Arrest Model Research Articles

Abstract 197: Establishing a Novel Pulse Wave Velocity-Guided Mouse Model of Cardiac Arrest With Different Durations

Background: Neurological and cardiovascular injuries are the leading causes of death following cardiac arrest (CA). Few rodent models recapitulate these post-resuscitation symptoms. Aims: To develop extended ischemic CA models under Pulse Wave Velocity ( PWV) guidance with consistent post-CA brain injury (PCABI) and coronary dysfunction as potential therapeutic targets and mechanical studies. Methods: Forty-eight mice were randomized into four experimental groups (control, 8-, 12-, and 16-min CA). Potassium chloride (KCL) was intravenously injected, resulting in immediate asystole. Mice were resuscitated with an injection of epinephrine and manual chest compressions. PWV was monitored for the left carotid artery velocity and coronary flow reserve (CFR). Resuscitability, synaptic density in the hippocampal CA1 region, blood-brain barrier (BBB), and neurologic deficit scores (NDS) were also evaluated. Results: The PWV could monitor rapid asystole after KCL injection, improve cardiopulmonary resuscitation (CPR) success rates, and avoid the pre-matured end of resuscitation. Compared to the standard control, mice with 8-min CA had preserved CFR, mild loss of synaptic density (p>0.05), mild hypothermal, and a normal electrocardiogram. They maintained BBB integrity with no significant change to neurologic function. Compared with a 92% CPR success rate in 8 min-CA mice, 12 min-CA mice had 83%, and 16 min-CA mice had 58% resuscitability. Twelve min-CA mice had significantly impaired CFR at 24 hours and high lethality (40%, P<0.05) within the first three days; 16 min-CA mice worsened (33% survival rate, p<0.01). The 24 hrs electron microscope showed that CA-induced synaptic vesicle densities were ischemic time-dependent [350±60 (control) vs. 289±64 (8 min CA) vs. 269±34 (12 min CA) vs. 181±41/field (16 min CA)], consistent with NDS. The cerebrum and hippocampus were the most valuable regions, indicated by Evans blue evaluation at 48 hrs after CA. Conclusions: We established elongated PWV-guided CA models as with successful CPR, post-CA neurological deficits, leaky BBB, loss of synaptic density, coronary endothelial dysfunction, and even death in mice, which closely recapitulated the post-resuscitation symptoms in survived patients after CPR.

Abstract 316: Reperfusion With Mild versus Moderate Hypothermia in a Swine Model of Extracorporeal Cardiopulmonary Resuscitation

Background: Targeted temperature management (TTM) at lower temperatures has shown variable neuroprotective benefits in clinical trials of cardiac arrest. We hypothesized that moderate hypothermia at the time of VA-ECMO reperfusion followed by early rewarming would reduce brain injury in a swine model of refractory VF, compared to mild hypothermia. Methods: Fourteen female pigs had electrically induced VF and conventional CPR for 30 minutes. Animals were cannulated to VA-ECMO and randomized to TTM to 34°C for 4 hours (mild hypothermia, n=7) or 24°C for 1 hour followed by early rewarming to 34°C over 3 hours (moderate hypothermia, n=7). Cooling was initiated upon ECMO reperfusion by circulating ice water through the oxygenator. Brain temperature and cerebral and systemic hemodynamics were continuously monitored. After four hours of post-arrest and ECMO care, brain tissue was obtained for examination. Groups were compared using paired t- and Wilcoxon rank sum tests. Results: The mean time to target brain temperature was 5 and 35 minutes in the mild and moderate groups, respectively (Panel, A). CPR hemodynamics were similar. Carotid blood flow (CBF) was higher in moderate hypothermia animals (79.0±1.56 vs 60.7±1.86% pre-arrest baseline, P <0.001) throughout the post-arrest period. There were no differences in ECMO flow, mean arterial pressure, vasopressor/fluid requirement, bleeding, or thromboelastography. No significant difference in histologic damage score was observed between groups (10.5 [7, 11.8] vs 13 [9, 20], with 24°C vs 34°C respectively P =0.25; Panel, B). Immunohistochemistry markers for white matter and neuronal injury also did not significantly diverge. Conclusion: In a swine model of refractory cardiac arrest treated with ECPR, moderate hypothermia initiated upon reperfusion followed by early rewarming did not appear to be neuroprotective. Histological brain injury at 4 hours post-resuscitation was not affected by the degree of hypothermia.

