Ventricular Fibrillation Cardiac Arrest Model Research Articles

A ventricular fibrillation cardiac arrest model with extracorporeal cardiopulmonary resuscitation in rats: 8 minutes arrest time leads to increased myocardial damage but does not increase neuronal damage compared to 6 minutes.

Extracorporeal cardiopulmonary resuscitation (ECPR) is an emerging strategy in highly selected patients with refractory cardiac arrest (CA). Animal models can help to identify new therapeutic strategies to improve neurological outcome and cardiac function after global ischemia in CA. Aim of the study was to establish a reproducible ECPR rat model of ventricular fibrillation CA (VFCA) that leads to consistent neuronal damage with acceptable long-term survival rates, which can be used for future research. Male Sprague Dawley rats were resuscitated with ECPR from 6 min (n = 15) and 8 min (n = 16) VFCA. Animals surviving for 14 days after return of spontaneous resuscitation (ROSC) were compared with sham operated animals (n = 10); neurological outcome was assessed daily until day 14. In the hippocampal cornu ammonis 1 region viable neurons were counted. Microglia and astrocyte reaction was assessed by Iba1 and GFAP immunohistochemistry, and collagen fibers in the myocardium were detected in Azan staining. QuPath was applied for quantification. Of the 15 rats included in the 6 min CA group, all achieved ROSC (100%) and 10 (67%) survived to 14 days; in the 8 min CA group, 15 (94%) achieved ROSC and 5 (31%) reached the endpoint. All sham animals (n = 10) survived 2 weeks. The quantity of viable neurons was significantly decreased, while the area displaying Iba1 and GFAP positive pixels was significantly increased in the hippocampus across both groups that experienced CA. Interestingly, there was no difference between the two CA groups regarding these changes. The myocardium in the 8 min CA group exhibited significantly more collagen fibers compared to the sham animals, without differences between 6- and 8-min CA groups. However, this significant increase was not observed in the 6 min CA group. Our findings indicate a uniform occurrence of neuronal damage in the hippocampus across both CA groups. However, there was a decrease in survival following an 8-min CA. Consequently, a 6-min duration of CA resulted in predictable neurological damage without significant cardiac damage and ensured adequate survival rates up to 14 days. This appears to offer a reliable model for investigating neuroprotective therapies.

Abstract 231: Volume And Direction Of Carotid Blood Flow During Cardiopulmonary Resuscitation In A Porcine Model Of Ventricular Fibrillation

Introduction: Hemodynamics during cardiopulmonary resuscitation (CPR) is not well understood. We aimed to quantitatively evaluate the volume and direction of carotid blood flow (CBF) during CPR in a porcine model of ventricular fibrillation (VF) cardiac arrest. Methods: Nineteen male domestic pigs were intubated and ventilated mechanically. Following baseline measurements, VF was electrically induced. CBF was measured continuously using a flow probe positioned around the common carotid arteries. After 0 or 5 min no-flow time of untreated VF, CPR was initiated, involving chest compressions and ventilation with oxygen. CPR was continued for 25 min, with mechanical (L1, L2, and L3) and manual (M1 and M2) CPR alternated at 5 min intervals. A Friedman test was used to compare the groups in each phase. Post hoc analysis was performed using a Wilcoxon signed-rank test (Bonferroni corrected). Results: CBF was calculated as the average of each phase. The net flow was calculated through subtracting the retrograde flow from the anterograde flow. Average net flow (median, interquartile range [IQR], mL/min) during CPR was 58.1 (24.0-111.3), 19.8 (8.4-24.9), 21.2 (9.5-37.9), 15.4 (8.4-24.9), and 16.4 (10.3-30.1) in phases L1, M1, L2, M2, and L3, respectively ( p < 0.001, L1 vs. M1). The ratio (median, IQR, %) of retrograde to anterograde flow was 41.3 (16.7-58.7), 48.6 (33.1-60.4), 42.2 (36.5-76.4), 49.1 (39.4-68.5), and 50.0 (38.0-79.0) in phases L1, M1, L2, M2, and L3, respectively ( p = 0.299). Conclusions: In this VF cardiac arrest model, the net flow of the carotid artery during CPR decreased with time. Both mechanical and manual CPR produced substantial retrograde flow, although the ratio of retrograde to anterograde flow did not change.

Volumetric Capnography Monitoring and Effects of Epinephrine on Volume of Carbon Dioxide Elimination during Resuscitation after Cardiac Arrest in a Swine Pediatric Ventricular Fibrillatory Arrest.

