bluuebunny/crossref_metadata_2025_split huggingface dataset:
The Role of Free Radicals in the Pathogenesis of Amiodarone Toxicity
Authors: VERECKEI ANDRAS , BLAZOVICS ANNA , GYORGY ISTVAN , FEHER ERZSEBET , TOTH MIKLOS , SZENASK GABOR , ZSINKA AGNES , FOLDIAK GABOR , FEHER JANOS 
Published: May 2007

Free Radicals and Amiodarone Toxicity. Introduction: In vitro and in vivo studies were performed to elucidate the pathogenesis of amiodarone toxicity. Methods and Results: Rats were treated with amiodarone alone (500 mg/kg body weight per day) or together with antioxidants (silibinin or MTDQ‐DA: 50 mg/kg body weight per day) or with either antioxidanl alone. They received amiodarone for 30 days and antioxidant for 33 days (3 days pretreatment) In vitro, amiodarone induced a dose‐dependent chemiluminescence signal, which was inhibited by the two dihydroquinolin‐type antioxidants (MTDQ‐DA, CH 402). Chemiluminometric results from liver homogenate demonstrated that simultaneous treatment with silibinin partially prevented the liver homogenate superoxide anion radical scavenger capacity decreasing effect of amtodarone. Amiodarone treatment caused a significant increase of NADPH and Fe3+ induced lipid peroxidalion in the liver microsomal fraction, which antioxidants (silibinin, MTDQ‐DA) were unable to prevent. Light microscopy of the lung tissue in amiodarone‐treated rats showed accumulation of foamy macrophages with thickening of the interalveolar septa, pneumonitis, and variable interstitial tibrosis. Antioxidant treatment did not prevent these changes. Electron micrographs of lung from amiodarone‐treated ruts showed lysosomal phospholipoidosis, intralysosomal electron dense deposits, and increased lysosome number and size. In contrast to rats treated with amiodarone alone, those treated with both amiodarone and silibinin had significantly fewer lysosomes (P < 0.01); the lysosome size, shape, and internal characteristics remained he same. Simultaneous treatment with silibinin and amiodarone decreased lysosomal phospholipoidosis compared to amiodarone treatment alone. Simultaneous treatment with MTDQ‐DA and amiodarone did not show any beneficial effect. Pulse radiolysis and cobalt 60‐gamma (60Co‐γ) radiolysis studies showed that the main free radical product in a reducing environment was a very reactive aryl radical formed after the partial deiodination of the amiodarone molecule. The radioseasitizing effect of amiodarone was also verified in rat liver microsomal preparations using in vivo amiodarone with or without MTDQ‐DA pretreatment and 60Co‐γ irradiation with or without the in vitro addition of antioxidants (CH 402, MTDQ‐DA). In vivo, the MTDQ‐DA treatment also had a radiosensitizing effect; however, the in vitro addition of both antioxidants resulted in a radio‐protective effect. The aryl radical also may emerge in vivo during the metabolism of amiodarone. Conclusion: These observations suggest that amiodarone in vitro and in vivo generates free radicals that may play a role in the pathogenesis of amiodarone toxicity beside other well‐established mechanisms, and antioxidants may have a partial protective effect against amiodarone toxicity.
Morphology of the Cardiac Conduction System in Patientswith Electrophysiologically Proven Dual Atrioventricular Nodal Pathways
Authors: YEN HO SIEW , McCOMB JANET M. , SCOTT CHRISTOPHER D. , ANDERSON ROBERT H. 
Published: May 2007

Conduction System in Dual AV Nodal Pathways. Introduction: Although the electrophysiologic criteria for dual atrioventricular nodal pathways are well established, the anatomical substrate is still unclear. Methods and Results: We examined the hearts from 10 patients who had been studied electrophysiologically prior to cardiac transplantation. All 10 patients were male, aged 22 to 60years. Nine of the 10 patients had dual atrioventricular nodal pathways according to acceptedcriteria. Histologic studies of the atrioventricular conduction system showed normal structureof the atrioventricular node in all 10 hearts, with minor variations within the node in 3 cases, within the penetrating bundle in 3 cases, and within the nonbranching bundle in 3 cases. Theatrial approaches to the atrioventricular node were generally scanty in 6 hearts. The solitarycase that was shown electrophysiologically to lack dual pathways had no obvious difference inthe structure of the nodal area other than sparsity of transitional cells. We were unable tolocate any extranodal atrial tracts as described by other investigators. Conclusion: The anatomical substrate for conduction over dual pathways may he too subtleto be detected by gross morphologic studies. Since dual pathways were unmasked in allpatients but one during electrophysiologic studies, it may be that the potential for these pathways is ubiquitous.
“Paradoxical” AH Shortening Caused By Proximal Coronary Sinus Stimulation During Orthodromic Reciprocating Tachycardia
Authors: SUZUKI FUMIO , HARADA TOMO‐O , KAWARA TOKUHIRO , TANAKA KAZUSHI , HIRAO KENZO , HIEJIMA KAZUMASA , LEHMANN MICHAEL H. 
Published: May 2007

