Ventricular Fibrillation Intervals Research Articles

Abstract 196: Association Between Continuous Carotid Blow Flow And Continuous Cerebral Perfusion Indexes Assessment By NIRS In A Porcine Model Of Ventricular Fibrillation During CPR

[Background]: Maintenance of cerebral blood flow during cardiopulmonary resuscitation (CPR) is a critical factor affecting the neurological outcome of patients after cardiac arrest. However, dynamic indicator of cerebral blood flow during CPR is not established. Near infrared spectroscopy (NIRS) is a non-invasive technique capable of detecting changes in cerebral blood volume continuously. The aim of this study is to compare cerebral perfusion during CPR obtained by continuous measure of carotid blow flow (CBF) using flow sensor with continuous cerebral perfusion indices (CPI) assessment by NIRS in a porcine model of ventricular fibrillation (VF) cardiac arrest. [Methods]: CBF during CPR were measured in 21 swine (25± 3 kg) using extra-vascular flow probes positioned around the common carotid arteries. The optodes of the NIRS were attached to the skull bone. Following baseline measurements, VF was electrically induced. After the interval of untreated VF, CPR was continued for 25 min, during which mechanical and manual CPR was alternated at every 5 min intervals. CBF and CPI were measured continuously during CPR. The mean volume of CBF and CPI was calculated average 10 beats in each phase. Correlations between CBF volume and CPI were analyzed by Spearman's rank correlation. [Results]: The followability of CBF and CPI during CPR was good. The Spearman's rank correlation coefficient between CBF volume and CPI was different by sections and it was suggested that the CBF volume was too small to assess the correlation in many sections. If the sections with CBF volume>0.4 ml were extracted and reanalyzed, the rate of sections correlated between CBF volume and CPI were increased (Spearman’s correlation coefficient≧0.4 was 41.3%, Spearman’s correlation coefficient≧0.7 was 17.5%).(Table) [Conclusions]: It was suggested that CPI by NIRS can reflect the CBF during CPR in the sections where enough CBF is.

Abstract 253: Trajectory of Ventricular Fibrillation Prognostic Status During Cardiopulmonary Resuscitation

Background: Resuscitation from out-of-hospital cardiac arrest (OHCA) due to ventricular fibrillation (VF) typically involves continuous CPR cycles interrupted every 2 minutes for rhythm analysis and potential defibrillation. Quantitative measures of the VF ECG waveform have been proposed to guide therapy for VF arrest because they are associated with myocardial energetics, are dynamic over the course of resuscitation, and predict outcome. However, while VF waveform measures have until recently have required CPR interruption to accurately gauge prognostic status, CPR interruptions are associated with a lower chance of survival. We used a novel waveform measure previously-validated during active CPR to estimate the course of VF status through the 2-minute CPR cycle between consecutive shocks. Methods: We conducted an observational study of patients with VF OHCA who experienced recurrent VF for at least 90 seconds following initial shock. We used the continuous defibrillator ECG to calculate the VF waveform measure as a function of predicted probability of survival-with-intact-neurologic-status at 1-s intervals over the course of resuscitation between shocks. Results: We collected 499 VF ECG segments (≥90 seconds) during CPR from 313 patients. The trajectory of the average prognostic VF measure had a 3-phase time-dependent pattern (Fig. 1). During CPR, the slope of the measure decreased during the initial 25 s of VF (slope = -12%/min) and was relatively flat during the subsequent 65-s interval of VF (slope = +1%/min). Furthermore, slope decreased sharply following the cessation of CPR for rhythm analysis, charge, and shock (slope = -23%/min). Conclusion: On average, a novel VF waveform measure assessed during the scheduled cycle of CPR and rhythm analysis between consecutive shocks was characterized by a period of decline, stabilization, and then decline. Whether these changes in VF status can be used to improve care for individual patients is uncertain.

Fuzzy and Sample Entropies as Predictors of Patient Survival Using Short Ventricular Fibrillation Recordings during out of Hospital Cardiac Arrest.

