Ischemic Ventricular Fibrillation Research Articles

Systematic review of swine models for ventricular fibrillation induction in evaluating cardiopulmonary resuscitation methods

Background and purpose: Ventricular fibrillation (VF) has been studied using a variety of swine models, historically balloon occlusion of the coronary artery and asphyxiation, and more recently, percutaneous electrical induction. These methods differ in face and construct validity, as well as requirement for expertise, cost, and duration. This study aimed to provide a systematic review these methods and their selection in research. Methods: Electronic searches were conducted in PubMed, Scopus, and Google Scholar. The Utstein-Style Guidelines for Uniform Reporting of Laboratory cardiopulmonary resuscitation (CPR) research were used to identify the extracted variables by two independent investigators. Discrepancy was resolved by discussion with the third investigator. Results: We included 236 studies published from 1990 to 2024. The most commonly used method was electrical induction using a pacing wire cannulated through the external jugular vein into the right ventricle (n = 112), followed by transthoracic electrical induction (n = 28), asphyxiation (n = 20), electrical induction via two subcutaneous needles (n = 15), and balloon occlusion (n = 10). The mean and standard deviation (SD) of the untreated VF duration were 6.9 and 5.0 minutes, respectively. Female and male pigs were used exclusively in 52 and 45 studies, respectively; both sexes were used in 31 studies; 106 studies not reporting the sex. The mean weight of the pigs was 30.2 ± 12.4 kg in 209 studies, and the number of pigs used in the studies ranged from 2 to 271 with a median of 20 (interquartile range: 15–30) pigs in 223 studies. The four most commonly used drugs for anesthesia/preparation were ketamine (n = 145), propofol (n = 76), isoflurane (n = 68), and pentobarbital (n = 61), either alone or in combination. Higher current and voltage were used for less invasive methods. Conclusions: The two most common electric method to induce VF were invasive pacing at the right ventricle and non-invasive transthoracic electrical induction. Asphyxiation was the most common ischemic VF induction. The choice of the VF induction method depends on cost, expertise, feasibility, and the nature of the CPR intervention to be tested.

PO-05-150 A CASE OF QUINIDINE RESPONSIVE PURKINJE-MEDIATED POLYMORPHIC VENTRICULAR TACHYCARDIA

Polymorphic ventricular tachycardia (PMVT) has several different etiologies including ischemic ventricular fibrillation (VF), VF in coronary artery disease without active ischemia, idiopathic VF, and Torsades De Pointes (TdP). To review a case of quinidine responsive Purkinje mediated PMVT and the importance of considering alternative formulations of quinidine. N/A A 74-year-old female with no cardiac history presented with an inferior STEMI. An echocardiogram showed LV ejection fraction of 25% with multiple regional wall motion abnormalities. Left heart catheterization revealed multivessel disease for which she underwent CABG x 2 (LIMA to LAD, SVG to PDA) with intraoperative course complicated by VT requiring lidocaine drip. Ventricular arrhythmias initially seemed responsive to lidocaine; however, 4 days after CABG the patient was noted to have increased ectopic burden on telemetry and ultimately developed PMVT that required defibrillation (Fig 1A, 1B). Repeat catheterization revealed patent stents. Telemetry and ECGs were typical for Purkinje-mediated PMVT, so the patient was started on quinidine sulfate IR 400 mg every 8 hours with successful lidocaine wean and improvement in ectopic burden, with cessation of PMVT. Unfortunately, approximately 9 days after quinidine sulfate initiation the patient was noted to have rising LFTs with a normal abdominal ultrasound, platelet count, and white blood cell count, prompting discontinuation of quinidine. Without quinidine she had recurrence of PVCs that triggered bouts of PMVT (Fig 1C). PVC ablation was considered, targeting short-coupled PVCs in the border zone of scar that could be triggers for the patient’s PMVT. However, it was felt that the patient was too tenuous for ablation. Ultimately, she was trialed on quinidine gluconate ER formulation. This was started as once daily dosing and titrated up to 12-hour dosing with suppression of PVCs/PMVT and no further LFT derangements. The patient ultimately underwent ICD implant for secondary prevention and was discharged home. Purkinje mediated PMVT can occur in patients with coronary artery disease without acute ischemia. We describe a case of quinidine mediated hepatitis that was overcome by switching formulation from quinidine sulfate IR to quinidine gluconate ER. It is essential that hospitals, particularly arrhythmia referral centers, keep quinidine supplies in stock because this medication can be lifesaving during arrhythmic storms.

