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Refractoriness
Kinds of Refractoriness Selected AbstractsCharacterization of the Electroanatomical Substrate in Human Atrial Fibrillation: The Relationship between Changes in Atrial Volume, Refractoriness, Wavefront Propagation Velocities, and AF BurdenJOURNAL OF CARDIOVASCULAR ELECTROPHYSIOLOGY, Issue 3 2007PIPIN KOJODJOJO M.R.C.P. Introduction: Progressive remodeling occurs in experimental models of AF whereby slowing of conduction, shortening of refractoriness, and atrial dilatation are associated with an increased vulnerability to atrial fibrillation (AF). This study investigates the relative changes in atrial geometry and electrophysiology with increasing AF burden in humans. Methods and Results: Patients undergoing ablation of AF or left-sided accessory pathways were recruited. Atrial volumes were determined by echocardiography. Wavefront propagation velocities (WPV), specifically in the direction of activation, were calculated from pre-ablation activation (CartoÔ) maps of both atria. Dispersion, adaptation of, and effective refractoriness (ERP) were measured at 3 sites. A composite arrhythmogenic index (Atrial Volume/WPV × ERP) was derived to compare the degree of electroanatomical remodeling with AF burden. Fifty-nine patients (22 paroxysmal AF, 19 recurrent persistent AF, and 18 controls) were recruited. AF subjects had slower right atrial WPV (P = 0.01), but no difference in left atrial WPV compared with controls. ERP was reduced globally (P < 0.05), with increased dispersion (P < 0.05). WPV and ERP did not distinguish between patients with paroxysmal or persistent AF. Biatrial volumes were greater only in patients with persistent AF (P < 0.01). There was a stepwise increase in the AI with increasing AF burden (P < 0.0001). Conclusion: An arrhythmogenic substrate exists in human AF, characterized by globally decreased refractoriness with greater dispersion, slower right atrial conduction, and atrial dilatation. Persistence of AF is not accompanied by any further electrical remodeling, but only atrial dilatation. The degree of electroanatomical remodeling is associated with the clinical pattern of AF. [source] Electrophysiological determinants of hypokalaemia-induced arrhythmogenicity in the guinea-pig heartACTA PHYSIOLOGICA, Issue 4 2009O. E. Osadchii Abstract Aim:, Hypokalaemia is an independent risk factor contributing to arrhythmic death in cardiac patients. In the present study, we explored the mechanisms of hypokalaemia-induced tachyarrhythmias by measuring ventricular refractoriness, spatial repolarization gradients, and ventricular conduction time in isolated, perfused guinea-pig heart preparations. Methods:, Epicardial and endocardial monophasic action potentials from distinct left ventricular (LV) and right ventricular (RV) recording sites were monitored simultaneously with volume-conducted electrocardiogram (ECG) during steady-state pacing and following a premature extrastimulus application at progressively reducing coupling stimulation intervals in normokalaemic and hypokalaemic conditions. Results:, Hypokalaemic perfusion (2.5 mm K+ for 30 min) markedly increased the inducibility of tachyarrhythmias by programmed ventricular stimulation and rapid pacing, prolonged ventricular repolarization and shortened LV epicardial and endocardial effective refractory periods, thereby increasing the critical interval for LV re-excitation. Hypokalaemia increased the RV-to-LV transepicardial repolarization gradients but had no effect on transmural dispersion of APD90 and refractoriness across the LV wall. As determined by local activation time recordings, the LV-to-RV transepicardial conduction and the LV transmural (epicardial-to-endocardial) conduction were slowed in hypokalaemic heart preparations. This change was attributed to depressed diastolic excitability as evidenced by increased ventricular pacing thresholds. Conclusion:, These findings suggest that hypokalaemia-induced arrhythmogenicity is attributed to shortened LV refractoriness, increased critical intervals for LV re-excitation, amplified RV-to-LV transepicardial repolarization gradients and slowed ventricular conduction in the guinea-pig heart. [source] High seizure frequency prior to antiepileptic treatment is a predictor of pharmacoresistant epilepsy in a rat model of temporal lobe epilepsyEPILEPSIA, Issue 1 2010Wolfgang Löscher Summary Purpose:, Progress in the management of patients with medically intractable epilepsy is impeded because we do not fully understand why pharmacoresistance happens and how it can be predicted. The presence of multiple seizures prior to medical treatment has been suggested as a potential predictor of poor outcome. In the present study, we used an animal model of temporal lobe epilepsy to investigate whether pharmacoresistant rats differ in seizure frequency from pharmacoresponsive animals. Methods:, Epilepsy with spontaneous recurrent seizures (SRS) was induced by status epilepticus. Frequency of SRS was determined by video/EEG (electroencephalography) monitoring in a total of 33 epileptic rats before onset of treatment with phenobarbital (PB). Results:, Thirteen (39%) rats did not respond to treatment with PB. Before treatment with PB, average seizure frequency in PB nonresponders was significantly higher than seizure frequency in responders, which, however, was due to six nonresponders that exhibited > 3 seizures per day. Such high seizure frequency was not observed in responders, demonstrating that high seizure frequency predicts pharmacoresistance in this model, but does not occur in all nonresponders. Discussion:, The data from this study are in line with clinical experience that the frequency of seizures in the early phase of epilepsy is a dominant risk factor that predicts refractoriness. However, resistance to treatment also occurred in rats that did not differ in seizure frequency from responders, indicating that disease severity alone is not sufficient to explain antiepileptic drug (AED) resistance. These data provide further evidence that epilepsy models are useful in the search for predictors and mechanisms of pharmacoresistance. [source] Ring chromosome 20 syndrome: A link between epilepsy onset and neuropsychological impairment in three childrenEPILEPSIA, Issue 11 2009Aglaia Vignoli Summary Purpose:, Ring chromosome 20 [r(20)] syndrome is a well-defined chromosomal disorder characterized by epilepsy, mild-to-moderate mental retardation, and lack of recognizable dysmorphic features. Epilepsy is often the most important clinical manifestation of the syndrome, even if its appearance is not constantly precocious. Seizures are frequently drug resistant. Methods:, We describe three children with [r(20)] syndrome in whom the onset of epilepsy (age at onset range: 4 years and 6 months to 9 years and 4 months) determined a kind of epileptic status (age at onset range: 6 years and 10 months to 9 years and 8 months) with dramatic neuropsychological deterioration. This epileptic status lasted for several months because of refractoriness to most antiepileptic drugs (AEDs), but it was treated successfully with a combination of valproate and lamotrigine in two children. Results:, As soon as seizures stopped, the children showed prompt recovery with partial restoration of the neuropsychological impairment. Conclusion:, This clinical picture can be described