bluuebunny/crossref_metadata_2025 huggingface dataset:
Profiling of alterations in platelet proteins during storage of platelet concentrates
Authors: Thiele Thomas , Steil Leif , Gebhard Simon , Scharf Christian , Hammer Elke , Brigulla Matthias , Lubenow Norbert , Clemetson Kenneth J. , Völker Uwe , Greinacher Andreas
Published: May 2007

BACKGROUND: The quality of platelet concentrates (PCs) is primarily determined in vitro by selective methods (e.g., pH, aggregometry), which provide only limited information on certain platelet (PLT) characteristics. In contrast, proteomic technologies provide a comprehensive overview of the PLT proteome. High interassay variability, however, limits meaningful assessment of samples taken from the same product over time or before and after processing.

STUDY DESIGN AND METHODS: Differential in‐gel electrophoresis (DIGE) and mass spectrometry were applied to analyze changes in the PLT proteome during storage of PCs.

RESULTS: DIGE provides a comprehensive and reproducible overview of the cytoplasmic PLT proteome (median standard deviation of protein spot intensities, 5%‐9%). Although 97 percent of cytosolic PLT proteins remained unchanged over a 9‐day storage period, septin 2 showed characteristic alterations that preceded by several days more widespread alterations affecting numerous other proteins. Also β‐actin and gelsolin are potential marker proteins for changes in the PLT proteome. Interestingly septin 2 and gelsolin are affected during apoptosis, indicating that apoptosis in PCs may have an impact on PLT storage.

CONCLUSION: DIGE is a tool for comprehensively assessing the impact of storage on the global proteome profile of therapeutic PCs. Most of the changes detected are in high‐abundance PLT proteins.
Physiological Modulation of Cardiac Gap Junction Channels
Authors: VEENSTRA RICHARD D.
Published: May 2007

Cardiac Gap Junction Channel Regulation. Synchronization of pacemaker activity and cardiac action potential propagation is dependent upon the maintenance of electrical communication via gap junctions. Gap junction channels in mammalian heart are formed by a 43‐kilodalton (kD) protein, connexin43, and have a unitary conductance of 50 picosiemens (pS). In embryonic chick heart, three gap junction proteins of 42, 43, and 45 kD have been cloned, the functional properties of which have not been individually identified. Unitary channel conductances ranging from 40‐240 pS have been reported, but conductances of 40‐80 and 160 pS are most frequently observed in embryonic chick heart. Developmental changes in transjunctional voltage dependence are known to occur and may be correlated with differential expression of the three chick connexins during development. Gap junction conductance (gj) is highly regulated, being maintained or increased by ATP and cAMP‐dependent pathways. Conversely, gj is reduced by treatment with various lipophilic agents (e.g., n‐alkanols, arachidonic acid, halothane), large transjunctional potentials, increasing intracellular cation (e.g., H+, Ca2+) concentrations, and tyrosine phophorylation of rat connexin43. It is unclear at this time if any of the regulatory mechanisms can mediate beat‐to‐beat fluctuations in gj of normal myocardium. Most available evidence indicates that this modulation occurs by the open‐closed gating of individual channels rather than effects on the unitary channel conductance. The precise molecular mechanisms are not yet known, but the functional expression of gap junction proteins should allow for determination of the functional domains responsible for direct and indirect modulation of the cardiac gap junction proteins.
Enantioselective Actions of Tocainide on the Electrophysiologic Properties of the Guinea Pig Papillary Muscle
Authors: VANHOUTTE FILIP , VEREECKE JOHAN , VERBEKE NORBERT , CARMELIET EDWARD
Published: May 2007

Enantioselective Electrophysiologic Actions of Tocainide. The electrophysiologic effects of the R (−) and S(+) enantiomers of tocainide, a Class IB antiarrhythmic drug, were studied in the guinea pig papillary muscle, using the standard microelectrode technique. The results can be summarized as follows: (1) R(−) tocainide HCI, 100 mg/L (437 μM), was more potent in reducing the maximal rate of depolarization (τmax) than S(+) tocainide HCl. At a stimulation frequency of 1 Hz, in the presence of 5.4 mM external K+, τmax was reduced an average of 44% in the presence of R(−) tocainide while only 26% in the presence of S(+) tocainide. The inhibition was mainly due to tonic block. The amount of tonic block, as well as phasic block, were different for both enantiomers. (2) The recovery of drug‐occupied channels during the diastolic interval was slower in the presence of R(−) tocainide (τ= 491 msec) than in the presence of S(+) tocainide (τ= 241 msec). Decreasing the stimulation interval caused proportionally more reduction of Vmax in the presence of R(−) tocainide than in the presence of S(+) tocainide. (3) Voltage dependence of block of τmax was also more pronounced with R(−) tocainide. Inactivation curves were shifted toward more negative potentials of 14 mV in the presence of R(−) tocainide, while S(+) tocainide provoked a shift of only 7 mV.
Treatment of a Patient with an Adenosine‐Sensitive Ventricular Tachycardia Using Digoxin
Authors: COOK JAMES R. , KIRCHHOFFER JAMES B. , FITZGERALD THOMAS F.
Published: May 2007

Digitalis and Ventricular Tachycardia. Digoxin was used to treat a patient with an adenosine‐sensitive ventricular arrhythmia. The patient had an exercise‐induced ventricular tachycardia that was evaluated electrophysiologically and displayed characteristics of a triggered arrhythmia. The tachycardia was terminated reproducibly with 12 mg of intravenous adenosine. After treatment with digoxin (serum level = 1.7 ng/mL), the arrhythmia could no longer be initiated with programmed electrical stimulation or exercise treadmill testing. The patient has since remained symptom free for 10 months. The autonomic effects of digitalis are proposed to mediate drug efficacy in this form of ventricular tachycardia.
Reflex Control of the Heart and Circulation: Implications for Cardiovascular Electrophysiology
Authors: SMITH MICHAEL L. , CARLSON MARK D. , THAMES MARC D.
Published: May 2007

