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Electrophysiological Characteristics (electrophysiological + characteristic)
Selected AbstractsElectrophysiological Characteristics and Catheter Ablation in Patients with Paroxysmal Supraventricular Tachycardia and Paroxysmal Atrial FibrillationJOURNAL OF CARDIOVASCULAR ELECTROPHYSIOLOGY, Issue 4 2008SHIH-LIN CHANG M.D. Introduction: Paroxysmal supraventricular tachycardia (PSVT) is often associated with paroxysmal atrial fibrillation (AF). However, the relationship between PSVT and AF is still unclear. The aim of this study was to investigate the clinical and electrophysiological characteristics in patients with PSVT and AF, and to demonstrate the origin of the AF before the radiofrequency (RF) ablation of AF. Methods and Results: Four hundred and two consecutive patients with paroxysmal AF (338 had a pure PV foci and 64 had a non-PV foci) that underwent RF ablation were included. Twenty-one patients (10 females; mean age 47 ± 18 years) with both PSVT and AF were divided into two groups. Group 1 consisted of 14 patients with inducible atrioventricular nodal reentrant tachycardia (AVNRT) and AF. Group 2 consisted of seven patients with Wolff-Parkinson-White (WPW) syndrome and AF. Patients with non-PV foci of AF had a higher incidence of AVNRT than those with PV foci (11% vs. 2%, P = 0.003). Patients with AF and atypical AVNRT had a higher incidence of AF ectopy from the superior vena cava (SVC) than those with AF and typical AVNRT (86% vs. 14%, P = 0.03). Group 1 patients had smaller left atrial (LA) diameter (36 ± 3 vs. 41 ± 3 mm, P = 0.004) and higher incidence of an SVC origin of AF (50% vs. 0%, P = 0.047) than did those in Group 2. Conclusion: The SVC AF has a close relationship with AVNRT. The effect of atrial vulnerability and remodeling may differ between AVNRT and WPW syndrome. [source] Electrophysiological Characteristics Of The Ca2+ -Activated Cl, Channel Family Of Anion Transport ProteinsCLINICAL AND EXPERIMENTAL PHARMACOLOGY AND PHYSIOLOGY, Issue 11 2000Catherine M Fuller SUMMARY 1. A protein isolated from the bovine tracheal epithelium behaves as a Ca2+ -activated Cl, channel (CaCC) when incorporated into planar lipid bilayers. 2. An antibody raised against this protein was used to screen a cDNA expression library and resulted in the isolation of a cDNA clone that exhibited nearly identical electrophysiological characteristics to the isolated endogenous protein when expressed. 3. Recent cloning of several related proteins has revealed that the cloned bovine CaCC is one of a large and growing family. All new family members so far examined are associated with the appearance of a novel Ca2+ -mediated Cl, conductance when heterologously expressed. 4. This new group of proteins may underlie the Ca2+ -mediated Cl, conductance upregulated in the cystic fibrosis (CF) knockout mouse and thought to be responsible for the escape from the significant airway pathology associated with CF. [source] A model of thalamocortical relay cellsTHE JOURNAL OF PHYSIOLOGY, Issue 3 2005Paul A. Rhodes It is well established that the main intrinsic electrophysiological properties of thalamocortical relay cells, production of a low threshold burst upon release from hyperpolarized potential and production of a train of single spikes following stimulation from depolarized potentials, can be readily modelled using a single compartment. There is, however, another less well explored intrinsic electrophysiological characteristic of relay cells for which models have not yet accounted: at somatic potentials near spike threshold, relay cells produce a fast ragged high threshold oscillation in somatic voltage. Optical [Ca2+] imaging and pharmacological tests indicate that this oscillation correlates with a high threshold Ca2+ current in the dendrites. Here we present the development of a new compartment model of the thalamic relay cell guided by the simultaneous constraints that it must produce the familiar regular spiking relay mode and low threshold rebound bursts which characterize these cells, as well as the less-studied fast