Minutes Of Ventricular Fibrillation Research Articles

Use of a Portable Mechanical Ventilator during Cardiopulmonary Resuscitation is Feasible, Improves Respiratory Parameters, and Prevents the Decrease of Dynamic Lung Compliance.

For practical and protective ventilation during cardiopulmonary resuscitation (CPR), a 150-grams mechanical ventilator (VLP2000E) that limits peak inspiratory pressure (PIP) during simultaneous ventilation with chest compressions was developed. To evaluate the feasibility of VLP2000E ventilation during CPR and to compare monitored parameters versus bag-valve ventilation. A randomized experimental study with 10 intubated pigs per group. After seven minutes of ventricular fibrillation, 2-minute CPR cycles were delivered. All animals were placed on VLP2000E after achieving return of spontaneous circulation (ROSC). Bag-valve and VLP2000E groups had similar ROSC rate (60% vs. 50%, respectively) and arterial oxygen saturation in most CPR cycles, different baseline tidal volume [0.764 (0.068) vs. 0.591 (0.123) L, p = 0.0309, respectively] and, in 14 cycles, different PIP [52 (9) vs. 39 (5) cm H2O, respectively], tidal volume [0.635 (0.172) vs. 0.306 (0.129) L], ETCO2[14 (8) vs. 27 (9) mm Hg], and peak inspiratory flow [0.878 (0.234) vs. 0.533 (0.105) L/s], all p < 0.0001. Dynamic lung compliance (≥ 0.025 L/cm H2O) decreased after ROSC in bag-valve group but was maintained in VLP2000E group [0.019 (0.006) vs. 0.024 (0.008) L/cm H2O, p = 0.0003]. VLP2000E ventilation during CPR is feasible and equivalent to bag-valve ventilation in ROSC rate and arterial oxygen saturation. It produces better respiratory parameters, with lower airway pressure and tidal volume. VLP2000E ventilation also prevents the significant decrease of dynamic lung compliance observed after bag-valve ventilation. Further preclinical studies confirming these findings would be interesting.

IVABRADINE-INDUCED HEART RATE REDUCTION INCREASES THE SEVERITY OF POSTRESUSCITATION MYOCARDIAL DYSFUNCTION IN A RAT MODEL OF CARDIOPULMONARY RESUSCITATION.

Aims: A rapid heart rate (HR) that occurs after cardiopulmonary resuscitation (CPR) is a short-term compensatory mechanism preserving cardiac output. However, if of long duration, it is unfavorable for myocardial function postresuscitation because of disrupted balance between myocardial oxygen supply and demand. This raises the assumption that such a sustained fast HR should be regulated. The present study aimed to investigate the follow-on effect of ivabradine (a specific inhibitor of the I f current of the sinoatrial node)-induced HR reduction (HRR) on postresuscitation myocardial function in a rat model of CPR. Methods and results: Six minutes of ventricular fibrillation and 8 min of CPR were performed on Sprague-Dawley rats. All 32 resuscitated animals were then randomized into saline and ivabradine groups, each group having nonsurvival and survival subgroups (n = 8 each). Saline or ivabradine (0.5 mL/kg) was administered at 1 h postresuscitation. Heart rate, myocardial function as expressed by cardiac output, ejection fraction, and myocardial performance index were assessed at baseline and hourly from 1 to 5 h postresuscitation. Heart rate variability was analyzed at baseline and at 1, 3, and 5 h postresuscitation. Serum epinephrine and cardiac troponin I at baseline and at 1, 3, and 5 h postresuscitation in nonsurvival subgroup were measured. Survival duration in the survival subgroup was observed. The baseline HR was approximately 390 beats/min (bpm). After resuscitation, an average increase of Δ ≈ +15 bpm (relative ratio ≈ +3.8%) with a resultant HR of 405 bpm lasting more than 5 h occurred. Ivabradine group achieved a steady HRR of Δ ≈ -30 bpm (relative ratio ≈ -7.4%) as compared with saline group ( P < 0.01). Postresuscitation myocardial function was significantly worse in the ivabradine group (all P < 0.01). Heart rate variability was significantly impaired in the ivabradine group (all P < 0.05). Serum cardiac troponin I and epinephrine concentration were significantly higher in the ivabradine group (all P < ?0.01). Survival duration was significantly shortened in the ivabradine group as compared with the saline group (388 vs. 526 min, P < ?0.01). Conclusions: Ivabradine-induced HRR increases the severity of postresuscitation myocardial dysfunction and shortens survival duration in a rat model of CPR.

Noninvasive Versus Invasive Brain Temperature Measurement During Targeted Temperature Management: A Preclinical Study in a Swine Cardiac Arrest Model.

