Minutes Of Ventricular Fibrillation Research Articles

Hands‐On Defibrillation Has the Potential to Improve the Quality of Cardiopulmonary Resuscitation and Is Safe for Rescuers— A Preclinical Study

BackgroundRecently, it has been demonstrated that rescuers could safely provide a low, static downward force in direct contact with patients during elective cardioversion. The purpose of our experimental study was to investigate whether shock delivery during uninterrupted chest compressions may have an impact on cardiopulmonary resuscitation (CPR) quality and can be safely performed in a realistic animal model of CPR.Methods and ResultsTwenty anesthetized swine were subjected to 7 minutes of ventricular fibrillation followed by CPR according to the 2010 American Heart Association Guidelines. Pregelled self-adhesive defibrillation electrodes were attached onto the torso in the ventrodorsal direction and connected to a biphasic defibrillator. Animals were randomized either to (1) hands-on defibrillation, where rescuers wore 2 pairs of polyethylene gloves and shocks were delivered during ongoing chest compressions, or (2) hands-off defibrillation, where hands were taken off during defibrillation. CPR was successful in 9 out of 10 animals in the hands-on group (versus 8 out of 10 animals in the hands-off group; not significant). In the hands-on group, chest compressions were interrupted for 0.8% [0.6%; 1.4%] of the total CPR time (versus 8.2% [4.2%; 9.0%]; P=0.0003), and coronary perfusion pressure was earlier restored to its pre-interruption level (P=0.0205). Also, rescuers neither sensed any kind of electric stimulus nor did Holter ECG reveal any serious cardiac arrhythmia.ConclusionsHands-on defibrillation may improve CPR quality and could be safely performed during uninterrupted chest compressions in our standardized porcine model.

A 35-Year-Old Pregnant Woman Presenting with Sudden Cardiac Arrest Secondary to Peripartum Cardiomyopathy

We present a case of successful resuscitation from cardiac arrest after 25 minutes of ventricular fibrillation (VF) secondary to peripartum cardiomyopathy. This case highlights a rare disease, but also, more importantly, the successful use of the five links of survival: early access to 9-1-1, early cardiopulmonary resuscitation (CPR), early defibrillation, early advanced life support, and postresuscitative care. We also demonstrate the importance of high-quality resuscitation practices in order to achieve a successful outcome. Manual compressions can be performed at a guidelines-compliant rate. With training, users are able to achieve high compression fractions. Pre/post shock delays can be minimized to further increase compression fraction. Nationally, CPR interruptions are often long. We recommend closer attention to uninterrupted 2-minute cycles of CPR, minimizing delays in CPR through training, and a focus on a closely choreographed approach. User review of transthoracic impedance feedback data should play a vital role in a cardiac arrest quality-improvement program.

Pharmacological postconditioning with sevoflurane after cardiopulmonary resuscitation reduces myocardial dysfunction

IntroductionIn this study, we sought to examine whether pharmacological postconditioning with sevoflurane (SEVO) is neuro- and cardioprotective in a pig model of cardiopulmonary resuscitation.MethodsTwenty-two pigs were subjected to cardiac arrest. After 8 minutes of ventricular fibrillation and 2 minutes of basic life support, advanced cardiac life support was started. After successful return of spontaneous circulation (N = 16), animals were randomized to either (1) propofol (CONTROL) anesthesia or (2) SEVO anesthesia for 4 hours. Neurological function was assessed 24 hours after return of spontaneous circulation. The effects on myocardial and cerebral damage, especially on inflammation, apoptosis and tissue remodeling, were studied using cellular and molecular approaches.ResultsAnimals treated with SEVO had lower peak troponin T levels (median [IQR]) (CONTROL vs SEVO = 0.31 pg/mL [0.2 to 0.65] vs 0.14 pg/mL [0.09 to 0.25]; P < 0.05) and improved left ventricular systolic and diastolic function compared to the CONTROL group (P < 0.05). SEVO was associated with a reduction in myocardial IL-1β protein concentrations (0.16 pg/μg total protein [0.14 to 0.17] vs 0.12 pg/μg total protein [0.11 to 0.14]; P < 0.01), a reduction in apoptosis (increased procaspase-3 protein levels (0.94 arbitrary units [0.86 to 1.04] vs 1.18 arbitrary units [1.03 to 1.28]; P < 0.05), increased hypoxia-inducible factor (HIF)-1α protein expression (P < 0.05) and increased activity of matrix metalloproteinase 9 (P < 0.05). SEVO did not, however, affect neurological deficit score or cerebral cellular and molecular pathways.ConclusionsSEVO reduced myocardial damage and dysfunction after cardiopulmonary resuscitation in the early postresuscitation period. The reduction was associated with a reduced rate of myocardial proinflammatory cytokine expression, apoptosis, increased HIF-1α expression and increased activity of matrix metalloproteinase 9. Early administration of SEVO may not, however, improve neurological recovery.