oscillation occurring at near-threshold somatic potentials. We arrive at a model cell which is capable of the production of isolated high threshold Ca2+ spikes in distal branch segments, driven by a rapidly inactivating intermediate threshold Ca2+ channel. Further, the model produces the low threshold spike behaviour of the relay cell without requiring high T-current density in the distal dendritic segments. The results thus support a new picture of the dendritic tree of relay cells which may have implications for the manner in which thalamic relay cells integrate descending input from the cortex. [source] Cardiac L-type calcium current is increased in a model of hyperaldosteronism in the ratEXPERIMENTAL PHYSIOLOGY, Issue 6 2009Beatriz Martin-Fernandez Accumulating evidence supports the importance of aldosterone as an independent risk factor in the pathophysiology of cardiovascular disease. It has been postulated that aldosterone could contribute to ventricular arrhythmogeneity by modulation of cardiac ionic channels. The aim of this study was to analyse ex vivo the electrophysiological characteristics of the L-type cardiac calcium current (ICaL) in a model of hyperaldosteronism in the rat. Aldosterone was administered for 3 weeks, and cardiac collagen deposition and haemodynamic parameters were analysed. In addition, RT-PCR and patch-clamp techniques were applied to study cardiac L-type Ca2+ channels in isolated cardiomyocytes. Administration of aldosterone induced maladaptive cardiac remodelling that was related to increased collagen deposition, diastolic dysfunction and cardiac hypertrophy. In addition, ventricular myocytes isolated from the aldosterone-treated group showed increased ICaL density and conductance and prolongation of the action potential duration. No changes in kinetics or in voltage dependence of activation and inactivation of ICaL were observed, but relative expression of CaV1.2 mRNA levels was higher in cardiomyocytes isolated from the aldosterone-treated group. The present study demonstrates that aldosterone treatment induces myocardial fibrosis, cardiac hypertrophy, increase of ICaL density, upregulation of L-type Ca2+ channels and prolongation of action potential duration. It could be proposed that aldosterone, through these mechanisms, might exert pro-arrhythmic effects in the pathological heart. [source] Potent Antiarrhythmic Effects of Chronic Amiodarone in Canine Pulmonary Vein Sleeve PreparationsJOURNAL OF CARDIOVASCULAR ELECTROPHYSIOLOGY, Issue 7 2009SERGE SICOURI M.D. Objectives: To examine the effects of chronic amiodarone on the electrophysiology of canine pulmonary vein (PV) sleeve preparations and left ventricular wedge preparation. Background: Amiodarone is commonly used for the treatment of ventricular and supraventricular arrhythmias. Ectopic activity arising from the PV plays a prominent role in the development of atrial fibrillation (AF). Methods: Standard microelectrode techniques were used to evaluate the electrophysiological characteristics of superfused PV sleeve (left superior or inferior) and arterially perfused left ventricular (LV) wedge preparations isolated from untreated and chronic amiodarone-treated dogs (amiodarone, 40 mg/kg daily for 6 weeks). Results: In PV sleeves, chronic amiodarone (n = 6) induced a significant increase in action potential duration at 90% repolarization (APD90) and a significant use-dependent reduction in Vmax leading to 1:1 activation failure at long cycle lengths (basic cycle length of 124 ± 15 ms in control vs 420 ± 320 ms after chronic amiodarone [P < 0.01]). Diastolic threshold of excitation increased from 0.3 ± 0.2 to 1.8 ± 0.7 mA (P < 0.01). Delayed and late phase 3 early afterdepolarizations and triggered activity could be induced in PV sleeve preparations using acetylcholine (ACh, 1 ,M), high calcium ([Ca2+]o= 5.4 mM), isoproterenol (Iso, 1 ,M), or their combination in 6 of 6 untreated PV sleeves, but in only 1 of 5 chronic amiodarone-treated PV sleeve preparations. Vmax, conduction velocity, and 1:1 activation failure were much more affected in PV sleeves versus LV wedge