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Effective Refractory Period (effective + refractory_period)

Distribution by Scientific Domains

Medical Sciences	90%
Life Sciences	10%

Distribution within Medical Sciences

Cardiovascular Disease	91%
Pharmacology & Pharmaceutical Medicine	5%

Kinds of Effective Refractory Period

atrial effective refractory period

Selected Abstracts

Alcohol Intake is Significantly Associated with Atrial Flutter in Patients under 60 Years of Age and a Shorter Right Atrial Effective Refractory Period

PACING AND CLINICAL ELECTROPHYSIOLOGY, Issue 3 2008
GREGORY M. MARCUS M.D.
Background: Although evidence suggests that alcohol is associated with atrial fibrillation (AF), the association between alcohol and atrial flutter (AFL) has not been examined. The mechanism connecting alcohol and atrial arrhythmias is unknown. Methods: Alcohol intake was determined in 195 consecutive patients with AF and AFL. Control subjects included patients with other supraventricular arrhythmias (n = 132) and healthy subjects (n = 54). Because of important competing risk factors for atrial arrhythmias in the elderly, stratification by age was performed. In a subset, atrial effective refractory periods (AERPs) were obtained from the high right atrium and proximal and distal coronary sinus. Results: AF and AFL patients were significantly more likely to be daily alcohol drinkers (27% vs 14% of controls, P = 0.001). In multivariable analysis, AFL patients , 60 years of age were significantly more likely to be daily drinkers than to drink no alcohol compared to controls (odds ratio 17, 95% confidence interval 1.6,192.0, P = 0.019). Progressively more frequent alcohol intake was significantly associated with a progressively greater odds of AFL in patients , 60 years of age (P = 0.045). Neither AF subjects of any age nor AFL subjects > 60 years of age exhibited significant associations with alcohol after multivariable adjustment. Right AERPs shortened significantly with increasing amounts of alcohol intake (P = 0.025), whereas left AERPs were not associated with alcohol intake. Conclusions: Alcohol intake is positively associated with AFL in younger patients. The mechanism may be related to a shortening of the right AERP. [source]

Chamber-specific effects of hypokalaemia on ventricular arrhythmogenicity in isolated, perfused guinea-pig heart

EXPERIMENTAL PHYSIOLOGY, Issue 4 2009
Oleg 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]

Characterization of Sustained Atrial Tachycardia in Dogs with Rapid Ventricular Pacing-Induced Heart Failure

JOURNAL OF CARDIOVASCULAR ELECTROPHYSIOLOGY, Issue 5 2003
Bruce S. Stambler M.D.
Introduction: Atrial arrhythmias often complicate congestive heart failure (CHF). We characterized inducible atrial tachyarrhythmias and electrophysiologic alterations in dogs with CHF and atrial enlargement produced by rapid ventricular pacing. Methods and Results: Endocardial pacing leads were implanted in the right ventricle, right atrium, and coronary sinus in 18 dogs. The right ventricular lead was connected to an implanted pacemaker capable of rapid ventricular pacing. The atrial leads were used to perform electrophysiologic studies in conscious animals at baseline in all dogs, during CHF induced by rapid ventricular pacing at 235 beats/min in 15 dogs, and during recovery from CHF in 6 dogs. After20 ± 7 daysof rapid ventricular pacing, inducibility of sustained atrial tachycardia (cycle length120 ± 12 msec) was enhanced in dogs with CHF. Atrial tachycardia required a critical decrease in atrial burst pacing cycle length (,130 msec) for induction and often could be terminated by overdrive pacing. Calcium antagonists (verapamil, flunarizine, ryanodine) terminated atrial tachycardia and suppressed inducibility. Effective refractory periods at 400- and 300-msec cycle lengths in the right atrium and coronary sinus were prolonged in dogs with CHF. Atrial cells from dogs with CHF had prolonged action potential durations and reduced resting potentials and delayed afterdepolarizations (DADs). Mitochondria from atrial tissue from dogs with CHF were enlarged and had internal cristae disorganization. Conclusions: CHF promotes inducibility of sustained atrial tachycardia. Based on the mode of tachycardia induction, responses to pacing and calcium antagonists, and presence of DADs, atrial tachycardia in this CHF model has a mechanism most consistent with DAD-induced triggered activity resulting from intracellular calcium overload.(J Cardiovasc Electrophysiol, Vol. 14, pp. 499-507, May 2003) [source]

Chamber-specific effects of hypokalaemia on ventricular arrhythmogenicity in isolated, perfused guinea-pig heart

Age-Related Increase in Atrial Fibrillation Induced by Transvenous Catheter-Based Atrial Burst Pacing: An In Vivo Rat Model of Inducible Atrial Fibrillation

JOURNAL OF CARDIOVASCULAR ELECTROPHYSIOLOGY, Issue 1 2010
DONGZHU XU M.D.
AF Rat Model Induced by Transvenous Catheter Pacing.,Introduction: Large animal models of atrial fibrillation (AF) are well established, but limited experimental reports exist on small animal models. We sought to develop an in vivo rat model of AF using a transvenous catheter and to evaluate the model's underlying characteristics. Methods and Results: Echocardiogram, surface electrocardiogram (ECG), and atrial effective refractory period (AERP) were recorded at baseline in young (3 months) and middle-aged (9 months) Wistar rats. AF inducibility and duration were measured through transvenous electrode catheter in young (n = 11) and middle-aged rats (n = 11) and middle-aged rats treated with either pilsicainide (1 mg/kg iv, n = 7) or amiodarone (10 mg/kg iv, n = 9). Degrees of interstitial fibrosis and cellular hypertrophy in the atria were assessed histologically. The P-wave duration and AERP were significantly longer and echocardiographic left atrial dimension significantly larger in middle-aged versus young rats. AF was inducible in >90% of all procedures in both untreated rat groups, whereas AF inducibility was reduced by the antiarrhythmic drugs. The AF duration was significantly longer in middle-aged than in young rats and was significantly shortened by treatment with either pilsicainide or amiodarone. Histologic analysis revealed significant increases in atrial interstitial fibrosis and cellular diameter in middle-aged versus young rats. Conclusions: Transvenous catheter-based AF is significantly longer in middle-aged than in young rats and is markedly reduced by treatment with antiarrhythmic drugs. This rat model of AF is simple, reproducible, and reliable for examining pharmacologic effects on AF and studying the process of atrial remodeling.(J Cardiovasc Electrophysiol, Vol. 21, pp. 88,93, January 2010) [source]