Changes in myocardial connexin 43 during ventricular fibrillation

To observe changes in connexin 43 (Cx43) after ventricular fibrillation (VF) and the effects of rotigaptide (ZP123) on Cx43. Thirty domestic pigs were randomly assigned to three groups (10 in each group): sham group, model group and ZP123 group. VF was induced by an 80 V AC transthoracic shock for 5 seconds with the use of subcutaneous needles. Before the induction of VF, animals in ZP123 group were administered with ZP123 (1 μg/kg bolus+10 μg×kg(-1)×h(-1) dissolved in 50 ml normal saline and pumped for 15 minutes ). Those in model group received 50 ml normal saline pumped for 15 minutes. For pigs in sham group VF was not induced and no fluid was given. After 8 minutes of VF, animals were euthanized and myocardial tissues were harvested along the long axis of each left ventricular free wall. Immunofluorescence combined with laser scanning confocal microscope was used to detect the distribution of Cx43. Western blotting was used for quantitative determination of Cx43 protein expression. Immunofluorescence signals for Cx43 in sham group were strong and regularly distributed. In model group, Cx43 signals were weak and distributed in heterogeneity, while in ZP123 group, Cx43 signals were enhanced and their distribution were much more orderly. Compared with sham group, the percentage area and the optical densities (A value) of Cx43 fluorescence signals and Cx43 protein expression were significantly decreased in model group [the percentage area: (0.64±0.36)% vs.(1.27±0.19)%, A value: 15 201± 2 613 vs. 30 634±4 975, Cx43 protein expression: 0.72±0.08 vs. 0.97±0.07, all P<0.05]. The level of Cx43 expression in ZP 123 group [the percentage area (0.96±0.16)%, A value 22 100±4 404, Cx43 protein expression 0.82±0.04] was much higher than model group (all P<0.05). During VF, down-regulation of myocardial Cx43 expression occurred, which could be attenuated by administration of ZP123.

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.

Evaluation of cerebral metabolism by 1H-magnetic resonance spectroscopy for 4°C saline-induced therapeutic hypothermia in pig model of cardiac arrest

Background Previous studies have shown that therapeutic hypothermia could improve neurologic recovery when induced after cardiac arrest, but dynamic changes in cerebral metabolism have not been studied at low temperature. In this study, we aim to evaluate hypothermia-induced changes in pigs' cerebral metabolism by 1H-magnetic resonance spectroscopy ( 1H-MRS). Material and Methods Ten anesthetized Landrace (25-30 kg) pigs were randomized into 2 groups and subjected to 4 minutes of ventricular fibrillation, followed by cardiopulmonary resuscitation. The hypothermic group was given an infusion of 30 mL/kg of 4°C normal saline (NS) at an infusion rate of 1.33 mL/kg per minute starting after restoration of spontaneous circulation (ROSC), then 10 mL/kg per hour for 4 hours. The control group received the same infusion of room temperature NS. Core temperature and hemodynamic variables were monitored at baseline and repeatedly for 240 minutes after ROSC. The 1H-MRS scans were obtained at baseline, 1 hour, and 3 hours after successful ROSC to observe the dynamic changes of cerebral metabolism at different temperatures. Results The mean reduction of temperature was 1.5°C ± 0.4°C in the hypothermic group. There was no difference in hemodynamic variables between groups. 1H-MRS detected statistically significant ( P < .01) changes in cerebral metabolism between the control and hypothermia groups ( P < .01). Conclusions Infusion of 4°C NS can effectively reduce cerebral metabolism after successful cardiopulmonary resuscitation and have a protective effect on the recovery of neurologic function. The 1H-MRS technology can be used as a powerful tool to evaluate interventions in the treatment of cardiopulmonary resuscitation.

