Abstract 129: Gasping During Cardiac Arrest Before Cardiopulmonary Resuscitation Increases Cerebral Oximetry in a Swine Model

Circulation ◽  
2020 ◽  
Vol 142 (Suppl_4) ◽  
Author(s):  
Nelly Rojas-Salvador ◽  
Bayert Salverda ◽  
Johanna C Moore ◽  
Michael Lick ◽  
Guillaume P Debaty ◽  
...  
Keyword(s):  
Cardiac Arrest ◽  
Near Infrared ◽  
Venous Blood ◽  
Intrathoracic Pressure ◽  
Aortic Pressure ◽  
Cerebral Oximetry ◽  
Right Atrial ◽  
Swine Model ◽  
Therapeutic Implications ◽  
The Impact

Introduction: Spontaneous gasping (SG) during cardiac arrest is associated with favorable neurological outcomes. SG lowers intrathoracic pressure (ITP), enhancing flow of respiratory gases to the lungs and venous blood to the heart, while simultaneously lowering intracranial pressure (ICP). The impact of SG on regional cerebral oximetry (rSO2) is unknown. Hypothesis: During untreated ventricular fibrillation (VF), SG will increase rSO2 until the gasping effort declines. Methods: Swine (~40 kg) were intubated and anesthetized with isoflurane. After 8 min of untreated VF, conventional mechanical CPR at 100 compressions/min was performed. Intrathoracic pressure (ITP), mean aortic pressure (MAP), ICP, right atrial pressure (RAP) and calculated cerebral perfusion pressure (CerPP) were measured continuously. rSO2 was measured continuously with near-infrared spectroscopy (Equanox 7600, Nonin Medical). These parameters were assessed before and during SG, and during CPR. Data are expressed as mean ± SD. A paired Student’s t- test was used. Results: SG occurred in 19/22 pigs during untreated VF, with 9.2 ± 4.3 gasps/pig. For pigs that gasped, the individual gasp duration was 1.74 ± 0.52 sec and the maximum negative ITP (mmHg) was -3.24 ± 1.93 mmHg. rSO2 increased in 9/19 (47%) pigs from 54.7% ± 4.1 to 57.8% ± 4.8 during SG (p<0.001). Figure 1 shows rSO2 from 2 representative pigs, A) with and B) without SG. SG also decreased ITP (p<0.001), RAP (p=0.02) and ICP (p<0.001), and increased MAP (p<0.001) and CerPP (p<0.001). After 8 min of untreated VF, rSO2 for all 22 pigs was 49.3% ± 3.7. After 30 and 60 sec of CPR, rSO2 values were 54.6% ± 3.8 and 57.8% ± 3.8, respectively. Conclusions: rSO2 values increased in nearly half of animals with SG. This increase in rSO2 with SG was equal to the level of rSO2 achieved after 1 minute of CPR. Further study is warranted to determine potential prognostic and therapeutic implications of SG-induced increases rSO2 during cardiac arrest.

Abstract 372: Regional Cerebral Saturation in a Swine Model of Goal-directed Resuscitation of Prolonged Ventricular Fibrillation Cardiac Arrest

Circulation ◽  
2020 ◽  
Vol 142 (Suppl_4) ◽  
Author(s):  
Cornelia Genbrugge ◽  
David D Salcido ◽  
Allison C Koller ◽  
Caelie Kern ◽  
James J Menegazzi
Keyword(s):  
Cardiac Arrest ◽  
Ventricular Fibrillation ◽  
Near Infrared ◽  
Swine Model ◽  
Coronary Perfusion ◽  
Fixed Rate ◽  
Group A ◽  
Group B ◽  
Cerebral Saturation ◽  
The Impact