The aim of this study was to examine the use of volumetric capnography monitoring to assess cardiopulmonary resuscitation (CPR) effectiveness by correlating it with cardiac output (CO), and to evaluate the effect of epinephrine boluses on both end-tidal carbon dioxide (EtCO 2 ) and the volume of CO 2 elimination (VCO 2 ) in a swine ventricular fibrillation cardiac arrest model. Planned secondary analysis of data collected to investigate the use of noninvasive monitors in a pediatric swine ventricular fibrillation cardiac arrest model was performed. Twenty-eight ventricular fibrillatory arrests with open cardiac massage were conducted. During CPR, EtCO 2 and VCO 2 had strong correlation with CO, measured as a percentage of baseline pulmonary blood flow, with correlation coefficients of 0.83 ( p < 0.001) and 0.53 ( p = 0.018), respectively. However, both EtCO 2 and VCO 2 had weak and nonsignificant correlation with diastolic blood pressure during CPR 0.30 ( p = 0.484) (95% confidence interval [CI], -0.51-0.83) and 0.25 ( p = 0.566) (95% CI, -0.55-0.81), respectively. EtCO 2 and VCO 2 increased significantly after the first epinephrine bolus without significant change in CO. The correlations between EtCO 2 and VCO 2 and CO were weak 0.20 ( p = 0.646) (95% CI, -0.59-0.79), and 0.27 ( p = 0.543) (95% CI, -0.54-0.82) following epinephrine boluses. Continuous EtCO 2 and VCO 2 monitoring are potentially useful metrics to ensure effective CPR. However, transient epinephrine administration by boluses might confound the use of EtCO 2 and VCO 2 to guide chest compression.

The efficiency of ventilation in out-of-hospital cardiopulmonary resuscitation: ananimal study

Objective To study the efficiency of ventilationin in out-of-hospital cardiopulmonary resuscitation(CPR) by performing compression-only CPR or conventional CPR in rats of different causes of cardiac arrest(CA). Methods Forty five SD rats were randomly divided into 5 groups: asphyxia-conventional group(group A, n=10), asphyxia-compression-only group(group B, n=10), ventricular fibrillation-conventional group(group C, n=10), ventricular fibrillation-compression-only group(group D, n=10), group sham(n=5). The model of asphyxial CA was made by clamping endotracheal tube at expiration in group A and group B. The model of ventricular fibrillation CA was made by transoesophageal cardiac pacing in group C and group D. Bystander CPR was initiated 4 min later. Conventional CPR(compression∶ventilation=30∶2) was performed in group A and group C, compression-only CPR was performed in group B and group D. For animals that did not attain return of spontaneous circulation(ROSC) during the 8 min bystander CPR period, advanced life support(ALS) was provided. The animals which did not attain ROSC after 10 min ALS should be given up. The pathological specimens of brain, ventricular wall and right lower lobe of the lung were collected after 24 h, and the samples were collected in the death of 24 h. Post-resuscitation treatment had been performed in all successfully resuscitated animals for 1 h. At 24 h after ROSC, rats were sacrificed for histological analysis. The vilai signs was monitored for 1 h in goup sham, rats were sacrificed for histological analysis after survival 24 h. The major outcome measure was rates of ROSC, and the secondary was the survival rates of 24 h. Blood samples were drawn for blood gas analysis during resuscitation in the pathologic findings. Results Rates of ROSC were higher in group A and group C compared with group B and group D, but the difference was not significant. Survival rates of 24 h were compared, group A and group C were significantly higher than group B and group D(P<0.05), and the tissue damage in group A and group C were milder than group B and group D. Conclusions Conventional bystander CPR was associated with a higher survival of 24 h than compression-only CPR. Conventional bystander CPR might be the preferable approach of resuscitation for adult patients with witnessed out-of-hospital CA, whether cardiogenic or non-cardiogenic CA. Key words: Cardiac arrest; Cardiopulmonary resuscitation; Artificial ventilation

The Ventricular Fibrillation Waveform Approach to Direct Postshock Chest Compressions in a Swine Model of VF Arrest

BackgroundIn retrospective swine and human investigations of ventricular fibrillation (VF) cardiac arrest, the amplitude-spectral area (AMSA), determined from the VF waveform, can predict defibrillation and a return of spontaneous circulation (ROSC). ObjectivesWe hypothesized that an algorithm using AMSA in real time to direct postshock chest compression (CC) duration would shorten the time to ROSC and improve neurological outcome in a swine model of VF cardiac arrest with acute myocardial infarction (AMI) or nonischemic myocardium. MethodsAMI was induced by occlusion of the left anterior descending artery. VF was untreated for 10 min. Animals were randomized to either traditional resuscitation with 2 min of CC after each shock or to an AMSA-guided algorithm where postshock CCs were shortened to 1 min if the preshock AMSA exceeded 20 mV-Hz. ResultsA total of 48 animals were studied, 12 in each group (AMI vs. normal, and traditional vs. AMSA-guided). There was a nonsignificant shorter time to ROSC with an AMSA-guided approach in AMI swine (17.2 ± 3.4 vs. 18.5 ± 4.7 min, p = NS), and in normal swine (13.5 ± 1.1 vs. 14.4 ± 1.2, p = NS). Neurological outcome was similar between traditional and AMSA-guided animals. AMSA predicted ROSC (p < 0.001), and a threshold of 20 mV-Hz gave a sensitivity of 89%, with specificity of 29%. ConclusionAlthough AMSA predicts ROSC in a swine model of VF arrest in both AMI and normal swine, a waveform-guided approach that uses AMSA to direct postshock CC duration does not significantly shorten the time to ROSC or alter neurological outcome.

