Ventricular Fibrillation In Swine Research Articles

Abstract 246: Therapeutic Hypothermia Mimicking Peptide Administration During Cardiopulmonary Resuscitation Improved Cardiac Arrest Survival in Swine

Background: Out-of-hospital sudden cardiac arrest is a leading cause of death in the United States, affecting over 350,000 people per year with an overall survival rate around 10%. CPR, defibrillation, and therapeutic hypothermia are common resuscitation strategies, but hypothermia is difficult to implement timely to achieve survival benefit. A cell-permeable peptide TAT-PHLPP9c has been shown to alter metabolic pathways similar to hypothermia, and decreases the release of two biomarkers, taurine and glutamate, during the high osmotic stress of heart stunning and brain injury in a mouse arrest model. Hypothesis: TAT-PHLPP9c, given during CPR, enhances 24-hour survival in a swine ventricular fibrillation (VF) model. Methods: In 14 (8 controls and 6 treated) sedated, intubated, and mechanically ventilated swine, after 5 min of VF, ACLS with vest CPR and periodic defibrillations was performed. Venous blood samples were collected at baseline, after 2 min of CPR, and at 2 and 30 min after return of spontaneous circulation (ROSC). The animals were survived up to 24 hrs and plasma samples were analyzed for glutamate and taurine in 2 controls and 1 animal given peptide. Results: Three of the control animals had ROSC, but none survived for 24 hrs, while 4 of 6 treated animals achieved neurologically intact survival at 24 hrs (p < 0.02). Compared to baseline, both taurine and glutamate plasma concentrations increased in the control group, but the increase was reduced substantially by the peptide treatment at 30 min after ROSC (Figure). Conclusion: The use of the cooling mimicking peptide TAT-PHLPP9c administered during CPR significantly improved 24-hour survival in this swine model of cardiac arrest. It reduced the increase of cerebral and myocardial metabolic biomarkers, which encourages utilizing a strategy of cell-permeable peptides for intravenous administration for more rapid onset of hypothermia-like salutary effects than are possible with current CPR cooling devices.

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.

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.

GW25-e0299 Zp123 Reduces Defibrillation Energy by Preventing Connexion-43 Remodeling in Prolonged Ventricular Fibrillation in Swine

GW25-e0299 Zp123 Reduces Defibrillation Energy by Preventing Connexion-43 Remodeling in Prolonged Ventricular Fibrillation in Swine

GW24-e1013 ZP123 reduces energy required for defibrillation by preventing connexin43 remodeling during prolonged ventricular fibrillation in swine

ObjectivesIn ventricular fibrillation, the uncoupling of gap junctions slows conduction velocity and increases action-potential dispersion, which slows and diminishes defibrillation. We studied how the peptide ZP123, a gap-junction enhancer, might...

Electrocardiogram frequency change by extracorporeal blood perfusion in a swine ventricular fibrillation model

BackgroundExtracorporeal cardiopulmonary resuscitation (ECPR) refers to the application of extracorporeal blood circulation with oxygenation as a resuscitation tool. The objective of this study is to observe the frequency component changes in the electrocardiogram (ECG) by ECPR during prolonged ventricular fibrillation (VF).MethodsSix swine were prepared as a VF model. Extracorporeal blood circulation with a pulsatile blood pump and oxygenator was set up for the model. ECG signals were measured for 13 min during VF and analyzed using frequency analysis methods. The median frequency (MF), dominant frequency (DF), and amplitude spectrum area (AMSA) were calculated from a spectrogram obtained using short-time Fourier transform (STFT).ResultsMF decreased from 11 Hz at the start to 9 Hz at 2 min after VF and then increased to 11 Hz at 4.5 min after VF. DF started at 7 Hz and increased to 11 Hz within the first min and decreased to 9 Hz at 2 min, then increased to 12 Hz at 4.5 min after VF. Both frequency components decreased gradually from 4.5 min until 10 min after VF. After the oxygenated blood perfusion was initiated, both MF and DF increased remarkably and exceeded 12 and 14 Hz, respectively. Similarly, AMSA decreased gradually for the first 10 min, but increased remarkably and varied beyond 13 mV∙Hz after the oxygenated blood supply started. Remarkable frequency increases in ECG due to the oxygenated blood perfusion during ECPR were observed in the swine VF model.ConclusionsThe ECG frequency analysis during ECPR can give the resuscitation provider important information about the cardiac perfusion status and the appropriateness of the ECPR setup as well as the prediction of defibrillation success.

