Swine Model Of Cardiac Arrest Research Articles

Feasibility of profound hypothermia as part of extracorporeal life support in a pig model

ObjectiveTo investigate the feasibility of a refined aortic flush catheter and pump system to induce emergency preservation and resuscitation before extracorporeal cardiopulmonary resuscitation in a normovolemic cardiac arrest swine model simulating near real size/weight conditions of adults. MethodsIn this feasibility study, 8 female Large White breed pigs weighing 70 to 80 kg underwent ventricular fibrillation cardiac arrest for 15 minutes, followed by 4°C aortic flush (150 mL/kg for the brain; 50 mL/kg for the spine) via a new hardware ensued by resuscitation with extracorporeal cardiopulmonary resuscitation. ResultsBrain temperature was lowered from 39.9°C (interquartile range [IQR] 39.6-40.3) to 24.0°C (IQR 20.8-28.9) in 12 minutes (IQR 11-16) with a median cooling rate of 1.3°C (IQR 0.7-1.6) per minute. A median of 776 mL (IQR 673-840) per minute with a median pump pressure of 1487 mm Hg (IQR 1324-1545) were pumped to the brain. ConclusionsWith the new hardware, we were able to cool the brain within a few minutes in a large pig cardiac arrest model. The exact position; the design, diameter, and length of the flush catheter; and the brain perfusion pressure seem to be critical to effectively reduce brain temperature. Redistribution of peripheral blood could lead to sterile inflammation again and might be avoided.

Left Ventricular Compressions Improve Hemodynamics in a Swine Model of Out-of-Hospital Cardiac Arrest

ABSTRACTIntroduction: We hypothesized that chest compressions located directly over the left ventricle (LV) would improve hemodynamics, including coronary perfusion pressure (CPP), and return of spontaneous circulation (ROSC) in a swine model of cardiac arrest. Methods: Transthoracic echocardiography (echo) was used to mark the location of the aortic root and the center of the left ventricle on animals (n = 26) which were randomized to receive chest compressions in one of the two locations. After a period of ten minutes of ventricular fibrillation, basic life support (BLS) with mechanical cardiopulmonary resuscitation (CPR) was initiated and performed for ten minutes followed by advanced cardiac life support (ACLS) for an additional ten minutes. During BLS the area of maximal compression was verified using transesophageal echo. CPP and other hemodynamic variables were averaged every two minutes. Results: Mean CPP was not significantly higher in the LV group during all time intervals of resuscitation; mean CPP was significantly higher in the LV group during the 12–14 minute interval of BLS and during minutes 22–30 of ACLS (p < 0.05). Aortic systolic and diastolic pressures, right atrial systolic pressures, and end-tidal CO2 (ETCO2) were higher in the LV group during all time intervals of resuscitation (p < 0.05). Nine of the left ventricle group (69%) achieved ROSC and survived to 60 minutes compared to zero of the aortic root group (p < 0.001). Conclusions: In our swine model of cardiac arrest, chest compressions over the left ventricle improved hemodynamics and resulted in a greater proportion of animals with ROSC and survival to 60 minutes.

SELECTIVE AORTIC ARCH PERFUSION FOR THE REVERSAL OF HAEMORRHAGE-INDUCED TRAUMATIC CARDIAC ARREST IN A SWINE MODEL OF NON-COMPRESSIBLE TORSO HAEMORRHAGE

Objectives & BackgroundHaemorrhage is the leading cause of potentially survivable trauma death. Selective Aortic Arch Perfusion (SAAP) is an experimental resuscitative intervention that has the potential to improve trauma survival:...

