Prolonged Ventricular Fibrillation Research Articles

A Model of Long-Term Ventricular Fibrillation in Isolated Rat Hearts

Ventricular fibrillation (VF) is a fatal arrhythmia with a high incidence in cardiac patients, but VF arrest under perfusion is a neglected method of intraoperative arrest in the field of cardiac surgery. With recent advances in cardiac surgery, the demand for prolonged VF studies under perfusion has increased. However, the field lacks simple, reliable, and reproducible animal models of chronic ventricular fibrillation. This protocol induces long-term VF through alternating current (AC) electrical stimulation of the epicardium. Different conditions were used to induce VF, including continuous stimulation with a low or high voltage to induce long-term VF and stimulation for 5 min with a low or high voltage to induce spontaneous long-term VF. The success rates of the different conditions, as well as the rates of myocardial injury and recovery of cardiac function, were compared. The results showed that continuous low-voltage stimulation induced long-term VF and that 5 min of low-voltage stimulation induced spontaneous long-term VF with mild myocardial injury and a high rate of recovery of cardiac function. However, the low-voltage, continuously stimulated long-term VF model had a higher success rate. High-voltage stimulation provided a higher rate of VF induction but showed a low defibrillation success rate, poor recovery of cardiac function, and severe myocardial injury. On the basis of these results, continuous low-voltage epicardial AC stimulation is recommended for its high success rate, stability, reliability, reproducibility, low impact on cardiac function, and mild myocardial injury.

Regional and Temporal Variation of Ventricular and Conduction Tissue Activity During Ventricular Fibrillation in Canines.

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Abstract 372: Regional Cerebral Saturation in a Swine Model of Goal-directed Resuscitation of Prolonged Ventricular Fibrillation Cardiac Arrest

Introduction: The characteristics and limitations of near-infrared spectroscopy (NIRS) measurement of regional cerebral saturation (rSO2) for reflecting key moment-to-moment physiological changes needed to guide cardiopulmonary resuscitation (CPR) have yet to be fully determined. Objective: Examine the impact of NIRS sensor placement and resuscitation process variation on rSO2 measurements during prolonged cardiac arrest. Methods: Thirty mixed-breed domestic pigs (mean weight: 25.0kg+/-2.0) were sedated (ketamine / xylazine), anesthetized (fentanyl), paralyzed (vecuronium) and mechanically ventilated. Micromanometer pressure transducers were placed in the aorta and right atrium via femoral cutdown to measure central pressures, including mean arterial pressure (MAP) and coronary perfusion pressure (CPP). Two NIRS sensors were placed on the cranium: one on the skin surface and one on the bare skull. Ventricular fibrillation was induced electrically and untreated for 8 minutes followed by CPR. Initial BLS phase: 4 minutes of CPR at 100 compressions per minute (CPM) and 2 inches depth with manual ventilations (30:2). Randomized ALS phase: CPR with a pressor-titrated (Group A) or a compression rate/depth-titrated (Group B) strategy targeting 25mmHg CPP. Group A animals received pressor doses q1min and fixed rate/depth CPR. Group B animals received increasing rates and depth of CPR with epinephrine q3min. Defibrillation was attempted at 6min CPR q2min. rSO2 was compared between skin and skull across phases of resuscitation with t-tests and generalized estimating equations (GEE). Results: Mean skin and skull rSO2 differed marginally overall (63.8 vs 62.0, p < 0.001), at baseline (69.9 vs 64.9, p < 0.001), during BLS CPR (56.9 vs 48.7, p < 0.001), during ALS CPR (59.5 vs 51.0, p < 0.001), and following ROSC (70.0 vs 60.5, p<0.001). rSO2 measured on either skull or skin both varied throughout phases of the experiment but not between CPR groups. In GEE models, rSO2 measured on skin or skull was not associated with MAP at baseline, but was directly associated during BLS (coef 0.13; p<0.001) & ALS CPR (coef 0.09; p<0.001), and after ROSC (coef 0.02; p=0.017). Conclusion: rSO2 measures differ between skin and skull though both correlate with MAP.