as abrupt epileptic encephalopathy. [source] Hierarchical processing of sound location and motion in the human brainstem and planum temporaleEUROPEAN JOURNAL OF NEUROSCIENCE, Issue 1 2005Katrin Krumbholz Abstract Horizontal sound localization relies on the extraction of binaural acoustic cues by integration of the signals from the two ears at the level of the brainstem. The present experiment was aimed at detecting the sites of binaural integration in the human brainstem using functional magnetic resonance imaging and a binaural difference paradigm, in which the responses to binaural sounds were compared with the sum of the responses to the corresponding monaural sounds. The experiment also included a moving sound condition, which was contrasted against a spectrally and energetically matched stationary sound condition to assess which of the structures that are involved in general binaural processing are specifically specialized in motion processing. The binaural difference contrast revealed a substantial binaural response suppression in the inferior colliculus in the midbrain, the medial geniculate body in the thalamus and the primary auditory cortex. The effect appears to reflect an actual reduction of the underlying activity, probably brought about by binaural inhibition or refractoriness at the level of the superior olivary complex. Whereas all structures up to and including the primary auditory cortex were activated as strongly by the stationary as by the moving sounds, non-primary auditory fields in the planum temporale responded selectively to the moving sounds. These results suggest a hierarchical organization of auditory spatial processing in which the general analysis of binaural information begins as early as the brainstem, while the representation of dynamic binaural cues relies on non-primary auditory fields in the planum temporale. [source] Recovery and refractoriness of auditory evoked fields after gaps in click trainsEUROPEAN JOURNAL OF NEUROSCIENCE, Issue 11 2004Alexander Gutschalk Abstract When clicks are presented in a train at a rate above ,5 Hz, they evoke a sustained field in human auditory cortex that can be recorded by magnetoencephalography. In this study we evaluated how this sustained field continues when a click train is interrupted by a silent gap. The stimuli were click trains with interclick intervals of either 12 or 24 ms, which produce pitches of 83.3 or 41.7 Hz, respectively. The click trains were 996 ms in duration with a gap of 12, 24, 48, 96, or 192 ms beginning 504 ms post-stimulus onset. The sustained field for click trains with short gaps was similar to the one evoked by a continuous click train. Subtraction of the response evoked by a solitary click train of 504 ms enabled estimation of the sustained field in the interval after the gap. The comparison revealed that the sustained field amplitude after the gap was larger than that at the onset of the initial click train in the interval from 150 to 350 ms after onset, and the difference decreased with gap duration. In contrast, the transient P1m was refractory for gaps up to 48 ms, but had nearly recovered its initial amplitude for gaps of 192 ms. We discuss how these results might relate to the perception, i.e. if an interrupted click train is perceived as one continuous sound with a transient gap or as two successive events. [source] Chamber-specific effects of hypokalaemia on ventricular arrhythmogenicity in isolated, perfused guinea-pig heartEXPERIMENTAL PHYSIOLOGY, Issue 4 2009Oleg E. Osadchii Diuretic-induced hypokalaemia has been shown to promote cardiac arrhythmias in hypertensive patients. The present study was designed to determine whether hypokalaemia increases arrhythmic susceptibility of the left ventricle (LV) or the right ventricle (RV), or both. Proarrhythmic effects of hypokalaemic perfusion (2.5 mm K+ for 30 min) were assessed in isolated guinea-pig heart preparations using simultaneous recordings of volume-conducted electrocardiogram and monophasic action potentials from six ventricular epicardial sites. Effective refractory periods, ventricular fibrillation thresholds and inducibility of tachyarrhythmias by programmed electrical stimulation and tachypacing were determined at the LV and the RV epicardial stimulation sites. Hypokalaemia promoted spontaneous ventricular ectopic activity, an effect attributed to non-uniform prolongation of ventricular repolarization resulting in increased RV-to-LV transepicardial dispersion of refractoriness and action potential duration. Furthermore, hypokalaemic perfusion was associated with reduced ventricular fibrillation threshold and increased inducibility of tachyarrhythmias by programmed electrical stimulation and tachypacing as determined at the LV stimulation site. In contrast, the RV stimulation revealed no change in arrhythmic susceptibility of the RV chamber. Consistently, hypokalaemia reduced the LV effective refractory period but had no effect on the RV refractoriness. This change enabled generation of premature propagating responses by extrastimulus application at earlier time points during LV repolarization. Increased prematurity of extrastimulus-evoked propagating responses was associated with exaggerated local inhomogeneities in intraventricular conduction and action potential duration in hypokalaemic LV, thus creating a favourable stage for re-entrant tachyarrhythmias. Taken together, these findings suggest that proarrhythmic effects of hypokalaemia are mostly attributed to increased LV arrhythmogenicity in the guinea-pig heart. [source] Dynamic Effects of Exercise and Different Escape Rhythms on the Supernormal Period of an Accessory PathwayJOURNAL OF CARDIOVASCULAR ELECTROPHYSIOLOGY, Issue 6 2007JEREMY J. LUM M.D. Spontaneous conduction during the supernormal period (SNP) of accessory pathways (AP) is rare and observed only during atrio-ventricular block (AVB). The effect of exercise and different escape rhythms on the SNP is unknown. We evaluated these factors on the SNP of a para-Hisian AP after a failed ablation complicated by AVB. The SNP onset and duration were later and longer during paced versus junctional rhythm. Exercise caused linear shortening of the SNP that was directly related to junctional cycle length. The SNP is a dynamic window shifting in parallel with AP refractoriness and affected by exercise and type of escape rhythm. [source] Characterization of the Electroanatomical Substrate in Human Atrial Fibrillation: The Relationship between Changes in Atrial Volume, Refractoriness, Wavefront Propagation Velocities, and AF BurdenJOURNAL OF CARDIOVASCULAR ELECTROPHYSIOLOGY, Issue 3 2007PIPIN KOJODJOJO M.R.C.P. Introduction: Progressive remodeling occurs in experimental models of AF whereby slowing of conduction, shortening of refractoriness, and atrial dilatation are associated with an increased vulnerability to atrial fibrillation (AF). This study investigates the relative changes in atrial geometry and electrophysiology with increasing AF burden in humans. Methods and Results: Patients undergoing ablation of AF or left-sided accessory pathways were recruited. Atrial volumes were determined by echocardiography. Wavefront propagation velocities (WPV), specifically in the direction of activation, were calculated from pre-ablation activation (CartoÔ) maps of both atria. Dispersion, adaptation of, and effective refractoriness (ERP) were measured