Isoproterenol antagonizes drug-induced prolongation of action potential duration in humans

1993 ◽  
Vol 71 (10-11) ◽  
pp. 755-760 ◽  
Author(s):  
David Newman ◽  
Paul Dorian ◽  
Randi Feder-Elituv
Keyword(s):  
Steady State ◽  
Action Potential ◽  
Action Potential Duration ◽  
Refractory Period ◽  
Cycle Length ◽  
Monophasic Action Potential ◽  
Class Iii ◽  
State Action ◽  
Cycle Lengths ◽  
Prolongation Of Action Potential

The effects of an isoproterenol infusion on the duration of the human right ventricular endocardial monophasic action potential at 90% repolarization were recorded in the absence and in the presence of an antiarrhythmic drag regimen containing class III effects in two similar groups of patients. The drugs used were amiodarone (N = 3, 300 ± 50 mg), sotalol plus quinidine (N = 11, 156 ± 13 mg sotalol, 1688 ± 594 mg quinidine), and sotalol alone (N = 3, 300 ± 20 mg). All patients had underlying coronary disease but no evidence of inducible ischemia. In the absence of antiarrhythmic drug, isoproterenol did not significantly change the relationship of action potential duration at 90% repolarization to cycle length; there was a linear decrease in action potential duration by 19.8% between a paced cycle length of 600 and 300 ms. Isoproterenol did not significantly shorten the action potential duration at any cycle length. However, isoproterenol decreased the ventricular effective refractory period at 400 ms drive from 240 ± 5.0 to 225 ± 6.0 ms (p < 0.05) accompanied by no change in the ratio of refractory period to steady-state action potential duration. In the presence of class III drug effects, the action potential duration was increased by an average of 9.2% at all paced cycle lengths longer than 300 ms (p < 0.05). The ventricular refractory period was increased from 240 ± 5 to 269 ± 9.0 ms (p < 0.05 compared with baseline) with a concomitant increase in the ratio of refractory period to action potential duration from 96 ± 2 to 103 ± 2% (p < 0.05 compared with baseline). With infusion of isoproterenol in the presence of a class III containing regimen, the drug-prolonged action potential duration was shortened (p < 0.05) by an average of 8.1% at all cycle lengths longer than 300 ms. These results suggest that isoproterenol simulation of enhanced sympathetic tone can antagonize drug prolongation of action potential duration and that in the absence of drugs, the effects of isoproterenol on the steady-state action potential duration are modest. The clinical utility of class III agents may be augmented by the addition of concomitant β-blockade.Key words: action potential duration, antiarrhythmic drugs, isoproterenol.

Class III Antiarrhythmic Effects of Dofetilide in Rabbit Atrial Myocardium

1996 ◽  
Vol 1 (3) ◽  
pp. 229-234 ◽  
Author(s):  
Regan T. Pallandi ◽  
Nigel H. Lovell ◽  
Terence J. Campbell
Keyword(s):  
Action Potential ◽  
Action Potential Duration ◽  
Interstimulus Interval ◽  
Class Iii ◽  
Atrial Myocardium ◽  
New Class ◽  
Class Iii Antiarrhythmic Agent ◽  
Prolongation Of Action Potential ◽  
Dose Dependent ◽  
Microelectrode Techniques

Background Dofetilide is a new class III antiarrhythmic agent with demonstrated efficacy in ventricular and atrial tachyarrhythmias. We investigated its class HI actions and their modulation by stimulation rate in rabbit atrial myocardium. Methods and Results Standard microelectrode techniques were used to record action potentials from rabbit atrial tissue at varying stimulation rates. Dofetilide produced a dose-dependent prolongation of action potential duration at concentrations from 1 nM to 1 μM at an interstimulus interval of 1000 ms. Action potential duration at 90% repolarization (action potential duration) was prolonged from 116 ± 11.7 ms in control solutions to 148 ± 13.9 ms at 1nM dofetilide and 186 ± 49.3 ms at 1 μM dofetilide ( P < .05 for 1 nM vs control; P < .01 for 1 μM vs control). Reduction of interstimulus interval to 500 ms had no significant effect on action potential duration prolongation by dofetilide. At faster rates than this, and particularly at an interstimulus interval less than 330 ms, a marked “reverse rate dependence” of the class III effect was observed. Specifically, the high therapeutic concentration of 10 nM showed no effect on action potential duration at interstimulus interval of 250 ms or 200 ms, and even at a concentration of 30 nM, the small class III effect was no longer statistically significant at these rates. Conclusion Dofetilide prolongs action potential duration in rabbit atrial myocardium, but this effect is significantly attenuated at stimulation rates above 2 Hz.