Cardiovascular Reflexes and Electrophysiology. The autonomic nervous system mediates control of the heart and circulation for several sensors located throughout the cardiovascular system. Afferent signals originate from mechanoreceptors located in the carotid sinus, aorta, chambers of the heart, and great veins near the heart, and from chemoreceptors in the aortic arch and carotid sinus. Efferent signals are transmitted through the vagus and sympathetic nerves to the heart and vascular tree. Hemodynamic and electrophysiologic homeostasis is maintained by beat‐to‐beat regulation via these reflexes. Several cardiovascular diseases are often accompanied by abnormal function of these reflexes; moreover, abnormalities of reflex control of the circulation often contribute to the pathophysiology of many cardiovascular diseases.
Alcohol Ablation of Ventricular Tachycardia
Authors: NORA MATTHEW O. , MILES WILLIAM M. , KLEIN LAWRENCE S. , DILLON JAMES C. , ZIPES DOUGLAS P.
Published: May 2007

Alcohol Ablation of Ventricular Tachycardia. Ventricular tachycardia that is refractory to medical management has been treated with surgical resection, catheter ablation, and antitachycardia pacemaker. In this case report we describe the use of transcoronary alcohol ablation to treat a patient's ventricular tachycardia. This is accomplished by using ethanol to destroy the site of origin or pathways used in ventricular tachycardia.
Effects of β‐Adrenergic Receptor Activation on Intracellular Calcium and Membrane Potential in Adult Cardiac Myocytes
Authors: YAMADA KATHRYN A. , CORR PETER B.
Published: May 2007

β‐Adrenergic Receptor Activation and Intracellular Ca2+. Introduction:β‐Adrenergic receptor agonists have been shown to increase the voltage‐dependent Ca2+ current in cardiac myocytes. Additionally, adrenergic receptor activation has been shown to increase intracellular Ca2+, to increase systolic Ca2+ transients and to enhance Ca2+ uptake into the sarcoplasmic reticulum, thereby accelerating relaxation. The present study was designed first to characterize the influences of β‐adrenergic receptor activation on intracellular Ca2+ activity as well as membrane potential in ventricular myocytes characterized as normal based on rigorous morphologic and electrophysiologic criteria. The second objective was to assess whether the increase in intracellular Ca2+ activity elicited by β‐adrenergic receptor activation could elicit afterdepolarizations and triggered activity.

Methods and Results: Intracellular Ca2+ and whole‐cell voltage recordings were measured in cells in which indo‐1 free acid was delivered intracellularly through the recording pipette. Isoproterenol produced complex Ca2+ transients underlying both early and delayed afterdepolarizations during pacing as well as aftertransients underlying triggered action potentials and delayed afterdepolarizations in the absence of pacing. The coupling interval of Ca2+i aftertransients was frequency dependent and followed that of the delayed afterdepolarizations. Ca2+i after transient amplitudes, however, exhibited a biphasic response with frequency revealing that factors other than pacing frequency alone contribute to control of the amplitude of the aftertransients. Inhibition of sarcoplasmic reticular release of Ca2+ by ryanodine abolished Ca2+i aftertransients and afterdepolarizations otherwise elicited by isoproterenol.

Conclusion: These data demonstrate that normal cells stimulated by β‐adrenergic agonists exhibit marked changes in intracellular Ca2+ homeostasis that may serve as the substrate for abnormal ion fluxes that ultimately contribute to electrophysiologic derangements underlying arrhythmogenesis in the intact heart. (J Cardiovasc Electrophysiol, Vol. 3, pp. 209–224, June 1992)
Pathological Study of an Explanted Heart Due to Intractable Ventricular Fibrillation
Authors: BHARATI SAROJA , OLSHANSKY BRIAN , LEV MAURICE
Published: May 2007

Pathology of the Explanted Heart. A 35‐year‐old male had multiple admissions for polymorphic sustained ventricular tachycardia (VT) associated with cardiac arrest, uncontrolled by beta blockers and antiarrhythmic drugs including amiodarone. Electro‐physiologic testing was negative and there was no evidence for conduction system abnormalities. Retrograde atrioventricular (AV) conduction was present. The left ventricular ejection fraction was 68% with normal left ventricular size. Multiple myocardial biopsies were reported normal except for one suggesting myocarditis. Atrial pacing (rates > 90) and high‐dose isoproterenol (> 300 grams/min) helped suppress VT. A DDD pacer was implanted but VT still recurred. An internal cardioverter defibrillator was implanted with attempted selective ventricular sympathetic denervation. Six months later, he had a recurrent cardiac arrest that did not respond to internal defibrillator shocks. Multiple external shocks returned him to sinus rhythm. He underwent heart transplantation despite normal left ventricular function and no heart failure. Pathology of the explanted heart without the atria revealed a weight of 442 grams. Both* ventricles were hypertrophied and enlarged. Serial section examination of the conduction system revealed chronic myocarditis of the approaches to the AV node, the AV node, and beginning of the right bundle branch. The AV node was in part within the central fibrous body, and the AV bundle showed fibro‐fatty change and was left sided. There was marked fibrosis of the left bundle branch, chronic epicarditis, arteriolosclerosis of the summit of the ventricular septum, and fibrosis on both sides of the heart. Conclusions: (1) The above findings suggest that myocarditis of a smoldering type and/or fibrosis of the ventricular septum probably caused the intractable VT and fibrillation; and (2) A new indication for cardiac transplantation may include intractable VT associated with cardiac arrest. (J Cardiovasc Electrophysiol. Vol. 3, pp. 437–441, October 1992)
Molecular Biology of the Voltage‐Gated Potassium Channels of the Cardiovascular System
Authors: ROBERDS STEVEN L. , KNOTH KAREN M. , PO SUNNY , ANN BLAIR T. , BENNETT PAUL B. , HARTSHORNE ROBERT P. , SNYDERS DIRK J. , TAMKUN MICHAEL M.
Published: May 2007

