Possible arrhythmiogenic mechanism produced by ibuprofen
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Keywords:
Ibuprofen
Effective refractory period
Cardiac Electrophysiology
PR interval
BACKGROUND Concealed conduction is recognized as a major determinant of atrioventricular (AV) nodal filtering properties, but little is known about the underlying mechanisms. OBJECTIVES The purpose of this study was to consistently elicit concealed conduction through the AV node and to determine the involvement of slow and fast pathways in resultant changes in nodal function. METHODS The concealment zone (nodal effective refractory period minus nodal functional refractory period of atrium) was determined in six rabbit heart preparations with and without a conditioning cycle (10 ms longer than nodal effective refractory period). Nodal function curves were constructed for concealed cycle lengths selected within the concealment zone. Experiments were repeated after slow pathway ablation. RESULTS When assessed with a blocked beat alone, a narrow concealment zone (22 12 ms, n 3) was observed in 50% of the preparations. In contrast, when assessed with a blocked beat preceded by a conducted conditioning beat, a wider concealment zone (77 47 ms, n 6, P .03) was observed in all preparations. Increases in the concealed cycle length resulted in graded increases in the nodal effective refractory period and nodal functional refractory period and graded rightward shifts of the recovery curve as a whole, consistent with resetting of the excitability cycle in the slow and fast pathways. These effects were analogous to those expected from a conducted beat. Slow pathway ablation widened the concealment zone but failed to alter fast pathway resetting. CONCLUSION Our approach reveals a wide concealment zone consistently displayed in all preparations. Concealed conduction acts as a resetting mechanism of the excitability cycle in the slow and fast pathways similar to that expected from a conducted beat.
Effective refractory period
Beat (acoustics)
Ablation zone
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Effective refractory period
Sotalol
Refractory (planetary science)
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Relative contributions of the atria and the atrioventricular (AV) node to AV conduction were studied in isolated, blood-perfused dog hearts. The functional refractory period of the atria, although shorter than that of the AV node, determined the functional refractory period of the entire transmission system in 50% of the hearts. Slow atrial conduction of early beats greatly influenced the shape of the curve used to determine the functional refractory period of the transmission system. The atrial effective refractory period was also shorter than the effective refractory period of the AV node. However, the effective refractory period of the entire transmission system was equal to that of the atrium when the driving interval was longer than 320 msec, and it decreased as the driving interval was shortened. At driving intervals of 320 msec or less, the effective refractory period of the AV transmission system abruptly increased and became equal to the effective refractory period of the node. Conduction of early premature responses from near the sinoatrial node to the AV node was supernormal in 50% of the hearts. Supernormal conduction of premature atrial responses in the ventricles was also observed. The period of supernormal conduction in both tissues shifted toward greater prematurity as heart rate increased. The importance of the atrium in determining the functional properties of the AV transmission system has been previously underestimated.
Effective refractory period
Atrioventricular node
Atrium (architecture)
Refractory (planetary science)
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In order to observe further electrophysiologic characteristics of atrioventricular (AV) conduction,We compared atrial functional refractory peroid (AFRP) and atrioventricular nodal effective refractory period (AVNERP) in 8 dogs. AV condution was assessed by atrial extrastimulus technique using at least two basic cycle lengths. The electophysiologic parameters were recorded before and after administering intravenous Metoprolol to block the β receptor in the heart, and plotted into the AV conduction curve. As a result,the AVNERP could not be measured in any dog. AV conduction curve showed significant changes before and after the administration of Metoprolol at equivalent basic cycle length,AFRP also showed significant prolongation. It domonstrated that the refractory periods of cardiac conduction are obvious difference in different species. The properties that AVNERP is permanently shorter than AFRP in the dog may be functional manifestation of its physiologic characteristics.
Effective refractory period
Refractory (planetary science)
Atrioventricular block
Atrioventricular node
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The functional refractory period of atrioventricular (AV) transmission has been accepted as a measure of AV nodal refractoriness and has been assumed to be determined solely by conduction of interpolated extrasystoles through the AV node when it is partially refractory. In the present study, we found an important effect of the conduction time of the regular beats by measuring AV nodal conduction times of atrial extrasystoles from the His bundle of isolated, blood-perfused dog hearts. We separated three independent components that determine AV nodal conductivity: (1) a "basal conduction time" measured with a "postmature" extrasystole at low heart rates (<120 /min), (2) a rate-dependent increment in conduction time (previously called "fatigue") that affects both normal and premature cycles equally and (3) an exponential change in conduction time that depends entirely on the immediately preceding interval and, therefore, is not further affected by heart rate. The functional refractory period is one point defining this continuous exponential function. We showed that an important cause of the decrease in the functional refractory period that occurs when heart rate is increased is the change in the conduction time of the regular beats.