Effects of norepinephrine on kidney in a Swine model of cardiopulmonary resuscitation

Background The aim of this study was to study the effects of norepinephrine (NE)-induced hypertension (HT) on renal biochemistry, enzymology, and morphology after restoration of spontaneous circulation (ROSC) by cardiopulmonary resuscitation (CPR) in swine. Methods After 4 minutes of ventricular fibrillation, standard CPR was carried out. The survivors were then divided into 2 groups. The HT group (n = 5) received 0.4 to 1.0 μg kg −1 min −1 of NE continuously to maintain the mean arterial pressure (MAP) at 130% of the baseline (ie, MAP before ventricular fibrillation). The normal pressure (NP) group (n = 5) received 0.2 to 0.5 μg kg −1 min −1 NE continuously to maintain MAP at the baseline level. Hemodynamic status and oxygen metabolism were monitored, and blood urea nitrogen and creatinine were measured in blood samples obtained at baseline and at 10 minutes, 2 and 4 hours after ROSC. At 24 hours after ROSC, the animals were killed and the kidney was removed to determine Na +-K +-ATPase and Ca 2+-ATPase activities and histologic changes under a light and electron microscopy. Results mean arterial pressure, cardiac output, and coronary perfusion pressure were significantly higher ( P < .01), whereas the oxygen extraction ratio was lower in the HT group than in the NP group ( P < .05). Blood urea nitrogen and creatinine increased in the NP group but did not change in the HT group. Renal ATP enzyme activity was significantly higher in the HT group than the NP group (Na +-K +-ATP enzyme: 4.024 ± 0.740 U versus 3.190 ± 0.789 U, Ca 2+-ATP enzyme: 3.615 ± 0.668 versus 2.630 ± 0.816; both P < .05). The HT group showed less cellular edema, necrosis, and fewer damaged mitochondria compared with the NP group. Conclusion These data suggest that inducing HT by NE helps to maintain stable hemodynamic status and oxygen metabolism and may protect the kidney in terms of biochemistry, enzymology, and histology after CPR.

Protective head-cooling during cardiac arrest and cardiopulmonary resuscitation: the original animal studies

Prolonged standard cardiopulmonary resuscitation (CPR) does not reliably sustain brain viability during cardiac arrest. Pre-hospital adjuncts to standard CPR are needed in order to improve outcomes. A preliminary dog study demonstrated that surface cooling of the head during arrest and CPR can achieve protective levels of brain hypothermia (30°C) within 10 minutes. We hypothesized that protective head-cooling during cardiac arrest and CPR improves neurological outcomes. Twelve dogs under light ketamine-halothane-nitrous oxide anesthesia were arrested by transthoracic fibrillation. The treated group consisted of six dogs whose shaven heads were moistened with saline and packed in ice immediately after confirmation of ventricular fibrillation. Six control dogs remained at room temperature. All 12 dogs were subjected to four minutes of ventricular fibrillation and 20 minutes of standard CPR. Spontaneous circulation was restored with drugs and countershocks. Intensive care was provided for five hours post-arrest and the animals were observed for 24 hours. In both groups, five of the six dogs had spontaneous circulation restored. After three hours, mean neurological deficit was significantly lower in the treated group (P=0.016, with head-cooled dogs averaging 37% and the normothermic dogs 62%). Two of the six head-cooled dogs survived 24 hours with neurological deficits of 9% and 0%, respectively. None of the control group dogs survived 24 hours. We concluded that head-cooling attenuates brain injury during cardiac arrest with prolonged CPR. We review the literature related to the use of hypothermia following cardiac arrest and discuss some promising approaches for the pre-hospital setting.

Mild hypothermia alone or in combination with anesthetic post-conditioning reduces expression of inflammatory cytokines in the cerebral cortex of pigs after cardiopulmonary resuscitation