Cardiovascular K+ Channel Molecular Biology. K+ channels represent the most diverse class of voltage‐gated ion channels in terms of function and structure. Voltage‐gated K+ channels in the heart establish the resting membrane K permeability, modulate the frequency and duration of action potentials, and are targets of several antiarrhythmic drugs. Consequently, an understanding of K+ channel structure‐function relationships and pharmacology is of great practical interest. However, the presence of multiple overlapping currents in native cardiac myocytes complicates the study of basic K+ channel function and drug‐channel interactions in these cells. The application of molecular cloning technology to cardiovascular K+ channels has identified the primary structure of these proteins, and heterologous expression systems have allowed a detailed analysis of channel function and pharmacology without contaminating currents. To date six different K+ channels have been cloned from rat and human heart, and all have been functionally characterized in either Xenopus oocytes or mammalian tissue culture systems. This initial research is an important step toward understanding the molecular basis of the action potential in the heart. An important challenge for the future is to determine the cell‐specific expression and relative contribution of these cloned channels to cardiac excitability.
Pseudo‐Pacemaker Syndrome Following Inadvertent Fast Pathway Ablation for Atrioventricular Nodal Reentrant Tachycardia
Authors: HO KIM YOU , O'NUNAIN SEAN , TROUTON TOM , SOSA‐SUAREZ GUILLERMO , LEVINE ROBERT A. , GARAN HASAN , RUSKIN JEREMY N.
Published: May 2007

Pseudo‐Pacemaker Syndrome After AV Nodal Ablation. Atrioventricular nodal reentrant tachycardia that is refractory to drug treatment has recently been treated with radiofrequency catheter ablation. In this case report we describe a patient with atrioventricular nodal reentrant tachycardia in whom radiofrequency ablation of slow pathway was attempted, with inadvertent damage to the fast pathway. The patient developed marked first‐degree atrioventricular block associated with symptoms mimicking pacemaker syndrome.
Neural Control Mechanisms and Vasovagal Syncope
Authors: REA ROBERT F. , THAMES MARC D.
Published: May 2007

Vasovagal Syncope, Patients with recurrent unexplained syncope may have cardioinhibitory and vasodepressor responses provokable with head‐up tilt with or without exogenousbeta‐adrenergic stimulation. Although these responses are believed to be neurally mediated, the neural mechanisms involved are pourly understood. Numerous studies have documentedperipheral vasodilation, hypotension, and bradycardia at the time of syncope and several casereports have shown sudden withdrawal of vasoconstrictor sympathetic neural outflow to skeletal muscle in human subjects. In cats and rats, a similar response can be provoked with hemorrhage and is prevented by interruption of cardiac vagal C‐fiber afferents. In dogs, however, section of these fibers does not prevent the development of a vasodepressor response. Theprovocation of vasodepressor syncope during nitroprusside infusion in a heart transplantrecipient with presumed ventricular denervation also suggests that cardiac afferent nerves maynot be required for the development of vasodepressor responses in humans. Other potentialmechanisms include release of endogenous opioids or nitric oxide that may inhibit sympatheticnerve firing, and primary central nervous system activation (as in partial seizures) that triggerscardioinhibitory and vasodepressor responses. This article reviews our current understandingof the mechanisms involved in the development of neurally mediated syncope.
Calcium Current in Single Human Cardiac Myocytes
Authors: COHEN NERI M. , LEDERER W.J.
Published: May 2007

Calcium Current in Human Heart. Introduction: Significant species‐, issue‐, and age‐dependent differences have been described for the L‐type calcium current (ICa). Therefore, extrapolation data obtained from the many animal models to human cardiac physiology is difficult. In this study, we have characterized the voltage‐dependent properties of ICa from pediatric and adult, atrial and ventricular human heart tissue.

Methods and Results: ICa, was measured in single human heart muscle cells using the “whole cell,” voltage clamp method. Single myocytes were isolated from myocardial specimens obtained intraoperatively from both pediatric and adult patients (ages 3 months to 75 years) undergoing cardiac surgery. Cells obtained for these experiments appeared to be healthy; the resting potential was between ‐80 and ‐85 mV. The action potential shape and duration and current‐voltage relationship for 1Ca were similar to that reported by others for human heart cells. The steady‐state activation variable, dx was found to be similar in both pediatric atrial and ventricular cells but shifted approximately 5 mV negative in the adult atrial and ventricular cells. I, of all cells displayed biex‐ponential inactivation and steady‐state inactivation was incomplete at positive potentials (steady‐state inactivation curves turned up at positive potentials) consistent with inactivation arising from voltage‐dependent and calcium‐dependent processes as reported in heart cells from many species. The potential of maximal inactivation was more negative for adult cells (around ‐10 mV) than pediatric cells (around 0 mV). Estimates of the calcium “window” current, using a modified Hodgkin‐Huxlcy model, could explain measured differences in action potential shape and duration.

