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Monophasic Action Potentials (monophasic + action_potential)
Selected AbstractsAtrial Fibrillation in the Goat Induces Changes in Monophasic Action Potential and mRNA Expression of Ion Channels Involved in RepolarizationJOURNAL OF CARDIOVASCULAR ELECTROPHYSIOLOGY, Issue 11 2000HUUB M.W. VAN DER VELDEN PH.D. MAP Changes and Ion Channel Expression in Goat AF. Introduction: Sustained atrial fibrillation (AF) is characterized by a marked shortening of the atrial effective refractory period (AKRP) and a decrease or reversal of its physiolonic adaptation to heart rate. The aim of the present study was to investigate whether the AF-induced changes in AKKP in the goat are associated with changes in the atrial monophasic action potential (MAP) and whether an abnormal expression of specific ion channels underlies such changes. Methods and Results: Following thoracotomy, MAPs were recorded from the free wall of the right atrium hoth before induction of AF (control) and after cardioversion of sustained AF (>2 months) in chronically instrumented goats. In control goats. MAP duration at 80% repolarization (MAPD80) shortened (P < 0.01) from 132 ± 4 msec during slow pacing (400-msec interval) to 86 ± 10 msec during fast pacing (180 msec). After cardioversion of sustained AF, the MAPD80, during slow pacing was as short as 67 ± 5 msec (electrical remodeling). Increasing the pacing rate resulted in prolongation (P = 0.02) of the MAPD80 to 91 ± 6 msec. Also. MAPD20 (20% repolarization) shortened (P = 0.05) from 32 ± 4 msec (400 msec) to 14 ± 7 msec (180 msec) in the control goats, whereas it prolonged (P = 0.03) from 20 ± 3 msec (400 msec) to 33 ± 5 msec (180 msec) in sustained AF, mRNA expression of the L-type Ca2+ channel ,1c gene and Kv1.5 potassium channel gene, which underlie Ica, and Ikur respectively, was reduced in sustained.AF compared with sinus rhythm hy 32% (P = 0.01) and 45% (P < 0.01). respectively. No significant changes were found in the mRNA levels of the rapid Na+ channel, the Na+/Ca2+ exchanger, or the Kv4.2/4.3 channels responsible for I10. Conclusion: AF-induced electrical remodeling in the goat comprises shortening of MAPD and reversal of its physiologic rate adaptation. Changes in the time course of reploarization of the action potential are associated with changes in mRNA expression of the , subunit genes of the L.-type Ca2+ channel and the Kvl.5 potassium channel. [source] Increased Right Ventricular Repolarization Gradients Promote Arrhythmogenesis in a Murine Model of Brugada SyndromeJOURNAL OF CARDIOVASCULAR ELECTROPHYSIOLOGY, Issue 10 2010CLAIRE A. MARTIN M.R.C.P. Repolarization Gradients in Brugada Syndrome.,,Introduction: Brugada syndrome (BrS) is associated with loss of Na+ channel function and increased risks of a ventricular tachycardia exacerbated by flecainide but reduced by quinidine. Previous studies in nongenetic models have implicated both altered conduction times and repolarization gradients in this arrhythmogenicity. We compared activation latencies and spatial differences in action potential recovery between different ventricular regions in a murine Scn5a+/, BrS model, and investigated the effect of flecainide and quinidine upon these. Methods and Results: Langendorff-perfused wild-type and Scn5a+/, hearts were subjected to regular pacing and a combination of programmed electrical stimulation techniques. Monophasic action potentials were recorded from the right (RV) and left ventricular (LV) epicardium and endocardium before and following flecainide (10 ,M) or quinidine (5 ,M) treatment, and activation latencies measured. Transmural repolarization gradients were then calculated from the difference between neighboring endocardial and epicardial action potential durations (APDs). Scn5a+/, hearts showed decreased RV epicardial APDs, accentuating RV, but not LV, transmural gradients. This correlated with increased arrhythmic tendencies compared with wild-type. Flecainide increased RV transmural gradients, while quinidine decreased