AH Shortening During ORT. Introduction: During extrastimulation or entrainment of orthodromic atrioventricular (AV) reciprocating tachycardia (ORT), the atriuni‐His (AH) interval as measured at the His‐bundle recording site is expected to lengthen due to extrastimu‐Lation‐dependent or pacing rate‐dependent slowing of AV nodal conduction by impulses that penetrate the tachycardia circuit. We report 6 patients in whom the AH interval “paradoxically” shortened during ORT in response to extrastimulation and rapid pacing from the proximal coronary sinus. Methods and Results: Accessory pathway location was right anterior (1 patient), right anteroseptal (1 patient), and left anterior (4 patients). Cycle length of ORT was stahle (variation ≤ 5 msec) and ranged from 325 to 410 msec. During ORT, extrastimulation and rapid pacing were performed from the proximal coronary sinus and the right atrium. Extrastimulation from the proximal coronary sinus late in diastole caused significant shortening of AH interval in all patients hy a mean of 18 ± 3 msec (range 15 to 20 msec). AH shortening was demonstrated without a change of either the timing or morphologic appearance of the low septal right atrium at the H is‐bundle recording site. This phenomenon was not ohserved during right atrial extrastimulation. Rapid pacing from the proximal coronary sinus at cycle lengths of 305 to 390 msec (i.e., 15 to 20 msec shorter than the cycle length of each ORT) again demonstrated shortening of AH interval in all patients by a mean of 15 ± 3 msec (range 10 to 20 msec). By contrast, rapid pacing from the right atrium demonstrated classical AH prolongation at any paced cycle length. Conclusion: AH shortening without a change of either the timing or morphologic appearance of the low septal right atrium at the His‐handle recording site confirms the existence of a distinct posterior atrial input to the AV node. In this setting low septal right atrial activation is not requisite for AV nodal conduction. Whether activation of the low septal right atrium is essential for. or contributes to, AV nodal conduction of atrial impulses from locations other than the proximal coronary sinus needs to he determined.
Spontaneous Activity in Transgenic Mouse Heart:
Authors: KLINE RICHARD P. , SOROTA STEVE , DRESDNER KARL P. , STEINHELPER MARK E. , LANSON NICHOLAS A. , WIT ANDREW L. , CLAYCOMB WILLIAM C. , FIELD LOREN J. 
Published: May 2007

Spontaneous Activity in Transgenic Mouse Heart and AT‐1 Myocytes. Introduction: We have generated transgenic animals that heritably develop atrial tumors composed of difTerentiated proliferating cardiomyocytes. Experiments were initiated to characterize (he electrical properties of these cells. Methods and Results: We show that the primary atrial tumors are composed of discrete foci that exhibit spontaneous automatic activity. A direct correlation was observed between tumor size and firing rate of these foci. In addition to the primary atrial tumors, we examined the propertie.s of cultured cardiomyocytes isolated from a transplantable transgenic tumor lineage (designated AT‐1 cells). Cultured AT‐1 cells arc al.so spontaneously automatic. The action potential eontiguration from these preparations is similar to that observed in nontransgenic atrial cardiomyocytes, albeit somewbat more depolarized and of longer duration. As would be expected for cardiomyocytes of atrial origin, the transgenic cardiornyocyte preparations hyperpolarize during muscarinic stimulation due to increased K+ conductance mediated by a pertussis toxin sensitive G‐protein. Assessment of pbarmacologic blockage of the “if” pacemaker current suggests that the automaticity of both transgenic cardiomyocyte preparations may be of novel origin. In this context, the cultured AT‐1 cells sbowed spontaneous bebavior that was clearly of cellular origin; this activity was manifest as transient bursts of electrical activity followed by periods of electrical quiescence. this bursting pattern is unusual for normal adult cardiomyocytes, but has been observed in several other cell types. In the primary tumors, automatic behavior may arise from a similar cellular origin or alternatively from a microreentrant phenomena. Conclusion: Primary tumors and AT‐1 cells sbow essential atrial Electrophysiology with important novel features.
Effect of Rate on Changes in Conduction Velocity and Extracellular Potassium Concentration During Acute Ischemia in the In Situ Pig Heart
Authors: HARPER JAMES R. , JOHNSON TIMOTHY A. , ENGLE CONNIE L. , MARTIN DAVID G. , ELEET WILLIAM , GETTES LEONARD S. 
Published: May 2007