Conclusion: Human cardiac I, can be investigated using whole cell, voltage clamp methods and a modified Hodgkin‐Huxley model. Quantitative characterization of many of the properties of ICa in human heart tissue suggests that important species differences do exist and that further investigations are required to characterize the dependence of inactivation on [Ca2+]i in human heart cells. Since the array of characteristics of ICa in different species varies, the study of human myocardial cells per se continues to be important when examining human cardiac physiology.
Identifying the End of Ventricular Activation:
Authors: BERBARI EDWARD J. , LANDER PAUL , GESELOWITZ DAVID B. , SCHERLAG BENJAMIN J. , LAZZARA RALPH
Published: May 2007

Late Potentials: Epicardial and Body Surface. Introduction: Identification of the end of the QRS is perhaps the single most important feature obtained from the high resolution signal‐averaged electrocardiogram (SAECG). This point relies on computer algorithms to select a point ahove the noise levels. Prior studies to suhstantiate this approach using eleetrograms for comparison have demonstrated many examples of the hody surface recordings failing to detect the full extent of the late potentials.

Methods and Results: An animal model that generates late potentials was used in conjunction with epicardial cardiac mapping system to systematically examine the rea.sons for these failures. In I I of 13 dogs we found a concordance hetween the signal‐averaged recordings and Ihe epicardial recordings within 5 msec. The two discordant studies were attrihuted to a failure of epicardial mapping to record all late potential sources. Also, a means of accurately comparing measurements from the two recording technologies was required in this study as well as a new definition for identifying the end of activation currents in epicardial eleetrograms.

Conclusion: To achieve these results required approaches different from those used in the clinical setting to record the SAECG. These include: (1) the analysis of individual XYZ leads as opposed to the vector magnitude derived from these leads; (2) visual identification of very low level signals, as automatic algorithms often fail to detect low level signals: and (3) the use of finite impulse response digital filters instead of the bidirectional Butterworth filter.
Differences in Corrected QT Intervals at Minimal and Maximal Heart Rate May Identify Patients at Risk for Torsades de Pointes During Treatment with Antiarrhythmic Drugs
Authors: BUCKINGHAM THOMAS A. , BHUTTO ZAHIDA R. , TELFER EDWARD A. , ZBILUT JOSEPH
Published: May 2007

Change in QT Interval with HR May Predict Torsades. The mechanism of torsades de pointes as a proarrhythmic response to antiarrhythmic drugs is not clear. We hypothesized that the difference in the corrected QT interval (QTc, Bazett's formula) with varying autonomic tone and heart rate during 24‐hour ambulatory ECG would help identify patients at risk. Ten patients with antiarrhythmic drug‐induced torsades de pointes were compared with 28 controls. The QTc. at maximal and minimal heart rate during antiarrhythmic drug‐free ambulatory ECGs were measured. The mean QTc, at minimal heart rates for patients was 0.413 ± (KI02 seconds and 0.420 ± 0.072 seconds for controls (P = 0.715). The mean QTc, at maximal heart rates for patients was 0.555 ± 0.022 seconds and for controls was 0.439 ± 0.011 seconds (P = 0.00l). Mean QTc, between minimal and maximal heart rates were significantly different for patients (P = 0.015) but were not for controls (P = 0.151). Using an arbitrary QT, difference cutoff of 0.075 seconds, this approach identified patients at risk for antiarrhythmic drug‐induced torsades de pointes with a sensitivity of 70% (7 of 10) and a specificity of 89% (P < 0.003 by Chi‐square analysis with Vales’ correction). In conclusion, patients with antiarrhythmic drug‐induced torsades de pointes had a greater rise in QTc, from minimal to maximal heart rate during ambulatory ECG than controls. Further larger prospective trials will be required to establish the value of this approach to identify patients at risk for this type of proarrhythmia.
Effects of Partial and Complete Ablation of the Slow Pathway on Fast Pathway Properties in Patients with Atrioventricular Nodal Reentrant Tachycardia
Authors: STRICKBERGER S. ADAM , DAOUD EMILE , NIEBAUER MARK , WILLIAMSON BRIAN D. , MAN K. CHING , HUMMEL JOHN D. , MORADY FRED
Published: May 2007

Fast Pathway Properties. Introduction: The purpose of this study was to prospectively compare the effects of complete and partial ablation of slow pathway function on the fast pathway effective refractory period (ERP).

Methods and Results: The subjects were 20 patients (mean age 43 ± 13 years) with atrioventricular nodal reentrant tachycardia (AVNRT), no structural heart disease, and easily inducible AVNRT. Autonomic blockade was achieved with propranolol (0.2 mg/kg) and atropine (0.04 mg/kg). After elimination of AVNRT and during autonomic blockade, the presence of residual slow pathway function was determined by the presence of a single AV nodal echo and/or dual AV nodal physiology. After autonomic blockade and before ablation, the mean fast pathway ERP was 319 ± 44 msec and the mean slow pathway ERP was 251 ± 31 msec. After slow pathway ablation and during autonomic blockade, 7 patients had residual slow pathway function and 13 did not. Complete loss of slow pathway function was associated with a shortening of the fast pathway ERP from 334 ± 35 msec to 300 ± 62 msec (P < 0.01), while the fast pathway ERP did not change significantly in patients with residual slow pathway function (291 ± 29 msec vs 303 ± 38 msec, respectively; P = 0.08). A shortening of 30 msec or more in the fast pathway ERP was observed in 11 of 13 patients who did not have residual slow pathway function, compared to 0 of 7 patients with residual slow pathway function (P < 0.001).

Conclusion: Shortening of the fast pathway ERP after successful ablation of AVNRT is dependent upon complete loss of slow pathway function. This observation is consistent with electrotonic inhibition of the fast pathway by the slow pathway.
Double‐Pulse Defibrillation Using Pulse Separation Based on the Fibrillation Cycle Length
Authors: SWEENEY ROBERT J. , GILL ROBERT M. , REID PHILIP R.
Published: May 2007

Double‐Pulse Defibrillation Using FCL, Introduction: We investigated a method of defibrillation in which two shocks were delivered to the same electrodes with a separation hazed on the cycle length of the fibrillation event (FCL).

