Porcine Model Of Cardiac Arrest Research Articles

A Grouped Up-and-Down Method Used for Efficacy Comparison Between Two Different Defibrillation Waveforms.

Electrical defibrillation, which consists of delivering a therapeutic dose of the electrical current to the fibrillating heart with the aid of a defibrillator, is still the only effective way to treat life-threatening ventricular fibrillation (VF). However, the efficacy of electrical therapy for terminating VF is highly dependent on the waveform applied. When new defibrillation waveforms or techniques are developed, their efficacy needs to be accurately evaluated and compared to those in use. A common method for the comparison of defibrillation efficacy is to estimate and compare the individual defibrillation threshold (DFT) by constructing dose response curves or using an up-and-down method. Since DFT is calculated by repetitive and sequential shocks, there will be variability for each measurement and for each individual. This creates a considerable uncertainty for paired comparison. In this paper, a novel grouped up-and-down method is developed for the comparison of defibrillation efficacy between two different defibrillation waveforms or techniques. The efficacy of two commonly used biphasic defibrillation waveforms was compared in a porcine model of cardiac arrest using the developed method. Experimental results demonstrate that the proposed method is more sensitive for efficacy comparison and requires less defibrillation attempts compared with traditional DFT methods.

Ischemic Postconditioning during Cardiopulmonary Resuscitation Improves Cardiac Mitochondrial Respiration

Ischemic postconditioning (IPC) during cardiopulmonary resuscitation (CPR) increases neurologically intact survival in a porcine cardiac arrest model. We investigated the effect of IPC on mitochondrial respiration, an important therapeutic target for resuscitation, during CPR in this model. Blood pressure and ECG were continuously recorded. After 15 min of ventricular fibrillation, animals received standard CPR +/‐ IPC. IPC consisted of 3 cycles of 20 sec compression / 20 sec pause for the first 2 min of CPR. Cardiac mitochondria were isolated after 4 min. Closed‐cell respiration was measured for complex I (pyruvate+malate) and II (succinate+rotenone). In IPC‐treated animals vs. standard CPR, complex I and II respiratory control indices (RCI), calculated as the ratio of state 3:4 respiration, were higher (6.7±0.8 and 3.1±0.6 vs. 4.3±0.7 and 2.4±0.2, respectively) and complex I and II state 4 respiration (µmol O2*hr‐1*mg‐1) were lower (1.7±0.2 and 2.7±0.3 vs. 2.3±0.5 and 3.3±0.5, respectively). Blood pressure during CPR did not differ. In conclusion, IPC improved mitochondrial oxidative phosphorylation as early as 4 min after initiation of CPR, suggesting that CPR is a source of reperfusion injury and a critical time for intervention. Supported by NIH (R01 HL123227) and VA (CARA‐026‐10F).

Modeling cardiac arrest and resuscitation in the domestic pig.

Cardiac arrest remains a leading cause of death and permanent disability worldwide. Although many victims are initially resuscitated, they often succumb to the extensive ischemia-reperfusion injury inflicted on the internal organs, especially the brain. Cardiac arrest initiates a complex cellular injury cascade encompassing reactive oxygen and nitrogen species, Ca(2+) overload, ATP depletion, pro- and anti-apoptotic proteins, mitochondrial dysfunction, and neuronal glutamate excitotoxity, which injures and kills cells, compromises function of internal organs and ignites a destructive systemic inflammatory response. The sheer complexity and scope of this cascade challenges the development of experimental models of and effective treatments for cardiac arrest. Many experimental animal preparations have been developed to decipher the mechanisms of damage to vital internal organs following cardiac arrest and cardiopulmonary resuscitation (CPR), and to develop treatments to interrupt the lethal injury cascades. Porcine models of cardiac arrest and resuscitation offer several important advantages over other species, and outcomes in this large animal are readily translated to the clinical setting. This review summarizes porcine cardiac arrest-CPR models reported in the literature, describes clinically relevant phenomena observed during cardiac arrest and resuscitation in pigs, and discusses numerous methodological considerations in modeling cardiac arrest/CPR. Collectively, published reports show the domestic pig to be a suitable large animal model of cardiac arrest which is responsive to CPR, defibrillatory countershocks and medications, and yields extensive information to foster advances in clinical treatment of cardiac arrest.