IntroductionHypothermia improves survival and neurological recovery after cardiac arrest. Pro-inflammatory cytokines have been implicated in focal cerebral ischemia/reperfusion injury. It is unknown whether cardiac arrest also triggers the release of cerebral inflammatory molecules, and whether therapeutic hypothermia alters this inflammatory response. This study sought to examine whether hypothermia or the combination of hypothermia with anesthetic post-conditioning with sevoflurane affect cerebral inflammatory response after cardiopulmonary resuscitation.MethodsThirty pigs (28 to 34 kg) were subjected to cardiac arrest following temporary coronary artery occlusion. After seven minutes of ventricular fibrillation and two minutes of basic life support, advanced cardiac life support was started according to the current American Heart Association guidelines. Return of spontaneous circulation was achieved in 21 animals who were randomized to either normothermia at 38°C, hypothermia at 33°C or hypothermia at 33°C combined with sevoflurane (each group: n = 7) for 24 hours. The effects of hypothermia and the combination of hypothermia with sevoflurane on cerebral inflammatory response after cardiopulmonary resuscitation were studied using tissue samples from the cerebral cortex of pigs euthanized after 24 hours and employing quantitative RT-PCR and ELISA techniques.ResultsGlobal cerebral ischemia following resuscitation resulted in significant upregulation of cerebral tissue inflammatory cytokine mRNA expression (mean ± SD; interleukin (IL)-1β 8.7 ± 4.0, IL-6 4.3 ± 2.6, IL-10 2.5 ± 1.6, tumor necrosis factor (TNF)α 2.8 ± 1.8, intercellular adhesion molecule-1 (ICAM-1) 4.0 ± 1.9-fold compared with sham control) and IL-1β protein concentration (1.9 ± 0.6-fold compared with sham control). Hypothermia was associated with a significant (P < 0.05 versus normothermia) reduction in cerebral inflammatory cytokine mRNA expression (IL-1β 1.7 ± 1.0, IL-6 2.2 ± 1.1, IL-10 0.8 ± 0.4, TNFα 1.1 ± 0.6, ICAM-1 1.9 ± 0.7-fold compared with sham control). These results were also confirmed for IL-1β on protein level. Experimental settings employing hypothermia in combination with sevoflurane showed that the volatile anesthetic did not confer additional anti-inflammatory effects compared with hypothermia alone.ConclusionsMild therapeutic hypothermia resulted in decreased expression of typical cerebral inflammatory mediators after cardiopulmonary resuscitation. This may confer, at least in part, neuroprotection following global cerebral ischemia and resuscitation.

Hypothermia and Postconditioning after Cardiopulmonary Resuscitation Reduce Cardiac Dysfunction by Modulating Inflammation, Apoptosis and Remodeling

BackgroundMild therapeutic hypothermia following cardiac arrest is neuroprotective, but its effect on myocardial dysfunction that is a critical issue following resuscitation is not clear. This study sought to examine whether hypothermia and the combination of hypothermia and pharmacological postconditioning are cardioprotective in a model of cardiopulmonary resuscitation following acute myocardial ischemia.Methodology/Principal FindingsThirty pigs (28–34 kg) were subjected to cardiac arrest following left anterior descending coronary artery ischemia. After 7 minutes of ventricular fibrillation and 2 minutes of basic life support, advanced cardiac life support was started according to the current AHA guidelines. After successful return of spontaneous circulation (n = 21), coronary perfusion was reestablished after 60 minutes of occlusion, and animals were randomized to either normothermia at 38°C, hypothermia at 33°C or hypothermia at 33°C combined with sevoflurane (each group n = 7) for 24 hours. The effects on cardiac damage especially on inflammation, apoptosis, and remodeling were studied using cellular and molecular approaches. Five animals were sham operated. Animals treated with hypothermia had lower troponin T levels (p<0.01), reduced infarct size (34±7 versus 57±12%; p<0.05) and improved left ventricular function compared to normothermia (p<0.05). Hypothermia was associated with a reduction in: (i) immune cell infiltration, (ii) apoptosis, (iii) IL-1β and IL-6 mRNA up-regulation, and (iv) IL-1β protein expression (p<0.05). Moreover, decreased matrix metalloproteinase-9 activity was detected in the ischemic myocardium after treatment with mild hypothermia. Sevoflurane conferred additional protective effects although statistic significance was not reached.Conclusions/SignificanceHypothermia reduced myocardial damage and dysfunction after cardiopulmonary resuscitation possible via a reduced rate of apoptosis and pro-inflammatory cytokine expression.