Optimal defibrillation timing guided by ventricular fibrillation (VF) waveform analysis would contribute to improved survival of out-of-hospital cardiac arrest (OHCA) patients by minimizing myocardial damage caused by futile defibrillation shocks and minimizing interruptions to cardiopulmonary resuscitation. Recently, fuzzy entropy (FuzzyEn) tailored to jointly measure VF amplitude and regularity has been shown to be an efficient defibrillation success predictor. In this study, 734 shocks from 296 OHCA patients (50 survivors) were analyzed, and the embedding dimension (m) and matching tolerance (r) for FuzzyEn and sample entropy (SampEn) were adjusted to predict defibrillation success and patient survival. Entropies were significantly larger in successful shocks and in survivors, and when compared to the available methods, FuzzyEn presented the best prediction results, marginally outperforming SampEn. The sensitivity and specificity of FuzzyEn were 83.3% and 76.7% when predicting defibrillation success, and 83.7% and 73.5% for patient survival. Sensitivities and specificities were two points above those of the best available methods, and the prediction accuracy was kept even for VF intervals as short as 2s. These results suggest that FuzzyEn and SampEn may be promising tools for optimizing the defibrillation time and predicting patient survival in OHCA patients presenting VF.

Effect of sevoflurane-containing HTK solution on electrophysiological stability of rat donor heart during reperfusion

Objective To evaluate the effect of sevoflurane-containing HTK solution on electrophysiological stability of rat donor heart during reperfusion. Methods Male Sprague-Dawley rats, weighing 280-320 g, aged 3 months, in which a Langendorff-perfused isolated rat donor heart model was established, were used in this study.Sixteen donor hearts were obtained and divided into 2 groups (n=8 each) using a random number table method: control group (group C) and sevoflurane group (group S). HTK solution was used as preservation solution in group C. HTK solution containing 2.5% sevoflurane was used as preservation solution in group S. Hearts were stored for 6 h in the corresponding preservation solution at 4 ℃ and then reperfused, and the perfusion temperature was gradually restored to 37 ℃ in two groups.The time of spontaneous recovery of heart beat and development of arrhythmia were recorded.Heart rate, monophasic action potential (MAP) duration at 50% and 90% repolarization (MAPD50, MAPD90), MAP amplitude and maximum velocity and development of early after-depolarization and delayed after-depolarization were recorded at 30 and 45 min of reperfusion. Results Compared with group C, the time of spontaneous recovery of heart beat was significantly shortened, the incidence of ventricular fibrillation and arrhythmia score were decreased, the ventricular fibrillation interval was shortened, and MAPD50 and MAPD90 of epicardium and endocardium were shortened at 30 and 45 min of reperfusion (P 0.05). Early after-depolarization and delayed after-depolarization were not found in two groups. Conclusion Sevoflurane-containing HTK solution can maintain electrophysiological stability of rat donor heart during reperfusion and decrease the occurrence of arrhythmia. Key words: Anesthetics, inhalation; Heart transplantation; Cardiac electrophysiology

Abstract 127: Severity of Postresuscitation Myocardial Dysfunction Is Dependent on the Duration of Untreated Cardiac Arrest

Introduction: The duration of untreated ventricular fibrillation (VF) is one of the major determinant for outcome of cardiac arrest (CA). We investigated the relationship between different durations of untreated VF and post-resuscitation myocardial dysfunction and survival in a pig model. Methods: An established model of myocardial infarction followed by CA and CPR was used. Twenty pigs(35-43 Kg) were subjected to 3 different untreated VF intervals, prior to mechanical CPR and defibrillation: 8-10 min; 12-13 min; or 14-15 min. Arterial and central venous pressures were invasively monitored. Ejection fraction (EF) was echocardiographically assessed together with termodilution cardiac output (CO) and high sensitivity cardiac troponin T (hs-cTnT) assay. Ninety six hr survival was evaluated. Results: All the animals were resuscitated, except for 2 in the 14-15 min VF duration (Table). More than 80% of animals survived when the duration of VF was below 13 min, compared to only 17% after 14-15 min (Fig A). The duration of untreated VF correlated with the number of defibrillations required prior to resuscitation (r=0.60, p=0.01, Table). Longer durations of VF were characterized by higher post-resuscitation heart rate and right atrium pressure and by lower post-resuscitation CO and EF (p<0.01, Table). Ninety six hr EF recovered in all animals except in the pig that survived after 14-15 min VF. EF correlated with the number of defibrillation delivered (Fig B) and with hs-cTnT release (r=-0.84, p<0.0001). Conclusions: In this model, post-resuscitation myocardial dysfunction and survival were affected by the duration of untreated VF in a time-dependent manner.

