Cardiopulmonary Resuscitation Model 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.

EFFECT OF ARTESUNATE TREATMENT ON INTESTINAL INJURY AFTER CARDIOPULMONARY RESUSCITATION IN SWINE.

Intestinal injury is often caused by systemic ischemia-reperfusion injury early after cardiac arrest (CA) and resuscitation. Artesunate (Art) has been confirmed to protect vital organs against diverse of regional I/R injury. This study aimed to investigate the effect of Art on intestinal injury after CA and cardiopulmonary resuscitation (CPR) in swine. Twenty-two swine were randomly divided into three groups: sham (n = 6), CA/CPR (n = 8), and CA/CPR + Art (n = 8). The CA/CPR swine model was established by inducing 9 minutes of untreated ventricular fibrillation (VF) followed by 6 minutes of CPR. Five minutes after resuscitation, 4.8 mg/kg of Art was intravenously administered for 2 hours in the CA/CPR + Art group. Intestinal fatty acid-binding protein (iFABP) and diamine oxidase (DAO) concentrations were compared among the three groups before CA and at 1, 2, 4, and 24 hours after resuscitation. At 24 hours post-resuscitation, intestinal zonula occluden-1(ZO-1), occludin, apoptosis, caspase-3/gasdermin E (GSDME)-mediated pyroptosis proteins concentrations, and proinflammatory cytokine concentrations were examined to evaluate intestinal injury. During CPR, spontaneous circulation was achieved in 7 and 6 swine in the CA/CPR and CA/CPR + Art groups, respectively. Serum iFABP and DAO concentrations were significantly higher and intestinal tissue ZO-1 and occludin concentrations were significantly lower in the CA/CPR and CA/CPR + Art groups than in the sham group. However, Art treatment resulted in markedly improved levels of intestinal injury biomarkers compared with those in the CA/CPR group. Additionally, intestinal apoptosis and concentrations of caspase-3/GSDME-mediated pyroptosis proteins and proinflammatory cytokines were significantly higher in the CA/CPR and CA/CPR + Art groups than in the sham group. However, these variables were significantly lower in the CA/CPR + Art group than in the CA/CPR group. Art treatment effectively alleviates post-resuscitation intestinal injury, possibly by inhibiting the caspase-3/GSDME-mediated pyroptosis pathway in a swine CA and CPR model.

Protective role and mechanism of tubastatin A on renal and intestinal injuries after cardiopulmonary resuscitation in swine

To investigate the protective effect and potential mechanism of tubastatin A (TubA), a specific inhibitor of histone deacetylase 6 (HDAC6), on renal and intestinal injuries after cardiopulmonary resuscitation (CPR) in swine. Twenty-five healthy male white swine were divided into Sham group (n = 6), CPR model group (n = 10) and TubA intervention group (n = 9) using a random number table. The porcine model of CPR was reproduced by 9-minute cardiac arrest induced by electrical stimulation via right ventricle followed by 6-minute CPR. The animals in the Sham group only underwent the regular operation including endotracheal intubation, catheterization, and anesthetic monitoring. At 5 minutes after successful resuscitation, a dose of 4.5 mg/kg of TubA was infused via the femoral vein within 1 hour in the TubA intervention group. The same volume of normal saline was infused in the Sham and CPR model groups. Venous samples were collected before modeling and 1, 2, 4, 24 hours after resuscitation, and the levels of serum creatinine (SCr), blood urea nitrogen (BUN), intestinal fatty acid binding protein (I-FABP) and diamine oxidase (DAO) in serum were determined by enzyme-linked immunoadsordent assay (ELISA). At 24 hours after resuscitation, the upper pole of left kidney and terminal ileum were harvested to detect cell apoptosis by TdT-mediated dUTP-biotin nick end labeling (TUNEL), and the expression levels of receptor-interacting protein 3 (RIP3) and mixed lineage kinase domain-like protein (MLKL) were detected by Western blotting. After resuscitation, renal dysfunction and intestinal mucous injury were observed in the CPR model and TubA intervention groups when compared with the Sham group, which was indicated by significantly increased levels of SCr, BUN, I-FABP and DAO in serum. However, the serum levels of SCr and DAO starting 1 hour after resuscitation, the serum levels of BUN starting 2 hours after resuscitation, and the serum levels of I-FABP starting 4 hours after resuscitation were significantly decreased in the TubA intervention group when compared with the CPR model group [1-hour SCr (μmol/L): 87±6 vs. 122±7, 1-hour DAO (kU/L): 8.1±1.2 vs. 10.3±0.8, 2-hour BUN (mmol/L): 12.3±1.2 vs. 14.7±1.3, 4-hour I-FABP (ng/L): 661±39 vs. 751±38, all P < 0.05]. The detection of tissue samples indicated that cell apoptosis and necroptosis in the kidney and intestine at 24 hours after resuscitation were significantly greater in the CPR model and TubA intervention groups when compared with the Sham group, which were indicated by significantly increased apoptotic index and markedly elevated expression levels of RIP3 and MLKL. Nevertheless, compared with the CPR model group, renal and intestinal apoptotic indexes at 24 hours after resuscitation in the TubA intervention group were significantly decreased [renal apoptosis index: (21.4±4.6)% vs. (55.2±9.5)%, intestinal apoptosis index: (21.3±4.5)% vs. (50.9±7.0)%, both P < 0.05], and the expression levels of RIP3 and MLKL were significantly reduced [renal tissue: RIP3 protein (RIP3/GAPDH) was 1.11±0.07 vs. 1.39±0.17, MLKL protein (MLKL/GAPDH) was 1.20±0.14 vs. 1.51±0.26; intestinal tissue: RIP3 protein (RIP3/GAPDH) was 1.24±0.18 vs. 1.69±0.28, MLKL protein (MLKL/GAPDH) was 1.38±0.15 vs. 1.80±0.26, all P < 0.05]. TubA has the protective effect on alleviating post-resuscitation renal dysfunction and intestinal mucous injury, and its mechanism may be related to inhibition of cell apoptosis and necroptosis.