Combination of Intravenous Ascorbic Acid Administration and Hypothermia After Resuscitation Improves Myocardial Function and Survival in a Ventricular Fibrillation Cardiac Arrest Model in the Rat

Intravenous (IV) administration of ascorbic acid during cardiopulmonary resuscitation (CPR) was reported to facilitate defibrillation and improves survival in ventricular fibrillation (VF) cardiac arrest. We investigated whether IV administration of ascorbic acid after return of spontaneous circulation (ROSC) can improve outcomes in VF cardiac arrest in a rat model and its interaction with therapeutic hypothermia. Ventricular fibrillation-induced cardiac arrest followed by CPR and defibrillation was performed in male Wistar rats. After ROSC, the animals were equally randomized to the normothermia (NormoT), hypothermia (HypoT), ascorbic acid (AA+NormoT), and ascorbic acid plus hypothermia (AA+HypoT) groups. The AA+NormoT and AA+HypoT groups received IV ascorbic acid (100 mg/kg). In the HypoT and AA+HypoT groups, therapeutic hypothermia was maintained at 32°C for 2 hours. There were 12 rats in each group. Within 4 hours after ROSC, the HypoT, AA+NormoT, and AA+HypoT groups had significantly lower myocardial lipid peroxidation than the NormoT group. Within 4 hours following ROSC, the AA+NormoT group had a significantly better systolic function (dp/dt40 ) than the NormoT group (6887.9 mm Hg/sec, SD ± 1049.7 mm Hg/sec vs. 5953.6 mm Hg/sec, SD ± 1161.9 mm Hg/sec; p < 0.05). The AA+HypoT group also showed a significantly better diastolic function (-dp/dtmax ) than the HypoT group (dp/dt40 : 8524.8, SD ± 1166.7 mm Hg/sec vs. 7399.8 mm Hg/sec, SD ± 1114.5 mmHg/sec; dp/dtmax : -8183.4 mm Hg/sec, SD ± 1359.0 mm Hg/sec vs. -6573.7 mm Hg/sec, SD ± 1110.9 mm Hg/sec; p < 0.05) at the fourth hour following ROSC. Also at 4 hours, there was less myocytolysis in the HypoT, AA+NormoT, and AA+HypoT groups than the NormoT group. The HypoT, AA+NormoT, and AA+HypoT groups had significantly better survival rates and neurologic outcomes than the NormoT group. Compared with only five surviving animals in the NormoT group, there were nine, eight, and 10 in the HypoT, AA+NormoT, and AA+HypoT groups, respectively, with good neurologic outcomes at 72 hours. Intravenous ascorbic acid administration after ROSC in normothermia may mitigate myocardial damage and improve systolic function, survival rate, and neurologic outcomes in VF cardiac arrest of rat. Combination of ascorbic acid and hypothermia showed an additive effect in improving both systolic and diastolic functions after ROSC.

Protective effects of therapeutic hypothermia in post-resuscitation myocardium

Aim of the studyPost-resuscitation therapeutic hypothermia has been recommended because of its neuroprotective effects. However, a few studies have reported the effects of therapeutic hypothermia on the heart, especially in ventricular fibrillation cardiac arrest. The aim of this study was to determine whether therapeutic hypothermia attenuates post-resuscitation myocardial injury in a swine cardiac arrest model. MethodsA prospective animal study was performed in the university hospital animal research laboratory. Ventricular fibrillation cardiac arrest was induced in domestic pigs weighing 35–40kg. After 6min of no flow time, cardiopulmonary resuscitation was provided to pigs, and the restoration of spontaneous circulation (ROSC) was achieved. The subjects were randomly allocated to a normothermic (NT group, n=5) or hypothermic (HT group, n=5) group. In the HT group, therapeutic hypothermia (core temperature 32–34°C) was maintained for 24h, and rewarming was performed over a period of 8h. In the NT group, core temperature was maintained at 37°C throughout the experiments. Sixty hours after ROSC, blood and myocardial tissues were harvested. ResultsSerum troponin I was not significantly different between the groups. However, myocardial histological damage was attenuated in the HT group. Myocardial ATP contents were higher in the HT group than in the NT group. Immunohistochemistry for apoptosis-related protein showed that survivin expression was higher in the HT group, and XAF1 and cleaved caspase-3 expressions were lower in the HT group than in the NT group. ConclusionsTherapeutic hypothermia attenuated histological myocardial injury in ventricular fibrillation cardiac arrest model of pigs while preserving more ATP and decreased apoptosis.