Peer review report 2 on “Effects of humeral intraosseous versus intravenous epinephrine on pharmacokinetics and return of spontaneous circulation in a porcine cardiac arrest model”

Peer review report 2 on “Effects of humeral intraosseous versus intravenous epinephrine on pharmacokinetics and return of spontaneous circulation in a porcine cardiac arrest model”

Peer review report 3 on “Effects of humeral intraosseous versus intravenous epinephrine on pharmacokinetics and return of spontaneous circulation in a porcine cardiac arrest model”

Peer review report 3 on “Effects of humeral intraosseous versus intravenous epinephrine on pharmacokinetics and return of spontaneous circulation in a porcine cardiac arrest model”

Peer review report 1 on “Effects of humeral intraosseous versus intravenous epinephrine on pharmacokinetics and return of spontaneous circulation in a porcine cardiac arrest model”

Peer review report 1 on “Effects of humeral intraosseous versus intravenous epinephrine on pharmacokinetics and return of spontaneous circulation in a porcine cardiac arrest model”

Tilting for perfusion: Head-up position during cardiopulmonary resuscitation improves brain flow in a porcine model of cardiac arrest

IntroductionCerebral perfusion is compromised during cardiopulmonary resuscitation (CPR). We hypothesized that beneficial effects of gravity on the venous circulation during CPR performed in the head-up tilt (HUT) position would improve cerebral perfusion compared with supine or head-down tilt (HDT). MethodsTwenty-two pigs were sedated, intubated, anesthetized, paralyzed and placed on a tilt table. After 6min of untreated ventricular fibrillation (VF) CPR was performed on 14 pigs for 3min with an automated CPR device called LUCAS (L) plus an impedance threshold device (ITD), followed by 5min of L-CPR+ITD at 0° supine, 5min at 30° HUT, and then 5min at 30° HDT. Microspheres were used to measure organ blood flow in 8 pigs. L-CPR+ITD was performed on 8 additional pigs at 0°, 20°, 30°, 40°, and 50° HUT. ResultsCoronary perfusion pressure was 19±2mmHg at 0° vs. 30±3 at 30° HUT (p<0.001) and 10±3 at 30° HDT (p<0.001). Cerebral perfusion pressure was 19±3 at 0° vs. 35±3 at 30° HUT (p<0.001) and 4±4 at 30° HDT (p<0.001). Brain–blood flow was 0.19±0.04mlmin−1g−1 at 0° vs. 0.27±0.04 at 30° HUT (p=0.01) and 0.14±0.06 at 30° HDT (p=0.16). Heart blood flow was not significantly different between interventions. With 0, 10, 20, 30, 40 and 50° HUT, ICP values were 21±2, 16±2, 10±2, 5±2, 0±2, −5±2 respectively, (p<0.001), CerPP increased linearly (p=0.001), and CPP remained constant. ConclusionDuring CPR, HDT decreased brain flow whereas HUT significantly lowered ICP and improved cerebral perfusion. Further studies are warranted to explore this new resuscitation concept.

Abstract 304: The Effects of Compression Waveforms on the Outcomes of Cardiopulmonary Resuscitation in a Porcine Model of Cardiac Arrest