Prolonged repolarization in the early phase of ischemia is associated with ventricular fibrillation development in a porcine model.

Background: Repolarization prolongation can be the earliest electrophysiological change in ischemia, but its role in arrhythmogenesis is unclear. The aim of the present study was to evaluate the early ischemic action potential duration (APD) prolongation concerning its causes, expression in ECG and association with early ischemic ventricular fibrillation (phase 1A VF). Methods: Coronary occlusion was induced in 18 anesthetized pigs, and standard 12 lead ECG along with epicardial electrograms were recorded. Local activation time (AT), end of repolarization time (RT), and activation-repolarization interval (ARIc) were determined as dV/dt minimum during QRS-complex, dV/dt maximum during T-wave, and rate-corrected RT-AT differences, respectively. Patch-clamp studies were done in enzymatically isolated porcine cardiomyocytes. IK(ATP) activation and Ito1 inhibition were tested as possible causes of the APD change. Results: During the initial period of ischemia, a total of 11 pigs demonstrated maximal ARIc prolongation >10ms at 1 and/or 2.5min of occlusion (8 and 6 cases at 1 and 2.5min, respectively) followed by typical ischemic ARIc shortening. The maximal ARIc across all leads was associated with VF development (OR 1.024 95% CI 1.003-1.046, p = 0.025) and maximal rate-corrected QT interval (QTc) (B 0.562 95% CI 0.346-0.775, p < 0.001) in logistic and linear regression analyses, respectively. Phase 1A VF incidence was associated with maximal QTc at the 2.5min of occlusion in ROC curve analysis (AUC 0.867, p = 0.028) with optimal cut-off 456ms (sensitivity 1.00, specificity 0.778). The pigs having maximal QTc at 2.5min more and less than 450ms significantly differed in phase 1A VF incidence in Kaplan-Meier analysis (log-rank p = 0.007). In the patch-clamp experiments, 4-aminopyridine did not produce any effects on the APD; however, pinacidil activated IK(ATP) and caused a biphasic change in the APD with initial prolongation and subsequent shortening. Conclusion: The transiently prolonged repolarization during the initial period of acute ischemia was expressed in the prolongation of the maximal QTc interval in the body surface ECG and was associated with phase 1A VF. IK(ATP) activation in the isolated cardiomyocytes reproduced the biphasic repolarization dynamics observed in vivo, which suggests the probable role of IK(ATP) in early ischemic arrhythmogenesis.

Border zone repolarization duration as a predictor of early ischemic ventricular fibrillation

Ventricular fibrillation (VF) is a dangerous complication of acute myocardial infarction. Within an episode of acute ischemia, VFs are clustered into early (1A) and delayed (1B) phases based on different mechanisms. Our previous work demonstrated that prolonged repolarization duration in the border zone predisposed to VF development. A prolongation of action potential duration in the affected area is a frequent though not inevitable change at the very beginning of ischemia. However, the role of this phenomenon in arrhythmogenesis is unclear. The objective of the present study was to evaluate an association between early (1A phase) VF with repolarization duration in the border zone in an experimental porcine myocardial infarction model.Myocardial ischemia was induced in 19 anesthetized domestic pigs by ligation of the left anterior descending (n=9) or left circumflex (n=10) coronary arteries. Epicardial mapping was done with a 64‐lead epicardial array placed on the affected area with adjacent regions. Recordings were done in the baseline state and during ischemia with a custom‐designed system (16 bits; bandwidth 0.05 to 1000 Hz; sampling rate 4000 Hz). Local activation time (AT) and end of repolarization time (RT) were measured in each epicardial lead as the instants of a dV/dt minimum during QRS‑complex and dV/dt maximum during T‑wave, respectively. Activation‐repolarization interval (ARI, a surrogate for action potential duration) was taken as a rate‐corrected difference between RT and AT. Dispersion of repolarization (DOR) was calculated as a difference between the latest and earliest RTs throughout all recorded epicardial leads.Ten early VF episodes developed during first minutes of ischemia (1‐8 min). In logistic regression analysis, VF incidence was associated with ARI duration in the border zone (regression coefficient 1.02, 95% CI 1.003‐1.037, p=0.023), but not DOR (regression coefficient 1.005, 95%CI 0.990‐1.021, p=0.508) during first ten minutes of ischemia. In multivariate logistic regression analysis (baseline ARI duration vs the fact of ARI prolongation), VF incidence was associated only with the baseline ARI duration (regression coefficient 1.025, 95%CI 1.007‐1.044, p=0.005).Our data demonstrated the role of the prolonged repolarization duration in the development of 1A phase VF, which was independent of DOR and related to its baseline duration. Since the border zone is by definition at least partly accessible for blood flow, it may present a target for VF prevention therapy in a setting of acute myocardial ischemia.