Utility of the Ventricular Fibrillation Waveform to Predict a Return of Spontaneous Circulation and Distinguish Acute From Post Myocardial Infarction or Normal Swine in Ventricular Fibrillation Cardiac Arrest

In cardiac arrest, the ventricular fibrillation (VF) waveform, particularly amplitude spectral area (AMSA) and slope, predicts the return of spontaneous circulation (ROSC), but it is unknown whether the predictive utility differs in an acute myocardial infarction (MI), prior MI, or normal myocardium and if the waveform can distinguish the underlying myocardial state. We hypothesized that in a swine model of VF cardiac arrest, AMSA and slope predict ROSC after a shock independent of substrate and distinguish an acute from nonacute MI state. MI was induced by occlusion of the left anterior descending artery. Post MI swine recovered for a 2-week period before induction of VF. VF was untreated for 8 minutes in 10 acute MI, 10 post MI, and 10 control swine. AMSA and slope predicted ROSC after a shock independent of myocardial state. For AMSA >31 mV-Hz, the odds ratio was 62 (P≤0.001) compared with AMSA <19 mV-Hz. For slope >3.1 mV/s, odds ratio was 52 (P≤0.001) compared with slope <1.8 mV/s. With chest compressions, AMSA and slope were significantly lower for acute MI swine compared with control swine, whereas in post MI swine the waveform characteristics were similar to control swine. In particular, for an AMSA >33.5 mV-Hz, the sensitivity to identify an acute from nonacute (control or post MI) state was 83%. In a swine model of VF cardiac arrest, AMSA and slope predict ROSC independent of myocardial substrate. Furthermore, with chest compressions, the VF waveform evolves differently and may offer a means to distinguish an acute MI.

Continued breathing followed by gasping or apnea in a swine model of ventricular fibrillation cardiac arrest

BackgroundContinued breathing following ventricular fibrillation has here-to-fore not been described.MethodsWe analyzed the spontaneous ventilatory activity during the first several minutes of ventricular fibrillation (VF) in our isoflurane anesthesized swine model of out-of-hospital cardiac arrest. The frequency and type of ventilatory activity was monitored by pneumotachometer and main stream infrared capnometer and analyzed in 61 swine during the first 3 to 6 minutes of untreated VF.ResultsDuring the first minute of VF, the air flow pattern in all 61 swine was similar to those recorded during regular spontaneous breathing during anesthesia and was clearly different from the patterns of gasping. The average rate of continued breathing during the first minute of untreated VF was 10 breaths per minute. During the second minute of untreated VF, spontaneous breathing activity either stopped or became typical of gasping. During minutes 2 to 5 of untreated VF, most animals exhibited very slow spontaneous ventilatory activity with a pattern typical of gasping; and the pattern of gasping was crescendo-decrescendo, as has been previously reported. In the absence of therapy, all ventilatory activity stopped 6 minutes after VF cardiac arrest.ConclusionIn our swine model of VF cardiac arrest, we documented that normal breathing continued for the first minute following cardiac arrest.

Predictors of resuscitation outcome in a swine model of VF cardiac arrest: A comparison of VF duration, presence of acute myocardial infarction and VF waveform

Introduction Factors that affect resuscitation to a perfusing rhythm (ROSC) following ventricular fibrillation (VF) include untreated VF duration, acute myocardial infarction (AMI), and possibly factors reflected in the VF waveform. We hypothesized that resuscitation of VF to ROSC within 3 min is predicted by the VF waveform, independent of untreated VF duration or presence of acute MI. Methods AMI was induced by the occlusion of the left anterior descending coronary artery. VF was induced in normal ( N = 30) and AMI swine ( N = 30). Animals were resuscitated after untreated VF of brief (2 min) or prolonged (8 min) duration. VF waveform was analyzed before the first shock to compute the amplitude-spectral area (AMSA) and slope. Results Unadjusted predictors of ROSC within 3 min included untreated VF duration (8 min vs 2 min; OR 0.11, 95%CI 0.02–0.54), AMI (AMI vs normal; OR 0.11, 95%CI 0.02–0.54), AMSA (highest to lowest tertile; OR 15.5, 95%CI 1.7–140), and slope (highest to lowest tertile; OR 12.7, 95%CI 1.4–114). On multivariate regression, untreated VF duration ( P = 0.011) and AMI ( P = 0.003) predicted ROSC within 3 min. Among secondary outcome variables, favorable neurological status at 24 h was only predicted by VF duration (OR 0.22, 95% CI 0.05–0.92). Conclusions In this swine model of VF, untreated VF duration and AMI were independent predictors of ROSC following VF cardiac arrest. AMSA and slope predicted ROSC when VF duration or the presence of AMI were unknown. Importantly, the initial treatment of choice for short duration VF is defibrillation regardless of VF waveform.

