Induction Of Ventricular Fibrillation Research Articles

Pharmacological and toxicological activity of RSD921, a novel sodium channel blocker

BackgroundRSD921, the R,R enantiomer of the kappa (k) agonist PD117,302, lacks significant activity on opioid receptors. MethodsThe pharmacological and toxicological actions were studied with reference to cardiovascular, cardiac, antiarrhythmic, toxic and local anaesthetic activity. ResultsIn rats, dogs and baboons, RSD921 dose-dependently reduced blood pressure and heart rate. In a manner consistent with sodium channel blockade it prolonged the PR and QRS intervals of the ECG. Furthermore, in rats and NHP, RSD921 increased the threshold currents for induction of extra-systoles and ventricular fibrillation (VFt), and prolonged effective refractory period (ERP). In rats, RSD921 was protective against arrhythmias induced by electrical stimulation and coronary artery occlusion. Application of RSD921 to voltage-clamped rat cardiac myocytes blocked sodium currents. RSD921 also blocked transient (ito) and sustained (IKsus) outward potassium currents, albeit with reduced potency relative to sodium current blockade. Sodium channel blockade due to RSD921 in myocytes and isolated hearts was enhanced under ischaemic conditions (low pH and high extracellular potassium concentration). When tested on the cardiac, neuronal and skeletal muscle forms of sodium channels expressed in Xenopus laevis oocytes, RSD921 produced equipotent tonic block of sodium currents, enhanced channel block at reduced pH (6.4) and marked use-dependent block of the cardiac isoform. RSD921 had limited but quantifiable effects in subacute toxicology studies in rats and dogs. Pharmacokinetic analyses were performed in baboons. Plasma concentrations producing cardiac actions in vivo after intravenous administration of RSD921 were similar to the concentrations effective in the in vitro assays utilized. ConclusionsRSD921 primarily blocks sodium currents, and possesses antiarrhythmic and local anaesthetic activity.

Novel patterns of left ventricular mechanical activity during experimental cardiac arrest in pigs.

We conducted an experimental study to evaluate the presence of coordinated left ventricular mechanical myocardial activity (LVMA) in two types of experimentally induced cardiac arrest: ventricular fibrillation (VF) and pulseless electrical activity (PEA). Twenty anesthetized domestic pigs were randomized 1:1 either to induction of VF or PEA. They were left in nonresuscitated cardiac arrest until the cessation of LVMA and microcirculation. Surface ECG, presence of LVMA by transthoracic echocardiography and sublingual microcirculation were recorded. One minute after induction of cardiac arrest, LVMA was identified in all experimental animals. In the PEA group, rate of LVMA was of 106+/-12/min. In the VF group, we identified two patterns of LVMA. Six animals exhibited contractions of high frequency (VFhigh group), four of low frequency (VFlow group) (334+/-12 vs. 125+/-32/min, p<0.001). A time from cardiac arrest induction to asystole (19.2+/-7.2 vs. 7.3+/-2.2 vs. 8.3+/-5.5 min, p=0.003), cessation of LVMA (11.3+/-5.6 vs. 4.4+/-0.4 vs. 7.4+/-2.9 min, p=0.027) and cessation of microcirculation (25.3+/-12.6 vs. 13.4+/-2.4 vs. 23.2+/-8.7 min, p=0.050) was significantly longer in VFlow group than in VFhigh and PEA group, respectively. Thus, LVMA is present in both VF and PEA type of induced cardiac arrest and moreover, VF may exhibit various patterns of LVMA.