Abstract 13802: J Waves Observed in More Than 3 Electrocardiographic Leads Predict the Presence of Organized Myocardial Fibrotic or Fat Change in Non Ischemic Survivors of Ventricular Fibrillation

Introduction: The distribution of J waves and the presence of organized left ventricular (LV) myocardial damage may be related in non ischemic survivors of ventricular fibrillation (VF). Hypothesis: We hypothesize that the distribution of J waves can predict the presence of myocardial damage such as fibrotic or fat change in non ischemic survivors of VF. Methods: We conducted a retrospective analysis of 16 survivors of VF (12 males; 60±15 years) without any histories of previous myocardial infarction and underwent cardiac CT in which no significant coronary stenosis were observed and/or MRI before implantation of a cardioverter defibrillator. Results: On ECG, 3 patients had atrial fibrillation and 12 had J waves. On CT and/or MRI, 7 patients had organized LV myocardial fibrotic and/or fat change. The mean corrected QT interval was 451±47 and 415±5 msec in patients with and without J waves (P=0.147) and 458±32 and 429±48 msec in patients with and without myocardial fibrotic and/or fat change (P=0.202), respectively. The distribution of J waves was presented in the table. Presence of the J waves observed more than 3 ECG leads (N=4) and presence of myocardial fibrotic and/or fat change (N=7) significantly correlated each other in the Fisher's exact test (P=0.019). Presence of myocardial fibrotic and/or fat change were significantly greater in patients with J waves observed more than 3 ECG leads than those with J waves observed less than 4 ECG leads (100% vs 25%, P=0009). Presence of J waves observed more than 3 ECG leads were also significantly greater in patients with myocardial fibrotic and/or fat change than those without (57% vs 0%, P=0009). Conclusions: In non ischemic survivors of VF, if J waves were observed more than 3 ECG leads, the frequency of LV myocardial fibrotic and/or fat change was significantly higher than those without. The distribution and numbers of ECG leads with J waves and the presence of myocardial fibrotic and/or fat change may be useful to predict non ischemic VF.

Arrhythmic storm from ischemic ventricular fibrillation treated with intravenous quinidine

We present a case who developed an acute right ventricular infarction. The leads demonstrating ST-segment elevation were different than those expected based on previous publications. We explain why this happened with the aid of 3-dimentional imaging.Our case then developed an arrhythmic storm caused by ischemic ventricular fibrillation (VF). Emergency revascularization failed and the VF-storm failed to respond to sedation, lidocaine and amiodarone but responded to intravenous quinidine.

Polymorphic ventricular tachycardia, ischaemic ventricular fibrillation, and torsade de pointes: importance of the QT and the coupling interval in the differential diagnosis.

Distinctive types of polymorphic ventricular tachycardia (VT) respond differently to different forms of therapy. We therefore performed the present study to define the electrocardiographic characteristics of different forms of polymorphic VT. We studied 190 patients for whom the onset of 305 polymorphic VT events was available. The study group included 87 patients with coronary artery disease who had spontaneous polymorphic VT triggered by short-coupled extrasystoles in the absence of myocardial ischaemia. This group included 32 patients who had a long QT interval but nevertheless had their polymorphic VT triggered by ectopic beats with short coupling interval, a subcategory termed 'pseudo-torsade de pointes] (TdP). For comparison, we included 50 patients who had ventricular fibrillation (VF) during acute myocardial infarction ('ischaemic VF' group) and 53 patients with drug-induced TdP ('true TdP' group). The QT of patients with pseudo-TdP was (by definition) longer than that of patients with polymorphic VT and normal QT (QTc 491.4 ± 25.2 ms vs. 447.3 ± 55.6 ms, P < 0.001). However, their QT was significantly shorter than that of patients with true TdP (QTc 564.6 ± 75.6 ms, P < 0.001). Importantly, the coupling interval of the ectopic beat triggering the arrhythmia was just as short during pseudo-TdP as during polymorphic VT with normal QT (359.1 ± 38.1 ms vs. 356.6 ± 39.4 ms, P = 0.467) but was much shorter than during true TdP (581.2 ± 95.3 ms, P < 0.001). The coupling interval helps discriminate between polymorphic VT that occurs despite a long QT interval (pseudo-TdP) and polymorphic arrhythmias striking because of a long QT (true TdP).