Prediction of Countershock Success

Spectral analysis of the ventricular fibrillation (VF) ECG has been used for predicting countershock success, where the Fast Fourier Transformation (FFT) is the standard spectral estimator. Autoregressive (AR) spectral estimation should compute the spectrum with less computation time. This study compares the predictive power and computational performance of features obtained by the FFT and AR methods. In an animal model of VF cardiac arrest, 41 shocks were delivered in 25 swine. For feature parameter analysis, 2.5 s signal intervals directly before the shock and directly before the hands-off interval were used, respectively. Invasive recordings of the arterial pressure were used for assessing the outcome of each shock. For a proof of concept, a micro-controller program was implemented. Calculating the area under the receiver operating characteristic (ROC) curve (AUC), the results of the AR-based features called spectral pole power (SPP) and spectral pole power with dominant frequency (DF) weighing (SPPDF) yield better outcome prediction results (85%; 89%) than common parameters based on FFT calculation method (centroid frequency (CF), amplitude spectrum area (AMSA)) (72%; 78%) during hands-off interval. Moreover, the predictive power of the feature parameters during ongoing CPR was not invalidated by closed-chest compressions. The calculation time of the AR-based parameters was nearly 2.5 times faster than the FFT-based features. Summing up, AR spectral estimators are an attractive option compared to FFT due to the reduced computational speed and the better outcome prediction. This might be of benefit when implementing AR prediction features on the microprocessor of a semi-automatic defibrillator.

Periodic acceleration (pGz) CPR in a swine model of asphyxia induced cardiac arrest: Short-term hemodynamic comparisons

Asphyxia is one of the most common causes of pediatric cardiac arrest, and becoming a more frequently recognized cause in adults. Periodic acceleration (pGz) is a novel method of cardiopulmonary resuscitation (CPR). pGz is achieved by rapid motion of the supine body headward-footward that generates adequate perfusion and ventilation during cardiac arrest. In a swine ventricular fibrillation cardiac arrest model, pGz produced a higher return of spontaneous circulation (ROSC), superior neurological outcome, less echocardiography evidence of post resuscitation myocardial stunning, and decreased indices of tissue injury. In contrast to standard chest compression CPR, pGz does not produce rib fractures. We investigated the feasibility of pGz in severe asphyxia cardiac arrest and assessed whether beneficial effects seen in the VF model of cardiac arrest could be realized. Sixteen swine weight 4+/-1 kg were anesthetized, tracheally intubated, and instrumented to measure, hemodynamics and echocardiography. Asphyxia was induced by occlusion of the tracheal tube. After loss of aortic pulsations (median time 10 min) animals were observed for three additional minutes following which all were in cardiac arrest. The animals were then randomized to receive 10 min of pGz or standard chest compression ventilation performed with a commercial device (Thumper). A single dose of epinephrine (adrenaline) and sodium bicarbonate were given and defibrillation attempted if appropriate for a maximum of 10 min. Both groups received fractional inspired O2 concentration of 100% during CPR and after resuscitation. Four animals in each group (50%) had an initial ROSC, however only two of the four initial survivors remained alive 3h after ROSC. There were no significant differences in blood pressure, coronary perfusion pressure during CPR and after early ROSC between groups. pGz treated animals had significantly lower pulmonary artery pressure; 20+/-4 mmHg compared to Thumper 46+/-5 mmHg, 30 min after ROSC (p<0.01). Surviving animals in both groups had severe myocardial dysfunction at 30 min after ROSC. At necropsy, 25% of the Thumper treated animals had rib fractures, while none occurred in the pGz group. In a lethal model of asphyxia cardiac arrest, pGz is equivalent to standard CPR, with respect to acute outcomes and resuscitation survival rates but is associated with significantly lower pulmonary artery pressures and does not produce traumatic rib fractures.

External cardiac defibrillation during wet-surface cooling in pigs

Objective During surface cooling with ice-cold water, safety and effectiveness of transthoracic defibrillation was assessed. Methods In a pig ventricular fibrillation cardiac arrest model, once (n = 6), defibrillation was done first in a dry and then in a wet condition using the ThermoSuit System (Life Recovery Systems, HD, LLC, Kinnelon, NJ), which circulates a thin layer of ice-cold water (≈4°C) over the skin surface. Another time (n = 6), defibrillation was done first in a wet and then in a dry condition. Success of defibrillation was defined as restoration of spontaneous circulation, and the current and voltage of the defibrillation signal was measured. Results There was a tendency toward less number of shocks needed for achieving restoration of spontaneous circulation in the wet condition as compared with the number of shocks needed in the dry condition. The energy delivered in both dry and wet conditions was 144 ± 3 J. Discussion Transthoracic defibrillation is safe and effective in a wet condition after cooling with ice-cold water.

