followed by CPR and blinded randomized administration of the peptides or saline control. Four experimental groups were included: 1) saline, 2) TAT-PHLPP9c (7.5 mg/kg), 3) TAT-PIF (7.5 mg/kg), 4) TAT-PHLPP9c and TAT-PIF. Survival was evaluated at 4 hour post-ROSC. Results: In cardiomyocytes, compared to saline, both TAT-PHLPP9c and TAT-PIF independently increased AktSer473 phosphorylation, and the combined treatment of both peptides synergistically enhanced p-AktSer473. For AktThr308 site, TAT-PIF increased its phosphorylation while TAT-PHLPP9c induced a slight increase of its phosphorylation. Enhanced phosphorylation was also seen with the combined treatment. In mice, compared to saline control, both peptides improved 4-h survival when given alone, but the combined treatment improved 4-h survival synergistically over 30%. Conclusions: The cocktail of TAT-PHLPP9c and TAT-PIF may be a novel treatment regimen for improving outcome following cardiac arrest.

Enterococcal Prosthetic Valve Infective Endocarditis Presenting as Complete Heart Block with Intramyocardial Abscess Causing Asystolic Cardiac Arrest

The extension of an intracardiac abscess causing complete heart block is a rare complication of infective endocarditis that is associated with a high mortality. Early identification of conduction abnormalities and a low threshold for suspecting infective endocarditis is crucial to provide prompt management to prevent intracardial extension of infection. We report a case of a patient presenting with complete heart block in the setting of profound hyperkalemia, and was then found to have enterococcal prosthetic valve endocarditis, which was complicated by an intracardiac aortic root abscess which led to asystolic cardiac arrest. The development of heart block in endocarditis serves as a marker for poor prognosis and can signify progression of infection. Management therefore requires immediate pacing, antibiotic delivery to lessen infectious burden, and evaluation for consideration of surgical options such as valve replacement. It is therefore recommended for patients with endocarditis complicated by conduction abnormalities or intracardial abscesses to be treated by a multi-disciplinary team consisting of cardiologists, cardiothoracic surgeons, and infectious disease specialists.

Mild hypoxia as therapy for post-ischemic mitochondrial injury

Introduction: Mitochondrial injury occurs following cellular ischemia in the setting of myocardial infarction, stroke, and cardiac arrest (CA). Effective strategies for reducing injury are limited. Hypoxia has shown benefit in reversing mitochondrial mediated neurodegenerative disease but is little studied in the setting of post-ischemic injury and is regarded as potentially harmful. In this study, we investigated the effects of mild hypoxia on global post-ischemic injury following CA. We hypothesized that brief mild hypoxia following CA would improve mitochondrial function resulting in improved cellular metabolism and physiological recovery. Methods and Results: Anesthetized C57BL6 mice underwent brief asystolic CA (12 min) followed bycardiopulmonary resuscitation(CPR). One hour following successful CPR, mice were randomized to receive a brief episode (6 hours) of normoxia (21% O2) or hypoxia (10% O2) in an environmental chamber. Post intervention, the mice were returned to room air (21% O2). Mild hypoxia improved cardiac mitochondrial complex 1 respiration in the heart by 28% and ATP-related oxygen consumption by 49% (n=3, P<0.05 vs normoxia, respectively) compared to normoxia treated mice. Hypoxia was further associated with improved glucose oxidation in heart as evidenced by decreases in pyruvate dehydrogenase kinase 4 (PDK4) gene and protein expression (n=4, P<0.05 vs normoxia, respectively) as well as decreases in pyruvate dehydrogenase phosphorylation (n=4, P<0.05, respectively) in heart. Hypoxia decreased lactate dehydrogenase (LDH) expression and lactate concentration in heart compared to normoxia treated controls (n=4, P<0.05 vs normoxia, respectively). ROS production in heart by 20% (n=6, P<0.05) was also decreased by mild hypoxia when compared to normoxia post CA. These changes were associated with improved recovery of myocardial function, neurological recovery, and 10-day survival following CA (n=13, P<0.05 vs normoxia, respectively). Conclusion: Brief mild hypoxia treatment following global ischemic injury paradoxically improved recovery of myocardial mitochondrial respiration and metabolism and was associated with improved physiological recovery and survival. Post-ischemia hypoxia is a potential therapeutic strategy for mitochondrial ischemic injury and requires further study. No financial disclosures. This is the full abstract presented at the American Physiology Summit 2023 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

EFFECTS OF M101-AN EXTRACELLULAR HEMOGLOBIN-APPLIED DURING CARDIOPULMONARY RESUSCITATION: AN EXPERIMENTAL RODENT STUDY.