Effect of ZP123, a Gap Junction Modifier, on Prolonged Ventricular Fibrillation in Swine

Objectives: It was the aim of this study to investigate the effect of ZP123 on prolonged ventricular fibrillation (VF) in swine. Methods: VF was electrically induced in 20 pigs. The animals randomly received either ZP123 or saline control infusion before VF. After 8 min of untreated VF, cardiopulmonary resuscitation and biphasic defibrillation shocks were applied. VF mean frequency (VF_mf) and mean amplitude (VF_ma), hemodynamics, outcome of defibrillation and the rate of return of spontaneous circulation (ROSC) were analyzed. Results: Compared with the control group, VF_mf was higher but VF_ma lower during the 8 min of VF in the drug group (11.8 ± 2.1 vs. 10.4 ± 2.0 Hz and 0.24 ± 0.10 vs. 0.31 ± 0.16 mV, respectively; p < 0.05). Hemodynamic variables in the 2 groups were comparable (p > 0.05). The defibrillation threshold was lower and the rate of successful defibrillation was higher in the drug group compared with the control group (92.2 ± 26.4 vs. 133.3 ± 28.9 J and 90 vs. 30%, respectively; p < 0.05). The rate of ROSC was not different between the 2 groups (40 vs. 30%; p > 0.05). Conclusion: In prolonged VF, ZP123 could decrease the defibrillation threshold and improve the rate of successful defibrillation. However, it could not improve the rate of ROSC – which may be due to its side effect of decreasing VF_ma.

Effects on electricalrestitution of given esmolol during cardiopulmonary resuscitation in a swine ventricularfibrillation model

：Objective To investigatethe effect on electrical restitution of β1-adrenergic receptor antagonist esmolol administered duringcardiopulmonary resuscitation in the porcine ventricular fibrillation model. MethodVentricular fibrillation untreated for four minutes was induced by dynamic steady statepacing protocol in 40 healthy male pigs, in which local unipolar electrograms wererecorded using one 10-electrode catheter that was sutured to the left ventrieularepicarditan. During CPR, animals were randomized into two groups to receive saline asplacebo or esmolol after two standards doses of epinephrine. At postresuscitation 2-hour,six pigs were randomly selected from each group and the second VF induction was performed.Local activation-recovery intervals (ARI) restitutions and the VF inducibility betweencontrol group and esmolol group were compared. Western blotting was performed to determinecardiac ryanodine receptor (RyR2) protein expression, and their phosphorylation status.Results No sig-nificant differences were observed at the restoration of spontaneouscirculation between two groups. Higher postre-suseitation 2-hour survival rate wasobserved in the esmolol group. Esmolol significantly flattened ARI restitution slope,lessened regional difference of ARI restitution, decreased the VF inducibility, andalleviated RyR2 hyper-phosphorylation. Conclusions Esmolol given during CPR significantlyimproved postresuscitation 2-hour survival rate. Its effects on modulating electricalrestitution property and intracellular calcium handling make up the most important reasonswhy β1-blockadesignificantly reduced the onset and maintenance of VF. Key words: Veutricularfibrillation; Action potentials; Restitution property; Cardiac ryanodinereceptor; Beta-adrenergic receptor

Transmural recording of shock potential gradient fields, early postshock activations, and refibrillation episodes associated with external defibrillation of long-duration ventricular fibrillation in swine