Ranolazine Exerts Potent Effects on Atrial Electrical Properties and Abbreviates Atrial Fibrillation Duration in the Intact Porcine Heart

JOURNAL OF CARDIOVASCULAR ELECTROPHYSIOLOGY, Issue 7 2009
KAPIL KUMAR M.D.
Introduction: In vitro studies and ambulatory ECG recordings from the MERLIN TIMI-36 clinical trial suggest that the novel antianginal agent ranolazine may have the potential to suppress atrial arrhythmias. However, there are no reports of effects of ranolazine on atrial electrophysiologic properties in large intact animals. Methods and Results: In 12 closed-chest anesthetized pigs, effects of intravenous ranolazine (,9 ,M plasma concentration) on multisite atrial effective refractory period (ERP), conduction time (CT), and duration and inducibility of atrial fibrillation (AF) initiated by intrapericardial acetylcholine were investigated. Ranolazine increased ERP by a median of 45 ms (interquartile range 29,50 ms; P < 0.05, n = 6) in right and left atria compared to control at pacing cycle length (PCL) of 400 ms. However, ERP increased by only 28 (24,34) ms in right ventricle (P < 0.01, n = 6). Ranolazine increased atrial CT from 89 (71,109) ms to 98 (86,121) ms (P = 0.04, n = 6) at PCL of 400 ms. Ranolazine decreased AF duration from 894 (811,1220) seconds to 621 (549,761) seconds (P = 0.03, n = 6). AF was reinducible in 1 of 6 animals after termination with ranolazine compared with all 6 animals during control period (P = 0.07). Dominant frequency (DF) of AF was reduced by ranolazine in left atrium from 11.7 (10.7,20.5) Hz to 7.6 (2.9,8.8) Hz (P = 0.02, n = 6). Conclusions: Ranolazine, at therapeutic doses, increased atrial ERP to greater extent than ventricular ERP and prolonged atrial CT in a frequency-dependent manner in the porcine heart. AF duration and DF were also reduced by ranolazine. Potential role of ranolazine in AF management merits further investigation. [source]

Heterogeneity of Ventricular Fibrillation Dominant Frequency During Global Ischemia in Isolated Rabbit Hearts

JOURNAL OF CARDIOVASCULAR ELECTROPHYSIOLOGY, Issue 8 2007
Ch.B. , JANE CALDWELL M.B.
Introduction: Ventricular fibrillation (VF) studies show that ECG-dominant frequency (DF) decreases as ischemia develops. This study investigates the contribution of the principle ischemic metabolic components to this decline. Methods and Results: Rabbit hearts were Langendorff-perfused at 40 mL/min with Tyrode's solution and loaded with RH237. Epicardial optical action potentials were recorded with a photodiode array (256 sites, 15 × 15 mm). After 60 seconds of VF (induced by burst pacing), global ischemia was produced by low flow (6 mL/min), or the solution changed to impose hypoxia (95% N2/5% CO2), low pHo (6.7, 80% O2/20% CO2), or raised [K+]o (8 mM). DF of the optical signals was determined at each site. Conduction velocity (CV), action potential duration (APD90), effective refractory period (ERP), activation threshold, dV/dtmax, and membrane potential were measured in separate experiments during ventricular pacing. During VF, ischemia decreased DF in the left ventricle (LV) (to [58 ± 6]%, P < 0.001), but not the right (RV) ([93 ± 5]%). Raised [K+]o reproduced this DF pattern (LV: [67 ± 12]%, P < 0.001; RV: [95 ± 9]%). LV DF remained elevated in hypoxia or low pHo. During ventricular pacing, ischemia decreased CV in LV but not RV. Raised [K+]o did not change CV in either ventricle. Ischemia and raised [K+]o shortened APD90 without altering ERP. LV activation threshold increased in both ischemia and raised [K+]o and was associated with diastolic depolarization and decreased dV/dtmax. Conclusions: These results suggest that during VF, decreased ECG DF in global ischemia is largely due to elevated [K+]o affecting the activation thresholds in the LV rather than RV. [source]

Reversal of Electrical Remodeling After Cardioversion of Persistent Atrial Fibrillation