Abstract 321: Manual vs Automated Ventilation During Automated Head-Up Cardiopulmonary Resuscitation in a Porcine Model

Background: The efficacy of mechanical ventilation during CPR with the combination of active compression-decompression, an impedance threshold device, and head-up positioning, collectively termed automated head-up (AHUP)-CPR, is unknown. Hypothesis: Hemodynamic and ventilatory parameters will be similar with manual bag ventilation (MBV) versus automated bag ventilation (ABV) during AHUP-CPR in a porcine model of cardiac arrest. Aim: Assess the proof-of-concept that ABV is safe and effective during AHUP-CPR. Methods: Nine male and female swine (~40 kg) were anesthetized and ventilated. VF was induced and left untreated for 8 min. AHUP-CPR was performed at 105 compressions/min for 7 min using MBV, followed by 6 min using an automated mechanical bag compressor to deliver 10ml/kg of tidal volume (TV) over 1 sec at 10 breaths/min. Pigs were randomized during ABV to a synchronized (Sync) breath delivered at the start of decompression or an asynchronous (Async) breath. Cerebral perfusion pressure, coronary perfusion pressure, end-tidal CO2, intracranial pressure, esophageal intrathoracic pressure, peak airway pressure (PAP), inspiratory and expiratory TVs as well as arterial blood gases were continuously measured. Values (mean ± SD) were compared by paired and unpaired student’s t-tests with a Bonferroni correction. Results: Parameters during the last minute of MBV and ABV are summarized in the table. No significant differences were observed in hemodynamic and ventilatory parameters, except for PAP and pO2 values which were significantly lower with MBV. No significant differences were also observed between the Sync and Async ABV modes. Conclusion: Manual and mechanical ventilation resulted in overall similar physiological effects. The clinical relevance of the observed significant differences in PAP and pO2 is unclear. Additional studies are warranted to further assess the safety and effectiveness of mechanical ventilation during AHUP-CPR.

Abstract 318: Glibenclamide May Have a Neuroprotective and Cardioprotective Role Beyond Cerebral Edema in an Asphyxial Model of Cardiac Arrest

Background: Cardiac arrest (CA) is a leading cause of mortality and long-term disability. There are no therapeutics approved for neuro- and cardio-protection. Novel therapeutics are urgently needed to improve patient outcomes. Glibenclamide is a second-generation sulfonylurea drug and inhibitor of SUR1-TRPM4. Little is known about its role in cardioprotection and synaptic density. Aims: To evaluate the effect of glibenclamide on coronary flow reserve (CFR), blood-brain barrier (BBB) permeability, and synaptic density in an asphyxial mouse model of CA. Methods: We used an asphyxial mouse model of CA; potassium chloride was injected into the right internal jugular vein, resulting in asystole. Chest compressions and epinephrine were administered following 12 minutes of no-flow time. Successfully resuscitated mice (n=24) were randomized to receive intravenous glibenclamide or vehicle; the glibenclamide group received a loading dose of 10 μg/kg immediately upon return of spontaneous circulation followed by 1.6 μg every 12 hours up to day 3. Pulse Doppler Velocity (PWV) was used to monitor the CFR and left carotid artery velocity. Synaptic density was quantified with ex vivo autoradiographs after injection of 18 F-SynVesT-2 in the brain (3, 24, and 72 hrs). Evans blue staining and general neurologic deficit scores were assessed 24 hours post-resuscitation. Results: Treatment with glibenclamide resulted in an increase in CFR (1.37±0.11 vs. 1.17±0.06, p=0.01) and carotid peak velocity (61.38±12.81 cm/s vs. 46.83±6.3 cm/s, p<0.05). Whole brain synaptic density was increased in the mice treated with glibenclamide, suggesting a reduction in synaptic density loss. BBB disruption in the cerebrum was significantly lower in Glibenclamide treated mice (0.00022±0.000014/mg vs. 0.000471±0.000088/mg, p<0.01). Mice treated with Glibenclamide had lower neurologic deficit scores (1.83±2.89 vs 4.75±3.84, p<0.05). Conclusions: Glibenclamide given immediately following the return of spontaneous circulation improved CFR, decreased BBB disruption, reduced synaptic density loss, and improved neurologic deficit scores, suggesting both cardio- and neuro-protective effects.

