Swine Model Of Cardiac Arrest Research Articles

Detecting pneumothorax during cardiopulmonary resuscitation: The potential of defibrillator measured transthoracic impedance

IntroductionPneumothorax is a potentially life-treating condition that can represents a complication of cardiopulmonary resuscitation (CPR). An increase in the total amount of air within the thorax may act as an insulator increasing transthoracic impedance (TTI). The aim of this study was to evaluate the effects of pneumothorax on TTI and on resuscitation success in a swine model of cardiac arrest (CA) and CPR. MethodsForty pigs undergoing CA and prolonged CPR, and with a chest CT scan performed after resuscitation were included in the study. Pneumothorax was classified as mild, moderate, or severe whether the space occupied by the gas was <15 %, 15–50 %, or >50 % of the hemithorax. TTI was measured and recorded by the defibrillator before each defibrillation, and the last one was used for the analyses. Rate of return of spontaneous circulation (ROSC) and survival up to 96 h were assessed. ResultsSeven (17%) animals had mild-moderate pneumothorax and 10 (25%) severe pneumothorax. Mean TTI was significantly higher in pigs with pneumothorax compared to those without. The rate of ROSC was significantly lower in pigs with pneumothorax compared to those without (53% vs 83%). TTI increased progressively with the size of pneumothorax (mean TTI: 55 O no pneumothorax, vs 62 O mild-moderate vs 66 O severe pneumothorax). Rib fractures were present in all animals with mild-moderate and severe pneumothorax, and in 91% of those without. The total number of rib fractures was significantly higher in animals with severe pneumothorax compared to those without pneumothorax. ConclusionPneumothorax causes TTI increases which are proportional to the size of the pneumothorax and ultimately reduce resuscitation success. High prevalence of chest skeletal injuries was observed in this study regardless of the presence of pneumothorax with higher amount of rib fractures in animals with severe pneumothorax. TTI measured by defibrillator can be used to detect the presence of pneumothorax during CPR. Future studies should explore this concept of TTI as a diagnostic tool, in order to improve resuscitation outcome in patients with pneumothorax.

Exploratory Feasibility Study of Cerebral Cooling by Transpulmonary Cooling During Cardiac Arrest in a Swine Cardiac Arrest Model

Exploratory Feasibility Study of Cerebral Cooling by Transpulmonary Cooling During Cardiac Arrest in a Swine Cardiac Arrest Model

The Self-Expandable Impella CP (ECP) as a Mechanical Resuscitation Device.

The survival rate of cardiac arrest (CA) can be improved by utilizing percutaneous left ventricular assist devices (pLVADs) instead of conventional chest compressions. However, existing pLVADs require complex fluoroscopy-guided placement along a guidewire and suffer from limited blood flow due to their cross-sectional area. The recently developed self-expandable Impella CP (ECP) pLVAD addresses these limitations by enabling guidewire-free placement and increasing the pump cross-sectional area. This study evaluates the feasibility of resuscitation using the Impella ECP in a swine CA model. Eleven anesthetized pigs (73.8 ± 1.7 kg) underwent electrically induced CA, were left untreated for 5 min and then received pLVAD insertion and activation. Vasopressors were administered and defibrillations were attempted. Five hours after the return of spontaneous circulation (ROSC), the pLVAD was removed, and animals were monitored for an additional hour. Hemodynamics were assessed and myocardial function was evaluated using echocardiography. Successful guidewire-free pLVAD placement was achieved in all animals. Resuscitation was successful in 75% of cases, with 3.5 ± 2.0 defibrillations and 1.8 ± 0.4 mg norepinephrine used per ROSC. Hemodynamics remained stable post-device removal, with no adverse effects or aortic valve damage observed. The Impella ECP facilitated rapid guidewire-free pLVAD placement in fibrillating hearts, enabling successful resuscitation. These findings support a broader clinical adoption of pLVADs, particularly the Impella ECP, for CA.

REMIMAZOLAM IMPROVES THE MARKERS OF POSTRESUSCITATION CEREBRAL INJURY IN A SWINE MODEL OF CARDIAC ARREST.