Percutaneous left ventricular assist in ischemic cardiac arrest

Ischemic cardiac arrest represents a challenge for optimal emergency revascularization therapy. A percutaneous left ventricular assist device (LVAD) may be beneficial. To determine the effect of a percutaneous LVAD during cardiac arrest without chest compressions and to assess the effect of fluid loading. Totally, 16 pigs randomized to either conventional or intensive fluid with LVAD support during ventricular fibrillation (VF). Acute experimental trial with pigs under general anesthesia. Farm pigs of both sexes. After randomization for fluid infusion, VF was induced by balloon occlusion of the proximal left anterior descending artery. LVAD and fluid were started after VF had been induced. Brain, kidney, myocardial tissue perfusion, and cardiac index were measured with the microsphere injection technique at baseline, 3, and 15 minutes. Additional hemodynamic monitoring continued until 30 minutes. At 15 minutes, vital organ perfusion was maintained without significant differences between the two groups. Mean cardiac index at 3 minutes of VF was 1.2 L x min(-1) x m2 (29% of baseline, p < 0.05). Mean perfusion at 3 minutes was 65% in the brain and 74% in the myocardium compared with baseline (p < 0.05), then remained unchanged during the initial 15 minutes. At 30 minutes, LVAD function was sustained in 11 of 16 animals (8 of 8 intensified fluid vs. 3 of 8 conventional fluid) and was associated with intensified fluid loading (p < 0.001). During VF, a percutaneous LVAD may sustain vital organ perfusion. A potential clinical role of the device during cardiac arrest has yet to be established.

Improved outcomes of cardiopulmonary resuscitation in rats with myocardial infarction treated with allogenic bone marrow mesenchymal stem cells*

We hypothesized that rats in which myocardial infarction had been treated with mesenchymal stem cells (MSCs) would have better outcomes following the global myocardial ischemia of cardiac arrest and cardiopulmonary resuscitation (CPR) compared with rats in which myocardial infarction had been treated with phosphate buffer solution (PBS). Prospective, randomized controlled study. University-affiliated research institute. Male Sprague-Dawley rats. Myocardial infarction was induced in 18 male Sprague-Dawley rats. Four weeks later, animals were randomized to receive 5 x 10 MSCs labeled with red fluorescent dye gel (PKH26) in PBS or a PBS-alone injection into right femoral vein. Echocardiographically measured myocardial function, including ejection fraction, left ventricular end-diastolic volume, and left ventricular end-systolic volume, was quantitated 2 and 4 weeks after administering MSCs or PBS. Four weeks after MSCs or PBS injection, 6 minutes of ventricular fibrillation (VF) and 6 minutes of CPR were performed before defibrillation. Myocardial function, including cardiac index, left ventricular, dP/dt max (dP/dt max), left ventricular negative dP/dt min (-dP/dt min), and left ventricular diastolic pressure, was measured before inducing VF and hourly following return of spontaneous circulation. Labeled MSCs were observed in 5-mum cryostat sections from each harvested heart. Significant improvements in ejection fraction, left ventricular end-diastolic volume, left ventricular end-systolic volume, cardiac index, dP/dt max, -dP/dt min, and left ventricular diastolic pressure followed injection of MSCs before inducing VF. Following return of spontaneous circulation, myocardial function was significantly better in animals pretreated with MSCs; this was associated with significantly increased duration of postresuscitation survival. Myocardial function before and after CPR and duration of survival after CPR were significantly improved in animals in which myocardial infarction was treated with MSCs. MSCs existing in the myocardium resisted a secondary ischemic event and provided better postresuscitation myocardial function.

The Effect of the Preshock Pause on Coronary Perfusion Pressure Decay and Rescue Shock Outcome in Porcine Ventricular Fibrillation

Objective. We sought to determine the effect of the preshock pause (PSP) on coronary perfusion pressure (CPP) decay and subsequent rescue shock (RS) outcome in porcine ventricular fibrillation (VF). Methods. Retrospective analysis of digitally recorded CPP tracings was performed. Ventricular fibrillation was electrically induced in all animals and resuscitation was standardized in all experiments. The first RS was delivered after an average of 10.8 minutes of VF (7.4 minutes of nontreatment and 3.4 minutes of resuscitation). The continuous CPP tracing segments, during the hands-off period prior to the first two rescue shocks, were imported into a spreadsheet and analyzed using descriptive statistics as well as univariate and multivariate statistical methods. The RS outcome for each animal was recorded as failed or return of spontaneous circulation (ROSC) (a systolic blood pressure of 80 mmHg or greater, sustained continuously for at least 1 minute). Results. We included 196 rescue shocks (120 first RS [RS1], 76 second RS [RS2]) from 120 swine. The mean CPP following the last compression before RS was 23.4 mmHg (standard error of the mean [SEM]: 1.3). The median PSP duration was 4.1 seconds (interquartile range [IQR]: 3.3, 6.1). The mean CPP just prior to RS was 7.6 mmHg (SEM: 0.6). Overall, the RS was successful (ROSC) in 57 of 120 (0.47 [95% confidence interval (CI): 0.38, 0.56]) attempts. Univariate results showed a counterintuitive positive correlation between PSP and maximum CPP for RS1 (r = 0.548, p < 0.001). Conclusion. During the resuscitation PSP in these porcine studies of prolonged VF, CPP dropped precipitously, but RS outcome was not adversely affected.