We aimed to evaluate correlation and agreement between noninvasive brain temperature (TBN) and invasive brain temperature (TBI) measurement during targeted temperature management (TTM) in a swine cardiac arrest model. Defibrillation attempts were provided after 5 minutes of ventricular fibrillation and 12 minutes of cardiopulmonary resuscitation in five pigs. After return of spontaneous circulation, TTM was provided with induction and maintenance phases with a target temperature of 33°C for 6 hours and a rewarming phase with a rewarming rate of 1°C/h for 4 hours. TBN and TBI were measured using a double sensor method and an intracranial catheter, respectively. Pulmonary artery temperature (TP), esophageal temperature (TE), and rectal temperature (TR) were measured. Primary outcomes were correlation and agreement between TBN and TBI and secondary outcomes were correlation and agreement among TBN and other temperatures. The Pearson correlation coefficient (PCC) between TBN and TBI was 0.95 (p < 0.001) during the whole TTM phases. PCCs between TBN and TBI during the induction, maintenance, and rewarming phases were 0.91 (p < 0.001), 0.88 (p < 0.001), and 0.94 (p < 0.001) and 95% limits of agreement (LoAs) between TBN and TBI were (-0.27°C to 0.78°C), (-0.18°C to 0.54°C), and (-0.93°C to 0.88°C), respectively. Correlation between TBN and TBI during the maintenance phase was higher than correlation between TBN and TE (PCC = 0.74, p < 0.001) or TP (PCC = 0.81, p < 0.001). The 95% LoAs were narrowest between TBN and TP in the induction phase (-0.58 to 0.11), between TBN and TBI in the maintenance phase (-0.54 to 0.18), and between TBN and TR in the rewarming phase (-0.96 to 0.84). Noninvasive brain temperature showed good correlation with invasive brain temperature during TTM in a swine cardiac arrest model. Correlation was highest during the rewarming phase and lowest during the maintenance phase. Agreement between the two measurements was not clinically acceptable.

Hemodynamic efficacy of a motor-driven automatic device performing simultaneous sternothoracic cardiopulmonary resuscitation compared to standard cardiopulmonary resuscitation in an animal model of cardiac arrest

The aim of this study was to investigate hemodynamic effects and resuscitation outcomes of simultaneous sternothoracic cardiopulmonary resuscitation (SST-CPR) with a prototype of a motor-driven automatic device, comparing to manual standard CPR (S-CPR), in an animal model of ventricular fibrillation (VF). 20 male pigs were randomized to receive standard CPR (S-CPR group) or CPR with an automatic SST-CPR device (A-CPR group) after 5 minutes of VF. Five minutes of basic life support CPR was performed, followed by 10 minutes of advanced life support CPR. Hemodynamic variables including systolic blood pressure (SBP), diastolic blood pressure (DBP), coronary perfusion pressure (CPP), and end-tidal carbon dioxide tension (ETCO2), and resuscitation outcomes including rate of restoration of spontaneous circulation (ROSC) and 2-hour survival were compared between two groups. Ten animals among the A-CPR group and 8 animals among the S-CPR group were included in the final analysis. SBP was higher in the A-CPR group than in the S-CPR group during CPR (p = 0.046). The DBP, CPP and ETCO2 were not different between two groups (p = 0.412, 0.585, and 0.243, respectively). ROSC rate was 38% in the S-CPR group and 10% in the A-CPR group (p = 0.275). The 2-hour survival rate was 25% in the S-CPR group and 0% in the A-CPR group (p = 0.183). In a swine model of cardiac arrest, CPR with a prototype of a motor-driven automatic SST-CPR device, compared with standard CPR, produced higher systolic blood pressure, but there was no difference in diastolic pressure, coronary perfusion pressure, ROSC rate and 2-hour survival rate.

Effect of Amiodarone and Hypothermia on Arrhythmia Substrates During Resuscitation.

BackgroundAmiodarone is administered during resuscitation, but its antiarrhythmic effects during targeted temperature management are unknown. The purpose of this study was to determine the effect of both therapeutic hypothermia and amiodarone on arrhythmia substrates during resuscitation from cardiac arrest.Methods and ResultsWe utilized 2 complementary models: (1) In vitro no‐flow global ischemia canine left ventricular transmural wedge preparation. Wedges at different temperatures (36°C or 32°C) were given 5 µmol/L amiodarone (36‐Amio or 32‐Amio, each n=8) and subsequently underwent ischemia and reperfusion. Results were compared with previous controls. Optical mapping was used to measure action potential duration, dispersion of repolarization (DOR), and conduction velocity (CV). (2) In vivo pig model of resuscitation. Pigs (control or targeted temperature management, 32–34°C) underwent ischemic cardiac arrest and were administered amiodarone (or not) after 8 minutes of ventricular fibrillation. In vitro: therapeutic hypothermia but not amiodarone prolonged action potential duration. During ischemia, DOR increased in the 32‐Amio group versus 32‐Alone (84±7 ms versus 40±7 ms, P<0.05) while CV slowed in the 32‐Amio group. Amiodarone did not affect CV, DOR, or action potential duration during ischemia at 36°C. Conduction block was only observed at 36°C (5/8 36‐Amio versus 6/7 36‐Alone, 0/8 32‐Amio, versus 0/7 32‐Alone). In vivo: QTc decreased upon reperfusion from ischemia that was ameliorated by targeted temperature management. Amiodarone did not worsen DOR or CV. Amiodarone suppressed rearrest caused by ventricular fibrillation (7/8 without amiodarone, 2/7 with amiodarone, P=0.041), but not pulseless electrical activity (2/8 without amiodarone, 5/7 with amiodarone, P=0.13).ConclusionsAlthough amiodarone abolishes a beneficial effect of therapeutic hypothermia on ischemia‐induced DOR and CV, it did not worsen susceptibility to ventricular tachycardia/ventricular fibrillation during resuscitation.