Introduction: Previous studies have manifested that those sedatives acting on γ-aminobutyric acid A (GABAa) receptor could produce effective brain protection against regional and global ischemic stimulation. The present study was designed to investigate the effect of a novel GABAa receptor agonist, remimazolam postconditioning (RP) on cerebral outcome after global ischemic stimulation induced by cardiac arrest and resuscitation in swine. Methods: A total of 24 swine were used in this study, in which the animals were randomly divided into the following three groups: sham group (n = 6), cardiopulmonary resuscitation (CPR) group (n = 9), and CPR + RP group (n = 9). The experimental model was established by the procedure of 10 min of cardiac arrest and 5 min of CPR. Those resuscitated swine in the CPR + RP group received an intravenous infusion of 2.5 mg/kg of remimazolam within 60 min. Postresuscitation cerebral injury biomarkers and neurological function were evaluated for a total of 24 h. At 24 h after resuscitation, brain cortex was harvested to evaluate the severity of pathologic damage, including tissue inflammation, oxidative stress, apoptosis, and necroptosis. Results: Baseline characteristics and CPR outcomes were not significantly different between the CPR and CPR + RP groups. After resuscitation, significantly greater cerebral injury and neurological dysfunction were observed in the CPR and CPR + RP groups than in the sham group. However, remimazolam postconditioning significantly alleviated cerebral injury and improved neurological dysfunction after resuscitation when compared with the CPR group. At 24 h after resuscitation, tissue inflammation, oxidative stress, and cell apoptosis and necroptosis were significantly increased in the CPR and CPR + RP groups when compared with the sham group. Nevertheless, the severity of pathologic damage mentioned previously were significantly milder in those swine treated with the remimazolam when compared with the CPR group. Conclusions: In a swine model of cardiac arrest and resuscitation, the remimazolam administered after resuscitation significantly improved the markers of postresuscitation cerebral injury and therefore protected the brain against global ischemic stimulation.

A remote-controlled automatic chest compression device capable of moving compression position during CPR: A pilot study in a mannequin and a swine model of cardiac arrest.

Recently, we developed a chest compression device that can move the chest compression position without interruption during CPR and be remotely controlled to minimize rescuer exposure to infectious diseases. The purpose of this study was to compare its performance with conventional mechanical CPR device in a mannequin and a swine model of cardiac arrest. A prototype of a remote-controlled automatic chest compression device (ROSCER) that can change the chest compression position without interruption during CPR was developed, and its performance was compared with LUCAS 3 in a mannequin and a swine model of cardiac arrest. In a swine model of cardiac arrest, 16 male pigs were randomly assigned into the two groups, ROSCER CPR (n = 8) and LUCAS 3 CPR (n = 8), respectively. During 5 minutes of CPR, hemodynamic parameters including aortic pressure, right atrial pressure, coronary perfusion pressure, common carotid blood flow, and end-tidal carbon dioxide partial pressure were measured. In the compression performance test using a mannequin, compression depth, compression time, decompression time, and plateau time were almost equal between ROSCER and LUCAS 3. In a swine model of cardiac arrest, coronary perfusion pressure showed no difference between the two groups (p = 0.409). Systolic aortic pressure and carotid blood flow were higher in the LUCAS 3 group than in the ROSCER group during 5 minutes of CPR (p < 0.001, p = 0.008, respectively). End-tidal CO2 level of the ROSCER group was initially lower than that of the LUCAS 3 group, but was higher over time (p = 0.022). A Kaplan-Meier survival analysis for ROSC also showed no difference between the two groups (p = 0.46). The prototype of a remote-controlled automated chest compression device can move the chest compression position without interruption during CPR. In a mannequin and a swine model of cardiac arrest, the device showed no inferior performance to a conventional mechanical CPR device.

Hemodynamic Effect of Repeated Epinephrine Doses Decreases With Cardiopulmonary Resuscitation Cycle Progression.