at 3 sites. A composite arrhythmogenic index (Atrial Volume/WPV × ERP) was derived to compare the degree of electroanatomical remodeling with AF burden. Fifty-nine patients (22 paroxysmal AF, 19 recurrent persistent AF, and 18 controls) were recruited. AF subjects had slower right atrial WPV (P = 0.01), but no difference in left atrial WPV compared with controls. ERP was reduced globally (P < 0.05), with increased dispersion (P < 0.05). WPV and ERP did not distinguish between patients with paroxysmal or persistent AF. Biatrial volumes were greater only in patients with persistent AF (P < 0.01). There was a stepwise increase in the AI with increasing AF burden (P < 0.0001). Conclusion: An arrhythmogenic substrate exists in human AF, characterized by globally decreased refractoriness with greater dispersion, slower right atrial conduction, and atrial dilatation. Persistence of AF is not accompanied by any further electrical remodeling, but only atrial dilatation. The degree of electroanatomical remodeling is associated with the clinical pattern of AF. [source] Validation of ECG Indices of Ventricular Repolarization Heterogeneity: A Computer Simulation StudyJOURNAL OF CARDIOVASCULAR ELECTROPHYSIOLOGY, Issue 10 2005BART HOOFT VAN HUYSDUYNEN M.D. Introduction: Repolarization heterogeneity (RH) is functionally linked to dispersion in refractoriness and to arrhythmogenicity. In the current study, we validate several proposed electrocardiogram (ECG) indices for RH: T-wave amplitude, -area, -complexity, and -symmetry ratio, QT dispersion, and the Tapex-end interval (the latter being an index of transmural dispersion of the repolarization (TDR)). Methods and Results: We used ECGSIM, a mathematical simulation model of ECG genesis in a human thorax, and varied global RH by increasing the standard deviation (SD) of the repolarization instants from 20 (default) to 70 msec in steps of 10 msec. T-wave amplitude, -area, -symmetry, and Tapex-end depended linearly on SD. T-wave amplitude increased from 275 ± 173 to 881 ± 456 ,V, T-wave area from 34 × 103± 21 × 103 to 141 × 103± 58 × 103,V msec, T-wave symmetry decreased from 1.55 ± 0.11 to 1.06 ± 0.23, and Tapex-end increased from 84 ± 17 to 171 ± 52 msec. T-wave complexity increased initially but saturated at SD = 50 msec. QT dispersion increased modestly until SD = 40 msec and more rapidly for higher values of SD. TDR increased linearly with SD. Tapex-end increased linearly with TDR, but overestimated it. Conclusion: T-wave complexity did not discriminate between differences in larger RH values. QT dispersion had low sensitivity in the transitional zone between normal and abnormal RH. In conclusion, T-wave amplitude, -area, -symmetry, and, with some limitations, Tapex-end and T-wave complexity reliably reflect changes in RH. [source] Mechanism of Propensity to Atrial Fibrillation in Patients Undergoing Isthmus Ablation for Typical Atrial FlutterJOURNAL OF CARDIOVASCULAR ELECTROPHYSIOLOGY, Issue 2 2005HEMANTH RAMANNA M.D. Background: Patients undergoing isthmus ablation for atrial flutter (AFL) may reveal postablation atrial fibrillation (AF). The electrophysiological mechanism is unclear. In patients with idiopathic AF, enhanced spatial dispersion of right atrial refractoriness was the substrate for the initiation of AF. We hypothesize that dispersion of right atrial refractoriness in patients undergoing AFL ablation is the major cause of postablation AF. Methods: Consecutive patients (n = 42) undergoing isthmus ablation for typical AFL were included. Twelve right atrial unipolar electrograms were recorded. Inducibility of AF was assessed by a pacing protocol, starting with one extrastimulus, followed by more aggressive pacing until AF was induced. Mean fibrillatory intervals were used to assess local refractoriness of each recording site. Spatial dispersion of right atrial refractoriness was calculated as the coefficient of dispersion (CD-value: standard deviation of the mean of all local mean fibrillatory intervals as a percentage of the overall mean fibrillatory interval). A CD-value of 3.0 or less was defined as normal, whereas CD-value greater than 3.0 was considered enhanced dispersion. PES and refractoriness analysis were followed by isthmus ablation. Results: Of the 42 patients, 29 had CD-value of 3.0 or less. In these 29 patients, AF was induced with 1 extrastimulus in only 1 patient, with 2 extrastimuli in 4 patients and burst pacing was required to induce AF in 24 of these 29 patients. Prior to the procedure, 5 of 29 patients had AF episodes, after ablation 6 of 29 patients. Of the 42 patients, 13 had CD-value greater than 3.0, AF was induced with a single extrastimulus in 11 patients, with 2 extrastimuli in the remaining 2 patients. Of the 13 patients, 11 had AF episodes both before and after ablation (P < 0.001). Conclusion: Enhanced spatial dispersion of right atrial refractoriness may be the substrate for propensity to AF in patients with AFL. The substrate was associated with enhanced inducibility of atrial fibrillation. [source] Effect of Chronic Amiodarone Therapy on Excitable Gap During Typical Human Atrial FlutterJOURNAL OF CARDIOVASCULAR ELECTROPHYSIOLOGY, Issue 12 2004PHILIPPE MAURY M.D. Introduction: Class I antiarrhythmic drugs increase duration of the excitable gap (EG) during typical atrial flutter whereas intravenous class III drugs decrease the EG. The effect of chronic oral amiodarone therapy on the EG is unknown. Methods and Results: EG was prospectively determined by introducing a premature stimulus and analyzing the response pattern during typical atrial flutter in 30 patients without antiarrhythmic drugs and in 20 patients under chronic oral amiodarone therapy. EG was calculated by the difference between the longest coupling interval leading to resetting and the effective atrial refractory period (EARP). A fully EG was defined by the portion of EG where the response curve of the return cycles was flat. A partially EG was defined by the portion of EG where the return cycle increases while coupling interval decreases. A resetting response curve was constructed by plotting the duration of the return cycle against the value of the coupling interval. Cycle length (CL; 222 ± 17 vs 267 ± 20 msec, P < 0.0001), EARP (128 ± 16 vs 152 ± 18 msec, P < 0.0001), and EG (54 ± 19 vs 70 ± 21 msec, P = 0.01) were significantly longer in patients taking amiodarone than in controls. Compared to CL, the relative part of the EARP (57 ± 7 vs 57 ± 6%, P = 0.96) and EG (24 ± 7 vs 26 ± 8%, P = 0.41) were comparable in both groups. The fully EG was larger in patients under chronic amiodarone therapy than in controls (39 ± 21 vs 26 ± 20 msec, P = 0.03). Neither duration of the partially EG (28 ± 15 vs 31 ± 15 msec, P = 0.42) nor slope of the ascending portion of the resetting response curve (1.15 ± 0.5 vs 1.13 ± 0.4 msec/msec, P = 0.71) differed between the two groups. Conclusion: EG in patients under chronic amiodarone therapy is significantly larger than in controls, mainly because of a longer fully EG. This observation may be explained by opposite effects on conduction velocity and refractoriness. [source] On the Atrial Response to Focal Discharges in ManJOURNAL OF CARDIOVASCULAR ELECTROPHYSIOLOGY, Issue 6 2004HEMANTH RAMANNA M.D. Introduction: Triggers and vulnerability are key factors for the occurrence of atrial fibrillation (AF). The aim of this study was to assess