Introduction: The characteristics and limitations of near-infrared spectroscopy (NIRS) measurement of regional cerebral saturation (rSO2) for reflecting key moment-to-moment physiological changes needed to guide cardiopulmonary resuscitation (CPR) have yet to be fully determined. Objective: Examine the impact of NIRS sensor placement and resuscitation process variation on rSO2 measurements during prolonged cardiac arrest. Methods: Thirty mixed-breed domestic pigs (mean weight: 25.0kg+/-2.0) were sedated (ketamine / xylazine), anesthetized (fentanyl), paralyzed (vecuronium) and mechanically ventilated. Micromanometer pressure transducers were placed in the aorta and right atrium via femoral cutdown to measure central pressures, including mean arterial pressure (MAP) and coronary perfusion pressure (CPP). Two NIRS sensors were placed on the cranium: one on the skin surface and one on the bare skull. Ventricular fibrillation was induced electrically and untreated for 8 minutes followed by CPR. Initial BLS phase: 4 minutes of CPR at 100 compressions per minute (CPM) and 2 inches depth with manual ventilations (30:2). Randomized ALS phase: CPR with a pressor-titrated (Group A) or a compression rate/depth-titrated (Group B) strategy targeting 25mmHg CPP. Group A animals received pressor doses q1min and fixed rate/depth CPR. Group B animals received increasing rates and depth of CPR with epinephrine q3min. Defibrillation was attempted at 6min CPR q2min. rSO2 was compared between skin and skull across phases of resuscitation with t-tests and generalized estimating equations (GEE). Results: Mean skin and skull rSO2 differed marginally overall (63.8 vs 62.0, p < 0.001), at baseline (69.9 vs 64.9, p < 0.001), during BLS CPR (56.9 vs 48.7, p < 0.001), during ALS CPR (59.5 vs 51.0, p < 0.001), and following ROSC (70.0 vs 60.5, p<0.001). rSO2 measured on either skull or skin both varied throughout phases of the experiment but not between CPR groups. In GEE models, rSO2 measured on skin or skull was not associated with MAP at baseline, but was directly associated during BLS (coef 0.13; p<0.001) & ALS CPR (coef 0.09; p<0.001), and after ROSC (coef 0.02; p=0.017). Conclusion: rSO2 measures differ between skin and skull though both correlate with MAP.

Cerebral oxygenation monitoring in patients during and after cardiac arrest -- a narrative review of current methods and evidence

2021 ◽  
Keyword(s):  
Cardiac Arrest ◽  
Near Infrared ◽  
Cerebral Oxygenation ◽  
The Body ◽  
Narrative Review ◽  
Oxygen Balance ◽  
Monitoring Methods ◽  
Venous Oxygen Saturation ◽  
Oxygenation Monitoring ◽  
The Impact

Hypoxic-ischemic brain injury (HIBI) is a leading cause of mortality in post-cardiac arrest (post-CA) patients who successfully survive the initial cardiopulmonary resuscitation (CPR) but later die in the Intensive Care Unit (ICU). Therefore, a key priority of post-resuscitation ICU care is to prevent and limit the impact of HIBI by optimizing the balance between cerebral oxygen delivery and demand. Traditionally, an optimal systemic oxygen balance is considered to ensure the brain’s oxygen balance. However, the validity of this assumption is uncertain, as the brain constitutes only 2%of the body mass while accounting for approximately 20% of basal oxygen consumption at rest. Hence, there is a real need to monitor cerebral oxygenation realistically. Several imaging and bedside monitoring methods are available for cerebral oxygenation monitoring in post-CA patients. Unfortunately, each of them has its limitations. Imaging methods require transporting a critically ill unstable patient to the scanner. Moreover, they provide an assessment of the oxygenation state only at a particular moment, while brain oxygenation is dynamic. Bedside methods, specifically near-infrared spectroscopy (NIRS), brain tissue oxygen tension (PbtO2), and jugular venous oxygen saturation monitoring (SjvO2), have not often been used in studies involving post-CA patients. Hence there is ambiguity regarding clear recommendations for using these bedside monitors. Presently, the most promising option seems to be using the NIRS as an indicator of effective CPR. We present a narrative review focusing on bedside methods and discuss the evidence for their use in adult patients after cardiac arrest.

Abstract 273: Noninvasive Mitochondrial Modulation: Neuroprotection in a Translational Model of Cardiac Arrest and Resuscitation

Circulation ◽  
2019 ◽  
Vol 140 (Suppl_2) ◽  
Author(s):  
Joseph M Wider ◽  
Erin Gruley ◽  
Jennifer Mathieu ◽  
Emma Murphy ◽  
Rachel Mount ◽  
...  
Keyword(s):  
Cardiac Arrest ◽  
Brain Injury ◽  
Near Infrared ◽  
Small Animal ◽  
Spontaneous Circulation ◽  
Infrared Light ◽  
Swine Model ◽  
Treatment Groups ◽  
The Brain ◽  
Neuroprotective Therapies