JOURNAL OF CARDIOVASCULAR ELECTROPHYSIOLOGY, Issue 5 2004
MERRITT H. RAITT M.D.
Introduction: In animals, atrial fibrillation results in reversible atrial electrical remodeling manifested as shortening of the atrial effective refractory period, slowing of intra-atrial conduction, and prolongation of sinus node recovery time. There is limited information on changes in these parameters after cardioversion in patients with persistent atrial fibrillation. Methods and Results: Thirty-eight patients who had been in atrial fibrillation for 1 to 12 months underwent electrophysiologic testing 10 minutes and 1 hour after cardioversion. At 1 week, 19 patients still in sinus rhythm returned for repeat testing. Reverse remodeling of the effective refractory period was not uniform across the three atrial sites tested. At the lateral right atrium, there was a highly significant increase in the effective refractory period between 10 minutes and 1 hour after cardioversion (drive cycle length 400 ms: 204 ± 17 ms vs 211 ± 20 ms, drive cycle length 550 ms: 213 ± 18 ms vs 219 ± 23 ms, P < 0.001). The effective refractory period at the coronary sinus and distal coronary sinus did not change in the first hour but had increased by 1 week. The corrected sinus node recovery time did not change in the first hour but was shorter at 1 week (606 ± 311 ms vs 408 ± 160 ms, P = 0.009). P wave duration also was shorter at 1 week (135 ± 18 ms vs 129 ± 13 ms, P = 0.04) consistent with increasing atrial conduction velocity. Conclusion: The atrial effective refractory period increases, sinus node function improves, and atrial conduction velocity goes up in the first week after cardioversion of long-standing atrial fibrillation in humans. Reverse electrical remodeling of the effective refractory period occurs at different rates in different regions of the atrium. (J Cardiovasc Electrophysiol, Vol. 15, pp. 507-512, May 2004) [source]

Autonomic Blockade Unmasks Maturational Differences in Rate-Dependent Atrioventricular Nodal Conduction and Facilitation in the Mouse

JOURNAL OF CARDIOVASCULAR ELECTROPHYSIOLOGY, Issue 2 2003
SAMIR SABA M.D.
Maturational Differences in Murine AVN Conduction. Introduction: In large animals, rate-dependent AV nodal (AVN) properties of conduction are modulated by autonomic inputs. In this study, we investigated whether the properties of AVN conduction and facilitation are altered by autonomic blockade in the mouse and whether this effect is age dependent. Methods and Results: Young (age 4,6 weeks; n = 11) and adult (age 8,9 months; n = 11) female mice underwent in vivo electrophysiologic testing, before and after autonomic blockade. After autonomic blockade, the adult mice had significantly longer AVN effective refractory period (AVNERP; 67 ± 14 msec vs 56 ± 4 msec, P = 0.05) and functional refractory period (AVNFRP; 81 ± 10 msec vs 72 ± 4 msec, P = 0.05). With autonomic blockade, the increase from baseline of AVN Wenckebach cycle length (,AVW; 1.8 ± 8.1 msec vs 8.8 ± 3.3 msec, P = 0.04), as well as of AVNERP (,AVNERP; 3.5 ± 3.5 msec vs 21.4 ± 12.6 msec, P = 0.002) and AVNFRP (,AVNFRP; 2.3 ± 3.2 msec vs 12.8 ± 9.0 msec, P = 0.008), was significantly larger in adult than in young mice. Compared with young mice, adult mice were less likely to exhibit AVN facilitation (44% vs 90%, P = 0.03) and had smaller maximal shortening of AVN conduction times after the "test beat" for any coupling of the "facilitating beat" (4 ± 4 msec vs 7 ± 3 msec, P = 0.05). Conclusion: Complete autonomic blockade significantly increases AVN conduction times and refractory periods in adult but not in young mice. Adult mice also exhibit less AVN facilitation. Our results confirm that, like in larger animals, rate-dependent murine AVN properties of conduction are under autonomic regulation. Adult mice have higher sympathetic AVN inputs at baseline, leading to slower conduction after autonomic blockade. (J Cardiovasc Electrophysiol, Vol. 14, pp. 191-195, February 2003) [source]

Identification and Characterization of Atrioventricular Parasympathetic Innervation in Humans

JOURNAL OF CARDIOVASCULAR ELECTROPHYSIOLOGY, Issue 8 2002
KARA 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]

Atrioventricular Nodal Reentrant Tachycardia in Children: Effect of Slow Pathway Ablation on Fast Pathway Function

JOURNAL OF CARDIOVASCULAR ELECTROPHYSIOLOGY, Issue 3 2002
GEORGE F. VAN HARE M.D.
AV Nodal Reentry in Children.Introduction: Prior studies in adults have shown significant shortening of the fast pathway effective refractory period after successful slow pathway ablation. As differences between adults and children exist in other characteristics of AV nodal reentrant tachycardia (AVNRT), we sought to characterize the effect of slow pathway ablation or modification in a multicenter study of pediatric patients. Methods and Results: Data from procedures in pediatric patients were gathered retrospectively from five institutions. Entry criteria were age < 21 years, typical AVNRT inducible with/without isoproterenol infusion, and attempted slow pathway ablation or modification. Dual AV nodal pathways were defined as those with > 50 msec jump in A2-H2 with a 10-msec decrease in A1-A2. Successful ablation was defined as elimination of AVNRT inducibility. A total of 159 patients (age 4.4 to 21 years, mean 13.1) were studied and had attempted slow pathway ablation. AVNRT was inducible in the baseline state in 74 (47%) of 159 patients and with isoproterenol in the remainder. Dual AV nodal pathways were noted in 98 (62%) of 159 patients in the baseline state. Ablation was successful in 154 (97%) of 159 patients. In patients with dual AV nodal pathways and successful slow pathway ablation, the mean fast pathway effective refractory period was 343 ± 68 msec before ablation and 263 ± 64 msec after ablation. Mean decrease in the fast pathway effective refractory period was 81 ± 82 msec (P < 0.0001) and was not explained by changes in autonomic tone, as measured by changes in sinus cycle length during the ablation procedure. Electrophysiologic measurements were correlated with age. Fast pathway effective refractory period was related to age both before (P = 0.0044) and after ablation (P < 0.0001). AV block cycle length was related to age both before (P = 0.0005) and after ablation (P < 0.0001). However, in dual AV nodal pathway patients, the magnitude of change in the fast pathway effective refractory period after ablation was not related to age. Conclusion: Lack of clear dual AV node physiology is common in pediatric patients with inducible AVNRT (38%). Fast pathway effective refractory period shortens substantially in response to slow pathway ablation. The magnitude of change is large compared with adult reports and is not completely explained by changes in autonomic tone. Prospective studies in children using autonomic blockade are needed. [source]