Enhanced external counterpulsation improves cardiac function in Beagles after cardiopulmonary resuscitation.

The aim of this study was to investigate the influence of enhanced external counterpulsation (EECP) on the cardiac function of beagle dogs after prolonged ventricular fibrillation. Twenty-four adult male beagles were randomly divided into control and EECP groups. Ventricular fibrillation was induced in the animals for 12 min, followed by 2 min of cardiopulmonary resuscitation. They then received EECP therapy for 4 h (EECP group) or not (control group). The hemodynamics was monitored using the PiCCO2 system. Blood gas and hemorheology were assessed at baseline and at 1, 2, and 4 h after return of spontaneous circulation (ROSC). The myocardial blood flow (MBF) was quantified by 18F-flurpiridaz PET myocardial perfusion imaging at baseline and 4 h after ROSC. Survival time of the animals was recorded within 24 h. Ventricular fibrillation was successfully induced in all animals, and they achieved ROSC after cardiopulmonary resuscitation. Survival time of the control group was shorter than that of the EECP group [median of 8 h (min 8 h, max 21 h) vs median of 24 h (min 16 h, max 24 h) (Kaplan Meyer plot analysis, P=0.0152). EECP improved blood gas analysis findings and increased the coronary perfusion pressure and MBF value. EECP also improved the cardiac function of Beagles after ROSC in multiple aspects, significantly increased blood flow velocity, and decreased plasma viscosity, erythrocyte aggregation index, and hematocrit levels. EECP improved the hemodynamics of beagle dogs and increased MBF, subsequently improving cardiac function and ultimately improving the survival time of animals after ROSC.

Effect of flunarizine on defibrillation outcomes and early refibrillation in a canine model of prolonged ventricular fibrillation

New Findings What is the central question of this study? Can successful electrical shock in combination with a delayed after‐depolarization (DAD) blocker suppress early refibrillation episodes following long duration ventricular fibrillation (LDVF)? What is the main finding and its importance? Flunarizine significantly reduced the activation of LDVF and early ventricular fibrillation (VF) recurrence following LDVF, suggesting that DADs potentially contribute to refibrillation in prolonged VF. Thus, DAD inhibition can be used as an adjunctive therapy for electrical defibrillation to treat prolonged VF and suppress refibrillation following LDVF. This study attempts to detect changes in the defibrillation threshold (DFT) at different stages of ventricular fibrillation (VF) (short duration VF, SDVF; long duration VF, LDVF) and during early refibrillation following successful defibrillation of LDVF by giving flunarizine, a blocker of delayed after‐depolarizations (DADs). Twelve beagles were divided into two groups (the control group, n = 6; and the flunarizine group, n = 6). Two 64‐electrode basket catheters were deployed into the left and the right ventricles for global endocardium mapping. The DFTs of SDVF and LDVF were determined at 20 s and 7 min, respectively, after VF induction in each group. Any refibrillation episodes were recorded within 15 min after the first successful defibrillation of LDVF. In the flunarizine group, the SDVF‐DFT values before and after the drug were not significantly different. The 7 min LDVF‐DFTs were markedly reduced by 26% (P < 0.05, the control group) and 38% (P < 0.01, the flunarizine group) compared to the 20 s SDVF‐DFTs within each group. The difference between SDVF‐DFT and LDVF‐DFT after flunarizine was larger than that in the control group (213 ± 65 vs. 120 ± 84 V, P < 0.05). The number of refibrillation episodes per animal (1.3 ± 1.0) following successful defibrillation of LDVF after flunarizine was 48% of that in controls (2.7 ± 2.0, P < 0.05). The effect of flunarizine on SDVF‐DFT and LDVF‐DFT indicates that the role of DADs in the defibrillation mechanism may differ as VF continues. Flunarizine significantly reduced early VF recurrence following LDVF, suggesting that DADs potentially contribute to refibrillation in a canine model of prolonged VF.

