scholarly journals Dynamic restitution of action potential duration during electrical alternans and ventricular fibrillation

1998 ◽  
Vol 275 (5) ◽  
pp. H1635-H1642 ◽  
Author(s):  
Marcus L. Koller ◽  
Mark L. Riccio ◽  
Robert F. Gilmour Jr.
Keyword(s):  
Ventricular Fibrillation ◽  
Action Potential ◽  
Action Potential Duration ◽  
Cycle Length ◽  
Strong Relationship ◽  
Standard Protocol ◽  
Diastolic Interval ◽  
Cycle Lengths ◽  
Electrical Alternans ◽  
Kinetics Of

The restitution kinetics of action potential duration (APD) were investigated in paced canine Purkinje fibers (P; n = 9) and endocardial muscle (M; n = 9), in isolated, perfused canine left ventricles during ventricular fibrillation (VF; n = 4), and in endocardial muscle paced at VF cycle lengths (simulated VF; n = 4). Restitution was assessed with the use of two protocols: delivery of a single extrastimulus after a train of stimuli at cycle length = 300 ms (standard protocol), and fixed pacing at short cycle lengths (100–300 ms) that induced APD alternans (dynamic protocol). The dynamic protocol yielded a monotone increasing restitution function with a maximal slope of 1.13 ± 0.13 in M and 1.14 ± 0.17 in P. Iteration of this function reproduced the APD dynamics found experimentally, including persistent APD alternans. In contrast, the standard protocol yielded a restitution relation with a maximal slope of 0.57 ± 0.18 in M and 0.84 ± 0.20 in P, and iteration of this function did not reproduce the APD dynamics. During VF, the restitution kinetics at short diastolic interval were similar to those determined with the dynamic protocol (maximal slope: 1.72 ± 0.47 in VF and 1.44 ± 0.49 in simulated VF). Thus APD dynamics at short coupling intervals during fixed pacing and during VF were accounted for by the dynamic, but not the standard, restitution relation. These results provide further evidence for a strong relationship among the kinetics of electrical restitution, the occurrence of APD alternans, and complex APD dynamics during VF.

scholarly journals Intramural optical mapping of Vm and Cai2+ during long-duration ventricular fibrillation in canine hearts

2012 ◽  
Vol 302 (6) ◽  
pp. H1294-H1305 ◽  
Author(s):  
Wei Kong ◽  
Raymond E. Ideker ◽  
Vladimir G. Fast
Keyword(s):  
Ventricular Fibrillation ◽  
Action Potential ◽  
Short Duration ◽  
Action Potential Duration ◽  
Cycle Length ◽  
The Other ◽  
Membrane Voltage ◽  
Long Duration ◽  
Intracellular Ca ◽  
Rapid Pacing

Intramural gradients of intracellular Ca2+ (Cai2+) Cai2+ handling, Cai2+ oscillations, and Cai2+ transient (CaT) alternans may be important in long-duration ventricular fibrillation (LDVF). However, previous studies of Cai2+ handling have been limited to recordings from the heart surface during short-duration ventricular fibrillation. To examine whether abnormalities of intramural Cai2+ handling contribute to LDVF, we measured membrane voltage ( Vm) and Cai2+ during pacing and LDVF in six perfused canine hearts using five eight-fiber optrodes. Measurements were grouped into epicardial, midwall, and endocardial layers. We found that during pacing at 350-ms cycle length, CaT duration was slightly longer (by ≃10%) in endocardial layers than in epicardial layers, whereas action potential duration (APD) exhibited no difference. Rapid pacing at 150-ms cycle length caused alternans in both APD (APD-ALT) and CaT amplitude (CaA-ALT) without significant transmural differences. For 93% of optrode recordings, CaA-ALT was transmurally concordant, whereas APD-ALT was either concordant (36%) or discordant (54%), suggesting that APD-ALT was not caused by CaA-ALT. During LDVF, Vm and Cai2+ progressively desynchronized when not every action potential was followed by a CaT. Such desynchronization developed faster in the epicardium than in the other layers. In addition, CaT duration strongly increased (by ∼240% at 5 min of LDVF), whereas APD shortened (by ∼17%). CaT rises always followed Vm upstrokes during pacing and LDVF. In conclusion, the fact that Vm upstrokes always preceded CaTs indicates that spontaneous Cai2+ oscillations in the working myocardium were not likely the reason for LDVF maintenance. Strong Vm-Cai2+ desynchronization and the occurrence of long CaTs during LDVF indicate severely impaired Cai2+ handling and may potentially contribute to LDVF maintenance.