Background: Previous studies have demonstrated that different mechanical compression waveforms yield different hemodynamic efficacy. In the present study, we investigated the effects of two different compression waveforms on the hemodynamics and defibrillation efficacy in a pig model of CPR. Methods: Ventricular fibrillation was electrically induced in ten male domestic pigs weighing between 35 - 40 kg and untreated for 7 mins. The animals were then randomized to receive chest compression with either trapezoidal (TW) or sinusoidal (SW) waveform. After a total 5 mins of CPR, defibrillation was attempted. ECG, aortic blood pressure (AP), right atrium blood pressure (RAP) and carotid blood flow (CBF) were continuously record and analyzed after the experiments were completed. Results: All animals were resuscitated. The total defibrillation attempts in the TW group were significantly fewer than the SW group (1.6±0.9 vs. 11±7.8, p=0.03) prior to successful resuscitation. Amplitude spectrum analysis (AMSA) and signal integral were significantly greater in each minute of CPR in the TW group when compared with the SW group (Figure 1). Significantly greater CPPs were observed in the TW group during the last 3 mins of CPR. Mean CBF showed no difference during CPR between the two groups, but the dynamic forward CBF in the first 4 mins of CPR was significantly greater in the TW group (Figure 2). Conclusions: Chest compression with trapezoidal waveform improved hemodynamics and defibrillation efficacy in the pig model of CPR. Compression waveform therefore became another important factor to be considered during mechanical chest compression.

Abstract 289: Effect of Elevated Legs on Hemodynamic Performance During Cardiopulmonary Resuscitation in a Porcine Model of Cardiac Arrest

Purpose of the study: During advanced life support (ALS) end-tidal carbon dioxide (EtCO 2 ) reflects cardiac output (CO). A recent clinical study found an association between passive leg raising (PLR) and increased EtCO 2 during ALS. This may reflect a transient increase in pulmonary blood flow and CO, but might cause a detrimental decrease in coronary perfusion pressure (CPP). We evaluated the effect of PLR during experimental ALS in a randomized, factorial design. Materials and methods: In nine anesthetized domestic pigs (30±1.8 kg) ventricular fibrillation was induced electrically. After 3 minutes of no-flow, mechanical chest compressions (5cm @ 100 min -1 ) were started. During four 5-minute segments of CPR we measured CO, EtCO 2 , perfusion pressures, carotid and cerebral cortical microcirculatory blood flow (MBF) and CPP (the average of the positive pressure difference between decompression aortic pressure (AP) and right atrial pressure (RAP)) at minute 2 and 4. Interventions were provided in a randomized sequence with PLR vs supine position, with or without epinephrine (0.5mg iv). Values are given as mean±standard deviation. Results: PLR did not increase EtCO2 compared to supine position (3.1±0.7 vs 3.0±0.8 kPa), but CO was minimally increased from 1.1±0.3 to 1.2±0.3 Lmin -1 ,(p=0.003). PLR did not significantly increase AP (57±15 vs. 48±18 mmHg, p=0.3), but RAP was higher (43±10 vs. 31±7, p=0.003). However, no difference was found in CPP due to marked variation in both groups (median(range): PLR 20 (9,43) and supine 17(9,58)). The effect of epinephrine during this experimental setup was minimal. Conclusion: We did not find a positive effect of PLR during experimental ALS, but there were no obviously detrimental effects either.

Abstract 138: Remote Ischemic Postconditioning Alleviates Postresuscitation Inflammatory Response and Pulmonary Edema in a Porcine Model of Cardiac Arrest

Introduction: Systemic ischemia-reperfusion injury produced by CA and resuscitation can result in severe post-cardiac arrest syndrome; which includes systemic inflammatory response and multiple organ dysfunction syndrome such as acute pulmonary edema. We previously demonstrated that remote ischemic post-conditioning (RIpostC) improved post-resuscitation myocardial and cerebral function in a rat model of CA. In this study, we investigated the effects of RIpostC on inflammatory response and pulmonary edema after CPR in a porcine model. Hypothesis: RIpostC would alleviate post-resuscitation inflammatory response and pulmonary edema in a porcine model of CA. Methods: Fourteen male domestic pigs weighing 37 ± 2 kg were utilized. Ventricular fibrillation was electrically induced and untreated for 10 mins. The animals were then randomized to receive RIpostC or control. Coincident with the start of CPR, RIpostC was induced by four cycles of 5 mins of limb ischemia and then 5 mins of reperfusion. Defibrillation was attempted after 5 mins of CPR. The resuscitated animals were monitored for 4 hrs and observed for an additional 68 hrs. Results: Six of the seven animals in each group were successfully resuscitated. After resuscitation, significantly lower levels of tumor necrosis factor-α and interleukin-6 were measured in the animals that received RIpostC when compared with the control group. Post-resuscitation extra-vascular lung water index was lower in the RIpostC group than in the control group; in which the differences were significant at 2,3 and 4 hrs (Table). Conclusion: In a porcine model of CA, RIpostC significantly alleviates post-resuscitation inflammatory response and pulmonary edema.