Abstract 590: Evaluation of the Effects of Cardiac Arrest and CPR Using Intracardiac Echocardiography

For every minute of cardiac arrest, mortality increases by 10%. Still, the variablity of meaningful neurologic survival suggests multiple factors involved in the hypoxia and encephalopathy of cardiac arrest (CA). We studied the cardiac chamber environment during ventricular fibrillation and asystole using direct ultrasound visualization using real-time intracardiac echocardiography (ICE). Four pigs were studied under general anesthesia per protocol. Venous access was obtained for catheter placement within the right heart. A bipolar paciing wire was placed into the right ventricle. A 10 French Acuson ICE catheter was placed into the right atrium using fluoroscopy. Baseline images were obtained. Ventricular fibrillation was induced using direct current energy. 30 minutes of ventricular fibrillation and terminal asystole was observed. Chest compressions were delivered intermittently with direct visualization of effects. Intra-chamber thrombus was quantified by chamber and by arrhythmia. All subjects began to form intracardiac thrombus within 1 minute of ventricular fibrillation. The persistence of sinus rhythm during fibrillation prevented thrombus formation in the atria and the basal portions of both ventricles. The thrombus was predominantly in the right heart within the first 4 minutes of CA. ICE documents that chest compressions completely clear the thrombus when delivered within the first five minutes of CA. Asystole led to more solidified thrombus that was more difficult to clear. Thrombus formation during CA is marked and may be a predominant reason for neurologic damage post resuscitation. Asystole was associated with complete chamber thrombus in comparison to ventricular fibrillation.

The Proinflammatory Cytokine Response following Resuscitation in the Swine Model Depends on the Method of Ventricular Fibrillation Induction

A systemic inflammatory response has been reported following resuscitation from cardiac arrest. The purpose of this study was to compare the magnitude of the tumor necrosis factor-alpha (TNF-alpha) response in two different swine models of ventricular fibrillation (VF) arrest. This was a randomized comparative trial conducted with domestic swine (N = 28, mean weight 40 kg, range 34-49 kg) of both genders. Anesthetized and instrumented swine were randomized to electrically induced VF (n = 14) or spontaneous VF induced by occlusion of a coronary artery (n = 14). After 8 minutes of VF, countershocks were given and standard advanced cardiac life support was initiated. Resuscitated animals were observed for 3 hours, and hemodynamics, base excess, and TNF-alpha concentrations were measured at intervals. TNF-alpha concentrations were significantly greater in the ischemic VF group throughout the postresuscitation period. Multivariate modeling demonstrated that the TNF-alpha level was dependent on the method of VF induction and correlated with ischemia time (untreated VF period plus time to restoration of circulation) and the degree of postresuscitation hypoperfusion as reflected in base excess measurements. This study demonstrates that TNF-alpha concentrations increase after resuscitation from cardiac arrest and that the TNF-alpha response is more profound in animals subjected to ischemic, spontaneous VF. The observed differences may be due to a longer resuscitation time and persistent postresuscitation hypoperfusion in the ischemic VF group. These differences need to be considered in studies evaluating mechanisms of postresuscitation organ dysfunction and defining mortality markers.

Intramural Foci During Long Duration Fibrillation in the Pig Ventricle

For more than 50 years, it has been assumed that ventricular fibrillation (VF) is maintained solely by reentry in the working myocardium. This hypothesis has never been tested by recording VF with electrodes spaced sufficiently close to map activation sequences in 3D. We recorded the first 10 minutes of electrically induced VF from the anterior left ventricular (LV) free wall near the insertion of the anterior papillary muscle in 6 pigs. A 3D transmural unipolar electrode array consisting of a 9x9 array of needles with 2-mm spacing and 6 electrodes 2 mm apart on each needle was used for recordings. Automatic analyses were performed to recognize 3D reentry and foci. Our results showed that intramural reentry is present early but not late during VF in the mapped region. The incidence of reentry in working myocardium decreases almost to 0 after 3 minutes of VF. In contrast, intramural foci are present during early VF and, as VF continues, increase in incidence, so that by 10 minutes of VF, 27% of wavefronts arise from intramural foci. These results suggest that, particularly after the first 3 minutes of VF, mechanisms other than local reentry in the working myocardium maintain VF in the anterior LV free wall near the root of the anterior papillary muscle. Intramural foci may play an important role in later VF maintenance. It remains to be determined if these foci arise from Purkinje fibers attributable to abnormal automaticity, afterdepolarizations, or reentry.