Methods and Results: In pentobarbital anesthetized dogs, a computerized system determined the FCL from the fibrillation event, computed the desired double‐pulse (DP) shock separation, and immediately delivered the DP shocks. In group 1, energy for 50% success at defibrillation (E50) was measured using separations from 55% to 95% of the FCL and remeasured after administration of flecainide, clofilium, or vehicle to change the FCL. Both drugs increased 1(1 by = 25%. Plots of E50 versus %FCL aligned before and after drug showed that the optimum pulse separation followed the FCL. In group 2, E50s were measured for 55% to 185% FCL separations in clofilium or vehicle‐treated animals. The optimum DP £50 was at 85% FCL and was not significantly different from the single‐shock E50. In group 3, no differences were found when comparing the probability of success versus total energy relationships for single and optimum DP shocks. Group 4 compared E50s for single and DP shocks using a single‐catheter configuration and three‐electrode configurations (catheter‐subdermal patch). E50s for single and DP shocks were equal using the single‐catheter configuration but DP shocks required = 20% more energy in the three‐electrode configurations.

Conclusion: In single‐pathway lead configurations, two shocks with 85% FCL separation can be reliably combined to defibrillate using the same total energy as a larger single shock. Since the energy is unchanged but the total duration is doubled, DP shock currents are reduced by 20% to 30%.
Elimination of AV Nodal Reentrant Tachycardia with 2:1 VA Block by Posteroseptal Ablation
Authors: MILES WILLIAM M. , HUBBARD JOYCE E. , ZIPES DOUGLAS P. , KLEIN LAWRENCE S.
Published: May 2007

AV Nodal Reentrant Tachycardia. AV nodal reentry capable of VA block during tachycardia was successfully eliminated using a posteroseptal ablation pulse delivered well away from the site of earliest atrial activation during tachycardia. A possible explanation is that the arrhythmia represented typical AV nodal reentrant tachycardia with transient intra atrial conduction block during tachycardia.
Electrophysiologic Changes in Ischemic Ventricular Myocardium: I. Influence of Ionic, Metabolic, and Energetic Changes
Authors: CASCIO WAYNE E. , JOHNSON TIMOTHY A. , GETTES LEONARD S.
Published: May 2007

Myocardial Ischemia. Myocardial ischemia leads to significant changes in the intracellular and extracellular ionic milieu, high‐energy phosphate compounds, and accumulation of metabolic by‐products. Changes are measured in extracellular pH and K+ and intracellular pH, Ca2+, Na+ Mg2+, ATP, ADP, and inorganic phosphate. Alterations of membrane currents occur as a consequence of these ionic changes, adrenergic receptor stimulation, and accumulation of lactate, amphipathic compounds, and adenosine. Changes in the volume of the extracellular and intracellular spaces contribute further to the ultimate perturbations of active and passive membrane properties that underlie alterations in excitability, abnormal automaticity, refractoriness, and conduction. These characteristic changes of electrophysiologic properties culminate in loss of excitability and failure of impulse propagation and form the substrate for ventricular arrhythmias mediated through abnormal impulse formation and reentry. The ability to detail the changes in ions, metabolites, and high‐energy phosphate compounds in both the extracellular and intracellular spaces and to correlate them directly with the simultaneously occurring electrophysiologic changes have greatly enhanced our understanding of the electrical events that characterize the ischemic process and hold promise for permitting studies aimed at developing interventions that may lessen the lethal consequences of ischemia.
Tachycardia‐Induced Cardiomyopathy in a Cardiac Transplant Recipient: Treatment with Radiofrequency Catheter Ablation
Authors: OTT PETER , KELLY PATRICIA A. , MANN DAVID E. , DAMLE ROGER S. , REITER MICHAEL J. , LINDENFELD JoANN
Published: May 2007

Tachycardia‐Induced Cardiomyopathy. Introduction: Two years after orthotopic cardiac transplantation, a 60‐year‐old man presented with unexplained congestive heart failure and an incessant atrial tachycardia.

Methods and Results: Electrophysiologic evaluation identified the underlying arrhythmia as automatic atrial tachycardia with site of origin at the high anterior lateral right atrial wall. Radiofrequency catheter ablation successfully eliminated the tachycardia, which resulted in prompt improvement of this patient's congestive heart failure.

Conclusion: This is the first reported case of tachycardia‐induced cardiomyopathy in a cardiac transplant patient. Radiofrequency catheter ablation can he used successfully in this patient population.
Histologic Evolution of Radiofrequency Lesions in an Old Human Myocardial Infarct Causing Ventricular Tachycardia
Authors: BARTLETT THOMAS G. , MITCHELL RICHARD , FRIEDMAN PETER L. , STEVENSON WILLIAM G.
Published: May 2007

Histology of RF Lesions. Introduction: Radiofrequency (RF) ablation of ventricular tachycardia (VT) late after myocardial infarction may be difficult due to characteristics of the infarct containing the reentry circuit. RF lesions in these infarcts in humans have not been characterized.

Methods and Results: Catheter mapping and ablation of VT originating from an anterior wall infarct was performed 8 days and again 12 hours prior to death. Pacing identified a region of abnormal conduction where RF ablation terminated VT. This region contained strips of myocytes sandwiched between endocardial fibrosis and dense scar. RF lesions ranged from 2 × 2 mm to 5 × 10 mm and were up to 3 mm in depth. Acute lesions showed superficial thrombus and early coagulation necrosis without inflammation. Older lesions showed coagulation necrosis, sparse neutrophil infiltrate, minimal granulation tissue, hemorrhage, and mixed inflammatory infiltrate along the lumen without re‐endothelialization.