Abstract 149: Role of Pre and Intra-Arrest Hemodynamics in Evolution of the Ventricular Fibrillation Electrocardiogram Waveform

Purpose: Quantitative waveform measures (QWM) of the ventricular fibrillation (VF) waveform have been shown in laboratory and clinical studies to be predictive of return of spontaneous circulation (ROSC) and survival to hospital discharge. During resuscitation, QWM are responsive to hemodynamic changes resulting from CPR. It is not known whether the trajectory of QWM are affected by pre-arrest hemodynamics or intra-arrest arterio-venous pressure equilibration. We sought to investigate the role of hemodynamics on the evolution of VF before and during prolonged VF. Methods: We pooled data from six previous porcine experiments. Each modeled prolonged VF and included electrical induction of VF which was left untreated for up to 10 minutes, followed by attempted resuscitation. All animals were instrumented with pressure transducers (Millar, MikroTip) placed via femoral cutdown in the aorta and right atrium, as well as Lead II surface ECG. Signals were recorded continuously at 1000Hz with a data acquisition unit (PowerLab, ADInstruments). Mean baseline central arterial (CAP) and central venous pressure (CVP) were calculated from 1- minute of immediate pre-VF pressure traces. Coronary perfusion pressure (CPP) during untreated VF was calculated as the continuous difference between the CAP and CVP channels. Median slope (MS), a QWM, was calculated in 1-second windows and interpolated to the full length of the intra-arrest ECG. For trajectory analysis, CPP and MS traces were normalized on a 0-1 scale and grouped by morphological similarity. Pearson’s Correlation coefficient was calculated between corresponding CPP and MS traces. Results: A total of 141 experiments were included in the analysis. Overall mean (SD) correlation between CPP and MS was 0.56 (0.29). CPP-MS correlation strength did not correlate with baseline pressures. However, trajectory analysis revealed multiple patterns of hemodynamic and QWM evolution through untreated VF, with the most well-defined (mean coeff. = 0.58) indicating a shared bimodality temporally offset between CPP and MS. Conclusions: Hemodynamics during untreated VF show some correlation with the trajectory of QWM of the VF signal. More work is needed to understand the mechanism of this relationship.

Selective beta-blocker esmolol improves cerebral cortex microcirculation in a swine ventricular fibrillation model.

This study aimed to identify whether esmolol attenuates cerebral cortex microcirculation blood flow due to epinephrine in prolonged ventricular fibrillation (VF) and cardiopulmonary resuscitation (CPR), and may improve neurological prognosis. Male pigs were randomized into the esmolol+epinephrine group (group EE), the epinephrine group (group EP), and the normal saline group (group NS) (n = 8 each group). Untreated VF for 8 minutes was induced in pigs. After CPR for 2 minutes, group EE received esmolol (500 µg/kg)+epinephrine (20 µg/kg), group EP received epinephrine 20 µg/kg, and group NS received 5 mL normal saline. Then, a 120 J electric shock was delivered. If the return of spontaneous circulation (ROSC) failed, epinephrine (20 µg/kg) was repeated in group EP and EE, followed by another 2 minutes of CPR, a 150 J electric shock was delivered every 2 minutes until ROSC. Cerebral microcirculation images were obtained at 0.5, 6, 12, and 24 hours by cranial windows after ROSC. Cerebral performance category scores and neurological deficit scores (NDS) were calculated. The frontal cortices were harvested after the animals were euthanized. The NDS, the perfused vessel density, and the microcirculatory flow index of group EE were better than other two groups. The morphology of endothelial cells in the group EE remained intact; however, it was destroyed in the group EP. Administration of esmolol with epinephrine may alleviate the impairment of cerebral microcirculation blood flow caused by the administration of epinephrine in prolonged VF and thereby improves neurological outcomes in a swine model.