Sodium Nitroprusside Enhanced CPR and intra-CPR Hypothermia

<span style=font-size:11.0pt;font-family: times= new= roman,serif;mso-fareast-font-family:times= roman=>1. Abstract <span style=font-size:10.0pt;font-family: times= new= roman,serif;mso-fareast-font-family:times= roman=>1.1. <span lang=FR style=font-size:10.0pt; font-family: times= new= roman,serif;mso-ansi-language:fr=>Objective : Therapeutic Hypothermia (TH) is thought to improve neurologically intact survival when applied after Return of Spontaneous Circulation (ROSC) is achieved in patients who suffer a cardiac arrest. Intra-CPR cooling may accelerate the time to reach TH and thus enhance its neurological benefit. Sodium Nitroprusside Enhanced Cardiopulmonary Resuscitation (SNPeCPR) has been shown to accelerate intra-CPR cooling compared to standard CPR. The aim of this study is to assess which method of therapeutic hypothermia is the most efficient in decreasing brain temperature during SNPeCPR. <span style=font-size:10.0pt;font-family: times= new= roman,serif;mso-fareast-font-family:times= roman=>1.2. <span style=font-size:10.0pt;font-family: times= new= roman,serif=>Methods: <span style=font-size:10.0pt; font-family: times= new= roman,serif=>This study included 24 intubated and anesthetized swine. After induction of Ventricular Fibrillation (VF), animals were randomized to one of the following groups: 500cc cold saline infusion (group A), 500cc cold saline infusion plus surface cooling with ice packs (group B), surface cooling only (group C) or control/no cooling method applied (group D). After 10 minutes of VF, CPR was initiated. One minute after the initiation of CPR, the randomized intervention was initiated and abdominal binding was applied. SNP (2 mg) was administered at minutes 1, 4 and 8. Animals were defibrillated at minute10. <span style=font-size:10.0pt;font-family: times= new= roman,serif;mso-fareast-font-family:times= roman;color:black;= mso-themecolor:text1=>1.3. Results: Within 4 minutes of CPR, animals that received intravenous cold saline (Group A and Group B) had decreased their brain temperature by 0.5 <span style=font-size:10.0pt; font-family: times= new= roman,serif;color:red;mso-ansi-language:pt=> ° C lower compared to the groups that had not (Group C and Group D). Group B presented a superior heat exchange rate from blood to skin compared to group A. <span style=font-size:10.0pt;font-family: times= new= roman,serif;mso-fareast-font-family:times= roman=>1.4. <span lang=FR style=font-size:10.0pt; font-family: times= new= roman,serif;mso-ansi-language:fr=>Conclusion : It was observed that cold saline infusion during SNPeCPR accelerates cooling of the brain. Ice packs work synergistically by optimizing heat transfer from the blood to the skin. Further studies will assess the potential neurologic benefit of the combination of SNPeCPR with intra-CPR infusion of cold saline. <span style=font-size:11.0pt;font-family: times= new= roman,serif;mso-fareast-font-family:times= roman=>2. Keywords: Cardiac Arrest; Cardiopulmonary Resuscitation; Therapeutic Hypothermia

Early repolarization is involved in ventricular fibrillation in patients with variant angina.

Variant angina (VA) is caused by reversible coronary artery spasm, which is characterized by chest pain with ST segment elevations on a standard 12-lead electrocardiogram (ECG) at rest. VA attack often causes lethal ventricular arrhythmia. The early repolarization (ER) pattern is associated with ventricular fibrillation (VF). However, whether the ER pattern is involved in VF in patients with VA is not known. We investigated the association between the ER pattern and VF in patients with VA. Fifty patients underwent induction of ST elevation on 12-lead ECGs with total or nearly total occlusion by provocation test (VA patients). Twelve of these patients underwent induction of VF or had documented VF before hospital admission (VF occurrence group). The J-wave morphology was characterized as exhibiting notching or slurring. The amplitude of each J wave was measured manually with amplified waveforms. ER patterns were observed significantly more often in the VF occurrence group than in the non-VF occurrence group (P=0.007). The J-wave amplitude was significantly higher in the VF occurrence group compared with the non-VF occurrence group (P=0.02). Univariate analyses suggested that age, smoking, and ER patterns were associated with VF. Upon multivariate analyses, age (odds ratio [OR]=0.880; 95% confidence interval [CI]: 0.794-0.975; P=0.014) and ER patterns (OR=8.937; 95% CI:1.661-48.06; P=0.011) predicted VF independently. These data suggest that an ER pattern in VA patients is a risk factor for VF. The ER pattern may be one of the useful factors for adaptation of implantation of implantable cardioverter-defibrillator in patients with coronary spasm-induced VF.