Cerebral hemodynamic effects of head-up CPR in a porcine model

AimTo assess the hemodynamic effects of head elevation on cerebral perfusion during cardiopulmonary resuscitation (CPR) in a porcine model of cardiac arrest. MethodsVF was induced in eight 65 kg pigs that were treated with CPR after five minutes of no flow. Mean arterial pressure (MAP) was measured at the descending thoracic aorta. Internal carotid artery blood flow (CBF) was measured with an ultrasound probe. Cerebral perfusion pressure (CerPP) was calculated in two ways (CerPPICAP and CerPPreported) using the same intracranial pressure (ICP) measurement. CePPreported was calculated as MAP-ICP. CerPPICAP was calculated by using intracranial arterial pressure (ICAP) – ICP. The animals were switched between head up (HUP) and supine (SUP) CPR every five minutes for a total of twenty minutes of resuscitation. ResultsMAP and coronary perfusion pressure measurements were similar in both CPR positions (p = 0.36 and p = 0.1, respectively). ICP was significantly lower in the HUP CPR group (14.7 ± 1 mm Hg vs 26.9 ± 1 mm Hg, p < 0.001) as was ICAP (30.1 ± 2 mm Hg vs 42.6 ± 1 mmHg, p < 0.001). The proportional decrease in ICP and ICAP resulted in similar CerPPICAP comparing HUP and SUPCPR (p = 0.7). CBF was significantly lower during HUPCPR when compared to SUPCPR (58.5 ± 3 ml/min vs 78 ± 4 ml/min, p < 0.001). A higher CerPPreported was found during the HUP compared to SUP-CPR, when MAP was used (36.6 ± 2 mm Hg vs 23 ± 2 mm Hg, p < 0.001) without correcting for the hydrostatic pressure drop. ConclusionHUP did not affect cerebral perfusion pressure and it significantly decreased internal carotid blood flow.

Methylene blue as an adjuvant during cardiopulmonary resuscitation: an experimental study in rats

IntroductionMethylene Blue (MB) has been shown to attenuate oxidative, inflammatory, myocardial, and neurological lesions during ischemia-reperfusion and has great potential during cardiac arrest. This study aimed to determine the effects of MB combined with epinephrine during cardiac arrest on myocardial and cerebral lesions. MethodThirty-eight male Wistar rats were randomly assigned to four groups: the sham group (SH, n = 5), and three groups subjected to cardiac arrest (n = 11/group) and treated with EPI 20 µg.kg−1 (EPI), EPI 20 µg.kg−1 + MB 2 mg.kg−1 (EPI + MB), or saline 0.9% 0.2 ml (CTL). Ventricular fibrillation was induced by direct electrical stimulation in the right ventricle for 3 minutes, and anoxia was maintained for 5 minutes. Cardiopulmonary Resuscitation (CPR) consisted of medications, ventilation, chest compressions, and defibrillation. After returning to spontaneous circulation, animals were observed for four hours. Blood gas, troponin, oxidative stress, histology, and TUNEL staining measurements were analyzed. Groups were compared using generalized estimating equations. ResultsNo differences in the Returning of Spontaneous Circulation (ROSC) rate were observed among the groups (EPI: 63%, EPI + MB: 45%, CTL: 40%, p = 0.672). The mean arterial pressure immediately after ROSC was higher in the EPI+MB group than in the CTRL group (CTL: 30.5 [5.8], EPI: 63 [25.5], EPI+MB: 123 [31] mmHg, p = 0.007). Serum troponin levels were high in the CTL group (CTL: 130.1 [333.8], EPI: 3.70 [36.0], EPI + MB: 43.7 [116.31] ng/mL, p < 0.05). ConclusionThe coadministration of MB and epinephrine failed to yield enhancements in cardiac or brain lesions in a rodent model of cardiac arrest.

Effect of no-flow period on the vasopressor effect of initial epinephrine administration in cardiac arrest

