Porcine Model Of Cardiac Arrest Research Articles

Xenon: An Emerging Neuroprotectant With Potential Application for Cardiac Arrest Care.

Xenon is an inert, highly polarizable noble gas with demonstrated safety and application in general anesthesia for over 50 years. A potent inhibitor of the N-methyl-D-aspartate subtype of glutamate receptors, xenon has a well-documented ameliorating effect on excitotoxic neuronal injury in numerous cellular and animal models of hypoxic-ischemic brain injury. The most important determinant of overall survival and morbidity in out-of-hospital cardiac arrest is the severity of neurological injury. The only approved neuroprotective strategy in this setting is mild therapeutic hypothermia, which has demonstrated significant, albeit modest, improvements in mortality. The combination therapy of therapeutic hypothermia and xenon in porcine models of cardiac arrest has shown a greater improvement in functional outcomes than either intervention alone, thereby prompting the study of combination therapy in randomized clinical trials. The treatment of postarrest patients with xenon and mild hypothermia is safe and demonstrates favorable cardiovascular features, including a reduced heart rate, a reduction in troponin elevations, and a decreased need for vasopressors. Combination therapy is superior in protecting white matter integrity than hypothermia alone, but did not significantly impact neurological outcomes at 6-month follow-up. Despite an abundance of preclinical evidence supporting xenon's neuroprotective properties, its translational potential in postcardiac arrest care is indeterminate due to a lack of adequately-powered studies.

Brain perfusion evaluated by regional tissue oxygenation as a possible quality indicator of ongoing cardiopulmonary resuscitation. An experimental porcine cardiac arrest study.

Relationship between regional tissue oxygenation (rSO2) and microcirculatory changes during cardiac arrest (CA) are still unclear. Therefore, we designed an experimental study to correlate rSO2, microcirculation and systemic hemodynamic parameters in a porcine model of CA. Ventricular fibrillation was induced in 24 female pigs (50±3kg) and left for three minutes untreated followed by five minutes of mechanical CPR. Regional and peripheral saturations were assessed by near-infrared spectroscopy, sublingual microcirculation by Sidestream Dark Field technology and continuous hemodynamic parameters, including systemic blood pressure (MAP) and carotid blood flow (CF), during baseline, CA and CPR periods. The Wilcoxon Signed-Rank test, the Friedman test and the partial correlation method were used to compare these parameters. Brain and peripheral rSO2 showed a gradual decrease during CA and only an increase of brain rSO2 during mechanical CPR (34.5 to 42.5; p=0.0001), reflected by a rapid decrease of microcirculatory and hemodynamic parameters during CA and a slight increase during CPR. Peripheral rSO2 was not changed significantly during CPR (38 to 38.5; p=0.09). We only found a moderate correlation of cerebral/peripheral rSO2 to microcirculatory parameters (PVD: r=0.53/0.46; PPV: r=0.6/0.5 and MFI: r=0.64/0.52) and hemodynamic parameters (MAP: r=0.64/0.71 and CF: 0.71/0.67). Our experimental study confirmed that monitoring brain and peripheral rSO2 is an easy-to-use method, well reflecting the hemodynamics during CA. However, only brain rSO2 reflects the CPR efforts and might be used as a potential quality indicator for CPR.

Haemodynamic outcomes during piston-based mechanical CPR with or without active decompression in a porcine model of cardiac arrest