How Atrial Premature Beats Could Have Contributed to Inappropriate ICD Therapy?

Case report: A 55-year-old weman was reffered for secondary prevention of sustained ventricular tachycardia (VT). The heart rate of her VT was 220 beats/min. Her treated with an CURRENT DR CD2211-36Q (Sr. Jude Medical) dual chamber implantable cardioverter defibrillator (ICD). The ventricular fibrillation (VF) zone was programmed to deliver shock at a detection threshold of 200 beats/min. The ventricular tachycardia zone was programmed to antitachycardia pacing at a detection threshold of 182 beats/min. An additional VT monitoring zone was programmed to 150 beats/min. At the next day of implantation, she received inappropriate shock. On the interrogation, the ICD shock followed a sinus tachycardia that averaged 133/min and isolated atrial premature beats. How atrial premature beats could have contributed to inappropriate ICD therapy? In this case, atrial premature beat intervals met the VF detection interval while the average interval satisfied the VT monitoring interval. Therefore, these premature beats were binned as VF. When the 12 such isolated atrial premature beats were recorded, the VF detection criterion was satisfied and shock delivered. For the reduction of the risk of inappropriate shock deliverly, we reprogrammed the monitoring zone to turn off. Conclusion: To our knowledge, an inappropriate shock in the sinus tachycardia with isolated atrial premature beats due to binning non-consecutive VF intervals has not been reported.

RR-interval irregularity precedes ventricular fibrillation in ST elevation acute myocardial infarction

Sudden cardiac arrest is a leading cause of death in industrialized countries, and ischemic ventricular fibrillation (VF) is a frequent cause. The purpose of this study was to determine whether patients with ST elevation myocardial infarction (STEMI) who develop ischemic VF show more overall RR-interval irregularity (RRI) than do STEMI patients without ischemic VF. Ischemic VF was identified in 41 patients from 1,473 digital 12-lead Holter recordings from three separate STEMI studies. Continuous 3-lead and 12-lead electrocardiogram (ECG) snapshots recorded every minute were compared between all ischemic VF patients and 123 random patients without ischemic VF. Time intervals from start of Holter to ischemic VF and equivalent intervals in the controls were used for calculations. ECG variables related to conduction intervals and severity of ischemia were measured using the most ischemic 12-lead ECG. RRI was calculated as the square root of the mean squared differences of successive RR intervals. For RRI, all QRS complexes, including ventricular ectopic beats, were used. No baseline differences were observed between the study and control groups, except for male preponderance among ischemic VF patients (90% vs 72%, P = .019). QRS interval, ECG ischemia severity, RRI, and number of ventricular ectopic beats were significantly associated with ischemic VF. Multivariate analysis revealed RRI (odds ratio 1.006, 95% confidence interval 1.001-1.010, P = .016) and ST deviation score (odds ratio 1.073, 95% confidence interval 1.041-1.106, P <.001) as the only statistically significant predictors of ischemic VF. In the period before ischemic VF, RRI and ST deviation score are associated with ischemic VF in STEMI patients. These findings could have important pathophysiologic and clinical implications.