them, in line with their respective pro- and antiarrhythmic effects. In contrast, Scna5+/, hearts showed slowed conduction times in both RV and LV, exacerbated not only by flecainide but also by quinidine, in contrast to their differing effects on arrhythmogenesis. Conclusion: We use a murine genetic model of BrS to systematically analyze LV and RV action potential kinetics for the first time. This establishes a key role for accentuated transmural gradients, specifically in the RV, in its arrhythmogenicity. (J Cardiovasc Electrophysiol, Vol. 21, pp. 1153-1159) [source] Ventricular Fibrillation Induced by Stretch Pulse: Implications for Sudden Death Due to Commotio CordisJOURNAL OF CARDIOVASCULAR ELECTROPHYSIOLOGY, Issue 9 2006FRANK BODE M.D. Introduction: Nonpenetrating chest wall impact (commotio cordis) may lead to sudden cardiac death due to the acute initiation of ventricular fibrillation (VF). VF may result from sudden stretch during a vulnerable window, which is determined by repolarization inhomogeneity. Methods: We examined action potential morphologies and VF inducibility in response to sudden myocardial stretch in the left ventricle (LV). In six Langendorff perfused rabbit hearts, the LV was instrumented with a fluid-filled balloon. Increasing volume and pressure pulses were applied at different times of the cardiac cycle. Monophasic action potentials (MAPs) were recorded simultaneously from five LV epicardial sites. Inter-site dispersion of repolarization was calculated in the time and voltage domains. Results: Sudden balloon inflation induced VF when pressure pulses of 208,289 mmHg were applied within a window of 35,88 msec after MAP upstroke, a period of intrinsic increase in repolarization dispersion. During the pressure pulse, MAPs revealed an additional increase in repolarization dispersion (time domain) by 9 ± 6 msec (P < 0.01). The maximal difference in repolarization levels (voltage domain) between sites increased from 19 ± 3% to 26 ± 3% (P < 0.05). Earliest stretch-induced activation was observed near a site with early repolarization, while sites with late repolarization showed delayed activation. Conclusions: Sudden myocardial stretch can elicit VF when it occurs during a vulnerable window that is based on repolarization inhomogeneity. Stretch pulses applied during this vulnerable window can lead to nonuniform activation. Repolarization dispersion might play a crucial role in the occurrence of fatal tachyarrhythmias during commotio cordis. [source] Phytanic Acid Accumulation Is Associated with Conduction Delay and Sudden Cardiac Death in Sterol Carrier Protein-2/Sterol Carrier Protein-x Deficient MiceJOURNAL OF CARDIOVASCULAR ELECTROPHYSIOLOGY, Issue 11 2004GEROLD MÖNNIG M.D. Introduction: The sterol carrier protein-2 gene encodes two functionally distinct proteins: sterol carrier protein-2 (SCP2, a peroxisomal lipid carrier) and sterol carrier protein-x (SCPx, a peroxisomal thiolase known as peroxisomal thiolase-2), which is involved in peroxisomal metabolism of bile acids and branched-chain fatty acids. We show in this study that mice deficient in SCP2 and SCPx (SCP2null) develop a cardiac phenotype leading to a high sudden cardiac death rate if mice are maintained on diets enriched for phytol (a metabolic precursor of branched-chain fatty acids). Methods and Results: In 210 surface and 305 telemetric ECGs recorded in wild-type (C57BL/6; wt; n = 40) and SCP2 null mice (n = 40), no difference was observed at baseline. However, on diet, cycle lengths were prolonged in SCP2 null mice (262.9 ± 190 vs 146.3 ± 43 msec), AV conduction was prolonged (58.3 ± 17 vs 42.6 ± 4 ms), and QRS complexes were wider (19.1 ± 5 vs 14.0 ± 4 ms). In 11 gene-targeted Langendorff-perfused hearts isolated from SCP2 null mice after dietary challenge, complete AV blocks (n = 5/11) or impaired AV conduction (Wenckebach point 132 ± 27 vs 92 ± 10 msec; P < 0.05) could be confirmed. Monophasic action potentials were not different between the two genotypes. Left ventricular function studied by echocardiography was