Supervulnerable Phase Immediately After Termination of Atrial Fibrillation

JOURNAL OF CARDIOVASCULAR ELECTROPHYSIOLOGY, Issue 3 2002
MATTIAS DUYTSCHAEVER M.D.
Supervulnerable Phase After Termination of AF.Introduction: Recent studies with the implantable atrial cardioverter have shown that atrial fibrillation (AF) recurs almost immediately after successful cardioversion in about 27% of cases. In the present study, we determined the electrophysiologic properties of the caprine atrium immediately after spontaneous termination of AF both before and after 48 hours of AF-induced electrical remodeling. Methods and Results: In eight goats, atrial effective refractory period (AERP), intra-atrial conduction velocity, and atrial wavelength were measured during sinus rhythm both before (t = 0) and after 48 hours (t = 48) of electrically maintained AF (baseline). After baseline, a 5-minute paroxysm of AF was induced, during which the refractory period (RPAF) was determined. AERP, conduction velocity, and atrial wavelength also were measured immediately after spontaneous restoration of sinus rhythm (post-AF values). Both in normal and remodeled atria, immediately after AF, AERP and conduction velocity were markedly decreased compared with baseline (P < 0.01). In normal atria, post-AF AERP (107 ± 14 msec) gradually prolonged from its AF value (114 ± 17 msec) to its baseline value (138 ± 13 msec). Conduction velocity decreased from 130 ± 9 cm/sec to 117 ± 9 cm/sec. After 48 hours of AF, AERP had shortened to 74 ± 8 msec. RPAF was 89 ± 9 msec. Surprisingly, immediately after termination of AF, AERP shortened further to 58 ± 6 msec (P < 0.01). Post-AF conduction velocity decreased from 136 ± 11 cm/sec to 122 ± 10 cm/sec (P < 0.01). As a result, the post-AF atrial wavelength became as short as 7.1 ± 1 cm. These changes were transient, and all parameters gradually returned to baseline within 1 to 2 minutes after conversion of AF. Conclusion: Due to a combined decrease in AERP and conduction velocity, marked shortening of the atrial wavelength occurs during the first minutes after conversion of AF. In electrically remodeled atria, this results in a transient ultrashort value of AERP (< 60 msec) and atrial wavelength (7.1 cm). These observations imply a highly vulnerable substrate for reentry immediately after termination of AF. During this supervulnerable phase, both early and later premature beats reinitiated immediate recurrences of AF. [source]

Effects of Estrogen on Cardiac Electrophysiology in Female Mice

JOURNAL OF CARDIOVASCULAR ELECTROPHYSIOLOGY, Issue 3 2002
SAMIR SABA M.D.
Estrogen and Cardiac Electrophysiology.Introduction: Understanding the molecular mechanisms that underlie gender- and hormonal-related differences in susceptibility to cardiac arrhythmias has been hampered by the lack of a suitable animal model. We examined the effect of hormonal status on the electrophysiologic (EP) properties of the mouse heart in an in vivo, closed chest model. Methods and Results: Fifty-three female C57/J mice aged 10 to 12 weeks were studied. Thirty-six mice underwent bilateral ovariectomies; 18 received estrogen (OVX + E) and 18 received placebo (OVX). Seventeen female mice underwent only sham surgery. All animals underwent in vivo EP studies. Select EP parameters were measured after quinidine treatment. Data were analyzed by a blinded observer. Compared with the intact female mice, the PR and AH intervals were significantly shorter in the OVX mice, and these parameters normalized with estrogen replacement (PR = 45.9 ± 4.5 msec in the intact mice, 42.1 ± 4.3 msec in the OVX group, and 46.9 ± 3.5 msec in the OVX + E group, P < 0.005; AH = 36.5 ± 4.9 msec in the intact mice, 34.4 ± 4.7 msec in the OVX group, and 38.8 ± 2.7 msec in the OVX + E group, P = 0.03). The right ventricular effective refractory period was significantly shorter in the OVX mice versus the intact mice, and this also normalized with estrogen replacement. Hormonal status did not significantly affect any other EP variable, including QT interval. Conclusion: In female mice, estrogen prolongs AV nodal conduction and the right ventricular effective refractory period. Taken together, these data suggest that hormonal status affects aspects of cardiac EP function. Future application of this mouse model will be helpful in determining the molecular pathways that mediate hormonal differences in cardiac EP. [source]

Effect of Gender on Atrial Electrophysiologic Changes Induced by Rapid Atrial Pacing and Elevation of Atrial Pressure