During and immediately after cardiac arrest, cerebral oxygen delivery is impaired mainly by microthrombi and cerebral vasoconstriction. This may narrow capillaries so much that it might impede the flow of red blood cells and thus oxygen transport. The aim of this proof-of-concept study was to evaluate the effect of M101, an extracellular hemoglobin-based oxygen carrier (Hemarina SA, Morlaix, France) derived from Arenicola marina , applied during cardiac arrest in a rodent model, on markers of brain inflammation, brain damage, and regional cerebral oxygen saturation. Twenty-seven Wistar rats subjected to 6 min of asystolic cardiac arrest were infused M101 (300 mg/kg) or placebo (NaCl 0.9%) concomitantly with start of cardiopulmonary resuscitation. Brain oxygenation and five biomarkers of inflammation and brain damage (from blood, cerebrospinal fluid, and homogenates from four brain regions) were measured 8 h after return of spontaneous circulation. In these 21 different measurements, M101-treated animals were not significantly different from controls except for phospho-tau only in single cerebellum regions ( P = 0.048; ANOVA of all brain regions: P = 0.004). Arterial blood pressure increased significantly only at 4 to 8 min after return of spontaneous circulation ( P < 0.001) and acidosis decreased ( P = 0.009). While M101 applied during cardiac arrest did not significantly change inflammation or brain oxygenation, the data suggest cerebral damage reduction due to hypoxic brain injury, measured by phospho-tau. Global burden of ischemia appeared reduced because acidosis was less severe. Whether postcardiac arrest infusion of M101 improves brain oxygenation is unknown and needs to be investigated.

Asystole, A Rare Cardiac Complication of Lateral Medullary Infarction: Case report and Literature Review. (P2-5.010)

<h3>Objective:</h3> We report a case of lateral medullary infarction leading to asystole, and we discuss the diagnosis, management, and prognosis of patients with this rare complication. <h3>Background:</h3> Clinical presentations of lateral medullary stroke vary. Wallenberg syndrome is the most common presentation, which includes vertigo with nystagmus, ataxia, ipsilateral sensory deficits in the face, bulbar muscle weakness, and ipsilateral Horner’s syndrome. The nucleus tractus solitarius, the dorsal vagal nucleus, and the nucleus ambiguous in the lateral medulla oblongata play a critical role in autonomic regulation and have centers for respiratory, cardiac, and vasomotor reflexes. Despite this, cardiac arrhythmias such as asystole are a rare clinical manifestation of lateral medullary stroke. <h3>Design/Methods:</h3> Case report and literature review. <h3>Results:</h3> A 64-year-old man with hypertension, previously involved in a motor vehicle accident, presented with acute onset dysphagia, left facial droop, and left eye ptosis. CT of the head did not show any acute stroke or hemorrhage. CT angiography of the head and neck showed left vertebral artery (V3/V4 segment) occlusion. He received IV thrombolysis. Post thrombolysis, he had bradycardia evolving to asystole and brief cardiac arrest. MRI of the brain revealed acute left posterior lateral medullary stroke and MR angiography showed left vertebral artery dissection. Cardiac work-up was unrevealing, and he eventually required placement of a dual-chamber pacemaker. Given the absence of respiratory factors and structural heart disease, the bradycardia and asystole were attributed to the lateral medullary stroke. <h3>Conclusions:</h3> Despite the recognized role of the lateral medulla in autonomic regulation, cardiac arrhythmias are rarely associated with lateral medullary infarction. Precise mechanisms are yet to be elucidated, but it remains important to recognize them as a potential complication of this stroke. <b>Disclosure:</b> Dr. Gutierrez Quiceno has nothing to disclose. Dr. Gowda has nothing to disclose. Dr. Kakadia has nothing to disclose.