Combined Therapy With Polyethylene Glycol-20k and MCC950 Preserves Post-Resuscitated Myocardial Function in a Rat Model of Cardiac Arrest and Cardiopulmonary Resuscitation.

BackgroundTo investigate the therapeutic potential of combined therapy with polyethylene glycol‐20k (PEG‐20k) and MCC950 on post‐resuscitation myocardial function in a rat model of cardiac arrest.Methods and ResultsThirty rats were randomized into 5 groups: Sham, Control, PEG‐20k, MCC950, PEG‐20k+ MCC950. Except for sham, animals were subjected to 6 minutes of ventricular fibrillation followed by 8 minutes cardiopulmonary resuscitation. Two milliliters PEG‐20k was administered by intravenous injection coincident with the start of cardiopulmonary resuscitation; MCC950 (10 mg/kg), a highly selective NLRP3 inflammasome inhibitor, was delivered immediately after restoration of spontaneous circulation. Myocardial function, sublingual microcirculation, mitochondrial function, plasma cardiac troponin I, and interleukin‐1β, expression of proteins in SIRT1 (sirtuin 1)/PGC‐1α (peroxisome proliferator‐activated receptor gamma coactivator 1‐alpha) and NLRP3 (the NOD‐like receptor family protein 3) inflammasome pathways were evaluated. Following cardiopulmonary resuscitation, myocardial function was compromised with a significantly decreased cardiac output, ejection fraction, and increased myocardial performance index, cardiac troponin I. Sublingual microcirculation was disturbed with impaired perfused vessel density and microvascular flow index. Cardiac arrest reduced mitochondrial routine respiration, Complex I‐linked respiration, respiratory control rates and oxidative phosphorylation coupling efficiency. PEG‐20k or MCC950 alone restored mitochondrial respiratory function, restituted sublingual microcirculation, and preserved myocardial function, whereas a combination of PEG‐20k and MCC950 further improved these aspects. PEG‐20k restored the expression of SIRT1 and PGC‐1α, and blunted activation of NLRP3 inflammasomes. MCC950 suppressed expression of cleaved‐caspase‐1/pro‐caspase‐1, ASC (apoptosis‐associated speck‐like protein), GSDMD [gasdermin d], and interleukin‐1β.ConclusionsCombined therapy with PEG‐20k and MCC950 is superior to either therapy alone for preserving post‐resuscitated myocardial function, restituting sublingual microcirculation at restoration of spontaneous circulation at 6 hours. The responsible mechanisms involve upregulated expression of SIRT1/PGC1‐α in tandem with inhibition of NLRP3 inflammasomes.

Abstract 253: The Efficacy of Left Ventricular versus Traditional Chest Compressions During Selective Aortic Arch Perfusion to Treat Traumatic Cardiopulmonary Arrest in a Swine Model

Introduction: Recent evidence has demonstrated that closed chest compressions (CC) directly over the left ventricle (LV) during traumatic cardiopulmonary arrest (TCPA) improve hemodynamics and return of spontaneous circulation (ROSC) when compared to traditional chest compressions. Selective Aortic Arch Perfusion (SAAP) is also able to improve hemodynamics as well as control hemorrhage during TCPA. Hypothesis: We hypothesized that LV compressions would increase ROSC when compared to traditional compressions in an animal model of TCPA where SAAP was being used. We also compared LV and Traditional compressions with SAAP to historical controls that received compressions without SAAP. Methods: Transthoracic echo was used to mark the location of the aortic root and the center of the left ventricle on animals (n=24, 12 in each arm) which were randomized to receive chest compressions in one of the two locations. One third of each animal’s blood volume was removed and ventricular fibrillation (VF) was induced to simulate traumatic cardiac arrest. After a period of ten minutes of VF, basic life support (BLS) with mechanical CPR was initiated and performed for ten minutes followed by advanced life support (ALS) and blood transfusion for an additional ten minutes. The SAAP balloon was inflated at minute 6 of BLS. Hemodynamic variables were averaged every two minutes. The same model was used for historical controls (n=26, 13 in each arm) without the use of SAAP, so comparisons were treated as a single study with a factorial design. Results: There were no differences in hemodynamic variables, ROSC (p=0.67) or survival (p=0.64) between SAAP groups. However, when the LV animals were compared to historic controls without SAAP, LV animals had higher ROSC (p=0.02) and survival rates (p=0.04) than Traditional animals. Conclusions: SAAP does not appear to show a synergistic effect with LV compressions, however, SAAP combined with LV compressions improves ROSC and survival when compared to Traditional compressions in our swine model of TCPA. More investigation into SAAP and compression position should be studied to improve treatment of TCPA.