Effective refractory period
Atrioventricular node
Bundle branches
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The aim of this study was to test the electrophysiological effects of continuous enhanced vagal tone on dual atrioventricular (AV) nodal and accessory pathways.This study included 10 patients with typical, slow-fast AV nodal reentrant tachycardia (AVNRT) and 10 patients with AV reciprocating tachycardia. Electrophysiological data were measured before and during continuous vagal enhancement by using phenylephrine infusion (0.6 to 1.5 microg/kg per min). For patients with AVNRT, during phenylephrine infusion, 1:1 conduction times over the anterograde fast and slow and retrograde fast pathways were prolonged (453+/-64 to 662+/-120 ms, P<0.001; 379+/-53 to 443+/-95 ms, P<0.05; 405+/-112 to 442+/-118 ms, P<0.05). The effective refractory period and functional refractory period of the anterograde fast pathway were prolonged with phenylephrine (394+/-73 to 544+/-128 ms, P<0.001; 454+/-60 to 596+/-118 ms, P<0.001). In contrast, the effective refractory period and functional refractory period of the anterograde slow and retrograde fast were not significantly changed. No significant change was observed in the conduction or refractoriness of the accessory pathways in patients with AV reciprocating tachycardia nor in atrial or ventricular refractoriness.Enhanced vagal tone produces disparate effects on the refractoriness of the slow and fast AV nodal conduction pathways, with the anterograde fast pathway being the most sensitive. These changes are conducive to induction of AVNRT with a premature atrial complex and may explain in part the relatively common occurrence of AVNRT during sleep or other periods of presumed increased parasympathetic tone.
Effective refractory period
Atrioventricular node
Phenylephrine
Orthodromic
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Effective refractory period
Refractory (planetary science)
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Effective refractory period
Beat (acoustics)
Atrioventricular node
Ablation zone
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Summary Dofetilide, clofilium, and risotilide, three drugs known to prolong cardiac action potentials and refractory periods, were studied by using a perfused isolated rabbit heart preparation with intermittent premature pacing and bipolar surface electrograms. The rate-related effects of these drugs on atrioventricular (AV) conduction were tested by pacing at a long (400 ms) and a short (250 ms) basic cycle length (BCL). All three drugs increased refractory periods in a concentration-dependent manner in most segments of the AV axis. The maximal atrio-His (AH) conduction interval (AHmax) and ΔAH (AHmax - AHmin) produced by premature pacing was decreased by the highest concentration of each drug at the 400-ms BCL, whereas only clofilium reduced AHmax and ΔAH at the 250-ms BCL. Changes in ΔAH correlated best with changes in the atrial functional refractory period. The His-Purkinje system conduction interval (HV), represented by ΔHV, was unaffected by any drug at either BCL. These results show that if atrial or nodal refractory periods are increased sufficiently, AHmax but not AHmin was decreased at the 400-ms BCL. Because dofetilide and risotilide did not affect AHmax at the 250-ms BCL, these drugs may be less effective at preventing AV nodal reentrant tachycardias than a drug such as clofilium that displays less rate dependency.
Effective refractory period
Dofetilide
Refractory (planetary science)
Atrioventricular node
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A class III antiarrhythmic agent that preferentially increases the effective refractory period without altering conduction velocity holds considerable promise for the treatment of life-threatening cardiac arrhythmias dependent on a reentrant mechanism. In the present study, the cellular electrophysiologic effects of a novel class III antiarrhythmic agent, UK-66,914, were evaluated. UK-66,914 prolonged action potential duration and extended the effective refractory period in isolated canine ventricular muscle and Purkinje fibers in a concentration-dependent manner, beginning at a threshold concentration of 0.1 microM. Analogous effects were found in isolated rabbit atrium beginning at a threshold concentration of 2 microM. At concentrations of UK-66,914 up to 20 microM there was no effect on the maximum rate of phase 0 depolarization (Vmax) or the amplitude of the action potential. In guinea pig papillary muscles. UK-66,914 at concentrations from 0.1 to 20 microM increased the effective refractory period at stimulation frequencies of 1 or 5 Hz, but did not slow conduction velocity. Therefore, UK-66,914 exhibits high selectivity for a class III antiarrhythmic effect in normal tissue. To elucidate the mechanisms responsible for the increase in effective refractory period, voltage clamp procedures were used in guinea pig ventricular myocytes. UK-66,914 reduced the amplitude of outward tail currents following depolarizing clamp steps with little effect either on the background K+ current or calcium currents, indicating that UK-66,914 selectively blocked the time-dependent potassium current. In anesthetized dogs, UK-66,914 (10 micrograms/kg to 1 mg/kg i.v.) prolonged both atrial and ventricular effective refractory periods, but in contrast to the studies performed in vitro, the minimum effective doses required to increase the effective refractory period in atria and ventricle were the same. Therefore, UK-66,914 is a potent selective class III antiarrhythmic agent, which owes its electrophysiologic profile to blockade of the time-dependent potassium current.
Effective refractory period
Purkinje fibers
Antiarrhythmic agent
Papillary muscle
Atrium (architecture)
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