spatial dispersion of atrial refractoriness and vulnerability in response to both focal discharges as well as programmed electrical stimulation in patients undergoing ablation of atrial arrhythmogenic foci. Methods and Results: Twenty-nine patients were studied, and 12 right atrial unipolar electrograms were recorded. Inducibility of AF was assessed by a pacing protocol that started with one extrastimulus, followed by more aggressive pacing until AF was obtained. Mean fibrillatory intervals were used to assess the local refractoriness of each recording site. Spatial dispersion of refractoriness was calculated as the coefficient of dispersion (CD value: standard deviation of the mean of all local mean fibrillatory intervals as a percentage of the overall mean fibrillatory interval). Based on our previous study, a CD value , 3.0 was defined as normal, whereas a CD value >3.0 was considered enhanced spatial dispersion of refractoriness. Fifteen of 29 patients had normal dispersion of refractoriness (mean CD value 1.65 ± 0.43), and AF was inducible with burst pacing only. These patients had focal discharges causing rapid atrial tachycardia with a focal activation pattern. Activation mapping of focal activity was possible in 14 of 15 patients. Focal triggering of AF occurred in only 1 of 15 patients. Fourteen of 29 patients had enhanced dispersion (mean CD value 4.2 ± 0.72). AF was inducible with a single extrastimulus in 11 of 14 patients (P < 0.001). Focal triggering of AF occurred in all 14 patients. Conclusion: Spatial dispersion of atrial refractoriness determines whether focal atrial discharges trigger AF with disorganized activity or, alternatively, only rapid atrial tachycardia. (J Cardiovasc Electrophysiol, Vol. 15, pp. 1-8, June 2004) [source] Inhibitors of the Na+/H+ Exchanger Cannot Prevent Atrial Electrical Remodeling in the GoatJOURNAL OF CARDIOVASCULAR ELECTROPHYSIOLOGY, Issue 4 2004YURI BLAAUW M.D. Introduction: It has been suggested that blockade of the Na+/H+ exchanger (NHE1) can prevent atrial fibrillation (AF)-induced electrical remodeling and the development of AF. Methods and Results: AF was maintained by burst pacing in 10 chronically instrumented conscious goats. Intravenous and oral dosages of two NHE1 blockers (EMD87580 and EMD125021) resulted in plasma levels several magnitudes higher than required for effective NHE1 blockade. Shortening of atrial refractoriness immediately after 5 minutes of AF was not prevented by NHE1 blockade. In remodeled atria, increasing dosages of EMD87580 and EMD125021 did not reverse shortening of the atrial refractory period or reduce the duration of AF episodes. The cycle length during persistent AF also was not affected. Oral pretreatment with EMD87580 (8 mg/kg bid) starting 3 days before AF could not prevent electrical remodeling. After 24 and 48 hours of remodeling, the duration of AF paroxysms was 47 ± 32 seconds and 135 ± 63 seconds compared to 56 ± 17 seconds and 136 ± 52 seconds in placebo-treated animals (P > 0.8), respectively. Conclusion: In the goat model of AF, the Na+/H+ exchanger inhibitors EMD87580 and EMD125021 did not prevent or revert AF-induced electrical remodeling. This indicates that activation of the Na+/H+ exchanger is not involved in the intracellular pathways of electrical remodeling. This does not support the suggestion that blockers of the Na+/H+ exchanger may be beneficial for prevention and treatment of AF. (J Cardiovasc Electrophysiol, Vol. 15, pp. 440-446, April 2004) [source] Identification and Characterization of Atrioventricular Parasympathetic Innervation in HumansJOURNAL OF CARDIOVASCULAR ELECTROPHYSIOLOGY, Issue 8 2002KARA J. QUAN M.D. AV Parasympathetic Innervation.Introduction: We hypothesized that in humans there is an epicardial fat pad from which parasympathetic ganglia supply the AV node. We also hypothesized that the parasympathetic nerves innervating the AV node also innervate the right atrium, and the greatest density of innervation is near the AV nodal fat pad. Methods and Results: An epicardial fat pad near the junction of the left atrium and right inferior pulmonary vein was identified during cardiac surgery in seven patients. A ring electrode was used to stimulate this fat pad intraoperatively during sinus rhythm to produce transient complete heart block. Subsequently, temporary epicardial wire electrodes were sutured in pairs on this epicardial fat pad, the high right atrium, and the right ventricle by direct visualization during coronary artery bypass surgery in seven patients. Experiments were performed in the electrophysiology laboratory 1 to 5 days after surgery. Programmed atrial stimulation was performed via an endocardial electrode catheter advanced to the right atrium. The catheter tip electrode was moved in 1-cm concentric zones around the epicardial wires by fluoroscopic guidance. Atrial refractoriness at each catheter site was determined in the presence and absence of parasympathetic nerve stimulation (via the epicardial wires). In all seven patients, an AV nodal fat pad was identified. Fat pad stimulation during and after surgery caused complete heart block but no change in sinus rate. Fat pad stimulation decreased the right atrial effective refractory period at 1 cm (280 ± 42 msec to 242 ± 39 msec) and 2 cm (235 ± 21 msec to 201 ± 11 msec) from the fat pad (P = 0.04, compared with baseline). No significant change in atrial refractoriness occurred at distances > 2 cm. The response to stimulation decreased as the distance from the fat pad increased. Conclusion: For the first time in humans, an epicardial fat pad was identified from which parasympathetic nerve fibers selectively innervate the AV node but not the sinoatrial node. Nerves in this fat pad also innervate the surrounding right atrium. [source] Arrhythmogenesis of T Wave Alternans Associated with Surface QRS Complex Alternans and the Role of Ventricular Prematurity: Observations from a Canine Model of LQT3 SyndromeJOURNAL OF CARDIOVASCULAR ELECTROPHYSIOLOGY, Issue 6 2002MASAOMI CHINUSHI M.D. Intramural TWA and Its Arrhythmogenesis.Introduction: T wave alternans (TWA) is characterized by cycle-to-cycle changes in the QT interval and/or T wave morphology. It is believed to amplify the underlying dispersion of ventricular repolarization. The aim of this study was to examine the mechanisms and arrhythmogenesis of TWA accompanied by QRS complex and/or blood pressure (BP) waveform alternans, using transmural ventricular electrogram recordings in an anthopleurin-A model of long QT syndrome. Methods and Results: The cardiac cycle length was gradually shortened by interruption of vagal stimulation, and TWA was induced in six canine hearts. Transmural unipolar electrograms were recorded with plunge needle electrodes from endocardial (Endo), mid-myocardial (Mid), and epicardial (Epi) sites, along with the surface ECG and BP. The activation-recovery interval (ARI) was measured to estimate local refractoriness. During TWA, ARI alternans was greater at the Mid than the Epi/Endo sites, and it was associated with the development of marked spatial dispersion of ventricular repolarization. As TWA increased, ventricular activation of the cycles associated with shorter QT intervals displayed delayed conduction at the Mid sites as a result of a critically longer ARI of the preceding cycle and longer QT interval, while normal conduction was preserved at the