Extracorporeal Life Support Increases Survival After Prolonged Ventricular Fibrillation Cardiac Arrest in the Rat.

ABSTRACTBackground:Extracorporeal life support (ECLS) for cardiopulmonary resuscitation (CPR) may increase end organ perfusion and thus survival when conventional CPR fails. The aim was to investigate, if after ventricular fibrillation cardiac arrest in rodents ECLS improves outcome compared with conventional CPR.Methods:In 24 adult male Sprague–Dawley rats (460–510 g) resuscitation was started after 10 min of no-flow with ECLS (consisting of an open reservoir, roller pump, and membrane oxygenator, connected to cannulas in the jugular vein and femoral artery, n = 8) or CPR (mechanical chest compressions plus ventilations, n = 8) and compared with a sham group (n = 8). After return of spontaneous circulation (ROSC), all rats were maintained at 33°C for 12 h. Survival to 14 days, neurologic deficit scores and overall performance categories were assessed.Results:ECLS leads to sustained ROSC in 8 of 8 (100%) and neurological intact survival to 14 days in 7 of 8 rats (88%), compared with 5 of 8 (63%) and 1 of 8 CPR rats. The median survival time was 14 days (IQR: 14–14) in the ECLS and 1 day (IQR: 0 to 5) for the CPR group (P = 0.004).Conclusion:In a rat model of prolonged ventricular fibrillation cardiac arrest, ECLS with mild hypothermia produces 100% resuscitability and 88% long-term survival, significantly better than conventional CPR.

Early Effects of Prolonged Cardiac Arrest and Ischemic Postconditioning during Cardiopulmonary Resuscitation on Cardiac and Brain Mitochondrial Function in Pigs

BackgroundOut-of-hospital cardiac arrest (CA) is a prevalent medical crisis resulting in severe injury to the heart and brain and an overall survival of less than 10%. Mitochondrial dysfunction is predicted to be a key determinant of poor outcomes following prolonged CA. However, the onset and severity of mitochondrial dysfunction during CA and cardiopulmonary resuscitation (CPR) is not fully understood. Ischemic postconditioning (IPC), controlled pauses during the initiation of CPR, has been shown to improve cardiac function and neurologically favorable outcomes after 15min of CA. We tested the hypothesis that mitochondrial dysfunction develops during prolonged CA and can be rescued with IPC during CPR (IPC-CPR). MethodsA total of 63 swine were randomized to no ischemia (Naïve), 19min of ventricular fibrillation (VF) CA without CPR (Untreated VF), or 15min of CA with 4min of reperfusion with either standard CPR (S-CPR) or IPC-CPR. Mitochondria were isolated from the heart and brain to quantify respiration, rate of ATP synthesis, and calcium retention capacity (CRC). Reactive oxygen species (ROS) production was quantified from fresh frozen heart and brain tissue. ResultsCompared to Naïve, Untreated VF induced cardiac and brain ROS overproduction concurrent with decreased mitochondrial respiratory coupling and CRC, as well as decreased cardiac ATP synthesis. Compared to Untreated VF, S-CPR attenuated brain ROS overproduction but had no other effect on mitochondrial function in the heart or brain. Compared to Untreated VF, IPC-CPR improved cardiac mitochondrial respiratory coupling and rate of ATP synthesis, and decreased ROS overproduction in the heart and brain. ConclusionsFifteen minutes of VF CA results in diminished mitochondrial respiration, ATP synthesis, CRC, and increased ROS production in the heart and brain. IPC-CPR attenuates cardiac mitochondrial dysfunction caused by prolonged VF CA after only 4min of reperfusion, suggesting that IPC-CPR is an effective intervention to reduce cardiac injury. However, reperfusion with both CPR methods had limited effect on mitochondrial function in the brain, emphasizing an important physiological divergence in post-arrest recovery between those two vital organs.