JOURNAL OF CARDIOVASCULAR ELECTROPHYSIOLOGY, Issue 9 2001
HUNG-FAT TSE M.D.
Atrial Electrical Remodeling.Introduction: The incidence of atrial fibrillation is greater in men than in women, but the reasons for this gender difference are unclear. The purpose of this study was to evaluate the effects of gender on the atrial electrophysiologic effects of rapid atrial pacing and an increase in atrial pressure. Methods and Results: Right atrial pressure and effective refractory period (ERP) were measured during sinus rhythm and during atrial and simultaneous AV pacing at a cycle length of 300 msec in 10 premenopausal women, 11 postmenopausal women, and 24 men. The postmenopausal women were significantly older than the premenopausal women (61 ± 8 years vs 34 ± 10 years; P < 0.01). During sinus rhythm, mean atrial ERP in premenopausal women was shorter (211 ± 19 msec) than in postmenopausal women and age-matched men (242 ± 18 msec and 246 ± 34 msec, respectively; P < 0.05). Atrial ERPs in all patients shortened significantly during atrial and simultaneous AV pacing. However, the degree of shortening during atrial pacing (43 ± 8 msec vs 70 ± 20 msec and 74 ± 21 msec; P < 0.05) and during simultaneous AV pacing (48 ± 16 msec vs 91 ± 27 msec and 84 ± 26 msec; P < 0.05) was significantly less in premenopausal women than in postmenopausal women or age-matched men. Conclusion: The results of this study demonstrate a significant gender difference in atrial electrophysiologic changes in response to rapid atrial pacing and an increase in atrial pressure. The effect of menopause on the observed changes suggests that the gender differences may be mediated by the effects of estrogen on atrial electrophysiologic properties. [source]

Atrial Fibrillation in the Goat Induces Changes in Monophasic Action Potential and mRNA Expression of Ion Channels Involved in Repolarization

JOURNAL OF CARDIOVASCULAR ELECTROPHYSIOLOGY, Issue 11 2000
HUUB 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]

Atrial, SA Nodal, and AV Nodal Electrophysiology in Standing Horses: Normal Findings and Electrophysiologic Effects of Quinidine and Diltiazem

JOURNAL OF VETERINARY INTERNAL MEDICINE, Issue 1 2007
Colin C. Schwarzwald
Background: Although atrial arrhythmias are clinically important in horses, atrial electrophysiology has been incompletely studied. Hypotheses: Standard electrophysiologic methods can be used to study drug effects in horses. Specifically, the effects of diltiazem on atrioventricular (AV) nodal conduction are rate-dependent and allow control of ventricular response rate during rapid atrial pacing in horses undergoing quinidine treatment. Animals: Fourteen healthy horses. Methods: Arterial blood pressure, surface electrocardiogram, and right atrial electrogram were recorded during sinus rhythm and during programmed electrical stimulation at baseline, after administration of quinidine gluconate (10 mg/kg IV over 30 minutes, n = 7; and 12 mg/kg IV over 5 minutes followed by 5 mg/kg/h constant rate infusion for the remaining duration of the study, n = 7), and after coadministration of diltiazem (0.125 mg/kg IV over 2 minutes repeated every 12 minutes to effect). Results: Quinidine significantly prolonged the atrial effective refractory period, shortened the functional refractory period (FRP) of the AV node, and increased the ventricular response rate during atrial pacing. Diltiazem increased the FRP, controlled ventricular rate in a rate-dependent manner, caused dose-dependent suppression of the sinoatrial node and produced a significant, but well tolerated decrease in blood pressure. Effective doses of diltiazem ranged from 0.125 to 1.125 mg/kg. Conclusions and Clinical Importance: Standard electrophysiologic techniques allow characterization of drug effects in standing horses. Diltiazem is effective for ventricular rate control in this pacing model of supraventricular tachycardia. The use of diltiazem for rate control in horses with atrial fibrillation merits further investigation. [source]

Abnormal Atrioventricular Node Conduction and Atrioventricular Nodal Reentrant Tachycardia in Patients Older Versus Younger Than 65 Years of Age

PACING AND CLINICAL ELECTROPHYSIOLOGY, Issue 2009
MIHAELA GRECU M.D.
Study Objective: We examined the possible role of atrioventricular node (AVN) conduction abnormalities as a cause of AVN reentrant tachycardia (RT) in patients >65 years of age. Study Population: Slow pathway radiofrequency catheter ablation (RFCA) was performed in 104 patients. Patients in group 1 (n = 14) were >65 years of age and had AV conduction abnormalities associated with structural heart disease. Patients in group 2 (n = 90) were <65 years of age and had lone AVNRT. Results: Patients in group 1 versus group 2 (66% vs. 46% men) had a first episode of tachycardia at an older age than in group 2 (68 ± 16.8 vs 32.5 ± 18.8 years, P = 0.007). The history of arrhythmia was shorter in group 1 (5.4 ± 3.8 vs 17.5 ± 14, P = 0.05) and was associated with a higher proportion of patients with underlying heart disease than in group 2 (79% vs 3%, P < 0.001). The electrophysiological measurements were significantly shorter in group 2: atrial-His interval (74 ± 17 vs 144 ± 44 ms, P = 0.005), His-ventricular (HV) interval (41 ± 5 vs 57 ± 7 ms, P = 0.001), Wenckebach cycle length (329 ± 38 vs 436 ± 90 ms, P = 0.001), slow pathway effective refractory period (268 ± 7 vs 344 ± 94 ms, P = 0.005), and tachycardia cycle length (332 ± 53 vs 426 ± 56 ms, P = 0.001). The ventriculoatrial block cycle length was similar in both groups. The immediate procedural success rate was 100% in both groups, and no complication was observed in either group. One patient in group 2 had recurrence of AVNRT. One patient with a 98-ms HV interval underwent permanent VVI pacemaker implantation before RFCA procedure. Conclusion: In patients undergoing RFCA for AVNRT at >65 years of age had a shorter history of tachycardia-related symptoms than patients with lone AVNRT. The longer AVN conduction intervals and refractory period might explain the late development of AVNRT in group 1. [source]

The Electrophysiological Characteristics in Patients with Ventricular Stimulation Inducible Fast-Slow Form Atrioventricular Nodal Reentrant Tachycardia

PACING AND CLINICAL ELECTROPHYSIOLOGY, Issue 10 2006
PI-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]

Electrophysiologic Characteristics and Radiofrequency Catheter Ablation in Children with Wolff-Parkinson-White Syndrome