Alda-1 alleviates brain injury after cardiopulmonary resuscitation by regulating acyl-CoA synthetase long-chain family member 4/glutathione peroxidase 4 pathway-mediated ferroptosis in swine

To investigate whether the acetaldehyde dehydrogenase 2 specific activator, Alda-1, can alleviate brain injury after cardiopulmonary resuscitation (CPR) by inhibiting cell ferroptosis mediated by acyl-CoA synthetase long-chain family member 4/glutathione peroxidase 4 (ACSL4/GPx4) pathway in swine. Twenty-two conventional healthy male white swine were divided into Sham group (n = 6), CPR model group (n = 8), and Alda-1 intervention group (CPR+Alda-1 group, n = 8) using a random number table. The swine model of CPR was reproduced by 8 minutes of cardiac arrest induced by ventricular fibrillation through electrical stimulation in the right ventricle followed by 8 minutes of CPR. The Sham group only experienced general preparation. A dose of 0.88 mg/kg of Alda-1 was intravenously injected at 5 minutes after resuscitation in the CPR+Alda-1 group. The same volume of saline was infused in the Sham and CPR model groups. Blood samples were collected from the femoral vein before modeling and 1, 2, 4, 24 hours after resuscitation, and the serum levels of neuron specific enolase (NSE) and S100 β protein were determined by enzyme-linked immunosorbent assay (ELISA). At 24 hours after resuscitation, the status of neurologic function was evaluated by neurological deficit score (NDS). Thereafter, the animals were sacrificed, and brain cortex was harvested to measure iron deposition by Prussian blue staining, malondialdehyde (MDA) and glutathione (GSH) contents by colorimetry, and ACSL4 and GPx4 protein expressions by Western blotting. Compared with the Sham group, the serum levels of NSE and S100β after resuscitation were gradually increased over time, and the NDS score was significantly increased, brain cortical iron deposition and MDA content were significantly increased, GSH content and GPx4 protein expression in brain cortical were significantly decreased, and ACSL4 protein expression was significantly increased at 24 hours after resuscitation in the CPR model and CPR+Alda-1 groups, which indicated that cell ferroptosis occurred in the brain cortex, and the ACSL4/GPx4 pathway participated in this process of cell ferroptosis. Compared with the CPR model group, the serum levels of NSE and S100 β starting 2 hours after resuscitation were significantly decreased in the CPR+Alda-1 group [NSE (μg/L): 24.1±2.4 vs. 28.2±2.1, S100 β (ng/L): 2 279±169 vs. 2 620±241, both P < 0.05]; at 24 hours after resuscitation, the NDS score and brain cortical iron deposition and MDA content were significantly decreased [NDS score: 120±44 vs. 207±68, iron deposition: (2.61±0.36)% vs. (6.31±1.66)%, MDA (μmol/g): 2.93±0.30 vs. 3.68±0.29, all P < 0.05], brain cortical GSH content and GPx4 expression in brain cortical was significantly increased [GSH (mg/g): 4.59±0.63 vs. 3.51±0.56, GPx4 protein (GPx4/GAPDH): 0.54±0.14 vs. 0.21±0.08, both P < 0.05], and ACSL4 protein expression was significantly decreased (ACSL4/GAPDH: 0.46±0.08 vs. 0.85±0.13, P < 0.05), which indicated that Alda-1 might alleviate brain cortical cell ferroptosis through regulating ACSL4/GPx4 pathway. Alda-1 can reduce brain injury after CPR in swine, which may be related to the inhibition of ACSL4/GPx4 pathway mediated ferroptosis.

Ventilation during continuous compressions or at 30:2 compression-to-ventilation ratio results in similar arterial oxygen and carbon dioxide levels in an experimental model of prolonged cardiac arrest

