Induction Of Cardiac Arrest Research Articles

Beating Heart Pulmonary Valve Replacement: Technique of Pulmonary Valve Replacement with a Biological Valve

Pulmonary valve replacement is traditionally performed using cardioplegia in order to induce cardiac arrest during the operation. However, the induction of cardiac arrest is known to be associated with several postoperative complications. Therefore, over the years new cardioprotective techniques have been introduced: one of which is the on-pump beating heart technique. The technique of pulmonary valve replacement on a beating heart could be efficacious in reducing the incidence of cardiac dysfunction or injury which can be associated with the use of cardioplegia. Such as the avoidance of aortic cross-clamping observed in the beating heart technique may be linked with lower risks of stroke and other aortic complications. Therefore, the technique that we present combines the advantages of operating on a beating heart and being on-pump in the context of complex re-do operations of the pulmonary valve.

Effect of first epinephrine administration time on cerebral perfusion pressure and cortical cerebral blood flow in a porcine cardiac arrest model

ObjectiveThe optimal time for epinephrine administration and its effects on cerebral blood flow (CBF) and microcirculation remain controversial. This study aimed to assess the effect of the first administration of epinephrine on cerebral perfusion pressure (CePP) and cortical CBF in porcine cardiac arrest model. MethodsAfter 4 min of untreated ventricular fibrillation, eight of 24 swine were randomly assigned to the early, intermediate, and late groups. In each group, epinephrine was administered intravenously at 5, 10, and 15 min after cardiac arrest induction. CePP was calculated as the difference between the mean arterial pressure and intracranial pressure. Cortical CBF was measured using a laser Doppler flow probe. The outcomes were CePP and cortical CBF measured continuously during cardiopulmonary resuscitation (CPR). Mean CePP and cortical CBF were compared using analysis of variance and a linear mixed model. ResultsThe mean CePP was significantly different between the groups at 6–11 min after cardiac arrest induction. The mean CePP in the early group was significantly higher than that in the intermediate group at 8–10 min and that in the late group at 6–9 min and 10–11 min. The mean cortical CBF was significantly different between the groups at 9–11 min. The mean cortical CBF was significantly higher in the early group than in the intermediate and late group at 9–10 min. ConclusionEarly administration of epinephrine was associated with improved CePP and cortical CBF compared to intermediate or late administration during the early period of CPR.

Changes of antioxidant enzymes in the kidney after cardiac arrest in the rat model.

Globally, cardiac arrest (CA) is a leading cause of death and disability. Asphyxial CA (ACA)-induced kidney damage is a crucial factor in reducing the survival rate. The purpose of this study was to investigate the role of antioxidant enzymes in histopathological renal damage in an ACA rat model at different time points. A total of 88 rats were divided into five groups and exposed to ACA except for the sham group. To evaluate glomerular function and oxidative stress, serum levels of blood urea nitrogen (BUN) and creatinine (Crtn) and malondialdehyde (MDA) levels in renal tissues were measured. To determine histopathological damage, hematoxylin and eosin staining, periodic acid-Schiff staining, and Masson's trichrome staining were performed. Expression levels of antioxidant enzymes including superoxide dismutase-1 (SOD-1), superoxide dismutase-2 (SOD-2), catalase (CAT), and glutathione peroxidase (GPx) were measured by immunohistochemistry (IHC). Survival rate of the experimental rats was reduced to 80% at 6 h, 55% at 12 h, 42.9% at 1 day, and 33% at 2 days after return of spontaneous circulation. Levels of BUN, Crtn, and MDA started to increase significantly in the early period of CA induction. Renal histopathological damage increased markedly from 6 h until two days post-CA. Additionally, expression levels of antioxidant enzymes were significantly decreased at 6 h, 12 h, 1 day, and 2 days after CA. CA-induced oxidative stress and decreased levels of antioxidant enzymes (SOD-1, SOD-2, CAT, GPx) from 6 h to two days could be possible mediators of severe renal tissue damage and increased mortality rate.