BackgroundExperimental active compression-decompression (ACD) CPR is associated with increased haemodynamic outcomes compared to standard mechanical chest compressions. Since no clinically available mechanical chest compression device is capable of ACD-CPR, we modified the LUCAS 2 (Physio-Control, Lund, Sweden) to deliver ACD-CPR, hypothesising it would improve haemodynamic outcomes compared with standard LUCAS CPR on pigs with cardiac arrest.MethodsThe modified LUCAS delivering 5 cm compressions with or without 2 cm active decompression above anatomical chest level was studied in a randomized crossover design on 19 Norwegian domestic pigs. VF was electrically induced and untreated for 2 min. Each pig received ACD-CPR and standard mechanical CPR in three 180-s. phases. We measured aortic, right atrial, coronary perfusion, intracranial and oesophageal pressure, cerebral and carotid blood flow and cardiac output. Two-sided paired samples t-test was used for continuous parametric data and Wilcoxon test for non-parametric data. P < 0.05 was considered significant.ResultsDue to injuries/device failure, the experimental protocol was completed in nine of 19 pigs. Cardiac output (l/min, median, (25, 75-percentiles): 1.5 (1.1, 1.7) vs. 1.1 (0.8, 1.5), p < 0.01), cerebral blood flow (AU, 297 vs. 253, mean difference: 44, 95% CI; 14–74, p = 0.01), and carotid blood flow (l/min, median, (25, 75-percentiles): 97 (70, 106) vs. 83 (57, 94), p < 0.01) were higher during ACD-CPR compared to standard mechanical CPR. Coronary perfusion pressure (CPP) trended towards higher in end decompression phase.ConclusionCardiac output and brain blood flow improved with mechanical ACD-CPR and CPP trended towards higher during end-diastole compared to standard LUCAS CPR.

Single Ventilation during Cardiopulmonary Resuscitation Results in Better Neurological Outcomes in a Porcine Model of Cardiac Arrest.

PurposeRecent basic life support (BLS) guidelines recommend a 30:2 compression-to-ventilation ratio (CV2) or chest compression-only cardiopulmonary resuscitation (CC); however, there are inevitable risks of interruption of high-quality cardiopulmonary resuscitation (CPR) in CV2 and hypoxemia in CC. In this study, we compared the short-term outcomes among CC, CV2, and 30:1 CV ratio (CV1).Materials and MethodsIn total, 42 pigs were randomly assigned to CC, CV1, or CV2 groups. After induction of ventricular fibrillation (VF), we observed pigs for 2 minutes without any intervention. Thereafter, BLS was started according to the assigned method and performed for 8 minutes. Defibrillation was performed after BLS and repeated every 2 minutes, followed by rhythm analysis. Advanced cardiac life support, including continuous chest compression with ventilation every 6 seconds and intravenous injection of 1 mg epinephrine every 4 minutes, was performed until the return of spontaneous circulation (ROSC) or 22 minutes after VF induction. Hemodynamic parameters and arterial blood gas profiles were compared among groups. ROSC, 24-hour survival, and neurologic outcomes were evaluated at 24 hours.ResultsThe hemodynamic parameters during CPR did not differ among the study groups. Partial pressure of oxygen in arterial blood and arterial oxygen saturation were lowest in the CC group, compared to those in the other groups, during the BLS period (p=0.002 and p<0.001, respectively). The CV1 groups showed a significantly higher rate of favorable neurologic outcome (swine CPC 1 or 2) than the other groups (p=0.044).ConclusionCPR with CV1 could promote better neurologic outcome than CV2 and CC.

Detection of spontaneous pulse using the acceleration signals acquired from CPR feedback sensor in a porcine model of cardiac arrest.

BackgroundReliable detection of return of spontaneous circulation with minimal interruptions of chest compressions is part of high-quality cardiopulmonary resuscitation (CPR) and routinely done by checking pulsation of carotid arteries. However, manual palpation was time-consuming and unreliable even if performed by expert clinicians. Therefore, automated accurate pulse detection with minimal interruptions of chest compression is highly desirable during cardiac arrest especially in out-of-hospital settings.ObjectiveTo investigate whether the acceleration (ACC) signals acquired from accelerometer-based CPR feedback sensor can be used to distinguish perfusing rhythm (PR) from pulseless electrical activity (PEA) in a porcine model of cardiac arrest.MethodsCardiac arrest was induced in 49 male adult pigs. ECG, arterial blood pressure (ABP) and ACC waveforms were simultaneously recorded during CPR. 3-second segments containing compression-free signals during chest compression pauses were extracted and only those segments with organized rhythm were used for analysis. PR was defined as systolic arterial pressure >60 mmHg and pulse pressure >10 mmHg, while PEA was defined as an organized rhythm that does not meet the above criteria for PR. Peak correlation coefficient (CCp) of the cross-correlation function between pre-processed ECG and ACC, was used to discriminate PR and PEA.Results63 PR and 153 PEA were identified from the total of 1025 extracted segments. CCp was significantly higher for PR as compared to PEA (0.440±0.176 vs. 0.067±0.042, p<0.01) and highly correlated with ABP (r = 0.848, p<0.001). The area under the receiver operating characteristic curve, sensitivity, specificity and accuracy were 0.965, 93.6%, 97.5% and 96.7% for the ACC-based automatic spontaneous pulse detection.ConclusionsIn this animal model, the ACC signals acquired from an accelerometer-based CPR feedback sensor can be used to detect the presence of spontaneous pulse with high accuracy.

