Porcine Model Of Cardiac Arrest Research Articles

The association of regional cerebral oximetry and neurologically intact survival in a porcine model of cardiac arrest

BackgroundThe objective of this study was to determine if regional cerebral oximetry (rSO2) assessed during CPR would be predictive of survival with favorable neurological function in a prolonged model of porcine cardiac arrest. This study also examined the relative predictive value of rSO2 and end-tidal carbon dioxide (ETCO2), separately and together. MethodsThis study is a post-hoc analysis of data from a previously published study that compared conventional CPR (C-CPR) and automated head-up positioning CPR (AHUP-CPR). Following 10 min of untreated ventricular fibrillation, 14 pigs were treated with either C-CPR (C-CPR) or AHUP-CPR. rSO2, ETCO2, and other hemodynamic parameters were measured continuously. Pigs were defibrillated after 19 min of CPR. Neurological function was assessed 24 h later. ResultsThere were 7 pigs in the neurologically intact group and 7 pigs in the poor outcomes group. Within 6 min of starting CPR, the mean difference in rSO2 by 95% confidence intervals between the groups became statistically significant (p < 0.05). The receiver operating curve for rSO2 to predict survival with favorable neurological function reached a maximal area under the curve value after 6 min of CPR (1.0). The correlation coefficient between rSO2 and ETCO2 during CPR increased towards 1.0 over time. The combined predictive value of both parameters was similar to either parameter alone. ConclusionSignificantly higher rSO2 values were observed within less than 6 min after starting CPR in the pigs that survived versus those that died. rSO2 values were highly predictive of survival with favorable neurological function.

Lung tissue injury and hemodynamic effects of ventilations synchronized or unsynchronized to continuous chest compressions in a porcine cardiac arrest model

AimCompare lung injury and hemodynamic effects in synchronized ventilations (between two chest compressions) vs. unsynchronized ventilations during cardiopulmonary resuscitation (CPR) in a porcine model of cardiac arrest. MethodsTwenty pigs were randomized to either synchronized or unsynchronized group. Ventricular fibrillation was induced electrically and left for 1.5 minutes. Four minutes of basic chest compression:ventilation (30:2) CPR was followed by eight minutes of either synchronized or unsynchronized ventilations (10/min) during continuous compressions before defibrillation was attempted. Aortic, right atrial and intracerebral pressures, carotid and cerebral blood flow and cardiac output were measured. Airway monitoring included capnography and respiratory function monitor. Macro- and microscopic lung injuries were assessed post-mortem. ResultsThere were no significant differences between groups in any of the measured hemodynamic variables or inspiration time (0.4 vs. 1.0 s, p = 0.05). The synchronized ventilation group had lower median peak inspiratory airway pressure (57 vs. 94 cm H2O, p < 0.001), lower minute ventilation (3.7 vs. 9.4 l min−1, p < 0.001), lower pH (7.31 vs. 7.53, p < 0.001), higher pCO2 (5.2 vs. 2.5 kPa, p < 0.001) and lower pO2 (31.6 vs. 54.7 kPa, p < 0.001) compared to the unsynchronized group after 12 minutes of CPR. There was significant lung injury after CPR in both synchronized and unsynchronized groups. ConclusionSynchronized and unsynchronized ventilations resulted in similar hemodynamics and lung injury during continuous mechanical compressions of pigs in cardiac arrest. Animals that received unsynchronized ventilations with one second inspiration time at a rate of ten ventilations per minute were hyperventilated and hyperoxygenated.Institutional protocol number: FOTS, id 6948.

A new method to evaluate carotid blood flow by continuous Doppler monitoring during cardiopulmonary resuscitation in a porcine model of cardiac arrest