BackgroundIn refractory out-of-hospital cardiac arrest, transportation to hospital with continuous chest compressions (CCC) from a chest compression device and ventilation with 100% oxygen through an advanced airway is common practice. Despite this, many patients are hypoxic and hypercapnic on arrival, possibly related to suboptimal ventilation due to the counterpressure caused by the CCC. We hypothesized that a compression/ventilation ratio of 30:2 would provide better ventilation and gas exchange compared to asynchronous CCC during prolonged experimental cardiopulmonary resuscitation (CPR).MethodsWe randomized 30 anaesthetized domestic swine (weight approximately 50 kg) with electrically induced ventricular fibrillation to the CCC or 30:2 group and bag-valve ventilation with a fraction of inspired oxygen (FiO2) of 100%. We started CPR after a 5-min no-flow period and continued until 40 min from the induction of ventricular fibrillation. Chest compressions were performed with a Stryker Medical LUCAS® 2 mechanical chest compression device. We collected arterial blood gas samples every 5 min during the CPR, measured ventilation distribution during the CPR using electrical impedance tomography (EIT) and analysed post-mortem computed tomography (CT) scans for differences in lung aeration status.ResultsThe median (interquartile range [IQR]) partial pressure of oxygen (PaO2) at 30 min was 110 (52–117) mmHg for the 30:2 group and 70 (40–171) mmHg for the CCC group. The median (IQR) partial pressure of carbon dioxide (PaCO2) at 30 min was 70 (45–85) mmHg for the 30:2 group and 68 (42–84) mmHg for the CCC group. No statistically significant differences between the groups in PaO2 (p = 0.40), PaCO2 (p = 0.79), lactate (p = 0.37), mean arterial pressure (MAP) (p = 0.47) or EtCO2 (p = 0.19) analysed with a linear mixed model were found. We found a deteriorating trend in PaO2, EtCO2 and MAP and rising PaCO2 and lactate levels through the intervention. There were no differences between the groups in the distribution of ventilation in the EIT data or the post-mortem CT findings.ConclusionsThe 30:2 and CCC protocols resulted in similar gas exchange and lung pathology in an experimental prolonged mechanical CPR model.

IVABRADINE-INDUCED HEART RATE REDUCTION INCREASES THE SEVERITY OF POSTRESUSCITATION MYOCARDIAL DYSFUNCTION IN A RAT MODEL OF CARDIOPULMONARY RESUSCITATION.

Aims: A rapid heart rate (HR) that occurs after cardiopulmonary resuscitation (CPR) is a short-term compensatory mechanism preserving cardiac output. However, if of long duration, it is unfavorable for myocardial function postresuscitation because of disrupted balance between myocardial oxygen supply and demand. This raises the assumption that such a sustained fast HR should be regulated. The present study aimed to investigate the follow-on effect of ivabradine (a specific inhibitor of the I f current of the sinoatrial node)-induced HR reduction (HRR) on postresuscitation myocardial function in a rat model of CPR. Methods and results: Six minutes of ventricular fibrillation and 8 min of CPR were performed on Sprague-Dawley rats. All 32 resuscitated animals were then randomized into saline and ivabradine groups, each group having nonsurvival and survival subgroups (n = 8 each). Saline or ivabradine (0.5 mL/kg) was administered at 1 h postresuscitation. Heart rate, myocardial function as expressed by cardiac output, ejection fraction, and myocardial performance index were assessed at baseline and hourly from 1 to 5 h postresuscitation. Heart rate variability was analyzed at baseline and at 1, 3, and 5 h postresuscitation. Serum epinephrine and cardiac troponin I at baseline and at 1, 3, and 5 h postresuscitation in nonsurvival subgroup were measured. Survival duration in the survival subgroup was observed. The baseline HR was approximately 390 beats/min (bpm). After resuscitation, an average increase of Δ ≈ +15 bpm (relative ratio ≈ +3.8%) with a resultant HR of 405 bpm lasting more than 5 h occurred. Ivabradine group achieved a steady HRR of Δ ≈ -30 bpm (relative ratio ≈ -7.4%) as compared with saline group ( P < 0.01). Postresuscitation myocardial function was significantly worse in the ivabradine group (all P < 0.01). Heart rate variability was significantly impaired in the ivabradine group (all P < 0.05). Serum cardiac troponin I and epinephrine concentration were significantly higher in the ivabradine group (all P < ?0.01). Survival duration was significantly shortened in the ivabradine group as compared with the saline group (388 vs. 526 min, P < ?0.01). Conclusions: Ivabradine-induced HRR increases the severity of postresuscitation myocardial dysfunction and shortens survival duration in a rat model of CPR.

Hierarchical first aid training scheme for elementary and middle school students: the practices from the construction of "Baoan Model" social emergency medicine training