Abstract P16: The Decreases of Left Ventricle Volume and Area During VF Affect Resuscitation Outcomes

Introduction: Dynamic changes in dimensions of left ventricle (LV) during cardiac arrest might influence the efficacy of CPR. However, the relationships between change in LV dimensions during cardiac arrest and CPR hemodynamic and outcomes remain to be studied. In the present study, we investigated changes of left ventricular volume and area during prolonged untreated ventricular fibrillation (VF) and related those change to coronary perfusion pressure (CPP) during CPR and resuscitation outcomes. Hypothesis: Decreased LV volume and area during prolonged VF interval would yield low CPP and poor resuscitation outcomes. Methods: In 12 domestic male pigs weighing 40±3 kg, VF was electrically induced and untreated for 15 min. CPR was performed for a 5 min interval prior to defibrillation. CPR was continued until return of spontaneous circulation (ROSC) or for a max of 15 minutes. Diastolic aortic and right atrial pressures were measured and CPP was calculated. LV dimensions were continuously assessed by echocardiographic measurement during the 15 minutes of untreated VF. Results: 6 animals were successfully resuscitated. During the 15 minute interval of VF, LV area and volume reduced in all the animals. In animals that were not resuscitated LV dimensions were significantly lower compared to those in resuscitated animals (p=0.01). These differences were observed after 10 minutes of untreated VF. The animals with greater reduction in LV dimension during VF, achieved significantly lower CPP during CPR in contrast to animals with larger LV during VF (Table ). Conclusion: Greater decrease in LV volume and area during cardiac arrest are associated with low CPP during CPR and poor resuscitation outcome. LV dimensions prior to start CPR might therefore affect the effectiveness of resuscitation interventions.

Prediction of Successful Defibrillation in Human Victims of Out-of-Hospital cArdiac Arrest: A Retrospective Electrocardiographic Analysis

In the present study we sought to examine the efficacy of an electrocardiographic parameter, 'amplitude spectrum area' (AMSA), to predict the likelihood that any one electrical shock would restore a perfusing rhythm during cardiopulmonary resuscitation in human victims of out-of-hospital cardiac arrest. AMSA analysis is not invalidated by artefacts produced by chest compression and thus it can be performed during CPR, avoiding detrimental interruptions of chest compression and ventilation. We hypothesised that a threshold value of AMSA could be identified as an indicator of successful defibrillation in human victims of cardiac arrest. Analysis was performed on a database of electrocardiographic records, representing lead 2 equivalent recordings from automated external defibrillators including 210 defibrillation attempts from 90 victims of out-of-hospital cardiac arrest. A 4.1 second interval of ventricular fibrillation or ventricular tachycardia, recorded immediately preceding the delivery of the shock, was analysed using the AMSA algorithm. AMSA represents a numerical value based on the sum of the magnitude of the weighted frequency spectrum between two and 48 Hz. AMSA values were significantly greater in successful defibrillation (restoration of a perfusing rhythm), compared to unsuccessful defibrillation (P < 0.0001). An AMSA value of 12 mV-Hz was able to predict the success of each defibrillation attempt with a sensitivity of 0.91 and a specificity of 0.97. In conclusion, AMSA analysis represents a clinically applicable method, which provides a real-time prediction of the success of defibrillation attempts. AMSA may minimise the delivery of futile and detrimental electrical shocks, reducing thereby post-resuscitation myocardial injury.

Nupafant, a PAF‐antagonist prototype for suppression of ventricular fibrillation without liability for QT prolongation?

British Journal of Pharmacology (2006) 149, 966. doi:10.1038/sj.bjp.0706958

Nupafant, a PAF‐antagonist prototype for suppression of ventricular fibrillation without liability for QT prolongation?