Correlation of end tidal carbon dioxide, amplitude spectrum area, and coronary perfusion pressure in a porcine model of cardiac arrest.

Amplitude Spectrum Area (AMSA) values during ventricular fibrillation (VF) correlate with myocardial energy stores and predict defibrillation success. By contrast, end tidal CO2 (ETCO2) values provide a noninvasive assessment of coronary perfusion pressure and myocardial perfusion during cardiopulmonary resuscitation (CPR). Given the importance of the timing of defibrillation shock delivery on clinical outcome, we tested the hypothesis that AMSA and ETCO2 correlate with each other and can be used interchangably to correlate with myocardial perfusion in an animal laboratory preclinical, randomized, prospective investigation. After 6 min of untreated VF, 12 female pigs (32 ± 1 Kg), isoflurane anesthetized pigs received sequentially 3 min periods of standard (S) CPR, S‐CPR+ an impedance threshold device (ITD), and then active compression decompression (ACD) + ITD CPR. Hemodynamic, AMSA, and ETCO2 measurements were made with each method of CPR. The Spearman correlation and Friedman tests were used to compare hemodynamic parameters. ETCO2, AMSA, coronary perfusion pressure, cerebral perfusion pressure were lowest with STD CPR, increased with STD CPR + ITD and highest with ACD CPR + ITD. Further analysis demonstrated a positive correlation between AMSA and ETCO2 (r = 0.37, P = 0.025) and between AMSA and key hemodynamic parameters (P < 0.05). This study established a moderate positive correlation between ETCO2 and AMSA. These findings provide the physiological basis for developing and testing a novel noninvasive method that utilizes either ETCO2 alone or the combination of ETCO2 and AMSA to predict when defibrillation might be successful.

Spontaneous hypertrophic cardiomyopathy in pigs: A possible cause of misleading results in porcine models of cardiac arrest and cardiopulmonary resuscitation

Spontaneous hypertrophic cardiomyopathy in pigs: A possible cause of misleading results in porcine models of cardiac arrest and cardiopulmonary resuscitation

Comparison of continuous compression with regular ventilations versus 30:2 compressions-ventilations strategy during mechanical cardiopulmonary resuscitation in a porcine model of cardiac arrest.

A compression-ventilation (C:V) ratio of 30:2 is recommended for adult cardiopulmonary resuscitation (CPR) by the current American Heart Association (AHA) guidelines. However, continuous chest compression (CCC) is an alternative strategy for CPR that minimizes interruption especially when an advanced airway exists. In this study, we investigated the effects of 30:2 mechanical CPR when compared with CCC in combination with regular ventilation in a porcine model. Sixteen male domestic pigs weighing 39±2 kg were utilized. Ventricular fibrillation was induced and untreated for 7 min. The animals were then randomly assigned to receive CCC combined with regular ventilation (CCC group) or 30:2 CPR (VC group). Mechanical chest compression was implemented with a miniaturized mechanical chest compressor. At the same time of beginning of precordial compression, the animals were mechanically ventilated at a rate of 10 breaths-per-minute in the CCC group or with a 30:2 C:V ratio in the VC group. Defibrillation was delivered by a single 150 J shock after 5 min of CPR. If failed to resuscitation, CPR was resumed for 2 min before the next shock. The protocol was stopped if successful resuscitation or at a total of 15 min. The resuscitated animals were observed for 72 h. Coronary perfusion pressure, end-tidal carbon dioxide and carotid blood flow in the VC group were similar to those achieved in the CCC group during CPR. No significant differences were observed in arterial blood gas parameters between two groups at baseline, VF 6 min, CPR 4 min and 30, 120 and 360 min post-resuscitation. Although extravascular lung water index of both groups significantly increased after resuscitation, no distinct difference was found between CCC and VC groups. All animals were successfully resuscitated and survived for 72 h with favorable neurologic outcomes in both groups. However, obviously more numbers of rib fracture were observed in CCC animals in comparison with VC animals. There was no difference in hemodynamic efficacy and gas exchange during and after resuscitation, therefore identical 72 h survival with intact neurologic function was observed in both VC and CCC groups. However, the incidence of rib fracture increases during the mechanical CPR strategy of CCC combined with regular ventilations.