Stone heart syndrome after prolonged cardioplegia induced cardiac arrest in open-heart surgery – a pilot study on pigs

ObjectivesTo investigate Stone Heart Syndrome (SHS) as consequence of prolonged ischemic arrest in an experimental study on pigs in regards to onset of SHS and pathological changes. Outcomes defined as aortic cross clamp (ACC) time until onset of SHS and cellular changes characterized by SHS. MethodsEight pigs were included to undergo normothermic cardioplegia induced cardiac arrest ranging from 80 to 240 minutes of ACC. Duration of ACC was defined as time from initiation of aortic cross clamping until cessation. Normothermic, cardioplegic solution administered directly into the arterial system, though in a reduced dose compared to clinical practice. Myocardial contracture evaluated by palpation of the myocardium. Biopsies were collected from the left ventricle just after the induction of cardiac arrest and after reperfusion. Biopsies were evaluated for pathological changes indicative of SHS by electron microscopy. ResultsSix pigs completed the full trial, while two were lost to bleeding. Pigs undergoing 80 to 120 minutes of ACC regained heart rhythm either spontaneously or after defibrillation. Pigs undergoing more than 180 minutes of ACC had contracted hearts with no electrocardiographic response indicating the development of SHS. Electron microscopy findings after ACC of 80 to 120 minutes showed no or low degrees of cellular changes, whereas pig hearts with more than 180 minutes of ACC showed severe mitochondrial changes, endothelial damage, and shortening of sarcomeres consistent with SHS. ConclusionDevelopment of SHS in pigs was ACC time dependent and solely avoided when ACC was limited to a maximum of 120 minutes.

Abstract 296: Adult Swine Model of Ventricular Fibrillation Arrest for Resuscitation with Perfluorocarbon Emulsions

Background: The purpose of this study was to develop a model of ventricular fibrillation arrest with reliable outcomes and minimally invasive methods to study the use of perfluorocarbon emulsions (PFC) as agents to prevent ischemia-reperfusion injury after cardiac arrest as quantified by known biomarkers. Methods: Female Yorkshire swine underwent anesthesia and minimally invasive instrumentation for monitoring under ultrasound. Cardiac arrest was induced with spinal needle insertion at the apex and right parasternal space. Ventricular fibrillation was reliably obtained in all animals on initial attempts. A three-minute circulatory arrest state was observed. Administration of PFC was concurrent with resuscitation including closed chest compressions, epinephrine, amiodarone, and defibrillation at 1J/kg. Primary endpoint was induction of cardiac arrest and tolerance of PFC with return of spontaneous circulation. Blood levels of glial fibrillary acidic protein (GFAP) and ubiquitin C-Terminal Hydrolase-L1 (UCLH1) were secondary end points for three animals. Results: Six of six animals were induced into ventricular fibrillation on initial attempt and two of three survival experiments were able to obtain spontaneous circulation. PFC with pretreatment was tolerated well and no signs of increased pulmonary pressures. GFAP, UCHL1 were significantly lower in intervention animals compared to controls. Conclusions: The results obtained from this preliminary study and technical refinements via additional donated animals have allowed us to make modifications in the choice of PFC, vascular access, and anticoagulation plan. This model provides a consistent method for inducing ventricular fibrillation with minimally invasive techniques. The PFC tested was well tolerated. More robust evaluation of PFC as resuscitative agents is needed with appropriately powered studies.

Limb Ischemic Postconditioning Alleviates Postcardiac Arrest Syndrome through the Inhibition of Mitochondrial Permeability Transition Pore Opening in a Porcine Model.

Objective Previously, the opening of mitochondrial permeability transition pore (mPTP) was confirmed to play a key role in the pathophysiology of postcardiac arrest syndrome (PCAS). Recently, we demonstrated that limb ischemic postconditioning (LIpostC) alleviated cardiac and cerebral injuries after cardiac arrest and resuscitation. In this study, we investigated whether LIpostC would alleviate the severity of PCAS through inhibiting mPTP opening. Methods Twenty-four male domestic pigs weighing 37 ± 2 kg were randomly divided into three groups: control, LIpostC, and LIpostC+atractyloside (Atr, the mPTP opener). Atr (10 mg/kg) was intravenously injected 30 mins prior to the induction of cardiac arrest. The animals were subjected to 10 mins of untreated ventricular fibrillation and 5 mins of cardiopulmonary resuscitation. Coincident with the beginning of cardiopulmonary resuscitation, LIpostC was induced by four cycles of 5 mins of limb ischemia and then 5 mins of reperfusion. The resuscitated animals were monitored for 4 hrs and observed for an additional 68 hrs. Results After resuscitation, systemic inflammation and multiple organ injuries were observed in all resuscitated animals. However, postresuscitation systemic inflammation was significantly milder in the LIpostC group than in the control group. Myocardial, lung, and brain injuries after resuscitation were significantly improved in the LIpostC group compared to the control group. Nevertheless, pretreatment with Atr abolished all the protective effects induced by LIpostC. Conclusion LIpostC significantly alleviated the severity of PCAS, in which the protective mechanism was associated with the inhibition of mPTP opening.