Conclusion: In this patient, RF lesions had sufficient depth but not width to interrupt the thin, but potentially broad, sheets of myocytes in the reentry circuit. In thinned areas, RF lesions can extend to the epicardium. Selecting sites with abnormal electrograms confines RF lesions to the infarct region. Inflammation and hemorrhage could conceivably cause delayed effects of RF.
A Randomized, Double‐Blind, Placebo‐Controlled, Dose‐Ranging Study of Dofetilide in Patients with Inducible Sustained Ventricular Tachyarrhythmias
Authors: ECHT DEBRA S. , LEE JOHN T. , MURRAY KATHERINE T. , VORPERIAN VICKEN , BORGANEELI S. MARCUS , CRAWFORD DIANE M. , FRIEDRICH TIEMAN , RODEN DAN M.
Published: May 2007

Dofetilide and Ventricular Tachyarrhythmias. Introduction: Dofetilide is a new antiarrhythmic agent with potent Ik blocking properties in vitro. We developed a dose‐ranging, placebo‐controlled study design to define the range of effective doses and to evaluate the clinical electrophysiology of intravenous dofetilide in patients in whom sustained ventricular tachycardia or fibrillation was reproducibly inducible at baseline electrophysiologic testing.

Methods and Results: The initial four patients received low doses that were increased in subsequent groups of four if adverse effects were absent. In each group of four patients, one patient was randomly assigned to placebo (double blind). Twenty‐four patients were studied at six incremental loading and maintenance infusion regimens. Dofetilide (0.1 to 8.0 ng/ml.) produced concentration‐related increases in the %δ of QT (r = 0.79, P <0.001). QTc (r = 0.60, P =0.02), RR (r = 0.62, P < 0.02), and right ventricular effective refractory period (cycle length 600 msec; r = 0.68, P = 0.04). Placebo produced no changes in any of these measurements. Sustained ventricular tachycardia or ventricular fibrillation was no longer inducible in 1 of 6 patients receiving placebo and 8 of 18 receiving dofetilide (4 to 13 sec nonsustained ventricular tachycardia was induced in 4 of these 8). One patient developed torsades de pointes at a high concentration (5.3 ng/mL).

Conclusions: We conclude that: (1) dofetilide produces concentration‐related Ig blocking effects in patients: (2) an incremental dose‐ranging study design aids in identifying the range of doses demonstrating electrophysiologic effects and efficacy; (3) a concomitant placebo group provides important data to assess reproducibility of results over time; and (4) further studies of dofetilide's efficacy and toxicity should be conducted.
Baroreflex Sensitivity
Authors: La ROVERE MARIA TERESA , MORTARA ANDREA , SCHWARTZ PETER J.
Published: May 2007

Baroreflex Sensitivity. Baroreflex sensitivity (BRS) has rapidly gained considerable attention as a result of multiple experimental and clinical reports on its prognostic value after a myocardial infarction. This article reviews the several aspects related to the use and significance of BRS. The methodology of baroreflex testing in man is described. The complex pathophysiology underlying BRS and the hypotheses proposed to explain its frequent reduction after a myocardial infarction are discussed. The section on experimental data also provides a rationale to understand the relation between increased vagal activity and reduced propensity for ventricular fibrillation. The article focuses largely on the clinical studies relating BRS and risk of cardiac mortality and also discusses the several attempts to modify this marker of reflex vagal activation.
Description and Evaluation of the Res‐QTM Arrhythmia Control Device
Authors: MILLER RAYMOND E. , WILKOFF BRUCE L.
Published: May 2007

The Res‐QTM Arrhythmia Control Device. The Res‐QTM Arrhythmia Control Device (Intermedics Inc.) is one of the latest entries into the growing implantable cardioverter defibrillator (ICD) market. Dysrhythmias are classified according to their zone of detection, with a bradycardia zone, up to 3 tachycardia zones, and a fibrillation zone. Detection criterion, therapies, and redetection criterion within each zone are independently programmable, tailoring the setup to each individual's needs. In a hierarchical manner, this allows efficacy, urgency, and patient comfort to be appropriately balanced. Tachycardia therapy options include antitachycardia pacing (ATP), low‐energy cardioversion, and high‐energy shock, while VVI pacing provides bradycardia therapy. ATP programming is extremely flexible. Biphasic waveform and a maximum output of 700 V have yielded a high rate of successful implantation. Unique features include the multiprogrammable sensing autogain, which tracks evoked T waves during pacing, as well as the use of the pulse generator to perform implant testing. Major strengths include programming flexibility and individualized therapy for multiple dysrhythmias. The major shortcoming relates to a lack of stored electrograms. Although long‐term follow‐up is not yet available, the Res‐QTM appears to be a capable challenger to a peer group of advanced generation ICDs.
Entrainment Techniques for Mapping Atrial and Ventricular Tachycardias
Authors: STEVENSON WILLIAM G. , SAGER PHILIP T. , FRIEDMAN PETER L.
Published: May 2007

Entrainment Mapping. Many atrial tachycardias, atrial flutter, and postmyocardial infarction ventricular tachycardias are due to reentry through large “macroreentrant” circuits. These circuits can be difficult to define by catheter mapping of the activation sequence. Entrainment techniques allow the relation of a mapping site to the reentrant circuit to be assessed on a site‐by‐site basis during catheter mapping. Regions of abnormal conduction that are in the reentrant circuit can be distinguished from bystander sites outside the circuit. A mapping site classification to guide catheter ablation is reviewed
Nonuniform Heating Patterns of Commercial Electrodes for Radiofrequency Catheter Ablation
Authors: MIROTZNIK MARK S. , SCHWARTZMAN DAVID
Published: May 2007

Heating Patterns of Ablation Electrodes. Introduction: Previous investigations of the biophysics of myocardial ablation using radiofrequency energy have focused mainly on the electrode‐myocardial interface. Relatively little has been written about the overall function of commercial electrodes used for ablation. The purpose of this study was to evaluate the heating patterns of several commercial electrodes used for myocardial ablation.