To share the implementation experience of hierarchical first aid training scheme for elementary and middle school students in Baoan District of Shenzhen City and evaluate its effect of training. During August 2018 and August 2019, elementary and middle schools students who participated in the first aid training held by emergency rescue training center of Baoan District were enrolled. Baseline information including the number of students, the number of attending tutors, the number of cardiopulmonary resuscitation (CPR) training models, automated external defibrillator (AED) models were recorded. According to hierarchical levels of three age, students received different courses with content from simple to hard: the course of elementary school students was consisting of dialing 120, smart animation on how to identify accidental damage, demonstration of AED and Hemlick techniques, CPR practise (40 minutes). The course of junior high school students was consisted of how to dial 120, how to identify accidental damage and simple disposal, application of CPR and AED, practice CPR and AED and Hemlick techniques (90 minutes). The course of high school students was consisted of how to dial 120, identify accidental damage and right disposal, identification of out-of-hospital cardiac arrest, the key-point of CPR and AED, practice CPR and AED, Hemlick techniques and hemostatic bandage (120 minutes). At the end of course, elementary school students were voluntary for skill assessment; junior high school students only were compulsory for skill assessment in small classes but not required in large classes, just for demonstration; additionally, the whole high school students were compulsory for skill assessment. The characteristics of first aid training students at different levels were collected in order to compare the differences on the usage of CPR training model and AED training model, the distribution of emergency resource, the ratio for passing examination. A total of 12 896 students and 2 086 training instructors took parted in 200 lists of first aid training courses, 8 557 CPR models and 8 493 AED models were used. On average, there are 65.27±5.61 students in each session, and 10.52±10.43 training instructors. There are 43.09±19.06 CPR training models and 42.77±18.61 AED training models. The mean ratio of student to tutor was 6.07±1.47, student to CPR model was 1.54±1.02, and student to AED model was 1.54±1.03. In the end of course, 10 494 students participated in the examination with the participation rate of 81.37%; 10 114 students passed the examination with the passing rate of 96.38%. Hierarchical analysis showed: compare to elementary school students, the average number of junior high school students in every training session significantly increased (cases: 69.94±8.77 vs. 58.69±6.12, P < 0.05), but the average number of high school students in every training session significantly decreased (cases: 57.35±5.79 vs. 58.69±6.12, P < 0.05). The proportion of instructors in junior high school students' training significantly reduced (5.94±1.39 vs. 6.48±2.02, P < 0.05). The examination ratio of junior high school students and high school students was increased significantly [81.07% (6 667/8 224), 100% (2 313/2 313) vs. 64.18% (1 514/2 359), both P < 0.05], but the ratio of passing the examination was significantly reduced [95.47% (6 365/6 667), 96.88% (2 241/2 313) vs. 99.60%(1 508/1 514), both P < 0.01]. This might be related to the low difficulty of elementary school students' assessment and the low proportion of compulsory examination. Hierarchical scheme is feasible for first aid training in elementary and middle school students, the content of course should be desighed from easy to hard. Synchronously, sufficient training instructors and training models should be equipped to ensure the quality.

Adrenaline improves regional cerebral blood flow, cerebral oxygenation and cerebral metabolism during CPR in a porcine cardiac arrest model using low-flow extracorporeal support

BackgroundThe effects of adrenaline on cerebral blood vessels during cardiopulmonary resuscitation (CPR) are not well understood. We developed an extracorporeal CPR model that maintains constant low systemic blood flow while allowing adrenaline-associated effects on cerebral vasculature to be assessed at different mean arterial pressure (MAP) levels independently of the effects on systemic blood flow. MethodsAfter eight minutes of cardiac arrest, low-flow extracorporeal life support (ECLS) (30 ml/kg/min) was started in fourteen pigs. After ten minutes, continuous adrenaline administration was started to achieve MAP values of 40 (n = 7) or 60 mmHg (n = 7). Measurements included intracranial pressure (ICP), cerebral perfusion pressure (CePP), laser-Doppler-derived regional cerebral blood flow (CBF), cerebral regional oxygen saturation (rSO2), brain tissue oxygen tension (PbtO2) and extracellular cerebral metabolites assessed by cerebral microdialysis. ResultsDuring ECLS without adrenaline, regional CBF increased by only 5% (25th to 75th percentile: −3 to 14; p = 0.2642) and PbtO2 by 6% (0–15; p = 0.0073) despite a significant increase in MAP to 28 mmHg (25–30; p < 0.0001) and CePP to 10 mmHg (8–13; p < 0.0001). Accordingly, cerebral microdialysis parameters showed a profound hypoxic-ischemic pattern. Adrenaline administration significantly improved regional CBF to 29 ± 14% (p = 0.0098) and 61 ± 25% (p < 0.001) and PbtO2 to 15 ± 11% and 130 ± 82% (both p < 0.001) of baseline in the MAP 40 mmHg and MAP 60 mmHg groups, respectively. Importantly, MAP of 60 mmHg was associated with metabolic improvement. ConclusionThis study shows that adrenaline administration during constant low systemic blood flow increases CePP, regional CBF, cerebral oxygenation and cerebral metabolism.

Reliability of mechanical ventilation during continuous chest compressions: a crossover study of transport ventilators in a human cadaver model of CPR

BackgroundPrevious studies have stated that hyperventilation often occurs in cardiopulmonary resuscitation (CPR) mainly due to excessive ventilation frequencies, especially when a manual valve bag is used. Transport ventilators may provide mandatory ventilation with predetermined tidal volumes and without the risk of hyperventilation. Nonetheless, interactions between chest compressions and ventilations are likely to occur. We investigated whether transport ventilators can provide adequate alveolar ventilation during continuous chest compression in adult CPR.MethodsA three-period crossover study with three common transport ventilators in a cadaver model of CPR was carried out. The three ventilators ‘MEDUMAT Standard²’, ‘Oxylog 3000 plus’, and ‘Monnal T60’ represent three different interventions, providing volume-controlled continuous mandatory ventilation (VC-CMV) via an endotracheal tube with a tidal volume of 6 mL/kg predicted body weight. Proximal airflow was measured, and the net tidal volume was derived for each respiratory cycle. The deviation from the predetermined tidal volume was calculated and analysed. Several mixed linear models were calculated with the cadaver as a random factor and ventilator, height, sex, crossover period and incremental number of each ventilation within the period as covariates to evaluate differences between ventilators.ResultsOverall median deviation of net tidal volume from predetermined tidal volume was − 21.2 % (IQR: 19.6, range: [− 87.9 %; 25.8 %]) corresponding to a tidal volume of 4.75 mL/kg predicted body weight (IQR: 1.2, range: [0.7; 7.6]). In a mixed linear model, the ventilator model, the crossover period, and the cadaver’s height were significant factors for decreased tidal volume. The estimated effects of tidal volume deviation for each ventilator were − 14.5 % [95 %-CI: −22.5; −6.5] (p = 0.0004) for ‘Monnal T60’, − 30.6 % [95 %-CI: −38.6; −22.6] (p < 0.0001) for ‘Oxylog 3000 plus’ and − 31.0 % [95 %-CI: −38.9; −23.0] (p < 0.0001) for ‘MEDUMAT Standard²’.ConclusionsAll investigated transport ventilators were able to provide alveolar ventilation even though chest compressions considerably decreased tidal volumes. Our results support the concept of using ventilators to avoid excessive ventilatory rates in CPR. This experimental study suggests that healthcare professionals should carefully monitor actual tidal volumes to recognise the occurrence of hypoventilation during continuous chest compressions.