Abstract 15: Hypoxia As Therapy For Mitochond​Rial Injury Following Cardiac Arrest

Introduction: Mitochondrial injury occurs following cardiac arrest (CA) and contributes to myocardial stunning and anoxic brain injury. Hypoxia has been proposed as a therapeutic strategy for neurodegenerative diseases associated with mitochondrial respiration defects, but its benefits in the post-CA setting remain unexplored. Here, we hypothesized mild hypoxia as therapy for post-CA mitochondrial injury. Methods and Results: Mice underwent brief asystolic CA (12 min) followed by cardiopulmonary resuscitation (CPR). One hour following successful CPR, mice were randomized to receive a brief episode (6 hours) of hyperoxia (33% O 2 ), normoxia (21% O 2 ), or hypoxia (10% O 2 ) in an environmental chamber. Post exposure, the mice were returned to room air (21% O 2 ). Hypoxia improved myocardial fractional shortening compared to normoxia and hyperoxia (Hypoxia: 45.6±2.3 %, Normoxia: 40.0±0.8 %, Hyperoxia: 29.0±4.0 %, n=5, P&lt;0.05, respectively). Hypoxia also elevated neurological scores (Hypoxia: 8.4±1.3, Hyperoxia: 5.6±1.2, n=5, P&lt;0.05) 48 hours post CA compared to hyperoxia. Ten-day survival was prolonged by hypoxia (Hypoxia: 87.5 %, Normoxia: 62.5 %, Hyperoxia: 12.5 %, n=10, P&lt;0.05, respectively). Hypoxia also improved mitochondrial function (28% increase in basic oxygen consumption and 49% increase in ATP-related oxygen consumption, n=3, P&lt;0.05, respectively) and a 20% decrease in ROS production (n=6, P&lt;0.05) compared to normoxia. Conclusion: This study has two important findings: First , we demonstrate that oxygen availability in the early post-CA period is a critical determinant of long-term post-CA outcomes. Second , we show that mild hypoxic therapy in the early post-CA period improves early mitochondrial function and long-term post-CA outcomes. These findings reveal an important oxygen-dependent therapeutic window following resuscitation from CA that has implications for post-CA critical care.

Abstract 104: Taurine As Biomarker And Therapeutic Target For Cardiac Arrest

Introduction: Out-of-hospital cardiac arrest (CA) is a leading cause of death with high mortality. Most patients die from post-CA syndrome due to ischemia/reperfusion injury-triggered responses. Taurine and glutamate, amino acids with cellular activities that are expressed primarily in heart and brain tissues, respectively, are released in response to CA. Hypothesis: Taurine and glutamate levels in blood reflect the extent of injury of CA. Taurine and glutamate could potentially regulate CA outcomes. Methods: Adult CA patients (n=51, 19 survivors, S and 32 nonsurvivors, NS; 35 received cooling treatment, C while 16 did not, NC) at an urban academic ED were enrolled from 2018-2019. Plasma taurine and glutamate collected at various time points including hospital arrival, 6, 24, 48 and 72 hours after arrival, and measured with commercially available assay kits. In a mouse model, 8-min asystolic cardiac arrest was induced with KCl, followed by initiation of CPR and randomized to blinded administration of taurine (50 mg/kg) or saline placebo at 90 second during CPR. Survival (4h) and mean arterial blood pressure (MAP) were evaluated. The Wilcoxon test and generalized estimating equation were used for comparison at each time point and longitudinal trend analysis for human data. Kaplan-Meier estimate and T-test were used for survival and mean comparison in mice. p &lt;0.05 was considered statistically significant. Results: Plasma taurine and glutamate levels were highest at R0 and decreased over time in both S and NS, and were higher in NS than S. Taurine levels were significantly associated with survival (NS 66.24±41.36 vs. S 37.48±19.46 at 6h, p &lt;0.05) while glutamate levels were not. Taurine levels in both C and NC groups demonstrated a significantly decreasing trend over time, but the C group showed more reduction ( p &lt;0.05), while glutamate levels showed no significant trend. In mice, compared to saline, taurine treatment markedly improved 4h survival and MAP post-ROSC. Conclusions: Decreased release of taurine into blood is correlated with CA survival and may regulate CA outcomes. It has high translational potential as a biomarker for predicting CA survival, guiding cooling treatment, and serving as a therapeutic target to improve CA outcomes.