Epi site. Delayed conduction at the Mid sites manifested as surface ECG QRS and BP waveform alternans, and spontaneous ventricular tachyarrhythmias developed in absence of ventricular prematurity. In other instances, in absence of delayed conduction during TWA, ventricular premature complexes infringed on a prominent spatial dispersion of ventricular repolarization of cycles with long QT intervals and initiated ventricular tachyarrhythmia. Conclusion: TWA accompanied by QRS alternans may signal a greater ventricular electrical instability, since it is associated with intramural delayed conduction, which can initiate ventricular tachyarrhythmia without ventricular premature complexes. [source] Reentry Site During Fibrillation Induction in Relation to Defibrillation Efficacy for Different Shock WaveformsJOURNAL OF CARDIOVASCULAR ELECTROPHYSIOLOGY, Issue 5 2001Ph.D., RAYMOND E. IDEKER M.D. Reentry Site and Defibrillation Waveform Efficacy.Introduction: Unsuccessful defibrillation shocks may reinitiate fibrillation by causing postshock reentry. Methods and Results: To better understand why some waveforms are more efficacious for defibrillation, reentry was induced in six dogs with 1-, 2-, 4-, 8-, and 16-msec monophasic and 1/1- (both phases 1 msec) 2/2-, 4/4-, and 8/8-msec biphasic shocks. Reentry was initiated by 141 ± 15 V shocks delivered from a defibrillator with a 150- , F capacitance during the vulnerable period of paced rhythm (183 ± 12 msec after the last pacing stimulus). The shock potential gradient field was orthogonal to the dispersion of refractoriness. Activation was mapped with 121 electrodes covering 4 × 4 cm of the right ventricular epicardium, and potential gradient and degree of recovery of excitability were estimated at the sites of reentry. Defibrillation thresholds (DFTs) were estimated by an up-down protocol for the same nine waveforms in eight dogs internally and in nine other dogs externally. DFT voltages for the different waveforms were positively correlated with the magnitude of shock potential gradient and negatively correlated with the recovery interval at the site at which reentry was induced by the waveform during paced rhythm for both internal (DFT = 1719 + 64.5 , V , 11.1RI; R2= 0.93) and external defibrillation (DFT = 3445 + 150 , V , 22RI; R2= 0.93). Conclusion: The defibrillation waveforms with the lowest DFTs were those that induced reentry at sites of low shock potential gradient, indicating efficacious stimulation of myocardium. Additionally, the site of reentry induced by waveforms with the lowest DFTs was in myocardium that was more highly recovered just before the shock, perhaps because this high degree of recovery seldom occurs during defibrillation due to the rapid activation rate during fibrillation. [source] Focal Atrial Fibrillation: Experimental Evidence for a Pathophysiologic Role of the Autonomic Nervous SystemJOURNAL OF CARDIOVASCULAR ELECTROPHYSIOLOGY, Issue 5 2001PATRICK SCHAUERTE M.D. Focal AF and Autonomic Nerves.Introduction: Focal paroxysmal atrial fibrillation (AF) was shown recently to originate in the pulmonary veins (PVs) and superior vena cava (SVC). In the present study, we describe an animal model in which local high-frequency electrical stimulation produces focal atrial activation and AF/AT (atrial tachycardia) with electrogram characteristics consistent with clinical reports. Methods and Results: In 21 mongrel dogs, local high-frequency electrical stimulation was performed by delivering trains of electrical stimuli (200 Hz, impulse duration 0.1 msec) to the PVs/SVC during atrial refractoriness. Atrial premature depolarizations (APDs), AT, and AF occurred with increasing highfrequency electrical stimulation voltage. APD/AT/AF originated adjacent to the site of high-frequency electrical stimulation and were inducible in 12 of 12 dogs in the SVC and in 8 of 9 dogs in the left superior PV (left inferior PV: 7/8, right superior PV: 6/8; right inferior PV: 4/8). In the PVs, APDs occurred at 13 ± 8 V and AT/AF at 15 ± 9 V (P < 0.01; n = 25). In the SVC, APDs were elicited at 19 ± 6 V and AT/AF at 26 ± 6 V (P < 0.01; n = 12). High-frequency electrical stimulation led to local refractory period shortening in the PVs. The response to high-frequency electrical stimulation was blunted or prevented after beta-receptor blockade and abolished by atropine. In vitro, high-frequency electrical stimulation induced a heterogeneous response, with shortening of the action potential in some cells (from 89 ± 35 msec to 60 ± 22 msec; P < 0.001; n = 7) but lengthening of the action potential and development of early afterdepolarizations that triggered APD/AT in other cells. Action potential shortening was abolished by atropine. Conclusion: High-frequency electrical stimulation evokes rapid ectopic beats from the PV/SVC, which show variable degrees of conduction block to the atria and induce AF, resembling findings in patients with focal idiopathic paroxysmal AF. The occurrence of the arrhythmia in this animal model was likely due to alterations in local autonomic tone by high-frequency electrical stimulation. Further research is needed to prove absolutely that the observed effects of high-frequency electrical stimulation were caused by autonomic nerve stimulation. [source] QT Dispersion Does Not Represent Electrocardiographic Interlead Heterogeneity of Ventricular RepolarizationJOURNAL OF CARDIOVASCULAR ELECTROPHYSIOLOGY, Issue 8 2000MAREK MALIK Ph.D. QT Dispersion and Repolarization Heterogeneity. Introduction: QT dispersion (QTd, range of QT intervals in 12 ECG leads) is thought to reflect spatial heterogeneity of ventricular refractoriness. However, QTd may be largely due to projections of the repolarization dipole rather than "nondipolar" signals. Methods and Results: Seventy-eight normal subjects (47 ± 16 years, 23 women), 68 hypertrophic cardiomyopathy patients (HCM; 38 ± 15 years. 21 women), 72 dilated cardiomyopathy patients (DCM; 48 ± 15 years, 29 women), and 81 survivors of acute myocardial infarction (AMI; 63 ± 12 years, 20 women) had digital 12-lead resting supine ECGs recorded (10 ECGs recorded in each subject and results averaged). In each ECG lead, QT interval was measured under operator review by QT Guard (GE Marquette) to obtain QTd. QTd was expressed as the range, standard deviation, and highest-to-lowest quartile difference of QT interval in all measurable leads. Singular value decomposition transferred ECGs into a minimum dimensional time orthogonal space. The first three components represented the ECG dipole; other components represented nondipolar signals. The power of the T wave nondipolar within the total components was computed to measure spatial repolarization heterogeneity (relative T wave residuum, TWR). OTd was 33.6 ± 18.3, 47.0 ± 19.3, 34.8 ± 21.2, and 57.5 ± 25.3 msec in normals, HCM, CM, and AMI, respectively (normals vs DCM: NS, other P < 0.009). TWR was 0.029%± 0.031%, 0.067%± 0.067%, 0.112%± 0.154%, and 0.186%± 0.308% in normals, HCM, DCM, and AMI (HCM vs DCM: NS. other P < 0.006), The correlations between QTd and TWR were r = -0.0446, 0.2805, -0.1531, and 0.0771 (P = 0.03 for HCM, other NS) in normals, HCM, DCM, and AMI, respectively. Conclusion: Spatial heterogeneity of ventricular repolarization exists and is measurable in 12-lead resting ECGs. It differs between different clinical groups, but the so-called QT dispersion is unrelated to