preparations isolated from amiodarone-treated animals. Conclusions: The results point to potent effects of chronic amiodarone to preferentially suppress arrhythmogenic substrates and triggers arising from the PV sleeves of the dog. [source] Electrophysiological Characteristics and Catheter Ablation in Patients with Paroxysmal Supraventricular Tachycardia and Paroxysmal Atrial FibrillationJOURNAL OF CARDIOVASCULAR ELECTROPHYSIOLOGY, Issue 4 2008SHIH-LIN CHANG M.D. Introduction: Paroxysmal supraventricular tachycardia (PSVT) is often associated with paroxysmal atrial fibrillation (AF). However, the relationship between PSVT and AF is still unclear. The aim of this study was to investigate the clinical and electrophysiological characteristics in patients with PSVT and AF, and to demonstrate the origin of the AF before the radiofrequency (RF) ablation of AF. Methods and Results: Four hundred and two consecutive patients with paroxysmal AF (338 had a pure PV foci and 64 had a non-PV foci) that underwent RF ablation were included. Twenty-one patients (10 females; mean age 47 ± 18 years) with both PSVT and AF were divided into two groups. Group 1 consisted of 14 patients with inducible atrioventricular nodal reentrant tachycardia (AVNRT) and AF. Group 2 consisted of seven patients with Wolff-Parkinson-White (WPW) syndrome and AF. Patients with non-PV foci of AF had a higher incidence of AVNRT than those with PV foci (11% vs. 2%, P = 0.003). Patients with AF and atypical AVNRT had a higher incidence of AF ectopy from the superior vena cava (SVC) than those with AF and typical AVNRT (86% vs. 14%, P = 0.03). Group 1 patients had smaller left atrial (LA) diameter (36 ± 3 vs. 41 ± 3 mm, P = 0.004) and higher incidence of an SVC origin of AF (50% vs. 0%, P = 0.047) than did those in Group 2. Conclusion: The SVC AF has a close relationship with AVNRT. The effect of atrial vulnerability and remodeling may differ between AVNRT and WPW syndrome. [source] Surface Electrocardiographic Patterns and Electrophysiologic Characteristics of Atrial Flutter Following Modified Radiofrequency MAZE ProceduresJOURNAL OF CARDIOVASCULAR ELECTROPHYSIOLOGY, Issue 4 2007JOSEPH G. AKAR M.D., Ph.D. Introduction: The radiofrequency MAZE is becoming a common adjunct to cardiac surgery in patients with atrial fibrillation. While a variety of postoperative arrhythmias have been described following the original Cox-MAZE III procedure, the electrophysiological characteristics and surgical substrate of post-radiofrequency MAZE flutter have not been correlated. We sought to determine the location, ECG patterns, and electrophysiological characteristics of post-radiofrequency MAZE atrial flutter. Methods: Nine consecutive patients with post-radiofrequency MAZE flutter presented for catheter ablation 9 ± 10 months after surgery. Results: Only one patient (11%) had an ECG appearance consistent with typical isthmus-dependent right atrial (RA) flutter. However, on electrophysiological study, 3/9 patients (33%) had typical right counter-clockwise flutter entrained from the cavo-tricuspid isthmus, despite description of surgical isthmus ablation. Six patients (67%) had left atrial (LA) circuits. These involved the mitral annulus in 5/6 cases (83%) despite description of surgical mitral isthmus ablation in the majority (60%). LA flutters had a shorter cycle length compared with RA flutters (253 ± 39 msec and 332 ± 63 msec respectively, P < 0.05). After a mean of 8 ± 4 months following ablation, 8/9 patients (89%) were in sinus rhythm. Conclusion: Up to one-third of post-radiofrequency MAZE circuits are typical isthmus-dependent RA flutters, despite a highly atypical surface ECG morphology. Therefore, diagnostic electrophysiological studies should commence with entrainment at the cavo-tricuspid isthmus in order to exclude typical flutter, regardless of the surface ECG appearance. Incomplete surgical lesions at the mitral and cavo-tricuspid isthmus likely predispose to the development of post-radiofrequency MAZE flutter. [source] Electrophysiologically "complex" glial cells freshly isolated from the hippocampus are