A tourniquet assisted cardiopulmonary resuscitation augments myocardial perfusion in a porcine model of cardiac arrest

ObjectiveDuring cardiopulmonary resuscitation (CPR), myocardial blood flow generated by chest compression rarely exceeds 35% of its normal level. Cardiac output generated by chest compression decreases gradually with the prolongation of cardiac arrest and resuscitation. Early studies have demonstrated that myocardial blood flow during CPR is largely dependent on peripheral vascular resistance. In this study, we investigated the effects of chest compression in combination with physical control of peripheral vascular resistance assisted by tourniquets on myocardial blood flow during CPR. MethodsVentricular fibrillation was induced and untreated for 7min in ten male domestic pigs weighing between 33 and 37kg. The animals were then randomized to receive CPR alone or a tourniquet assisted CPR (T-CPR). In the CPR alone group, chest compression was performed by a miniaturized mechanical chest compressor. In the T-CPR group, coincident with the start of resuscitation, the thin elastic tourniquets were wrapped around the four limbs from the distal end to the proximal part. After 2min of CPR, epinephrine (20μg/kg) was administered via the femoral vein. After 5min of CPR, defibrillation was attempted by a single 150J shock. If resuscitation was not successful, CPR was resumed for 2min before the next defibrillation. The protocol was continued until successful resuscitation or for a total of 15min. Five minutes after resuscitation, the elastic tourniquets were removed. The resuscitated animals were observed for 2h. ResultsT-CPR generated significantly greater coronary perfusion pressure, end-tidal carbon dioxide and carotid blood flow. There was no difference in both intrathoracic positive and negative pressures between the two groups. All animals were successfully resuscitated with a single shock in both groups. There were no significant changes in hemodynamics observed in the animals treated in the T-CPR group before-and-after the release of tourniquets at post-resuscitation 5min. ConclusionsT-CPR improves myocardial and cerebral perfusion during CPR. It may provide a new and convenient method for augmenting myocardial and cerebral blood flow during CPR.

Caspase-3–mediated splenic lymphocyte apoptosis in a porcine model of cardiac arrest

BackgroundPostresuscitation immunologic dysfunction contributes to the low survival rate after successful resuscitation, but its mechanism remains poorly understood. The mitochondrial apoptosis pathway is initiated by the Bcl-2/Bax-controlled and caspase-3–mediated pathway, this study investigated whether mitochondrial pathway-mediated splenic lymphocyte apoptosis is involved in the postresuscitation immunosuppression in a porcine model of cardiac arrest. MethodsTwenty-eight Wuzhishan miniature pigs were randomly divided into 2 groups: return of spontaneous circulation (ROSC; n = 22) and sham-operated (n = 6). Return of spontaneous circulation was initiated after 8 minutes of untreated ventricular fibrillation. After successful ROSC, CD4+ and CD8+ lymphocyte subsets were determined by flow cytometry. Surviving pigs were randomly assigned to be humanely killed at 24 and 72 hours after ROSC (n = 8 per group). Spleens were removed for histopathologic analysis, Western blotting, quantitative real-time polymerase chain reaction, and terminal deoxynucleotidyl transferase-mediated dUTP nick end-labeling assay. ResultsA high degree of splenic lymphocyte apoptosis was observed in the ROSC group. Expression of Bax and activated caspase-3 was markedly increased in splenic tissue, whereas Bcl-2 was significantly decreased in the post-ROSC group compared with the sham-operated group (P < .05) at 24 and 72 hours after ROSC. The messenger RNA levels of activated caspase-3 of splenic tissue were significantly elevated at 24 and 72 hours after ROSC. ConclusionThese results demonstrates that Bcl-2/Bax and caspase-3–mediated mitochondrial apoptosis signaling pathway may contribute to abnormal splenic lymphocyte apoptosis, which may be one of the main pathologic mechanisms of postresuscitation disturbance of immunologic function in a porcine model of cardiac arrest.