PAF antagonists inhibit ischaemia-induced ventricular fibrillation (VF) in animals. However, unfavourable ancillary actions (on QT interval and coronary flow) have been reported with the PAF antagonist, BN-50739. If these are class actions, they would preclude development of PAF antagonists as novel anti-VF drugs. Our purpose was to examine this proposition using the hitherto untested PAF antagonist, nupafant. Two rat heart preparations (Langendorff and 'dual coronary' perfusion) were used to assay nupafant's effects on ischaemia-induced VF, coronary flow and QT interval, and to test for the site-selectivity necessary if any effects on VF are caused by PAF antagonism. Global (whole-heart) delivery of 10 microM nupafant, reduced the incidence of ischaemia-induced VF and widened QT interval without affecting coronary flow. Importantly, lower concentrations (0.1 and 1 microM) had no effect on VF, yet widened QT almost identically to 10 microM nupafant. When nupafant was delivered selectively to (and entrapped within) the involved region it partially protected against VF (P<0.05). This occurred without change in QT interval. Selective nupafant delivery to the uninvolved region was without effect. Nupafant protects against ischaemia-induced VF primarily by site-selective actions in the ischaemic region but, unlike BN-50739, the effect is unrelated to its QT widening action, and is not compromised by any effect on coronary flow. This establishes proof of concept that VF suppression by PAF antagonism need not invariably be associated with QT prolongation or vasodilatation, justifying further development of this drug class.

Precountershock cardiopulmonary resuscitation improves initial response to defibrillation from prolonged ventricular fibrillation: a randomized, controlled swine study.

To compare immediate countershocks (defibrillation 1st) with precountershock cardiopulmonary resuscitation (CPR 1st) for prolonged ventricular fibrillation (VF). Randomized, controlled trial. University animal laboratory. Thirty swine (27 +/- 1 kg). After 8 mins of untreated ventricular fibrillation, swine were randomly assigned to receive either immediate countershocks or CPR for 90 secs followed by countershocks. After the first set of shocks, nine of 15 CPR 1st animals attained return of spontaneous circulation vs. 0 of 15 defibrillation 1st animals (p <.001), and pulseless electrical activity occurred in only one of 15 CPR 1st animals vs. ten of 15 defibrillation 1st animals (p <.01). The ultimate outcomes in the two groups were not different: Return of spontaneous circulation and 24-hr survival occurred in 15 of 15 CPR 1st and 13 of 15 defibrillation 1st animals. Good neurologic outcome at 24 hrs occurred in 12 of 15 CPR 1st and nine of 15 defibrillation 1st animals. None of the animals was successfully resuscitated with defibrillation alone; all successfully resuscitated animals were provided with chest compressions during the resuscitation. The ventricular fibrillation median frequency by fast Fourier transformation decreased during the untreated ventricular fibrillation interval in both groups (9.7 +/- 0.3 Hz and 10.1 +/- 0.2 Hz after 1 min vs. 8.8 +/- 0.3 Hz and 8.9 +/- 0.5 Hz at 8 mins, respectively). Because the ventricular fibrillation median frequency substantially increased after CPR 1st, it was much higher in the CPR 1st group before the first shock (15.1 +/- 0.9 Hz vs. 8.9 +/- 0.5 Hz, p <.001). The ventricular fibrillation median frequency before the first countershock was much higher in the animals that attained return of spontaneous circulation after the first set of shocks vs. those that did not (16.1 +/- 1.3 Hz vs. 10.0 +/- 0.6 Hz, p <.0001) Precountershock CPR can result in substantial physiologic benefits and superior response to initial defibrillation attempts compared with immediate defibrillation in the setting of prolonged ventricular fibrillation.

Can local ventricular fibrillation interval predict ventricular refractory period in human hearts?

Assessment of the spatial dispersion of ventricular refractory periods has become an important part of electrophysiological study in both experimental and clinical settings, because inhomogeneity of ventricular refractoriness is associated with an increased risk of life-threatening ventricular arrhythmias. Previous animal studies in dog and sheep have demonstrated that local ventricular fibrillation (VF) intervals measured from the heart surface correlate well with the ventricular effective refractory periods measured from the same ventricular sites. We hypothesise that local VF intervals may also predict the ventricular refractory periods in human hearts, hence, can be used to assess the spatial dispersion of refractoriness and to predict the risk of ventricular arrhythmias.

Sodium-hydrogen exchange inhibition during ventricular fibrillation: Beneficial effects on ischemic contracture, action potential duration, reperfusion arrhythmias, myocardial function, and resuscitability.