immunopositive for the chondroitin sulfate proteoglycan NG2JOURNAL OF NEUROSCIENCE RESEARCH, Issue 6 2003Gary P. Schools Abstract We have recently described a subgroup of isolated glial fibrillary acidic protein-positive (GFAP+) hippocampal astrocytes that predominantly express outwardly rectifying currents (which we term "ORAs" for outwardly rectifying astrocytes), which are similar to the currents already described for hippocampal GFAP, "complex glia." We now report that post-recording staining of cells that were first selected as "complex" by morphology and then confirmed by their electrophysiological characteristics were NG2+ ,90% of the time. Also, the morphology of freshly isolated NG2+ cells differs from that of isolated GFAP+ ORAs in having a smaller and round cell body with thinner processes, which usually are collapsed back onto the soma. Upon detailed examination, NG2+ cells were found to differ quantitatively in some electrophysiological characteristics from GFAP+ ORAs. The outward, transient K+ currents (IKa) in the NG2+ cells showed a slower decay than the IKa in ORAs, and their density decreased in NG2+ cells from older animals. The other two major cation currents, the voltage-activated Na+ and outwardly delayed rectifier K+ currents, were similar in NG2+ cells and ORAs. To further distinguish isolated complex cells from outwardly rectifying GFAP+ astrocytes, we performed immunocytochemistry for glial markers in fixed, freshly isolated rat hippocampal glia. NG2+ cells were negative for GFAP and also for the astrocytic glutamate transporters GLT-1 and GLAST. Thus the isolated hippocampal NG2+ glial cells, though having an electrophysiological phenotype similar to that of ORAs, are an immunologically and morphologically distinct glial cell population and most likely represent NG2+ cells in situ. © 2003 Wiley-Liss, Inc. [source] Plasticity and ambiguity of the electrophysiological phenotypes of enteric neuronsNEUROGASTROENTEROLOGY & MOTILITY, Issue 9 2009K. Nurgali Abstract, Advances in knowledge of enteric neurons electrophysiological characteristics have led to the realisation that the properties of the neurons are dependent on the state of the intestine, the region, the method of recording and the species. Thus, under different experimental conditions, electrophysiological studies cannot provide a reliable signature that identifies the functional type of neuron. In the normal guinea-pig small intestine, taken as a model tissue, neurons can be separated into two electrophysiological groups, S and AH neurons. Combined morphological and physiological studies place several classes of motor and interneurons in the S group, and intrinsic primary afferent neurons in the AH group. There is some evidence for subgroups of S neurons, in which electrophysiological differences are correlated with functional subtypes, but these subgroups have been incompletely investigated. Morphologically characterized Dogiel type II (DII) neurons are recognisable in many species, from mouse to human, but their electrophysiological characteristics are only partly conserved across species or cannot be satisfactorily defined due to technical difficulties. There is a strong need for a comprehensive analysis of channels and currents of S/Dogiel type I neuron subtypes, similar to the comprehensive analysis of AH/DII neurons in the guinea-pig, and similar studies need to be conducted in human and other species. The purpose of this review is to highlight that criteria used for electrophysiological definition of enteric neurons might not be sufficient to distinguish between functional classes of neurons, due to intrinsic properties of neuronal subpopulations, plasticity in pathological conditions and differences in recording techniques. [source] The Electrophysiological Characteristics in Patients with Ventricular Stimulation Inducible Fast-Slow Form Atrioventricular Nodal Reentrant TachycardiaPACING AND CLINICAL ELECTROPHYSIOLOGY, Issue 10 2006PI-CHANG LEE M.D. Background: Atrioventricular nodal reentrant tachycardia (AVNRT) can usually be induced by atrial stimulation. However, it