Defibrillation testing is mandatory in patients with subcutaneous implantable cardioverter–defibrillator to confirm appropriate ventricular fibrillation detection

The subcutaneous implantable cardioverter-defibrillator (S-ICD) remains a new technology requiring accurate assessment of the various aspects of its functioning. Isolated cases of delayed sensing of ventricular arrhythmia have been described. The purpose of this multicenter study was to assess the quality of sensing during induced ventricular fibrillation (VF). One hundred thirty-seven patients underwent induction of VF at the end of the S-ICD implantation. VF induction was successful in 133 patients (97%). Mean time to first therapy was 16.2 ± 3.1 seconds, with a substantial range from 12.5 to 27.0 seconds. Four different detection profiles were arbitrarily defined: (1) optimal detection (n = 39 [29%]); (2) undersensing with moderate prolongation of time to therapy (<18 seconds; n = 68 [51%]); (3) undersensing with significant prolongation of the time to therapy (>18 seconds; n = 19 [14%]); and (4) absence of therapy or prolonged time to therapy related to noise oversensing (n = 7 [6%]). In some of the patients in the last group, despite induction of VF the initial counter was never filled, the device did not charge the capacitors, and the shock was not delivered because of a sustained diagnosis of noise (n = 5). A manual shock by the device or an external shock had to be delivered to restore the sinus rhythm. Our study demonstrated a marked sensing delay leading to prolonged time to therapy in a large number of S-ICD patients. A few worrisome cases of noise oversensing inhibiting the therapies were detected. These results support the need for systematic intraoperative defibrillation testing.

Reflected Conduction Attributed to Sodium Channel Distribution Within Cardiomyocytes: A Possible Mechanism of Ventricular Fibrillation Induction in Brugada Syndrome

Brugada syndrome is characterized by the ECGs with both a right bundle-branch block pattern and ST-segment elevation in the right precordial leads (V1-V3) and by the higher incidence of sudden cardiac death due to ventricular tachycardia/fibrillation. It is commonly believed that the lethal arrhythmias are elicited by the closely coupled premature ventricular contractions via the reflected conduction (i.e., phase-2 reentry) mechanism. Although loss of function mutation in cardiac sodium (Na) channels have been linked to Brugada syndrome, the relation between the loss of function in Na channels and the arrhythmogenic mechanism remains unclear. We have recently reported that the action potential propagation was greatly affected by the subcellular distribution of Na channels in a physiologically-accurate myofiber model where myocytes were electrically coupled with both gap junctions and intercellular cleft conductor (electric field mechanism). Here, we extended the simulation to the initiation of reflected conduction in Brugada syndrome. We conducted computer simulations of action potential propagation in the myofiber model, and investigated the effects of subcellular distributions of Na channels on the development of reflected conduction. We found that the myofiber model with specific subcellular Na channel distribution (all Na channels were distributed only in the intercalated disks and there were no Na channels along the lateral side of each myocyte) resulted in early repolarization followed by reflected conduction. Subcellular Na channel distribution might be responsible for fibrillation induction in Brugada syndrome.

Right Ventricular Outflow Tract Electroanatomical Abnormalities Predict Ventricular Fibrillation Inducibility in Brugada Syndrome

Electroanatomical mapping has demonstrated abnormal bipolar electrograms at the anterior aspect of the right ventricular outflow tract (RVOT) epicardium along with histopathologic evidence of fibrosis in patients with Brugada syndrome (BrS).1,2 These epicardial abnormalities are believed to serve as the electric substrate for ventricular fibrillation (VF) initiation and maintenance in BrS.1,2 We have recently demonstrated that patients with BrS display wide areas of endocardial unipolar voltage abnormalities that possibly reflect epicardial structural abnormalities at the free wall of the RVOT.3 We hypothesized that electroanatomical abnormalities detected by high-density endocardial unipolar voltage mapping at the RVOT predict VF inducibility during programmed ventricular stimulation (PVS). The study population consisted of 17 asymptomatic probands (15 males, 37.3±10.8 years) with spontaneous type 1 BrS ECG pattern referred for risk stratification with PVS. A comprehensive evaluation including late gadolinium enhancement cardiac magnetic resonance imaging ruled out structural heart disease in all patients. The study was approved by the Hospital Ethics Committee and written informed consent was obtained from all patients. High-density electroanatomical mapping of the RVOT during sinus rhythm was performed as described previously (Methods in the Data Supplement).3 In brief, a minimum of 800 points were sampled to …

Antiarrhythmic effect of antazoline in experimental models of acquired short- and long-QT-syndromes.