AimWe used a wearable carotid Doppler patch to study carotid blood flow patterns in a porcine model of cardiac arrest to identify return of spontaneous circulation (ROSC) and hemodynamics associated with different arrhythmias and the quality of compressions. MethodsTwenty Landrace pigs were used as models of cardiac arrest following a standard protocol. Carotid blood flow was monitored continuously using noninvasive ultrasound. Carotid spectral waveforms were captured during various arrhythmias and CPR. Typical carotid blood flow waveforms were recorded at the time of ROSC, and hemodynamic changes were compared with carotid blood flow parameters. ResultsThe results showed that the carotid blood flow waveforms varied with ventricular arrhythmia type. During CPR, compression depth correlated significantly with carotid maximal velocity (Vmax) (Spearman correlation coefficient (r) = 0.682, P < 0.001) and velocity–time integral (VTI) (r = 0.794, P < 0.001). Vmax and VTI demonstrated moderate predictive value for survival. The regular carotid blood flow pattern towards the brain was observed during ROSC, concurrent with compression waveforms. After ROSC, VTI and carotid pulse volume (cPV) showed similar trends as stroke volume (SV). The carotid minute volume (cMV) exhibited a similar trend as cardiac output (CO). ConclusionsCarotid blood flow monitoring could provide valuable information about different arrhythmias as well as the quality of CPR. Carotid flow monitoring allows for timely and effective identification of ROSC. In addition, it may provide valuable hemodynamic information after ROSC.

Hemodynamics, survival and neurological function with early versus delayed automated head-up CPR in a porcine model of prolonged cardiac arrest

AimTo determine if controlled head and thorax elevation, active compression-decompression cardiopulmonary resuscitation (CPR), and an impedance threshold device combined, termed automated head-up positioning CPR (AHUP-CPR), should be initiated early, as a basic (BLS) intervention, or later, as an advanced (ALS) intervention, in a severe porcine model of cardiac arrest. MethodsYorkshire pigs (n = 22) weighing ∼40 kg were anesthetized and ventilated. After 15 minutes of untreated ventricular fibrillation, pigs were randomized to AHUP-CPR for 25 minutes (BLS group) or conventional CPR for 10 minutes, followed by 15 minutes of AHUP-CPR (ALS group). Thereafter, epinephrine, amiodarone, and defibrillation were administered. Neurologic function, the primary endpoint, was assessed 24-hours later with a Neurological Deficit Score (NDS, 0 = normal and 260 = worst deficit score or death). Secondary outcomes included return of spontaneous circulation (ROSC), cumulative survival, hemodynamics and epinephrine responsivity. Data, expressed as mean ± standard deviation, were compared using Fisher's Exact, log-rank, Mann-Whitney U and unpaired t-tests. ResultsROSC was achieved in 10/11 pigs with early AHUP-CPR versus 6/11 with delayed AHUP-CPR (p = 0.14), and cumulative 24-hour survival was 45.5% versus 9.1%, respectively (p < 0.02). The NDS was 203 ± 80 with early AHUP-CPR versus 259 ± 3 with delayed AHUP-CPR (p = 0.035). ETCO2, rSO2, and responsiveness to epinephrine were significantly higher in the early versus delayed AHUP-CPR. ConclusionWhen delivered early rather than late, AHUP-CPR resulted in significantly increased hemodynamics, 24-hour survival, and improved neurological function in pigs after prolonged cardiac arrest. Based on these findings, AHUP-CPR should be considered a BLS intervention.

Abstract 169: Effect of Fingolimod-Induced Leucocyte Sequestration on Inflammatory Response and Neurological Damages in a Porcine Model of Cardiac Arrest

Introduction: Early alterations in immune function are observed after cardiac arrest, with sepsis-like syndrome and cerebral infiltration by leucocytes. Hypothesis: The pharmacological sequestration of leucocytes within lymphoid tissues with the sphingosine 1-phosphate analog fingolimod could mitigate the inflammatory response and provide neuroprotection after cardiac arrest. Methods: Anesthetized pigs underwent 14 min of ventricular fibrillation followed by resuscitation. Animals randomly received fingolimod (1 mg/kg i.v.) or saline two hours prior to cardiac arrest (n=6 in each group). Blood samples were collected for blood cells count and dosages of cytokines (Luminex) and neurofilament light chain (NFL, Quantmetrix). Neurological dysfunction was assessed 24 hours after cardiac arrest. Results: In the Fingolimod group, total blood leucocytes and lymphocytes counts were reduced as compared to Controls, both prior to and after cardiac arrest (Figure 1A). Conversely, blood levels of Interleukin [IL]-R1a, IL-6, IL-8, IL-18 were not different among groups (e.g., Figure 1B for IL-1Ra). As illustrated in Figures 1C and 1D, NFL blood levels and neurological dysfunction score were also not different in both groups after cardiac arrest. Conclusion: Despite reducing blood total leucocytes and lymphocytes count, fingolimod did mitigate neither the circulating levels of pro- or anti-inflammatory cytokines nor the neurological damage following cardiac arrest. Leucocytes sequestration in lymphocyte tissue might not be sufficient to provide neuroprotection after cardiac arrest. Figure 1: Blood lymphocytes (A), Interleukin-1Ra blood level (B), Neurofilament light chain blood level (NFL; C) and Neurological Dysfunction score at Day 1 after cardiac arrest