PACING AND CLINICAL ELECTROPHYSIOLOGY, Issue 5 2006
PI-CHANG LEE
Background: The majority of cardiac arrhythmias in children are supraventricular tachycardia, which is mainly related to an accessory pathway (AP)-mediated reentry mechanism. The investigation for Wolff-Parkinson-White (WPW) syndrome in adults is numerous, but there is only limited information for children. This study was designed to evaluate the specific electrophysiologic characteristics and the outcome of radiofrequency (RF) catheter ablation in children with WPW syndrome. Methods: From December 1989 to August 2005, a total of 142 children and 1,219 adults with atrioventricular reentrant tachycardia (AVRT) who underwent ablation at our institution were included. We compared the clinical and electrophysiologic characteristics between children and adults with WPW syndrome. Results: The incidence of intermittent WPW syndrome was higher in children (7% vs 3%, P=0.025). There was a higher occurrence of rapid atrial pacing needed to induce tachycardia in children (67% vs 53%, P=0.02). However, atrial fibrillation (AF) occurred more commonly in adult patients (28% vs 16%, P = 0.003). The pediatric patients had a higher incidence of multiple pathways (5% vs 1%, P < 0.001). Both the onset and duration of symptoms were significantly shorter in the pediatric patients. The antegrade 1:1 AP conduction pacing cycle length (CL) and antegrade AP effective refractory period (ERP) in children were much shorter than those in adults with manifest WPW syndrome. Furthermore, the retrograde 1:1 AP conduction pacing CL and retrograde AP ERP in children were also shorter than those in adults. The antegrade 1:1 atrioventricular (AV) node conduction pacing CL, AV nodal ERP, and the CL of the tachycardia were all shorter in the pediatric patients. Conclusion: This study demonstrated the difference in the electrophysiologic characteristics of APs and the AV node between pediatric and adult patients. RF catheter ablation was a safe and effective method to manage children with WPW syndrome. [source]

Electrophysiological Remodeling in Human Atrial Fibrillation

PACING AND CLINICAL ELECTROPHYSIOLOGY, Issue 7p2 2003
DAVID R. VAN WAGONER
Atrial fibrillation (AF) is a progressive disease characterized by cumulative electrophysiological and structural remodeling of the atria. Cellular electrophysiological studies have revealed marked reductions in the densities of the L-type voltage-gated Ca2+ current, ICa,L, the transient outward K+ current, ITO, and the ultra-rapid delayed rectifier K+ current, IKur, in atrial myocytes from patients in persistent or permanent AF. The density of the muscarinic K+ current (IKACh) is also reduced, however the inward rectifier K+ current (IK1) density is increased. The net shortening or lengthening of the action potential is dependent on the balance between changes in inward and outward currents. The prominent reduction in ICa,L appears to be sufficient to explain the observed decreases in action potential duration and effective refractory period that are characteristic of the fibrillating atria. Earlier studies have shown that calcium overload and perturbations in calcium handling play prominent roles in AF induced atrial remodeling. More recently, we have shown that AF is associated with evidence of oxidative injury to atrial tissue, and suggested that oxidative stress may directly contribute to the pathophysiology of AF. It is anticipated that insights gleaned from mechanistic studies will facilitate the development of improved pharmacological approaches to treat AF and to prevent the progression of arrhythmia. (PACE 2003; 26[Pt. II]:1572,1575) [source]

Relation of Age and Sex to Atrial Electrophysiological Properties in Patients with No History of Atrial Fibrillation

PACING AND CLINICAL ELECTROPHYSIOLOGY, Issue 5 2003
KOICHI SAKABE
Although atrial fibrillation is a common arrhythmia, especially in elderly men, little is known about age related changes in atrial electrophysiological properties or gender differences. The aim of this study was to analyze the effects of aging on vulnerability to atrial fibrillation and assessed gender differences in those age related changes. An electrophysiological study was performed on 73 patients with no history of atrial fibrillation, structural heart disease, or conditions with potential effects on cardiac hemodynamic or electrophysiological function, including 25 women (mean age 49 ± 18 years; range 12,84 years). The following atrial excitability parameters were assessed: spontaneous or paced (A1) and extrastimulated (A2) atrial electrogram widths, percent maximum atrial fragmentation(A2/A1 × 100), effective refractory period, wavelength index (effective refractory period/A2), and inducibility of atrial fibrillation. There were no significant differences in percent maximum atrial fragmentation (143 ± 28vs142 ± 35%), effective refractory period (241 ± 39vs238 ± 50 ms), wavelength index (2.9 ± 0.8vs3.1 ± 0.9), induction of atrial fibrillation (10 [21%] vs 7 [28%]), or age (50 ± 17vs 49 ± 20 years) between men and women. Age was not statistically different between those patients with and without induction of atrial fibrillation in men (48 ± 14vs50 ± 18 years) and women (48 ± 18vs49 ± 21 years). Percent maximum atrial fragmentation and effective refractory period were directly correlated with age in men (r = 0.35, P = 0.01; r = 0.46, P < 0.001, respectively) and women (r = 0.42, P = 0.04; r = 0.45, P = 0.02, respectively), though wavelength index did not correlate with age in men (r =,0.04) or women (r =,0.04) with no history of atrial fibrillation. Considering these findings, the authors conclude that the mechanism triggering atrial fibrillation may be different between older and younger patients with atrial fibrillation, because younger patients who have no marked substrate for atrial fibrillation may need many trigger beats to induce atrial fibrillation. (PACE 2003; 26:1238,1244) [source]

Effect of Different Pacing Protocols on the Induction of Atrial Fibrillation in a Transvenously Paced Sheep Model