Antazoline is a first-generation antihistamine with antiarrhythmic properties. This study examines potential electrophysiological effects of antazoline in short-QT-syndrome (SQTS) and long-QT-syndrome (LQTS). Sixty-five rabbit hearts were Langendorff-perfused. Action potential duration at 90% of repolarization (APD90), QT-interval, spatial dispersion (DISP), and effective refractory period (ERP) were measured. The IK, ATP-opener pinacidil (1 µM, n = 14) reduced APD90 (-14 ms, P < 0.01), QT-interval (-14 ms, P < 0.01), and ERP (-11 ms, P < 0.01), thus simulating acquired SQTS. Additional infusion of 20 µM antazoline prolonged repolarization. Under baseline conditions, ventricular fibrillation (VF) was inducible in 5 of 14 hearts (10 episodes) and in 5 of 14 pinacidil-treated hearts (21 episodes, P = ns). Antazoline significantly reduced induction of VF (0 episodes, P < 0.05 each). Further 17 hearts were perfused with 100 µM sotalol and 17 hearts with 300 µM erythromycin to induce acquired LQTS2. In both groups, prolongation of APD90, QT-interval, and ERP was observed. Spatial dispersion was increased (sotalol: +26 ms, P < 0.01; erythromycin: +31 ms, P < 0.01). Additional infusion of antazoline reduced DISP (sotalol: -22 ms, P < 0.01; erythromycin: -26 ms, P < 0.01). Torsade de pointes (TdP) occurred in 6 of 17 sotalol-treated (22 episodes, P < 0.05 each) and in 8 of 17 erythromycin-treated hearts (96 episodes P < 0.05 each). Additional infusion of antazoline completely suppressed TdP in both groups (P < 0.05 each). Acquired LQTS3 was induced by veratridine (0.5 µM, n = 17) and similar results were obtained (APD90: +24 ms, P < 0.01, QT-interval: +58 ms, P < 0.01, DISP: +38 ms, P < 0.01). Torsade de pointes occurred in 10 of 17 hearts (41 episodes, P < 0.05 each). Antazoline significantly reduced TdP (2 of 17 hearts, 4 episodes, P < 0.05 each). Antazoline significantly reduced induction of VF in an experimental model of acquired SQTS. In three experimental models of acquired LQTS, antazoline effectively suppressed TdP.

Single Ventilation during Cardiopulmonary Resuscitation Results in Better Neurological Outcomes in a Porcine Model of Cardiac Arrest.

PurposeRecent basic life support (BLS) guidelines recommend a 30:2 compression-to-ventilation ratio (CV2) or chest compression-only cardiopulmonary resuscitation (CC); however, there are inevitable risks of interruption of high-quality cardiopulmonary resuscitation (CPR) in CV2 and hypoxemia in CC. In this study, we compared the short-term outcomes among CC, CV2, and 30:1 CV ratio (CV1).Materials and MethodsIn total, 42 pigs were randomly assigned to CC, CV1, or CV2 groups. After induction of ventricular fibrillation (VF), we observed pigs for 2 minutes without any intervention. Thereafter, BLS was started according to the assigned method and performed for 8 minutes. Defibrillation was performed after BLS and repeated every 2 minutes, followed by rhythm analysis. Advanced cardiac life support, including continuous chest compression with ventilation every 6 seconds and intravenous injection of 1 mg epinephrine every 4 minutes, was performed until the return of spontaneous circulation (ROSC) or 22 minutes after VF induction. Hemodynamic parameters and arterial blood gas profiles were compared among groups. ROSC, 24-hour survival, and neurologic outcomes were evaluated at 24 hours.ResultsThe hemodynamic parameters during CPR did not differ among the study groups. Partial pressure of oxygen in arterial blood and arterial oxygen saturation were lowest in the CC group, compared to those in the other groups, during the BLS period (p=0.002 and p<0.001, respectively). The CV1 groups showed a significantly higher rate of favorable neurologic outcome (swine CPC 1 or 2) than the other groups (p=0.044).ConclusionCPR with CV1 could promote better neurologic outcome than CV2 and CC.

Tpeak-Tend interval during therapeutic hypothermia can predict upcoming ventricular fibrillation in subjects with aborted arrhythmic sudden cardiac death: 3-years follow-up results.