Background: Mitochondrial dysfunction contributes to cardiac arrest induced brain injury and has been a target for neuroprotective therapies. An emerging concept suggests that hyperactivation of neuronal mitochondria following resuscitation results in hyperpolarization of the mitochondrial membrane during reperfusion, which drives generation of excess reactive oxygen species. Previous studies from our group demonstrated that limiting mitochondrial hyperactivity by non-invasively modulating mitochondrial function with specific near infrared light (NIR) wavelengths can reduce brain injury in small animal models of global and focal ischemia. Hypothesis: Inhibitory wavelengths of NIR will reduce neuronal injury and improve neurocognitive outcome in a clinically relevant swine model of cardiac arrest. Methods: Twenty-eight male and female adult swine were enrolled (3 groups: Sham, CA/CPR, and CA/CPR + NIR). Cardiac arrest (8 minutes) was induced with a ventricular pacing wire and followed by manual CPR with defibrillation and epinephrine every 30 seconds until return of spontaneous circulation (ROSC), 2 of the 20 swine that underwent CA did not achieve ROSC and were not enrolled. Treatment groups were randomized prior to arrest and blinded to the CPR team. Treatment was applied at onset of ROSC by irradiating the scalp with 750 nm and 950 nm LEDs (5W) for 2 hours. Results: Sham-operated animals all survived (8/8), whereas 22% of untreated animals subjected to cardiac arrest died within 45 min of ROSC (CA/CPR, n= 7/9). All swine treated with NIR survived the duration of the study (CA/CPR + NIR, n=9/9). Four days following cardiac arrest, neurological deficit score was improved in the NIR treatment group (50 ± 21 CA/CPR vs. 0.8 ± 0.8 CA/CPR + NIR, p < 0.05). Additionally, neuronal death in the CA1/CA3 regions of the hippocampus, assessed by counting surviving neurons with stereology, was attenuated by treatment with NIR (17917 ± 5534 neurons/mm 3 CA/CPR vs. 44655 ± 5637 neurons/mm 3 CA/CPR + NIR, p < 0.05). All data is reported as mean ± SEM. Conclusions: These data provide evidence that noninvasive modulation of mitochondria, achieved by transcranial irradiation of the brain with NIR, mitigates post-cardiac arrest brain injury.

Abstract 246: Therapeutic Hypothermia Mimicking Peptide Administration During Cardiopulmonary Resuscitation Improved Cardiac Arrest Survival in Swine

Circulation ◽  
2020 ◽  
Vol 142 (Suppl_4) ◽  
Author(s):  
Matt Oberdier ◽  
Jing Li ◽  
Dan Ambinder ◽  
Xiangdong Zhu ◽  
Sarah Fink ◽  
...  
Keyword(s):  
Cardiac Arrest ◽  
Therapeutic Hypothermia ◽  
Venous Blood ◽  
Plasma Concentrations ◽  
Sudden Cardiac Arrest ◽  
The United States ◽  
Rapid Onset ◽  
Spontaneous Circulation ◽  
Control Group ◽  
Swine Model

Background: Out-of-hospital sudden cardiac arrest is a leading cause of death in the United States, affecting over 350,000 people per year with an overall survival rate around 10%. CPR, defibrillation, and therapeutic hypothermia are common resuscitation strategies, but hypothermia is difficult to implement timely to achieve survival benefit. A cell-permeable peptide TAT-PHLPP9c has been shown to alter metabolic pathways similar to hypothermia, and decreases the release of two biomarkers, taurine and glutamate, during the high osmotic stress of heart stunning and brain injury in a mouse arrest model. Hypothesis: TAT-PHLPP9c, given during CPR, enhances 24-hour survival in a swine ventricular fibrillation (VF) model. Methods: In 14 (8 controls and 6 treated) sedated, intubated, and mechanically ventilated swine, after 5 min of VF, ACLS with vest CPR and periodic defibrillations was performed. Venous blood samples were collected at baseline, after 2 min of CPR, and at 2 and 30 min after return of spontaneous circulation (ROSC). The animals were survived up to 24 hrs and plasma samples were analyzed for glutamate and taurine in 2 controls and 1 animal given peptide. Results: Three of the control animals had ROSC, but none survived for 24 hrs, while 4 of 6 treated animals achieved neurologically intact survival at 24 hrs (p < 0.02). Compared to baseline, both taurine and glutamate plasma concentrations increased in the control group, but the increase was reduced substantially by the peptide treatment at 30 min after ROSC (Figure). Conclusion: The use of the cooling mimicking peptide TAT-PHLPP9c administered during CPR significantly improved 24-hour survival in this swine model of cardiac arrest. It reduced the increase of cerebral and myocardial metabolic biomarkers, which encourages utilizing a strategy of cell-permeable peptides for intravenous administration for more rapid onset of hypothermia-like salutary effects than are possible with current CPR cooling devices.

scholarly journals Featured Article: Pyruvate preserves antiglycation defenses in porcine brain after cardiac arrest