Metformin prevents ischaemic ventricular fibrillation in metabolically normal pigs.

Metformin is the drug most often used to treat type 2 diabetes. Evidence suggests that metformin may reduce mortality of individuals with type 2 diabetes, but the mechanism of such an effect is unknown and outcomes of metformin treatment in people without diabetes have not been determined. If metformin favourably affected mortality of non-diabetic individuals, it might have even broader therapeutic utility. We evaluated the effect of metformin on myocardial energetics and ischaemic ventricular fibrillation (VF) in metabolically normal pigs. Domestic farm pigs were treated with metformin (30mgkg-1day-1 orally for 2-3weeks; n=36) or received no treatment (n=37). Under anaesthesia, pigs underwent up to 90min low-flow regional myocardial ischaemia followed by 45min of reperfusion. Pigs were monitored for arrhythmia, monophasic action potential morphology, haemodynamics and myocardial substrate utilisation, AMP-activated protein kinase (AMPK) phosphorylation activity and ATP concentration. Death due to VF occurred in 12% of pigs treated with metformin compared with 50% of untreated controls (p=0.03). The anti-fibrillatory effect of metformin was associated with attenuation of action potential shortening in ischaemic myocardium (p=0.02) and attenuation of the difference in action potential duration between ischaemic and non-ischaemic regions (p<0.001) compared with untreated controls. Metformin had no effect on myocardial contractile function, oxygen consumption, or glucose or lactate utilisation. During ischaemia, however, metformin treatment amplified the activation of AMPK and preserved ATP concentration in myocardium compared with untreated controls (each p<0.05). Chronic treatment of metabolically normal pigs with metformin at a clinically relevant dose reduces mortality from ischaemic VF. This protection is associated with preservation of myocardial energetics during ischaemia. Maintenance of myocardial ATP concentration during ischaemia is likely to prevent action potential shortening, heterogeneity of repolarisation, and propensity for lethal arrhythmia. The findings suggest that metformin might be protective in non-diabetic individuals with coronary heart disease.

E-CPR as a bridge for decision in the cath lab

Aim: Refractory cardiogenic shock (CS) complicates 5–7% of cases with ST-elevation myocardial infarction (STEMI), and is a leading cause of hospital death after myocardial infarction.1 CS complicating acute myocardial infarction (AMI) continues to have a high mortality of 40–50% despite early revascularization and adjunctive therapies.2 Extracorporeal membrane oxygenation (ECMO) technology has advanced significantly and is readily available at the bedside. This is a viable option for short-term support in the setting of acute cardiac ischemia. According to the 2003 USA National Registry of cardiopulmonary resuscitation (CPR), in-hospital cardiac arrest has a poor prognosis with an overall survival to hospital discharge rate of 17% with conventional CPR.3 One of the most common causes of cardiac arrest is ventricular fibrillation (VF) secondary to ischemia, which carries an improved prognosis if successfully defibrillated, with the rate of survival to hospital discharge being 34%.3 In cases with refractory ischemic VF, definitive therapy with percutaneous coronary intervention (PCI) may not be possible without anoxic brain injury secondary to hemodynamic collapse. CPR was introduced in the 1960s as a lifesaving method in patients with cardiac arrest.3 To supplement CPR in select patients, ECMO is used successfully for witnessed in-hospital cardiac arrest.3 In the setting of an AMI, bridging to a revascularization procedure is important in improving neurological outcome and overall survival. We report the profile and the outcome of patients in refractory VF resistant to defibrillation on ECMO support. Subsequent to revascularization, the patient's cardiac rhythm converted back to sinus rhythm with a single defibrillation shock with excellent neurological recovery. Methods: Since January 2014, we have been reviewing patients who had suffered from progressive severe refractory CS post STEMI undergoing emergency PCI on percutaneous veno-arterial (VA)-ECMO support. Results: For 11 male patients (mean age 50 ± 18 years), the mean duration of support was 7 ± 4 days. Of these patients, 9 (81%) were weaned successfully from ECMO. However, two patients on ECMO support died: one due to massive gastrointestinal bleeding and the other due to septic shock. Three other patients also died; one due to occluded stent on third day post-ECMO removal, one due to intracranial hemorrhage on second day post-ECMO removal, and one due to septic shock on fourth day post-ECMO removal. The 30-day survival was 54% (6/11 patients) without any neurological deficit. Conclusion: VA-ECMO has shown to be an option to bridge patients in CS and/or refractory VF to allow for a successful revascularization procedure and ultimately good neurological and survival outcome.