Methods and Results: The specific absorption rate, a unit of measure proportional to the initial rate of rise of the temperature at the electrode‐tissue interface and reflecting the energy deposition from the electrode, was measured during radiofrequency energy application at multiple points around each electrode. These measurements were combined to form a specific absorption rate pattern, which reflected the spatial pattern of energy deposition from the electrode. There was significant nonuniformity of the specific absorption rate pattern of each electrode evaluated. The proximal edge of the electrode and the curvature of the distal portion of the electrode were two sites of accentuated heating relative to the remaining portions of the electrode. The magnitude of this nonuniformity was similar between the 4‐mni length electrodes of different manufacturers, but increased progressively in larger (5‐ and 8‐mm length) electrodes.

Conclusions: The heating patterns of commercial electrodes used for myocardial ablation are nonuniform. These data have implications for electrode design and utilization.
Lidocaine and Nisoldipine Attenuate Almokalant‐Induced Dispersion of Repolarization and Early Afterdepolarizations In Vitro
Authors: ABRAHAMSSON CHRISTINA , CARLSSON LEIF , DUKER GÖRAN
Published: May 2007

Attenuation of Almokalant‐Induced Proarrhythmias In Vitro. Introduction: Treatment with Class III antiarrhythmic agents may lead to increased dispersion or repolarization and early afterdepolarizations (EADs), which are both likely substrates for torsades de pointes. Recent studies in vivo have shown that the prevalence of proarrhythmias induced by Class III agents may be reduced by Na+ or Ca2+‐blocking agents. In the present study, tentative mechanisms for this protective effect were investigated in vitro.

Methods and Results: Transmembrane action potentials were recorded simultaneously from rabbit isolated ventricular muscle (VM) and Purkinje fibers (PF). At a basic cycle length (BCL) of 500 msec, the Class III agent almokalant (0.1 μM) increased the dispersion by prolonging the action potential duration (APD) significantly more in the PF (33%± 4.2%, n = 18) than in the VM (17%± 5.9%, n = 18. P < 0.05). In six of the preparations, addition of 1, 5, and 25 μM lidocaine reduced the almokalant‐induced prolongation in a concentration‐dependent manner mainly in the PF, thereby decreasing the dispersion. At 5 μM lidocaine, the remaining prolongation was 7%± 12.2% (P < 0.05 vs time controls) in the PF and 14%± 6.4% in the VM, respectively. In six other preparations, the addition of 0.01, 0.05, and 0.25 μM nisoldipine did not reduce the almokalant‐induced prolongation in the PF and VM, hut attenuated the spike‐and‐dome appearance of the action potential in the PF. In separate experiments performed at a BCL of 1000 msec, EADs developed in 2 of 6 and 5 of 6 PF during superfusion with almokalant (0.3 and 1 μM, respectively) at an API) of 828 ± 41.4 msec. In six separate preparations pretreated with lidocaine (5 μ) the almokalant‐induced prolongation in the PF was less pronounced and EADs were not observed. Pretreatment with nisoldipine (0.05 μM) did not influence the response to almokalant, and in 4 of 6 preparations the APD exceeded 1000 msec. Despite this extensive prolongation, EADs did not appear.

Conclusion: At concentrations that did not affect the APD in the VM hut reduced the APD in the PE. lidocaine suppressed almokalant‐induced dispersion and the development of EADs. Nisoldipine, (m the other hand, inhibited almokalant‐induced EADs directly. Hence, (he primary APD‐prolonging effect of a Class III agent may he preserved, but the risk of proarrhythmary reduced, during concomitant treatment with low concentrations of a Na+‐ or Ca2+ blocking agent.
Nonuniform Anisotropy is Responsible for Age‐Related Slowing of Atrioventricular Nodal Reentrant Tachycardia
Authors: ANSELME FREDERIC , FREDERIKS JOOST , PAPAGEORGIOU PANOS , MONAHAN KEVIN M. , EPSTEIN LAURENCE M. , SPACH MADISON S. , JOSEPHSON MARK E.
Published: May 2007

Age‐Related Slowing of AVNRT. Introduction: AV nodal reentrant tachycardia cycle length has been shown to he longer in the elderly population. Microfibrosis associated with aging producing nonuniform anisotropic conduction or changes in membrane ionic properties could explain this finding.

Methods and Results: Forty‐five patients (33 women and 12 men) with typical AV nodal reentrant tachycardia were studied to analyze the effects of age on electrophysiologic characteristics of the tachycardia using high‐density catheter mapping of the triangle of Koch. We classified patients into group A (age ≤ 45 years, mean [± SD] 32.7 ± 8.8, n = 27) and group B (age > 45 years, mean [± SD] 61.1 ± 10.2, n =18). Retrograde atrial activation was recorded during tachycardia by means of a 2‐mm decapolar catheter at the His bundle, a quadripolar catheter at the high right atrium, a multipolar catheter (6 to 10 poles) in the coronary sinus, and a deflectable quadripolar catheter at the posterior triangle of Koch. The AH interval at the AV junction as well as HA intervals at several atrial sites were measured during tachycardia. HA intervals at all atrial recording sites except in the posterior triangle of Koch were significantly longer in group B, as well as the tachycardia cycle length (362 vs 329 msec, P = 0.01). The mean AH interval was prolonged by 24 msec in group B, but this difference did not reach statistical significance. A sequential pattern of retrograde atrial activation during tachycardia was more frequently recorded in group B.