Reperfusion injury protection during Basic Life Support improves circulation and survival outcomes in a porcine model of prolonged cardiac arrest

ObjectiveIschemic postconditioning (PC) using three intentional pauses at the start of cardiopulmonary resuscitation (CPR) improves outcomes after cardiac arrest in pigs when epinephrine (epi) is used before defibrillation. We hypothesized PC, performed during basic life support (BLS) in the absence of epinephrine, would reduce reperfusion injury and enhance 24h functional recovery. DesignProspective animal investigation. SettingAnimal laboratory SubjectsFemale farm pigs (n=46, 39±1kg). InterventionsProtocol A: After 12min of ventricular fibrillation (VF), 28 pigs were randomized to four groups: (A) Standard CPR (SCPR), (B) active compression-decompression CPR with an impedance threshold device (ACD-ITD), (C) SCPR+PC (SCPR+PC) and (D) ACD-ITD CPR+PC. Protocol B: After 15min of VF, 18 pigs were randomized to ACD-ITD CPR or ACD-ITD+PC. The BLS duration was 2.75min in Protocol A and 5min in Protocol B. Following BLS, up to three shocks were delivered. Without return of spontaneous circulation (ROSC), CPR was resumed and epi (0.5mg) and defibrillation delivered. The primary end point was survival without major adverse events. Hemodynamic parameters and left ventricular ejection fraction (LVEF) were also measured. Data are presented as mean±SEM. Measurements and Main ResultsProtocol A: ACD-ITD+PC (group D) improved coronary perfusion pressure after 3min of BLS versus the three other groups (28±6, 35±7, 23±5 and 47±7 for groups A, B, C, D respectively, p=0.05). There were no significant differences in 24h survival between groups. Protocol BLVEF 4h post ROSC was significantly higher with ACD-ITD+PC vs ACD-ITD alone (52.5±3% vs. 37.5±6.6%, p=0.045). Survival rates were significantly higher with ACD-ITD+PC vs. ACD-ITD alone (p=0.027). ConclusionsBLS using ACD-ITD+PC reduced post resuscitation cardiac dysfunction and improved functional recovery after prolonged untreated VF in pigs. Protocol number12-11.

Extended detection time to reduce shocks is safe in secondary prevention patients: The secondary prevention substudy of PainFree SST

Prolonged ventricular fibrillation (VF) detection has been shown to reduce implantable cardioverter-defibrillator (ICD) therapies and improve prognosis in primary prevention ICD patients. Data in secondary prevention patients are limited. The PainFree SST secondary prevention study is the largest trial of secondary prevention patients randomized between standard and prolonged detection to assess the safety of this strategy in these patients. A total of 705 secondary prevention patients implanted with an ICD in the PainFree SST trial were enrolled in this substudy; 353 patients were randomized to VF detection of 18/24 intervals and 352 patients to 30/40. All other VF parameters were standardized by protocol. The 1-year arrhythmic syncope-free rates in the standard and prolonged groups were 97.7% vs 96.9%, respectively, (P = .0034 for noninferiority). Freedom from all-cause syncope was 96% in both arms (P = .0013 for noninferiority). There was no difference in the time to first appropriate or inappropriate VF therapy. However, the rates of treated VF episodes were lower in the prolonged arm (1.48 per patient per year vs 0.44 per patient per year, P = .0001). A trend toward lower mortality in the prolonged group was not statistically different (5.6% 1 year, 12% 2 years vs 3.8% 1 year, 7.7% 2 years, adjusted hazard ratio = 0.60, P = .061). This large prospective randomized study shows that prolonged detection can safely be programmed in secondary prevention ICD patients with new or existing devices. This programming strategy decreases the rate of treated events and is not associated with an increased risk of syncope or mortality.