Rate Effects on Conduction and [K+]e During Ischemia. Introduction: The purpose nf our study was to determine if the slowing oflongitudinal intraventricular conduction in the in situ porcine heart during acute regional no‐flow ischemia was rate dependent. Further, we investigated whether any rate dependence could he correlated to a rate‐dependent component of the ischemiainduced rise in extracellular potassium concentration. [K+]e. Methods and Results: We studied in situ hearts in nine anesthetized open chest pigs in which acute no‐flow ischemia was induced by occlusion of the left anterior descending coronary artery. To determine the effects of steady‐state rate on the slowing of conduction and rise in [K+]e during ischemia, we varied the rate of stimulation during sequential occlusions from 90 to 150 beats/min. Longitudinal conduction velocity was determined by unipolar electrodes embedded in a plaque that was sutured to the epicardial surface in the center of the ischemic zone. Myocardial [K+]e was determined simultaneously by potassium‐sensitive electrodes placed at or within 1 to 2 mm of the epicardium in close proximity to the activation recording electrodes. Conduction vehxity decreased more rapidly at the more rapid rates of stimulation although the reduction in conduction velocity occurring prior to the onset of conduction block was similar at both rates. The potassium change was not rate dependent and rose at the same rate regardless of the rate of stimulation. Conclusion: Our study demonstrates that the steady‐state rate‐dependent component of the slowing of intraventricular conduction induced by acute ischemia in the in situ porcine heart occurs in the absence of a rate‐dependent component in the rise of [K+]e. Between rates of 90 and 150 beats/min, the rate dependence of the conduction slowing may be attributed to one or more potassium‐independent factors such as the rate‐dependent changes in resting membrane potential, in V̇max of the action potential upstroke, and in cell‐to‐cell uncoupling, which have hcen observed in other models of acute ischemia.
Generation of Reentry in Anisotropic Myocardium
Authors: PANFILOV ALEXANDER V. , KEENER JAMES P. 
Published: May 2007

Reentry in Anisotropic Myocardium. Introduction: We investigated numerically the effects of the rotation of finer axis orientation through the myocardial wall on wave propagation. Methods and Results: We show that because of this rotation and inherent discrete properties of myocardium, a premature stimulus can create unidirectional conduction block leading to reentry. Conclusion: The dynamics of the subsequent reentrant patterns are complicated by the presence of rotational anisotropy, as the center of reentry drifts, and the reentry terminates in finite time when it collides with the domain boundary.
Sequential Bilateral Bundle Branch Block During Dofetilide, A New Class III Antiarrhythmic Agent, In a Patient with Atrial Fibrillation
Authors: CRIJNS HARRY J.G.M. , KINGMA J. HERRE , GOSSELINK A.T. MARCEL , DALRYMPLE H.W. , De LANGEN CEES D.J. , LIE KI 
Published: May 2007

Sequential Bilateral BBB During Dofetilide. Introduction: I in mechanism of wide QRS complex tachycardias during dofetilide infusion was studied in a patient with atrial fibrillation. Methods and Results: Endocardial recording from the intraventricular conduction system showed that dofetilide caused “classic” aberrant conduction (Ashman phenomenon, typical QKS morphology) at high prematurity ratios (preceding interval = 1.78 X coupling interval 290), thus mimicking ventricular ectopy. In addition, there was frequent sequential bilateral bundle branch block, caused by a significant difference in preceding bundle‐to‐bundle intervals (mean difference ± 1 SD: 74 ± 26 msec). Conclusion: The present findings may prove helpful in the clinical assessment of wide QKS complex rhythms after dofetilide and possibly other “pure” Class III antiarrhythmics.
Site of Accessory Pathway Block After Radiofrequency Catheter Ablation in Patients with the Wolff‐Parkinson‐White Syndrome
Authors: CALKINS HUGH , MANN CHING , KALBFLEISCH STEVEN , LANGBERG JONATHAN J. , MORADY FRED 
Published: May 2007