Prolonged Tpeak-Tend interval has been shown to be markers of arrhythmogenesis in various cardiac disorders. However, its dynamicity is one of the obstacles to predict fatal ventricular arrhythmia. This study investigated whether Tpeak-Tend interval during therapeutic hypothermia (TH) is associated with ventricular fibrillation (VF) inducibility and clinical arrhythmia in subjects with aborted arrhythmic sudden cardiac death (SCD). The study group included 31 patients (24 males, age 39.1 ± 17.6 years) presenting with arrhythmic SCD in whom Tpeak-Tend interval and J-wave amplitude were measured in electrocardiogram (ECG) of the earliest medical contact and during TH; these patients underwent programmed ventricular stimulation. The summation of J-wave amplitude and QTc interval increased during TH. However, it was not associated with VF inducibility. Patients with inducible VF showed a small Tpeak-Tend interval dispersion in the baseline 12-lead ECG (68.8 ± 24.7 vs. 94.0 ± 55.6 ms, P = 0.044) and a marked increase of the dispersion during the TH (36.2 ± 51.2 vs. -6.1 ± 45.5 ms, P = 0.039). Twenty-four patients underwent implantable cardioverter defibrillator (ICD) implantation. Among them, the patients with long QTc, Tpeak-Tend, and precordial Tpeak-Tend during the TH developed VF more frequently (QTc, 511.9 ± 53.71 ms vs. 566.5 ± 56.08 ms, P = 0.038; Tpeak-Tend interval, 145.6 ± 38.4 ms vs. 185.7 ± 49.95 ms, P = 0.048; precordial Tpeak-Tend interval, 139.3 ± 35.11 ms vs. 185.7 ± 49.95 ms, P = 0.018). The initial VF inducibility was not related with the VF development in follow-up. In patients with aborted arrhythmic SCD, long Tpeak-Tend interval and QTc interval during TH could predict VF development in their follow-up.

Tea polyphenols down-regulate JNK phosphorylation to inhibit neuron apoptosis in rats with cardiac arrest

To study the effect of tea polyphenols (TP) on c-Jun N-terminal kinase 1/2 (JNK1/2) phosphorylation and cell apoptosis in brain tissues in rats with cardiac arrest (CA) following cardiopulmonary resuscitation (CPR). Healthy male Sprague-Dawley (SD) rats were randomly divided into sham group (n = 6), CA group (n = 12), and TP group (n = 12). The rats in CA and TP groups were induced ventricular fibrillation (VF) via esophagus stimulation with alternating current. Five minutes after CA, CPR was performed. Once restoration of spontaneous circulation (ROSC) was gained, normal saline (NS) and TP were injected intravenously in CA and TP groups with 10 mg/kg, respectively. Cortex of 6 rats in each group was harvested at 12 hours and 72 hours after ROSC. Cortex of sham group was harvested at 72 hours after operation without VF induction. The expressions of phosphorylated JNK1/2 (p-JNK1/2), JNK1/2, caspase-3, Bax and Bcl-2 were measured by Western Blot. Cell apoptosis was detected by TdT-mediated dUTP nick end labeling (TUNEL), and p-JNK/TUNEL double positive cells were detected by fluorescence double staining. Compared with sham group, the expressions of p-JNK, caspase-3 and Bax were increased, the expression of Bcl-2 was declined, and the apoptotic cells were significantly increased at 72 hours after ROSC in CA group. Compared with CA group, the phosphorylation of JNK was significantly declined at 12 hours and 72 hours after ROSC in TP group (the ratio of p-JNK1/2 and JNK1/2: 3.200±0.060 vs. 5.700±0.210, 1.400±0.060 vs. 5.400±0.090, both P < 0.05), the expressions of caspase-3 and Bax were decreased [caspase-3 (gray value): 42.00±5.23 vs. 54.00±7.84, 38.74±4.60 vs. 58.68±7.19; Bax (gray value): 38.04±6.21 vs. 68.76±6.08, 58.84±7.99 vs. 70.03±7.36, all P < 0.05], the expression of Bcl-2 was increased (gray value: 37.36±3.11 vs. 28.47±7.46, 48.78±6.55 vs. 29.54±3.13, both P < 0.05); the cell apoptosis rate was reduced at 72 hours [(31.14±4.51)% vs. (45.87±3.95)%, P < 0.01], and p-JNK/TUNEL double positive cells/TUNEL cells ratio was significantly decreased (10.00±0.85 vs. 52.70±3.05, P < 0.01). The inhibition of neuron apoptosis caused by TP after CPR in rats with CA is related to the inhibition of JNK1/2 phosphorylation.