Postischemic hyperoxia reduces hippocampal pyruvate dehydrogenase activity

The pyruvate dehydrogenase complex (PDHC) is a mitochondrial matrix enzyme that catalyzes the oxidative decarboxylation of pyruvate and represents the sole bridge between anaerobic and aerobic cerebral energy metabolism. Previous studies demonstrating loss of PDHC enzyme activity and immunoreactivity during reperfusion after cerebral ischemia suggest that oxidative modifications are involved. This study tested the hypothesis that hyperoxic reperfusion exacerbates loss of PDHC enzyme activity, possibly due to tyrosine nitration or S-nitrosation. We used a clinically relevant canine ventricular fibrillation cardiac arrest model in which, after resuscitation and ventilation on either 100% O 2 (hyperoxic) or 21–30% O 2 (normoxic), animals were sacrificed at 2 h reperfusion and the brains removed for enzyme activity and immunoreactivity measurements. Animals resuscitated under hyperoxic conditions exhibited decreased PDHC activity and elevated 3-nitrotyrosine immunoreactivity in the hippocampus but not the cortex, compared to nonischemic controls. These measures were unchanged in normoxic animals. In vitro exposure of purified PDHC to peroxynitrite resulted in a dose-dependent loss of activity and increased nitrotyrosine immunoreactivity. These results support the hypothesis that oxidative stress contributes to loss of hippocampal PDHC activity during cerebral ischemia and reperfusion and suggest that PDHC is a target of peroxynitrite.

Effect of nitric oxide synthase modulation on resuscitation success in a swine ventricular fibrillation cardiac arrest model

Background: We have demonstrated previously that the nitric oxide synthase (NOS) inhibitor N G-nitro- l-arginine ( l-NNA) decreases free radical generation and nitrosative injury via peroxynitrite formation after epicardial dc shocks. Objective: Our purpose was to explore the effects of NOS inhibition and NOS donation on cardiopulmonary resuscitation (CPR) success after cardiac arrest of variable duration. We used the non-selective NOS inhibitor l-NNA and the selective neuronal NOS inhibitor ARR-17477, the NOS donor S-nitroso- N-acetylpenicillamine (SNAP) and the vasodilator Enalaprilat, which lowers arterial pressure via a non-NO mechanism. Methods: Part I: 17 pigs undergoing 4 min supported (i.e. with closed-chest compression and ventilation) ventricular fibrillation (VF) were divided into two groups: a no- l-NNA group ( n = 8) receiving IV saline and an l-NNA group ( n = 9) receiving IV l-NNA (5 mg/kg) for 8 min before VF was induced. Part II: 35 pigs undergoing 6–8 min VF were randomized to three groups: a no- l-NNA group ( n = 13) receiving IV saline, an l-NNA group ( n = 11) receiving IV l-NNA (5 mg/kg) and an ARR17477 group ( n = 11) receiving IV ARR17477 (5 mg/kg) before VF. All animals in Part II underwent unsupported VF (no chest compression or ventilation) for 6 min ( n = 13) or 8 min ( n = 22); closed-chest compression, ventilation and epinephrine (adrenaline) were employed after defibrillation. Part III: 12 swine were divided into two groups: control ( n = 6) receiving saline and an LNNA group ( n = 6) receiving IV LNNA (5 mg/kg). Swine underwent 6 min unsupported VF and 2 min supported VF before defibrillation. Part IV: 25 animals were studied to determine the effect of the NO donor SNAP and the angiotensin-converting enzyme inhibitor Enalaprilat on coronary perfusion pressure (CPP). Results: In Part I, after defibrillation, with continued ventilation, chest compression and epinephrine, 8/9 l-NNA pigs achieved ROSC versus 4/8 control pigs ( p = 0.11). After 60 s of CPR, 7/9 pigs in the l-NNA group achieved ROSC versus 2/8 pigs in the no- l-NNA group ( p < 0.05). Only 2/9 pigs receiving l-NNA required epinephrine (1 mg) after defibrillation, compared to 6/8 pigs requiring at least one dose of epinephrine in the no- l-NNA group ( p < 0.05). In Part II, there was no significant difference between l-NNA, ARR17477 and control pigs in ROSC. However, control pigs required 6.8 ± 1.4S.E. mg epinephrine; l-NNA pigs and ARR17477 pigs required less epinephrine (3.7 ± 0.7 and 3.0 ± 0.3 mg, both p = 0.01). Shorter chest compression was required in the l-NNA group (252 ± 38 s, p < 0.05) and in ARR17477 group (222 ± 15 s, p < 0.05) compared to the control group (405 ± 77 s). In Part III, l-NNA infusion caused a significant increase in mean blood pressure at baseline, but did not change CPP throughout the experiment. In Part IV, there were no significant differences in the changes of mean blood pressure and CPP between SNAP and Enalaprilat group in all animals throughout the experiment. Conclusion: NOS inhibition pre-arrest did not improve survival, but did reduce requirements for epinephrine and closed-chest compression in a swine resuscitation model.