A Larval Zebrafish Model for Assessing Hypoxic‐Induced In Vivo Cardiomyocyte Damage: Time Course for Induction and Cardiac Output Recovery

Larval zebrafish are used to study regenerative properties of cardiac muscle and treatments that may enhance this process. Cardiac injury models in zebrafish larva currently include cryoinjury, laser ablation, pharmacological treatment and cardiac dysfunction mutations. Effective in damaging cardiomyocytes, these models lack the critical element of tissue hypoxia, which induces molecular cascades within cardiac muscle. We have developed a potentially more realistic model for studying cardiac arrest and recovery in larval zebrafish (Danio rerio) by using acute, severe hypoxic exposure to briefly induce cardiac arrest. Exposure to PO2s of 6–9 mmHg induces loss of mobility followed by cardiac arrest within 120 min in 5 days post fertilization (dpf) and within 40 min at 10 dpf. Approximately 90% of 5dpf larvae survived acute, severe hypoxic exposure, but survival fell to 30% by 10 dpf. Heart beat resumed in surviving larvae and returned to air‐saturated water at 4 min in 5 dpf and 6–8 min at 8–10 dpf. Heart rate, stroke volume and cardiac output in control 6–7 dpf larvae before hypoxic exposure were 188±5 bpm, 0.20±0.001nl and 35.5.3±2.2 nl/min (n=35), respectively. In larvae with hypoxia‐induced cardiac arrest, heart rate returned to control values by 24 h of recovery, but stroke volume and cardiac output remained ~50% depressed from control values at 24 h of recovery. Full restoration of cardiac performance was evident at 72h, indicating that regenerative properties of the zebrafish heart extend to critical physiological measures. Molecular markers for apoptosis (Caspase‐3) were elevated >5‐fold immediately after resumption of heart beat, peaking after 4 hours into the recovery period. A cell regeneration marker (PCNA) increased >4‐fold beginning after a lag of 2 hours, and was still elevated ~6 hours after resumption of heart beat, presumably contributing to recovery of heart function. The highly reproducible cardiac effects of acute hypoxia‐induced cardiac arrest in the larval zebrafish presents an alternative, realistic model for studying cardiac tissue hypoxia injury and recovery of function.Support or Funding InformationAstraZenecaTime course of changes in heart rate, stroke volume, and cardiac output in 5–7 day larval zebrafish following induction of cardiac arrest by acute hypoxic exposure (PO2 ~ 7–9 mmHg).Figure 1

Neuroprotective Effect of the Inhibitor Salubrinal after Cardiac Arrest in a Rodent Model.

Cardiac arrest (CA) yields poor neurological outcomes. Salubrinal (Sal), an endoplasmic reticulum (ER) stress inhibitor, has been shown to have neuroprotective effects in both in vivo and in vitro brain injury models. This study investigated the neuroprotective mechanisms of Sal in postresuscitation brain damage in a rodent model of CA. In the present study, rats were subjected to 6 min of CA and then successfully resuscitated. Either Sal (1 mg/kg) or vehicle (DMSO) was injected blindly 30 min before the induction of CA. Neurological status was assessed 24 h after CA, and the cortex was collected for analysis. As a result, we observed that, compared with the vehicle-treated animals, the rats pretreated with Sal exhibited markedly improved neurological performance and cortical mitochondrial morphology 24 h after CA. Moreover, Sal pretreatment was associated with the following: (1) upregulation of superoxide dismutase activity and a reduction in maleic dialdehyde content; (2) preserved mitochondrial membrane potential; (3) amelioration of the abnormal distribution of cytochrome C; and (4) an increased Bcl-2/Bax ratio, decreased cleaved caspase 3 upregulation, and enhanced HIF-1α expression. Our findings suggested that Sal treatment improved neurological dysfunction 24 h after CPR (cardiopulmonary resuscitation), possibly through mitochondrial preservation and stabilizing the structure of HIF-1α.

Battlefield Extracorporeal Cardiopulmonary Resuscitation for Out-of-Hospital Cardiac Arrest: A Feasibility Study During Military Exercises.