Epinephrine is administered to increase coronary perfusion pressure during advanced life support and promote short-term survival. Recent cardiopulmonary resuscitation (CPR) guidelines recommend an epinephrine dosing interval of 3 to 5 minutes during resuscitation; however, scientific evidence supporting this recommendation is lacking. Therefore, we aimed to investigate the hemodynamic effects of repeated epinephrine doses during CPR by monitoring augmented blood pressure after its administration in a swine model of cardiac arrest. A secondary analysis of data from a published study was performed using a swine cardiac arrest model. The epinephrine dose was fixed at 1 mg, and the first dose of epinephrine was administered after no-flow and low-flow times of 2 minutes and 8 minutes, respectively, and subsequently administered every 4 minutes. Four cycles of dosing intervals were defined because a previous study was terminated 26 minutes after the induction of ventricular fibrillation. Augmented blood pressures and corresponding timelines were determined. Augmented blood pressure trends following cycles and the epinephrine effect duration were also monitored. Among the 140 CPR cycles, the augmented blood pressure after epinephrine administration was the highest during the first cycle of CPR and decreased gradually with further cycle repetitions. The epinephrine effect duration did not differ between repeated cycles. The maximum blood pressure was achieved 78 to 97 seconds after epinephrine administration. Hemodynamic augmentation with repeated epinephrine administration during CPR decreased with cycle progression. Further studies are required to develop an epinephrine administration strategy to maintain its hemodynamic effects during prolonged resuscitation.

Abstract 308: Comparison of Cardiopulmonary Resuscitation Performance Between Integrated CPR Device Performing Chest Compression and External Defibrillation versus LUCAS3 With Automated External Defibrillator: A Animal and Manikin-Based Pilot Study

Background: Early chest compression and defibrillation are important components for successful resuscitation. The use of mechanical CPR has increased after the outbreak of COVID-19, and this trend continued in the post-pandemic period. We developed an automatic CPR performing chest compression and external defibrillation simultaneously following current CPR algorithm. Methods: This study was designed as a study to compare the performance of CPR and AED between automatic CPR apparatus (A-CPR) and commercially proven mechanical CPR device (LUCAS3) plus AED (C-CPR) during CPR in swine cardiac arrest model and the study to evaluate feasibility of A-CPR in simulated cardiac arrest model. Results: There were no significant differences in hemodynamic variables between the groups. Time to ECG analysis [38.0 sec in A-CPR, 48.0 sec in C-CPR, p =0.010], time to initial shock advice plus subsequent chest compression [46.0 sec in A-CPR, 57.0 sec in C-CPR, p =0.017], time to first defibrillation [48.5 sec in A-CPR, 65.0 sec in C-CPR, p =0.004], charge to shock interval [3.0 sec in A-CPR, 8.0 sec in C-CPR, p =0.001], and hands-off time [11.0 sec in A-CPR, 22.5 sec in C-CPR, p =0.001] were significantly shorter in A-CPR group than C-CPR group. In the simulation study, the pure chest compression time [101 sec in A-CPR, 110 sec in C-CPR, p&lt; 0.001], hands-off time [75 sec in A-CPR, 94 sec in C-CPR, p&lt; 0.001], time from power-on to first chest compression [55 sec in A-CPR, 82 sec in C-CPR, p&lt; 0.001], time to first shock delivery [40 sec in A-CPR, 51 sec in C-CPR, p= 0.001] were significantly shorter in A-CPR group than C-CPR group, respectively. Chest compression fraction showed a significant higher in A-CPR than C-CPR [57% in A-CPR, 54% in C-CPR, p &lt;0.001]. Conclusions: The A-CPR device demonstrated significant time savings effect than conventional mechanical CPR device and automated external defibrillation device. In addition, A-CPR and C-CPR showed similar hemodynamic effects and resuscitation outcomes in a swine model of 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.