The Effect of Adenosine A1 Receptor Antagonism on Return of Spontaneous Circulation andShort-Term Survival in Prolonged Ventricular Fibrillation

Background. Endogenous adenosine (ADO) is cardioprotective during ischemia andits myocardial concentration increases during untreated ventricular fibrillation (VF). We have previously shown that ADO A1 receptor (ADOA1R) antagonism hastens the time-dependent decay in VF waveform morphology during the circulatory phase of cardiac arrest. Objective. To determine the effect of ADOA1R antagonism on ROSC andshort-term survival in prolonged VF. Methods. Thirty-six swine were assigned by block randomization to one of three groups: a group that received only vehicle (control), an ADOA1R antagonist pretreatment group (pre), anda group that was given ADOA1R antagonist during resuscitation (during). The animals were instrumented under anesthesia, andADOA1R antagonist or vehicle, per group assignment, was infused 5 minutes prior to VF induction. At minute 8 of untreated VF, chest compression with ventilation was initiated anda standard drug cocktail, with ADOA1R antagonist or vehicle, was given. The first rescue shock (150 J biphasic) was delivered after 11 minutes of VF. Proportions with 95% confidence intervals (CIs) were calculated for the two outcome measures. Results. The baseline characteristics andchemistry values for the three groups were mathematically the same. The during group had a greater proportion of female animals (seven of 12) in comparison with the control group (two of 12) (p = 0.03). ADOA1R antagonism hastened the decay of VF as previously demonstrated, but the rate of ROSC was the same for all groups: control = seven of 12, pre = six of 12, andduring = seven of 12. There were also no differences in short-term survival: control = four of 12, pre = five of 12, andduring = seven of 12. Conclusions. In this study, ADOA1R antagonism had no effect on outcome whether given before induction of VF or upon resuscitation after 8 minutes of untreated VF. The role of endogenous ADO in prolonged VF remains unclear.

Abstract 4: Inducing Hypothermia During Resuscitation Improves Return Of Spontaneous Circulation In Prolonged Porcine Ventricular Fibrillation

Introduction: Induced hypothermia has been shown to improve survival and neurologic outcomes for ventricular fibrillation (VF) cardiac arrest. Clinical studies have not begun inducing hypothermia until after return of spontaneous circulation (ROSC). The effects of cooling during the resuscitation are not well-studied. Hypothesis: We hypothesized that inducing hypothermia at the start of resuscitation would increase the rates of ROSC and short-term survival (20 minutes) in an established porcine model of prolonged VF. We compared intra-resuscitation hypothermia (IRH) with a normothermic control group (CTL). Methods: We anesthetized and instrumented 28 domestic swine (mean mass 26.5 ±2.4 kgs) with ECG, esophageal temperature, and micromanometer-tipped aortic and right atrial catheters. We then randomly assigned them to IRH and CTL groups (n= 14 each). VF was electrically induced and untreated for 8 minutes. Then resuscitation was begun with mechanical chest compression and ventilation. Hypothermia was induced by rapid IV infusion of ice-cold normal saline (30 mL/kg) at the beginning of resuscitation in the IRH group. The CTL group got 30 mL/kg of body-temperature saline at the start of resuscitation. After 8 minutes of VF, two minutes of CPR was followed by delivery of drugs (epinephrine 0.1 mg/kg, vasopressin 40 U, and propranolol 1.0 mg) and 3 more minutes of CPR (first rescue shock at 13 minutes of VF). ROSC (systolic BP above 80 mmHg for one minute continuously) and survival were recorded, as was total fluid given and hematocrits. Temperatures are reported in degrees C. Rates were compared with 2-tailed Fisher’s exact test, with alpha=0.05. Results: Baseline temperatures at 8 minutes VF did not differ (IRH=37.9° and CTL=37.7°). Post-infusion temperatures at 13 minutes of VF were IRH=34.9° and CTL=37.9°. ROSC occurred in 12/14 (86%) IRH animals and in 6/14 (43%) CTL, with p=0.046. Survival occurred in 8/14 (57%) IRH animals and 4/14 (36%) CTL, with p=0.15. Total fluid volumes given and hematocrits did not differ between groups. Conclusions: IRH doubled the rate of ROSC compared to CTL. There was a non-significant 58% relative improvement in short-term survival. In this porcine model, rapid infusion of ice-cold saline quickly cooled during resuscitation.