Abstract 218: Effect of Airway Pressure and Localized Sternal Compression Upon Hemodynamics During Cardiopulmonary Resuscitation

Background: During cardiopulmonary resuscitation (CPR), chest compression (CC) and mechanical ventilation are cyclic in nature and each modulate the intrathoracic pressure (ITP). ITP is increased during the compression phase of CC, causing an increase in aortic pressure (AoP) and right atrial pressure (RAP) to drive forward blood flow. Similarly, positive pressure ventilation increases ITP during the inspiratory phase as pressure is transmitted through the lungs, which also has an impact on hemodynamics. The purpose of this analysis was to examine differences in hemodynamics during ventricular fibrillation (VF) arrest due to ventilation alone and during localized sternal CC of varying depths in a porcine model of cardiac arrest. Methods: Domestic swine (n = 8) underwent electrically induced VF with ten-minute downtime, followed by resuscitation with mechanical ventilation and CC with active lift to neutral chest position. Mechanical ventilation was delivered using pressure-controlled synchronized intermittent mandatory ventilation (SIMV) mode (Vt 10 mL/kg, 10 bpm, trigger -6 cmH 2 O, PEEP 5 cmH 2 O, FiO 2 100). CPR was initiated with three minutes of ventilation only, followed by one minute of break-in CC at 1.0 in and 1.5 in prior to increase to depth of 2.0 in. AoP, RAP, esophageal pressure (Pes), and airway pressure (Paw) were examined over the ventilation cycle to determine the effect of each treatment upon parameters. Results: Positive pressure ventilation caused similar changes to the Pes, RAP, and AoP values (3-5 mmHg). CC caused similar changes to Pes (3-5 mmHg), but much larger changes to the RAP and AoP (10-130 mmHg) depending on compression depth. Conclusions: The ITP is not uniform during CC, creating only modest changes to Pes. This suggests that CC generate blood pressures, and presumably flows, through mechanisms other than ITP modulation. Understanding this interaction could improve our understanding of blood flow during CPR.

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

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

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

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

A quantitative evaluation of aerosol generation during cardiopulmonary resuscitation.

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

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

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

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

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

Coagulofibrinolytic effects of recombinant soluble thrombomodulin in prolonged porcine cardiac arrest

AimTo evaluate coagulofibrinolytic abnormalities and the effects of ART-123 (recombinant human thrombomodulin alpha) in a porcine model of cardiac arrest and prolonged cardiopulmonary resuscitation (CA/CPR). MethodsFifteen pigs (n = 5 per group) underwent 8 minutes of no-flow CA followed by 50 minutes of mechanical CPR, while 2 pigs underwent sham arrest. CA/CPR animals were randomized to receive saline or 1 mg/kg ART-123 pre-arrest (5 minutes prior to ventricular fibrillation) or post-arrest (2 minutes after initiation of CPR). Arterial and venous blood samples were drawn at multiple time points for blood gas analysis and measurement of plasma and whole blood markers of coagulation and fibrinolysis. ResultsIn saline-treated CA/CPR, but not sham animals, robust and persistent activation of coagulation and fibrinolysis was observed throughout resuscitation. After 50 minutes of CPR, plasma tests and thromboelastography indicated a mix of hypercoagulability and consumptive coagulopathy. ART-123 had a robust anticoagulant effect, reducing both thrombin-antithrombin (TAT) complexes and d-dimer (p < 0.05 for each). The duration of anticoagulant effect varied depending on the timing of ART-123 administration. Similarly, ART-123 when given prior to cardiac arrest was found to have pro-fibrinolytic effects, increasing free tissue plasminogen activator (tPA, p = 0.02) and decreasing free plasminogen activator inhibitor-1 (PAI-1, p = 0.04). ConclusionA porcine model of prolonged CA/CPR reproduces many of the coagulofibrinolytic abnormalities observed in human cardiac arrest patients. ART-123 demonstrates a combination of anticoagulant and profibrinolytic effects, depending on the timing of its administration relative to cardiac arrest.