Abstract 139: Impedance Threshold Device and Active Decompression Improve Hemodynamics in a Swine Model of Prolonged CPR

Introduction: Cardiopulmonary resuscitation with the impedance threshold device and active decompression (ITD-ACD CPR) has been shown to improve chest compression generated blood flow relative to standard chest compression. Using our high-fidelity swine model of cardiac arrest treated with prolonged mechanical chest compression (MCC) we studied the effect of different lift heights (amount of lift above the natural zero point of the sternum) during active decompression. Methods: CPR was performed on six domestic swine (~30 kg) using standard physiological monitoring. Flow was measured in the abdominal aorta, inferior vena cava (IVC), right common carotid and external jugular, and left femoral artery. Ventricular fibrillation (VF) was electrically induced. MCC were started after ten minutes of VF. Four MCC waveforms were used: Standard CPR (2”, 100 CPM), and ITD-ACD CPR (2”, 80 CPM) with 0.5”, 1.0”, and 1.5” lift past the zero point. MCC waveforms were changed every 2 min in a crossover design and delivered for 56 minutes. Data were analyzed in CPR cycles which included four epochs of CPR, one of each waveform, constituting 8 minutes of compressions. Results: Lift height had a significant (p&lt;0.05) effect on carotid and jugular blood flow. Lift heights of 1.0 and 1.5” generated significantly more carotid blood flow in all 7 CPR cycles. A lift height of 1.5” generated significantly more jugular blood flow over all 7 CPR cycles. The interaction between duration of CPR and Jugular blood flow previously observed using this animal model was not observed. Carotid and jugular blood flow as a function of waveform and CPR cycle are shown in the figure. Conclusions: ITD-ACD CPR improved carotid and jugular blood flows, suggestive of improved cerebral perfusion. A lift height of 1.5” was required for significant improvement of jugular blood flows, while ITD-ACD CPR provided significantly better carotid blood flow than standard CPR at all lift heights.

Restitution characteristics of His bundle and working myocardium in isolated rabbit hearts.

The Purkinje system (PS) and the His bundle have been recently implicated as an important driver of the rapid activation rate after 1–2 minutes of ventricular fibrillation (VF). It is unknown whether activations during VF propagate through the His-Purkinje system to other portions of the the working myocardium (WM). Little is known about restitution characteristic differences between the His bundle and working myocardium at short cycle lengths. In this study, rabbit hearts (n = 9) were isolated, Langendorff-perfused, and electromechanically uncoupled with blebbistatin (10 μM). Pacing pulses were delivered directly to the His bundle. By using standard glass microelectrodes, action potentials duration (APD) from the His bundle and WM were obtained simultaneously over a wide range of stimulation cycle lengths (CL). The global F-test indicated that the two restitution curves of the His bundle and the WM are statistically significantly different (P<0.05). Also, the APD of the His bundle was significantly shorter than that of WM throughout the whole pacing course (P<0.001). The CL at which alternans developed in the His bundle vs. the WM were shorter for the His bundle (134.2±13.1ms vs. 148.3±13.3ms, P<0.01) and 2:1 block developed at a shorter CL in the His bundle than in WM (130.0±10.0 vs. 145.6±14.2ms, P<0.01). The His bundle APD was significantly shorter than that of WM under both slow and rapid pacing rates, which suggest that there may be an excitable gap during VF and that the His bundle may conduct wavefronts from one bundle branch to the other at short cycle lengths and during VF.

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.