To evaluate the feasibility of prehospital extracorporeal cardiopulmonary resuscitation (E-CPR) in the military exercise setting. Three 40kg Sus scrofa (wild swine) underwent controlled 35% blood loss and administration of potassium chloride to achieve cardiac arrest (CA). During CPR, initiated 1 minute after CA, the animals were transported to Role 1. Femoral vessels were cannulated, followed by E-CPR using a portable perfusion device. Crystalloid and blood transfusions were initiated, followed by tactical evacuation to Role 2 and 4-hour observation. All animals developed sustained asystole. Chest compressions supported effective but gradually deteriorating blood circulation. Two animals underwent successful E-CPR, with restoration of perfusion pressure to 80mmHg (70-90mmHg) 25 and 23 minutes after the induction of CA. After transportation to Role 2, one animal developed abdominal compartment syndrome as a result of extensive (9L) fluid replacement. The other animal received a lower volume of crystalloids (4L), and no complications occurred. In the third animal, multiple attempts to cannulate arteries were unsuccessful because of spasm and hypotension. Open aortic cannulation enabled the circuit to commence. No return of spontaneous circulation was ultimately achieved in either of the remaining animals. Our study demonstrates both the potential feasibility of battlefield E-CPR and the evolving capability in the care of severey injured combat casualties.

Inhibition of microRNA-155 Alleviates Neurological Dysfunction Following Transient Global Ischemia and Contribution of Neuroinflammation and Oxidative Stress in the Hippocampus.

Central pro-inflammatory cytokine (PIC) signal is involved in neurological deficits after transient global ischemia induced by cardiac arrest (CA). The present study was to examine the role of microRNA- 155 (miR-155) in regulating IL-1β, IL-6 and TNF-α in the hippocampus of rats with induction of CA. We further examined the levels of products of oxidative stress 8-isoprostaglandin F2α (8-iso PGF2α, indication of oxidative stress); and 8-hydroxy-2'-deoxyguanosine (8-OHdG, indication of protein oxidation) after cerebral inhibition of miR-155. CA was induced by asphyxia and followed by cardiopulmonary resuscitation in rats. ELISA and western blot analysis were used to determine the levels of PICs and products of oxidative stress; and the protein expression of NADPH oxidase (NOXs) in the hippocampus. In addition, neurological severity score and brain edema were examined to assess neurological functions. We observed amplification of IL-1β, IL-6 and TNF-α along with 8-iso PGF2α and 8-OHdG in the hippocampus of CA rats. Cerebral administration of miR-155 inhibitor diminished upregulation of PICs in the hippocampus. This also attenuated products of oxidative stress and upregulation of NOX4. Notably, inhibition of miR-155 improved neurological severity score and brain edema and this was linked to signal pathways of PIC and oxidative stress. We showed the significant role of blocking miR-155 signal in improving the neurological function in CA rats likely via inhibition of signal pathways of neuroinflammation and oxidative stress, suggesting that miR-155 may be a target in preventing and/or alleviating development of the impaired neurological functions during CA-evoked global cerebral ischemia.

Novel patterns of left ventricular mechanical activity during experimental cardiac arrest in pigs.

We conducted an experimental study to evaluate the presence of coordinated left ventricular mechanical myocardial activity (LVMA) in two types of experimentally induced cardiac arrest: ventricular fibrillation (VF) and pulseless electrical activity (PEA). Twenty anesthetized domestic pigs were randomized 1:1 either to induction of VF or PEA. They were left in nonresuscitated cardiac arrest until the cessation of LVMA and microcirculation. Surface ECG, presence of LVMA by transthoracic echocardiography and sublingual microcirculation were recorded. One minute after induction of cardiac arrest, LVMA was identified in all experimental animals. In the PEA group, rate of LVMA was of 106+/-12/min. In the VF group, we identified two patterns of LVMA. Six animals exhibited contractions of high frequency (VFhigh group), four of low frequency (VFlow group) (334+/-12 vs. 125+/-32/min, p<0.001). A time from cardiac arrest induction to asystole (19.2+/-7.2 vs. 7.3+/-2.2 vs. 8.3+/-5.5 min, p=0.003), cessation of LVMA (11.3+/-5.6 vs. 4.4+/-0.4 vs. 7.4+/-2.9 min, p=0.027) and cessation of microcirculation (25.3+/-12.6 vs. 13.4+/-2.4 vs. 23.2+/-8.7 min, p=0.050) was significantly longer in VFlow group than in VFhigh and PEA group, respectively. Thus, LVMA is present in both VF and PEA type of induced cardiac arrest and moreover, VF may exhibit various patterns of LVMA.

Regional Differences in Cerebral Glucose Metabolism After Cardiac Arrest and Resuscitation in Rats Using [18F]FDG Positron Emission Tomography and Autoradiography.