Composition of ex vivo perfusion solutions and kinetics define differential cytokine/chemokine secretion in a porcine cardiac arrest model of lung preservation.

Ex vivo lung perfusion (EVLP) uses continuous normothermic perfusion to reduce ischemic damage and to improve post-transplant outcomes, specifically for marginal donor lungs after the donation after circulatory death. Despite major efforts, the optimal perfusion protocol and the composition of the perfusate in clinical lung transplantation have not been identified. Our study aims to compare the concentration levels of cytokine/chemokine in different perfusion solutions during EVLP, after 1 and 9 h of cold static preservation (CSP) in a porcine cardiac arrest model, and to correlate inflammatory parameters to oxygenation capacities. Following cardiac arrest, the lungs were harvested and were categorized into two groups: immediate (I-EVLP) and delayed EVLP (D-EVLP), after 1 and 9 h of CSP, respectively. The D-EVLP lungs were perfused with either Steen or modified Custodiol-N solution containing only dextran (CD) or dextran and albumin (CDA). The cytokine/chemokine levels were analyzed at baseline (0 h) and after 1 and 4 h of EVLP using Luminex-based multiplex assays. Within 4 h of EVLP, the concentration levels of TNF-α, IL-6, CXCL8, IFN-γ, IL-1α, and IL-1β increased significantly (P < 0.05) in all experimental groups. The CD solution contained lower concentration levels of TNF-α, IL-6, CXCL8, IFN-γ, IL-2, IL-12, IL-10, IL-4, IL-1RA, and IL-18 (P < 0.05) compared with those of the Steen solution. The concentration levels of all experimental groups have correlated negatively with the oxygenation capacity values (P < 0.05). Protein concentration levels did not reach statistical significance for I-EVLP vs. D-EVLP and CD vs. CDA solutions. In a porcine cardiac arrest model, a longer period of CSP prior to EVLP did not result in an enhanced protein secretion into perfusates. The CD solution reduced the cytokine/chemokine secretion most probably by iron chelators and/or by the protecting effects of dextran. Supplementing with albumin did not further reduce the cytokine/chemokine secretion into perfusates. These findings may help in optimizing the preservation procedure of the lungs, thereby increasing the donor pool of organs.

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.

Abstract P3063: Selective Release Of Mitochondrial Dna After Brief Myocardial Ischemia

Objective: Mitochondrial DNA (mtDNA) is one of several pro-inflammatory damage-associated molecular patterns released from necrotic myocytes during myocardial infarction (MI). Based on our recent observation of a ~50-fold rise in circulating mtDNA after brief whole-body ischemia in a porcine model of cardiac arrest without ongoing MI, we hypothesized that ischemia-induced mtDNA release can occur in the absence of necrosis. Accordingly, we measured circulating mtDNA levels before and after localized myocardial ischemia of insufficient duration to produce myocyte necrosis in swine. Methods: Swine (n=6) were subjected to a 10-minute occlusion of the left anterior descending (LAD) coronary artery based on prior evidence that this duration of ischemia elicits myocardial injury without necrosis. Peripheral venous and coronary sinus (CS) blood samples collected at baseline (BL) as well as 1-hour and 24-hours after reperfusion were analyzed via qPCR to quantify mtDNA and nuclear DNA (nucDNA) release. Results were compared to a separate group of swine (n=6) subjected to a 75-minute LAD occlusion to produce MI. Results: Prolonged ischemia led to a significant rise in CS levels of mtDNA (6.2 ± 3.6-fold vs. BL; p&lt;0.05) and nucDNA (5.4 ± 2.0-fold vs. BL; p&lt;0.05) 1 hour after reperfusion, consistent with rapid non-selective DNA release after myocyte necrosis. In contrast, brief ischemia was associated with detectable elevations in CS mtDNA (4.6 ± 1.4-fold vs. BL; p&lt;0.05) but not nucDNA (2.1 ± 0.5-fold vs. BL; p=0.35) at this timepoint. However, the magnitude of DNA release after brief or prolonged ischemia was not sufficient to increase circulating mtDNA or nucDNA, as peripheral venous levels of mtDNA and nucDNA did not differ from BL at 1-hour or 24-hours post-reperfusion in either group. Conclusion: Brief myocardial ischemia is associated with selective release of mtDNA into circulation, providing a potential mechanism by which immune activation may occur after myocardial injury even when myocyte necrosis is absent. The magnitude of mtDNA release after brief myocardial ischemia is ~10-fold lower than that detected in peripheral blood after resuscitation from cardiac arrest, suggesting that mtDNA is released from other organs after brief whole-body ischemia.