Abstract 15140: Post-Myocardial Infarction Ventricular Septal Defect in a Patient With Mixed Connective Tissue Disorder

Mixed connective tissue disorder (MCTD) is associated with a broad range of cardiovascular abnormalities, including coronary artery disease (CAD). It has been proposed that chronic systemic inflammation plays a key role in the development of atherosclerotic disease. A 66-year-old female with a history of MCTD and hypertension presented with mild dyspnea and pleuritic chest pain after one week of persistent flu-like symptoms. Her blood pressure was 108/77 mmHg, pulse 92 bpm, saturating 98% on room air. She was comfortable and denied other risk factors such as diabetes, hyperlipidemia, or prior smoking history. On exam she was found to have a soft holosystolic murmur across her precordium. EKG showed sinus rhythm with small Q waves and ST elevation in V1-V6. She was taken for cardiac catheterization which revealed a thrombotic occlusion in the proximal left anterior descending artery (LAD) and a severe lesion in the left circumflex artery. She underwent angioplasty with one drug eluted stent placed to LAD. Left ventriculography revealed a VSD near the apex, and transthoracic echocardiogram showed a 7.6 mm muscular VSD with left to right shunt, ejection fraction of 35% and hypokinesis of the anterior wall. She became hypotensive and required vasopressors prior to coronary artery bypass grafting and primary closure of her apical VSD. Intraoperatively, a 2 cm VSD with 5 cm of necrotic surrounding tissue was noted. Post-operative complications included asystolic cardiac arrest, marked cardiogenic shock and multiorgan failure to which she ultimately succumbed. Post-myocardial infarction VSD is a rare complication of MI occurring in approximately 0.2% of cases. However, patients with MCTD can develop atypical symptoms, resulting in delayed presentation and therefore higher risk of mechanical complications. We highlight the importance of a thorough physical exam and high suspicion for mechanical complications in these patients even when hemodynamically stable.

SUDDEN CARDIOVASCULAR COLLAPSE DUE TO CALCIUM CHANNEL BLOCKER OVERDOSE: SUCCESSFUL MANAGEMENT WITH HIGH-DOSE INSULIN EUGLYCEMIC THERAPY

SUDDEN CARDIOVASCULAR COLLAPSE DUE TO CALCIUM CHANNEL BLOCKER OVERDOSE: SUCCESSFUL MANAGEMENT WITH HIGH-DOSE INSULIN EUGLYCEMIC THERAPY

Continuous heart rate dynamics preceding in-hospital pulseless electrical activity or asystolic cardiac arrest of respiratory etiology

IntroductionRespiratory failure is a common cause of pulseless electrical activity (PEA) and asystolic cardiac arrest, but the changes in heart rate (HR) pre-arrest are not well described. We describe HR dynamics prior to in-hospital cardiac arrest (IHCA) among PEA/asystole arrest patients with respiratory etiology. MethodsIn this retrospective study, we evaluated 139 patients with 3–24 hours of continuous electrocardiogram data recorded preceding PEA/asystole IHCA from 2010-2017. We identified respiratory failure cases by chart review and evaluated electrocardiogram data to identify patterns of HR changes, sinus bradycardia or sinus arrest, escape rhythms, and development right ventricular strain prior to IHCA. ResultsA higher proportion of respiratory cases (58/73, 79 %) fit a model of HR response characterized by tachycardia followed by rapid HR decrease prior to arrest, compared to non-respiratory cases (30/66, 45 %, p < 0.001). Among the 58 respiratory cases fitting this model, 36 (62 %) had abrupt increase in HR occurring 64 (IQR 23–191) minutes prior to arrest, while 22 (38 %) had stable tachycardia until time of HR decrease. Mean peak HR was 123 ± 21 bpm. HR decrease occurred 3.0 (IQR 2.0–7.0) minutes prior to arrest. Sinus arrest occurred during the bradycardic phase in 42/58 of cases; escape rhythms were present in all but 2/42 (5 %) cases. Right ventricular strain ECG pattern, when present, occurred at a median of 2.2 (IQR −0.05–17) minutes prior to onset of HR decrease. ConclusionIHCAs of respiratory etiology follow a model of HR increase from physiologic compensation to hypoxia, followed by rapid HR decrease prior to arrest.