it. [source] Changes in Left Ventricular Repolarization and Ion Channel Currents Following a Transient Rate Increase Superimposed on Bradycardia in Anesthetized DogsJOURNAL OF CARDIOVASCULAR ELECTROPHYSIOLOGY, Issue 6 2000MICHAEL RUBART M.D. Electrical Remodeling of the Heart due to Rate. Introduction: We previously demonstrated in dogs that a transient rate increase superimposed on bradycardia causes prolongation of ventricular refractoriness that persists for hours after resumption of bradycardia. In this study, we examined changes in membrane currents that are associated with this phenomenon. Methods and Results: The whole cell, patch clamp technique was used to record transmembrane voltages and currents, respectively, in single mid-myocardial left ventricular myocytes from dogs with 1 week of complete AV block; dogs either underwent 1 hour of left ventricular pacing at 120 beats/min or did not undergo pacing. Pacing significantly heightened mean phase 1 and peak plateau amplitudes by ,6 and ,3 mV, respectively (P < 0.02). and prolonged action potential duration at 90% repolarization from 235 ± 8 msec to 278 ± 8 msec (1 Hz; P = 0.02). Rapid pacing-induced changes in transmembrane ionic currents included (1) a more pronounced cumulative inactivation of the 4-aminopyridine-sensitive transient outward K+ current, I to over the range of physiologic frequencies, resulting from a ,30% decrease in the population of quickly reactivating channels; (2) increases in peak density of L-type Ca2+ currents, Ica.I.' by 15% to 35% between +10 and +60 mV; and (3) increases in peak density of the Ca2+ -activated chloride current, ICl.Ca' by 30% to 120% between +30 and +50 mV. Conclusion: Frequency-dependent reduction in Ito combined with enhanced ICa.I. causes an increase in net inward current that may he responsible for the observed changes in ventricular repolarization. This augmentation of net cation influx is partially antagonized by an increase in outward ICa.Cl. [source] Photoperiod,Testicular,Immune Interaction in a Seasonal Breeder Indian Palm Squirrel Funambulus pennanti During the Reproductively Inactive and Active PhasesJOURNAL OF NEUROENDOCRINOLOGY, Issue 1 2009R. Ahmad The differential effect of long (LD; 16 : 8 h light/dark), short (SD; 10 : 14 h light/dark) and natural day length (NDL; 12 : 12 h light/dark) during the reproductively inactive (RIP) and active (RAP) phases was assessed in relation to immunity and reproductive function of a tropical rodent Funambulus pennanti. They presented high immunity and low testicular activity during RIP and an opposite during RAP. SD increased spleen and thymus weight, leukocyte and lymphocyte counts, cell mediated immunity [i.e. blastogenic response in terms of percentage stimulation ratio of splenocytes and thymocytes (when challenged with concanavalin A)] and delayed type hypersensitivity to oxazolone. SD during RIP increased the above mentioned parameters and reduced testes weight compared to NDL groups. During RAP, LD reduced all the immunological parameters when compared with NDL and SD experiencing groups of RIP and RAP phases. The LD group reduced the immunological parameters compared to RAP, suggesting that LD had always an inhibitory effect on immune status being independent of reproductive phases. The intensity of the stimulatory effects of SD and inhibitory effects of LD during both reproductive phases was significantly different. We exposed another set of squirrels to the above photoperiodic schedule for prolonged period (30 weeks) during RAP. A clear testicular refractoriness followed by immunorefractoriness was observed in the group experiencing SD and LD for 30 weeks. The photorefractoriness presented by the testes was inversely related to the immunorefractoriness. The peripheral melatonin level of those squirrels reflected the photoperiodic signal perceived by squirrels for immunomodulation and gonadal function, suggesting that immune system and gonadal function might have coevolved. [source] Signaling mechanisms of melatonin in antiproliferation of hormone-refractory 22Rv1 human prostate cancer cells: implications for prostate cancer chemopreventionJOURNAL OF PINEAL RESEARCH, Issue 2 2007Chun W. Tam Abstract:, There is an unmet clinical demand for safe and effective pharmaceuticals/nutraceuticals for prostate cancer prevention and hormone-refractory prostate cancer treatment. Previous laboratory and human studies of our laboratory demonstrated an association between the antiproliferative action of melatonin and melatonin MT1 receptor expression in prostate cancer. The aim of this study was to determine, using a pharmacological approach, the signaling mechanisms of melatonin in hormone-refractory 22Rv1 human prostate cancer cell antiproliferation. Both immunoreactive MT1 and MT2 subtypes of G protein-coupled melatonin receptor were expressed in 22Rv1 cells. Melatonin inhibited, concentration dependently, cell proliferation, upregulated p27Kip1 gene transcription and protein expression, and downregulated activated androgen signaling in 22Rv1 cells. While the effects of melatonin were mimicked by 2-iodomelatonin, a high-affinity nonselective MT1 and MT2 receptor agonist, melatonin effects were blocked by luzindole, a nonselective MT1 and MT2 receptor antagonist, but were unaffected by 4-phenyl-2-propionamidotetraline, a selective MT2 receptor antagonist. Importantly, we discovered that the antiproliferative effect of melatonin exerted via MT1 receptor on p27Kip1 gene and protein upregulation is mediated by a novel signaling mechanism involving co-activation of protein kinase C (PKC) and PKA in parallel. Moreover, we also showed that a melatonin/MT1/PKC mechanism is involved in melatonin-induced downregulation of activated androgen signal transduction in 22Rv1 cells. Taken together with the known molecular mechanisms of prostate cancer progression and transition to androgen independence, our data provide strong support for melatonin to be a promising small-molecule useful for prostate cancer primary prevention and secondary prevention of the development and progression of hormone refractoriness. [source] Characterization of the Acute Cardiac Electrophysiologic Effects of Ethanol in DogsALCOHOLISM, Issue 9 2007Guilherme Fenelon Background: Alcohol has been related to atrial fibrillation (holiday heart syndrome), but its electrophysiologic actions remain unclear. Methods: We evaluated the effects of alcohol in 23 anesthetized dogs at baseline and after 2 cumulative intravenous doses of ethanol: first dose 1.5 ml/kg (plasma level 200 mg/dl); second dose 1.0 ml/kg (279 mg/dl). In 13 closed-chest dogs (5 with intact autonomic nervous system, 5 under combined autonomic blockade and 3 sham controls), electrophysiologic evaluation and monophasic action potential (MAP) recordings were undertaken in the right atrium and ventricle. In 5 additional dogs, open-chest biatrial epicardial mapping with 8 bipoles on Bachmann's bundle was undertaken. In the remaining 5 dogs, 2D echocardiograms and ultrastructural analysis were performed. Results: In closed-chest dogs with intact autonomic nervous system, ethanol had no effects on surface electrocardiogram and intracardiac variables. At a cycle length of 300 milliseconds, no effects were noted on atrial and ventricular refractoriness and on the right atrial MAP. These results were not altered by autonomic blockade. No changes