Ischemic post-conditioning and nitric oxide inhalation failed to demonstrate protective effect in comparison with mild hypothermia in porcine model of cardiac arrest

Ischemic post-conditioning and nitric oxide inhalation failed to demonstrate protective effect in comparison with mild hypothermia in porcine model of cardiac arrest

Differences in blood pressures and flows with and without vasopressors in a porcine model of cardiac arrest

Purpose: There is uncertainty about the safety and effectiveness of adrenaline use as a treatment for out of hospital cardiac arrest. In preparing for a randomized placebo controlled trial we sought to determine the relationship between the number of doses of adrenaline and outcome. Methods: Cardiac arrest cases were identified through the London Ambulance Service Out of Hospital Cardiac Arrest Registry. Patients who were treated for out of hospital cardiac arrest (irrespective of cause) and received one or more doses of adrenaline were eligible for inclusion. Data were collected between 2012 and 2013. Results: There were 3300 cardiac arrests where resuscitation was attempted and the patient received one or more doses of adrenaline. Survival for patients requiring adrenaline was 3.8% overall. Survival rates fell sequentially themore doses of adrenaline that were required (survival 17.7% for patients requiring a single dose of adrenaline falling to 1.4% amongst patients requiring 5 doses. There were no survivors amongst patients requiring 10 or more doses of adrenaline. Conclusion: Survival rates fell progressively with increasing doses of adrenaline. There were no survivors amongst patients requiring ten or more doses of adrenaline.

Increasing importance of release velocity with vasopressor use in a porcine model of cardiac arrest

Introduction:Wehave previously reported the benefit of faster release velocity on central blood flows in a porcine model of prolonged CPR without rescue shocks or vasopressor administration. We examined the importance of release velocity with vasopressor administration during the same model of prolonged CPR. Methods: CPR hemodynamics in four domestic swine were studied using standardmonitoring. Flowprobeswere placed on the inferior vena cava (IVC) and the right common carotid. Ventricular fibrillation (VF) was electrically induced. A mechanical chest compression (CC) device was started after ten minutes of untreated VF. CC release was changed so that sternal recoil lasted 100ms (WF1), 200ms (WF2), or 300ms (WF3). CC were delivered at a rate of 100 perminute and a depth of 48mm. Transitions between randomized waveforms occurred every 2min. Vasopressors were given every two minutes using the following pattern: epinephrine (1ml/kg), epinephrine (1ml/kg), vasopressin (40U/kg). Results: Throughout the first 18min of CC, aortic pressure was significantlyhigher and right atrial pressurewas significantly lower with WF1 and WF2 compared to WF3 (p<0.05). Carotid flow was higher with WF1 compared to WF3 (p<0.05). IVC flow was higher with WF1 in the first 8min of CC compared to WF3. Min 8 to 18 showed similar IVC flows for WF1 and WF2 which were higher than WF3 (p<0.05). During the first 18min of CC, IVC and carotid blood flows produced by WF3 with vasopressors were 3-fold less than those produced by WF3 in our no-vasopressor model. Conclusions: The use of vasopressors increased the impact of CC release velocity. The arterial-venous pressure difference, cerebral blood flow, and venous return were highest when the sternal recoil timewas 100ms. However, the use of vasopressors tended to decrease carotid and IVC flow and exacerbated the negative effect of slow release.

Reduction in carotid blood flow after epinephrine during CPR in a porcine model of cardiac arrest is probably related to an increased vascular bed resistance

Introduction: We have previously reported the detrimental effect of epinephrine (epi) during CPR on carotid blood flow (CBF) in an animal model. We now sought to investigate the epi-altered CBF profile in a porcine model of post-shock pulseless electrical activity (PEA) cardiac arrest.