Pulseless electrical activity and asystolic cardiac arrest in infants: identifying factors that influence outcomes.

There is limited information on pulseless electrical activity (PEA)/asystolic cardiac arrest (CA) in the infant population. The aim is to describe the incidence and factors associated with outcomes in infants with PEA/asystolic CA. Single-center retrospective chart review study of infants less than one year of age who suffer in-hospital PEA/asystolic CA from January 1 2011 to June 30 2019. The primary outcome was the return of spontaneous circulation. The secondary outcome was survival to discharge. CA occurred in 148 infants and PEA/asystolic was found in 38 (26%). Of those 29 (76%) achieved ROSC, and 12 (32%) survived to discharge. Infants on inotrope support or receiving longer duration of chest compressions and epinephrine had increase mortality. All infants with respiratory etiology of arrest survived to hospital discharge. PEA/asystolic CAs are uncommon. Poor prognostic indicators include the need for pre-arrest inotrope support and increased duration of chest compressions.

Accidental Hypothermia: 2021 Update.

Accidental hypothermia is an unintentional drop of core temperature below 35 °C. Annually, thousands die of primary hypothermia and an unknown number die of secondary hypothermia worldwide. Hypothermia can be expected in emergency patients in the prehospital phase. Injured and intoxicated patients cool quickly even in subtropical regions. Preventive measures are important to avoid hypothermia or cooling in ill or injured patients. Diagnosis and assessment of the risk of cardiac arrest are based on clinical signs and core temperature measurement when available. Hypothermic patients with risk factors for imminent cardiac arrest (temperature < 30 °C in young and healthy patients and <32 °C in elderly persons, or patients with multiple comorbidities), ventricular dysrhythmias, or systolic blood pressure < 90 mmHg) and hypothermic patients who are already in cardiac arrest, should be transferred directly to an extracorporeal life support (ECLS) centre. If a hypothermic patient arrests, continuous cardiopulmonary resuscitation (CPR) should be performed. In hypothermic patients, the chances of survival and good neurological outcome are higher than for normothermic patients for witnessed, unwitnessed and asystolic cardiac arrest. Mechanical CPR devices should be used for prolonged rescue, if available. In severely hypothermic patients in cardiac arrest, if continuous or mechanical CPR is not possible, intermittent CPR should be used. Rewarming can be accomplished by passive and active techniques. Most often, passive and active external techniques are used. Only in patients with refractory hypothermia or cardiac arrest are internal rewarming techniques required. ECLS rewarming should be performed with extracorporeal membrane oxygenation (ECMO). A post-resuscitation care bundle should complement treatment.

Ondansetron and Hypothermia Induced Cardiac Arrest in a 97-Year-Old Woman: A Case Report

Background: Ondansetron and hypothermia are both known to induce bradycardia or QT interval prolongation, thus placing affected patients at risk of cardiac arrest. Case Report: Herein, we report the case of a 97-year-old woman who initially presented with confusion and hypothermia, and experienced severe bradycardia and asystolic cardiac arrest after a 4 mg intravenous ondansetron bolus injection. Conclusion: Ondansetron is associated with bradycardia and QTc prolongation, both of which might be further exacerbated by hypothermia. Clinicians should be aware that administering ondansetron in patients with hypothermia might further increase the risk of adverse cardiac events and eventual cardiac arrest.