Mathematical model of modified hybrid pump mechanism for cardiopulmonary resuscitation

Background and objectiveThe “Cardiac pump theory” and “Thoracic pump theory” are representative theories of cardiopulmonary resuscitation (CPR) mechanisms. Based on these theories, many studies on mathematical modeling have been performed to help understand hemodynamics during CPR. However, there are parts that do not yet properly reflect the physiology of CPR. Therefore, this study aims to develop a lumped parameter model of CPR that can more accurately reflect the current CPR physiology. MethodsBy adding compartments of the superior and inferior vena cava of the thoracic cavity to the existing CPR model, and the “Hybrid pump” mechanism was applied to simulate CPR. To compare the hemodynamics of the conventional CPR model and the developed CPR model, various conditions, such as active compression–decompression CPR with an impedance threshold valve device (ACD–CPR+ITV), head-up-tilt (HUT), and head-down-tilt (HDT), were simulated. The coronary perfusion pressure (CPP) was compared by modulating the compression ratio of the atrium and ventricle with the thoracic pump factor. ResultsThe result for the comparison of coronary blood flow showed that the existing model is predominant in the compression phase, whereas the developed model is dominant in the relaxation phase. ACD–CPR + ITV results showed that the CPP decreased by 5 % in the existing model, and increased by about 46 % in the developed model, revealing a distinct hemodynamic difference between the two models. Likewise, as a result of comparing the hemodynamic differences of the two models according to the changes in tilt angle, the HUT showed similar trends, while the HDT showed slightly different results. The CPP varied accordingly with the ratio of the ventricular and atrial thoracic pump factor. ConclusionComparison of the hemodynamics with the existing model by simulating various conditions showed that the developed CPR model reflects the CPR physiology better. The model suggests that the hemodynamics may vary depending on the ventricle and atrium compression ratio. This study may provide an important basis for helping understand various situations and patient-specific hemodynamic characteristics during CPR through in-depth research, such as patient-specific model and parameter optimization.

Abstract 120: Artesunate Reduces the Severity of Post-Resuscitation Myocardial and Cerebral Dysfunction

Introduction: Artesunate (ART) possesses anti-inflammatory activity, which can mitigate the systemic inflammatory response in poor outcomes of cardiac arrest (CA). We investigated the effects of ART on myocardial and cerebral function, duration of survival, and inflammation in a rat model of CA and cardiopulmonary resuscitation (CPR). Hypothesis: ART reduces the severity of post resuscitation myocardial and cerebral dysfunction by alleviating inflammation in a rat model of CA and CPR. Methods: 30 male Sprague-Dawley rats weighing between 450g-550g were randomized into 3 groups: Sham (S), Control (C), and Artesunate (A). C and A were divided into subgroups: survival and non-survival (n=6). Ventricular fibrillation (VF) was induced and untreated for 6 min. A 4J defibrillation was attempted after 8 min of CPR. Phosphate buffer (1ml/kg, pH 7.9-8.1) or ART (2.4mg/kg), was administered at return of spontaneous circulation (ROSC). Myocardial function was measured at baseline and every hour for 4h post ROSC. Plasma levels of IL-6, TNF-α and cTnI were detected at baseline and 4h after ROSC. Survival animals were observed for an additional 72h. Neurologic deficit scores were recorded daily. Results: ART reduced the severity of post-resuscitation myocardial dysfunction compared to C. It attenuated IL-6, TNF-α and cTnI plasma levels 4h after ROSC (p&lt;0.05) (Fig. 1). Post-resuscitation cerebral function and survival rate also improved significantly (p&lt;0.05) (Fig. 2). Conclusion: ART reduces the severity of post-resuscitation myocardial and cerebral dysfunction, improves survival rate and attenuates inflammation in a rat of model of CA and CPR.