The correlation between the impedance cardiogram and end-tidal carbon dioxide during cardiopulmonary resuscitation in a porcine model of cardiac arrest

Introduction: Studies were conducted to evaluate cardiopulmonary resuscitation (CPR) in a simulated low gravitational field, such as Mars (hypoG), aimed at providing an insight into the performance of terrestrial CPR. Methods: Two studies were conducted to evaluate external chest compressions (ECC) depth and rate, as well as perceived exertion (RPE) and the physiological cost, when 4 sets of 30 ECCs were performed on a standard CPR mannequin for 1.5min during Mars simulation, using terrestrial (1Gz) as control. The first study (n=20; 2005 guidelines) also evaluated the electromyographic (EMG) activity of four muscles (triceps brachii, erector spinae, upper rectus abdominis, pectoralis major). The second study (n=30; 2010 guidelines) included range of elbow flexion, minute ventilation (VE) and peak oxygen consumption (VO2 peak) measurements. HypoG simulation was achieved using a body suspension device (BSD) and a counterweight system. Results: In both studies, subjects successfully performed ECCs at 1Gz and hypoG. In the first study, therewere increases from 1Gz values of 32% (p<0.001) for RPE and 44% (p=0.002) for HR when ECCswere performedduringMars simulation. In hypoG, the triceps brachii showed less activity when compared with the other three muscles studied (p<0.001). A higher RPE (p<0.05) was also seen in the second study, which was accompanied by an increased VE (11.4±5.9 to 37.5±10.3 Lmin−1, p<0.05) and VO2 peak (3.2±1.1 to 20.5±7.6 mLkg−1 min−1, p<0.05). The arm flexion angle during hypogravity CPR, compared to 1Gz CPR, was also increased (4.3±2.8◦ to 14.0±8.1◦, p<0.05). Conclusion: Simulated reduction of upper body weight did not decrease the ability to perform proper ECCs, however, it increased the physiological cost and altered performance of the ‘straight arm’ CPR technique. These findings could be used to improve terrestrial CPR, especially when physical disparities are encounteredwith the rescuer being smaller and lighter than the patient.

Miniaturized mechanical chest compressor improves calculated cerebral perfusion pressure without compromising intracranial pressure during cardiopulmonary resuscitation in a porcine model of cardiac arrest

ObjectiveOne of the major goals of cardiopulmonary resuscitation (CPR) is to provide adequate oxygen delivery to the brain for minimizing cerebral injury resulted from cardiac arrest. The optimal chest compression during CPR should effectively improve brain perfusion without compromising intracranial pressure (ICP). Our previous study has demonstrated that the miniaturized mechanical chest compressor improved hemodynamic efficacy and the success of CPR. In the present study, we investigated the effects of the miniaturized chest compressor (MCC) on calculated cerebral perfusion pressure (CerPP) and ICP. MethodsVentricular fibrillation was electrically induced and untreated for 7min in 13 male domestic pigs weighing 39±3kg. The animals were randomized to receive mechanical chest compression with the MCC (n=7), or the Thumper device (n=6). CPR was performed for 5min before defibrillation attempt by a single 150J shock. At 2.5min of CPR, the epinephrine at a dose of 20μg/kg was administered. Additional epinephrine was administered at an interval of 3min thereafter. If resuscitation was not successful, CPR was resumed for an additional 2min prior to the next defibrillation until successful resuscitation or for a total of 15min. Post-resuscitated animals were observed for 2h. ResultsSignificantly greater intrathoracic positive and negative pressures during compression and decompression phases of CPR were observed with the MCC when compared with the Thumper device. The MCC produced significantly greater coronary perfusion pressure and end-tidal carbon dioxide. There were no statistically significant differences in systolic and mean ICP between the two groups; however, both of the measurements were slightly greater in the MCC treated animals. Interestingly, the diastolic ICP was significantly lower in the MCC group, which was closely related to the significantly lower negative intrathoracic pressure in the animals that received the MCC. Most important, systolic, diastolic and mean calculated CerPP were all significantly greater in the animals receiving the MCC. ConclusionsIn the present study, mechanical chest compression with the MCC significantly improved calculated CerPP but did not compromise ICP during CPR. It may provide a safe and effective chest compression during CPR.Protocol number: P1205.