Haemodynamic impact of aortic balloon occlusion combined with percutaneous left ventricular assist device during cardiopulmonary resuscitation in a swine model of cardiac arrest

AimTo investigate the effect of tandem use of transient balloon occlusion of the descending aorta (AO) and percutaneous left ventricular assist device (pl-VAD) during cardiopulmonary resuscitation in a large animal model of prolonged cardiac arrest. MethodsVentricular fibrillation was induced and left untreated for 8 minutes followed by 16 minutes of mechanical CPR (mCPR) in 24 swine, under general anesthesia. Animals were randomized to 3 treatment groups (n = 8 per group): A) pL-VAD (Impella CP®) B) pL-VAD+AO, and C) AO. Impella CP® and the aortic balloon catheter were inserted via the femoral arteries. mCPR was continued during treatment. Defibrillation was attempted 3 times starting at minute 28 and then every 4 minutes. Haemodynamic, cardiac function and blood gas measurements were recorded for up to 4 hours. ResultsCoronary perfusion pressure (CoPP) in the pL-VAD+AO Group increased by a mean (SD) of 29.2(13.94) mmHg compared to an increase of 7.1(12.08) and 7.1(5.95) mmHg for groups pL-VAD and AO respectively (p = 0.02). Similarly, cerebral perfusion pressure (CePP) in pL-VAD+AO increased by a mean (SD) of 23.6 (6.11), mmHg compared with 0.97 (9.07) and 6.9 (7.98) mmHg for the other two groups (p < 0.001). The rate of return of spontaneous heartbeat (ROSHB) was 87.5%, 75%, and 100% for pL-VAD+AO, pL-VAD, and AO. ConclusionCombined AO and pL-VAD improved CPR hemodynamics compared to either intervention alone in this swine model of prolonged cardiac arrest.

A cell-penetrating PHLPP peptide improves cardiac arrest survival in murine and swine models.

Out-of-hospital cardiac arrest is a leading cause of death in the US, with a mortality rate over 90%. Preclinical studies demonstrate that cooling during cardiopulmonary resuscitation (CPR) is highly beneficial, but can be challenging to implement clinically. No medications exist for improving long-term cardiac arrest survival. We have developed a 20-amino acid peptide, TAT-PHLPP9c, that mimics cooling protection by enhancing AKT activation via PH domain leucine-rich repeat phosphatase 1 (PHLPP1) inhibition. Complementary studies were conducted in mouse and swine. C57BL/6 mice were randomized into blinded saline control and peptide-treatment groups. Following a 12-minute asystolic arrest, TAT-PHLPP9c was administered intravenously during CPR and significantly improved the return of spontaneous circulation, mean arterial blood pressure and cerebral blood flow, cardiac and neurological function, and survival (4 hour and 5 day). It inhibited PHLPP-NHERF1 binding, enhanced AKT but not PKC phosphorylation, decreased pyruvate dehydrogenase phosphorylation and sorbitol production, and increased ATP generation in heart and brain. TAT-PHLPP9c treatment also reduced plasma taurine and glutamate concentrations after resuscitation. The protective benefit of TAT-PHLPP9c was validated in a swine cardiac arrest model of ventricular fibrillation. In conclusion, TAT-PHLPP9c may improve neurologically intact cardiac arrest survival without the need for physical cooling.

Left ventricle chest compression improves ETCO2, blood pressure, and cerebral blood velocity in a swine model of cardiac arrest and cardiopulmonary resuscitation

IntroductionDuring cardiopulmonary resuscitation (CPR), high quality chest compressions are critical to organ perfusion, especially the brain. Yet, the optimal location for chest compressions is unclear. It was hypothesized that compared with the standard chest compression (SCC) location, left ventricle chest compressions (LVCCs) would result in greater end-tidal carbon dioxide (ETCO2), blood pressure (BP), and cerebral blood velocity (CBV) during CPR in swine. MethodsFemale Landrace swine (N = 32; 35 ± 2 kg) underwent two mins of untreated asphyxiated cardiac arrest (CA). Thereafter, swine were treated with three 2-min cycles of either SCC or LVCC mechanical basic life support CPR (LUCAS 3). ETCO2 (in-line sampling), BP (arterial catheter line), and CBV (transcranial Doppler) were measured during the pre-CA, untreated-CA, and CPR-treated phases. ResultsETCO2, BP, and CBV were similar between groups at pre- and during untreated-CA (P ≥ 0.188). During CPR, ETCO2 (36 ± 6 versus 24 ± 10 mmHg, P < 0.001), mean arterial BP (MAP; 49 ± 9 versus 37 ± 9 mmHg, P = 0.002), and CBV (11 ± 5 versus 5 ± 2 cm/s, P < 0.001) were significantly greater in the LVCC versus SCC group. Moreover, a greater proportion of animals obtained targets for ETCO2 (ETCO2 ≥ 20 mmHg; 52 % (17/33) versus 100 % (32/32), P < 0.001) and diastolic BP (DBP ≥ 25 mmHg; 82 % (33/40) versus 97 % (48/49), P = 0.020) in the LVCC versus SCC group. ConclusionIndicators of cardiac output, BP, and cerebral perfusion during CPR were greatest in the LVCC group, suggesting the quality of chest compressions during BLS CPR may be improved by performing compressions over the left ventricle compared to the centre of the chest.