similar in both strains. Phytanic acid but not pristanic acid accumulated in the phospholipid fraction of myocardial membranes isolated from SCP2 null mice. Conclusion: Accumulation of phytanic acid in myocardial phospholipid membranes is associated with bradycardia and impaired AV nodal and intraventricular impulse conduction, which could provide an explanation for sudden cardiac death in this model. [source] Prolonged Atrial Action Potential Durations and Polymorphic Atrial Tachyarrhythmias in Patients with Long QT SyndromeJOURNAL OF CARDIOVASCULAR ELECTROPHYSIOLOGY, Issue 10 2003PAULUS KIRCHHOF M.D. Introduction: Prolongation of the QT interval and torsades de pointes tachycardias due to altered expression or function of repolarizing ion channels are the hallmark of congenital long QT syndrome (LQTS). The same ion channels also contribute to atrial repolarization, and familial atrial fibrillation may be associated with a mutated KVLQT1 gene. We therefore assessed atrial action potential characteristics and atrial arrhythmias in LQTS patients. Methods and Results: Monophasic action potentials (MAPs) were simultaneously recorded from the right atrial appendage and the inferolateral right atrium in 10 patients with LQTS (8 with identifiable genotype) and compared to 7 control patients. Atrial arrhythmias also were compared to MAPs recorded in patients with persistent (n = 10) and induced (n = 4) atrial fibrillation. Atrial action potential durations (APD) and effective refractory periods (ERP) were prolonged in LQTS patients at cycle lengths of 300 to 500 msec (APD prolongation 30,41 msec; ERP prolongation 26,52 msec; all P < 0.05). Short episodes of polymorphic atrial tachyarrhythmias (polyAT, duration 4,175 sec) occurred spontaneously or during pauses after pacing in 5 of 10 LQTS patients, but not in controls (P < 0.05). P waves showed undulating axis during polyAT. Cycle lengths of polyAT were longer than during persistent and induced atrial fibrillation. Afterdepolarizations preceded polyAT in 2 patients. The electrical restitution curve was shifted to longer APD in LQTS patients and to even longer APD in LQTS patients with polyAT. Conclusion: This group of LQTS patients has altered atrial electrophysiology: action potentials are prolonged, and polyAT occurs. PolyAT appears to be a specific arrhythmia of LQTS reminiscent of an atrial form of "torsades de pointes."(J Cardiovasc Electrophysiol, Vol. 14, pp ***-***, October 2003) [source] Electrophysiologic Deterioration After One-Minute Fibrillation Increases Relative Biphasic Defibrillation EfficacyJOURNAL OF CARDIOVASCULAR ELECTROPHYSIOLOGY, Issue 6 2000OSCAR H. TOVAR M.D. Biphasic Shocks and One-Minute Fibrillation. Introduction: The probability of survival decreases to 70% after 2 minutes of ventricular fibriltation. Bipliasic shocks are more effective than monophasic shocks in terminating short-duration (<30 sec) ventricular fibrillation. We tested the hypotheses that developing ischemia changes the electrophysiologic characteristics of fibrillation and that the relative efficacy of biphasic shocks increases as electrophysiologic characteristics deteriorate. Methods and Results: Monophasic (12 msec) and biphasic (6/6 msec) shocks (1 to 4 A) were tested in random order in isolated rabbit hearts after 1-minute ischemic fibrillation. Monophasic action potentials showed only a sporadic occurrence of electrical diastole after 5 seconds of fibrillation (24% of action potentials in the right ventricle and 18% in the left ventricle). After 60 seconds of fibrillation, diastole (17.83 ± 1.14 msec in the right ventricle and 21.52 ± 1.16 msec in the left ventricle) appeared after almost every action potential (P < 0.0001 compared with 5 sec), despite a lack of change in fibrillation cycle length and dominant frequency. Monophasie I50 was 2.89 A, and biphasic I50 was 1.4 A (77% reduction in energy). Normalized curve width decreased 28%. Retrospective analysis showed that shocks delivered early in the fibrillation action potential bad a greater probability of