Blockade of CaMKII depresses conduction preferentially in the right ventricular outflow tract and promotes ischemic ventricular fibrillation in the rabbit heart.

Calcium/calmodulin-dependent protein kinase II (CaMKII) regulates the principle ion channels mediating cardiac excitability and conduction, but how this regulation translates to the normal and ischemic heart remains unknown. Diverging results on CaMKII regulation of Na+ channels further prevent predicting how CaMKII activity regulates excitability and conduction in the intact heart. To address this deficiency, we tested the effects of the CaMKII blocker KN93 (1 and 2.75 μM) and its inactive analog KN92 (2.75 μM) on conduction and excitability in the left (LV) and right (RV) ventricles of rabbit hearts during normal perfusion and global ischemia. We used optical mapping to determine local conduction delays and the optical action potential (OAP) upstroke velocity (dV/dtmax). At baseline, local conduction delays were similar between RV and LV, whereas the OAP dV/dtmax was lower in RV than in LV. At 2.75 μM, KN93 heterogeneously slowed conduction and reduced dV/dtmax, with the largest effect in the RV outflow tract (RVOT). This effect was further exacerbated by ischemia, leading to recurrent conduction block in the RVOT and early ventricular fibrillation (at 6.7 ± 0.9 vs. 18.2 ± 0.8 min of ischemia in control, P < 0.0001). Neither KN92 nor 1 μM KN93 depressed OAP dV/dtmax or conduction. Rabbit cardiomyocytes isolated from RVOT exhibited a significantly lower dV/dtmax than those isolated from the LV. KN93 (2.75 μM) significantly reduced dV/dtmax in cells from both locations. This led to frequency-dependent intermittent activation failure occurring predominantly in RVOT cells. Thus CaMKII blockade exacerbates intrinsically lower excitability in the RVOT, which is proarrhythmic during ischemia.NEW & NOTEWORTHY We show that calcium/calmodulin-dependent protein kinase II (CaMKII) blockade exacerbates intrinsically lower excitability in the right ventricular outflow tract, which causes highly nonuniform chamber-specific slowing of conduction and facilitates ventricular fibrillation during ischemia. Constitutive CaMKII activity is necessary for uniform and safe ventricular conduction, and CaMKII block is potentially proarrhythmic.

Sodium nitroprusside enhanced cardiopulmonary resuscitation improves short term survival in a porcine model of ischemic refractory ventricular fibrillation

IntroductionSodium nitroprusside (SNP) enhanced CPR (SNPeCPR) demonstrates increased vital organ blood flow and survival in multiple porcine models. We developed a new, coronary occlusion/ischemia model of prolonged resuscitation, mimicking the majority of out-of-hospital cardiac arrests presenting with shockable rhythms. HypothesisSNPeCPR will increase short term (4-h) survival compared to standard 2015 Advanced Cardiac Life Support (ACLS) guidelines in an ischemic refractory ventricular fibrillation (VF), prolonged CPR model. MethodsSixteen anesthetized pigs had the ostial left anterior descending artery occluded leading to ischemic VF arrest. VF was untreated for 5min. Basic life support was performed for 10min. At minute 10 (EMS arrival), animals received either SNPeCPR (n=8) or standard ACLS (n=8). Defibrillation (200J) occurred every 3min. CPR continued for a total of 45min, then the balloon was deflated simulating revascularization. CPR continued until return of spontaneous circulation (ROSC) or a total of 60min, if unsuccessful. SNPeCPR animals received 2mg of SNP at minute 10 followed by 1mg every 5min until ROSC. Standard ACLS animals received 0.5mg epinephrine every 5min until ROSC. Primary endpoints were ROSC and 4-h survival. ResultsAll SNPeCPR animals (8/8) achieved sustained ROSC versus 2/8 standard ACLS animals within one hour of resuscitation (p=0.04). The 4-h survival was significantly improved with SNPeCPR compared to standard ACLS, 7/8 versus 1/8 respectively, p=0.0019. ConclusionSNPeCPR significantly improved ROSC and 4-h survival compared with standard ACLS CPR in a porcine model of prolonged ischemic, refractory VF cardiac arrest.

