Abstract 203: A Pilot Study of Using Ice Slurry to Rapidly Induce Hypothermia in a Swine Model of Cardiac Arrest

Circulation ◽  
2018 ◽  
Vol 138 (Suppl_2) ◽  
Author(s):  
Yue Shao ◽  
Lynn Bailey ◽  
Yue Wu
Keyword(s):  
Body Weight ◽  
Cardiac Arrest ◽  
Pilot Study ◽  
Body Temperature ◽  
Time Window ◽  
Optimal Time ◽  
Swine Model ◽  
Ice Slurry ◽  
The Brain ◽  
Ice Fraction

Background: Therapeutic Hypothermia has been recommended by AHA to treat Out of Hospital Cardiac Arrest (OHCA) patients. Animal studies shown that the less time to reach target temperature (TT), the better the clinical outcome. Some animal experiments even suggested that there is an optimal time window that within which the TT should be reached for optimal outcome. In this pilot study, we developed a medical device to infuse a novel medical coolant, ice slurry which is a partially frozen saline, into the blood vessel to rapidly cool the brain. We aimed to evaluate the time to cool the brain temperature down to TT, which is 3°C below normal body temperature, in a swine model of OHCA protocol. Methods: Three Yorkshire swine between 40-50 kg were anesthetized. Bilateral temporal craniotomies were performed for placement of thermocouples at a depth of 1.25 cm for recording cortical temperatures. Two additional thermocouples were placed in esophageal and rectal for measuring the body temperature. A 9.5 French catheter was placed in the right femoral vein for ice slurry infusion. Ventricular fibrillation (VF) was induced by the occlusion of left anterior descending artery. After the onset of VF, there was a 3-minute stand-by followed by a 7-minute chest compression. Ice slurry infusion started at 10 minutes after the onset of VF. Ice slurry with a dosage of 50mL/kg body weight (up to 2L) was infused at constant flow rate while chest compression continues. Chest compressions continued throughout the slurry administration and for 3 minutes post infusion. Thermocouple data were recorded every second for offline processing. Results: In swine 1, 1970mL of ice slurry with 13% of ice fraction was infused into a 40kg pig at a flow rate of 120mL/min. The TT was reached at 22 minutes after the start of infusion. In swine 2 and 3, 2000mL of ice slurry with 25% of ice fraction was infused at 150mL/min into pigs with 49.7 kg and 41.7kg body weight, respectively. The TT were reached at 13min and 15min, respectively. Conclusions: Ice slurry infusion rapidly lowered the cortical temperature of young swine model in cardiac arrest. This rapid cooling method may meet the optimal time window suggested by animal experiment for dramatically improve the survival rate and neurologic outcome of OHCA.

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.

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.

Abstract 177: A Multimodal Neuroprotection Strategy Using Ketamine, Melatonin, and Limited Initial Reoxygenation Following Cardiac Arrest Does Not Improve MRI Cytotoxic Injury in a Swine Model: A Pilot Study

Circulation ◽  
2019 ◽  
Vol 140 (Suppl_2) ◽  
Author(s):  
Miriam Peckham ◽  
Adam DeHavenon ◽  
Matthew D Alexander ◽  
Scott McNally ◽  
Jeffrey Anderson ◽  
...  
Keyword(s):  
Cardiac Arrest ◽  
White Matter ◽  
Pilot Study ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Treated Group ◽  
Temperature Management ◽  
Control Group ◽  
Swine Model ◽  
Neuroprotective Strategy