2017 ◽  
Vol 242 (10) ◽  
pp. 1095-1103 ◽  
Author(s):  
Gary F Scott ◽  
Anh Q Nguyen ◽  
Brandon H Cherry ◽  
Roger A Hollrah ◽  
Isabella Salinas ◽  
...  
Keyword(s):  
Cardiac Arrest ◽  
Glutathione Reductase ◽  
Ischemia Reperfusion ◽  
Protein Glycation ◽  
Carbonyl Stress ◽  
Swine Model ◽  
Glyoxalase 1 ◽  
Cardiocerebral Resuscitation ◽  
The Impact ◽  
The Brain

Cardiac arrest (CA) and cardiocerebral resuscitation (CCR)-induced ischemia–reperfusion imposes oxidative and carbonyl stress that injures the brain. The ischemic shift to anaerobic glycolysis, combined with oxyradical inactivation of glyceraldehyde 3-phosphate dehydrogenase (GAPDH), provokes excessive formation of the powerful glycating agent, methylglyoxal. The glyoxalase (GLO) system, comprising the enzymes glyoxalase 1 (GLO1) and GLO2, utilizes reduced glutathione (GSH) supplied by glutathione reductase (GR) to detoxify methylglyoxal resulting in reduced protein glycation. Pyruvate, a natural antioxidant that augments GSH redox status, could sustain the GLO system in the face of ischemia–reperfusion. This study assessed the impact of CA-CCR on the cerebral GLO system and pyruvate’s ability to preserve this neuroprotective system following CA. Domestic swine were subjected to 10 min CA, 4 min closed-chest CCR, defibrillation and 4 h recovery, or to a non-CA sham protocol. Sodium pyruvate or NaCl control was infused (0.1 mmol/kg/min, intravenous) throughout CCR and the first 60 min recovery. Protein glycation, GLO1 content, and activities of GLO1, GR, and GAPDH were analyzed in frontal cortex biopsied at 4 h recovery. CA-CCR produced marked protein glycation which was attenuated by pyruvate treatment. GLO1, GR, and GAPDH activities fell by 86, 55, and 30%, respectively, after CA-CCR with NaCl infusion. Pyruvate prevented inactivation of all three enzymes. CA-CCR sharply lowered GLO1 monomer content with commensurate formation of higher molecular weight immunoreactivity; pyruvate preserved GLO1 monomers. Thus, ischemia–reperfusion imposed by CA-CCR disabled the brain’s antiglycation defenses. Pyruvate preserved these enzyme systems that protect the brain from glycation stress. Impact statement Recent studies have demonstrated a pivotal role of protein glycation in brain injury. Methylglyoxal, a by-product of glycolysis and a powerful glycating agent in brain, is detoxified by the glutathione-catalyzed glyoxalase (GLO) system, but the impact of cardiac arrest (CA) and cardiocerebral resuscitation (CCR) on the brain’s antiglycation defenses is unknown. This study in a swine model of CA and CCR demonstrated for the first time that the intense cerebral ischemia–reperfusion imposed by CA-resuscitation disabled glyoxalase-1 and glutathione reductase (GR), the source of glutathione for methylglyoxal detoxification. Moreover, intravenous administration of pyruvate, a redox-active intermediary metabolite and antioxidant in brain, prevented inactivation of glyoxalase-1 and GR and blunted protein glycation in cerebral cortex. These findings in a large mammal are first evidence of GLO inactivation and the resultant cerebral protein glycation after CA-resuscitation, and identify novel actions of pyruvate to minimize protein glycation in postischemic brain.

P1230Impact of regulated junctophilin-2 clustering at axial tubule junctions on atrial excitation-contraction coupling and therapeutic implications

2019 ◽  
Vol 40 (Supplement_1) ◽  
Author(s):  
S Brandenburg ◽  
J Pawlowitz ◽  
B Eikenbusch ◽  
T Kohl ◽  
S Sossalla ◽  
...  
Keyword(s):  
Left Atrial ◽  
De Novo ◽  
Electron Tomography ◽  
Pressure Overload ◽  
Aortic Pressure ◽  
Subcellular Localisation ◽  
Loss Of Function ◽  
Therapeutic Implications ◽  
Ec Coupling ◽  
The Impact