Abstract 211: UAMC-3203 Reduces the Severity of Post-resuscitation Myocardial Dysfunction in a Rat Model of Cardiac Arrest and Cardiopulmonary Resuscitation

Introduction: Previous studies have demonstrated that ferroptosis, a newly defined iron-dependent cell death, mediates ischemia/reperfusion induced cardiomyopathy. However, it is unclear whether ferroptosis plays a role in post-resuscitation myocardial dysfunction (PRMD). This study investigated the effects of UAMC-3203, a novel analog of ferroptosis specific inhibitors, on myocardial function after cardiopulmonary resuscitation (CPR). Hypothesis: Administration of UAMC-3203 during CPR alleviates PRMD in a rat model of cardiac arrest (CA) and CPR. Methods: 18 male Sprague-Dawley rats weighing between 450-550g were randomized into 3 groups: 1) Sham, 2) Control, and 3) UAMC-3203 (5mg/kg, IP at start of precordial compression). Ventricular fibrillation (VF) was induced and continued for 6min. CPR was then initiated for 8min, after which defibrillation was attempted. Ejection fraction (EF), cardiac output (CO) and myocardial performance index (MPI) were measured by echocardiography at baseline, 15min, 1h, 3h and 6h respectively after return of spontaneous circulation (ROSC). Results: A significant reduction in cardiac function was observed after resuscitation. At 15 minutes after ROSC, ultrasound showed no difference in cardiac function between UAMC and control. However, at 1, 3, and 6 h after ROSC, UAMC significantly improved myocardial function (p&lt;0.05) (Fig. 1). Conclusion: A ferroptosis-specific inhibitor, UAMC-3203, alleviated PRMD significantly in a rat of model of CA and CPR. Further study is needed to determine the benefit of this agent in larger animals and potential safety in humans before it can be tested in clinical resuscitation.

Abstract 142: Combined Therapy with Polyethylene Glycol-20k and MCC950 Preserves Post-resuscitation Myocardial Mitochondrial Function in a Rat Model of Cardiac Arrest and Cardiopulmonary Resuscitation

Introduction: Mitochondrial dysfunction from global ischemic-reperfusion (I/R) injury is a major contributor to post-resuscitation myocardial dysfunction. Polyethylene Glycol-20k (PEG-20k) shortens the no-flow phenomenon and improves microcirculation while MCC950 selectively inhibits activation of the NLRP3-inflammasome ensuing pyroptosis. We evaluated the effect of combined therapy with PEG-20k and MCC950 on myocardial mitochondrial function as measured by electron transport chain complex respiration in a rat model of cardiac arrest (CA) and cardiopulmonary resuscitation (CPR). Methods: 30 Sprague-Dawley rats weighing between 450-550 g were randomized into five groups (n=6): (1) sham (S); (2) control (C); (3) PEG-20k (P); (4) MCC950 (M); (5) combined (P&amp;M). Ventricular fibrillation (VF) was electrically induced and untreated for 6min, followed by 8min CPR. Resuscitation was attempted with a 4J defibrillation. 2mL P was infused over 2 min at the beginning of CPR, while M (10mg/kg) was administered intraperitoneal (IP) immediately after return of spontaneous circulation (ROSC). At ROSC 6hr, 100mg of heart was harvested, transferred directly into ice-cold K medium (1mL), and homogenized to obtain a 10% homogenate. Homogenates (50μL) were transferred to calibrated Oxygraph-2 chambers. Mitochondrial function was measured using high resolution respirometry. Oxygen flux was corrected and expressed by tissue wet weight, pmol/(min*mg). Data were analyzed by one-way analysis of variance (one-way ANOVA) followed by Tukey’s post hoc test for comparisons between multiple groups. Results: Complex I respiration in C was compromised at ROSC 6hr compared to S (564.0±160.0 vs 2729.5±339.5, p&lt;0.001). As expected, P and M restored complex I respiration (1224.4±328.6, p&lt;0.001) and (1804.4±293.1, p&lt;0.01) compared to C. P&amp;M further consolidated Complex I respiration function recovery (2527.6±145.5). Conclusion: Combined Therapy with PEG-20k and MCC950 preserves post-resuscitation myocardial mitochondrial function in a rat model of CA and CPR.

Effects of different adrenaline doses on cerebral oxygenation and cerebral metabolism during cardiopulmonary resuscitation in pigs

BackgroundThe influence of adrenaline during cardiopulmonary resuscitation (CPR) on the neurological outcome of cardiac arrest survivors is unclear. As little is known about the pathophysiological effects of adrenaline on cerebral oxygen delivery and cerebral metabolism we investigated its effects on parameters of cerebral oxygenation and cerebral metabolism in a pig model of CPR. MethodsFourteen pigs were anesthetized, intubated and instrumented. After 5 min of cardiac arrest CPR was started and continued for 15 min. Animals were randomized to receive bolus injections of either 15 or 30 μg/kg adrenaline every 5 min after commencement of CPR. ResultsMeasurements included mean arterial pressure (MAP), intracranial pressure (ICP), cerebral perfusion pressure (CPP), cerebral regional oxygen saturation (rSO2), brain tissue oxygen tension (PbtO2), arterial and cerebral venous blood gases and cerebral microdialysis parameters, e.g. lactate/pyruvate ratio. Adrenaline induced a significant increase in MAP and CPP in all pigs. However, increases in MAP and CPP were short-lasting and tended to decrease with repetitive bolus administration. There was no statistical difference in any parameter of cerebral oxygenation or metabolism between study groups. ConclusionsBoth adrenaline doses resulted in short-lasting CPP peaks which did not translate into improved cerebral tissue oxygen tension and metabolism. Further studies are needed to determine whether other dosing regimens targeting a sustained increase in CPP, may lead to improved brain oxygenation and metabolism, thereby improving neurological outcome of cardiac arrest patients.

Impact of Pit-Crew Cardiopulmonary Resuscitation on Out-of-Hospital Cardiac Arrest in Saskatoon.