Conversion to Purkinje-Related Monomorphic Ventricular Tachycardia After Ablation of Ventricular Fibrillation in Ischemic Heart Disease.

Catheter ablation is an effective therapy for ventricular fibrillation (VF) arising from the Purkinje system in ischemic heart disease. However, some patients experience newly emergent monomorphic ventricular tachycardia (VT) after the ablation of VF. We evaluated the prevalence and mechanism of monomorphic VT after VF ablation. Twenty-one consecutive patients with primary VF because of ischemic heart disease who underwent catheter ablation were retrospectively analyzed. Twenty of 21 patients were in electrical storm. Ventricular premature contractions triggering VF arose from the left Purkinje system and were targeted for ablation. Before the ablation, 14 of 21 patients had only VF, and the other 7 had VF and concomitant monomorphic VT. Four of the 14 patients with only VF (29%) exhibited newly emergent monomorphic VT after VF ablation. Three of these patients had Purkinje-related VTs, which were successfully eliminated by the ablation of a Purkinje network located in the same low-voltage area as the site of prior successful VF ablation. During a median follow-up of 28 months (interquartile range, 16-68 months), VF recurred in 6 of 21 patients (29%); however, there were neither electrical storms nor monomorphic VT, and all recurring arrhythmias were controlled by medical therapy alone. Over one fifth of patients with primary ischemic VF experienced newly emergent Purkinje-related monomorphic VT after VF ablation. The circuit of the monomorphic VT associated with the Purkinje network was located in the same low-voltage area as the Purkinje tissue that triggered VF and could be suppressed by additional ablation.

P130: Incidence and characteristics of ventricle fibrillation in patients with ST-elevation myocardial infarction in a suburban pre-hospital setting

Introduction:Background: Ischemic ventricular fibrillation (VF) is highly related to ST elevation myocardial infarction (STEMI). Pre-hospital STEMI patients have been shown to also develop VF during ambulance transport. However, there is limited literature exploring the characteristics of this specific population of VF. Objective: To determine the incidence of pre-hospital VF, and evaluate some demographic and electrocardiogram (ECG) characteristics of STEMI patients having VF while transported by ambulance in a Quebec suburban pre-hospital setting. Methods: A retrospective study from 8th August 2006 to 6th December 2015 of 937 STEMI patients transported by ambulance in the Chaudiere-Appalaches region, south of Quebec City. Destination for treatment was either Catherization Laboratory (CL) or the nearest Emergency Department (ED) for reperfusion treatment and was mainly based upon a maximum transport time of 60 minutes, from the first confirmed STEMI-ECG to the CL. Demographics and ECG characteristics were extracted from the patients care records. SPSS-20 was used for descriptive statistics. Results: 937 patients (259 women &amp; 678 men) diagnosed with STEMI were included in the study. Patients were regrouped in V1-V4 leads STEMI (336; 35.9%) and in other leads STEMI (651; 64.1%). 52 (5.55%) of all STEMI patients had FV during ambulance transport. There were 10 women (27,4%) and 42 men (72,6%). Of these, 28 had V1-V4 STEMI (28/336; 8.33%) while 24 had other leads STEMI (24/651; 3.69%). Relative risk of FV is higher (225%) with V1-V4 STEMI compared to other leads STEMI. Regarding age groups, patients from 60 to 70 years old represent 38.4% (20/52) of FV for 25.7% (241/937) of STEMI patients while those over 80 years old had 3.85% (2/52) of FV, but were 17% (159/937) of all STEMI patients. Men seem also more at risk for FV (16/20) especially between 60 and 70 years old compare to other age group. Conclusion: In this suburban area, VF occurred in 5.55% of STEMI patient’s transported by ambulance. STEMI patients over 80 years old had a low rate of FV. Being a man, 60 to 70 years old, with a STEMI located in V1-V4, seems to be associated with a higher risk of VF. More studies are needed to confirm these results and explore other characteristics associated to pre-hospital VF.