Abstract 13264: Varying Ventilation Strategies During Cardiac Arrest Has Minimal Impact on Hemodynamics

Introduction: Prolonged duty cycle ventilation and hyperventilation are associated with reduced venous return during CPR. Meanwhile, the 30:2 compressions-ventilation method requires pauses in compressions, which could also negatively affect hemodynamics. We investigated the effect of varying ventilation strategies on hemodynamics in a swine model of cardiac arrest. Hypothesis: Continuous ventilations with a short duty cycle, as compared to longer duty cycles and standard 30:2 ventilation, would be associated with improvements in hemodynamics. Methods: CPR was performed on eight domestic swine (~30 kg) using standard physiological monitoring. Blood flow was measured in the inferior vena cava (IVC). Ventricular fibrillation (VF) was electrically induced. Mechanical chest compressions (CC) were started after four minutes of VF. CC were delivered at a rate of 100 compressions per minute and a depth of 2” for a total of 12 min. Animals were intubated and mechanically ventilated throughout the experiment. Three ventilation strategies were tested: 1) continuous ventilator-driven ventilation (CV-DV) at a rate of 6 breaths per minute and a 0.20 duty cycle, 2) CV-DV at a rate of 6 breaths per minute and a 0.50 duty cycle, and 3) standard 30:2 at a 0.20 duty cycle. All tidal volumes were calculated as 7 ml/kg. PEEP was set to zero for all ventilations. Results: Across 12 minutes of CPR, aortic pressure and coronary perfusion pressure was greater with CV-DVs of 0.20 and 0.50 duty cycle as compared to 30:2 (Table). Overall net flow in the IVC was not different among ventilation strategies. Conclusions: As compared to the 30:2 method, CV-DVs at 0.20 and 0.50 duty cycles produced small increases in blood pressures but no changes in venous return. Further research is needed to determine if hemodynamics can be improved by synchronizing continuous ventilations to CC and if this association reflects elimination of the interruptions in chest compressions.

Effects of tibial and humerus intraosseous administration of epinephrine in a cardiac arrest swine model.

Compare maximum concentration (Cmax), time to maximum concentration (Tmax), mean serum concentration of epinephrine, return of spontaneous circulation (ROSC), time to ROSC, and odds of survival relative to epinephrine administration by humerus intraosseous (HIO), tibial intraosseous (TIO), and intravenous (IV) routes in a swine cardiac arrest model. Prospective, between subjects, randomized experimental design. TriService Research Facility. Yorkshire-cross swine (n = 28). Swine were anesthetized and placed into cardiac arrest. After 2 minutes, cardiopulmonary resuscitation was initiated. After an additional 2 minutes, a dose of 1 mg of epinephrine was administered by HIO, TIO, or the IV routes. Blood samples were collected over 4 minutes and analyzed by high-performance liquid chromatography tandem mass spectrometry. ROSC, time to ROSC, Cmax, Tmax, mean concentrations over time, and odds ratio. There was no significant difference in rate of the ROSC among the TIO, HIO, and IV groups (p > 0.05). There were significant differences in Cmax: the HIO group was significantly higher than the TIO group (p = 0.007), but no significant difference between the IV and HIO (p = 0.33) or the IV and TIO group (p = 0.060). The Tmax was significantly shorter for both the IV and HIO versus the TIO group (p < 0.05), but no difference between IV and HIO (p = 0.328). The odds of survival were higher in the HIO group compared to all other groups. The TIO and HIO provide rapid and reliable access to administer life-saving medications during cardiac arrest.

The comparison of humeral intraosseous and intravenous administration of vasopressin on return of spontaneous circulation and pharmacokinetics in a hypovolemic cardiac arrest swine model