209 Evaluation of acute cardiac damage in a porcine model of defibrillation

IntroductionTransthoracic defibrillation is performed to correct life threatening cardiac arrhythmias of the heart, i.e. ventricular fibrillation (VF) and ventricular tachycardia (VT). These are due to chaotic electrical excitation of the...

Comparison of early sequential hypothermia and delayed hypothermia on neurological function after resuscitation in a swine model

BackgroundWe utilized a porcine cardiac arrest model to compare early sequential hypothermia (ESH) with delayed hypothermia (DH) and no hypothermia (NH) to investigate the different effects on cerebral function after resuscitation. MethodsAfter return of spontaneous circulation (ROSC), resuscitated 24 pigs divided into three groups. The ESH group implemented early sequential hypothermia immediately, and the DH group implemented delayed hypothermia at 1 h after ROSC. The core temperature, hemodynamic parameters and oxygen metabolism were recorded. Cerebral metabolism variables and neurotransmitter in the extracellular fluid were collected through the microdialysis tubes. The bloods were analyzed for venous jugular bulb oxygen saturation, lactate and neuron specific nolase. The cerebral function was evaluated using the cerebral performance category and neurologic deficit score at 72h after ROSC and cerebral histology in the right posterior frontal lobe were collected. ResultsESH reached the target temperature earlier and showed more favorable outcomes of neurological function than DH. Specifically, early sequential hypothermia reduced cerebral oxygen and energy consumption and decreased extracellular accumulation of neurotransmitters after resuscitation and protected the integrity of the BBB during reperfusion. ConclusionsEarly sequential hypothermia could increase the protection of neurological function after resuscitation and produce better neurological outcomes.The institutional protocol number: 2010-D-013.

Effects of Mild Hypothermia on Cerebral Large and Small Microvessels Blood Flow in a Porcine Model of Cardiac Arrest.

The effect of mild hypothermia (MH) on microcirculation after resuscitation from cardiac arrest is controversial. The aim of this study was to determine whether MH improves or aggravates the disturbance of cerebral microcirculation. Twenty domestic male pigs were randomized into the MH group (n=8), non-hypothermia (NH) group (n=8) or sham operation group (n=4). In the MH group, the animals were initiated rapid intravascular cooling at 1h after return of spontaneous circulation (ROSC) from 8min ventricular fibrillation, and the core temperature was reduced to 33°C for 12h and then rewarmed to 37°C. In the NH group, animals did not receive hypothermia treatment after ROSC. In the sham operation group, the same surgical procedure was performed, but without inducing ventricular fibrillation and hypothermia treatment. The cerebral microvascular flow index (MFI) of large microvessel (diameter>20μm) and small microvessel (diameter<20μm) was measured after ROSC. Cerebral oxygen extraction ratio, internal jugular venous-artery lactate difference, and CO2 difference were also calculated. Cerebral MFI dramatically reduced after ROSC, and MH further aggravated the decrease in MFI of small microvessel compared with NH (p<0.05). Internal jugular venous-arterial lactate difference and CO2 difference, and oxygen extraction ratio were all significantly increased after ROSC. MH significantly decreased the values compared with NH (p<0.05). MH decreases cerebral small microvessel blood flow and cerebral metabolism after ROSC compared with NH. However, the total effect is that cerebral oxygen supply-demand relationship is improved during hypothermia.