Introduction: Reperfusion/ischemic brain injury following arrest is a major cause of death/disability among patients surviving to admission. Aside from targeted temperature management, no proven neuroprotective strategies exist. Melatonin (anti-epileptic/antioxidant) and ketamine (glutamate inhibitor), along with controlled reintroduction of oxygenated blood have been proposed to reduce secondary injury. Hypothesis: We hypothesized that a combination of above therapies would reduce the ischemic burden measured on MRI following cardiac arrest if administered upon initial reperfusion. Methods: 6 swine underwent isoflurane anesthesia and control MRI (DTI b2000/20 directions, DSC). Swine were randomized to fixed periods of cardiac arrest (2 swine to 20 min and 1 to 30 min in both control and treated groups), and ECMO catheters placed in the distal aorta and right atrium, then ventricular fibrillation induced by a bipolar pacing catheter. Following ischemia, swine were reperfused at 2.8-3.5 L/min with either unblended oxygenated blood in the control group, or 21% oxygenated blood increased to 30% after 4 minutes and then titrated to maintain PaO2 of 80-100 mm Hg, melatonin 5 mg/kg bolus then 5 mg/kg/hr and ketamine 4 mg/kg/hr for 2 hours in the treated group. After 4 min swine were defibrillated until return of heartbeat. Animals were weaned from pump, decannulated, and epinephrine and fluid boluses administered for hemodynamic support, then re-imaged within 2 hours post-resuscitation using same protocol. Whole brain ADC measurements were performed on gray and white matter. Frontal lobe regions of interest drawn for DSC perfusion parameters. Results: Baseline hemodynamic parameters: BP, Heart Rate, End-Tidal CO2, and SpO2 were similar between animals. There was no difference in percent change ADC in gray or white matter between treated and untreated swine (p=0.9), or difference in CBV (p=0.67). CBF showed an upward trend in treated animals (p=0.17). Conclusions: A multimodal neuroprotective strategy of melatonin, ketamine, and controlled reoxygenation failed to demonstrate measurable impact on MRI markers of ischemia-reperfusion injury in this pilot study. The translation of promising neuroprotectants might be triaged using the employed model.

scholarly journals Symptom-based early-stage differentiation between SARS-CoV-2 versus other respiratory tract infections—Upper Silesia pilot study

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Justyna Mika ◽  
Joanna Tobiasz ◽  
Joanna Zyla ◽  
Anna Papiez ◽  
Małgorzata Bach ◽  
...  
Keyword(s):  
Pilot Study ◽  
Body Temperature ◽  
Respiratory Tract ◽  
Older Patients ◽  
Respiratory Tract Infections ◽  
Early Stage ◽  
Patient Groups ◽  
Project Data ◽  
Tract Infections ◽  
Infection Stage

AbstractIn the DECODE project, data were collected from 3,114 surveys filled by symptomatic patients RT-qPCR tested for SARS-CoV-2 in a single university centre in March-September 2020. The population demonstrated balanced sex and age with 759 SARS-CoV-2( +) patients. The most discriminative symptoms in SARS-CoV-2( +) patients at early infection stage were loss of taste/smell (OR = 3.33, p < 0.0001), body temperature above 38℃ (OR = 1.67, p < 0.0001), muscle aches (OR = 1.30, p = 0.0242), headache (OR = 1.27, p = 0.0405), cough (OR = 1.26, p = 0.0477). Dyspnea was more often reported among SARS-CoV-2(-) (OR = 0.55, p < 0.0001). Cough and dyspnea were 3.5 times more frequent among SARS-CoV-2(-) (OR = 0.28, p < 0.0001). Co-occurrence of cough, muscle aches, headache, loss of taste/smell (OR = 4.72, p = 0.0015) appeared significant, although co-occurrence of two symptoms only, cough and loss of smell or taste, means OR = 2.49 (p < 0.0001). Temperature > 38℃ with cough was most frequent in men (20%), while loss of taste/smell with cough in women (17%). For younger people, taste/smell impairment is sufficient to characterise infection, whereas in older patients co-occurrence of fever and cough is necessary. The presented study objectifies the single symptoms and interactions significance in COVID-19 diagnoses and demonstrates diverse symptomatology in patient groups.

Effects of Propofol on Hemodynamic Profile in Adults Receiving Targeted Temperature Management

2021 ◽  
pp. 001857872110323
Author(s):  
W. Anthony Hawkins ◽  
Jennifer Y. Kim ◽  
Susan E. Smith ◽  
Andrea Sikora Newsome ◽  
Ronald G. Hall
Keyword(s):  
Cardiac Arrest ◽  
Body Temperature ◽  
Multivariate Regression ◽  
Primary Outcome ◽  
Targeted Temperature Management ◽  
Temperature Management ◽  
Hemodynamic Changes ◽  
Failure Assessment ◽  
Hemodynamic Profile ◽  
Median Change