The American Heart Association (AHA) recommends intravenous (IV) or intraosseous (IO) vasopressin in Advanced Cardiac Life Support (ACLS). Obtaining IV access in hypovolemic cardiac arrest patients can be difficult, and IO access is often obtained in these life threatening situations. No studies have been conducted to determine the effects of humeral IO (HIO) access with vasopressin in the return of spontaneous circulation (ROSC). Our study compared the kinetics of vasopressin and ROSC with HIO with IV access in the hypovolemic swine model. Twenty-two Yorkshire swine were divided into three groups: HIO (n = 7), IV (n = 8), and a control group (n = 7). The IV and HIO group received vasopressin and cardiopulmonary resuscitation (CPR), while the control group received only CPR. All subjects were exsanguinated 31 percent of their blood volume, placed in cardiac arrest, and resuscitated per ACLS. Subjects that achieved ROSC were then monitored for 20 minutes. Blood samples (10 mL) collected at 0.5, 1, 1.5, 2, 2.5, 3, and 4 minutes after vasopressin injection and analyzed for maximum concentration (Cmax) and time to maximum concentration (Tmax). Data were analyzed using a multivariate analysis of variance (MANOVA) and a Fisher's Exact Test. ROSC was achieved in every subject that received vasopressin via the HIO route. Data analysis using a MANOVA pairwise comparison revealed no difference between mean Cmax (p = 0.601) and Tmax (p = 0.771) of vasopressin administered IV versus HIO routes. Analysis of the mean serum concentrations at time intervals using a repeated measures analysis of variance found no difference (p > 0.05). A Fisher's Exact Test revealed no difference in rate of ROSC between HIO and IV groups (p > 0.05). Odds ratio determined that there was a 33 times higher chance of survival among HIO subjects versus control (CPR and Defibrillation; p = 0.03) and no difference in the survivability of the HIO or IV groups (p = 0.52). The data from this study strongly suggest that there is no significant difference in ROSC, time to ROSC, hemodynamics, or pharmacokinetics between HIO vasopressin and IV vasopressin. This research reinforces current AHA guidelines recommending the use of HIO route early over delaying care awaiting IV access.

The effects of sternal intraosseous and intravenous administration of amiodarone in a hypovolemic swine cardiac arrest model.

This study compared the effects of amiodarone via sternal intraosseous (SIO) and intravenous (IV) routes on return of spontaneous circulation (ROSC), time to ROSC, concentration maximum (Cmax), time to maximum concentration (Tmax), and mean concentrations over time in a hypovolemic cardiac arrest model. Prospective, between subjects, randomized experimental design. TriService Research Facility. Yorkshire-cross swine (n = 28). Swine were anesthetized and placed into cardiac arrest. After 2 minutes, cardiopulmonary resuscitation was initiated. After an additional 2 minutes, amiodarone 300 mg was administered via the tibial intraosseous TIO or the IV route. Blood samples were collected over 5 minutes. The plasma concentrations were analyzed using high-performance liquid chromatography tandem mass spectrometry. ROSC, time to ROSC, Cmax, Tmax, and mean concentrations over time. A multivariate analyses of variance indicated that there were no significant differences in the SIO and IV groups in ROSC (p = 0.191), time to ROSC (p > 0.05), Tmax mean 88.1 ± 24.8 seconds versus 49.5 ± 21.8 seconds (p = 0.317), or Cmax mean 92,700 ± 161,112 ng/mL versus 64,159.8 ± 14,174.8 ng/mL (p = 0.260). A repeated analyses of variance indicated that there were no significant differences between the groups relative to concentrations over time (p > 0.05). The SIO provides rapid and reliable access to administer life-saving medications during cardiac arrest.

Enalapril protects against myocardial ischemia/reperfusion injury in a swine model of cardiac arrest and resuscitation

There is strong evidence to suggest that angiotensin-converting enzyme inhibitors (ACEIs) protect against local myocardial ischemia/reperfusion (I/R) injury. This study was designed to explore whether ACEIs exert cardioprotective effects in a swine model of cardiac arrest (CA) and resuscitation. Male pigs were randomly assigned to three groups: sham-operated group, saline treatment group and enalapril treatment group. Thirty minutes after drug infusion, the animals in the saline and enalapril groups were subjected to ventricular fibrillation (8 min) followed by cardiopulmonary resuscitation (up to 30 min). Cardiac function was monitored, and myocardial tissue and blood were collected for analysis. Enalapril pre-treatment did not improve cardiac function or the 6-h survival rate after CA and resuscitation; however, this intervention ameliorated myocardial ultrastructural damage, reduced the level of plasma cardiac troponin I and decreased myocardial apoptosis. Plasma angiotensin (Ang) II and Ang-(1–7) levels were enhanced in the model of CA and resuscitation. Enalapril reduced the plasma Ang II level at 4 and 6 h after the return of spontaneous circulation whereas enalapril did not affect the plasma Ang-(1–7) level. Enalapril pre-treatment decreased the myocardial mRNA and protein expression of angiotensin-converting enzyme (ACE). Enalapril treatment also reduced the myocardial ACE/ACE2 ratio, both at the mRNA and the protein level. Enalapril pre-treatment did not affect the upregulation of ACE2, Ang II type 1 receptor (AT1R) and MAS after CA and resuscitation. Taken together, these findings suggest that enalapril protects against ischemic injury through the attenuation of the ACE/Ang II/AT1R axis after CA and resuscitation in pigs. These results suggest the potential therapeutic value of ACEIs in patients with CA.