P4-5 - A Case Report of Left Ventricular Noncompaction With Syncope Due to Adams-Stokes Syndrome, Requiring ICD Implantation

Objective: I reported a case diagnosed as left ventricular noncompaction (LVNC) after Adams-Stokes syndrome complicated with traumatic subarachnoid hemorrhage and acute subdural hematoma. Case Presentation: A 78-year-old man with family history of sudden death was diagnosed as atrial fibrillation and suspected as dilated cardiomyopathy by home doctor. After he fell down and had head trauma because of syncope during walking without symptom, he got seizure at home, transferred to our hospital by helicopter emergency medical service. Head CT showed traumatic subarachnoid hemorrhage and acute subdural hematoma, and Adams-Stokes syndrome was suspected. His echocardiography showed left ventricular ejection fraction about 30% with diffuse hypokinesis, and remarkable trabeculations at lateral wall with blood flow confirmed by color Doppler. Cardiac magnetic resonance showed trabeculations at lateral wall with late gadlinium enhancement and noncompaction to compaction ratio above 2. Considering these findings, we diagnosed as LVNC. Holter electrocardiography showed non-sustained ventricular tachycardia, and electrophysiological study resulted in induction of ventricular tachycardia and ventricular fibrillation. We decided ICD implantation with judgement as class I. He was discharged with carvedilol 10 mg, perindopril 6 mg, spironolactone 25 mg. Conclusion: I experienced a rare case of LVNC after syncope due to Adams-Stokes syndome, requiring ICD implantation.

Mechanically Induced Ectopy via Stretch-Activated Cation-Nonselective Channels Is Caused by Local Tissue Deformation and Results in Ventricular Fibrillation if Triggered on the Repolarization Wave Edge (Commotio Cordis).

External chest impacts (commotio cordis) can cause mechanically induced premature ventricular excitation (PVEM) and, rarely, ventricular fibrillation (VF). Because block of stretch-sensitive ATP-inactivated potassium channels curtailed VF occurrence in a porcine model of commotio cordis, VF has been suggested to arise from abnormal repolarization caused by stretch activation of potassium channels. Alternatively, VF could result from abnormal excitation by PVEM, overlapping with normal repolarization-related electric heterogeneity. Here, we investigate mechanisms and determinants of PVEM induction and its potential role in commotio cordis-induced VF. Subcontusional mechanical stimuli were applied to isolated rabbit hearts during optical voltage mapping, combined with pharmacological block of ATP-inactivated potassium or stretch-activated cation-nonselective channels. We demonstrate that local mechanical stimulation reliably triggers PVEM at the contact site, with inducibility predicted by local tissue indentation. PVEM induction is diminished by pharmacological block of stretch-activated cation-nonselective channels. In hearts where electrocardiogram T waves involve a well-defined repolarization edge traversing the epicardium, PVEM can reliably provoke VF if, and only if, the mechanical stimulation site overlaps the repolarization wave edge. In contrast, application of short-lived intraventricular pressure surges neither triggers PVEM nor changes repolarization. ATP-inactivated potassium channel block has no effect on PVEM inducibility per se, but shifts it to later time points by delaying repolarization and prolonging refractoriness. Local mechanical tissue deformation determines PVEM induction via stretch-activation of cation-nonselective channels, with VF induction requiring PVEM overlap with the trailing edge of a normal repolarization wave. This defines a narrow, subject-specific vulnerable window for commotio cordis-induced VF that exists both in time and in space.

Ventricular fibrillation induced by high-output ICD shock: report of cases and review of literature

This report highlights the importance of realising that even the modern-day implantable cardioverter defibrillators (ICDs) with R wave synchronised appropriate shocks have a potential proarrhythmic effect. We present two cases...

Intensive Exercise Training Improves Cardiac Electrical Stability in Myocardial-Infarcted Rats.