Cardiac arrest is an important cause of morbidity and mortality. Brain injury severity and prognosis of cardiac arrest patients are related to the cerebral areas affected. To this aim, we evaluated the variability and the distribution of brain glucose metabolism after cardiac arrest and resuscitation in an adult rat model. Ten rats underwent 8-min cardiac arrest, induced with a mixture of potassium and esmolol, and resuscitation, performed with chest compressions and epinephrine. Eight sham animals received anesthesia and experimental procedures identical to the ischemic group except cardiac arrest induction. Brain metabolism was assessed using [18F]FDG autoradiography and small animal-dedicated positron emission tomography. The absolute glucose metabolism measured with [18F]FDG autoradiography 2h after cardiac arrest and resuscitation was lower in the frontal, parietal, occipital, and temporal cortices of cardiac arrest animals, showing, respectively, a 36% (p=0.006), 32% (p=0.016), 36% (p=0.009), and 32% (p=0.013) decrease compared to sham group. Striatum, hippocampus, thalamus, brainstem, and cerebellum showed no significant changes. Relative regional metabolism indicated a redistribution of metabolism from cortical area to brainstem and cerebellum. Our data suggest that cerebral regions have different susceptibility to moderate global ischemia in terms of glucose metabolism. The neocortex showed a higher sensibility to hypoxia-ischemia than other regions. Other subcortical regions, in particular brainstem and cerebellum, showed no significant change compared to non-ischemic rats.

The Right Ventricle Is Dilated During Resuscitation From Cardiac Arrest Caused by Hypovolemia: A Porcine Ultrasound Study.

Dilation of the right ventricle during cardiac arrest and resuscitation may be inherent to cardiac arrest rather than being associated with certain causes of arrest such as pulmonary embolism. This study aimed to compare right ventricle diameter during resuscitation from cardiac arrest caused by hypovolemia, hyperkalemia, or primary arrhythmia (i.e., ventricular fibrillation). Thirty pigs were anesthetized and then randomized to cardiac arrest induced by three diffrent methods. Seven minutes of untreated arrest was followed by resuscitation. Cardiac ultrasonographic images were obtained during induction of cardiac arrest, untreated cardiac arrest, and resuscitation. The right ventricle diameter was measured. Primary endpoint was the right ventricular diameter at the third rhythm analysis. University hospital animal laboratory. Female crossbred Landrace/Yorkshire/Duroc pigs (27-32 kg). Pigs were randomly assigned to cardiac arrest caused by either hypovolemia, hyperkalemia, or primary arrhythmia. At the third rhythm analysis during resuscitation, the right ventricle diameter was 32 mm (95% CI, 29-35) in the hypovolemia group, 29 mm (95% CI, 26-32) in the hyperkalemia group, and 25 mm (95% CI, 22-28) in the primary arrhythmia group. This was larger than baseline for all groups (p = 0.03). When comparing groups at the third rhythm analysis, the right ventricle was larger for hypovolemia than for primary arrhythmia (p < 0.001). The right ventricle was dilated during resuscitation from cardiac arrest caused by hypovolemia, hyperkalemia, and primary arrhythmia. These findings indicate that right ventricle dilation may be inherent to cardiac arrest, rather than being associated with certain causes of arrest. This contradicts a widespread clinical assumption that in hypovolemic cardiac arrest, the ventricles are collapsed rather than dilated.

Detection of Pulmonary Embolism During Cardiac Arrest-Ultrasonographic Findings Should Be Interpreted With Caution.

The aim of this study was to test the hypothesis that the right ventricle is more dilated during resuscitation from cardiac arrest caused by pulmonary embolism, compared with hypoxia and primary arrhythmia. Twenty-four pigs were anesthetized and cardiac arrest was induced using three different methods. Pigs were resuscitated after 7 minutes of untreated cardiac arrest. Ultrasonographic images were obtained and the right ventricular diameter was measured. University hospital animal laboratory. Female crossbred Landrace/Yorkshire/Duroc pigs (27-32 kg). Pigs were randomly assigned to cardiac arrest induced by pulmonary embolism, hypoxia, or primary arrhythmia. There was no difference at baseline. During induction of cardiac arrest, the right ventricle dilated in all groups (p < 0.01 for all). The primary endpoint was right ventricle diameter at the third rhythm analysis: 32 mm (95% CI, 29-36) for pulmonary embolism which was significantly larger than both hypoxia: 23 mm (95% CI, 20-27) and primary arrhythmia: 25 mm (95% CI, 22-28)-the absolute difference was 7-9 mm. Physicians with basic training in focused cardiac ultrasonography were able to detect a difference in right ventricle diameter of approximately 10 mm with a sensitivity of 79% (95% CI, 64-94) and a specificity of 68% (95% CI, 56-80). The right ventricle was more dilated during resuscitation when cardiac arrest was caused by pulmonary embolism compared with hypoxia and primary arrhythmia. However, the right ventricle was dilated, irrespective of the cause of arrest, and diagnostic accuracy by physicians with basic training in focused cardiac ultrasonography was modest. These findings challenge the paradigm that right ventricular dilatation on ultrasound during cardiopulmonary resuscitation is particularly associated with pulmonary embolism.