Effects of Thoracic Epidural Anesthesia with and without Autonomic Nervous System Blockade on Cardiac Monophasic Action Potentials and Effective Refractoriness in Awake Dogs

2001 ◽  
Vol 95 (1) ◽  
pp. 132-138 ◽  
Author(s):  
Andreas Meissner ◽  
Lars Eckardt ◽  
Paulus Kirchhof ◽  
Thomas Weber ◽  
Norbert Rolf ◽  
...  
Keyword(s):  
Action Potential ◽  
Epidural Anesthesia ◽  
Action Potential Duration ◽  
Action Potentials ◽  
Monophasic Action Potential ◽  
Thoracic Epidural Anesthesia ◽  
Thoracic Epidural ◽  
Monophasic Action Potentials ◽  
Cycle Lengths

Background The effects of thoracic epidural anesthesia (TEA) on myocardial repolarization and arrhythmogenicity are only incompletely understood. This is primarily because of the lack of appropriate experimental models. In most of the studies performed thus far, TEA was used in anesthetized animals. Baseline anesthesia itself may have modified the effects of TEA. This study investigates right atrial and ventricular repolarization by recording monophasic action potentials after TEA in awake dogs. The authors hypothesized that an antiarrhythmic role of TEA exists, which may be related to a direct effect of TEA on myocardial repolarization. Methods The hypothesis was tested in an in vivo canine model, in which atrial and ventricular myocardial action potential duration and refractoriness are recorded by means of monophasic action potential catheters. Results Thoracic epidural anesthesia significantly increased ventricular monophasic action potential duration for cycle lengths shorter than 350 ms. Changes in monophasic action potential duration were paralleled by a concomitant prolongation of effective refractory period (ERP) at higher rates so that the ratio of ERP to action potential duration was unaffected. Conclusions This model helps to study the role of TEA on ventricular repolarization and arrhythmogenicity. Because lengthening of repolarization and prolongation of refractoriness may, in some circumstances, be antiarrhythmic, TEA may be protective against generation of ventricular arrhythmias mediated, e.g., by increased sympathetic tone. The results also imply that the beneficial role of TEA might be stronger at the ventricular site as compared with the atrium. At atrial sites there was only a trend toward prolongation of repolarization even at short cycle lengths.

scholarly journals Restitution slope is principally determined by steady-state action potential duration

2017 ◽  
Vol 113 (7) ◽  
pp. 817-828 ◽  
Author(s):  
Michael J. Shattock ◽  
Kyung Chan Park ◽  
Hsiang-Yu Yang ◽  
Angela W. C. Lee ◽  
Steven Niederer ◽  
...  
Keyword(s):  
Steady State ◽  
Action Potential ◽  
Action Potential Duration ◽  
State Action

Dose-Dependent Effects of Ranolazine on Reentrant Ventricular Arrhythmias Induced After Subacute Myocardial Infarction in Rabbits

2019 ◽  
Vol 25 (1) ◽  
pp. 65-71 ◽  
Author(s):  
Vassileios Moschovidis ◽  
Vassileios Simopoulos ◽  
Soultana Stravela ◽  
Konstantina Dipla ◽  
Apostolia Hatziefthimiou ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Ventricular Tachycardia ◽  
Action Potential ◽  
Refractory Period ◽  
Ventricular Arrhythmias ◽  
Cycle Length ◽  
Sustained Ventricular Tachycardia ◽  
Effective Refractory Period ◽  
Monophasic Action Potential ◽  
Coronary Artery Ligation