ObjectivesWhether a longer no-flow (NF) interval affects the magnitude of response to epinephrine in the resuscitation has not been well studied. Therefore, this study aimed to evaluate the effect of NF interval on the vasopressor effect of initial epinephrine administration in a porcine model. MethodsWe enrolled 20 pigs from two randomized porcine experimental studies using a ventricular fibrillation (VF) cardiac arrest model. The first experiment subjects were resuscitated after 4 min of NF (Short NF group), followed by three cycles (6 min) of chest compression using a mechanical cardiopulmonary resuscitation device before epinephrine administration. Second experiment subjects received 6 min of NF (Long NF group), two cycles (4 min) of chest compressions, and administration of epinephrine. Defibrillation for VF was delivered 8 and 10 min after VF induction in the Short NF and Long NF groups, respectively. The mean arterial pressure (MAP) and cerebral perfusion pressure (CePP) in the 2-min resuscitation period after epinephrine administration were compared between the study groups using the Wilcoxon rank-sum test. The mean differences in the parameters between phases were also compared. ResultsSeven pigs in the Short NF group and 13 pigs in the Long NF group were included in the analysis. All 2-min resuscitation phases from 6 to 16 min after VF induction were compared between the study groups. The Short NF group showed higher MAP and CePP in all phases (p < 0.01). Change of mean MAP after the epinephrine administration was significantly different between the study groups: mean difference (95% confidence interval) of 16.6 (15.8–17.4) mmHg in the Short NF group and 4.2 (3.9–4.5) mmHg in the Long NF group. ConclusionIn the porcine VF cardiac arrest model, 6 min of NF before resuscitation may affect the vasopressor effect of the initial epinephrine administered compared to 4 min of NF. A short NF may play a role in maximizing the effect of epinephrine in advanced cardiovascular life support.

A quantitative evaluation of aerosol generation during cardiopulmonary resuscitation.

It is unclear if cardiopulmonary resuscitation is an aerosol-generating procedure and whether this poses a risk of airborne disease transmission to healthcare workers and bystanders. Use of airborne transmission precautions during cardiopulmonary resuscitation may confer rescuer protection but risks patient harm due to delays in commencing treatment. To quantify the risk of respiratory aerosol generation during cardiopulmonary resuscitation in humans, we conducted an aerosol monitoring study during out-of-hospital cardiac arrests. Exhaled aerosol was recorded using an optical particle sizer spectrometer connected to the breathing system. Aerosol produced during resuscitation was compared with that produced by control participants under general anaesthesia ventilated with an equivalent respiratory pattern tocardiopulmonary resuscitation. A porcine cardiac arrest model was used to determine the independent contributions of ventilatory breaths, chest compressions and external cardiac defibrillation to aerosol generation. Time-series analysis of participants with cardiac arrest (n = 18) demonstrated a repeating waveform of respiratory aerosol that mapped to specific components of resuscitation. Very high peak aerosol concentrations were generated during ventilation of participants with cardiac arrest with median (IQR [range]) 17,926 (5546-59,209 [1523-242,648]) particles.l-1 , which were 24-fold greater than in control participants under general anaesthesia (744 (309-2106 [23-9099]) particles.l-1 , p < 0.001, n = 16). A substantial rise in aerosol also occurred with cardiac defibrillation and chest compressions. In a complimentary porcine model of cardiac arrest, aerosol recordings showed a strikingly similar profile to the human data. Time-averaged aerosol concentrations during ventilation were approximately 270-fold higher than before cardiac arrest (19,410 (2307-41,017 [104-136,025]) vs. 72 (41-136 [23-268]) particles.l-1 , p = 0.008). The porcine model also confirmed that both defibrillation and chest compressions generate high concentrations of aerosol independent of, but synergistic with, ventilation. In conclusion, multiple components of cardiopulmonary resuscitation generate high concentrations of respiratory aerosol. We recommend that airborne transmission precautions are warranted in the setting of high-risk pathogens, until the airway is secured with an airway device and breathing system with a filter.

Sodium Bicarbonate and Calcium Chloride for the Treatment of Hyperkalemia-Induced Cardiac Arrest: A Randomized, Blinded, Placebo-Controlled Animal Study.