Abstract 11243: Novel Peptide for Cardiopulmonary Resuscitation

Introduction: While effective for out-of-hospital cardiac arrest, therapeutic hypothermia can be difficult to timely implement clinically. No drugs exist for improving neurologically intact survival. We have developed a novel peptide (TAT-PHLPP) that inhibits PH domain and Leucine rich repeat Protein Phosphatases (PHLPP), leading to Akt activation and mimicking of the protective effects of therapeutic hypothermia without the need of physical cooling. Hypothesis: We hypothesize that when administered intravenously during CPR, TAT-PHLPP improves neurologically intact survival. Methods: We conducted parallel studies in mouse and swine models. In C57BL6 mice (n = 72), we induced a 8 or 12-min asystolic cardiac arrest with KCl, followed by initiation of CPR and blinded randomized administration of TAT-PHLPP (7.5 mg/kg) or saline placebo. The primary outcomes were 4-h and 5-day survival, mean arterial blood pressure (MAP) and cerebral blood flow (CBF). We assessed PHLPP-NHERF1 binding and glucose utilization (via pyruvate dehydrogenase (PDH) phosphorylation and ATP generation). In 16 swine, we induced 5 min of VF followed by ACLS with vest CPR and administered two doses of TAT-PHLPP or saline. Survival (24 h) and neurological function were assessed. Plasma biomarkers taurine and glutamate levels in mice were measured and validated in CA patients (n=68) with a shockable rhythm at the time of hospital arrival, 6, 24, 48, and 72 h post-hospital arrival. Results: In mice, compared to saline, TAT-PHLPP significantly improved 4-h and 5-day survival, increased post-ROSC MAP and CBF, inhibited PHLPP-NHERF1 binding, increased p-Akt, decreased p-PDH (increased activity) at 15 min post-ROSC, enhanced ATP generation in both heart and brain, and reduced plasma taurine and glutamate levels. In swine, TAT-PHLPP improved 24 h neurologically intact survival (1/9 in control vs. 6/7 with peptide, p &lt; 0.01). In patients, taurine levels were higher in non-survivors (n=44) than survivors (n=24) at 6 h of post-hospital arrival (65.9 ± 34.8 vs. 45.6 ±23.7, p&lt; 0.001). Conclusions: TAT-PHLPP has high translational potential as a first-of-class biologic treatment to reproduce critical outcomes of therapeutic hypothermia and improve cardiac arrest survival.

Cerebrospinal fluid is a significant fluid source for anoxic cerebral oedema.

Cerebral oedema develops after anoxic brain injury. In two models of asphyxial and asystolic cardiac arrest without resuscitation, we found that oedema develops shortly after anoxia secondary to terminal depolarizations and the abnormal entry of CSF. Oedema severity correlated with the availability of CSF with the age-dependent increase in CSF volume worsening the severity of oedema. Oedema was identified primarily in brain regions bordering CSF compartments in mice and humans. The degree of ex vivo tissue swelling was predicted by an osmotic model suggesting that anoxic brain tissue possesses a high intrinsic osmotic potential. This osmotic process was temperature-dependent, proposing an additional mechanism for the beneficial effect of therapeutic hypothermia. These observations show that CSF is a primary source of oedema fluid in anoxic brain. This novel insight offers a mechanistic basis for the future development of alternative strategies to prevent cerebral oedema formation after cardiac arrest.

Asystolic cardiac arrest following liposomal amphotericin\xa0B infusion: anaphylaxis or compliment activation-related pseudoallergy?

Allergic reaction to liposomal amphotericin B is rare. We report a case of cardiac arrest in a 64-year-old woman following liposomal amphotericin B infusion, requiring resuscitation. We also present the results of subsequent skin prick and intradermal testing to liposomal amphotericin on the patient and three healthy controls, highlighting the need for further research into the immunopathogenesis of this reaction.