In the prehospital setting, pit-crew models of cardiopulmonary resuscitation (CPR) have shown improvements in survival after out-of-hospital cardiac arrest (OHCA). Certain districts in North America have adopted this model, including Saskatoon, Saskatchewan, Canada. Our objectives were to determine whether pit-crew CPR has an impact on survival to discharge after OHCA in Saskatoon, Canada. This was a retrospective pre- and postintervention study. All adult patients who had an OHCA between January 1, 2011 and December 31, 2017 of presumed cardiac origin, in which the resuscitation attempt included CPR by trained prehospital responders, were considered for analysis. Our primary outcome was survival to discharge. Survival to admission and return of spontaneous circulation were secondary outcomes. There were 860 OHCAs considered for our study. After 46 exclusions there were 442 in the non-pit-crew group (average age 63.7years; 64.5% male) and 372 in the pit-crew group (average age 63.5years; 67.5% male). Survival to discharge after an OHCA was 10.4% (95% confidence interval 7.7-13.6%) in the non-pit-crew group and 12.4% (95% CI 9.2-16.2%) in the pit-crew group, which did not meet statistical significance. Return of spontaneous circulation and survival to admission were 48.4% and 31.3%, respectively, in the non-pit-crew group and 46.7% and 32.3%, respectively, in the pit-crew group. In our study, implementation of a pit-crew CPR model was not associated with an improvement in survival to discharge after OHCA.

Effects of brain necroptosis and cytokines expression array on brain injury in rats with cardiac arrest

To investigate the underlying molecular mechanisms of brain injury in rats after cardiac arrest and cardiopulmonary resuscitation (CPR) by observing necroptosis of brain cells and changes of 90 cytokines in brain tissue. Sprague-Dawley (SD) rats were divided into Sham group (n = 10) and cardiac arrest group (n = 10) according to random number table method. The model of asphyxia cardiac arrest for 6 minutes followed by CPR model was established. Tracheal intubation in Sham rats were routinely performed without inducing cardiac arrest. Neurological deficit score (NDS) was evaluated, blood samples were collected and rats were sacrificed, then serum S100B level was measured by enzyme linked immunosorbent assay (ELISA) on the third day after CPR. Necroptotic cells in brain were detected by immunofluorescence staining. The levels of 90 cytokines expression in brain were measured by antibody array. The relative ratio of the two groups of protein expression ≥ 1.5 or ≤ 0.5 and P < 0.05 represented the differential expression protein. There were 8 rats successfully resuscitated and 2 died in cardiac arrest group. There were 8 rats selected in Sham group to match the sample size. Compared with Sham group, the NDS score of cardiac arrest group was significantly lower [63.0 (62.5, 64.3) vs. 80.0 (80.0, 80.0), P < 0.01], and the level of serum S100B was significantly higher (ng/L: 47.96±10.16 vs. 16.56±5.60, P < 0.01). More necroptotic cells in cerebral cortex and hippocampus were found in cardiac arrest group [proportion of cells positive for TdT-mediated nick end labeling (TUNEL) and negative for caspase-3: (15.70±0.32)% vs. (8.00±0.28)% in cortex, (20.80±1.35)% vs. (9.00±4.00)% in hippocampus, both P < 0.05]. The levels of inflammatory cytokines [cytokine-induced neutrophil chemoattractant (CINC-2α/β, CINC-3), interferon-γ (IFN-γ)] and signal protein c-Src kinase (CSK) in brain significantly increased after cardiac arrest as compared to Sham group levels (ratio of cardiac arrest group to Sham group: CINC-2 α/β was 2.503±0.428, P = 0.024; CINC-3 was 2.369±0.142, P = 0.005; IFN-γ was 3.149±1.362, P = 0.044; CSK was 1.887±0.105, P = 0.001). However, the levels of neuroprotective cytokines ciliary neurotrophic factor (CNTF), glial cell-derived neurotrophic factor receptor (GFR α-1, GFR α-2), growth hormone (GH), growth hormone receptor (GHR), granulocyte-macrophage colony-stimulating factor (GM-CSF) and anti-inflammatory protein interleukin-10 (IL-10) significantly decreased after cardiac arrest (ratio of cardiac arrest group to Sham group: CNTF was 0.341±0.137, P = 0.036; GFRα-1 was 0.461±0.164, P = 0.044; GFRα-2 was 0.447±0.017, P = 0.033; GH was 0.450±0.136, P = 0.024; GHR was 0.508±0.128, P = 0.022; GM-CSF was 0.446±0.130, P = 0.035; IL-10 was 0.502±0.211, P = 0.017). Necroptosis is involved in brain injury after cardiac arrest. The molecular mechanisms of brain injury may be related to inflammatory response, neurogenesis disorder and impaired survival of nerve cells.