succeeding (89%) than shocks delivered late (30%; P < 0.001). Conclusion: After l-minute ischemic fibrillation, diastolic intervals occur during fibrillation. Therefore, defibrillation shocks have an approximately 29% probability of interacting with the fibrillation action potential during diastole. At this time, biphasic shocks produced a more deterministic defibrillation threshold and became even more efficacious (I50B/M = 0.48) than at short fibrillation durations (I50 B/M = 0.7). [source] Regional variations in action potential alternans in isolated murine Scn5a+/, hearts during dynamic pacingACTA PHYSIOLOGICA, Issue 2 2010G. D. K. Matthews Abstract Aim:, Clinical observations suggest that alternans in action potential (AP) characteristics presages breakdown of normal ordered cardiac electrical activity culminating in ventricular arrhythmogenesis. We compared such temporal nonuniformities in monophasic action potential (MAP) waveforms in left (LV) and right ventricular (RV) epicardia and endocardia of Langendorff-perfused murine wild-type (WT), and Scn5a+/, hearts modelling Brugada syndrome (BrS) for the first time. Methods:, A dynamic pacing protocol imposed successively incremented steady pacing rates between 5.5 and 33 Hz. A signal analysis algorithm detected sequences of >10 beats showing alternans. Results were compared before and following the introduction of flecainide (10 ,m) and quinidine (5 ,m) known to exert pro- and anti-arrhythmic effects in BrS. Results:, Sustained and transient amplitude and duration alternans were both frequently followed by ventricular ectopic beats and ventricular tachycardia or fibrillation. Diastolic intervals (DIs) that coincided with onsets of transient (tr) or sustained (ss) alternans in MAP duration (DI*) and amplitude (DI,) were determined. Kruskal,Wallis tests followed by Bonferroni-corrected Mann,Whitney U -tests were applied to these DI results sorted by recording site, pharmacological conditions or experimental populations. WT hearts showed no significant heterogeneities in any DI. Untreated Scn5a+/, hearts showed earlier onsets of transient but not sustained duration alternans in LV endocardium compared with RV endocardium or LV epicardium. Flecainide administration caused earlier onsets of both transient and sustained duration alternans selectively in the RV epicardium in the Scn5a+/, hearts. Conclusion:, These findings in a genetic model thus implicate RV epicardial changes in the arrhythmogenicity produced by flecainide challenge in previously asymptomatic clinical BrS. [source] An Acute Model for Atrial Fibrillation Arising from a Peripheral Atrial Site: Evidence for Primary and Secondary TriggersJOURNAL OF CARDIOVASCULAR ELECTROPHYSIOLOGY, Issue 5 2008BENJAMIN J. SCHERLAG Ph.D. Background: We previously demonstrated that acetylcholine (Ach) injected into cardiac ganglionated plexi (GP) causes pulmonary vein (PV) ectopy initiating atrial fibrillation (AF). Objective: To determine the effects of Ach applied at non-PV sites. Methods: Overall, 54 dogs were anesthetized with Na-pentobarbital. A right and left thoracotomy allowed the placement of multielectrode catheters to record from the superior PVs, mid portion of the atrium and the atrial appendages (AA). A monophasic action potential (MAP) was recorded from the AA. Ach (1, 10, 100 mM) was applied sequentially to the AA. Results: In 19 of 26 animals, Ach 100 mM on the right (n = 15) or left (n = 4) AA induced focal, sustained AF (,10 minutes) with rapid regular firing (cycle length = 37 ± 7 ms) at the AA. A clamp with teeth placed across the AA caused arrest in the AA. However, AF was sustained only when PV sites adjacent to the GP manifested complex fractionated atrial electrograms (CFAE). Clamping the AA prior to Ach (100 mM) application resulted in focal AF arising at the PVs but not at the AA. When a clamp without teeth was applied prior to Ach application, no AF at either AA or PV site could be induced. Conclusion: Isolation of the focal AF at the AA (primary trigger) by clamping caused cessation