Ranolazine has been found to prevent ventricular arrhythmias (VAs) during acute myocardial infarction (AMI). This study aimed to investigate its efficacy on VAs induced several days post-MI. For this purpose, 13 anesthetized rabbits underwent coronary artery ligation. Ten of these animals that survived AMI were reanesthetized 3 to 7 days later for electrophysiologic testing. An endocardial monophasic action potential combination catheter was placed in the right ventricle for simultaneous pacing and recording. Monophasic action potential duration, ventricular effective refractory period (VERP), and VAs induced by programmed stimulation were assessed. Measurements were performed during control pacing, and following an intravenous infusion of either a low-dose ranolazine (2.4 mg/kg, R1) or a higher dose ranolazine (4.8 mg/kg cumulative dose, R2). During control stimulation, 2 animals developed primary ventricular fibrillation (VF), 6 sustained ventricular tachycardia (sVT), and 2 nonsustained VT (nsVT). R1 did not prevent the appearance of VAs in any of the experiments; in contrast, it aggravated nsVT into sVT and complicated sVT termination in 2 of 6 animals. Sustained ventricular tachycardia cycle length and VERP were only slightly decreased after R1 (112 ± 5 vs 110 ± 6 ms and 101 ± 11 vs 98 ± 10 ms, respectively). R2 suppressed inducibility of control nsVT, VF, and sVT in 2 animals. In 4 animals with still inducible sVT, R2 significantly prolonged VT cycle length by 150 ± 23 ms ( P < .01), and VERP by 120 ± 7 ms ( P < .001) versus control. In conclusion, R2 exerted antiarrhythmic efficacy against subacute-MI VAs, whereas R1 rather aggravated than prevented these arrhythmias. Ventricular effective refractory period prolongation could partially explain the antiarrhythmic action of R2 in this rabbit model.

Action potential characterization in intact mouse heart: steady-state cycle length dependence and electrical restitution

2007 ◽  
Vol 292 (1) ◽  
pp. H614-H621 ◽  
Author(s):  
Björn C. Knollmann ◽  
Tilmann Schober ◽  
Andreas O. Petersen ◽  
Syevda G. Sirenko ◽  
Michael R. Franz
Keyword(s):  
Steady State ◽  
Action Potential ◽  
Action Potentials ◽  
Cycle Length ◽  
Molecular Mechanisms ◽  
Left Ventricular ◽  
Monophasic Action Potential ◽  
Mouse Heart ◽  
Intact Mouse ◽  
Length Dependence

Transgenic mice have been increasingly utilized to investigate the molecular mechanisms of cardiac arrhythmias, yet the rate dependence of the murine action potential duration and the electrical restitution curve (ERC) remain undefined. In the present study, 21 isolated, Langendorff-perfused, and atrioventricular node-ablated mouse hearts were studied. Left ventricular and left atrial action potentials were recorded using a validated miniaturized monophasic action potential probe. Murine action potentials (AP) were measured at 30, 50, 70, and 90% repolarization (APD30–APD90) during steady-state pacing and varied coupling intervals to determine ERCs. Murine APD showed rate adaptation as well as restitution properties. The ERC time course differed dramatically between early and late repolarization: APD30 shortened with increasing S1–S2 intervals, whereas APD90 was prolonged. When fitted with a monoexponential function, APD30 reached plateau values significantly faster than APD90 (τ = 29 ± 2 vs. 78 ± 6 ms, P < 0.01, n = 12). The slope of early APD90 restitution was significantly <1 (0.16 ± 0.02). Atrial myocardium had shorter final repolarization and significantly faster ERCs that were shifted leftward compared with ventricular myocardium. Recovery kinetics of intracellular Ca2+ transients recorded from isolated ventricular myocytes at 37°C (τ = 93 ± 4 ms, n = 18) resembled the APD90 ERC kinetics. We conclude that mouse myocardium shows AP cycle length dependence and electrical restitution properties that are surprisingly similar to those of larger mammals and humans.

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