Decreasing the time to defibrillation: A comparative study of defibrillator electrode designs

Introduction: Time to defibrillation ( T defib) is the most important modifiable factor affecting survival from cardiac arrest. Mortality increases by approximately 7–10% for each minute of defibrillation delay. The purpose of this study was to determine whether defibrillator electrode design complexity affects T defib. Methods: This was a randomized sequential design study utilizing a standardized ventricular fibrillation cardiac arrest model for CPR mannequins. We evaluated two common types of defibrillator electrode models: a single connector design and a double connector design that requires an adaptor. We compared the time required by cardiac arrest team leaders to apply the two types of defibrillator electrodes to a manikin, connect them to a defibrillator, and then deliver a first defibrillatory shock. The primary outcome was time to defibrillation. The secondary outcome was difficulty of application as perceived by the physician participants on a 10 cm visual analog scale. Results: Thirty-two residents performed a sequential assessment of both electrodes. The average T defib for the double connector model was 42.9 s longer than that of the single connector model (87.5 s versus 44.6 s, p < 0.001). As evaluated by the study participants, the single connector model was significantly easier to apply then the double connector model (1.3 cm versus 4.4 cm, p < 0.001). Conclusion: The single connector defibrillator electrode design was associated with a significantly shorter T defib than the double connector design. It also was judged to be easier to apply in this model. Ergonomic design of defibrillator electrodes can significantly impact time to defibrillation.

Decreasing the time to defibrillation: A crossover comparative study of Quik-Combo and padpro defibrillator electrodes

Study objectives: Time to defibrillation is the most important factor affecting survival from cardiac arrest. Mortality increases by approximately 7% to 10% for each minute that defibrillation is delayed. Therefore, any improvement in time to defibrillation could have an important impact on clinical survival. Valuable progress in shortening the inhospital "chain of survival" has been achieved with the development of cardiac monitored beds, dedicated cardiac arrest teams, and strategic location of defibrillators throughout the hospital. However, the specific impact of defibrillator electrodes on time to defibrillation has not been analyzed. The purpose of this study is to determine whether the choice of defibrillator electrodes affects the time to defibrillation. Methods: This was a randomized crossover design study. It was approved by the institutional review board. Internal medicine and emergency resident physicians supervise cardiac arrest teams at many teaching hospitals, so they were selected to test this equipment. The residents were blinded to the intent of the study. We compared the time required by the residents to apply to the patient, then connect to a defibrillator, and then deliver a shock for 2 leading defibrillator electrodes, the Quik-Combo (Medtronic Physio-Control, Redmond, WA) and the Padpro (model 2516 Padpro LLC, Ann Arbor, MI). Under scripted direction of advanced cardiac life support–trained research nurses, they used the equipment during a standardized ventricular fibrillation cardiac arrest model using cardiopulmonary resuscitation mannequins. The independent variable was the choice of defibrillator electrode. Sequence of testing for the electrodes was block randomized to control for the confounding variable of learning. The primary outcome was time to defibrillation (total time elapsed from the beginning of cardiac arrest to delivery of a defibrillatory shock). The secondary outcome was the ease of application as assessed by the resident physicians with a 10-cm visual analog scale. The minimum required sample size was calculated to be 26 trials for each defibrillator electrode study group, assuming a 20% treatment effect between models (2-sided, for α=0.05 and β=0.2). Statistical significance was analyzed using Student's t test for continuous variables. Results: Thirty residents performed a crossover assessment of both electrodes. The average time to defibrillation for the Padpro was approximately double that of the Quik-Combo (88.2 seconds versus 44.5 seconds, P P Conclusion: The Quik-Combo defibrillator electrode significantly decreased the time to defibrillation and was judged to be easier to apply in this cardiac arrest model. The average time to defibrillation difference of 44 seconds when extrapolated to the clinical setting has important implications for patient survival and morbidity. International guidelines endorse a goal time of only 2 to 4 minutes from collapse until defibrillation. We demonstrate that the choice of defibrillator electrodes can significantly influence accomplishment of that goal. Cardiopulmonary resuscitation is a complex team task under highly stressful conditions. Regularly training on standardized equipment is essential for efficient cardiac arrest team performance. Hospital and emergency medical services authorities should select the most reliable and ergonomically simple equipment to minimize any delays in defibrillation.

From Vivendi to Veolia environnement

In retrospective swine and human investigations of ventricular fibrillation (VF) cardiac arrest, the amplitude-spectral area (AMSA), determined from the VF waveform, can predict defibrillation and a return of spontaneous circulation (ROSC).We hypothesized that an algorithm using AMSA in real time to direct postshock chest compression (CC) duration would shorten the time to ROSC and improve neurological outcome in a swine model of VF cardiac arrest with acute myocardial infarction (AMI) or nonischemic myocardium.AMI was induced by occlusion of the left anterior descending artery. VF was untreated for 10 min. Animals were randomized to either traditional resuscitation with 2 min of CC after each shock or to an AMSA-guided algorithm where postshock CCs were shortened to 1 min if the preshock AMSA exceeded 20 mV-Hz.A total of 48 animals were studied, 12 in each group (AMI vs. normal, and traditional vs. AMSA-guided). There was a nonsignificant shorter time to ROSC with an AMSA-guided approach in AMI swine (17.2 ± 3.4 vs. 18.5 ± 4.7 min, p = NS), and in normal swine (13.5 ± 1.1 vs. 14.4 ± 1.2, p = NS). Neurological outcome was similar between traditional and AMSA-guided animals. AMSA predicted ROSC (p < 0.001), and a threshold of 20 mV-Hz gave a sensitivity of 89%, with specificity of 29%.Although AMSA predicts ROSC in a swine model of VF arrest in both AMI and normal swine, a waveform-guided approach that uses AMSA to direct postshock CC duration does not significantly shorten the time to ROSC or alter neurological outcome.