occurred in sham controls. In open-chest dogs, ethanol did not affect inter-atrial conduction time, conduction velocity, and wavelength. Atrial arrhythmias were not induced in any dog, either at baseline or after ethanol. Histological and ultrastructural findings were normal but left ventricular (LV) ejection fraction decreased in treated dogs (77 vs. 73 vs. 66%; p = 0.04). Conclusion: Ethanol at medium and high doses depresses LV systolic function but has no effects on atrial electrophysiological parameters. These findings suggest that acute alcoholic intoxication does not directly promote atrial arrhythmias. [source] Predictors of corticosteroid-dependent and corticosteroid-refractory inflammatory bowel disease: analysis of a Chinese cohort studyALIMENTARY PHARMACOLOGY & THERAPEUTICS, Issue 8 2009D. K. L. CHOW Summary Background, Patients with inflammatory bowel disease (IBD) who are corticosteroid-dependent or -refractory are at higher risk of developing disease- and treatment-related complications. Aims, To identify retrospectively clinical factors present at diagnosis that predict the occurrence of corticosteroid dependency and refractoriness in Crohn's disease (CD) and ulcerative colitis (UC) patients. Methods, A total of 310 IBD patients (134 CD, 176 UC) were observed for 2140 person years and their use of systemic corticosteroids was determined. Outcomes of corticosteroid dependency and refractoriness were recorded. Univariate and multivariate analyses were performed to determine the clinical factors associated with outcomes. Results, Seventy-seven (57.5%) CD and 95 (54.0%) UC patients had received corticosteroids during study period. In CD, thrombocytosis [Hazard ratio (HR):3.0] predicted, whereas colonic CD (HR:0.3) negatively predicted corticosteroid dependency. Stricturing phenotype (HR:4.5) predicted corticosteroid-refractory CD. For UC, thrombocytosis (HR:3.9) and extensive colitis (HR:1.7) predicted corticosteroid dependency. Presence of anaemia (HR:10.8) at diagnosis and initial requirement of total parenteral nutrition (TPN) (HR:18.8) predicted corticosteroid-refractory UC. The cumulative risks of surgery were 17.8% and 5.4% for CD and UC patients respectively at 1 year after starting corticosteroids. Conclusions, Thrombocytosis at diagnosis predicted corticosteroid-dependency in IBD. Stricturing phenotype of CD and the presence of anaemia in UC predicted subsequent course of corticosteroid refractoriness. [source] Ectopic Atrial Rhythm with Exit Block Following Catheter Ablation for Focal Atrial Tachycardias in a Patient with Prior Surgery for Atrial Septal DefectPACING AND CLINICAL ELECTROPHYSIOLOGY, Issue 6 2002KIMIE OHKUBO OHKUBO, K., et al.: Ectopic Atrial Rhythm with Exit Block Following Catheter Ablation for Focal Atrial Tachycardias in a Patient with Prior Surgery for Atrial Septal Defect. The patient was a 40-year-old woman with a history of surgery for atrial septal defect and catheter ablation for typical atrial flutter. An electrophysiological study was performed because she had palpitation and syncope. She had ectopic atrial rhythm originating from low lateral RA. Two focal atrial tachycardias ([1] superior vena cava-RA junction and [2] a low posteroseptal RA) were successfully ablated. Following catheter ablation for the second atrial tachycardia, she developed junctional rhythm because ectopic atrial rhythm showed exit block. However, atrial activation of junctional rhythm could conduct into the ectopic atrial rhythm focus and reset the rhythm when atrial activation of junctional rhythm reached the blocked line after atrial refractoriness by preceding ectopic atrial rhythm. [source] Effect of Different Pacing Protocols on the Induction of Atrial Fibrillation in a Transvenously Paced Sheep ModelPACING AND CLINICAL ELECTROPHYSIOLOGY, Issue 6 2001RIK WILLEMS WILLEMS, R. et al.: Effect of Different Pacing Protocols on the Induction of Atrial Fibrillation in a Transvenously Paced Sheep Model. In different animal models rapid atrial stimulation led to a shortening and maladaptation to rate of the atrial effective refractory period (AERP). This atrial electrical remodeling resulted in an increased vulnerability to atrial fibrillation (AF). These experimental findings formed the rationale for a stringent pursuit of sinus rhythm in patients with AF, since this would prevent or reverse atrial remodeling. This study tested the hypothesis that a reduction of arrhythmia burden would lead to a decreased vulnerability for AF. Different rapid atrial pacing protocols in a sheep model were used. During 15 weeks, 13 animals were continuously rapid paced and 7 animals were intermittently burst-paced, resulting in rapid atrial activation during 100% versus 33 ± 4% of the time, respectively. In the continuously paced group, 77% of the animals developed sustained AF (i.e., >1 hour) versus only 29% in the burst-paced group (P < 0.05). However, there was no difference in mean AERP shortening over time, nor maximal AERP shortening per animal, between both protocols. Minimal AERP was 103 ± 5 ms in the continuously paced group and 107 ± 5 in the burst-paced group (P = NS). Significant changes could be identified in effect on P wave duration, AVN function, and atrial dilation. Conduction slowing was more pronounced in the continuously paced group with a maximal P wave duration of 136 ± 4 ms in this group versus 116 ± 5 in the burst-paced group (P < 0.05). In the continuously paced group, the right atrial area significantly increased from 2.5 ± 0.1 cm2 at baseline to 4.2 ± 0.2 cm2. In the burst-paced group there was no significant atrial dilatation (from 2.6 ± 0.1 to 2.8 ± 0.1 cm2). In conclusion, limiting atrial arrhythmia burden slowed the development of sustained AF in this sheep model. This was not mediated by a decreased influence on atrial refractoriness but seemed to be dependent on smaller changes in atrial conduction and dimensions. [source] Regional Differences in Arrhythmogenic Aftereffects of High Intensity DC Stimulation in the VentriclesPACING AND CLINICAL ELECTROPHYSIOLOGY, Issue 5 2000ITSUO KODAMA Regional differences of the aftereffects of high intensity DC stimulation were investigated in isolated rabbit hearts stained with a voltage-sensitive dye (di-4-ANEPPS). Optical action potential signals were recorded from the epicardial surface of the right and left ventricular free wall (RVep, LVep) and from the right endocardial surface of the interventricular septum (IVS). Ten-millisecond monophasic DC stimulation (S2, 20,120 V) was applied to the signal recording spots during the early plateau phase of the action potential induced by basic stimuli (S1, 2.5 Hz). There was a linear relationship between S2 voltage and the S2 field intentisy (FI). S2 caused postshock additional depolarization. giving rise to a prolongation of the shocked action potential. With S2, 40 V (FI ,,20 V/cm), terminal repolarization of action potential was inhibited, and subsequent postshock S1 action potentials for 1,5 minutes were characterized by a decrease in the maximum diastolic potential and a decrease in the amplitude and a slowing of their upstroke phase. The higher the S2 voltage, the larger the aftereffects. The changes in postshock action potential configuration in RVep were significantly greater than those observed in LVep and IVS when compared at the same levels of S2 intensity. In RVep, 12 of 20 shocks of 120 V