Postresuscitation Treatment With Argon Improves Early Neurological Recovery in a Porcine Model of Cardiac Arrest

Effects of postresuscitation treatment with argon on neurologic recovery were investigated in a porcine model of cardiac arrest (CA) with an underlying acute myocardial infarction. The left anterior descending coronary artery was occluded in 12 pigs, and CA was induced. After 8 min of untreated CA, cardiopulmonary resuscitation was performed for 5 min before defibrillation. Following resuscitation, animals were subjected to 4-h ventilation with 70% argon/30% oxygen or 70% nitrogen/30% oxygen. Myocardial function was echocardiographically assessed, and serum neuron-specific enolase was measured. Animals were observed up to 72 h for assessment of survival and neurologic recovery. All the animals were resuscitated and survived for 72 h, except for a control pig. Ventilation with argon did not have any detrimental effects on hemodynamics and respiratory gas exchange. All the six argon-treated animals had a fast and complete 72-h neurologic recovery, in contrast to only two of the six controls (P < 0.05). Seventy-two-hour neurologic alertness score and neurologic deficit score were, respectively, 100 and 0 in the argon group and 79 and 29 in the control one (P < 0.01 and P < 0.05). Significantly lower increases in serum neuron-specific enolase (12% vs. 234%) and minimal histological brain injury (neuronal degeneration: 0 vs. 1) were also observed in argon-treated animals, in comparison to controls. In this model, postresuscitation treatment with argon allowed for a faster and complete neurologic recovery, without detrimental effects on hemodynamics and respiratory gas exchanges.

Abstract 203: Measurement of Cardiac Function in a Porcine Model of Cardiac Arrest Due to Massive Exsanguination

Background: While extremity hemorrhage can be stymied with a well placed tourniquet, vascular injury within the thorax and abdomen is not amenable to direct compression. Uncontrolled, noncompressible torso hemorrhage (NCTH) and the resultant cardiac arrest (CA) may account for up to 80% of preventable deaths in combat. We developed a porcine model of CA to test novel surgical interventions and are reporting measures of cardiovascular function during a simulated NCTH. Methods: Ten anesthetized Yorkshire pigs underwent tracheostomy, arterial and central line placement. Animals were awakened and sedated with midazolam titrated to a bispectral index of 75 ± 5. Spontaneously breathing, the animals were subjected to a computerized hemorrhage of 80% total blood volume (TBVH) over 20 minutes or until death, defined as mean arterial pressure (MAP)=0 mmHg and etCO2&lt;10. During hemorrhage, if minute ventilation decreased 25% from baseline (BL) for &gt;20 seconds, volume control ventilation was initiated. The Millar MPVS Ultra system continuously collected left ventricular (LV) and descending aortic pressures, as well as LV volume data via indwelling catheters. A repeated measures one-way ANOVA with Tukey’s procedure was performed on data collected at BL, 25%, 44%, 62% TBV hemorrhage, and CA, defined as a MAP&lt;20 mmHg. Data are presented as means±SEM. Results: Weight was 63.8±2.8kg. TBVH at CA was 2941±130ml (71.0±1.5%). Time to CA was 18:22±00:40min. In Table 1, * denotes a significant change (p&lt;0.05) in a variable from previous hemorrhage phase as marked by #. Conclusions: We developed a porcine model of CA secondary to exsanguination. We found that despite decreasing left ventricular volumes and pressures, cardiac contractility and conduction system function were maintained throughout hemorrhage. This suggests that lifesaving interventions (such as endovascular aortic balloon occlusion and extracorporeal life support) may be possible despite profound hypovolemia.