Microglial Activation and Neurological Outcomes in a Murine Model of Cardiac Arrest

BackgroundNeurological injury following successful resuscitation from sudden cardiac arrest (CA) is common. The pathophysiological basis of this injury remains poorly understood, and treatment options are limited. Microglial activation and neuroinflammation are established contributors to many neuropathologies, such as Alzheimer disease and traumatic brain injury, but their potential role in post-CA injury has only recently been recognized. Here, we hypothesize that microglial activation that occurs following brief asystolic CA is associated with neurological injury and represents a potential therapeutic target.MethodsAdult C57BL/6 male and female mice were randomly assigned to 12-min, KCl-induced asystolic CA, under anesthesia and ventilation, followed by successful cardiopulmonary resuscitation (n = 19) or sham intervention (n = 11). Neurological assessments of mice were performed using standardized neurological scoring, video motion tracking, and sensory/motor testing. Mice were killed at 72 h for histological studies; neuronal degeneration was assessed using Fluoro-Jade C staining. Microglial characteristics were assessed by immunohistochemistry using the marker of ionized calcium binding adaptor molecule 1, followed by ImageJ analyses for cell integrity density and skeletal analyses.ResultsNeurological injury in post-cardiopulmonary-resuscitation mice vs. sham mice was evident by poorer neurological scores (difference of 3.626 ± 0.4921, 95% confidence interval 2.618–4.634), sensory and motor functions (worsened by sixfold and sevenfold, respectively, compared with baseline), and locomotion (75% slower with a 76% decrease in total distance traveled). Post-CA brains demonstrated evidence of neurodegeneration and neuroinflammatory microglial activation.ConclusionsExtensive microglial activation and neurodegeneration in the CA1 region and the dentate gyrus of the hippocampus are evident following brief asystolic CA and are associated with severe neurological injury.

Post‐Cardiac Arrest Neurological Injury is Associated with Neuroinflammation and Mitochondrial Respiratory Deficiency

Background Cardiopulmonary resuscitation (CPR) following sudden cardiac death is associated with neurological injury but the pathophysiology of this injury remains poorly understood. In this study we investigated the effects of post-cardiac arrest CPR on neurological outcomes and hypothesized that injury would be associated with neuroinflammation and central nervous system mitochondrial injury. Method C57BL/6 adult mice underwent either asystolic cardiac arrest (CA) (N=19) followed by CPR or sham operation (SHAM) (N=12). Neurobehavioral assessment and survival analysis were made in animals following CPR. Brain tissue was harvested from both SHAM and CA mice for brain slice electrophysiological studies, microglial morphometric analysis, and mitochondrial respiration measurements. Results Post-CA neurological injury was evident as evaluated by neurological scores (difference of 3.626 ± 0.4921, 95%CI 2.618-4.634), sensory scores (difference of -65.79 ± 14.7 seconds, 95%CI -96.21 to -35.37), motor scores (difference of -107.2 ± 6.558 seconds, 95%CI -120.7 to -93.61) and video analysis of distance (mean difference of 8.361 meters ± 0.5061, 95%CI 10.52 to 6.203) and speed (difference of 0.0689 m/s ± 0.004242, 95%CI 0.08715 to 0.05065). 24 hours post-CA, synaptic long-term potentiation (LTP) and maximal mitochondrial oxygen consumption (OCR) (mean difference -107.4 ± 37.79 pmol/min, p=0.0467, N=3/group) were depressed. These outcomes were also associated with morphometric changes in microglia. Microglia demonstrated shorter process lengths per soma (mean difference of 139.5 ± 29.62, p=0.0013, N=4/group) as well as less process endpoints per soma (mean difference of 42.21 ± 9.123, p=0.0018, N=4/group) compared to control microglia, suggesting post-CA microglial activation. Conclusion These results indicate that neurological injury following post-CA CPR is associated with impaired synaptic plasticity, depressed mitochondrial respiration, and neuroinflammation. Future studies evaluating the basis and interactions of these post-CA phenomena are warranted.

Asystolic cardiac arrest with chest pain as initial features of eosinophilic granulomatosis with polyangiitis (Churg-Strauss syndrome).

Asystolic cardiac arrest with chest pain as initial features of eosinophilic granulomatosis with polyangiitis (Churg-Strauss syndrome).