Knowledge of the shock potential gradient (nablaV) and postshock activation is limited to internal defibrillation of short-duration ventricular fibrillation (SDVF). The purpose of this study was to determine these variables after external defibrillation of long-duration VF (LDVF). In six pigs, 115-20 plunge needles with three to six electrodes each were inserted to record throughout both ventricles. After the chest was closed, the biphasic defibrillation threshold (DFT) was determined after 20 seconds of SDVF with external defibrillation pads. After 7 minutes of LDVF, defibrillation shocks that were less than or equal to the SDVF DFT strength were given. For DFT shocks (1632 +/- 429 V), the maximum minus minimum ventricular voltage (160 +/- 100 V) was 9.8% of the shock voltage. Maximum cardiac nablaV (28.7 +/- 17 V/cm) was 4.7 +/- 2.0 times the minimum nablaV (6.2 +/- 3.5 V/cm). Although LDVF did not increase the DFT in five of the six pigs, it significantly lengthened the time to earliest postshock activation following defibrillation (1.6 +/- 2.2 seconds for SDVF and 4.9 +/- 4.3 seconds for LDVF). After LDVF, 1.3 +/- 0.8 episodes of spontaneous refibrillation occurred per animal, but there was no refibrillation after SDVF. Compared with previous studies of internal defibrillation, during external defibrillation much less of the shock voltage appears across the heart and the shock field is much more even; however, the minimum nablaV is similar. Compared with external defibrillation of SDVF, the biphasic external DFT for LDVF is not increased; however, time to earliest postshock activation triples. Refibrillation is common after LDVF but not after SDVF in these normal hearts, indicating that LDVF by itself can cause refibrillation without requiring preexisting heart disease.

TASER X26 Discharges in Swine Produce Potentially Fatal Ventricular Arrhythmias

Data from the authors and others suggest that TASER X26 stun devices can acutely alter cardiac function in swine. The authors hypothesized that TASER discharges degrade cardiac performance through a mechanism not involving concurrent acidosis. Using an Institutional Animal Care and Use Committee (IACUC)-approved protocol, Yorkshire pigs (25-71 kg) were anesthetized, paralyzed with succinylcholine (SCh; 2 mg/kg), and then exposed to two 40-second discharges from a TASER X26 with a transcardiac vector. Vital signs, blood chemistry, and electrolyte levels were obtained before exposure and periodically for 48 hours postdischarge. Electrocardiograms and echocardiography (echo) were performed before, during, and after the discharges. p-Values < 0.05 were considered significant. Electrocardiograms were unreadable during the discharges due to electrical interference, but echo images showed unmistakably that cardiac rhythm was captured immediately at a rate of 301 +/- 18 beats/min (n = 8) in all animals tested. Capture continued for the duration of the discharge and in one animal degenerated into fatal ventricular fibrillation (VF). In the remaining animals, ventricular tachycardia (VT) occurred postdischarge for 1-17 seconds, whereupon sinus rhythm was regained spontaneously. Blood chemistry values and vital signs were minimally altered postdischarge and no significant acidosis was seen. Extreme acid-base disturbances usually seen after lengthy TASER discharges were absent with SCh, but TASER X26 discharges immediately and invariably produced myocardial capture. This usually reverted spontaneously to sinus rhythm postdischarge, but fatal VF was seen in one animal. Thus, in the absence of systemic acidosis, lengthy transcardiac TASER X26 discharges (2 x 40 seconds) captured myocardial rhythm, potentially resulting in VT or VF in swine.

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.