Electronic Depth Adjustment in an Automatic Chest Compression Device for Rodents – Design and Implementation of a LabVIEW‐based Control Unit

IntroductionDespite best efforts of cardiopulmonary resuscitation (CPR), many patients still die or suffer severe cardio‐cerebral damage following cardiac arrest (CA). The quality of manual chest compressions (CC) rarely adheres to current guidelines with regards to CC rate, depth and fraction of time spent during CPR. Automated mechanical CC devices offer a reliable improvement in both the clinical arena and in research models. We describe the mechanical and programming aspects of the development of a depth controller for a pneumatic CC device for CPR in rodent CA model.Methods &amp; ResultsIn order to electronically control the amplitude/depth of the vertical CC piston (Weil Institute of Critical Care Medicine, Palm Springs, CA; Fig 1) that is pneumatically displaced between 0 and maximally 2 cm 200 times min−1 (duty cycle 1:1), a horizontally moving wedge was connected to a rack gearbox driven by a low‐voltage motor (Fischertechnik, Waldachtal, Germany) along a fixed rack. The unit was connected to a horizontally sliding potentiometer to monitor the exact position of the wedge and, therefore, the piston displacement which itself was monitored through a second, vertically sliding potentiometer. Both potentiometers were connected to an USB 6343 data acquisition system (DAQ, National Instruments, Austin, TX). The motor was connected to two analogue outputs of the DAQ (for movement and direction) via a commercially available low‐voltage amplifier. Stepwise movement of the wedge in either direction could be controlled by a momentary rocker switch connected to two analogue input channels of the DAQ (for deeper and shallower compressions) and its LabVIEW software which was programmed to allow precise control of the wedge’s position.ConclusionsWe report the design and construction of an inexpensive, LabVIEW‐based control unit to electronically adjust CC depth in a rodent model of CA and CPR. Neither the hardware, nor the software required to perform this highly specialized application were commercially available. This custom‐designed and ‐built device achieved its purpose of allowing electronic control and recording of the CC depth in this rodent model with high reliability and precision. Moreover, it constitutes the necessary basis of pre‐programmed or feedback‐assisted adjustments of variable CC depth in the future to improve neurologically favorable outcome after CA.Support or Funding InformationThis work was supported, in part, by institutional funds, and a Merit Review Award (I01 BX003482) from the U.S. Department of Veterans Affairs Biomedical Laboratory R&amp;D Service.Pneumatic chest compression device for rodents with added control unit for electronic depth adjustment.Figure 1

Confecção de modelo de baixo custo para treinamento de ressuscitação cardiopulmonar em cão

Cardiopulmonary resuscitation (CPR) should be started promptly in a situation of cardiorespiratory arrest (CRP). The Reassessment Campaign on Veterinary Resuscitation (RECOVER) proposes clinical recommendations for the application of the procedure in dogs and cats and also recognizes the need for cognitive and psychomotor skills to perform the entire protocol in an agile and efficient manner. In this way, an ideal training should cover didactic components and practice of manual skills, with the use of discriminated models and simulators. The use of alternative methods with synthetic models is supported by the increase in concerns about animal welfare, a demand that is presented by Veterinary Medicine scholars and residents of the Veterinary Hospital of the Federal University of Paraná (UFPR). In addition to the high cost of commercially available models, the objective of this work is to present a low-cost model for training CPR in dogs. After acquisition of a plush dog, a representative structure of the internal part of the chest was elaborated with a plastic packaging of powdered chocolate filled with silicon fiber. Then, the larynx cartilages were produced in silicone rubber of medium flexibility, adhered to a corrugated trachea. The molds of the hard palate and upper and lower dental arches were made of resin, painted with acrylic paint and fixed to a modified dental articulator. For the oral mucosa and tongue it was made low viscosity silicone elastomer structures. The model allowed to perform the procedures of thoracic compression and endotracheal intubation, steps included in the CPR. The model was tested by Veterinary Medicine professionals with experience in CPR, and a good result was reported. The presented CPR model allowed the simulation of the basic support to life and, being of low cost, can be made by other educational institutions with this same purpose.

Sedative depth on neurological outcomes in a juvenile rat model of cardiopulmonary resuscitation

The guidelines for cardiopulmonary resuscitation (CPR) in pediatric advanced life support suggest that midazolam is the preferred agent for sedation in patients with mild hypothermia, whereas children with cardiac arrest (CA) are at a crucial stage regarding their immature nervous system. Studies have shown that midazolam may have a detrimental effect on the developmental of the pediatric nervous system. Our previous study found that midazolam induced neuronal damage after CPR in young rats. It is speculated that: midazolam causes the potential injury of neurons by inhibiting mitochondrial autophagy expression and is an important factor for the poor prognosis in children after successful CPR. This project intends to adopt the modified asphyxiant CPR model in juvenile rats. Survival rate, neurological function and histopathological changes were evaluated to determine the protective effects of appropriate sedation depth on cerebral ischemia-reperfusion injury in juvenile rats after CPR. Combined with cell biology and molecular biology related technologies, the mechanism by which the mitochondrial pinkl-parkin signaling pathway induces autophagy to inhibit neuronal apoptosis may be key factor in the protective effects of sedation depth on the brain. The aim of this study is to provide experimental evidence and elucidate the mechanisms of improvement of cerebral ischemia-reperfusion injury by sedation depth in children after successful CPR and to lay a theoretical and experimental basis for clinical treatment.

Epinephrine during CPR significantly increases organ perfusion in a rat VF cardiac arrest model

Introduction: Epinephrine is an established vasopressor and the primary drug administrated during cardio pulmonary resuscitation (CPR). This study evaluates the influence of epinephrine on coronary perfusion pressure (CPP), mean atrial pressure (MAP) and end-tidal CO2 (ETCO2) in our rat VF CPR model.