Transthoracic impedance does not decrease with rapidly repeated countershocks in a swine cardiac arrest model

Study purpose: Successful defibrillation is dependent upon the delivery of adequate electrical current to the myocardium. One of the major determinant of current flow is transthoracic impedance. Prior work has suggested that impedance falls with repeated shocks during sinus rhythm. The purpose of this study was to evaluate changes in transthoracic impedance with repeated defibrillation shocks in an animal model of cardiac arrest due to ventricular fibrillation (VF). Methods: VF was electrically induced in anesthetized swine. After 5 min of untreated VF, monophasic or biphasic waveform defibrillation was attempted using a standard sequence of ‘stacked shocks’ (200, 300, then 360 J, if necessary) administered via adhesive electrodes. If one of the first three shocks failed to convert VF, conventional CPR was initiated and defibrillation (360 J) attempted 1 min later. Strength–duration curves for delivered voltage and current were measured during each shock and transthoracic impedance calculated. Animals requiring a minimum of four shocks were selected for study inclusion. Impedance data from sequential shocks were analyzed using mixed linear models to account for the repeated-measures design and the variability of the initial impedance of individual animals. Results: Thirteen animals (monophasic waveform, n=7, biphasic waveform, n=6) required at least four shocks to terminate VF (range 4–6). Transthoracic impedance did not change from the first shock in the 13 animals (46±8 Ω) to the fourth shock (46±9 Ω). In animals receiving more than four shocks, transthoracic impedance likewise did not change significantly from the first to the last shock, which terminated VF. The lack of a significant change in impedance was also observed when animals were analyzed according to defibrillation waveform. Conclusion: Transthoracic impedance does not change significantly with repeated shocks in a VF cardiac arrest model. This is likely due to the lack of reactive skin and soft tissue hyperemia and edema observed in non-arrest models.

Catecholamines in cardiac arrest: role of alpha agonists, beta-adrenergic blockers and high-dose epinephrine

Once initial defibrillation has failed, the advanced cardiac life support (ACLS) guidelines for cardiopulmonary resuscitation (CPR) recommend periodic intravenous administration of epinephrine to increase coronary artery perfusion pressure (CPP) via arterial vasoconstriction to [1]. During prolonged cardiac arrest coronary perfusion pressure and forward blood flow are the major determinants of successful resuscitation, for when CPP is too low, successful resuscitation is unlikely. When the CPP is marginal, resuscitation may be possible; however, 24-h survival is unlikely [2]. When CPR is able to generate CPP above 30 mmHg associated with adequate forward blood flow as reflected in an adequate end-tidal CO2 the 24-h survival rate is greatly improved [2]. The American Heart Association ACLS guidelines recommend epinephrine as the pressor agent of choice during prolonged CPR [1]. These recommendations are based on now classic works [2–8]. Yet, studies have accumulated over the years that have raised concern that epinephrine’s beta-adrenergic effect may increase the myocardial oxygen consumption of the fibrillating heart and predispose to post-defibrillation dysfunction and cardiac arrhythmias [9–16]. Added to this concern was the finding that endogenous catecholamine concentrations are high during ventricular fibrillation even in the absence of epinephrine administration [11]. Ditchey and associates found, in a canine ventricular fibrillation cardiac arrest model, that the balance between myocardial oxygen supply and demand was improved by the administration of propranolol and phenylephrine, an exogenous selective alpha-agonist [9]. The limitations of these studies, however, is that high-dose epinephrine was used and survival was not evaluated. High-dose epinephrine administered during resuscitation initially appeared to be useful, producing higher perfusion pressures, but high-dose epinephrine has not been shown in clinical trials [17,18] nor in some experimental trials [12,13] to improve survival. Studies from our laboratory found that high-dose epinephrine resulted in postresuscitative tachycardia, systemic hypertension and greater early mortality relative to the standard dose [12]. Other laboratories have also documented adverse effects of high-dose epinephrine when given during CPR, including post-resuscitation hyperadrenergic state [14], myocardial necrosis [15], and worsened post-arrest cardiomyopathy [16]. Although pure alpha-agonists have not been shown to be superior to epinephrine [19–22], one could speculate that a combination of an alpha-adrenergic agonist and a beta-blocker might improve hemodynamics during CPR and thus improve long-term survival while avoiding the post resuscitation problem of excessive beta stimulation. * Correspnding author. Tel.: +1-520-626-7383.