Abstract 120: Impact Of Mask Application On Aerosol Generation During Chest Compression And Defibrillation In A Swine Cardiac Arrest Model

Introduction: We previously demonstrated that defibrillation followed by chest compression generates more aerosols than chest compression or no-flow state alone. However, the best strategies to prevent aerosol spread during cardiac arrest (CA) resuscitation remain unknown. We hypothesized that mask applications could reduce aerosol spread during chest compressions and defibrillation in a swine CA model. Methods: To simulate witnessed CA with bystander-initiated CPR, 24 female non-intubated swine (43.8 [2.7] kg) underwent 4 minutes of untreated ventricular fibrillation CA followed by 10 two-minute cycles of mechanical chest compression and defibrillation without ventilation. The animals were randomized to receive no mask, cloth mask, surgical mask, N95 mask, or a sealed nose cone over their snouts during resuscitation (n=5/group except nose cone n=4). The diameter (0.3 - 10 μm) and quantity of particles generated during 45-second intervals of no-flow, chest compression, and after each defibrillation were measured 2 inches anterior to the snout. Results: There were no significant differences between total particles generated during chest compression after defibrillation in unmasked versus masked animals regardless of the mask type, while the nose cone significantly reduced total particles. These findings were consistent across all 10 defibrillations (Fig. 1a) and all particle sizes (Fig. 1b). Furthermore, the minimal pre- and post-defibrillation particles detected outside of the nose cone indicated that the ineffectiveness of masks in preventing aerosol spread during CA resuscitation was likely due to their inadequate fit (Fig. 1c). Conclusion: Mask application did not reduce aerosol spread during defibrillation followed by chest compression in a swine CA model. Our data indicate that mask fit is a critical parameter for reducing aerosol transport and do not support mask application on CA victims during bystander-initiated CPR.

Automated aortic endovascular balloon volume titration prevents re-arrest immediately after return of spontaneous circulation in a swine model of nontraumatic cardiac arrest

ObjectivesEndovascular aortic occlusion as an adjunct to cardiopulmonary resuscitation (CPR) for non-traumatic cardiac arrest is gaining interest. In a recent clinical trial, return of spontaneous circulation (ROSC) was achieved despite prolonged no-flow times. However, 66% of patients re-arrested upon balloon deflation. We aimed to determine if automated titration of endovascular balloon volume following ROSC can augment diastolic blood pressure (DBP) to prevent re-arrest. MethodsTwenty swine were anesthetized and placed into ventricular fibrillation (VF). Following 7 minutes of no-flow VF and 5 minutes of mechanical CPR, animals were subjected to complete aortic occlusion to adjunct CPR. Upon ROSC, the balloon was either deflated steadily over 5 minutes (control) or underwent automated, dynamic adjustments to maintain a DBP of 60 mmHg (Endovascular Variable Aortic Control, EVAC). ResultsROSC was obtained in ten animals (5 EVAC, 5 REBOA). Sixty percent (3/5) of control animals rearrested while none of the EVAC animals rearrested (p = 0.038). Animals in the EVAC group spent a significantly higher proportion of the post-ROSC period with a DBP > 60 mmHg [median (IQR)] [control 79.7 (72.5–86.0)%; EVAC 97.7 (90.8–99.7)%, p = 0.047]. The EVAC group had a statistically significant reduction in arterial lactate concentration [7.98 (7.4–8.16) mmol/L] compared to control [9.93 (8.86–10.45) mmol/L, p = 0.047]. There were no statistical differences between the two groups in the amount of adrenaline (epinephrine) required. ConclusionIn our swine model of cardiac arrest, automated aortic endovascular balloon titration improved DBP and prevented re-arrest in the first 20 minutes after ROSC.