Abstract 13922: Echocardiography During Resuscitation: A Paradox of Right Ventricular Dilatation in Cardiac Arrest Caused by Hypovolemia and Hyperkalemia - A Randomized Porcine Study

Introduction: The interpretation of echocardiographic findings from patients with spontaneous circulation is often extrapolated to cardiac arrest. In patients with spontaneous circulation, severe hypovolemia causes a reduction in right ventricular (RV) diameter, which may persist during cardiac arrest. In contrast, hyperkalemia may cause RV dilation by arresting the heart in diastole. Also, animal studies have demonstrated RV dilation in ventricular fibrillation (VF). Aim: To study the RV diameter during resuscitation from cardiac arrest caused by hypovolemia and hyperkalemia, compared to VF as control. Methods: Twenty-four pigs were randomized to 7 min. of cardiac arrest induced by hypovolemia, hyperkalemia, or VF. Animals were resuscitated in accordance with the AHA 2010 Advanced Life Support guidelines. Echocardiographic images were obtained before and during cardiac arrest. Primary endpoint: RV diameter at the third rhythm analysis. Results: In the hypovolemia group, an initial decrease in RV diameter during induction of cardiac arrest was followed by an abrupt increase at the onset of cardiac arrest. Onset of cardiac arrest also increased RV diameter in both the hyperkalemia and VF group (P&lt;0.01 for all) (Figure). At third rhythm analysis, the RV was dilated in all groups compared with baseline (P&lt;0.05). In the hypovolemia group, RV diameter was 32mm (95%CI 29-35) and significantly larger than in the VF group at 25mm (95%CI 22-28) (P=0.008). In the hyperkalemia group, RV diameter was 29mm (95%CI:26-32) which was not different from hypovolemia and VF (P=NS). Conclusion: The right ventricle is dilated during resuscitation from cardiac arrest caused by hypovolemia, hyperkalemia, and ventricular fibrillation. The interpretation of echocardiographic findings in the patient with spontaneous circulation should not be extrapolated to cardiac arrest. Right ventricular dilation may be a feature inherent to cardiac arrest, rather than specific to a certain cause.

Four ways to ventilate during cardiopulmonary resuscitation in a porcine model: a randomized study

BackgroundThe optimal method for out-of-hospital ventilation during cardiopulmonary rescue (CPR) is controversial.The aim of this study was to test different modes of ventilation during CPR for a prolonged period of 60 min.MethodsPigs were randomized to four groups after the induction of ventricular fibrillation, which was followed by one hour of mechanical cardiac compressions. The study comprised five pigs treated with free airways, five pigs treated with ventilators, six pigs treated with a constant oxygen flow into the tube, and six pigs treated with apnoeic oxygenation.ResultsThe free airway group was tested for 1 h, but in the first 15 min, the median PaO2 had already dropped to 5.1 kPa.The ventilator group was tested for 1 h and still had an acceptable median PaO2 of 10.3 kPa in the last 15 min. The group was slightly hyperventilated, with PaCO2 at 3.8 kPa, even though the ventilator volumes were unchanged from those before induction of cardiac arrest.In the group with constant oxygen flowing into the tube, one pig was excluded after 47 min due to blood pressure below 25 mmHg. For the remaining 5 pigs, the median PaO2 in the last 15 min was still 14.3 kPa, and the median PaCO2 was 6.2 kPa.The group with apnoeic oxygenation for 1 h had a resulting median PaO2 of 10.2 kPa and a median PaCO2 of 12.3 kPa in the last 15 min.DiscussionExcept for the free airway group, the other methods resulted in PaO2 above 10 kPa and PaCO2 between 3.8 and 12.3 kPa after one hour.ConclusionConstant oxgen flow and apnoeic oxygenation seemed to be useable alternatives to ventilator treatment.