Abstract Objectives Atrial dysfunction is highly prevalent and known to significantly aggravate heart failure. While rapid excitation-contraction (EC) coupling depends on axial tubule junctions in atrial myocytes (AMs), the mechanisms leading to atrial loss-of-function remain unclear. Junctophilin-2 (JP2), a tail-anchored protein of the sarcoplasmic reticulum, stabilizes the integrity of ventricular Ca2+ release units, which is disrupted in ventricular myocytes by reduced JP2 expression or proteolysis. Here we aim to characterize the abundance and subcellular localisation of JP2 in AMs, to assess the impact of decreased JP2 expression on atrial remodelling, and to investigate the potential to correct JP2 expression and atrial dysfunction. Results We identified 5-fold lower JP2 levels in atrial compared to ventricular tissue in mouse and human hearts by SDS-PAGE. Surprisingly, in AMs, this resulted in subcellular expression of large JP2 clusters at axial tubule junctions together with highly phosphorylated ryanodine receptor (RyR2) channels visualized by STED superresolution microscopy. Importantly, left atrial hypertrophy induced by aortic pressure overload led to an additional strong decrease in JP2 expression compared to sham control, disrupted junctional RyR2 clustering and EC-coupling. This loss-of-function mechanism was confirmed by conditional shRNA-mediated JP2 knockdown. Quantitative image analysis after atrial JP2 knockdown showed a 50% decrease in area overlap between RyR2 and JP2 in AMs (JP2 knockdown 0.03±0.003 μm2 vs. control 0.06±0.004 μm2, p<0.001), and a ∼2-fold increased Ca2+ spark frequency, consistent with decreased left atrial fractional shortening (JP2 knockdown 12.9±0.8% vs. control 16.5±0.9%, p<0.01). Whereas atrial-ventricular dysfunction due to aortic pressure overload resulted in 40% mortality, additional JP2 knockdown exacerbated mortality to 100% (n: 10 control vs. 9 JP2 knockdown mice). In contrast, transgenic JP2 overexpressor mice showed greatly improved atrial contractility without mortality after induced aortic pressure overload (n: 21 control vs. 16 JP2 overexpressor mice). JP2-OE not only augmented atrial RyR2-clustering, but induced the de-novo biogenesis of large poly-adic junctional membrane complexes, which were resolved by STED microscopy via high-resolution cholesterol-based membrane staining in live AMs and electron tomography. Conclusions Nanoscale imaging identifies a new subcellular mechanism of significantly limited atrial JP2 protein expression in large clusters at axial tubule junctions. In atrial hypertrophy, JP2 is further decreased with junctional RyR2 cluster disruption leading to impaired Ca2+ release and decreased contractility. Importantly, JP2 overexpression effectively protected from atrial dysfunction, providing a novel therapeutic rationale for atrial cardiomyopathies.

scholarly journals Brain monitoring using near-infrared spectroscopy to predict outcome after cardiac arrest: a novel phenotype in a rat model of cardiac arrest

2021 ◽  
Vol 9 (1) ◽  
Author(s):  
Ryosuke Takegawa ◽  
Kei Hayashida ◽  
Rishabh Choudhary ◽  
Daniel M. Rolston ◽  
Lance B. Becker
Keyword(s):  
Cardiac Arrest ◽  
Infrared Spectroscopy ◽  
Brain Injury ◽  
Near Infrared Spectroscopy ◽  
Near Infrared ◽  
Cerebral Oximetry ◽  
Neurological Outcomes ◽  
Non Invasive ◽  
Real Time Measurement ◽  
Ca Model

AbstractImproving neurological outcomes after cardiac arrest (CA) is the most important patient-oriented outcome for CA research. Near-infrared spectroscopy (NIRS) enables a non-invasive, real-time measurement of regional cerebral oxygen saturation. Here, we demonstrate a novel, non-invasive measurement using NIRS, termed modified cerebral oximetry index (mCOx), to distinguish the severity of brain injury after CA. We aimed to test the feasibility of this method to predict neurological outcome after asphyxial CA in rats. Our results suggest that mCOx is feasible shortly after resuscitation and can provide a surrogate measure for the severity of brain injury in a rat asphyxia CA model.

scholarly journals POCUS in cardiac arrest and its therapeutic implications – a case report

2021 ◽  
Vol 21 (84) ◽  
pp. e67-e69
Author(s):  
Wei Yang Lim ◽  
◽  
Kay Choong See ◽  
Keyword(s):  
Cardiac Arrest ◽  
Case Report ◽  
Critical Care Unit ◽  
Point Of Care ◽  
Definitive Treatment ◽  
Point Of Care Ultrasound ◽  
Prognostic Role ◽  
Therapeutic Implications ◽  
The Impact

Point of Care Ultrasound is an increasingly popular modality in the emergency department as well as in the critical care unit. Its applications are varied, centered on its role in diagnosis, thereby minimizing the time taken for the appropriate diagnosis to be made and hence incorporate definitive treatment. There are currently no international guidelines published with regards for point of care ultrasound in the context of cardiac arrest. We propose to delineate the impact of the role of point of care ultrasound in a patient with cardiac arrest, in the evaluation of the cause, its prognostic role, as well as possible implications for therapies based on a case report.

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