of activity in the AA, but AF continued due to secondary triggers arising from PVs. The possible mechanism(s) responsible for these findings are discussed, and various ancillary experiments (n = 28) were added to help elucidate mechanisms. [source] Atrial Fibrillation in the Goat Induces Changes in Monophasic Action Potential and mRNA Expression of Ion Channels Involved in RepolarizationJOURNAL OF CARDIOVASCULAR ELECTROPHYSIOLOGY, Issue 11 2000HUUB M.W. VAN DER VELDEN PH.D. MAP Changes and Ion Channel Expression in Goat AF. Introduction: Sustained atrial fibrillation (AF) is characterized by a marked shortening of the atrial effective refractory period (AKRP) and a decrease or reversal of its physiolonic adaptation to heart rate. The aim of the present study was to investigate whether the AF-induced changes in AKKP in the goat are associated with changes in the atrial monophasic action potential (MAP) and whether an abnormal expression of specific ion channels underlies such changes. Methods and Results: Following thoracotomy, MAPs were recorded from the free wall of the right atrium hoth before induction of AF (control) and after cardioversion of sustained AF (>2 months) in chronically instrumented goats. In control goats. MAP duration at 80% repolarization (MAPD80) shortened (P < 0.01) from 132 ± 4 msec during slow pacing (400-msec interval) to 86 ± 10 msec during fast pacing (180 msec). After cardioversion of sustained AF, the MAPD80, during slow pacing was as short as 67 ± 5 msec (electrical remodeling). Increasing the pacing rate resulted in prolongation (P = 0.02) of the MAPD80 to 91 ± 6 msec. Also. MAPD20 (20% repolarization) shortened (P = 0.05) from 32 ± 4 msec (400 msec) to 14 ± 7 msec (180 msec) in the control goats, whereas it prolonged (P = 0.03) from 20 ± 3 msec (400 msec) to 33 ± 5 msec (180 msec) in sustained AF, mRNA expression of the L-type Ca2+ channel ,1c gene and Kv1.5 potassium channel gene, which underlie Ica, and Ikur respectively, was reduced in sustained.AF compared with sinus rhythm hy 32% (P = 0.01) and 45% (P < 0.01). respectively. No significant changes were found in the mRNA levels of the rapid Na+ channel, the Na+/Ca2+ exchanger, or the Kv4.2/4.3 channels responsible for I10. Conclusion: AF-induced electrical remodeling in the goat comprises shortening of MAPD and reversal of its physiologic rate adaptation. Changes in the time course of reploarization of the action potential are associated with changes in mRNA expression of the , subunit genes of the L.-type Ca2+ channel and the Kvl.5 potassium channel. [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] 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] 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] Proarrhythmia as a Class Effect of Quinolones: Increased Dispersion of Repolarization and Triangulation of Action Potential Predict Torsades de PointesJOURNAL OF CARDIOVASCULAR ELECTROPHYSIOLOGY, Issue 6 2007PETER MILBERG M.D. Background: Numerous noncardiovascular drugs prolong repolarization and thereby increase the risk for patients to develop life-threatening tachyarrhythmias of the torsade de pointes (TdP) type. The development of TdP is an individual, patient-specific response to a repolarization-prolonging drug, depending on the repolarization reserve. The aim of the present study was to analyze the underlying mechanisms that discriminate hearts that will develop TdP from hearts that will not develop TdP. We therefore investigated the group of quinolone antibiotics that reduce repolarization reserve via IKr blockade in an intact heart model of proarrhythmia. Methods and Results: In 47 Langendorff-perfused, AV-blocked rabbit hearts, ciprofloxacin (n = 10), ofloxacin (n = 14), levofloxacin (n = 10), and moxifloxacin (n = 13) in concentrations from 100 ,M to 1,000 ,M were infused. Eight monophasic action potentials (MAPs) and an ECG were recorded simultaneously. After incremental pacing at cycle lengths from 900 ms to 300 ms to compare the action potential duration, potassium concentration was lowered