Abstract 16926: Cardiac Ultrasound Has the Potential to Detect Tension Pneumothorax as a Reversible Cause of Cardiac Arrest - An Experimental Porcine Study

Introduction: Survival from cardiac arrest (CA) with a non-shockable rhythm is unlikely unless a reversible cause is identified and treated. Tension pneumothorax (tPTX) is a potentially reversible cause of CA, however the diagnosis can easily be missed. Cardiac ultrasound has the potential to detect reversible causes of CA. tPTX is believed to compress the heart and great vessels, causing the diameter of the right ventricle (RV) to decrease. In ventricular fibrillation and hypoxia induced CA blood accumulates on the right side of the heart causing RV distension, however the cardiac ultrasonographic characteristics of tPTX before and during CA are unknown. Hypotheses: 1) In the period up to CA tPTX will decrease RV diameter compared to hypoxia induced CA. 2) At the onset of CA and start of CPR the RV diameter will increase, abolishing group difference. Methods: Pigs were randomized to CA induced by either unilateral tPTX (n=9) or hypoxia (n=9). tPTX was induced by injecting increments of air into the intrapleural cavity to a total volume of 50 ml/kg (90% of total lung capacity), while hypoxia was induced by gradually reducing the tidal volume over 30 min. tPTX was decompressed after 7 cycles of CPR. Subcostal 5-chamber ultrasound images of the RV were obtained during induction of CA and CPR. The primary endpoints were RV diameter at the onset CA and after 3 cycles of CPR. Results: At baseline the RV diameter was (mean (95%CI)): 24.2 (21.1-27.4) mm in the tPTX group and 24.2 (20.6-27.8) mm in the hypoxia group. Induction of CA, elicited a decrease in RV diameter in the tPTX group to 16.8 (13.0-20.6) mm and an increase in the hypoxia group to 36.2 (32.5-40.0) mm (p-value for comparison to baseline and between groups at CA; p&lt;0.01). After three cycles of CPR RV diameter was significantly smaller in the tPTX group at 11.8 (7.3-16.2) mm when compared to the hypoxia group of 28.2 (24.5-31.9) mm (p&lt;0.01). Immediately after decompression no difference existed between groups: tPTX 28.9 (23.4-34.3) mm vs. hypoxia 29.2 (20.1-38.2) mm (p = 0.94). Conclusion: tPTX causes a significantly smaller diameter of the RV compared to hypoxia prior to CA. This difference persisted during CPR, enabling cardiac ultrasound to detect tPTX as a reversible cause of CA. There was no RV difference after tPTX decompression.

Abstract 12018: Cardiac Ultrasound Performed During Cardiac Arrest has Potential to Detect Pulmonary Embolism as a Reversible Cause of Cardiac Arrest when Compared to Hypoxia and Ventricular Fibrillation - A Randomized Porcine Study

Introduction: Survival from non-shockable cardiac arrest is unlikely unless a reversible cause is identified and treated. Guidelines state that ultrasound has the potential to identify reversible causes. Currently, ultrasonographic findings from patients with spontaneous circulation are extrapolated to patients in cardiac arrest. While right ventricular (RV) dilation is a finding normally associated with pulmonary embolism (PE), porcine studies have shown that RV dilation is also seen in ventricular fibrillation (VF) and severe hypoxia. No studies have investigated how causes of cardiac arrest affect RV size during resuscitation. Hypothesis: The RV diameter is larger during resuscitation of cardiac arrest caused by PE when compared to hypoxia and VF. Methods: Pigs were anesthetized and randomized to cardiac arrest induced by VF, hypoxia, or PE. Advanced life support (ALS) was preceded by 7 minutes of untreated cardiac arrest. Cardiac ultrasound images of the RV from a subcostal 5-chamber view were obtained during induction of cardiac arrest and ALS. The RV diameter was measured two centimeters from the aortic valve at end diastole. RV diameter at 3rd rhythm analysis was the primary endpoint. Based on pilot studies a sample size of 8 animals in each group was needed. Results: Eight animals were included in each group. RV diameter was not statistically different at baseline (mean (95%CI)) in VF: 19.8 (18.0-21.5) mm, hypoxia: 19.8 (16.6-22.9) mm, and PE: 21.8 (19.2-24.3) mm. During induction of cardiac arrest the RV diameter increased to 29.6 (27.3-31.9) mm in the hypoxia group and 38.0 (33.4-42.6) mm in the PE group (difference to baseline and between groups, both p&lt;0.01). Induction of VF caused an immediate increase in the RV diameter to 25.0 (21.2-28.8) mm (difference to baseline p&lt;0.01). At 3rd rhythm analysis, RV diameter was 32.4 (28.6-36.2) mm in the PE group, which was significantly larger than both the hypoxia group at 23.3 (19.5-27.0) mm and the VF group at 24.9 (22.2-27.5) mm (difference between groups p&lt;0.01). Conclusions: Cardiac arrest due to VF, hypoxia, and PE all caused an increase in RV diameter. During resuscitation the RV was larger in PE compared to VF and hypoxia. Cardiac ultrasound thus has the potential to detect PE during resuscitation.