Comparison of the effects of sternal and tibial intraosseous administered resuscitative drugs on return of spontaneous circulation in a swine model of cardiac arrest.

Compare vasopressin, amiodarone, and epinephrine administration by sternal intraosseous (SIO), tibial intraosseous (TIO), and intravenous (IV) routes in a swine model of cardiac arrest. Prospective, randomized, between subjects, experimental design. Laboratory. Male Yorkshire-cross swine (N = 35), seven per group. Swine were randomized to SIO, TIO, IV, cardiopulmonary resuscitation (CPR) with defibrillation, or CPR-only groups. Ventricular fibrillation (VF) was induced under general anesthesia. Mechanical CPR began 2 minutes postarrest. Vasopressin (40 U) was administered to the SIO, TIO, and IV groups 4 minutes postarrest. Defibrillation was performed and amiodarone (300 mg) was administered 6 minutes postarrest. Defibrillation was repeated, and epinephrine (1 mg) was administered 10 minutes postarrest. Defibrillation was repeated every 2 minutes and epinephrine repeated every 4 minutes until return of spontaneous circulation (ROSC) or 26 postarrest minutes elapsed. Rate of ROSC, time to ROSC, and odds of ROSC. There were no significant differences in rate of ROSC between the SIO and TIO (p = 0.22) or IV groups (p = 1.0). Time to ROSC was five times less in the SIO group than the TIO group (p = 0.003) but not compared to IV (p = 0.125). Time to ROSC in the IV group was significantly less than the TIO group (p = 0.04). Odds of ROSC for the SIO group were five times higher compared to the TIO group but same as IV. Odds of ROSC in the IV group were higher than the TIO group. There was a statistically significant delay in the time to ROSC and a clinically significant difference in odds of ROSC when resuscitative drugs, including lipophilic amiodarone, were administered by the TIO route compared to the SIO and IV routes in a swine model of sudden cardiac arrest. Further investigations are warranted to isolate the mechanism behind these findings.

Feasibility of Biosignal‐guided Chest Compression During Cardiopulmonary Resuscitation: A Proof of Concept

Cardiac arrest is one of the leading causes of death in the United States and is treated by cardiopulmonary resuscitation (CPR). CPR involves both chest compressions and positive pressure ventilations when given by medical providers. Mechanical chest compression devices automate chest compressions and are beginning to be adopted by emergency medical services with the intent of providing high-quality, consistent chest compressions that are not limited by human providers who can become fatigued. Biosignals acquired from cardiac arrest patients have been characterized in their ability to track the effect of CPR on the patient. The authors investigated the feasibility and appropriate response of a biosignal-guided mechanical chest compression device in a swine model of cardiac arrest. After a custom signal-guided chest compression device was engineered, its ability to respond to biosignal changes in a swine model of cardiac arrest was tested. In a preliminary series of six swine, two biosignals were used: mean arterial pressure (MAP) and a mathematical derivative of the electrocardiogram waveform, median slope (MS). How these biosignals changed was observed when chest compression rate and depth were adjusted by the signal-guided chest compression device, independent of the user. Chest compression rate and depth were adjusted by the signal-guided chest compression device according to a preset threshold algorithm until either of the biosignals improved to satisfy a set "threshold" or until the chest compression rate and depth achieved maximum values. Defibrillation was attempted at the end of each resuscitation in an effort to achieve return of spontaneous circulation (ROSC). The signal-guided chest compression device responded appropriately to biosignals by changing its rate and depth. All animals exhibited positive improvements in their biosignals. During the course of the resuscitation, three of the six animals improved their MS biosignal to reach the MS threshold, while two of the six animals improved their MAP biosignal to reach the MAP threshold. In the six experiments conducted, defibrillation was attempted on five animals, and two animals achieved ROSC. In this proof-of-concept study, a signal-guided chest compression device was demonstrated to be capable of responding to biosignal input and delivering chest compressions with a broad range of rates and depths.