Inhibition of the sarcolemmal sodium-hydrogen exchanger isoform-1 (NHE-1) is emerging as a promising novel strategy for ameliorating myocardial injury associated with ischemia and reperfusion. We investigated whether NHE-1 inhibition (with cariporide) could minimize mechanical and electrical myocardial abnormalities that develop during ventricular fibrillation (VF) and improve outcome using a porcine model of closed-chest resuscitation. Two groups of 8 pigs each were subjected to 8 minutes of untreated VF and randomized to receive either a 3-mg/kg bolus of cariporide or 0.9% NaCl immediately before an 8-minute interval of conventional closed-chest resuscitation. Cariporide prevented progressive increases in left ventricular free-wall thickness (from 1.0+/-0.2 to 1.5+/-0.3 cm with NaCl, P<0.001 versus 0.9+/-0.1 to 1.1+/-0.3 cm with cariporide, P=NS), maintained the coronary perfusion pressure above resuscitability thresholds (10+/-8 versus 19+/-3 mm Hg before attempting defibrillation, P<0.05), and increased resuscitability (2 of 8 versus 8 of 8, P<0.005). In 2 additional groups of 4 pigs each subjected to a briefer interval of untreated VF, cariporide ameliorated postresuscitation shortening of the action potential duration (APD) at 30%, 60%, and 90% repolarization (ie, APD60 at 2 minutes after resuscitation; 75+/-29 versus 226+/-16 ms, P<0.05), minimized postresuscitation ventricular ectopic activity preventing recurrent VF, and lessened postresuscitation myocardial dysfunction. NHE-1 inhibition may represent a highly potent novel strategy for resuscitation from VF that can ameliorate myocardial manifestations of ischemic injury and improve the effectiveness and outcome of closed-chest resuscitation.

Precountershock cardiopulmonary resuscitation improves ventricular fibrillation median frequency and myocardial readiness for successful defibrillation from prolonged ventricular fibrillation: A randomized, controlled swine study

Study objective: After prolonged ventricular fibrillation (VF), precountershock cardiopulmonary resuscitation (CPR) will improve myocardial “readiness” for defibrillation compared with immediate defibrillation. Methods: After 10 minutes of untreated VF, 32 swine (27±1 kg) were randomly assigned to receive immediate countershocks (DEFIB), CPR for 3 minutes followed by countershocks (CPR), or CPR for 3 minutes plus intravenous epinephrine followed by countershocks (CPR+EPI). VF waveform was evaluated by fast Fourier transformation. Results: VF amplitude and median frequency by fast Fourier transformation decreased during the untreated VF interval in all groups, and the median frequency subsequently increased during each minute of precountershock CPR. Although the VF median frequency in the 3 groups did not differ after 10 minutes of untreated VF (8.9±0.8 Hz versus 8.4±0.5 Hz versus 7.3±0.5 Hz, respectively), immediately before the first shock the VF median frequency was much lower in the DEFIB group than in either the CPR or CPR+EPI groups (8.9±0.8 Hz versus 13.1±0.8 Hz versus 13.8±0.9 Hz, respectively; P <.01). None of the 10 animals in the DEFIB group attained return of spontaneous circulation after the first set of shocks versus 5 of 10 animals in the CPR group and 6 of 12 animals in the CPR+EPI group (DEFIB versus each CPR group; P <.05). Cardiac output 1 hour after resuscitation was substantially worse in the DEFIB group than in the CPR or CPR+EPI groups (74±7 mL/kg per minute versus 119±7 mL/kg per minute versus 104±15 mL/kg per minute; P <.05). Conclusion: Precountershock CPR can result in substantial physiologic benefits compared with immediate defibrillation in the setting of prolonged VF. Moreover, these benefits can be attained with or without the addition of intravenous epinephrine. [Ann Emerg Med. 2002;40:563-570.]

Successful ventricular defibrillation by the selective sodium-hydrogen exchanger isoform-1 inhibitor cariporide.