Assessment of nonpenetrating captive bolt stunning followed by electrical induction of cardiac arrest in veal calves.

The purpose of this study was to evaluate the impact of nonpenetrating captive bolt stunning followed by electrical induction of cardiac arrest on veal calf welfare, veal quality, and blood yield. Ninety calves from the same farm were randomly assigned to 1 of 2 treatment groups in a balanced unpaired comparison design. The first treatment group (the "head-only" method-application of the pneumatic nonpenetrating stun to the frontal plate of the skull at the intersection of 2 imaginary lines extending from the lateral canthus to the opposite poll [CONTROL]) was stunned with a nonpenetrating captive bolt gun ( = 45). The second group ( = 45) was stunned with a nonpenetrating captive bolt gun followed by secondary electrical induction of cardiac arrest (the "head/heart" method-initial application of the pneumatic nonpenetrating captive bolt stun followed by 1 s application of an electrical stun to the ventral region of the ribcage directly caudal to the junction of the humerus and scapula while the stunned calf was in lateral recumbence [HEAD/HEART]). Stunning efficacy was the indicator of animal welfare used in this study. All calves were instantly rendered insensible by the initial stun and did not display common indicators of return to consciousness. For meat quality evaluation, all samples were collected from the 12th rib region of the longissimus thoracis. Meat samples were evaluated for color, drip loss, ultimate pH, cook loss, and Warner-Bratzler shear force. The L* values (measure of meat color lightness) were darker ( < 0.05) in the HEAD/HEART group (45.08 ± 0.72) than the CONTROL group (47.10 ± 0.72). There were no differences ( > 0.05) observed in a* (redness) and b* (yellowness) values between treatments. No differences ( > 0.05) were observed in drip loss, ultimate pH, cook loss, and Warner-Bratzler shear force. The blood yield from the CONTROL group (7,217.9 ± 143.5 g) was greater ( < 0.05) than that from the HEAD/HEART group (6,656.4 ± 143.5 g). Overall, the data indicated no difference between the CONTROL and HEAD/HEART groups with regard to animal welfare because the initial stun was effective in all calves. However, longissimus thoracis L* and blood yield were negatively impacted by the HEAD/HEART method. The data in this study suggest that secondary induction of cardiac arrest is not necessary with effective nonpenetrating captive bolt stunning in veal calves.

Role of Endoplasmic Reticulum Stress in Brain Damage After Cardiopulmonary Resuscitation in Rats.

Postcardiac arrest syndrome yields poor neurological outcomes, but the mechanisms underlying this condition remain poorly understood. This study investigated whether endoplasmic reticulum (ER) stress-mediated apoptosis is induced in injured brain after resuscitation. Sprague-Dawley rats were subjected to 6 min of cardiac arrest (CA) and then resuscitated successfully. In the first experiment, animals were sacrificed 1, 3, 6, 12, or 24 h (n = 3 per group) after successful cardiopulmonary resuscitation. Brain tissues were analyzed by real-time polymerase chain reaction and Western blotting. In the second experiment, either dimethyl sulfoxide or salubrinal (Sal; 1 mg/kg), an ER stress inhibitor, was injected 30 min before the induction of CA (n = 10 per group). Neurological deficits were evaluated 24 h after CA. Brain specimens were analyzed using electron microscopy, terminal deoxynucleotidyl transferase dUTP nick end labeling assays and immunohistochemistry. We found that the messenger RNA and protein levels of glucose-regulated protein 78, X-box binding protein 1, C/EBP homologous protein, and caspase 12 were significantly elevated after resuscitation. We also observed that rats treated with Sal exhibited an improved neurological deficit score (32.3 ± 15.5 in the Sal group vs. 49.8 ± 20.9 in controls, P < 0.05). In addition, morphological improvements in the hippocampal ER were observed in the Sal group compared with the dimethyl sulfoxide group 24 h after reperfusion. Furthermore, in situ immunostaining revealed that markers of ER stress were significantly inhibited by Sal pretreatment. Our findings suggested that ER stress and the associated apoptotic pathways were activated in the hippocampus after resuscitation. Administration of Sal 30 min before cardiopulmonary resuscitation ameliorated neurological dysfunction 24 h after CA, possibly through the inhibition of ER stress after postresuscitation brain injury.