Abstract 17334: The Detrimental Effect of Chest Compression Interruptions on Coronary Perfusion Pressure Dynamics

Introduction: Guidelines for treatment of cardiac arrest recommend minimizing interruptions in chest compressions based on research indicating that interruptions compromise coronary perfusion pressure (CPP) and blood flow and reducing the likelihood of successful defibrillation. We investigated the dynamics of CPP before, during, and after compression interruptions and how they change over time. Methods: CPR was performed on domestic swine (~30 Kg) using standard physiological monitoring. Blood flow was measured in the abdominal aorta (AAo), the inferior vena cava, the right common carotid and external jugular. 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 (cpm) and at a depth of 2” for a total of 12 min. CPP was calculated as the difference between aortic and right atrial pressure at end-diastole per Utstein guidelines. CPP was determined for 5 compressions prior to the interruption, every 2 seconds during the CC interruption, and for 7 compressions after the interruption. Per protocol, 12 interruptions occurred at randomized time points. Results: Across 12 minutes of CPR, averaged CPP prior to interruption was significantly greater than the averaged CPP after the interruption (22.4±1.0 vs. 15.5±0.73 mmHg). As CPR continued throughout the 12 minutes, CPP during compressions decreased (First 6 min = 24.1±1.4 vs. Last 6 min = 20.1±1.3 mmHg, p=0.05), but the effect of interruptions remained constant resulting in a 20% drop in CPP for every 2 seconds irrespective of the prior CPP. The increase (slope) of CPP after resumption of compressions was significantly reduced over time (First 6 min = 1.47±0.18 vs. Last 6 min = 0.82±0.13 mmHg/compression). Conclusions: Chest compression interruptions have a detrimental effect on coronary perfusion and blood flow. The magnitude of this effect increases over time as a resuscitation effort continues. These data confirm the importance of providing uninterrupted CPR particularly in long duration resuscitations.

Abstract 16417: Resuscitative Endovascular Balloon Occlusion of the Aorta Improves Hemodynamics and Return of Spontaneous Circulation When Combined With Standard Closed Chest Compressions in a Swine Model of Traumatic Cardiac Arrest

Introduction: Recent evidence has demonstrated that closed chest compressions (CC) directly over the left ventricle (LV) during traumatic cardiopulmonary arrest (TCPA) improve hemodynamics and return of spontaneous circulation (ROSC) when compared to standard chest compressions. Resuscitative endovascular balloon occlusion of the aorta (REBOA) is also able to improve hemodynamics as well as control hemorrhage during TCPA. Hypothesis: We hypothesized that the combination of REBOA and closed chest compressions located over the LV would result in improved hemodynamics and ROSC in a swine model of TCPA. Methods: Transthoracic echo was used to mark the location of the aortic root and the center of the left ventricle on animals (n=52) which were randomized to receive chest compressions in one of the two locations. Half the animals in each group received REBOA placement so there were four arms. One third of each animal’s blood volume was removed and ventricular fibrillation (VF) was induced to simulate traumatic cardiac arrest. After a period of ten minutes of VF, basic life support (BLS) with mechanical CPR was initiated and performed for ten minutes followed by advanced cardiac life support (ACLS) and blood transfusion for an additional ten minutes. Animals with REBOA had the balloon inflated at minute 6 of BLS. Hemodynamic variables were averaged every two minutes. Results: ROSC increased among standard CC animals with REBOA (33%) compared to standard CC animals without REBOA (0.0%) (p=0.04). Among standard CC animals, aortic systolic blood pressure, right atrial systolic blood pressure and end tidal CO2 (ETCO2) increased during all time intervals of BLS (p&lt;0.005) with REBOA. ETCO2 also increased during BLS among LV CC animals with REBOA compared to LV CC animals without REBOA (p≤0.0001), however, ROSC and other hemodynamics were not significantly different. There was no difference in ROSC or hemodynamics between the LV CC and standard CC groups with REBOA. Conclusions: In our swine model of TCPA, ROSC and hemodynamics are improved among animals receiving standard closed chest compressions, however, there is no additional benefit with REBOA if compressions are performed over the LV.

Abstract 14109: Basic Life Support With Reperfusion Injury Protection Improves 24 Hour Survival Outcomes in a Porcine Model of Prolonged Cardiac Arrest