Site of Accessory Pathway Block. Introduction: Recent studies have demonstrated that the most common site of accessory pathway conduction block following the introduction of a premature atrial stimulus during atrial pacing is between the accessory pathway potential and the ventricular electrogram. consistent with block at the ventricular insertion of the accessory pathway. However, no prior study has evaluated the site of conduction block during radiofrequency catheter ablation procedures. Therefore, the objective of this study was to determine the site of conduction block after catheter ablation of accessory pathways by analyzing and comparing the local electrograms recorded before and after radiofrequency energy delivery at successful ablation sites. Methods and Results: The electrograms evaluated in this study were obtained from 85 consecutive patients who underwent successful radiofrequency catheter ablation of a manifest accessory pathway. The 50 left free‐wall accessory pathways were ablated using a ventricular approach and the 35 right free‐wall or posteroseptal accessory pathways were ablated using an atrial approach. The characteristics of local electrograms recorded immediately before and immediately after successful ablation of the accessory pathway were determined in each patient. The site of accessory pathway block was determined by comparing the amplitude, timing, and morphology of the local eleclrograms at successful sites of radiofrequency catheter ablation before and after delivery of radiofrequency energy. A putative accessory pathway potential was present at the successful target site in 74 of the 85 patients (87%). Conduction block occurred between the atrial electrogram and the accessory pathway potential in 66 patients (78%) and between the accessory pathway potential and the ventricular electrogram in eight patients (9%). The site of block could not be determined in 11 patients (13%) in whom an accessory pathway potential was absent. Conduction block occurred most frequently between the atrial electrogram and the accessory pathway potential regardless of accessory pathway location. No electrogram parameter or accessory pathway characteristic was predictive of the site of conduction block. Conclusion: The results of this study demonstrate that conduction block occurs most frequently between the local atrial electrogram and the accessory pathway potential during radiofrequency catheter ablation of accessory pathways. This is true regardless of whether the accessory pathway is ablated from the atrial or ventricular aspect of the mitral or tricuspid annulus.
Alpha1‐Adrenergic Blockade and Sudden Cardiac Death
Authors: VANOLI EMILIO , HULL STEPHEN S. , FOREMAN ROBERT D. , FERRARI ANTONIO , SCHWARTZ PETER J. 
Published: May 2007

Alpha1‐Adrenergic Blockade and Sudden Cardiac Death. Introduction: The primary goal of the present study was to test whether selective pharmacologic blockade of alpha1 receptors, and specifically of the subtype alpha1a could prevent ventricular fibrillation (VF) during acute myocardial ischemia. Background: The development of new autonomic interventions is of clinical interest in view of the failure of traditional; antiarrhythmic drugs to prevent sudden death. Experimental evidence indicates that alpha, receptors, and in particular the subtype alpha1a may he involved in the genesis of malignant arrhythmias during acute myocardial ischemia and reperfusion. Despite this evidence, questions have been raised about the actual antifibrillatorv efficacy of alpha‐adrenergic blockade in the acutely ischemic myocardium. The effects of prazosin and of abanoquil (UK 52,046), a highly selective alpha1a receptor blocker, were tested and compared with propranolol in a conscious animal preparation for sudden death. Methods and Results: Ten dogs with a 1‐month‐old anterior wall myocardial infarction were studied. These dogs had all developed, in control conditions, VF during a 2‐minute occlusion of the circumflex coronary artery while exercising (n=9) or lying on the table (n=1). Afterwards, the dogs underwent additional tests with the following intravenously administered drugs: abanoquil (n=10; 1μg/kg. prazosin (n=9; 0.1 mg/kg), and propranolol (n=10; 1 mg/kg). Internal control analysis was used. All dogs tested had recurrence of VF with both alpha‐adrenergic blockers. Propranolol significantly reduced heart rate during ischemia and prevented VF in 5 of 10 dogs tested (P < 0.05). When heart rate was kept constant by atrial pacing (n = 3), 2 of the 3 animals remained protected by propranolol. Just prior to onset of VF, heart rate was not significantly different in the control and in the abanoquil tests (237 ± 45 and 253 ± 34 beats/min, respectively), whereas it was higher (P < 0.05) with prazosin (288 ± 40 beats/min). Conclusions: Alpha, and alpha1a receptor blockers do not prevent VF secondary to acute myocardial ischemia in the presence of elevated sympathetic activity and heart rate. In the same setting, beta‐adrenergic blockade prevents the reflex heart rate increase due to ischemia and provides a significant protection.
Changes in Autonomic Tone Following Thrombolytic Therapy for Acute Myocardial Infarction:
Authors: ZABEL MARKUS , KLINGENHEBEN THOMAS , HOHNLOSER STEFAN H. 
Published: May 2007