Noninvasive Versus Invasive Brain Temperature Measurement During Targeted Temperature Management: A Preclinical Study in a Swine Cardiac Arrest Model.

We aimed to evaluate correlation and agreement between noninvasive brain temperature (TBN) and invasive brain temperature (TBI) measurement during targeted temperature management (TTM) in a swine cardiac arrest model. Defibrillation attempts were provided after 5 minutes of ventricular fibrillation and 12 minutes of cardiopulmonary resuscitation in five pigs. After return of spontaneous circulation, TTM was provided with induction and maintenance phases with a target temperature of 33°C for 6 hours and a rewarming phase with a rewarming rate of 1°C/h for 4 hours. TBN and TBI were measured using a double sensor method and an intracranial catheter, respectively. Pulmonary artery temperature (TP), esophageal temperature (TE), and rectal temperature (TR) were measured. Primary outcomes were correlation and agreement between TBN and TBI and secondary outcomes were correlation and agreement among TBN and other temperatures. The Pearson correlation coefficient (PCC) between TBN and TBI was 0.95 (p < 0.001) during the whole TTM phases. PCCs between TBN and TBI during the induction, maintenance, and rewarming phases were 0.91 (p < 0.001), 0.88 (p < 0.001), and 0.94 (p < 0.001) and 95% limits of agreement (LoAs) between TBN and TBI were (-0.27°C to 0.78°C), (-0.18°C to 0.54°C), and (-0.93°C to 0.88°C), respectively. Correlation between TBN and TBI during the maintenance phase was higher than correlation between TBN and TE (PCC = 0.74, p < 0.001) or TP (PCC = 0.81, p < 0.001). The 95% LoAs were narrowest between TBN and TP in the induction phase (-0.58 to 0.11), between TBN and TBI in the maintenance phase (-0.54 to 0.18), and between TBN and TR in the rewarming phase (-0.96 to 0.84). Noninvasive brain temperature showed good correlation with invasive brain temperature during TTM in a swine cardiac arrest model. Correlation was highest during the rewarming phase and lowest during the maintenance phase. Agreement between the two measurements was not clinically acceptable.

Alda-1, an Activator of ALDH2, Improves Postresuscitation Cardiac and Neurological Outcomes by Inhibiting Pyroptosis in Swine

Aldehyde dehydrogenase 2 (ALDH2) has been proven to protect the heart and brain against regional ischemia/reperfusion injury, in which the protective role is related to the inhibition of pyroptosis. In the present study, we investigated whether an ALDH2 activator N-(1,3-benzodioxol-5-ylmethyl)-2,6-dichloro-benzamide (Alda-1) would improve postresuscitation cardiac and neurological outcomes in a clinically relevant swine model of cardiac arrest (CA) and resuscitation. The animal model was established by 8min of untreated ventricular fibrillation and then 8min of cardiopulmonary resuscitation (CPR). After restoring spontaneous circulation, the animals were randomly divided to receive either Alda-1 (0.88mg/kg, n = 6) or saline (n = 5). Postresuscitation hemodynamic parameters, cardiac function, and cardiac and cerebral injuries were periodically measured for a total of 24h. At 24h postresuscitation, neurological function was evaluated, and then the animals were sacrificed, and cardiac and cerebral tissue samples were obtained for the measurements of oxidative stress, inflammation and pyroptosis. Consequently, postresuscitation cardiac and neurological dysfunction were significantly improved accompanied with significantly milder cardiac and cerebral injuries in the Alda-1 group compared with the CPR group. In addition, the increase in NLR family pyrin domain-containing 3 inflammasome expression and proinflammatory cytokine production, which indicated the occurrence of inflammatory response, were significantly less in the Alda1 group than in the CPR group. The expression level of gasdermin D used as a protein marker of pyroptosis was also significantly reduced in all resuscitated animals receiving Alda1 treatment. Moreover, the severity of oxidative stress indicated by the changes of 4-hydroxy-2-nonenal and malondialdehyde was significantly decreased in the heart and brain in all animals treated with Alda-1 compared to the CPR group. Thus, Alda-1 mitigated postresuscitation cardiac and neurological dysfunction and injuries possibly by inhibiting oxidative stress-mediated NLRP3 inflammasome activation and pyroptosis in a swine model of CA and resuscitation.