seldom may be induced with only ventricular stimulation, especially the fast-slow form of AVNRT. The purpose of this retrospective study was to investigate the specific electrophysiological characteristics in patients with the fast-slow form of AVNRT that could be induced with only ventricular stimulation. Methods: The total population consisted of 1,497 patients associated with AVNRT, and 106 (8.4%) of them had the fast-slow form of AVNRT and 1,373 (91.7%) the slow-fast form of AVNRT. In patients with the fast-slow form of AVNRT, the AVNRT could be induced with only ventricular stimulation in 16 patients, Group 1; with only atrial stimulation or both atrial and ventricular stimulation in 90 patients, Group 2; and with only atrial stimulation in 13 patients, Group 3. We also divided these patients with slow-fast form AVNRT (n = 1,373) into two groups: those that could be induced only by ventricular stimulation (Group 4; n = 45, 3%) and those that could be induced by atrial stimulation only or by both atrial and ventricular stimulation (n = 1.328, 97%). Results: Patients with the fast-slow form of AVNRT that could be induced with only ventricular stimulation had a lower incidence of an antegrade dual AVN physiology (0% vs 71.1% and 92%, P < 0.001), a lower incidence of multiple form AVNRT (31% vs 69% and 85%, P = 0.009), and a more significant retrograde functional refractory period (FRP) difference (99 ± 102 vs 30 ± 57 ms, P < 0.001) than those that could be induced with only atrial stimulation or both atrial and ventricular stimulation. The occurrence of tachycardia stimulated with only ventricular stimulation was more frequently demonstrated in patients with the fast-slow form of AVNRT than in those with the slow-fast form of AVNRT (15% vs 3%, P < 0.001). Patients with the fast-slow form of AVNRT that could be induced with only ventricular stimulation had a higher incidence of retrograde dual AVN physiology (75% vs 4%, P < 0.001), a longer pacing cycle length of retrograde 1:1 fast and slow pathway conduction (475 ± 63 ms vs 366 ± 64 ms, P < 0.001; 449 ± 138 ms vs 370 ± 85 ms, P = 0.009), a longer retrograde effective refractory period of the fast pathway (360 ± 124 ms vs 285 ± 62 ms, P = 0.003), and a longer retrograde FRP of the fast and slow pathway (428 ± 85 ms vs 362 ± 47 ms, P < 0.001 and 522 ± 106 vs 456 ± 97 ms, P = 0.026) than those with the slow-fast form of AVNRT that could be induced with only ventricular stimulation. Conclusion: This study demonstrated that patients with the fast-slow form of AVNRT that could be induced with only ventricular stimulation had a different incidence of the antegrade and retrograde dual AVN physiology and the specific electrophysiological characteristics. The mechanism of the AVNRT stimulated only with ventricular stimulation was supposed to be different in patients with the slow-fast and fast-slow forms of AVNRT. [source] Synaptic facilitation and enhanced neuronal excitability in the submucosal plexus during experimental colitis in guinea-pigTHE JOURNAL OF PHYSIOLOGY, Issue 3 2005Alan E. Lomax Intestinal secretion is regulated by submucosal neurones of the enteric nervous system. Inflammation of the intestines leads to aberrant secretory activity; therefore we hypothesized that the synaptic and electrical behaviours of submucosal neurones are altered during colitis. To test this hypothesis, we used intracellular microelectrode recording to compare the excitability and synaptic properties of submucosal neurones from normal and trinitrobenzene sulphonic acid (TNBS)-inflamed guinea-pig colons. Inflammation differentially affected the electrophysiological characteristics of the two functional classes of submucosal neurones. AH neurones from inflamed colons were more excitable, had shorter action potential durations and reduced afterhyperpolarizations. Stimulus-evoked fast and slow excitatory postsynaptic potentials (EPSPs) in S neurones were larger during colitis, and the incidence of spontaneous fast EPSPs was increased. In control preparations, fast EPSPs were almost completely blocked by the nicotinic receptor