Background: Propofol is a key component for the management of sedation and shivering during targeted temperature management (TTM) following cardiac arrest. The cardiac depressant effects of propofol have not been described during TTM and may be especially relevant given the stress to the myocardium following cardiac arrest. The purpose of this study is to describe hemodynamic changes associated with propofol administration during TTM. Methods: This single center, retrospective cohort study evaluated adult patients who received a propofol infusion for at least 30 minutes during TTM. The primary outcome was the change in cardiovascular Sequential Organ Failure Assessment (cvSOFA) score 30 minutes after propofol initiation. Secondary outcomes included change in systolic blood pressure (SBP), mean arterial pressure (MAP), heart rate (HR), and vasopressor requirements (VR) expressed as norepinephrine equivalents at 30, 60, 120, 180, and 240 minutes after propofol initiation. A multivariate regression was performed to assess the influence of propofol and body temperature on MAP, while controlling for vasopressor dose and cardiac arrest hospital prognosis (CAHP) score. Results: The cohort included 40 patients with a median CAHP score of 197. The goal temperature of 33°C was achieved for all patients. The median cvSOFA score was 1 at baseline and 0.5 at 30 minutes, with a non-significant change after propofol initiation ( P = .96). SBP and MAP reductions were the greatest at 60 minutes (17 and 8 mmHg; P < .05 for both). The median change in HR at 120 minutes was −9 beats/minute from baseline. This reduction was sustained through 240 minutes ( P < .05). No change in VR were seen at any time point. In multivariate regression, body temperature was the only characteristic independently associated with changes in MAP (coefficient 4.95, 95% CI 1.6-8.3). Conclusion: Administration of propofol during TTM did not affect cvSOFA score. The reductions in SBP, MAP, and HR did not have a corresponding change in vasopressor requirements and are likely not clinically meaningful. Propofol appears to be a safe choice for sedation in patients receiving targeted temperature management after cardiac arrest.

scholarly journals Non-invasive diffuse optical neuromonitoring during cardiopulmonary resuscitation predicts return of spontaneous circulation

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Tiffany S. Ko ◽  
Constantine D. Mavroudis ◽  
Ryan W. Morgan ◽  
Wesley B. Baker ◽  
Alexandra M. Marquez ◽  
...  
Keyword(s):  
Cardiac Arrest ◽  
Cardiopulmonary Resuscitation ◽  
Hemoglobin Concentration ◽  
Spontaneous Circulation ◽  
Youden Index ◽  
Swine Model ◽  
Return Of Spontaneous Circulation ◽  
Non Invasive ◽  
Tissue Optical Properties ◽  
Tenfold Cross Validation

AbstractNeurologic injury is a leading cause of morbidity and mortality following pediatric cardiac arrest. In this study, we assess the feasibility of quantitative, non-invasive, frequency-domain diffuse optical spectroscopy (FD-DOS) neuromonitoring during cardiopulmonary resuscitation (CPR), and its predictive utility for return of spontaneous circulation (ROSC) in an established pediatric swine model of cardiac arrest. Cerebral tissue optical properties, oxy- and deoxy-hemoglobin concentration ([HbO2], [Hb]), oxygen saturation (StO2) and total hemoglobin concentration (THC) were measured by a FD-DOS probe placed on the forehead in 1-month-old swine (8–11 kg; n = 52) during seven minutes of asphyxiation followed by twenty minutes of CPR. ROSC prediction and time-dependent performance of prediction throughout early CPR (< 10 min), were assessed by the weighted Youden index (Jw, w = 0.1) with tenfold cross-validation. FD-DOS CPR data was successfully acquired in 48/52 animals; 37/48 achieved ROSC. Changes in scattering coefficient (785 nm), [HbO2], StO2 and THC from baseline were significantly different in ROSC versus No-ROSC subjects (p < 0.01) after 10 min of CPR. Change in [HbO2] of + 1.3 µmol/L from 1-min of CPR achieved the highest weighted Youden index (0.96) for ROSC prediction. We demonstrate feasibility of quantitative, non-invasive FD-DOS neuromonitoring, and stable, specific, early ROSC prediction from the third minute of CPR.

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