Hemodynamic efficacy of a motor-driven automatic device performing simultaneous sternothoracic cardiopulmonary resuscitation compared to standard cardiopulmonary resuscitation in an animal model of cardiac arrest

The aim of this study was to investigate hemodynamic effects and resuscitation outcomes of simultaneous sternothoracic cardiopulmonary resuscitation (SST-CPR) with a prototype of a motor-driven automatic device, comparing to manual standard CPR (S-CPR), in an animal model of ventricular fibrillation (VF). 20 male pigs were randomized to receive standard CPR (S-CPR group) or CPR with an automatic SST-CPR device (A-CPR group) after 5 minutes of VF. Five minutes of basic life support CPR was performed, followed by 10 minutes of advanced life support CPR. Hemodynamic variables including systolic blood pressure (SBP), diastolic blood pressure (DBP), coronary perfusion pressure (CPP), and end-tidal carbon dioxide tension (ETCO2), and resuscitation outcomes including rate of restoration of spontaneous circulation (ROSC) and 2-hour survival were compared between two groups. Ten animals among the A-CPR group and 8 animals among the S-CPR group were included in the final analysis. SBP was higher in the A-CPR group than in the S-CPR group during CPR (p = 0.046). The DBP, CPP and ETCO2 were not different between two groups (p = 0.412, 0.585, and 0.243, respectively). ROSC rate was 38% in the S-CPR group and 10% in the A-CPR group (p = 0.275). The 2-hour survival rate was 25% in the S-CPR group and 0% in the A-CPR group (p = 0.183). In a swine model of cardiac arrest, CPR with a prototype of a motor-driven automatic SST-CPR device, compared with standard CPR, produced higher systolic blood pressure, but there was no difference in diastolic pressure, coronary perfusion pressure, ROSC rate and 2-hour survival rate.

Mesenchymal Stem Cells Alleviate Post-resuscitation Cardiac and Cerebral Injuries by Inhibiting Cell Pyroptosis and Ferroptosis in a Swine Model of Cardiac Arrest.

Following cardiopulmonary resuscitation (CPR), the ensuing cardiac and cerebral injuries contribute to the poor outcome of cardiac arrest (CA) victims, in which the pathogenetic process is possibly driven by cell pyroptosis and ferroptosis. Mesenchymal stem cells (MSCs) have been shown to be a promising strategy for post-resuscitation cardiac and cerebral protection in rat, but its effectiveness in the clinically relevant swine model and the potential protective mechanism remain unknown. The present study was designed to investigate whether MSCs administration could alleviate post-resuscitation cardiac and cerebral injuries through the inhibition of cell pyroptosis and ferroptosis in swine. Twenty-four male domestic swine were randomly divided into three groups: sham, CPR, and MSC. A dose of 2.5×106/kg of MSCs derived from human embryonic stem cells was intravenously infused at 1.5, and 3 days prior to CA. The animal model was established by 8 min of CA and then 8 min of CPR. After resuscitation, cardiac, cerebral function and injury biomarkers were regularly evaluated for a total of 24 h. At 24 h post-resuscitation, pyroptosis-related proteins (NLRP3, ASC, cleaved caspase-1, GSDMD), proinflammatory cytokines (IL-1β, IL-18), ferroptosis-related proteins (ACSL4, GPX4) and iron deposition in the heart, cortex and hippocampus were measured. Consequently, significantly greater cardiac, cerebral dysfunction and injuries after resuscitation were observed in the CPR and MSC groups compared with the sham group. However, the severity of cardiac and cerebral damage were significantly milder in the MSC group than in the CPR group. In addition, the expression levels of NLRP3, ASC, cleaved caspase-1, GSDMD and ACSL4, the contents of IL-1β and IL-18, and the level of iron deposition were significantly higher while the expression level of GPX4 was significantly lower in the heart, cortex and hippocampus in all resuscitated animals compared with the sham group. Nevertheless, MSCs administration significantly decreased post-resuscitation cardiac, cerebral pyroptosis and ferroptosis compared to the CPR group. Our results showed that the administration of MSCs significantly alleviated post-resuscitation cardiac and cerebral injuries in swine, in which the protective effects were related to the inhibition of cell pyroptosis and ferroptosis.