Introduction: Ischemic postconditioning (PC) using 3 intentional short pauses at the start of cardiopulmonary resuscitation (CPR) improves outcomes after cardiac arrest in pigs when epinephrine (epi) is used before defibrillation. Hypothesis: Basic life support (BLS) with PC will protect against reperfusion injury and enhance 24 hour functional recovery in the absence of epi. Methods: Female pigs (n=46; wt ~ 40 kg) were anesthetized (isoflurane). PC was delivered using 3 cycles alternating between automated CPR for 20 sec and no CPR for 20 sec at the start of each protocol. Protocol A: After 12 minutes of ventricular fibrillation (VF), 28 pigs were randomized in 4 groups: A/ Standard CPR (SCPR), B/ active compression-decompression with an impedance threshold device (ACD-ITD), C/ SCPR+PC (SCPR+PC) and D/ ACD-ITD+PC. Protocol B: After 15 min of VF, 18 pigs were randomized to ACD-ITD CPR or ACD-ITD + PC. The BLS duration was 2.75 min in Protocol A and 5 min in Protocol B. Following BLS up to 3 shocks were delivered. Without return of spontaneous circulation (ROSC) CPR was resumed and epi (0.5 mg) and defibrillation delivered. The primary end point was the incidence of major adverse outcomes at 24 h (defined as death or coma, refractory seizures and cardio-respiratory distress leading to euthanasia). Hemodynamic parameters and left ventricular ejection fraction (LVEF) were also measured. Data are presented as mean ± standard error of mean. Results: Protocol A: ACD-ITD CPR + PC (group D) provided the highest coronary perfusion pressure after 3 min of BLS compared with the 3 other groups (28 ± 6, 35 ± 7, 23 ± 5 and 47 ± 7 for groups A, B, C, D respectively, p= 0.05 by ANOVA). ROSC with BLS was achieved in 0, 3, 0, and 3 pigs in groups A, B, C and D, respectively (p=0.22) with no significant differences in 24-hour survival between groups. Protocol B: Four hours post ROSC, LVEF was significantly higher with ACD-ITD+IPC vs ACD-ITD alone (52.5 ± 3% vs. 37.5 ± 6.6%, p = 0.045). There was a significantly lower incidence of major adverse outcomes 24 hr after ROSC with ACD-ITD+PC compared with ACD-ITD alone (Log-rank comparison, p=0.027). Conclusion: BLS using ACD-ITD + PC mitigates post resuscitation cardiac dysfunction and facilitates neurological recovery after prolonged untreated VF in pigs.

Comparison Between 30:1 and 30:2 Compression-to-ventilation Ratios for Cardiopulmonary Resuscitation: Are Two Ventilations Necessary?

Controversy is continuing over the need for ventilation and the optimal compression-ventilation (CV) ratio during cardiopulmonary resuscitation (CPR). The aim of this study was to comparatively elucidate the effect on hemodynamics and arterial oxygen saturation of a single ventilation relative to two consecutive ventilations during CPR in a dog model of cardiac arrest. Twenty mongrel dogs were divided into two groups. After 3 minutes of ventricular fibrillation (VF), the single-ventilation group received CPR with a 30:1 CV ratio, and the two-ventilation group received CPR with a 30:2 CV ratio, all with room air for 7 minutes. Thereafter, continuous chest compressions and intermittent ventilation at rate of 10 per minute were followed for both groups for 10 minutes. Hemodynamic parameters, arterial blood gas profiles, and variables from CPR were compared at baseline and at 5, 10, 15, and 20 minutes after induction of VF. Hemodynamic parameters including aortic systolic and diastolic pressures, right atrial systolic and diastolic pressures, coronary perfusion pressure, end-tidal carbon dioxide tension, and arterial blood gas profiles including arterial oxygen tension, arterial oxygen saturation, and arterial carbon dioxide tension were not different between two groups during CPR. In the 30:1 group, the period of compression interruption was shorter and chest compression fraction was higher than that in the 30:2 group (6 sec/min vs. 10.9 sec/min, p < 0.001; 90.0% vs. 81.8%, p < 0.001). CPR with a 30:1 CV ratio, compared to CPR with a 30:2 CV ratio, results in comparable arterial oxygenation saturation and hemodynamics.

Prearrest hypothermia improved defibrillation and cardiac function in a rabbit ventricular fibrillation model

BackgroundHypothermia when cardiopulmonary resuscitation begins may help achieve defibrillation and return of spontaneous circulation (ROSC), but few data are available. ObjectiveThe objective of this study was to determine whether prearrest hypothermia improved defibrillation and cardiac function in a rabbit ventricular fibrillation (VF) model. ResultsThirty-six New Zealand rabbits were randomized equally to receive normothermia (Norm) (~39°C), post-ROSC hypothermia (~33°C), or prearrest hypothermia (~33°C). Ventricular fibrillation was induced by alternating current. After 4 minutes of VF, rabbits were defibrillated and given cardiopulmonary resuscitation until ROSC or no response (≥30 minutes). Hemodynamics and electrocardiogram were monitored; N-terminal pro–brain natriuretic peptideand troponin I were determined by enzyme-linked immunosorbent assay. Myocardial histology and echocardiographic data were evaluated. First-shock achievement of perfusion rhythm was more frequent in prearrest than normothermic animals (7/12 vs 1/12; P = .027). After ROSC, dp/dtmax was higher in prearrest than normothermic animals (P < .001). Left ventricular end-systolic pressure was higher in prearrest than normothermic animals (P = .001). At 240 minutes after ROSC, troponin I and N-terminal pro–brain natriuretic peptide were lower in prearrest than normothermic animals (15.74 ± 2.26 vs 25.09 ± 1.85 ng/mL and 426 ± 23 vs 284 ± 45 pg/mL, respectively), the left ventricular ejection fraction and cardiac output were lower in the Norm group than other 2 groups (P < .01). Myocardial histology was more disturbed in normothermic than post-ROSC and prearrest animals, but was not different in the latter 2 groups. ConclusionsInduction of hypothermia before VF led to improved cardiac function in a rabbit VF model through improving achievement of perfusing rhythm by first-shock defibrillation and facilitating resuscitation.