Current international guidelines recommend administrating calcium chloride and sodium bicarbonate to patients with hyperkalemia-induced cardiac arrest, despite limited evidence. The aim of this study was to evaluate the efficacy of calcium chloride and sodium bicarbonate on return of spontaneous circulation (ROSC) in a pig model of hyperkalemia-induced cardiac arrest. A randomized, blinded, placebo-controlled experimental pig study. Hyperkalemia was induced by continuous infusion of potassium chloride over 45 minutes followed by a bolus. After a no flow period of 7 minutes, pigs first received 2 minutes of basic cardiopulmonary resuscitation and subsequently advanced life support. The first intervention dose was administered after the fifth rhythm analysis, followed by a defibrillation attempt at the sixth rhythm analysis. A second dose of the intervention was administered after the seventh rhythm analysis if ROSC was not achieved. In case of successful resuscitation, pigs received intensive care for 1 hour before termination of the study. University hospital laboratory. Fifty-four female Landrace/Yorkshire/Duroc pigs (38-42 kg). The study used a 2 × 2 factorial design, with calcium chloride (0.1 mmol/kg) and sodium bicarbonate (1 mmol/kg) as the interventions. Fifty-two pigs were included in the study. Sodium bicarbonate significantly increased the number of animals achieving ROSC (24/26 [92%] vs. 13/26 [50%]; odds ratio [OR], 12.0; 95% CI, 2.3-61.5; p = 0.003) and reduced time to ROSC (hazard ratio [HR] 3.6; 95% CI, 1.8-7.5; p < 0.001). There was no effect of calcium chloride on the number of animals achieving ROSC (19/26 [73%] vs. 18/26 [69%]; OR, 1.2; 95% CI, 0.4-4.0; p = 0.76) or time to ROSC (HR, 1.5; 95% CI, 0.8-2.9; p = 0.23). Administration of sodium bicarbonate significantly increased the number of animals achieving ROSC and decreased time to ROSC. There was no effect of calcium chloride on the number of animals achieving ROSC or time to ROSC.

A ventricular fibrillation cardiac arrest model with extracorporeal cardiopulmonary resuscitation in rats: 8 minutes arrest time leads to increased myocardial damage but does not increase neuronal damage compared to 6 minutes.

Extracorporeal cardiopulmonary resuscitation (ECPR) is an emerging strategy in highly selected patients with refractory cardiac arrest (CA). Animal models can help to identify new therapeutic strategies to improve neurological outcome and cardiac function after global ischemia in CA. Aim of the study was to establish a reproducible ECPR rat model of ventricular fibrillation CA (VFCA) that leads to consistent neuronal damage with acceptable long-term survival rates, which can be used for future research. Male Sprague Dawley rats were resuscitated with ECPR from 6 min (n = 15) and 8 min (n = 16) VFCA. Animals surviving for 14 days after return of spontaneous resuscitation (ROSC) were compared with sham operated animals (n = 10); neurological outcome was assessed daily until day 14. In the hippocampal cornu ammonis 1 region viable neurons were counted. Microglia and astrocyte reaction was assessed by Iba1 and GFAP immunohistochemistry, and collagen fibers in the myocardium were detected in Azan staining. QuPath was applied for quantification. Of the 15 rats included in the 6 min CA group, all achieved ROSC (100%) and 10 (67%) survived to 14 days; in the 8 min CA group, 15 (94%) achieved ROSC and 5 (31%) reached the endpoint. All sham animals (n = 10) survived 2 weeks. The quantity of viable neurons was significantly decreased, while the area displaying Iba1 and GFAP positive pixels was significantly increased in the hippocampus across both groups that experienced CA. Interestingly, there was no difference between the two CA groups regarding these changes. The myocardium in the 8 min CA group exhibited significantly more collagen fibers compared to the sham animals, without differences between 6- and 8-min CA groups. However, this significant increase was not observed in the 6 min CA group. Our findings indicate a uniform occurrence of neuronal damage in the hippocampus across both CA groups. However, there was a decrease in survival following an 8-min CA. Consequently, a 6-min duration of CA resulted in predictable neurological damage without significant cardiac damage and ensured adequate survival rates up to 14 days. This appears to offer a reliable model for investigating neuroprotective therapies.

91 Early post-resuscitation heart rate and hemodynamics as predictors of survival with a good neurological outcome in a pig model of cardiac arrest

91 Early post-resuscitation heart rate and hemodynamics as predictors of survival with a good neurological outcome in a pig model of cardiac arrest

13 Therapeutic administration of risperidone attenuates renal oxidative stress following whole-body ischemia and reperfusion injury in a rat model of cardiac arrest

13 Therapeutic administration of risperidone attenuates renal oxidative stress following whole-body ischemia and reperfusion injury in a rat model of cardiac arrest

309 Argon attenuates myocardial injury by modulation of mitochondrial quality control processes in a rat model of cardiac arrest

309 Argon attenuates myocardial injury by modulation of mitochondrial quality control processes in a rat model of cardiac arrest

231 The Impact of Pre-Ventricular Fibrillation Induction Haemodynamics on Resuscitation Success in a Porcine Model of Long Duration Paediatric Cardiac Arrest

231 The Impact of Pre-Ventricular Fibrillation Induction Haemodynamics on Resuscitation Success in a Porcine Model of Long Duration Paediatric Cardiac Arrest

Protection of the endothelium and endothelial glycocalyx by hydrogen against ischaemia-reperfusion injury in a porcine model of cardiac arrest.