Ischemic Postconditioning Transiently Improves Cardiac Mitochondrial Function during Resuscitation in a Porcine Model of Cardiac Arrest

IntroductionIschemic postconditioning (IPC) is a technique of brief interruptions in blood flow at the onset of reperfusion to mitigate reperfusion injury after prolonged ischemia. When applied during cardiopulmonary resuscitation (CPR) following ventricular fibrillation (VF) cardiac arrest (CA) in a porcine model, IPC during CPR (IPC‐CPR) reduced adverse events and improved neurologically favorable survival 48 hours after return of spontaneous circulation (ROSC) compared to standard‐of‐care CPR (S‐CPR). IPC‐CPR also increased cardiac mitochondrial function prior to ROSC after 4 minutes of CPR compared to S‐CPR.ObjectiveWe investigated the effect of IPC‐CPR after prolonged VF CA on cardiac mitochondrial function 6 hours after ROSC.MethodsTwenty‐four female swine were intubated, anesthetized, and surgically prepared for continuous hemodynamic recording. Eight animals received no CA (Naïve, n=8) as a non‐ischemic control. The remaining animals received 15 minutes of untreated VF CA followed by CPR without (S‐CPR, n=8) or with IPC (IPC‐CPR, n=8). IPC was administered via three 20‐second pauses in chest compressions during the first 2 minutes of CPR. After 4 minutes of CPR, defibrillation was attempted. Six hours after ROSC, cardiac mitochondria were isolated via differential centrifugation for assessment of respiration, rate of ATP synthesis, and calcium retention capacity. ANOVA with Newman‐Keuls posthoc test was used for comparisons between treatments. The null‐hypothesis was rejected for p &lt; 0.05.ResultsROSC was obtained in all animals that received a CA. Cardiac mitochondrial function did not differ between Naïve, S‐CPR, and IPC‐CPR treated animals.ConclusionsIn a porcine model of prolonged VF CA, cardiac mitochondrial function normalizes within 6 hours of ROSC. The previously documented reduction in adverse events and improvement in survival with IPC‐CPR treatment may be mediated by acute changes in cardiac mitochondrial function earlier than 6 hours post‐ROSC, or by mechanisms independent of cardiac mitochondrial functionSupport or Funding InformationStipend support was provided by the American Heart Association 16PRE27600038 (TRM). Project support was provided by NIH 1R01 OD016727‐01 (DY).

Cardioprotective effect of nicorandil against myocardial injury following cardiac arrest in swine

IntroductionNicorandil, a vasodilatory drug used to treat angina, was reported to protect against myocardial ischemia-reperfusion injury in various animal models. However, its cardioprotective action following cardiac arrest is unknown. We examined the cardioprotective effects of nicorandil in a porcine model of cardiac arrest and resuscitation. MethodsVentricular fibrillation was induced electrically for 4min in anesthetized domestic swine, followed by cardiopulmonary resuscitation. Sixteen successfully resuscitated animals were randomized to saline control (n=8) or nicorandil (n=8) groups. Nicorandil (150μg/kg) was administered by central intravenous injection at onset of restoration of spontaneous circulation (ROSC), followed by 3μg/kg/min infusion until reperfusion end. Sham-operated animals received surgery only (n=4). Hemodynamic parameters were monitored continuously. Blood samples were taken at baseline, 5, 30, 180, and 360min after ROSC. Left ventricular ejection fraction was assessed by echocardiography at baseline and 6h after ROSC. The animals were euthanized 6h after ROSC, and the cardiac tissue was removed for analysis. Results6 h after ROSC, nicorandil had significantly improved all hemodynamic variables (all P<0.05) except the maximum rate of left ventricular pressure decline and heart rate (P>0.05) compared with the control group. Control animals showed elevated cardiac troponin I and lactate levels compared with sham animals, which were significantly decreased following nicorandil treatment (P<0.05). In the saline control group, the adenosine triphosphate (ATP) content was largely reduced but subsequently rescued by nicorandil (P<0.05). Histopathologic injury was reduced with nicorandil treatment. Nicorandil reduced cardiomyocyte apoptosis as evidenced by reduced terminal deoxynucleotidyl transferase dUTP nick-end labeling (TUNEL)-positive cells, decreased Bax and caspase-3 expression, and increased Bcl-2 expression in the myocardium (all P<0.05). ConclusionNicorandil exhibited cardioprotective effects on myocardial injury following cardiac arrest via improvement in post-resuscitation myocardial dysfunction and energy metabolism, reduction in myocardial histopathologic injury, and antiapoptotic effects.