PACING AND CLINICAL ELECTROPHYSIOLOGY, Issue 6 2001
RIK 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]

Clinical Significance of the Atrial Fibrillation Threshold in Patients with Paroxysmal Atrial Fibrillation

PACING AND CLINICAL ELECTROPHYSIOLOGY, Issue 5 2001
KEIJI INOUE
INOUE, K., et al.: Clinical Significance of the Atrial Fibrillation Threshold in Patients with Paroxysmal Atrial Fibrillation. AF threshold and the other electrophysiological parameters were measured to quantify atrial vulnerability in patients with paroxysmal atrial fibrillation (PAF, n = 47), and those without AF (non-PAF, n = 25). Stimulations were delivered at the right atrial appendage with a basic cycle length of 500 ms. The PAF group had a significantly larger percentage of maximum atrial fragmentation (%MAF, non-PAF: mean ± SD = 149 ± 19%, PAF: 166 ± 26%, P = 0.009), fragmented atrial activity zone (FAZ, non-PAF: median 0 ms, interquartile range 0,20 ms, PAF: 20 ms, 10,40 ms, P = 0.008). Atrial fibrillation threshold (AF threshold, non-PAF: median 11 mA, interquartile range 6,21 mA, PAF: 5 mA, 3,6 mA, P < 0.001) was smaller in the PAF group than in the non-PAF group. Sensitivity, specificity, and positive predictive value of electrophysiological parameters were as follows, respectively: %MAF (cut off at 150%, 78%, 52%, 76%), FAZ (cut off at 20 ms, 47%, 84%, 85%), AF threshold (cut off at 10 mA, 94%, 60%, 81%). There were no statistically significant differences between the non-PAF and PAF groups in the other parameters (effective refractory period, interatrial conduction time, maximum conduction delay, conduction delay zone, repetitive atrial firing zone, wavelength index), that were not specific for PAF. In conclusion, the AF threshold could be a useful indicator to evaluate atrial vulnerability in patients with AF. [source]

Atrial Fibrillation Induction and Determination of Atrial Vulnerable Period Using Very Low Energy Synchronized Biatrial Shock in Normal Subjects and in Patients with Atrial Fibrillation

PACING AND CLINICAL ELECTROPHYSIOLOGY, Issue 4 2000
HUNG-FAT TSE
The atrial vulnerable periods (A VP)for shock induction of atrial fibrillation (AF) in humans have not been clearly defined. Furthermore, the safety and efficacy of using low energy biatrial shock delivered transvenously for AF induction are unknown. We tested the safety and efficacy of using very low energy biatrial shocks, delivered between the right atrium and the coronary sinus for AF induction and used this technique to characterize the A VP in nine controls and nine patients with AF. Thirty-volt and 60-V 3/3-ms biphasic shocks were delivered, starting from 50 ms before the atrial effective refractory period with 20-ms increments until the end of the QRS interval to determine the AVP front, AVP end, and the AVP duration. Successful AF induction could be achieved in eight (89%) of the nine controls and in nine (100%) of the nine patients with AF without any complication. In patients with AF, the AVP front started significantly earlier within the QRS complex, and the AVP duration and the AVP duration/QRS percent ratios were also significantly greater as compared to controls. Furthermore, a higher induction shock energy in patients with AF was associated with an increase in AF inducibility and significantly increased the AVP duration and A VP duration/QRS percent ratio as compared to the controls. This study demonstrated the safe and efficacy of delivering a very low energy biatrial shock during the AVP within the R wave for AF induction. The characteristics of A VP in patients with AF were significantly different from normal subjects. [source]

Prevention of the Initiation of Atrial Fibrillation: Mechanism and Efficacy of Different Atrial Pacing Modes

PACING AND CLINICAL ELECTROPHYSIOLOGY, Issue 3 2000
WEN-CHUNG YU
Several atrial pacing modes have been reported to be effective in the prevention of atrial fibrillation (AF); they included biatrial pacing, dual site right atrial pacing, Bachmann's bundle (BB) pacing, and coronary sinus pacing. However, the relative efficacy and electrophysiological mechanisms of these pacing modes in the prevention of AF are not clear. In 15 patients (age 54 ± 14 years) with paroxysmal AF, P wave duration, effective refractory period, and atrial conduction time were determined with six different atrial drive pacings, that were right atrial appendage (RAA), BB, right posterior interatrial septum (RPS), distal coronary sinus (DCS), RAA plus RPS simultaneously (DSA), and RAA plus DCS simultaneously (BiA). All these patients consistently had AF induced with early RAA extrastimulation coupling to RAA drive pacing. No patient had AF induced with RAA extrastimulation coupled to BB, RPS, or DCS drive pacing, but seven and eight patients had AF induced with RAA extrastimulation coupled to DSA and BiA drive pacing, respectively. The P wave duration was longest during RAA pacing, and became shorter during other atrial pacing modes. Analysis of electrophysiological change showed that early RAA extrastimulation coupled to RAA drive pacing caused the longest atrial conduction delay among these atrial pacing modes; BB, RPS, and DCS drive pacing caused a greater reduction of this conduction delay than DSA and BiA drive pacing. In addition, the effective refractory periods of RAA determined with BB, RPS, and DCS drive pacing were similar and longer than that determined with DSA and BiA drive pacing. In patients with paroxysmal AF, this arrhythmia was readily induced with RAA extrastimuli coupled to RAA drive pacing. BB, RPS, and DCS pacing were similar and more effective than DSA and BiA pacing in preventing AF. [source]