Hydrogen is a potent antioxidant agent that can easily be administered by inhalation. The aim of the study was to evaluate whether hydrogen protects the endothelial glycocalyx layer after successful cardiopulmonary resuscitation (CPR). Fourteen anesthetized pigs underwent CPR after induced ventricular fibrillation. During CPR and return of spontaneous circulation, 2% hydrogen gas was administered to seven pigs (hydrogen group) and seven constituted a control group. Biochemistry and sublingual microcirculation were assessed at baseline, during CPR, at the 15th, 30th, 60th, 120th minute. All seven subjects from the hydrogen group and six subjects in the control group were successfully resuscitated after 6-10 minutes. At baseline, there were no statistically significant differences in examined variables. After the CPR, blood pH, base excess, and lactate showed significantly smaller deterioration in the hydrogen group than in the control group. By contrast, plasma syndecan-1 and the measured variables obtained via sublingual microcirculation did not change after the CPR; and were virtually identical between the two groups. In pigs, hydrogen gas inhalation during CPR and post-resuscitation care was associated with less pronounced metabolic acidosis compared to controls. However, we could not find evidence of injury to the endothelium or glycocalyx in any studied groups.

Albumin Infusion Reduces Fluid Loading for Postresuscitation Syndrome in a Pig Model of Refractory Cardiac Arrest Resuscitated With Venoarterial Extra Corporeal Membrane Oxygenation.

Hemodynamic instability in postresuscitation syndrome worsens survival and neurological outcomes. Venoarterial extracorporeal membrane oxygenation (VA ECMO) for refractory cardiac arrest might improve outcomes. Hemodynamical support under VA ECMO relies on norepinephrine and crystalloids. The present work aims to assess the effects of albumin (ALB) infusion in a swine model of ischemic refractory cardiac arrest implanted by VA ECMO. Cardiac arrest was performed in 18 pigs and VA ECMO was initiated after 30 minutes cardiopulmonary resuscitation (CPR). Pigs were randomly assigned to standard care (norepinephrine + crystalloids) versus ALB group (ALB + standard care). Hemodynamical assessments were performed over 6 hours. Severe hypoalbuminemia was observed in the control group and could be reversed with ALB infusion. Total crystalloid load was significantly reduced with ALB infusion (1,000 [1,000-2,278] ml vs. 17,000 [10,000-19,000] ml, ALB versus control group, respectively, p < 0.001). There was no significant impact with regard to lactate clearance (29.16% [12.5-39.32] and 10.09% [6.78-29.36] for control versus ALB groups, respectively, p = 0.185), sublingual capillary microvascular parameters, or cerebral near-infrared spectrometer (NIRS) values. Compared to standard care, ALB infusion was highly effective in reducing fluid loading in a porcine model of postresuscitation syndrome after refractory cardiac arrest treated with VA ECMO.

Percutaneous left ventricular assist devices in refractory cardiac arrest: The role of chest compressions

Recent studies describe an emerging role for percutaneous left ventricular assist devices such as Impella CP® as rescue therapy for refractory cardiac arrest. We hypothesized that the addition of mechanical chest compressions to percutaneous left ventricular assist device assisted CPR would improve hemodynamics by compressing the right ventricle and augmenting pulmonary blood flow and left ventricular filling. We performed a pilot study to test this hypothesis using a swine model of prolonged cardiac arrest. Eight Yorkshire swine were anesthetized, intubated, and instrumented for hemodynamic monitoring. They were subjected to untreated ventricular fibrillation for 5.75 (SD 2.90) minutes followed by mechanical chest compressions for a mean of 20.0 (SD 5.0) minutes before initiation of percutaneous left ventricular assist device. After percutaneous left ventricular assist device initiation, mechanical chest compressions was stopped (n=4) or continued (n=4). Defibrillation was attempted 4, 8 and 12 minutes after initiating percutaneous left ventricular assist device circulatory support. The percutaneous left ventricular assist device+mechanical chest compressions group had significantly higher percutaneous left ventricular assist device flow prior to return of spontaneous heartbeat at four- and twelve-minutes after percutaneous left ventricular assist device initiation, and significantly higher end tidal CO2 at 4-minutes after percutaneous left ventricular assist device initiation, when compared with the percutaneous left ventricular assist device alone group. Carotid artery flow was not significantly different between the two groups. The addition of mechanical chest compressions to percutaneous left ventricular assist device support during cardiac arrest may generate higher percutaneous left ventricular assist device and carotid artery flow prior to return of spontaneous heartbeat compared to percutaneous left ventricular assist device alone. Further studies are needed to determine if this approach improves other hemodynamic parameters or outcomes after prolonged cardiac arrest.