Automated pupillometry helps monitor the efficacy of cardiopulmonary resuscitation and predict return of spontaneous circulation.

We investigated the effectiveness of automated pupillometry on monitoring cardiopulmonary resuscitation (CPR) and predicting return of spontaneous circulation (ROSC) in a swine model of cardiac arrest (CA). Sixteen male domestic pigs were included. Traditional indices including coronary perfusion pressure (CPP), end-tidal carbon dioxide (ETCO2), regional cerebral tissue oxygen saturation (rSO2) and carotid blood flow (CBF) were continuously monitored throughout the experiment. In addition, the pupillary parameters including the initial pupil size before constriction (Init, maximum diameter), the end pupil size at peak constriction (End, minimum diameter), and percentage of change (%PLR) were measured by an automated quantitative pupillometer at baseline, at 1, 4, 7 min during CA, and at 1, 4, 7 min during CPR. ROSC was achieved in 11/16 animals. The levels of CPP, ETCO2, rSO2 and CBF were significantly greater during CPR in resuscitated animals than those non-resuscitated ones. Init and End were decreased and %PLR was increased during CPR in resuscitated animals when compared with those non-resuscitated ones. There were moderate to good significant correlations between traditional indices and Init, End, and %PLR (|r| = 0.46-0.78, all P < 0.001). Furthermore, comparable performance was also achieved by automated pupillometry (AUCs of Init, End and %PLR were 0.821, 0.873 and 0.821, respectively, all P < 0.05) compared with the traditional indices (AUCs = 0.809-0.946). The automated pupillometry may serve as an effective surrogate method to monitor cardiopulmonary resuscitation efficacy and predict ROSC in a swine model of cardiac arrest.

Chest compression by two-thumb encircling method generates higher carotid artery blood flow in swine infant model of cardiac arrest

ObjectiveTwo-Thumb(TT) technique provides superior quality chest compressions compared with Two-Finger(TF) in an instrumented infant manikin. Whether this translates to differences in blood flow, such as carotid arterial blood flow(CABF), has not been evaluated. We hypothesized that TT-CPR generates higher CABF and Coronary Perfusion Pressure(CPP) compared with TF-CPR in a neonatal swine cardiac arrest model. MethodsTwelve anesthetized & ventilated piglets were randomized after 3min of untreated VF to receive either TT-CPR or TF-CPR by PALS certified rescuers delivering a compression rate of 100/min. The primary outcome, CABF, was measured using an ultrasound transonic flow probe placed on the left carotid artery. CPP was calculated and end-tidal CO2(ETCO2) was measured during CPR. Data(mean±SD) were analyzed and p-value ≤0.05 was considered statistically significant. ResultsCarotid artery blood flow (% of baseline) was higher in TT-CPR (66.2±35.4%) than in the TF-CPR (27.5±10.6%) group, p=0.013. Mean CPP (mm Hg) during three minutes of chest compression for TT-CPR was 12.5±15.8 vs. 6.5±6.7 in TF-CPR, p=0.41 and ETCO2 (mm Hg) was 29.0±7.4 in TT-CPR vs. 20.7±5.8 in TF-CPR group, p=0.055. ConclusionTT-CPR achieved more than twice the CABF compared with TF-CPR in a piglet cardiac arrest model. Although CPP and ETCO2 were higher during TT-CPR, these parameters did not reach statistical significance. This study provides direct evidence of increased blood flow in infant swine using TT-CPR and further supports that TT chest compression is the preferred method for CPR in infants.

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

Neurologic 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.