Sodium-hydrogen exchanger isoform-1 (NHE-1) activation worsens functional myocardial abnormalities associated with ischemia and reperfusion. We hypothesize that these abnormalities may limit cardiac resuscitation from ventricular fibrillation (VF) and investigated whether NHE-1 inhibition with the benzoylguanidine derivative cariporide could improve resuscitability, postresuscitation myocardial function, and short-term survival in isolated heart and intact rat models of VF. Methods and Results-- In the isolated rat heart, VF was induced for 25 minutes. Perfusion was interrupted for the initial 10 minutes and restarted at 10% of baseline flow for the remaining 15 minutes (simulating chest compression). Cariporide ameliorated ischemic contracture, prevented postresuscitation diastolic dysfunction, and favored earlier return of contractile function. In the intact rat, cariporide, injected into the right atrium before chest compression was started (after 6 minutes of untreated VF), prompted spontaneous defibrillation between minutes 7 and 9 of chest compression in 6 of 8 rats. In contrast, electrical defibrillation was required in each of 8 control rats after completion of a predetermined 16-minute interval of VF. After resuscitation, cariporide-treated rats had less ventricular ectopic activity and normalized their hemodynamic function faster. Electrical defibrillation was then timed in control rats to match the time when spontaneous defibrillation occurred in cariporide-treated rats. With comparable VF duration, postresuscitation hemodynamic dysfunction was ameliorated by cariporide, but only when more severe ischemia was modeled by prolongation of the interval of untreated VF from 6 to 10 minutes. NHE-1 inhibition may represent a novel and remarkably effective intervention for resuscitation from VF.

Vasopressin versus epinephrine during cardiopulmonary resuscitation: a randomized swine outcome study

In animal models, vasopressin improves short-term outcome after cardiopulmonary resuscitation (CPR) for ventricular fibrillation compared to placebo, and improves myocardial and cerebral hemodynamics during CPR compared to epinephrine. This study was designed to test the hypothesis that vasopressin would improve 24-h neurologically intact survival compared to epinephrine. After a 2-min untreated ventricular fibrillation interval followed by 6 min of simulated bystander CPR, 35 domestic swine (weight, 25±1 kg) were randomly provided with a single dose of vasopressin (20 U or approximately 0.8 U kg −1 intravenously) or with epinephrine (0.02 mg kg −1 intravenously every 5 min). Ten minutes after initial medication administration (18 min after induction of ventricular fibrillation), standard advanced life support was provided, starting with defibrillation. Animals that were successfully resuscitated received 1 h of intensive care support and were observed for 24 h. Coronary perfusion pressures were higher in the vasopressin group 2 and 4 min after vasopressin administration (28±2 versus 18±1 mmHg, P<0.01, and 26±3 versus 18±2 mmHg, P<0.05, respectively). The vasopressin group tended to be successfully defibrillated on the first attempt more frequently (8/18 versus 3/17, P=0.15). Return of spontaneous circulation (ROSC) was attained in 12/18 (67%) vasopressin-treated pigs versus 8/17 (47%) epinephrine-treated pigs, P=0.24. Twenty-four hour neurologically normal survival occurred in 11/18 (61%) versus 7/17 (41%), respectively, P=0.24. In conclusion, vasopressin administration during CPR improved coronary perfusion pressure, but did not result in statistically significant outcome improvement.

Fast Fourier transform analysis of ventricular fibrillation intervals to predict ventricular refractoriness and its spatial dispersion.