The effect of resuscitation position on cerebral and coronary perfusion pressure during mechanical cardiopulmonary resuscitation in porcine cardiac arrest model

ObjectiveIt is unknown whether patient position is associated with the optimal cerebral (CePP) and coronary (CoPP) perfusion pressure. MethodsThis study utilized a randomized experimental design and anesthetized, intubated and paralyzed female pigs (n=12) (mean 42, SD 3kg). After 6min of untreated ventricular fibrillation, mechanical CPR with was performed for 3min in 0° supine position. The CPR was then performed for 5min in a position randomly assigned to either 1) head-up tilt (HUT) by three angles (30°, 45°, or 60°) or 2) head-down tilt (HDT) by three angles (30°, 45°, or 60°) and at 3) supine position between HUT and HDT positions. 4 Pigs were assigned to each angle of HUT or HDT position and 12 pigs were assigned to supine position. CePPs and CoPPs were measured and compared using MIXED procedure with pig as a random effect among angles and compared between angles with Tukey post-hoc analysis. ResultsWith 60°, 45°, 30° head-down, 0° (supine), and 30°, 45°, 60° head-up positioning, mean(SD) CePPs increased consistently as follows: 2.4(0.4), 9.3(1.6), 16.5(1.6), 27.0(1.5), 35.1(0.4), 39.4(0.6), and 39.9(0.3) mmHg, respectively. CoPPs were followings according to same angle: 12.9(2.5), 13.3(2.5), 12.8(0.4), 18.1(0.7), 30.3(0.4), 24.1(0.6), and 26.5(0.9) mmHg, respectively. The CePPs were peak at HUT(45°) and HUT(60°), but CoPP was peak in HUT(30°) and higher than HUT(45°) and HUT(60°). ConclusionCerebral perfusion pressure during mechanical CPR were similar and highest in the HUT(45° and 60°) positions whereas the peak coronary perfusion pressure was observed with HUT(30°).

A Novel Nonlinear Mathematical Model of Thoracic Wall Mechanics During Cardiopulmonary Resuscitation Based on a Porcine Model of Cardiac Arrest.

Cardiopulmonary resuscitation (CPR) is used widely to rescue cardiac arrest patients, yet some physiological aspects of the procedure remain poorly understood. We conducted this study to characterize the dynamic mechanical properties of the thorax during CPR in a swine model. This is an important step toward determining optimal CPR chest compression mechanics with the goals of improving the fidelity of CPR simulation manikins and ideally chest compression delivery in real-life resuscitations. This paper presents a novel nonlinear model of the thorax that captures the complex behavior of the chest during CPR. The proposed model consists of nonlinear elasticity and damping properties along with frequency dependent hysteresis. An optimization technique was used to estimate the model coefficients for force-compression using data collected from experiments conducted on swine. To track clinically relevant, time-dependent changes of the chest's properties, the data was divided into two time periods, from 1 to 10min (early) and greater than 10min (late) after starting CPR. The results showed excellent agreement between the actual and the estimated forces, and energy dissipation due to viscous damping in the late stages of CPR was higher when compared to the earlier stages. These findings provide insight into improving chest compression mechanics during CPR, and may provide the basis for developing CPR simulation manikins that more accurately represent the complex real world changes that occur in the chest during CPR.

Abstract 11983: Delayed Inhalation of Hydrogen Mitigates Neurological Dysfunction in a Porcine Model of Cardiac Arrest and Cardiopulmonary Resuscitation

Introduction: Immediate inhalation of hydrogen (H 2 ) has been demonstrated to improve post-resuscitation (PR) neurological dysfunction. However, early applying inhaled H 2 is not practical especially in out of hospital cardiac arrest because of the safety issue. In the present study, we investigated the effects of delayed treatments with H 2 on post resuscitation neurological function in a porcine model of prolonged cardiac arrest (CA). Hypothesis: Delayed inhalation of H 2 mitigates neurological dysfunction after resuscitation in a CA porcine model. Methods: Eighteen male domestic pigs weighing 39±2 kg were utilized. Ventricular fibrillation (VF) was induced electrically and CPR was initiated after 10 mins of untreated VF. All the animals were resuscitated successfully and randomized into two groups immediately following resuscitation: delayed inhalation of H 2 (DH group, N=9) or inhalation of room air (C group, N=9). Animals in the DH group were ventilated with 2% H 2 /21% oxygen from 2h post resuscitation (PR) to PR 4h. Serum levels of S100B and neuron-specific enolase (NSE) were measured by ELISA at baseline and PR 360 min. The neurological deficit score (NDS) and survival were evaluated daily for a total of 72 hours. Results: Better survival duration and NDS at 24h, 48h and 72h were observed in the DH group animals compared with those of the C group (Table). The serum levels of S100B and NSE were significantly lower in the DH group when compared with the C group (Figure). Conclusion: Delayed treatment of H 2 mitigates neurological injury and improves neurological dysfunction after resuscitation.