BackgroundModerate exercise training has been shown to decrease sudden cardiac death post myocardial infarction. However, the effects of intensive exercise are still controversial.Methods and ResultsFourteen myocardial‐infarcted rats were divided into sedentary (n=8) and intensive training groups (n=6) and 18 sham control rats to sedentary (n=10) and intensive training groups (n=8). Heart rate variability was obtained at weeks 1 and 8. The inducibility of ventricular tachycardia/fibrillation was assessed in a Langendorff system. Fast Fourier transforms were applied on the recorded ventricular tachycardia/fibrillations. Training reduces low to high frequency ratio of heart rate variability at week 8 compared with that at week 1 (P<0.05). In isolated hearts, the probability for ventricular tachycardia/fibrillation was decreased from 4.5±0.8% in sedentary controls to 1.56±0.2% in intensive training controls (P<0.05) and from 13.5±2.1% in the sedentary group to 5.4±1.2% in the intensive training group (P<0.01). Moreover, the pacing current required for ventricular fibrillation induction in the trained groups was increased following exercise (P<0.05). Fast Fourier transform analysis of ECG findings revealed an exercise‐induced ventricular fibrillation transition from a narrow, single‐peak spectrum at 17 Hz in sedentary controls to a broader range of peaks ranging from 13 to 22 Hz in the intensive training controls.ConclusionsIntensive exercise in infarcted rats leads to reduced ventricular fibrillation propensity and is associated with normalization of refractoriness and intrinsic spatiotemporal electrical variations.

148 Paediatric cardiac arrest: is there any myocardial damage in paediatric patients when adult defibrillation energies are administered?

PurposeWhen attempting defibrillation in an out-of-hospital paediatric patient, the use of a reduced energy is currently recommended in the resuscitation guidelines due to concerns surrounding potential myocardial damage. The purpose...

Effect of transthoracic impedance on defibrillation efficacy and safety in a porcine model

Objective Two different transthoracic impedances were made with an adjustable impedance instrument to compare the success rate of defibrillation, heart and skin damage in a porcine model. Methods A total of sixteen pigs were randomly(random number) divided into two groups: low impedance group (about 50 Ω, n=8) and high impedance group (about 100 Ω, n=8). Defibrillation (recommended 150 J) was first attempted at 15 s after induction of ventricular fibrillation(VF). If spontaneous circulation was not recovered, 2-minute chest compression and subsequent defibrillation attempts (maximum 200 J) were attempted. Model animal kept stabilization for 30 min after return of spontaneous circulation before induction of the next episode of VF, which was induced five episodes in each pig. Results In the low impedance group, VF was induced 39 times, 39 of 43 attempted defibrillations were successful. In the high impedance group, VF was induced 40 times, 40 of 70 attempted defibrillations were successful. The current and success rate of the first defibrillation were (34.9±3.2)A and 94.9% respectively in the low impedance group, while those of the high impedance group were (19.1±2.1)A and 50% respectively(both P<0.05). There were no significant differences in skin damage between two groups, but myocardial injury was lighter in the high impedance group. Conclusions Success rate of the first defibrillation with recommend 150 J obviously decreases with the increase of transthoracic impedance. The main factor of myocardial injury is current instead of the numbers of defibrillation. Key words: Defibrillation; Transthoracic impedance; Current; Myocardial injury; Pig

Beneficial Effect of Renal Denervation on Ventricular Premature Complex Induced Cardiomyopathy.

BackgroundFrequent ventricular premature complexes (VPCs) can lead to the development of dilated cardiomyopathy and sudden cardiac death. Renal artery sympathetic denervation (RDN) may protect the heart from remodeling. This study aimed to investigate the effect of frequent VPCs on structural and electrical properties and whether RDN can protect the heart from remodeling.Methods and ResultsEighteen rabbits were randomized to control (n=6), VPC (n=6), and VPC‐RDN (n=6) groups. Surgical and chemical RDNs were approached through bilateral retroperitoneal flank incisions in the VPC‐RDN group. Pacemakers were implanted to the left ventricular apex to produce 50% VPC burden for 5 weeks in the VPC and VPC‐RDN groups. In addition, ventricular myocardium was harvested for western blot and trichrome stain. Echocardiographic results showed left ventricular enlargement after 5‐week pacing in the VPC group, but not in the VPC‐RDN group, when compared to baseline. In biventricles, ion channel protein expressions of Nav1.5, Cav1.2, Kir2.1, and SERCA2 were similar among 3 groups. However, the degree of biventricular fibrosis was extensive in the VPC group, compared to the control and VPC‐RDN groups. Importantly, ventricular fibrillation inducibility was higher in the VPC group (41%) when comparing to the control (13%; P<0.05) and VPC‐RDN groups (13%; P<0.05), respectively.ConclusionsFrequent VPCs are associated with the development of cardiac structural remodeling and high ventricular fibrillation inducibility. RDN prevents cardiac remodeling and the occurrence of ventricular arrhythmia through antifibrosis.