antagonist hexamethonium, whereas fast EPSPs in inflamed S neurones were only partially inhibited by hexamethonium. In inflamed tissues, components of the fast EPSP in S neurones were sensitive to blockade of P2X and 5-HT3 receptors while these antagonists had little effect in control preparations. Control and inflamed S neurones were equally sensitive to brief application of acetylcholine, ATP and 5-HT, suggesting that synaptic facilitation was due to a presynaptic mechanism. Immunoreactivity for 5-HT in the submucosal plexus was unchanged by inflammation; this indicates that altered synaptic transmission was not due to anatomical remodelling of submucosal nerve terminals. This is the first demonstration of alterations in synaptic pharmacology in the enteric nervous system during inflammation. [source] Polyneuropathy associated with IgM vs IgG monoclonal gammopathy: comparison between clinical and electrophysiological findingsACTA NEUROLOGICA SCANDINAVICA, Issue 1 2010M. Vrethem Vrethem M, Reiser N, Lauermann C, Svanborg E. Polyneuropathy associated with IgM vs IgG monoclonal gammopathy: comparison between clinical and electrophysiological findings. Acta Neurol Scand: 2010: 122: 52,57. © 2009 The Authors Journal compilation © 2009 Blackwell Munksgaard. Objective,,, The neuropathy associated with IgM monoclonal gammopathy (IgM-MG) is regarded as a sensorimotor, mainly demyelinating neuropathy. It is not fully known whether the neuropathy in IgG-MG is caused by the same mechanisms and shows the same electrophysiological characteristics. We aimed at making a comparison between clinical and neurophysiological findings in these two conditions. Patients and methods,,, Twenty-seven patients with IgM-associated neuropathy [18 with anti-myelin-associated glycoprotein (anti-MAG) antibodies] were compared with 15 age-matched patients with IgG-associated neuropathy. Results,,, Patients with IgM-associated neuropathy (especially those with anti-MAG antibodies) had significantly clinically more severe disabilities with involvement of both motor and sensory functions compared with patients with IgG-associated neuropathy in whom clinical sensory disturbances were more prominent than motor dysfunction. Motor and sensory conduction velocities were significantly lower and distal latencies significantly longer in the IgM group than in the IgG group concerning the median, ulnar and peroneal nerves. Fifty-four per cent of the patients in the IgM group did not present a sensory response of the median nerve vs 13% in the IgG group. There was also a significant difference concerning absent responses from the peroneal and sural nerves in the IgM vs IgG group (peroneal: 48% vs 13%, sural: 88% vs 27%). Conclusion,,, Polyneuropathy associated with IgM-MG, especially when associated with anti-MAG antibodies, appears to have more of a demyelinating involvement that meets the criteria for demyelination. This was not as clear in those associated with IgG. The IgG neuropathy showed less and milder deficit in the electrophysiological studies. [source] Studying electrophysiological characteristics in children with congenital sensory nystagmus- case presentationsACTA OPHTHALMOLOGICA, Issue 2009J BRECELJ Purpose In classification of sensory congenital nystagmus (CN) is important to recognize the underlying retinal or visual pathway dysfunction. The aim was to distinguish ERGs and VEPs charcteristics which may identify among variety of disorders associated with sensory CN. Methods In infants and small children that were ophthalmologically classified as sensory CN were ERGs and VEPs recorded simultaneously in the same session. ERGs were detected without dilated pupils and with skin electrodes. Under darkened laboratory conditions were ERGs recorded to white (cone/rod mediated response) and dim blue (rod mediated response) flash and under lighten room were ERGs recorded to white, red and 30 Hz flicker flash (cone mediated responses). VEPs were recorded from three occipital electrodes to flash and onset stimulation. Results Cases with abnormal ERGs showed: in Leber's congenital amaurosis were undetectable