Dofetilide-Induced Long QT and Torsades de Pointes

ANNALS OF NONINVASIVE ELECTROCARDIOLOGY, Issue 3 2007
Mehmet K. Aktas M.D.
Dofetilide, a new class III antiarrhythmic agent, has been approved as an antiarrhythmic agent for the treatment of atrial fibrillation and atrial flutter. Dofetilide selectively inhibits the rapid component of the delayed rectifier potassium current resulting in a prolongation of the effective refractory period. Like other drugs that affect potassium currents, the prolonged QT interval occurring in the patients treated with dofetilide can be complicated by torsades de pointes. We report four cases of dofetilide-induced QT prolongation and torsades de pointes. We discuss the risk factors for the development of dofetilide-induced long QT and torsades de pointes and review the current literature. [source]

Electrophysiological effects of 5-hydroxytryptamine on isolated human atrial myocytes, and the influence of chronic , -adrenoceptor blockade

BRITISH JOURNAL OF PHARMACOLOGY, Issue 8 2003
Davide Pau
5-Hydroxytryptamine (5-HT) has been postulated to play a proarrhythmic role in the human atria via stimulation of 5-HT4 receptors. The aims of this study were to examine the effects of 5-HT on the L-type Ca2+ current (ICaL) action potential duration (APD), the effective refractory period (ERP) and arrhythmic activity in human atrial cells, and to assess the effects of prior treatment with , -adrenoceptor antagonists. Isolated myocytes, from the right atrial appendage of 27 consenting patients undergoing cardiac surgery who were in sinus rhythm, were studied using the whole-cell perforated patch-clamp technique at 37°C. 5-HT (1 nM,10 ,M) caused a concentration-dependent increase in ICaL, which was potentiated in cells from , -blocked (maximum response to 5-HT, Emax=299±12% increase above control) compared to non- , -blocked patients (Emax=220±6%, P<0.05), but with no change in either the potency (log EC50: ,7.09±0.07 vs ,7.26±0.06) or Hill coefficient (nH: 1.5±0.6 vs 1.5±0.3) of the 5-HT concentration,response curve. 5-HT (10 ,M) produced a greater increase in the APD at 50% repolarisation (APD50) in cells from , -blocked patients (of 37±10 ms, i.e. 589±197%) vs non- , -blocked patients (of 10±4 ms, i.e. 157±54%; P<0.05). Both the APD90 and the ERP were unaffected by 5-HT. Arrhythmic activity was observed in response to 5-HT in five of 17 cells (29%) studied from , -blocked, compared to zero of 16 cells from the non- , -blocked patients (P<0.05). In summary, the 5-HT-induced increase in calcium current was associated with a prolonged early plateau phase of repolarisation, but not late repolarisation or refractoriness, and the enhancement of these effects by chronic , -adrenoceptor blockade was associated with arrhythmic potential. British Journal of Pharmacology (2003) 140, 1434,1441. doi:10.1038/sj.bjp.0705553 [source]

CALCIUM ANTAGONIST PROPERTY OF CPU228, A DOFETILIDE DERIVATIVE, CONTRIBUTES TO ITS LOW INCIDENCE OF TORSADES DE POINTES IN RABBITS

CLINICAL AND EXPERIMENTAL PHARMACOLOGY AND PHYSIOLOGY, Issue 4 2007
Zhi-Jiang Huang
SUMMARY 1Torsades de pointes (TDP) is a severe adverse effect during the clinical use of dofetilide, a selective blocker of the rapid component of the delayed rectifier potassium channel (IKr). The present study was designed to test whether CPU228, a derivative of dofetilide with calcium (Ca2+) antagonist properties, could reduce TDP without reducing the blockade of IKr. 2The incidence of TDP in a rabbit model and the effective refractory period (ERP) were measured and compared for dofetilide and CPU228. Suppression of IKr and the L-type Ca2+ current (ICa,L) and the Ca2+ transients of isolated cardiomyocytes were investigated by whole-cell patch-clamp and Fluo-3 dye spectrophotometry. 3The incidence of TDP was greatly reduced by CPU228 relative to dofetilide, occurring in only one of six rabbits compared with five of six rabbits following dofetilide (P < 0.05). In isolated atria, prolongation of ERP by CPU228 was less than that of dofetilide and no reverse frequency dependence was observed. Negative inotropism by CPU228 was significant against positive inotropism by dofetilide. CPU228 inhibited both IKr and ICa,L currents and the IC50 for ICa,L inhibition was 0.909 µmol/L. At 3 µmol/L, CPU228 significantly suppressed the Ca2+ transients. 4CPU228 is able to block ICa,L, contributing to decreased TDP, while also blocking IKr activity. By combined blockade of IKr and ICa,L, CPU228 shares the property of complex Class III anti-arrhythmic agents. [source]

John B. Barlow: Master clinician and compleat cardiologist

CLINICAL CARDIOLOGY, Issue 1 2000
Tsung O. Cheng M.D.
Abstract This paper reports the case of a 76-year-old man in whom atrial flutter with varying atrioventricular block and intermittent right bundle-branch block was found. This is the first report on tachycardia-dependent right bundle-branch block associated with supernormal conduction in a case of atrial flutter. When an impulse is conducted to the ventricles beyond 0.72 s after a QRS complex of right bundle-branch block configuration, the impulse falls after the abnormally long effective refractory period of the right bundle branch and passes through the right bundle branch. When the conducted impulse occurs within 0.72 s after a QRS complex of right bundle-branch block configuration, the impulse usually falls in the refractory period and is blocked in the right bundle branch; however, only when the impulse occurs 0.48 or 0.49 s after that does it fall in the supernormal period and passes through the right bundle branch. The findings in the present report strengthen our previous suggestion that the presence of supernormal conduction plays an important role in the initiation of reentrant ventricular tachycardia. [source]