Short period of mild hypothermia improves resuscitation outcome in a porcine model of prolonged ventricular fibrillation

Objective To investigate the resuscitation outcome after a short period of mild hypothermia in porcine model of prolonged ventricular fibrillation (VF). Methods Fourteen male healthy domestic swine weighting 34 to 36 kg were used. VF was induced electrically and maintained untreated for 11 mins, followed by manual cardiopulmonary resuscitation (CPR) procedure. Two investigators initiated chest compression and bag-valve mask ventilation in pattern of 2 min rotation. A biphasic wave of 120 J electric defibrillation (ED) was attempted 6 mins after CPR. If there was no return of spontaneous circulation (ROSC), CPR was restored and ED was delivered when necessarily. Resuscitation was considered unsuccessful if absence of ROSC for 12 mins. However, if ROSC occurred, animals were randomly(random number) diveded into normothermia (NT) group and hypothermia treatment (CH) group. Animals in CH group were immediately cooled by using intravenous infusion of ice-cold saline and surface cooling. Core temperature was reduced to 32-34 degrees centigrade within 120 mins and maintained at this level for 2 h. Active rewarming was completed within 2 h until baseline body temperature was reached. Data of hemodynamic variables, blood-gas analysis and blood lactate before VF of two groups were recorded. Meawhile, cardiac output (CO), heart rate and Tc after ROSC were recorded. Neurological defect scores (NDS) were evaluated every 24 h until 96 h after ROSC. Variables were compared using either Fisher test or repeated measures analysis of variance, followed by Bonferroni for multiple comparisons. A two-sided P value<0.05 was regarded statistically significant. Results There was no significant difference in body weight, mean arterial pressure, CO, pH, pressure of end-tidal carbon dioxide (ETCO2) and lactate between groups before VF. In the period of CPR, there were also no significant difference in total resuscitation time, first shock success rate, ROSC rate, shock ROSC rate, total number of shock and doses of epinephrine. However, animals in CH group survived longer time than that in NT groups [（96.00±0.00)h vs (49.71±43.65)h,P=0.031]. Meanwhile, the survival rate of 96 h was significantly higher in CH than that in NT (P<0.05). For neurological function, there was a obviously better NDS in CH group than that in NT group within ROSC 96 h (P<0.05). Conclusion Even a short duration of 2 hour mild hypothermia could improve resuscitation outcome in porcine model of 11 minute VF. Key words: Cardiopulmonary resuscitation; Mild hypothermia; Short duration; Resuscitation outcome

Extracorporeal Membrane Oxygenation as a Procedural Rescue Strategy for Transcatheter Aortic Valve Replacement Cardiac Complications.

Cardiovascular complications during or after transcatheter aortic valve replacement (TAVR) are associated with extremely high mortality, but extracorporeal membrane oxygenation (ECMO) can be used as procedural rescue option to improve outcomes when patients experience respiratory or cardiac arrest. From 2012 to 2014, 230 patients underwent TAVR and 10 patients (4.3%) required emergent venous-arterial ECMO support. Mean age was 83 years, median Society of Thoracic Surgeons (STS) score was 15, and mean aortic gradient was 45 mm Hg. Median left ventricular ejection fraction was 35%. Access for most ECMOs was femoral; two patients required central arterial and femoral venous access. Extracorporeal membrane oxygenation was initiated in response to hemodynamic collapse due to perforation of left ventricle (n = 2), aortic root rupture (n = 1), moderate-to-severe aortic insufficiency (n = 1), left main impingement (n = 1), valve embolization (n = 1), severe hypotension and cardiac arrest after prolonged rapid pacing sequence (n = 1), ventricular fibrillation (n = 2), and ventricular tachycardia (n = 1). Median time of ECMO support was 87 minutes. There were three hospital deaths. Post-TAVR mean aortic gradient was 8 mm Hg and median hospital stay was 19 days. Additional procedures included valve-in-valve placement (n = 1), percutaneous coronary intervention (n = 1), surgical LV repair (n = 2), surgical valve replacement (n = 1), aortic root rupture repair, and coronary bypass grafting (n = 1). Extracorporeal membrane oxygenation is rescue therapy for hemodynamic instable patients who develop TAVR-related cardiac complications.