Effects of intraosseous epinephrine in a cardiac arrest swine model

BackgroundInterruptions in cardiopulmonary resuscitation (CPR) to obtain vascular access reduces blood flow to vital organs. Tibial intraosseous (TIO) access may be a faster alternative to intravenous (IV) access for delivery of vasoactive medications. The purpose of this study was to examine the differences in pharmacokinetics and pharmacodynamics of TIO- and IV-delivered epinephrine. Materials and methodsA prospective, between subjects, experimental design comparing Cmax, Tmax, return of spontaneous circulation (ROSC), and time to ROSC. Adult male swine were divided into three equal groups (n = 7) all received CPR and defibrillation: the second group received IV epinephrine and the third group received tibial intraosseous epinephrine. Swine were placed in cardiac arrest for 2 min before CPR was initiated. After 2 min of CPR, epinephrine was delivered by IV or TIO, and serial blood samples were collected over 4 min. ResultsThere were no significant differences between IV versus TIO epinephrine in achieving ROSC, time to ROSC, and Cmax. A one-way analysis of variance demonstrated a significant difference between the IV and TIO groups in Tmax (P = 0.025). A Fisher exact test demonstrated a significant difference between IV epinephrine versus CPR/Defib only (P = 0.035) and TIO epinephrine versus CPR/Defib only (P = 0.010) in achieving ROSC. A multivariate analysis of variance showed significant differences in IV versus intraosseous epinephrine concentration at specific time intervals: 60 (P = 0.023), 90 (P = 0.001), and 120 (P < 0.000) sec. ConclusionsIn the context of ROSC, epinephrine delivered via TIO route is a clinically relevant alternative to IV administration. When IV access cannot be immediately obtained in cardiac arrest patients, TIO access should be considered.

Effects of tibial intraosseous and IV administration of vasopressin on kinetics and survivability in cardiac arrest

PurposePurposes of this study were to compare tibial intraosseous (TIO) and intravenous (IV) administration of vasopressin relative to return of spontaneous circulation (ROSC) and time to ROSC in an adult swine cardiac arrest model. In addition, the purposes were to compare the concentration maximum (Cmax), time to maximum concentration (Tmax), and odds of ROSC. MethodsThis was a between-subjects, prospective experimental study. Yorkshire swine (N = 21) were randomly assigned to 1 of 3 groups: TIO, IV, or control groups. The swine were anesthetized and instrumented, and then cardiac arrest was induced and sustained for 2 minutes. Cardiopulmonary resuscitation was initiated and continued for 2 minutes. Vasopressin was then administered via the TIO or IV route. Blood samples were collected for 4 minutes to determine the Cmax and Tmax of vasopressin. Concentration maximum and Tmax were calculated by use of liquid chromatography with mass spectrometry. ResultsThere was no difference in ROSC between the TIO and IV groups (P = .63). The Cmax of vasopressin was significantly higher in the IV group compared to the TIO group (P = .017). However, there was no significant difference in ROSC, time to ROSC, or Tmax between groups (P > .05). All subjects had ROSC in both the IV and TIO groups, and none had ROSC in the control group. There was 225 times greater chance of survival for both the IV and TIO groups compared to the control group. ConclusionThe data support that the TIO is an effective route for vasopressin in a cardiac arrest model.