Abstract 98: Spontaneous Refibrillation Following External Defibrillation of Long Duration Ventricular Fibrillation in Swine

Background: Following successful defibrillation of the long duration ventricular fibrillation (LDVF) associated with sudden cardiac arrest (SCA), refibrillation occurs in over half of resuscitation attempts. In experimental animals with normal hearts, refibrillation almost never occurs following short duration VF lasting &lt; 1 min (SDVF). It is not known if refibrillation following LDVF is due to the cardiac disease that caused the initial LDVF of SCA or if the LDVF itself causes abnormalities that can initiate VF. Further, the mechanism of refibrillation initiation is unknown. We tested the hypothesis that refibrillation occurs frequently following LDVF in previously normal hearts and propagates from a common area within the heart. Methods : In 6 pigs, 115–120 plunge needles containing 3– 6 electrodes each were inserted throughout the heart. With the chest closed, external defibrillation pads were placed in a left lateral to right lateral configuration. Following successful defibrillation of 20 s of SDVF, the animal was observed for spontaneous VF for at least 4 min. After termination of 7 min of LDVF, the animal was placed on cardiopulmonary bypass and observed for 15 min for spontaneous VF. Results: Following LDVF, 1.33 ±0.8 episodes of spontaneous VF occurred in each animal. The mean time to VF was 71 s (range 5 – 139 s) following defibrillation of LDVF. Three animals had a second episode of VF within 3 min of termination of LDVF. Earliest sites of origin of spontaneous VF occurred equally in the LV (3), RV (3), and septum (2) and arose equally from the endocardium (3), epicardium (2), and myocardium (3). Refibrillation originated in the posterior half of the ventricles 75% of the time. The first refibrillation cycle appeared focal in 75% of cases and reentrant in 25%. Premature ventricular beats arising out of the posterior RV base immediately preceded 75% of VF episodes. Conclusions: Spontaneous VF is common after defibrillation of LDVF but not SDVF in previously health swine, indicating that refibrillation does not require preexisting cardiac disease but can be caused by the detrimental effects of LDVF. Most episodes of refibrillation begin as focal activity within the posterior half of the ventricles.

Role of maximum rate of depolarization in predicting action potential duration during ventricular fibrillation

During ventricular fibrillation (VF) only 39% of the variation in action potential duration (APD) is accounted for by the previous diastolic interval [DI((n-1))], i.e., restitution, and the previous APD [APD((n-1))], i.e., memory. We tested the hypothesis that a characteristic of the AP upstroke, the maximum rate of depolarization (V(max)), also helps account for its APD. A floating microelectrode was used to make transmembrane recordings at 16,000 samples/s from the anterior left ventricular wall during four 20-s episodes of VF in each of six pigs. V(max), time from V(max) to 60% repolarization (APD(60)), and DI were calculated throughout all episodes. Stepwise linear regression was used to determine how well each APD(60) (APD(60n)) was predicted by V(max) of that AP, the four previous DIs (n-1, n - 2, n - 3, n - 4), and the three previous APD(60)s (n-1, n - 2, n - 3). V(max) entered in the regression equation significantly more often (86% of VF episodes) than either APD((n-1)) (47% of episodes) or DI((n-1)) (58% of episodes). When these three variables entered first or second, their coefficients were almost always positive, consistent with a longer APD associated with 1) a larger V(max), 2) a longer APD((n-1)), and 3) a longer DI((n-1)). R(2) of the regression for all entered variables was 0.51 +/- 0.01 (mean +/- SD). During the first 20 s of VF in swine, V(max) is a more important determinant of APD than the previous DI (restitution) or the previous APD (memory). All variables together account for only one-half of APD variation during VF.

Is all ventricular fibrillation the same? A comparison of ischemically induced with electrically induced ventricular fibrillation in a porcine cardiac arrest and resuscitation model*