both rod and cone mediated responses from early infancy; in cone-rod retinal dystrophy abnormal cone and rod mediated responses progressed in time; in achromatopsia abnormal cone mediated responses did not progress in time; in congenital stationary night blindness a negative ERG did not progress in time. Cases with abnormal VEPs showed: in ocular albinism VEP contralateral asymmetry; in achiasmia VEP ipsilateral asymmetry; in severe optic nerve hypoplasia flash VEP was non-recordable, while in moderate optic nerve hypoplasia flash and pattern onset VEP findings might not correlate with clinic findings. Conclusion Sensory CN is associated with a variety of disorders affecting the retina, optic nerve, chiasm and electrophysiology may characterize retinal or postretinal pathway dysfunction and therefore help in early diagnosis. [source] Electrophysiological Characteristics Of The Ca2+ -Activated Cl, Channel Family Of Anion Transport ProteinsCLINICAL AND EXPERIMENTAL PHARMACOLOGY AND PHYSIOLOGY, Issue 11 2000Catherine M Fuller SUMMARY 1. A protein isolated from the bovine tracheal epithelium behaves as a Ca2+ -activated Cl, channel (CaCC) when incorporated into planar lipid bilayers. 2. An antibody raised against this protein was used to screen a cDNA expression library and resulted in the isolation of a cDNA clone that exhibited nearly identical electrophysiological characteristics to the isolated endogenous protein when expressed. 3. Recent cloning of several related proteins has revealed that the cloned bovine CaCC is one of a large and growing family. All new family members so far examined are associated with the appearance of a novel Ca2+ -mediated Cl, conductance when heterologously expressed. 4. This new group of proteins may underlie the Ca2+ -mediated Cl, conductance upregulated in the cystic fibrosis (CF) knockout mouse and thought to be responsible for the escape from the significant airway pathology associated with CF. [source] Familial And Acquired Long QT Syndrome And The Cardiac Rapid Delayed Rectifier Potassium CurrentCLINICAL AND EXPERIMENTAL PHARMACOLOGY AND PHYSIOLOGY, Issue 10 2000Harry J Witchel SUMMARY 1. Long QT syndrome (LQTS) is a cardiac disorder characterized by syncope, seizures and sudden death; it can be congenital, idiopathic, or iatrogenic. 2. Long QT syndrome is so-named because of the connection observed between the distinctive polymorphic ventricular tachycardia torsade de pointes and prolongation of the QT interval of the electrocardiogram, reflecting abnormally slowed ventricular action potential (AP) repolarization. Acquired LQTS has many similar clinical features to congenital LQTS, but typically affects older individuals and is often associated with specific pharmacological agents. 3. A growing number of drugs associated with QT prolongation and its concomitant risks of arrhythmia and sudden death have been shown to block the ,rapid' cardiac delayed rectifier potassium current (IKr) or cloned channels encoded by the human ether-a-go-go -related gene (HERG; the gene believed to encode native IKr). Because IKr plays an important role in ventricular AP repolarization, its inhibition would be expected to result in prolongation of both the AP and QT interval of the electrocardiogram. 4. The drugs that produce acquired LQTS are structurally heterogeneous, including anti-arrhythmics, such as quinidine, non-sedating antihistamines, such as terfenadine, and psychiatric drugs, such as haloperidol. In addition to heterogeneity in their structure, the electrophysiological characteristics of HERG/IKr inhibition differ between agents. 5. Here, clinical observations are associated with cellular data to correlate acquired LQTS with the IKr/HERG potassium (K+) channel. One strategy for developing improved compounds in those drug classes that are currently associated with LQTS could be to design drug structures that preserve clinical efficacy but are modified to avoid pharmacological interactions with IKr. Until such time, awareness of the QT-prolongation risk of particular agents is important for the clinician. [source] | |||||||||||||