Left rib fractures during cardiopulmonary resuscitation are associated with hemodynamic variations in a pig model of cardiac arrest

BackgroundChest compressions (CC) are the cornerstone of cardiopulmonary resuscitation (CPR). But CC are also known to cause injuries, specifically rib fractures. The effects of such fractures have not been examined yet. This study aimed to investigate hemodynamic effects of rib fractures during mechanical CPR in a porcine model of cardiac arrest (CA). MethodsWe conducted a retrospective hemodynamic study in 31 pigs that underwent mechanical CC. Animals were divided into three groups based on the location of rib fractures: No Broken Ribs group (n = 11), Left Broken Ribs group (n = 13), and Right Broken Ribs group (n = 7). Hemodynamic measurements were taken at 10 seconds before and 10, 30, and 60 seconds after rib fractures. ResultsBaseline hemodynamic parameters did not differ between the three groups. Systolic aortic pressure was overall higher in the Left Broken Ribs group than in the No Broken Ribs group at 10, 30, and 60 seconds after rib fracture (p = 0.02, 0.01, and 0.006, respectively). The Left Broken Ribs group had a significantly higher right atrial pressure compared to the No Broken Rib group after rib fracture (p = 0.02, 0.01, and 0.03, respectively). There was no significant difference for any parameter for the Right Broken Ribs group, when compared to the No Broken Ribs group. ConclusionAn increase in main hemodynamic parameters was observed after left rib fractures while right broken ribs were not associated with any change in hemodynamic parameters. Reporting fractures and their location seems worthwhile for future experimental studies.

CPR: cardiac phosphatase in resuscitation.

Out-of-hospital cardiac arrest is associated with a dismal mortality rate and low long-term survival. A large pharmacological knowledge gap exists in identifying drugs that preserve neurological function and increase long-term survival after cardiac arrest. In this issue of the JCI, Li, Zhu, and colleagues report on their engineering of a 20-amino acid cell-permeable peptide (TAT-PHLPP9c) that antagonized the phosphatase PHLPP1 and prevented PHLPP1-mediated dephosphorylation and AKT inactivation. TAT-PHLPP9c administration maintained activated AKT after arrest and led to AKT-mediated beneficial effects on the heart, brain, and metabolism, resulting in increased cardiac output and cerebral blood flow and rescue of ATP levels in affected tissues. TAT-PHLPP9c improved neurological outcomes and increased survival after cardiac arrest in murine and porcine models of cardiac arrest. These findings provide proof of concept that pharmacological targeting of PHLPP1 may be a promising approach to augmenting long-term survival after cardiac arrest.

EFFECTS OF MESENCHYMAL STEM CELLS ON POSTRESUSCITATION RENAL AND INTESTINAL INJURIES IN A PORCINE CARDIAC ARREST MODEL.

Objectives: Systemic ischemia-reperfusion triggered by cardiac arrest (CA) and resuscitation often causes postresuscitation multiple organ injuries. Mesenchymal stem cells (MSCs) have been proven to be a promising treatment for regional renal and intestinal ischemia reperfusion injuries. This study aimed to investigate the effects of MSCs on renal and intestinal injuries after cardiopulmonary resuscitation (CPR) in a porcine CA model. Methods: Twenty-two male pigs were randomly assigned to the sham (n = 6), CA/CPR (n = 8), and CA/CPR + MSC (n = 8) groups. Mesenchymal stem cells were differentiated from human embryonic stem cells and then intravenously administered at a dose of 2.5 × 10 6 /kg at 1.5 and 3 d before the CA/CPR procedure. The experimental model was established by 8 min of untreated CA, followed by 8 min of CPR. Renal and intestinal injuries were evaluated based on the serum levels of creatinine, serum urea nitrogen, intestinal fatty acid-binding protein, and diamine oxidase at 1, 2, 4, and 24 h after resuscitation. At the end of the experiment, pathological damage was determined by cell apoptosis and ferroptosis in the renal and intestinal tissues. Results: During CPR, five pigs in the CA/CPR group and seven pigs in the CA/CPR + MSC group were successfully resuscitated. After resuscitation, the serum levels of creatinine, serum urea nitrogen, intestinal fatty acid-binding protein, and diamine oxidase were significantly increased in the CA/CPR and CA/CPR + MSC groups compared with those in the sham group. However, MSC administration significantly decreased the levels of renal and intestinal injury biomarkers compared with those in the CA/CPR group. Cell apoptosis and ferroptosis, which were indicated by the levels of apoptotic cells, iron deposition, lipid peroxidation, antioxidants, and ferroptosis-related proteins, were observed in renal and intestinal tissues after resuscitation in the CA/CPR and CA/CPR + MSC groups. Nevertheless, both were significantly milder in the CA/CPR + MSC group than in the CA/CPR group. Conclusions: MSC administration was effective in alleviating postresuscitation renal and intestinal injuries possibly through inhibition of cell apoptosis and ferroptosis in a porcine CA model.