The standard porcine cardiac arrest model uses electrical induction of ventricular fibrillation. Reported restoration of spontaneous circulation and survival rates in this model are as high as 90% for ventricular fibrillation durations of 7-10 mins, values substantially greater than rates in the clinical population (i.e., 20% to 30%). A high first shock success rate, infrequent refibrillation, and short times for restoration of spontaneous circulation are typical of the model. The purpose of this study was to determine whether ischemic induction of ventricular fibrillation in swine followed by standard advanced cardiac life support would result in short-term outcomes approximating those observed in human victims of out-of-hospital ventricular fibrillation. Randomized comparative trial. Translational research laboratory. Domestic swine (n = 40, mean weight 40 +/- 4 kg, range 34-47 kg) of both genders. Swine were instrumented and randomized to either electrical ventricular fibrillation induction or ischemic ventricular fibrillation, produced by balloon occlusion of the mid-left anterior descending coronary artery (n = 20 per group). Transthoracic impedance was measured and 30 Omega added in series for all animals. The balloon remained inflated during resuscitation efforts in ischemic ventricular fibrillation animals. After 7 mins of ventricular fibrillation, cardiopulmonary resuscitation was initiated and defibrillation was attempted 1 min later. Epinephrine and antiarrhythmics were administered as per guidelines. Resuscitation was terminated if restoration of spontaneous circulation had not occurred after 15 mins of advanced cardiac life support. Although the number of countershocks required to initially terminate ventricular fibrillation was not different (electrical ventricular fibrillation 1.9 +/- 1.6, ischemic ventricular fibrillation 2.4 +/- 2.0), the refibrillation rate was higher in the ischemic ventricular fibrillation group (4.9 +/- 4 vs. 0.8 +/- 1 episodes/animal, p < .001), resulting in a greater number of shocks before restoration of spontaneous circulation (total shocks for ischemic ventricular fibrillation 9.4 +/- 5.6 vs. electrical ventricular fibrillation 2.7 +/- 2.2, p < .001). Time to restoration of spontaneous circulation was longer in the ischemic ventricular fibrillation group (430 +/- 234 secs vs. 149 +/- 120 secs, p < .001). Restoration of spontaneous circulation rates were not different (electrical ventricular fibrillation 90% vs. ischemic ventricular fibrillation 65%). However, survival to 6 hrs was greater in the electrical ventricular fibrillation group (18 of 20, 90%) than in the ischemic ventricular fibrillation group (8 of 20, 40%, p = .002). Resuscitation from ischemic ventricular fibrillation is more difficult than electrical ventricular fibrillation and is characterized by greater time to restoration of spontaneous circulation, frequent refibrillation, greater number of countershocks, higher epinephrine dose during resuscitation efforts, profound cardiac dysfunction, and a short-term survival rate approaching clinical experience. Ischemically induced ventricular fibrillation is a more clinically relevant model for the evaluation of resuscitation interventions.

Role of the Posterior Papillary Muscle and Purkinje Potentials in the Mechanism of Ventricular Fibrillation in Open Chest Dogs and Swine: Effects of Catheter Ablation

Papillary muscle (PM) ablation may terminate ventricular fibrillation (VF) in rabbit hearts. Whether or not PM ablation prevents ventricular fibrillation (VF) induction in large animals is unknown. We performed noncontact endocardial mapping and/or high-density epicardial mapping during VF in 12 dogs and 16 swine and tested the effects of posterior PM (PPM) ablation on VF inducibility. During VF in progressive global ischemia (3 swine and 2 dogs), the highest dominant frequency (DF) was near PPM. The majority of the reentrant wavefronts during a propranolol infusion (swine) were anchored to the PPM. Purkinje potentials onset were recorded on the PPM both during sinus rhythm and during VF. Radiofrequency (RF) ablation of the endocardium on the PPM with a linear extension of the ablation line from the PPM to the mitral valve annulus and then the left ventricular apex in 7 dogs reduced the VF inducibility from 100% at baseline to 22% after ablation (P < 0.0001). RF applications to the anterolateral wall of dogs (n = 3) did not prevent VF induction. The application of RF energy near the PPM frequently initiated VF in swine (n = 7), preventing subsequent testing of VF inducibility. In dogs and swine, the highest DF and majority of reentrant wavefronts during VF with acute global ischemia or during a propranolol infusion were located on the PPM. RF ablation targeted at the PPM reduced the inducibility of VF in normal dogs. However, the same ablation provoked incessant VF in swine, preventing subsequent testing of VF inducibility.