Abstract 16289: Can We Personalize CPR? Challenges With Hemodynamics, Monitoring, and Pharmacology

Introduction: Coronary perfusion pressure (CPP) guided CPR improves survival over guideline CPR. EtCO2 has also been used to guide CPR. These efforts reflect that one-size-fits-all CPR is sub-optimal, but assume that CPP and EtCO2 guidance will result in similar definitions of “high quality” chest compressions (CC). A mechanistic study of the interaction between CC, blood flow, CPP, and EtCO2 has not been done. Methods: CPR was performed on 21 domestic swine (~30 Kg) using standard physiological monitoring. Flow was measured in the abdominal aorta, the inferior vena cava (IVC), the right renal artery and vein, the right common carotid and external jugular. Ventricular fibrillation (VF) was electrically induced. Mechanical CC were started after ten minutes of VF. CC waveforms varied so that sternal release occurred over 100 ms, 200 ms, or 300 ms. CC were delivered at a rate of 100 per minute and at a depth of 1.25” (n=9), 1.9” (n=8), or 1.9” with vasopressor use (n=4) for a total of 54 min. CC release times changed every 2 min and were randomized. Results: In the first 18 min of CPR, EtCO2 was optimized by a 100 ms release (27.2±2.5 mmHg) vs. a 200 ms (24.7±2.5 mmHg; p = .005) or 300 ms release (25.1±2.5 mmHg; p= 0.03). CPP was optimized by a 200 ms release (6.7±1.0 mmHg) vs. a 100 ms (5.7±1.0 mmHg; p = 0.03) or 300 ms (4.9±1.0 mmHg; p &lt; 0.01) release. Deeper CC increased blood flow in the IVC (1.5±0.2 vs. 0.12±0.2 mL/comp: p&lt;0.001) and carotid artery (0.4±0.03 vs. 0.2±0.03 mL/comp: p&lt;0.001) and changed the distribution of blood flow. In prolonged CPR, CC efficacy decayed with time, particularly with 1.25” CC, and resulted in distinct periods of to and fro flow (sloshing). Vasopressor effects appeared to be time dependent, but trended towards improved CPP at the expense of significantly reduced carotid blood flow. Conclusions: CPP and EtCO2 provide insight into two distinct aspects of CC generated blood flow, and consequently cannot be simultaneously optimized. CC generated blood flow transitions from forward blood flow to sloshing as a function of time and CC depth. Pressure measurements are insufficient to titrate vasopressor use, as tissue perfusion can collapse while maintaining the CPP. We currently lack the monitoring and the physiological understanding required to personalize CPR.

Long-Duration Ventricular Fibrillation Exhibits 2 Distinct Organized States

Previous studies showed that endocardial activation during long-duration ventricular fibrillation (VF) exhibits organized activity. We identified and quantified the different types of organized activity. Two 64-electrode basket catheters were inserted, respectively, into the left ventricle and right ventricle of dogs to record endocardial activation from the endocardium during 7 minutes of VF (controls, n=6). The study was repeated with the K(ATP) channel opener pinacidil (n=6) and the calcium channel blocker flunarizine (n=6). After 2 minutes of VF without drugs, 2 highly organized left ventricular endocardial activation patterns were observed: (1) ventricular electric synchrony pattern, in which endocardial activation arose focally and either had a propagation sequence similar to sinus rhythm or arose near papillary muscles, and (2) stable pattern, in which activation was regular and repeatable, sometimes forming a stable re-entrant circuit around the left ventricular apex. Between 3 and 7 minutes of VF, the percent of time ventricular electric synchrony was present was control=25%, flunarizine=24% (P=0.44), and pinacidil=0.1% (P<0.001) and the percent of time stable pattern was present was control=71%, flunarizine=48% (P<0.001), and pinacidil=56% (P<0.001). The remainder of the time, nonstable re-entrant activation with little repeatability was present. After 3 minutes, VF exhibits 2 highly organized endocardial activation patterns 96% of the time, one potentially arising focally in the Purkinje system that was prevented with a K(ATP) channel opener but not a calcium channel blocker and the other potentially arising from a stable re-entrant circuit near the apical left ventricular endocardium.

Effects of hypothermia on the liver in a swine model of cardiopulmonary resuscitation.