Post-infarction ventricular fibrillation mechanisms: Insights from combined body surface potential mapping and late gadolinium-enhanced CMR

Background The mechanisms involved in the sustenance of scarrelated ventricular fibrillation (VF) are poorly understood. Recent developments in body surface potential mapping (BSM) now enable non-invasive, real-time and wholeheart assessment of cardiac activation during VF. We sought to analyze the relationships between focal/reentrant activities during VF and scar characteristics on late gadonlinium-enhanced (LGE) CMR in patients with ischemic VF. Methods 7 patients with history of prior myocardial infarction who presented a VF episode underwent CMR prior to ICD implantation. LGE imaging was performed on a 1.5T system (Avanto, Siemens Medical Solutions, Erlangen, Germany) 15 min after the injection of 0.2 mmol/Kg gadoterate meglumine, using an inversion recovery-prepared and respiratory navigated 3D Turbo FLASH sequence with fat saturation, in order to acquire a whole heart volume at high spatial resolution (pixel size 1.25 × 1.25

Acute right ventricular myocardial injury and sudden cardiac arrest in a patient with persistent spontaneous coronary vasospasm.

Coronary vasospasm is a rare diagnosis resulting in sudden arrhythmic cardiac arrest. We report a case of a healthy, non-smoking elderly woman resuscitated from arrhythmic cardiac arrest. She had persistent spontaneous coronary vasospasm, leading to right ventricular myocardial injury and failure, and shock. She responded quickly to intravenous normal saline bolus infusion, but had irreversible neurological sequelae. Additionally, she had atrial fibrillation preceding ischemic ventricular fibrillation, a rare finding in coronary vasospasm-related cardiac arrest. We suggest immediate coronary angiography of patients in sudden arrhythmic cardiac arrest with acute right ventricular failure for a prompt, accurate diagnosis and appropriate management of the coronary vasospasm.

Abstract 12911: Metformin Preserves ATP Concentration, Attenuates Action Potential Shortening, and Prevents Ventricular Fibrillation During Low-flow Ischemia in Normal Hearts

Introduction: Metformin (MET) is the most common drug used to treat type 2 diabetes, in part because it is believed to reduce cardiovascular mortality. However, it is unknown whether MET provides protection from ischemic ventricular fibrillation (VF) in the normal heart. In a region of ischemic myocardium, reduced energy charge causes ATP-sensitive potassium channels to open, shortening the action potential (AP). The resulting dispersion of AP duration and refractoriness may predispose to VF. We determined effects of MET on myocardial ATP concentration, AP, and VF during regional ischemia in metabolically normal pigs. Methods: Normal domestic pigs were treated with a clinically relevant dose of MET (30 mg/kg/d, n=25) for 2-3 weeks and compared with untreated controls (CTL, n=23). Under anesthesized, open-chest conditions, phospho-AMP activated protein kinase (pAMPK, Thr172) was measured in myocardial biopsies taken before ischemia (n=8 each group). Low-flow ischemia was induced by 50% LAD flow reduction. [ATP] was measured in myocardial biopsies at 15 min ischemia (MET n=8, CTL n=7). Monophasic AP was recorded at baseline and at 15 min ischemia. Survival free of VF was observed during 90 min of ischemia and 45 min reperfusion. Results: pAMPK was 85% greater in MET than in CTL (p&lt;0.001), establishing a myocardial effect of MET prior to ischemia. MET had no effect on non-ischemic AP duration. At 15 min ischemia, [ATP] was higher in MET than CTL (4.1 vs 3.5 μmol/g, p=0.039), with less AP shortening from baseline in MET (4±2%) than in CTL (13±2%, p&lt;0.001). Survival free of VF was greater in MET pigs than CTL (Figure). Conclusions: Chronic treatment with a clinically relevant dose of MET activates AMPK, preserves [ATP] and prevents AP shortening during ischemia, and diminishes the propensity for ischemic VF in metabolically normal pigs. Based on these findings, MET may have therapeutic utility beyond type 2 diabetes, extending to ischemic protection of the normal heart.

The Effect of Dobutamine on Susceptibility to Ischemia‐Induced Ventricular Fibrillation in the Isolated Rat Heart