Abstract 16996: Controlled Pauses (“Stutter”) CPR Did Not Improve ROSC or 4-hour Survival in a Porcine Model of VF-induced Cardiac Arrest

Introduction: Ischemic post-conditioning (IPC) has shown promise in mitigating ischemia-reperfusion injury. Controlled pauses during CPR (CP-CPR) following cardiac arrest (CA) and prolonged downtime may help invoke IPC mechanisms and have been shown to improve neurological outcome in swine. We tested whether CP-CPR would improve return of spontaneous circulation (ROSC) and/or 4-hr survival rates, compared with standard CPR from a mechanical chest compression device (M-CPR), following prolonged downtime in a porcine model of ventricular fibrillation (VF)-induced CA. Methods: Twenty anesthetized and instrumented pigs were block randomized to two protocols. Following 10 min of VF, mechanical CPR was initiated (100 comp/min, 50% duty cycle, 2 inch depth). Over the first 5 minutes of CPR, the M-CPR protocol group received continuous chest compressions, while the CP-CPR protocol included four 20-sec pauses in compressions starting at 40, 100, 160, and 220 sec. All other interventions were the same in the two groups. After 5 minutes, a first shock was delivered during a pause. If the shock failed to convert to a perfusing rhythm for ≥ 30 s with a systolic aortic pressure (sAoP) ≥ 50 mmHg for at least the first three contiguous sAoP values, CPR was continued in 2 min cycles, followed by a shock (if indicated) at the end of each cycle, for up to 10 cycles. As soon as these criteria were met between two CPR cycles, ROSC was documented and a post-resuscitation protocol was initiated. During the post-resuscitation protocol, inotropic agents were provided as needed to maintain sAoP ≥ 50 mmHg. Survival was declared if the sAoP was maintained above threshold for 4 hrs following ROSC. Results: Nineteen animals were successfully instrumented for data gathering (9 CP-CPR, 10 M-CPR). In the CP-CPR and M-CPR groups respectively, 3/9 (33%) vs. 5/10 (50%) achieved ROSC (p = 0.46); when ROSC was achieved, time to ROSC was 7.7±1.2 min vs. 5.8±1.1 min (p = 0.08). All animals that achieved ROSC survived to 4 hours. Conclusions: In a porcine model of CA following prolonged VF, CP-CPR did not improve ROSC or 4-hr survival. The trend towards delayed time to ROSC suggests controlled pauses may impair initial resuscitation, even if they ultimately improve neurological outcome. Further studies are warranted.

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.

Abstract 19360: Potassium Infusion at the Onset of CPR Prevents Mitochondrial Impairment After Prolonged VF Arrest

Introduction: Potassium-based cardioplegia has been used for decades in cardiac surgery to preserve cardiac tissue while inducing cardiac standstill. Recent studies have also shown that animals can be successfully resuscitated after infusion of potassium at the beginning of cardiopulmonary resuscitation (CPR). This study tested the hypothesis that infusion of potassium at the onset of CPR prevents mitochondrial impairment caused by reperfusion injury after prolonged cardiac arrest. Methods: After 15 minutes of untreated ventricular fibrillation (VF), 18 pigs were randomized to receive control saline, 50 mEq potassium (low-dose), or 100 mEq potassium (high-dose) via central venous catheter at the initiation of CPR. All animals received mechanical CPR with active compression/decompression, an impedance threshold device, and epinephrine per standard AHA protocols. Cardiac tissue was harvested after 4 minutes of CPR without defibrillation. Primary endpoints included mitochondrial respiratory control index (RCI) and mitochondrial calcium retention capacity (CRC). Secondary endpoints included the hemodynamic assessment. Results: Infusion of potassium at the onset of CPR had no effect on hemodynamics including coronary perfusion pressure (25 vs. 28, p=0.7 for Control and low-dose KCl, respectively). Despite similar hemodynamics, potassium infusion improved RCI comparing control to low-dose KCl infusion using both complex I (4.3 vs. 6.1, p=0.01) and complex II (2.4 vs. 3.3, p=0.003) substrates. High-dose KCl did not provide additional respiration benefit. Potassium infusion also increased CRC. With complex I substrates, high-dose KCl enhanced CRC compared to controls [1361 vs. 1040, (in nmol), p=0.008, respectively]. Low-dose KCl increased CRC with complex II (1337 vs. 1597, p=0.02, for control and low-dose KCl, respectively) while high-dose KCl did not provide additional benefit. Conclusions: Potassium infusion at the initiation of CPR prevents reperfusion-induced mitochondrial damage. This improvement was independent of the perfusion pressure achieved during CPR. Improvement of mitochondrial function and stability is observed within the first four minutes of CPR providing an improved substrate for establishing ROSC.