The study aimed to explore the effects of hypothermia state induced by 4 ºC normal saline (NS) on liver biochemistry, enzymology and morphology after restoration of spontaneous circulation (ROSC) by cardiopulmonary resuscitation (CPR) in swine. After 4 minutes of ventricular fibrillation (VF), standard CPR was carried out. Then the survivors were divided into two groups: low temperature group and normal temperature group. The low temperature (LT) group (n=5) received continuously 4 ºC NS at the speed of 1.33 mL/kg per minute for 22 minutes, then at the speed lowering to 10 mL/kg per hour. The normal temperature (NT) group (n=5) received NS with normal room temperature at the same speed of the LT group. Hemodynamic status and oxygen metabolism were monitored and the levels of serum alanine aminotransferase (ALT), aspartate aminotransferase (AST) and lactate dehydrogenase (LDH) were measured in blood samples obtained at baseline and at 10 minutes, 2 hours and 4 hours after ROSC. At 24 hours after ROSC, the animals were killed and the liver was removed to determine the Na(+)-K(+)-ATPase and Ca(2+)-ATPase enzyme activities and histological changes under a light or electron microscope. Core temperature was decreased in the LT group (P<0.05), while HR, MAP and CPP were not significantly decreased (P>0.05) compared with the NT group (P>0.05). The oxygen extraction ratio was lower in the LT group than in the NT group (P<0.05). The serum levels of ALT, AST and LDH increased in both groups but not significantly in the LT group. The enzyme activity of liver ATP was much higher in the LT group (Na(+)-K(+)-ATP enzyme: 8.64±3.32 U vs. 3.28±0.71 U; Ca(2+)-ATP enzyme: 10.92±2.12 U vs. 2.75±0.78 U, P<0.05). The LT group showed less cellular edema, inflammation and few damaged mitochondria as compared with the NT group. These data suggested that infusing 4 ºC NS continuously after ROSC could quickly lower the core body temperature, while maintaining a stable hemodynamic state and balancing oxygen metabolism, which protect the liver in terms of biochemistry, enzymology and histology after CPR.

Abstract 80: Infliximab Is Superior to Etanercept for the Treatment of Postresuscitation Myocardial Dysfunction in a Swine Model of Ventricular Fibrillation

Introduction: Infliximab, a monoclonal antibody directed against the inflammatory cytokine TNF-α, has been shown to attenuate the myocardial dysfunction and hemodynamic decompensation associated with post-cardiac arrest syndrome. The aim of this study was to compare the effects of etanercept, a TNF-α receptor antagonist, to infliximab in a swine model of ventricular fibrillation (VF). Methods: Under general anesthesia, VF was induced electrically in domestic swine (n=30). After 7 minutes of VF, standard ACLS resuscitation was performed. Animals achieving return of spontaneous circulation (ROSC) were randomized to immediately receive infliximab (5 mg/kg, n=10) or etanercept (0.3 mg/kg [4 mg/m2], n=10) or vehicle (250 mL normal saline [NS], n=10) and LV function and hemodynamics were monitored for 3 hours. Results: Following ROSC, mean arterial pressure (MAP), stroke work (SW), and LV dP/dt fell from prearrest values in all groups. However, at the 30 minute nadir, infliximab-treated animals had higher MAP than either the NS group (difference 14.4 mm Hg, 95% confidence interval [CI] 4.2-24.7) or the etanercept group (19.2 mm Hg, 95% CI 9.0-29.5), higher SW than the NS group (10.3 gm-m, 95% CI 5.1-15.5, Figure) or the etanercept group (8.9 gm-m, 95% CI 4.0-14.4) and greater LV dP/dt than the NS group (282.9 mm Hg/sec, 95% CI 169.6-386.1) or the etanercep group (228.9 mm Hg/sec, 95% CI 115.6-342.2). Conclusions: In conclusion, only infliximab demonstrated a beneficial effect on post cardiac arrest hemodynamics and LV function in this swine model. Etanercept was no better in this regard than saline.

Different types of long-duration ventricular fibrillation: Can they be identified by electrocardiography

We tested the hypothesis that after 2 minutes of ventricular fibrillation (VF), periods of highly organized activations occur on the endocardium, arising from an intramural mother rotor or triggered activity originating in the Purkinje fibers. In 6 anesthetized dogs, we recorded electrically induced VF from two-thirds of the endocardium with a 64-electrode basket catheter. In another 12 dogs, the study was repeated with the addition of the early afterdepolarization blocker pinacidil in 6 animals and the delayed afterdepolarization blocker flunarizine in the other 6 animals. We found that, in addition to periods of disorganized chaotic activation (type I pattern), at between 3 and 7 minutes of VF, 2 highly organized patterns were observed (type II pattern, regular activity and type III pattern, triggered activity). When present, these patterns were observed in all 64 electrodes simultaneously. Type II arises from the apex and may be an intramural mother rotor and type III arises focally in Purkinje fibers and may be caused by early afterdepolarizations. The optimal defibrillation strategy may be different for the 3 different VF patterns. Therefore, it is important to determine if these 3 patterns can be differentiated from the body surface electrocardiogram.