Abstract 41: Early Post-Resuscitation Levels of Cytochrome- c and Interleukin-6 after Prolonged Porcine Cardiac Arrest

Background: The identification of serum biomarkers of ischemic injury could provide a means of assessing interventions designed to limit reperfusion injury after return of spontaneous circulation (ROSC). We sought to characterize the early post-ROSC timecourse of two candidate biomarkers of ischemic injury (cytochrome- c and IL-6) in a swine model of ventricular fibrillation (VF). We hypothesized that these two biomarkers would be elevated immediately after ROSC. Methods: Twenty-five mixed breed domestic swine were anesthetized and instrumented with ECG, temperature probe, and aortic and right atrial pressure transducers. VF was induced with a transthoracic shock and untreated for 8 minutes. Then mechanical CPR was done for 2 minutes, before drugs were given (epinephrine, vasopressin, and propranolol) with 3 additional minutes of CPR (first defibrillation attempt at 13 minutes of VF). Blood samples were drawn at the end of instrumentation (i.e. just prior to VF), and at 20, 40, and 60 minutes after ROSC. Samples were centrifuged and serum extracted. Cytochrome- c was analyzed via Western immunoblotting. IL-6 was analyzed with ELISA. Results: No cytochrome- c was detected in any animal, at any timepoint through 60 min. IL-6 was similar to baseline levels through 40 min, but was 121% of baseline at 60. Conclusions: Neither biomarker was elevated immediately after ROSC. Mitochondrial damage (as indicated by the absence of cytochrome- c ) may be delayed by as much as an hour after ROSC, hinting at a possible therapeutic window for interventions like hypothermia. Likewise, inflammatory cascades (as indicated by IL-6) may not begin immediately post-ROSC, but might by one hour.

Combination pharmacotherapy with delayed countershock vs standard advanced cardiac life support after prolonged ventricular fibrillation

Objective. To test the hypothesis that combination pharmacotherapy with delayed countershock would produce higher rates of return of spontaneous circulation (ROSC) and one-hour survival when compared with standard Advanced Cardiac Life Support (ACLS) therapy. Methods. A prospective, block-randomized, blinded, laboratory experiment was conducted in an established swine model of prolonged ventricular fibrillation (VF). Fifty-six female domestic swine were anesthetized, instrumented, and shocked into VF with a bipolar pacing catheter. The VF was untreated for 8 minutes, then basic CPR was done mechanically for 1 minute. At 9 minutes of VF, the animals were randomized to treatment with one of seven therapies: group 1, combination pharmacotherapy with epinephrine (0.20 mg/kg), lidocaine (1.0 mg/kg), bretylium (5.0 mg/kg), propranolol (1.0 mg), and U-74389G (3.0 mg/ kg); group 2, epinephrine (0.20 mg/kg); group 3, lidocaine (1.0 mg/kg) and bretylium (5.0 mg/kg); group 4, propranolol (1.0 mg); group 5, U-74389G (3.0 mg/kg); group 6, normal saline solution (volume equal to that for group 1); and group 7, standard ACLS (first countershock at 9 minutes of VF). Initial countershocks for groups 1-6 were given after 11 minutes of VF. Data were analyzed with two-tailed Fisher's exact test, with alpha set at 0.05. Results. Return of spontaneous circulation occurred in group 1 = 8/8 (100%); group 2 = 7/8 (88%); group 3 = 3/8 (38%); group 4 = 3/8 (38%); group 5 = 5/8 (63%); group 6 = 4/8 (50%); and group 7 = 3/8 (38%). One-hour survival occurred in group 1 = 8/8 (100%); group 2 = 5/8 (63%); group 3 = 2/8 (25%); group 4 = 2/8 (25%); group 5 = 3/8 (38%); group 6 = 2/8 (25%); and group 7 = 1/8 (13%). Conclusions. Combination pharmacotherapy with delayed countershock (group 1) produced significantly higher rates of ROSC (p = 0.03) and one-hour survival (p = 0.001) when compared with standard ACLS in this porcine model of prolonged VF. PREHOSPITAL EMERGENCY CARE 2000;4:31-37