Prediction of Return of Spontaneous Circulation in a Pediatric Swine Model of Cardiac Arrest Using Low-Resolution Multimodal Physiological Waveforms.

Monitoring physiological waveforms, specifically hemodynamic variables (e.g., blood pressure waveforms) and end-tidal CO2 (EtCO2), during pediatric cardiopulmonary resuscitation (CPR) has been demonstrated to improve survival rates and outcomes when compared to standard depth-guided CPR. However, waveform guidance has largely been based on thresholds for single parameters and therefore does not leverage all the information contained in multimodal data. We hypothesize that the combination of multimodal physiological features improves the prediction of the return of spontaneous circulation (ROSC), the clinical indicator of short-term CPR success. We used machine learning algorithms to evaluate features extracted from eight low-resolution (4 samples per minute) physiological waveforms to predict ROSC. The waveforms were acquired from the 2nd to 10th minute of CPR in pediatric swine models of cardiac arrest (N = 89, 8-12 kg). The waveforms were divided into segments with increasing length (both forward and backward) for feature extraction, and machine learning algorithms were trained for ROSC prediction. For the full CPR period (2nd to 10th minute), the area under the receiver operating characteristics curve (AUC) was 0.93 (95% CI: 0.87-0.99) for the multivariate model, 0.70 (0.55-0.85) for EtCO2 and 0.80 (0.67-0.93) for coronary perfusion pressure. The best prediction performances were achieved when the period from the 6th to the 10th minute was included. Poor predictions were observed for some individual waveforms, e.g., right atrial pressure. In conclusion, multimodal waveform features carry relevant information for ROSC prediction. Using multimodal waveform features in CPR guidance has the potential to improve resuscitation success and reduce mortality.

PB1214 Characterization of Dynamic Changes to Fibrinolysis in Porcine Model of Cardiac Arrest

PB1214 Characterization of Dynamic Changes to Fibrinolysis in Porcine Model of Cardiac Arrest

Assessment of the Effects of Sodium Nitroprusside Administered Via Intracranial Subdural Catheters on the Cerebral Blood Flow and Lactate Using Dynamic Susceptibility Contrast Magnetic Resonance Imaging and Proton Magnetic Resonance Spectroscopy in a Pig Cardiac Arrest Model.

Background Cerebral blood flow (CBF) is impaired in the early phase after return of spontaneous circulation. Sodium nitroprusside (SNP) administration via intracranial subdural catheters improves cerebral cortical microcirculation. We determined whether the SNP treatment improves CBF in the subcortical tissue and evaluated the effects of this treatment on cerebral lactate. Methods and Results Sixty minutes after return of spontaneous circulation following 14 minutes of untreated cardiac arrest, 14 minipigs randomly received 4 mg SNP or saline via intracranial subdural catheters. CBF was measured in regions of interest within the cerebrum and thalamus using dynamic susceptibility contrast-magnetic resonance imaging. After return of spontaneous circulation, CBF was expressed as a percentage of the baseline value. In the saline group, the %CBF in the regions of interest within the cerebrum remained at approximately 50% until 3.5 hours after return of spontaneous circulation, whereas %CBF in the thalamic regions of interest recovered to approximately 73% at this time point. The percentages of the baseline values in the cortical gray matter and subcortical white matter were higher in the SNP group (group effect P=0.026 and 0.025, respectively) but not in the thalamus. The cerebral lactate/creatine ratio measured using magnetic resonance spectroscopy increased over time in the saline group but not in the SNP group (group-time interaction P=0.035). The thalamic lactate/creatine ratio was similar in the 2 groups. Conclusions SNP administered via intracranial subdural catheters improved CBF not only in the cortical gray matter but also in the subcortical white matter. The CBF improvement by SNP was accompanied by a decrease in cerebral lactate.