Adenosine induced ventricular fibrillation in a structurally normal heart: a case report

BackgroundAdenosine is the first-line pharmacotherapy for termination of supraventricular tachycardia through its action on the atrioventricular node. However, pro-arrhythmic effects of adenosine are also recognised, most notably in the presence of pre-excited atrial fibrillation. In this case report, we describe the induction of ventricular fibrillation in a patient with no demonstrable accessory pathway, nor any other structural heart disease. This rare, idiosyncratic reaction has never previously been reported and is of relevance given the widespread and routine use of adenosine in clinical practice.Case presentationA 26-year-old woman of Cypriot origin presented to our emergency department with a sudden onset of palpitations and chest discomfort. She was healthy, with no previous medical history and no regular medications. An electrocardiogram demonstrated a narrow complex tachycardia with a rate of 194 beats per minute. Following failure of vagal maneuvers to terminate the tachycardia, the assessing physician administered a single intravenous dose of 6 mg adenosine. Our patient instantaneously developed coarse ventricular fibrillation and circulatory collapse. Cardiopulmonary resuscitation was initiated and our patient was rapidly defibrillated to sinus rhythm with a single 150 J direct current shock. A 900-mg loading dose of intravenous amiodarone was commenced and our patient was managed in the cardiac high dependency unit. No further arrhythmias were identified on continuous cardiac monitoring.On review, her presenting electrocardiogram had demonstrated rapidly conducted atrial fibrillation with no evidence of ventricular pre-excitation. Concordantly, her resting electrocardiogram was not suggestive of any accessory pathway. This was conclusively excluded on invasive electrophysiology study, with negative programmed ventricular stimulation up to three extrastimuli. Extensive laboratory investigations were unremarkable and failed to identify an underlying cause for her episode of atrial fibrillation. Furthermore, cardiac magnetic resonance imaging demonstrated a structurally normal heart, with no edema, fibrosis or infarction as well as normal coronary artery anatomy.ConclusionsAdenosine remains a safe and highly efficacious therapy for supraventricular tachycardia. However, this unusual case demonstrates the ability of adenosine to induce circulatory collapse and reminds the clinician that prompt access to resuscitation, defibrillation, and transcutaneous pacing equipment is mandatory with every administration of this drug.

Colchicine Increases Ventricular Vulnerability in an Experimental Whole‐Heart Model

The traditional gout medication colchicine has been reported to effectively prevent atrial fibrillation recurrence after atrial fibrillation ablation or cardiac surgery in a few clinical trials. Severe adverse events have not yet been reported. The aim of the present study was to assess possible direct electrophysiological effects in an experimental whole-heart model. Ten rabbit hearts were isolated and Langendorff-perfused. Thereafter, colchicine was administered in two concentrations (1 and 3 μM). Eight endo- and epicardial monophasic action potentials and a 12-lead ECG showed a stable QT interval and action potential duration during colchicine infusion. Furthermore, there was no significant increase in dispersion of repolarization. However, colchicine induced a dose-dependent significant decrease of effective refractory period (ERP; 1 μM: -19 ms, 3 μM: -22 ms; p < 0.05). In the present study, acute infusion of colchicine in isolated rabbit hearts resulted in a reduction of ERP in the presence of a stable myocardial repolarization. This led to a significantly elevated inducibility of ventricular fibrillation. In 4 of 10 hearts, incessant ventricular fibrillation occurred. These results suggest a pro-arrhythmic or toxic effect of colchicine and underline that further clinical studies on potential adverse effects should be conducted before the drug can be recommended for routine use after atrial fibrillation ablation.