Abstract 12914: The Effect of Isosorbidemononitrate on Myocardium in a Swine Model of Cardiac Arrest

Introduction: To investigate the protective effect of isosorbidemononitrate (IM) on myocardial injury after the return of spontaneous circulation (ROSC) in a swine model of ventricular fibrillation cardiac arrest (VFCA). Methods: Ventricular fibrillation was induced and untreated for 8 minutes in twenty domestic pigs. Defibrillation was attempted after 2 minutes of CPR. The animals were randomized into two groups: IM group (n=10) and saline control group (SA group, n=10). IM (2μg/kg/min) or the same volume of saline was administered for 6 hrs post-resuscitation. Post resuscitation myocardial function was evaluated using pulse-induced contour cardiac output (PiCCO) at 1, 6 and 24 hrs after ROSC. Serum troponin I was tested using the enzyme-linked immunosorbent assay (ELISA) at the same time points during 24 hours post-resuscitation. Echocardiography and transmission electron microscopy were performed at 72 hrs after ROSC. The duration of survival was monitored in all animals. Results: Significantly greater ejection fraction (EF) and cardiac output (CO) in the IM group at 1, 6 and 24 hrs after ROSC (Fig.1). Troponin I in the IM group was significantly lower than that in the SA group at 6 and 24 hrs after ROSC. Better cardiac function (Table 1) and less ultrastructural deterioration were observed in the MI group at 72 hrs after resuscitation. However, there is no significant difference in the duration of survival between the two groups. Conclusions: In a swine model of cardiac arrest, isosorbidemononitrate attenuated post-resuscitation myocardial dysfunction.

Mild hypothermia inhibits systemic and cerebral complement activation in a swine model of cardiac arrest.

Complement activation has been implicated in ischemia/reperfusion injury. This study aimed to determine whether mild hypothermia (HT) inhibits systemic and cerebral complement activation after resuscitation from cardiac arrest. Sixteen minipigs resuscitated from 8 minutes of untreated ventricular fibrillation were randomized into two groups: HT group (n=8), treated with HT (33°C) for 12 hours; and normothermia group (n=8), treated similarly as HT group except for cooling. Blood samples were collected at baseline and 0.5, 6, 12, and 24 hours after return of spontaneous circulation (ROSC). The brain cortex was harvested 24 hours after ROSC. Complement and pro-inflammatory markers were detected using enzyme-linked immunosorbent assay. Neurologic deficit scores were evaluated 24 hours after ROSC. C1q, Bb, mannose-binding lectin (MBL), C3b, C3a, C5a, interleukin-6, and tumor necrosis factor-α levels were significantly increased under normothermia within 24 hours after ROSC. However, these increases were significantly reduced by HT. Hypothermia decreased brain C1q, MBL, C3b, and C5a contents 24 hours after ROSC. Hypothermic pigs had a better neurologic outcome than normothermic pigs. In conclusion, complement is activated through classic, alternative, and MBL pathways after ROSC. Hypothermia inhibits systemic and cerebral complement activation, which may provide an additional mechanism of cerebral protection.

Cardiopulmonary Arrest and Resuscitation in Severe Sepsis and Septic Shock: A Research Model.

Cardiopulmonary resuscitation in patients with severe sepsis and septic shock is challenging and usually unsuccessful. The aim of the present study is to describe our swine model of cardiac arrest and resuscitation in severe sepsis and septic shock. In this prospective randomized animal study, 10 healthy female Landrace-Large White pigs with an average weight of 20 ± 1 kg (aged 19 - 21 weeks) were the study subjects. Septicemia was induced by an intravenous infusion of a bolus of 20-mL bacterial suspension in 2 min, followed by a continuous infusion during the rest of the experiment. After septic shock was confirmed, the animals were left untreated until cardiac arrest occurred. All animals developed pulseless electrical activity between the fifth and sixth hours of septicemia, whereas five (50%) of 10 animals were successfully resuscitated. Coronary perfusion pressure was statistically significantly different between surviving and nonsurviving animals. We found a statistically significant correlation between mean arterial pressure and unsuccessful resuscitation (P = 0.046), whereas there was no difference in end-tidal carbon dioxide (23.05 ± 1.73 vs. 23.56 ± 1.70; P = 0.735) between animals with return of spontaneous circulation and nonsurviving animals. During the 45-min postresuscitation monitoring, we noted a significant decrease in hemodynamic parameters, although oxygenation indices and lactate clearance were constantly increased (P = 0.001). This successful basic swine model was for the first time developed and may prove extremely useful in future studies on the periarrest period in severe sepsis and septic shock.