A technique of fast Fourier transform analysis has been used to derive mean ventricular fibrillation (VF) intervals, and to confirm that these VF intervals predict ventricular refractory periods. Twenty episodes of VF were induced by a rapid ventricular pacing in 12 sheep. VF activations in a 10-second period were simultaneously acquired from 64 epicardial sites with an electrode sock. The VF electrograms were analyzed by a fast Fourier transform analysis. The dominant peak frequency of the VF spectrum in each epicardial site was converted into milliseconds and served as a mean VF interval. The dominant peak frequency of VF electrograms ranged from 8.1 to 11.5 Hz, and the corresponding mean VF intervals were 87 to 124 ms. In five sheep, the mean VF intervals and the effective refractory periods were determined by the extrastimulus technique obtained from 29 epicardial sites. There was a very good correlation between the two parameters when the effective refractory periods were determined at a basic cycle length of 300 ms (r = 0.89, P < 0.001) and 400 ms (r = 0.87, P < 0.001), respectively. VF was induced twice in eight sheep. The maximum difference in the mean VF intervals between the two VF episodes in the same sheep was 3 ms (P > 0.05). In conclusion, mean VF intervals determined by the fast Fourier transform analysis have a good reproducibility and a good correlation with ventricular refractory periods measured by the classic extrastimulus technique. The mean VF intervals could serve as an index of ventricular refractoriness.

Effect of sustained stretch on dispersion of ventricular fibrillation intervals in normal rabbit hearts.

To determine the effect of acute left ventricular dilatation on refractoriness in normal hearts. During sustained ventricular fibrillation (VF) in isolated perfused hearts, recording of local activation time yields VF intervals which provide an index of local refractoriness. Simultaneous measurement from multiple sites enables study of spatial aspects of changes in refractoriness. We studied the effects of stretch on the magnitude and dispersion of changes in VF interval in 10 isolated, Langendorff-perfused rabbit hearts using a flexible epicardial array containing 240 unipolar electrodes. The left ventricular pressure was increased from 0 to 40 mmHg by inflation of an intraventricular balloon during sustained VF. The current threshold for VF induction fell from 64 +/- 11 mA to 43 +/- 11 mA (mean +/- SE, P < 0.01) following ventricular dilatation. Mean VF interval at 0 mmHg was 79.8 +/- 1.3 ms and fell to 70.2 +/- 1.7 ms (P < 0.01) at 40 mmHg. There was a corresponding increase in dispersion of VF interval (coefficient of variation) from 8.13 +/- 0.8 to 13.3 +/- 0.8 (P < 0.01). There was regional heterogeneity in the areas of greatest reduction in VF interval, which varied between hearts. Following balloon inflation there was an increase in the number of activation waves. Acute ventricular dilatation produces spatially heterogeneous changes in refractoriness which would predispose to the maintenance of reentrant arrhythmias.

Tedisamil increases coherence during ventricular fibrillation and decreases defibrillation energy requirements.

Drugs which primarily prolong cardiac refractoriness decrease defibrillation voltage and energy requirements in animals and man. The effect of such drugs on ventricular fibrillation itself is not well understood. We hypothesized that tedisamil, an investigational antiarrhythmic drug which blocks Ito and IK repolarizing potassium channels, would increase organization of epicardial electrograms during ventricular fibrillation while it lowered defibrillation energy requirements. We measured magnitude-squared coherence, a measure of spatial organization, and ventricular fibrillation (VF) cycle length, ventricular effective refractory period (VERP), and monophasic action potential duration (APD90) as well as defibrillation energy threshold (E50) at baseline and after 150 micrograms/kg of tedisamil (n = 13) or saline control (n = 6) in an open chest dog model. After tedisamil, mean magnitude-squared coherence increased by 132 +/- 133%, from 0.15 +/- 0.08 to 0.31 +/- 0.16 (P < 0.001); VF cycle length increased from 121 +/- 24 to 190 +/- 63 ms (P < 0.001) and became more regular, with the coefficient of variation between adjacent VF intervals decreasing from 14.1 +/- 6.9 to 3.9 +/- 2.2% (P < 0.001). Mean E50 decreased from 8.9 +/- 3.8 to 6.1 +/- 2.7 joules (P < 0.001); VERP increased from 158 +/- 30 to 201 +/- 31 ms (P < 0.001), and APD90 increased from 177 +/- 25 to 244 +/- 45 ms (P < 0.001) after tedisamil. No electrophysiologic parameter was changed after saline infusion. Tedisamil increases both spatial coherence and temporal regularity of ventricular fibrillation. These effects on 'order' during VF may be in part responsible for the observed reduction in defibrillation energy requirements.