Abstract 12002: Delayed Inhalation of Hydrogen Improves Myocardial dysfunction in a Porcine Model of Cardiac Arrest and Cardiopulmonary Resuscitation

Introduction: Immediate inhalation of hydrogen (H 2 ) has been demonstrated to improve post-resuscitation (PR) myocardial dysfunction. In this study, we investigated the effects of delayed treatments with H 2 on myocardial dysfunction in a porcine model of cardiac arrest (CA). Hypothesis: Delayed inhalation of H 2 improves myocardial dysfunction after resuscitation in a CA porcine model. Methods: Twenty male pigs weighing 39±2 kg were utilized. Ventricular fibrillation was electrically induced and untreated for 10 mins. All the animals were successfully resuscitated manually and then randomized into two groups: delayed inhalation of H 2 (DH group) or continuous inhalation of room air (C group). Animals in DH group were ventilated with 2% H 2 /21% oxygen from PR 2h till PR 4h. Left ventricle pressure (LVP) was recorded continuously and cardiac output (CO) was measured by the thermo-dilution technique at baseline (BL) and then hourly after resuscitation for 6 hours. Serum levels of troponin T (Tn T) and N-terminal probrain natriuretic peptide (NTpro-BNP) were measured by ELISA at BL, PR 180 min and PR 360 min. Results: Deteriorations in maximum rate of LVP increase (dp/dtmax), maximum rate of LVP decline (-dp/dtmax) and CO were observed in all the animals after PR 4 h (Figure 1). However, better dp/dtmax, -dp/dtmax and CO were achieved in the DH group after PR 5h when compared with the C group. Although levels of both Tn T and NTpro-BNP in serum increased after resuscitation, they were significantly lower in animals of DH group in comparison with C group (Figure 2). Conclusion: Delayed treatment of H 2 attenuates myocardial injury and improves myocardial dysfunction after resuscitation.

Abstract 11891: Nitroglycerin Improves Microcirculation During and After Cardiopulmonary Resuscitation in a Porcine Model of Cardiac Arrest

Introduction: We have previously demonstrated that vasopressors administered during cardiopulmonary resuscitation (CPR) significantly decrease microcirculatory flow. In the present study, we investigated the effects of nitroglycerin on the macrocirculation macro and microcirculation and microcirculation during and after CPR in a porcine model of cardiac arrest (CA). Hypothesis: Nitroglycerin improves microcirculation but without undesirable effects on the macrocirculation during and after resuscitation. Methods: Ten male domestic pigs weighing 40±2 kg were utilized. Ventricular fibrillation was electrically induced and untreated for 5 min. The animals were then randomized to receive NTG (N group) or saline (C group). Coincident with the start of CPR, NTG (5 μg/kg) or saline was administrated into the right atrium. Defibrillation was attempted by a single 150 J shock after 5 min of CPR. Hemodynamics were recorded continuously and sublingual microcirculation was assessed with the orthogonal polarisation spectral (OPS) at baseline (BL), 1, 5 min of CPR and 1, 5 min after resuscitation. Results: All animals were resuscitated successfully resuscitated. There were no differences in coronary perfusion pressure (CPP), end-tidal carbon dioxide (ETCO 2 ) between the two groups (Figure 1). Sublingual perfused vessel density (PVD) and microcirculatory flow index (MFI) were significantly better in NTG treated animals than those of control animals during and after CPR. Conclusion: Administration of nitroglycerin at the onset of CPR improves microcirculation without undesirable effects on macrocirculation during and after resuscitation.