High central venous pressure amplitude predicts successful defibrillation in a porcine model of cardiac arrest

AimIncreasing venous return during cardiopulmonary resuscitation (CPR) has been shown to improve hemodynamics during CPR and outcomes following cardiac arrest (CA). We hypothesized that a high central venous pressure amplitude (CVP-A), the difference between the maximum and minimum central venous pressure during chest compressions, could serve as a robust predictor of return of spontaneous circulation (ROSC) in addition to traditional measurements of coronary perfusion pressure (CPP) and end-tidal CO2 (etCO2) in a porcine model of CA. MethodsAfter 10 min of ventricular fibrillation, 9 anesthetized and intubated female pigs received mechanical chest compressions with active compression/decompression (ACD) and an impedance threshold device (ITD). CPP, CVP-A and etCO2 were measured continuously. All groups received biphasic defibrillation (200 J) at minute 4 of CPR and were classified into two groups (ROSC, NO ROSC). Mean values were analyzed over 3 min before defibrillation by repeated-measures Analysis of Variance and receiver operating characteristic (ROC). ResultsFive animals out of 9 experienced ROSC. CVP-A showed a statistically significant difference (p = 0.003) between the two groups during 3 min of CPR before defibrillation compared to CPP (p = 0.056) and etCO2 (p = 0.064). Areas-under-the-curve in ROC analysis for CVP-A, CPP and etCO2 were 0.94 (95% Confidence Interval 0.86, 1.00), 0.74 (0.54, 0.95) and 0.78 (0.50, 1.00), respectively. ConclusionIn our study, CVP-A was a potentially useful predictor of successful defibrillation and return of spontaneous circulation. Overall, CVP-A could serve as a marker for prediction of ROSC with increased venous return and thereby monitoring the beneficial effects of ACD and ITD.

Femoral artery collapse ratio as an indicator of chest compression quality during cardiopulmonary resuscitation in a porcine cardiac arrest model

Cardiopulmonary resuscitation (CPR) quality is crucial for improving patient survival rates after cardiac arrest. This study aimed to investigate the usefulness of femoral artery collapse ratio (systolic diameter/diastolic diameter ratio) measurement using M-mode ultrasound versus end-tidal carbon dioxide (ETCO2) for the assessment of high-quality CPR in a porcine cardiac arrest model. A total of 10 male mongrel pigs (age range, 16–20 weeks; weight, 45–50 kg) were used. After anesthesia, the carotid artery was dissected and exposed. The animals were instrumented with an arterial catheter in the exposed carotid artery to monitor arterial blood pressure. Cardiac arrest was induced by injecting potassium chloride (KCl, 40 equivalents of weight). The animals underwent chest compression using a mechanical device, and the chest compression depth and ETCO2 were measured using a defibrillator. To obtain hemodynamic information, two investigators performed an ultrasound examination on both femoral arteries. One examiner measured the femoral peak systolic velocity (PSV), while the other measured the diameters of the femoral artery (systolic diameter and diastolic diameter) in a transverse or longitudinal position using the M-mode of the linear ultrasound probe. As the compression depth increased, ETCO2, femoral artery diameter, collapse ratio (systolic diameter/diastolic diameter), and blood flow increased; however, PSV decreased. The ETCO2 and collapse ratio were positively correlated. The femoral artery collapse ratio, measured using the M-mode ultrasound, could be an alternative and simple method to evaluate high-quality CPR.