Sudden cardiac death due to ventricular fibrillation (VF) continues to be a major cause of mortality, but the triggers of VF in ischemia remain poorly understood. Our hypothesis is that VF is triggered in myocardial ischemia as a result of ATP depletion, which causes ionic imbalance and electrical dysfunction that creates an arrhythmogenic substrate. The purpose of this study was to test this hypothesis by determining the effect of increasing cardiac ATP consumption on susceptibility to VF using a classical inotrope, dobutamine.Isolated rat hearts (n=12 per group) were perfused in the Langendorff mode with modified Krebs containing 3 mM K+. Dobutamine or vehicle was locally infused in a randomized and blinded manner to achieve a concentration of dobutamine of 3µM. After a further 15 min, regional ischemia was induced by coronary artery occlusion and maintained for 30 min. VF was determined from the ECG, and cardiac function was evaluated using an intraventricular balloon.Dobutamine increased heart rate and left ventricular developed pressure compared to controls as expected. The incidence of VF (75% vs 67%; P=NS) and time to onset of VF (892±68s vs 730±80s; P=NS) were similar in control and dobutamine groups respectively. Dobutamine reduced ischemic contracture, with end diastolic pressure 36±6 vs 15±3 mmHg after 25 min ischemia in control and dobutamine groups respectively (P&lt;0.05). Thus, although β1 stimulation by dobutamine increased cardiac work, it did not increase susceptibility to ischemic VF.

J波と虚血性心室細動の関係―冠攣縮狭心症における検討―

J波と虚血性心室細動の関係―冠攣縮狭心症における検討―

Does the combination of hyperkalemia and KATP activation determine excitation rate gradient and electrical failure in the globally ischemic fibrillating heart?

Ventricular fibrillation (VF) in the globally ischemic heart is characterized by a progressive electrical depression manifested as a decline in the VF excitation rate (VFR) and loss of excitability, which occur first in the subepicardium (Epi) and spread to the subendocardium (Endo). Early electrical failure is detrimental to successful defibrillation and resuscitation during cardiac arrest. Hyperkalemia and/or the activation of ATP-sensitive K(+) (KATP) channels have been implicated in electrical failure, but the role of these factors in ischemic VF is poorly understood. We determined the VFR-extracellular K(+) concentration ([K(+)]o) relationship in the Endo and Epi of the left ventricle during VF in globally ischemic hearts (Isch group) and normoxic hearts subjected to hyperkalemia (HighK group) or a combination of hyperkalemia and the KATP channel opener cromakalim (HighK-Crom group). In the Isch group, Endo and Epi values of [K(+)]o and VFR were compared in the early (0-6 min), middle (7-13 min), and late (14-20 min) phases of ischemic VF. A significant transmural gradient in VFR (Endo > Epi) was observed in all three phases, whereas a significant transmural gradient in [K(+)]o (Epi > Endo) occurred only in the late phase of ischemic VF. In the Isch group, the VFR decrease and inexcitability started to occur at much lower [K(+)]o than in the HighK group, especially in the Epi. Combining KATP activation with hyperkalemia only shifted the VFR-[K(+)]o curve upward (an effect opposite to real ischemia) without changing the [K(+)]o threshold for asystole. We conclude that hyperkalemia and/or KATP activation cannot adequately explain the heterogeneous electrical depression and electrical failure during ischemic VF.

Administration of Amiodarone During Resuscitation Is Associated with Higher Tumor Necrosis Factor-α Levels in the Early Postarrest Period in the Swine Model of Ischemic Ventricular Fibrillation

To compare the early postarrest inflammatory cytokine response between animals administered amiodarone (AMIO) and lidocaine (LIDO) intra-arrest during resuscitation from ventricular fibrillation (VF). Domestic swine (n=32) were placed under general anesthesia and instrumented before spontaneous VF was induced by balloon occlusion of the left anterior descending coronary artery. After 7 min of VF, standard ACLS resuscitation was performed and animals were randomized to either bolus AMIO (5 mg/kg, n=13) or LIDO (1 mg/kg, n=14) for recurrent or refractory VF. A non-antiarrhythmic (n=5) was also used for comparison. Following return of spontaneous circulation (ROSC), tumor necrosis factor (TNF)-α levels were drawn at 30 and 60 min. Groups were comparable with respect to prearrest hemodynamics and resuscitation variables. In the postarrest period, the LIDO and non-antiarrhythmic group demonstrated virtually identical TNF-α response trajectories. However, TNF-α levels were significantly higher in AMIO- than LIDO-treated animals at 30 min (geometric mean 539 versus 240 pg/mL, 2.2-fold higher, 95% confidence interval [CI] 1.3-3.8-fold higher, P=0.003) and at 60 min (geometric mean 570 versus 204 pg/mL, 2.8-fold higher, 95% CI 1.1-7.0-fold higher, P=0.03). Significant differences in the postarrest TNF-α levels were observed between animals treated with AMIO as compared to those treated with LIDO. Improved rates of ROSC seen with AMIO may come at the expense of a heightened proinflammatory state in the postcardiac arrest period.