Heart Rate Variability in Acute MI. Introduction: Little data are available on changes in autonomic tone during the first 24 hours of acute infarction in patients undergoing thromholytic therapy. Particularly, the association of changes in autonomic tone to reperfusion of the infarctrelated artery has not been evaluated in man. Heart rate variability (HRV) is a noninvasive tool to assess cardiac autonomic tone, which carries prognostic information in postinfarction patients. Methods and Results: To assess changes in autonomic tone with ungiographically assessed success of thrombolysis in patients with acute infarction, the proportion of adjacent RR intervals different by greater than 50 msec (pNN50) was analyzed from 24‐hour Holler monitoring initiated before the start of thrombolytic therapy in 103 consecutive patients. Mean heart rate (HR) and pNN50 were available in 95 of 103 patients and were separately analyzed for the first hour after initiation of thrombolysis (reperfusion phase) and the first 24 hours. As assessed by coronary angiography 90 minutes after start of thrombolysis, 74 patients (78%) had successful coronary artery reperfusion. HR averaged 72 ± 13/min for the first hour in all 95 patients and 74 ± 13/min for the first 24 hours. The respective values for pNN50 were 11±2%± 11±7% for the first hour and 9±7%± 9±2% for the first 24 hours. Patients with inferior myocardial infarction (MI) had a lower mean HR of 72 ± 12/min versus 76 ± 13/min (P = 0±11) and a higher pNN50 (11±2%± 9±8% versus 7±6%± 8±3%, P = 0±01) compared to patients with anterior MI. The mean HR correlated weakly with pNN50 (r = ‐0±33, P < 0±01). For patients with coronary artery patency after 90 minutes, mean HR was 70 ± 12/min for the first hour compared to 80 ± 13/min for patients without (P = 0±003). For the first 24 hours, these values were 72 ± 12/min compared to 80 ± 14/min (P = 0±02). For the first hour, pNN50 averaged 12±6%± 12±4% for patients with successful reperfusion compared to 6±6%± 7±3% for patients without (P = 0±024). For the first 24 hours, these values were 9±2%± 8±5% compared to 11±5%± 11±3% (P = NS). Patients with inhospital ventricular fibrillation (n = 8) had a higher mean HR throughout the first 24 hours (88 ±16/min vs 73 ± 12/min, P = 0±008) compared to patients with an uneventful course. Additionally, there was a trend toward a lower HRV in patients with ventricular fibrillation. Conclusion: Thrombolysis‐induced reperfusion of the infarct‐related artery results in a higher vagal tone during the early hours of MI as compared to failed reperfusion. This finding is independent from intfarct location and associated with a trend toward a lower incidence of ventricular fibrillation during the acute phase of infarction.
Alpha1‐Adrenergic Receptor Modulation of Repolarization in Canine Purkinje Fibers
Authors: HO LEE JAE , ROSEN MICHAEL R. 
Published: May 2007

Alpha‐Agonists and Repolarization. Introduction: Alpha‐adrenergic receptor stimulation increases contractility and prolongs repolarization. These effects are modulated by α1‐adrenergic receptor‐mediated inhibition of transsarcolemmal potassium currents. Methods and Results: We used standard microelectrode techniques to study the actions of 4‐aminopyridine (4‐AP), which blocks the transient outward current, Ito, and WAY‐123,398, which blocks the delayed rectifier, Ik, on canine Purkinje fiber action potential prolongation induced by phenylephrine. At a basic cycle length of 1 second, phenylephrine (0.1 to 10 μ) dose‐dependently prolonged action potential duration at 90% repolarization (APD90) from 331 ± 10 msec to 400 ± 12 msec (P < 0.05) at phenylephrine, 10 μ. Phenylephrine did not change phase 1 or plateau height. 4‐AP (0.1 mM) decreased phase 1 magnitude, shifted plateau height to more positive potentials (from 0.1 ± 1.8 mV to 14.3 ± 1.1 mV [P < 0.05]), and shortened APD90 from 318 ± 9 msec to 294 ± 8 msec (P < 0.05). 4‐AP did not block phenylephrine effects on APD90, which increased, at 10 μ phenylephrine, from 294 ± 8 msec to 342 ± 6 msec (P < 0.05). In contrast, WAY‐123,398 (0.1 μ) prolonged APD90 from 360 ± 6 msec to 452 ± 6 msec (P < 0.05), and had no effect on plateau height. In the presence of WAY‐123,398, phenylephrine no longer increased APD9o. Conclusion: (1) Agents that block Ito shorten APD in Purkinje fibers; and (2) the α‐agonist mediated increase of APD in canine Purkinje fibers can be explained by inhibition of Ik.