Abstract 12827: Detection of Spontaneous Pulse Using Acceleration Signals Acquired From CPR Feedback Sensor in Porcine Model of Cardiac Arrest

Background: Reliable detection of return of spontaneous circulation (ROSC) without long interruptions of chest compressions is part of high-quality cardiopulmonary resuscitation (CPR) and routinely done by checking pulsation of carotid or femoral arteries. The purpose of the current study was to investigate whether acceleration signals acquired from a CPR feedback sensor can be used to distinguish perfusing rhythm from pulseless electrical activity (PEA) in a porcine model of cardiac arrest. Methods: The experimental data were collected from 50 male adult pigs with prolonged cardiac arrest and CPR. ECG, arterial blood pressure and acceleration signals were synchronously recorded at a sample rate of 300 Hz. The acceleration signal (ACC) was acquired from an accelerometer-based CPR sensor that was placed on the surface of the animal’s chest over the heart. During chest compression pauses 3-second segments of signals were extracted. ROSC was defined as systolic arterial pressure (SAP) &gt;60 mmHg and pulse pressure (PP) &gt;10 mmHg in the presence of an organized rhythm. ACC was pre-processed using a narrow band-pass filter with the center frequency from 0.5 to 7.5Hz. Cross-correlation function was calculated between ECG and filtered ACC to obtain the peak correlation coefficient (CCp). Area under the receiver operating characteristic curve (AUC) was used to evaluate the ability of CCp to detect ROSC. Results: A total of 216 segments were obtained with 63 in perfusing rhythm and 153 in PEA. The filtered ACC tracings (ACC’) in perfusing rhythm showed periodic oscillations synchronized with R waves, but no periodic oscillations were observed for PEA. Compared with PEA, heart rate (159.0±50.7 vs. 86.0±44.9 bpm, p &lt;0.01), SAP (143.3±38.3 vs. 18.9±13.3 mmHg, p &lt;0.01), pulse pressure (42.3±14.5 vs. 5.6±8.3 mmHg, p &lt;0.01) and CCp (0.443±0.171 vs. 0.096±0.085, p &lt;0.01) were significantly higher for perfusing rhythm. The AUC was 0.95 when CCp was used to differentiate ROSC from PEA. Using a cut-off threshold of 0.244, the sensitivity and specificity were 90.5% respectively. Conclusions: In this animal model, the acceleration signals acquired from a CPR feedback sensor can be used to distinguish perfusing rhythm from PEA.

Abstract 11607: Effects of Delayed Treatment With Inhaled Hydrogen on Oxidative Stress and Inflammatory Cytokines After Resuscitation in a Porcine Model of Cardiac Arrest

Introduction: Immediate treatment with inhaled hydrogen (H 2 ) has been demonstrated to attenuate oxidative stress conditions and inflammatory cytokines in serum after resuscitation from cardiac arrest. However, early applying inhaled H 2 is not practical especially in out of hospital cardiac arrest because of the safety issue. In the present study, we investigated the effects of delayed treatment with H 2 on oxidative stress and inflammatory cytokines in a porcine model of cardiac arrest (CA). Hypothesis: Delayed inhalation of H 2 reduces proinflammatory cytokines but without effect on oxidative stress after resuscitation in a CA porcine model. Methods: Twenty male domestic pigs weighing 39±2 kg were studied. Ventricular fibrillation (VF) was induced electrically and CPR was initiated after 10 min of untreated VF. Animals were randomized into two groups immediately after successfully resuscitation: delayed inhalation of H 2 (DH group) or continuous inhalation of room air (C group). DH group animals were ventilated with 2% H 2 /21% oxygen from post-resuscitation 120 min (PR120) until PR240 min. Serum levels of oxidative product (8-iso-PGF 2α ) and proinflammatory cytokines (tumor necrosis factor-α [TNF-α], interleukin-6 [IL-6], and high-mobility group box protein 1 [HMGB1]) were measured by ELISA at baseline (BL), PR30, PR180 and PR360. Results: Serum levels of 8-iso-PGF 2α in all the animals were significantly increased at PR30 then decreased to the levels of BL after PR180. The levels of TNF-α, IL-6 and HMGB1 in serum of all animals were elevated after PR180. Although no significant differences in the levels of 8-iso-PGF 2α were observed between both groups, the levels of TNF-α, IL-6 and HMGB1 were significantly lower in DH group animals when compared with those in C group (Figure). Conclusions: Delayed treatment with H2 attenuates proinflammatory cytokines but without effect on oxidative stress conditions after resuscitation.