Blinded Evaluation of Combination Drug Therapy for Prolonged Ventricular Fibrillation Using a Swine Model of Sudden Cardiac Arrest

ABSTRACTDespite experimental evidence supporting the use of resuscitation drugs in the treatment of sudden cardiac arrest (CA), there are no good human clinical data to support the decades-old practice of giving these medications during out-of-hospital CA resuscitation. We hypothesized that the lack of efficacy in clinical practice in ventricular fibrillation (VF) is the failure-based manner in which resuscitation drugs have historically been administered (one at a time interspersed with chest compressions and a defibrillation attempt, giving the next only if the previous one was ineffective). The aim of this study was to determine if giving and circulating a combination of commonly available, historically used resuscitation drugs together, prior to the first defibrillation attempt after prolonged VF, might improve short-term outcomes compared with the failure-based serial drug approach used in the past. We used a well-established swine model of sudden prolonged untreated VF. Animals were randomized to receive epinephrine (0.01 mg/kg), vasopressin (0.5 U/kg), amiodarone (4 mg/kg), and sodium bicarbonate (1.0 mEq/kg) in series (SERIES group [n = 53]) or a combination of epinephrine (0.01 mg/kg), vasopressin (0.5 U/kg), amiodarone (4 mg/kg), sodium bicarbonate (1.0 mEq/kg), and metoprolol (0.2 mg/kg) (COCKTAIL group) delivered in rapid succession at the beginning of the attempted resuscitation (n = 27). Data were analyzed descriptively. Baseline characteristics and chemistries between the two groups were the same. Termination of VF was statistically similar in the two groups: 88.7% (47/53) versus 85.2% (23/27) p = 0.66, with an adjusted relative risk ratio (RRR) of 0.94 (0.37, 1.15). However, ROSC was higher in the SERIES group (56.6% [30/53] versus 22.2% [6/27], adjusted RRR = 2.83; [1.16, 3.84] p = 0.029) as was 20-minute survival (52.8% [28/53] versus 18.5% [5/27], adjusted RRR = 3.15 [1.14, 4.54] p = 0.032). The combination of drugs studied, at these dosages, inexplicably worsened short-term outcomes after prolonged untreated VF.

Centhaquin improves the outcome of cardiopulmonary resuscitation in a swine model of prolonged ventricular fibrillation

Centhaquin improves the outcome of cardiopulmonary resuscitation in a swine model of prolonged ventricular fibrillation

Extracorporeal live support increases survival after prolonged ventricular fibrillation cardiac arrest in the rat as compared to conventional cardiopulmonary resuscitation

Extracorporeal live support increases survival after prolonged ventricular fibrillation cardiac arrest in the rat as compared to conventional cardiopulmonary resuscitation

Extracorporeal live support improves cerebral perfusion pressure during and haemodynamic stability following resuscitation from prolonged ventricular fibrillation cardiac arrest in the rat

s / Resuscitation 96S (2015) 5–42 9 Conclusion: ECPR avoids hypercarbia and improves perfusion pressures during resuscitation as compared to CPR. After ROSC, haemodynamic stability is improved in a prolonged VFCA rat model. http://dx.doi.org/10.1016/j.resuscitation.2015.09.020