resulted in a prolonged refractoriness to S1 (> 1 s), and the arrest was often followed by oscillation of membrane potential. Ventricular tachycardia or fibrillation ensued from the oscillation in five cases. No such long arrest or serious arrhythmias were elicited in LVep and IVS. These results suggest that RVep is more susceptible than LVep and IVS for arrhythmogenic aftereffects of high intensity DC stimulation. [source] Electrophysiologicai Characteristics of the Atrium in Sinus Node Dysfunction With and Without Postpacing Atrial FihriliationPACING AND CLINICAL ELECTROPHYSIOLOGY, Issue 3 2000ANTONIO DE SISTI DE SISTI, A., ET AL.: Electrophysiologicai Characteristics of the Atrium in Sinus Node Dysfunction With and Without Postpacing Atrial Fibrillation . In patients with sinus node dysfunction (SND) with or without associated paroxysmal atrial fibrillation (AF), the effectiveness of atrial pacing in reducing the incidence of AF is not definitive. In addition, despite several studies involving large populations of implanted patients, little attention has been paid to the electrophysioiogicai (EP) atrial substrate and the effect of permanent atrial pacing. The aim of this study is to correlate EP data and the risk of AF after DDD device implantation. We reviewed FP data of 38 consecutive patients with SND. mean age 70 ± 8 years, who were investigated free of antiarrhythmic treatment, for the evaluation of the atrial substrate. We also considered as control group 25 subjects, mean age 63 ± 14 years, referred to our EP laboratory for unexplained syncope or various atrioventricular disturbances. Following pharmacological washout and at a drive cycle length of 600 ms. effective and functional refractory periods (ERP, FRP), Sl-Al and S2-A2 latency, Al and A2 conduction duration, and latent vulnerability index (EHP/A2) were measured. AF induction was tested with up to three extrastimuli at paced cycle lengths of 600 and 400 ms in 20 patients. Induction of sustained AF (> 30 seconds) was considered as the endpoint. P wave duration on the surface ECG in lead II/Vl was also measured. DDD pacing mode was chosen in all patients with the minimal atrial rate programmed between 60 and 75 beats/min (mean 64 ± 4 beats/min). After implantation, the patients were followed-up for 29 ± 17 months and clinically documented occurrence of AF was determined. When comparing patients with SND and subjects of the control group, we did not find any significant statistical differences in terms of ERP (237 ± 33 vs 250 ± 29 ms), FRP (276 ± 30 vs 280 ± 32 ms) and Sl-Al (39 ± 16 vs 33 ± 11 ms) and S2-A2 latency (69 ± 24 vs 63 ± 25 ms). In contrast, we observed significant differences regarding Al (55 ± 19 vs 39 ± 13 ms; P < 0.001), A2 (95 ± 34 vs 57 ± 18 ms; P < 0.001) and P wave duration (104 ± 18 vs 94 ± 15 ms; P < 0.05), and ERP/A2 (2.8 ± 1.2 vs 4.8 ± 1.6; P < 0.001). When comparing patients with (n = 11) or without (n =27) postpacing AF occurrence, we did not find any difference with reference to ERP, FRP. Sl-Al, S2-A2, Al duration, or follow-up duration. In patients with postpacing AF occurrence, A2 was longer (116 ± 41 vs 87 ± 27 ms; P < 0.01), FRP/A2 lower (2.1 ± 0.4 vs 3.1 ± 1.4; P < 0.05), P wave more prolonged (116 ± 22 vs 99 ± 14 ms; P < 0.01), and preexisting AF history predominant (6/11 vs 5/27 patients; P < 0.05). No difference was observed between patients with (n = 8) and without (n = 12) AF induction during the EP study. In patients with SND, the atrial refractoriness appears normal and the most important abnormality concerns conduction slowing disturbances. Persistence of AF despite pacing stresses the importance of mechanisms responsible for AF not entirely brady-dependent. In this setting, more prolonged atrial conduction disturbances, responsible for a low vulnerability index, and a preexisting history of AF enable us to identify a high risk patient group for AF in the follow-up. sinus node dysfunction, atrial fibrillation, electrophysiologicai study, atrial pacing [source] The Comparative Effects of Drive and Test Stimulus Intensity on Myocardial Excitability and VulnerabilityPACING AND CLINICAL ELECTROPHYSIOLOGY, Issue 1 2000HOWARD S. FRIEDMAN The number and intensity of stimuli that set basic cycle length in cardiac electrophysiological studies can influence the electrical properties assessed by extrastimuli. The relative contribution of drive (S1) and test (S2) stimulus intensity in defining myocardial excitability and vulnerability has not been reported. The purpose of this investigation was to assess this interaction and to determine whether a trial and ventricular findings differed. The effects of S1 and S2 intensity on a trial and ventricular stimulus-intensity-refractory-period curves were determined in open-chest dogs: comparisons were made between curves with S1 intensity varied between diastolic threshold (DT) and 10 mA and S2 intensity maintained at DT and those with S, intensity maintained at DT and S2 intensity varied between DT and 10 mA. S1 -S2 was held constant and S1 -S2 varied. The effects of different stimulation sites, cycle length, number of stimulations, and neural blockade were assessed. S3 intensity amplification shifted atrial stimulus-intensity-refractory period curves in the direction of increased excitability and vulnerability; the changes were, more pronounced than those obtained by modulating S2 intensity. The changes produced by increasing S1 intensity were evident at different cycle lengths and were enhanced by an increased number of stimulations, but were not evident when S1 and S2 were delivered at different atrial sites. Although beta-blockade attenuated the effects of increasing S1 intensity somewhat, the addition of cholinergic blockade virtually abolished it. Ventricular refractoriness was also changed by modulation of S1 intensity, but the changes were less striking. In the atrium, modulation of S1 intensity has greater effects of stimulus-intensity-refractory-period relations than modulation ofS2 intensity; in the ventricle, the converse is true. [source] Nonmyeloablative allogeneic bone marrow transplantation for treatment of myelodysplastic syndrome complicated by recent intracerebral hemorrhageAMERICAN JOURNAL OF HEMATOLOGY, Issue 4 2004Korenori Ohtsubo Abstract A patient with intracerebral hemorrhage is considered ineligible for hematopoietic stem cell transplantation (HSCT). We report a 49-year-old woman with myelodysplastic syndrome (MDS) complicated by refractoriness to platelet transfusion and intracerebral hemorrhage, who underwent allogeneic bone marrow transplantation from an HLA-identical unrelated male donor. Nine days before the scheduled transplantation, she developed dysarthria and right hemiparesis; computed tomography (CT) of the brain disclosed an acute hematoma in the left parietal lobe exceeding 3 cm in diameter. She underwent conditioning with reduced-intensity, including fludarabine (30 mg/m2/day on days ,8 to ,3), busulfan (4 mg/kg/day on days ,6 and ,5), and total body irradiation (4 Gy on day ,2). Two weeks after transplantation, dysarthria and right hemiparesis began to resolve, and CT showed spontaneous resolution of the hematoma. Simultaneously, engraftment was confirmed. Thus, recent stroke may be not an absolute contraindication for HSCT. Am. J. Hematol. 77:400,404, 2004. © 2004 Wiley-Liss, Inc. 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