Abstract 214: Serum VEGF Levels Are Inversely Associated with Ionized Calcium Levels During the Early Postarrest Period

BACKGROUND: Vascular endothelial growth factor (VEGF) is a signaling peptide released in response to hypoxia that induces the influx of calcium into endothelial cells. Decreases in serum levels of ionized calcium (iCa2+) are observed following resuscitation from cardiac arrest. We hypothesized that elevations in VEGF would correlate with the decrease in iCa2+ observed in a swine model of cardiac arrest. METHODS: Thirty-five mixed breed Yorkshire swine were premedicated, intubated, and placed under general anesthesia with inhaled isoflurane and nitrous oxide. Under fluoroscopic guidance, balloon occlusion of the left anterior descending coronary artery was performed, just distal to the first septal perforator to induce ventricular fibrillation (VF). Following 7 minutes of untreated VF, standard ALS resuscitation was attempted. Upon return of spontaneous circulation, blood was sampled at 0, 15, and 30 min post arrest for levels of iCa2+ and VEGF. RESULTS: iCa2+ demonstrated an inverse correlation with VEGF levels, with a Spearman rank correlation of rho=-0.52, p&lt;0.0001. In generalized linear mixed modeling (FIGURE 1), a 1 pg/mL increase in VEGF concentrations was associated with a decrease in iCa2+ of 0.001 mg/dL (95% CI 0.003-0.001, p&lt;0.0001). CONCLUSIONS: VEGF is inversely associated with iCa2+ during the early post arrest period. Its production may be responsible for the observed decrease in circulating iCa2+, which may in turn contribute to post arrest hypotension and myocardial dysfunction.

ABSTRACT 117

Background and aims: Neurological outcome following cardiopulmonary arrest in children is poor and depends upon the quality and technique of CPR delivered. Active compression-decompression CPR (ACD-CPR) has been shown to result in improved hemodynamic outcomes, but neurological outcome has not yet been evaluated. We have developed a novel adhesive glove device (AGD) that allows us to achieve active compression-decompression CPR in neonate and pediatric piglet models of cardiac arrest. Aims: We hypothesized that ACD-CPR delivered by the adhesive glove device (AGD-CPR) results in better brain perfusion as compared to S-CPR and, thus, resulting in improved neurological outcome. Methods: Prospective, randomized, controlled survival animal study. Ten anesthetized & ventilated piglets of either sex (~12Kg) were randomized after 8 minutes of untreated VF to receive either Standard CPR (S-CPR) or AGD-CPR for 5 minutes. Neurologic outcome were determined using an already established multiple neurological deficit score by a veterinary neurologist at baseline and 24 hours after CPR. Data (mean±SD) were analyzed using Wilcoxon Mann-Whitney test; p-value ≤0.05 was considered significant. Results: AGD-CPR group exhibited better neurological outcome as compared to S-CPR group. Furthermore, four animals on the S-CPR group were blind, while all animals on the AGD-CPR group were visual.Table 1: Neurological outcome scoresConclusions: ACD-CPR delivered by our novel adhesive glove device (AGD-CPR) results in better neurological outcome in a swine model of cardiac arrest.

Hypothermia-Induced Neuroprotection is Associated with Reduced Mitochondrial Membrane Permeability in a Swine Model of Cardiac Arrest

Correction to: Journal of Cerebral Blood Flow &amp; Metabolism (2013) 33, 928–934; doi: 10.1038/jcbfm.2013.33 ; published online 13 March 2013 A fund grant number was incorrectly omitted from the Acknowledgements. The following sentence should be read with the Funding Statement: ‘This work was supported by the Liaoning Province Nature Science Foundation (Grant No. 2013023020).’