Conclusions: Since the delayed activation to the atrium was heterogeneous, transverse nonuniform anisotropic conduction is a likely explanation of these age‐related modifications of AV nodal reentrant tachycardia characteristics.
Facilitation of Sustained Bundle Branch Reentry by Atrial Fibrillation
Authors: BLANCK ZALMEN , JAZAYERI MOHAMMAD , AKHTAR MASOOD
Published: May 2007

Sustained Bundle Branch Reentry. An electrophysiologic evaluation was performed in a patient with an idiopathic dilated cardiomyopathy and syncope. Ventricular tachycardia was not inducible despite the use of a variety of pacing maneuvers during sinus rhythm. Only after the electrical induction of atrial fibrillation did sustained bundle branch reentrant tachycardia (with both right and left bundle branch block QRS configurations) spontaneously occur and become reproducibly induced during right ventricular pacing. Ablation of the right bundle branch eliminated reproducibility of the tachycardia.
Evidence for the Presence of M Cells in the Guinea Pig Ventricle
Authors: SICOURI SERGE , QUIST MICHAEL , ANTZELEVITCH CHARLES
Published: May 2007

M Cells in the Guinea Pig. Introduction: Recent studies have described the presence of M cells in the deep layers of the canine and human ventricle displaying electrophysiologic and pharmacologic features different from those of epicardial (EPI) and endocardial (ENDO) cells. The M cell is distinguished electrophysiologically by the ability of its action potential to prolong disproportionately to that of other myocardial cells with slowing of the stimulation rate and pharmacologically by its unique sensitivity to Class III antiarrhythmic agents. The present study was designed to test the hypothesis that similar cells are present in the guinea pig ventricle.

Methods and Results: We used a dermatome to obtain thin strips of left ventricular free wall from the hearts of guinea pigs (8 to 14 weeks old) and standard microelectrode techniques to record transmembrane activity. Action potential duration measured at 90% repolarization (APD90) was significantly longer in mid‐myocardial (MID) cells than in surface EPI or ENDO cells at all basic cycle lengths (BCLs) tested. At a BCL of 300 msec, APD90 was 102 ± 21, 136 ± 9, and 95 ± 15 msec in EPI, MID, and ENDO cells (mean ± SD; n = 12). At a BCL of 5000 msec, APD90 was 133 ± 14, 185 ± 24, and 135 ± 13 msec in EPI, MID, and ENDO cells ([K+]0= 4 mM). Thus, APD‐rate relations were more pronounced in the MID cells. MID cells were also more sensitive to agents with Class III actions (e.g., d,I‐sotalol: 10 to 100 μM), exhibiting a greater APD prolongation than EPI or ENDO. d,I‐Sotalol also induced early afterdepolarizations in MID cells hut not in EPI or ENDO cells. The rate of rise of the action potential upstroke (Vmax) was significantly greater in MID cells: 129 ± 13, 240 ± 42, and 192 ± 28 V/sec in EPI, MID, and ENDO cells (n = 10 to 18).

Conclusion: Our results demonstrate the existence of important transmural electrical heterogeneity in guinea pig ventricular myocardium. The study provides data in support of the existence of M cells in the mid‐myocardial layers of the guinea pig ventricle exhibiting longer APDs and a greater sensitivity to agents with Class III antiarrhythmic action.
Spectral Turbulence Versus Time‐Domain Analysis of Signal‐Averaged ECG Used for the Prediction of Different Arrhythmic Events in Survivors of Acute Myocardial Infarction
Authors: COPIE XAVIER , HNATKOVA KATERINA , STAUNTON ANNE , JOH CAMM A. , MALIK MAREK
Published: May 2007

Spectral Turbulence SAECG After MI. Introduction: Spectral turbulence analysis of the signal‐averaged ECG (SAECG) combines spectral analysis with statistical evaluation of spectrograms of individual parts of the QRS complex. It has been suggested that it may be superior to conventional time‐domain analysis of the SAECG.

Methods and Results: This study compared the power of conventional time‐domain (40 to 250Hz) and spectral turbulence analyses of SAECG for the prediction of cardiac death, ventricular tachycardia, sudden arrhythmic death, and arrhythmic events (ventricular tachycardia or fibrillation, and/or sudden arrhythmic death) after acute myocardial infarction in 603 patients. The population excluded patients with bundle branch block and other conduction abnormalities. During the first 2 years of follow‐up, there were 40 cardiac deaths, 21 cases of ventricular tachycardia, 11 sudden arrhythmic deaths, and 29 arrhythmic events. The positive predictive accuracy of spectral turbulence analysis was significantly higher than time‐domain analysis for cardiac death at most levels of sensitivity (e.g., 26% vs 20% at 40% sensitivity, P < 0.05). The positive predictive accuracies of the two techniques were not statistically different for the prediction of ventricular tachycardia. For the prediction of sudden arrhythmic death and arrhythmic events, the positive predictive accuracy of spectral turbulence was better than that of time‐domain analysis only at the higher levels of sensitivity (9% vs 2%, P < 0.001 for sudden arrhythmic death at 60% sensitivity, and 14% vs 11%, P < 0.05 for arrhythmic events at 60% sensitivity).

Conclusions: Spectral turbulence analysis is essentially equivalent to time‐domain analysis for the prediction of arrhythmic events after myocardial infarction. However, it performed significantly better than time‐domain analysis for the prediction of cardiac death.