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.

Variation in the dominant period during ventricular fibrillation.

Time-varying periodicities are commonly observed in biological time series. In this paper, we discuss three different algorithms to detect and quantify change in periodicity. Each technique uses a sliding window to estimate periodic components in short subseries of a longer recording. The three techniques we utilize are based on: 1) standard Fourier spectral estimation; 2) an information theoretic adaption of linear (autoregressive) modeling; and 3) geometric properties of the embedded time series. We compare the results obtained from each of these methods using artificial data and experimental data from swine ventricular fibrillation (VF). Spectral estimates have previously been applied to VF time series to show a time-dependent trend in the dominant frequency. We confirm this result by showing that the dominant period of VF, following onset, first decreases to a minimum and then rises to a plateau. Furthermore, our algorithms detect longer period correlations which may indicate the presence of additional periodic oscillations or more complex nonlinear structure. We show that in general this possibly nonlinear structure is most apparent immediately after the onset of VF.

Scaling structure of electrocardiographic waveform during prolonged ventricular fibrillation in swine.

Ventricular fibrillation (VF) is the most common arrhythmia causing sudden cardiac death. However, the likelihood of successful defibrillation declines with increasing duration of VF. Because the morphology of the electrocardiogram (ECG) waveform during VF also changes with time, this study examined a new measure that describes the VF waveform and distinguishes between early and late VF. Surface ECG recordings were digitized at 200 samples/s from nine swine with induced VF. A new measure called the scaling exponent was calculated by examining the power-law relationship between the summation of amplitudes of a 1,024-point (5.12 second) waveform segment and the time scale of measurement. The scaling exponent is a local estimate of the fractal dimension of the ECG waveform. A consistent power-law relationship was observed for measurement time scales of 0.005-0.040 seconds. Calculation of the scaling exponent produced similar results between subjects, and distinguished early VF (< 4-minute duration) from late VF (> or = 4-minute duration). The scaling exponent was dependent on the order of the data, supporting the hypothesis that the surface ECG during VF is a deterministic rather than a random signal. The waveform of VF results from the interaction of multiple fronts of depolarization within the heart, and may be described using the tools of nonlinear dynamics. As a quantitative descriptor of waveform structure, the scaling exponent characterizes the time dependent organization of VF.

Physiologic measurement of the ventricular fibrillation ECG signal: estimating the duration of ventricular fibrillation.

Estimating the duration of ventricular fibrillation may help determine the best initial therapy and provide estimates of the most appropriate dose of epinephrine to administer during cardiac arrest and resuscitation. In addition, estimating this time can provide a more sound methodologic approach to stratifying patients in the analysis of cardiac arrest studies. In an initial series of studies in swine, we attempted to determine whether changes in the frequency or amplitude (power) of the ventricular fibrillation ECG signal during cardiac arrest could be used to estimate this time. These studies characterized the dynamics of both the total power and the frequency distribution of the power in the ECG over time during ventricular fibrillation in swine. Our purpose was to determine whether sufficient information existed in either parameter to estimate the duration of ventricular fibrillation. The median frequency of the power spectrum was used to track power distribution. Both parameters followed a dynamic and repeatable pattern. A mathematical model of median frequency was developed and used with data obtained from additional swine to estimate the duration of ventricular fibrillation. The model estimated the duration of ventricular fibrillation to within +/- 1.3 minutes of the actual duration from one to ten minutes after the onset of ventricular fibrillation. We recently characterized the time course of the median frequency during ventricular fibrillation in human beings. The median frequency was extracted from each four-second segment of the ventricular fibrillation ECG recordings and plotted versus time from the onset of cardiac arrest. The median frequency in human beings followed a repeatable time course during ventricular fibrillation.(ABSTRACT TRUNCATED AT 250 WORDS)