to provoke TdP. All antibiotics led to a significant increase in QT interval and MAP duration, and exhibited reverse-use dependence. Eight simultaneously recorded MAPs demonstrated an increase in dispersion of repolarization in the presence of all antibiotics. MAP triangulation (ratio: MAP90/50) and fluctuation of consecutive action potentials were increased for all tested drugs at high concentrations. In the presence of low potassium concentration, all quinolones led to TdP: ciprofloxacin, 4 out of 10 (40%); ofloxacin, 3 out of 14 (21%); moxifloxacin, 9 out of 13 (69%); and levofloxacin, 2 out of 10 (20%). Hearts that developed TdP demonstrated a significant greater influence on dispersion of repolarization and on triangulation as compared with hearts without TdP. Conclusion: Quinolone antibiotics may be proarrhythmic due to a significant effect on myocardial repolarization. The individual response of a heart to develop TdP in this experimental model is characterized by a greater effect on dispersion of repolarization and on triangulation of action potential as compared with hearts that do not develop TdP. [source] Pro arrhythmic Effects of Ibutilide in a Canine Model of Pacing Induced CardiomyopathyPACING AND CLINICAL ELECTROPHYSIOLOGY, Issue 2 2000MING-HSIUNG HSIEH The authors developed a canine model of pacing induced cardio my apathy to study the possible mechanisms of ibutilide induced torsades de pointes (TP) in heart failure. Thirteen dogs received intravenous ibutilide after acute AV block for 60 minutes, and after implantation of a VVI pacemaker, with a rate of 270 beats/min for 2,3 weeks. Twelve-lead ECG and right and left ventricle monophasic action potentials were recorded at different right ventricle pacing cycle lengths from 600 ms to 1200 ms during the study. The results showed ibutilide could significantly prolong ventricular repolarization and increase the dispersion in a dose dependent and reverse use dependent manner. Furthermore, after ihutilide administration, cardiomyopathic dogs had a greater dispersion of ventricular repolarization, and also had higher incidences of early afterdepolarizations and spontaneous or pacing induced TP than acute AV block dogs. [source] Potentiation of E-4031-induced torsade de pointes by HMR1556 or ATX-II is not predicted by action potential short-term variability or triangulationBRITISH JOURNAL OF PHARMACOLOGY, Issue 8 2007G Michael Background and purpose: Torsade de pointes (TdP) can be induced by a reduction in cardiac repolarizing capacity. The aim of this study was to assess whether IKs blockade or enhancement of INa could potentiate TdP induced by IKr blockade and to investigate whether short-term variability (STV) or triangulation of action potentials preceded TdP. Experimental approach: Experiments were performed in open-chest, pentobarbital-anaesthetized, ,1 -adrenoceptor-stimulated, male New Zealand White rabbits, which received three consecutive i.v. infusions of either the IKr blocker E-4031 (1, 3 and 10 nmol kg,1 min,1), the IKs blocker HMR1556 (25, 75 and 250 nmol kg,1 min,1) or E-4031 and HMR1556 combined. In a second study rabbits received either the same doses of E-4031, the INa enhancer, ATX-II (0.4, 1.2 and 4.0 nmol kg,1) or both of these drugs. ECGs and epicardial monophasic action potentials were recorded. Key results: HMR1556 alone did not cause TdP but increased E-4031-induced TdP from 25 to 80%. ATX-II alone caused TdP in 38% of rabbits, as did E-4031; 75% of rabbits receiving both drugs had TdP. QT intervals were prolonged by all drugs but the extent of QT prolongation was not related to the occurrence of TdP. No changes in STV were detected and triangulation was only increased after TdP occurred. Conclusions and implications: Giving modulators of ion channels in combination substantially increased TdP but, in this model, neither STV nor triangulation of action potentials could predict TdP. British Journal of Pharmacology (2007) 152, 1215,1227; doi:10.1038/sj.bjp.0707513; published online 29 October 2007 [source] | |||||||||||||