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Introduction: Therapeutic hypothermia (TH) is known as the most efficient treatment for reducing brain injury during postresuscitation care. However, there have been limited data that show the benefits of prolonged TH, especially in a clinically relevant large animal cardiac arrest model. The aim of this study as to investigate whether 48 hrs of therapeutic hypothermia (TH) is more effective to attenuate brain apoptosis than 24 hrs and to determine whether the antiapoptotic effects of TH are associated with the suppressions of the cleavage of protein kinase C-delta (δPKC), the cytosolic release of cytochrome c, and the cleavage of caspase 3 in a swine cardiac arrest model. Methods: This was a prospective laboratory study conducted on male domestic pigs. After 6 mins of no flow time that was induced by ventricular fibrillation, cardiopulmonary resuscitation was provided, and the return of spontaneous circulation (ROSC) was achieved. The animals were randomly assigned to the following groups: sham, normothermia (NT), 24 hrs of TH (24-TH), or 48 hrs (48-TH). TH (core temperature, 32 - 34°) was maintained for 24 or 48 hrs post-ROSC, and the animals were rewarmed for 8 hrs. At 60 hrs post-ROSC, the animals were sacrificed, and brain tissues were harvested. We examined cellular apoptosis and neuronal damage in the brain hippocampal cornu ammonis 1 region. We also measured the cleavage of δPKC, the cytosolic release of cytochrome c, and the cleavage of caspase 3 in the hippocampus. Results: The 48-TH attenuated cellular apoptosis and neuronal damage when compared to NT. There was also a decrease in the cleavage of δPKC, the cytosolic release of cytochrome c, and the cleavage of caspase 3. However, 24-TH did not significantly attenuate cellular apoptosis or neuronal damage. Conclusions: We found that 48 hrs of TH was more effective in attenuating brain apoptosis than 24 hrs of TH. We also found that the antiapoptotic effects of TH were associated with the suppressions of the cleavage of δPKC, the cytosolic release of cytochrome c, and the cleavage of caspase 3.

Automatic heart rate complexity monitoring in a swine model of cardiac arrest due to massive exsanguination

checking postimplant results is usually obtained by mean of clinic (New York Heart Association [NYHA] class improvement) and instrumental (ejection fraction [EF] and left ventricular volumes by means of echocardiogram) evaluation. Objective of the present study was to evaluate the association between the novel nonlinear index, calculated from electrocardiogram (ECG) preprocedure and postprocedure, compared with traditional linear indices to assess the reliability and effectiveness in evaluating results of resynchronization therapy. Methods: We have used OntoCare System (OntoMed LLC) tomeasure CRT impact among patients who received CRT via pacemaker or defibrillator in combination with optimal pharmacological therapy, according to guidelines. Particularly, we measured the impact of stimulation analyzing the ECG performed before and after implant. Electrocardiogram complexity values have been considered significant (the difference between basal and stimulated ECG) when ≥25%. The OntoCare system measures complexity analyzing the structure of information, in particular the multidimensional structure of the ECG, taking into account the interactions between ECG channels and establishing an innovative means of characterizing generic dynamical systems and biologic signals. Results: We retrospectively analyzed 87 patient ECGs implantedwith CRT in our center. New York Heart Association class, left ventricular echocardiography (ECHO) measurements, and EF preimplant and postimplant have been analyzed and compared with complexity values. The OntoCare system found that 69 (79%) of 87 patients had a significant impact of therapy (complexity value threshold, 25%), whereas in the remaining 18 (21%) of 87 patients, there is no variation in the complexity. We then compared the 2 groups, called responder (R) and nonresponder (NR), respectively, with clinical and instrumental data in our possession. If we compare the values before and after the implant, we find that left ventricular end-diastolic volume (LVEDV) changes from 190 to 159 mL (−31 mL; P= .039) in R group and from 214 to 201 mL (−13 mL; P = .62) in NR group. The EF increases from 28.1% to 37.2% (+9.1%; P= .0001) in R group and from 27.3% to 33.6% (+6.3%; P = .0005) in NR group; NYHA class changes from 2.84 to 1.69 (−1.15, P = .01) in R group and from 2.55 to 2.65 (+0.1; P = .5) in NR group. Conclusions: Even if results are drawn from a small sample of patients with retrospective analysis, this study shows that the complexity index is reliable and effective in providing prognostic data in patients implanted with CRT. In addition, complexity index shows a strong association with other parameters (EF, ECHO measurements, and NYHA class) traditionally used to evaluate efficacy of CRT.