Cycle length effect on restitution of action potential duration in dog cardiac fibers

1983 ◽  
Vol 244 (6) ◽  
pp. H782-H792 ◽  
Author(s):  
V. Elharrar ◽  
B. Surawicz
Keyword(s):  
Steady State ◽  
Action Potential ◽  
Action Potential Duration ◽  
Fiber Types ◽  
Ventricular Muscle ◽  
Purkinje Fibers ◽  
Hyperbolic Curve ◽  
Cycle Lengths ◽  
Kinetics Of ◽  
State Curve

Electrical restitution of action potential duration (APD) was determined in Purkinje (n = 8) and ventricular muscle (n = 6) fibers at two different basic cycle lengths (BCL, 1,500 and 500 ms). Restitution curves, normalized for the longest APD (the plateau of restitution), fitted the sum of a fast (T1) and a slow (T2) exponential component. The T1 was shorter in ventricular muscle than Purkinje fibers (89 +/- 5 and 143 +/- 9; mean +/- SE, P less than 0.05), whereas the T2 did not differ (1,448 +/- 231 and 1,439 +/- 211). The BCL altered the APD value during the plateau of restitution but did not change the two exponential components. In both fiber types, the relation between APD and BCL during steady state fitted a hyperbolic curve that predicts the achievement of the maximum APD at long BCL. The restitution curves crossed the steady-state curve at two points outlining three different zones of APD intervals: early premature, late premature, and postmature. The APD during restitution was longer than the steady state in the late premature zone and shorter than the steady-state APD in the post-mature and early premature zones. The APD per se, independent of BCL, did not influence the kinetics of restitution in Purkinje fibers.

Cycle length-dependent action potential duration in canine cardiac Purkinje fibers

1984 ◽  
Vol 247 (6) ◽  
pp. H936-H945 ◽  
Author(s):  
V. Elharrar ◽  
H. Atarashi ◽  
B. Surawicz
Keyword(s):  
Steady State ◽  
Action Potential ◽  
Action Potential Duration ◽  
Cycle Length ◽  
Slow Inward Current ◽  
Tetraethylammonium Chloride ◽  
Inward Current ◽  
Purkinje Fibers ◽  
Cardiac Purkinje Fibers ◽  
Kinetics Of

We studied the effects of pharmacologic probes that affect predominantly the Na inward current [tetrodotoxin (TTX), lidocaine], the slow inward current [cobalt, isoproterenol, verapamil], and the potassium currents [tetraethylammonium chloride (TEA), SG-75] on the duration of the action potential (APD) of canine cardiac Purkinje fibers during steady state and restitution. A schema is proposed in which the APD during steady state or restitution is determined by three factors: maximum action potential duration (APDmax), kinetics of restitution, and “memory.” The predicted APDmax was 469 +/- 34 (SE) ms (n = 27) in control. It was prolonged (P less than 0.05) by cobalt, verapamil, and TEA and shortened (P less than 0.05) by TTX, lidocaine, isoproterenol, and SG-75. In control, the kinetics of restitution were described by a sum of two exponentials with time constant T1 = 137 +/- 9 ms and T2 = 1,665 +/- 135 ms (n = 27), respectively. T1 was prolonged (P less than 0.05) by TTX, lidocaine, and verapamil but was not changed by other probes. None of the probes studied altered the T2 of restitution or the memory factor, computed at a cycle length of 500 ms from the predicted APDmax and the plateau of restitution. Low temperature (31 degrees C) prolonged APDmax and T1 and reduced the memory. We conclude that each of the proposed three factors is controlled by different mechanisms and that a TTX-sensitive current appears to contribute to the process of restitution of APD.

scholarly journals Role of maximum rate of depolarization in predicting action potential duration during ventricular fibrillation

2007 ◽  
Vol 293 (4) ◽  
pp. H2530-H2536 ◽  
Author(s):  
Jian Huang ◽  
Kang-An Cheng ◽  
Derek J. Dosdall ◽  
William M. Smith ◽  
Raymond E. Ideker
Keyword(s):  
Ventricular Fibrillation ◽  
Action Potential ◽  
Action Potential Duration ◽  
Maximum Rate ◽  
Important Determinant ◽  
Left Ventricular ◽  
Ventricular Wall ◽  
Stepwise Linear Regression ◽  
Diastolic Interval

During ventricular fibrillation (VF) only 39% of the variation in action potential duration (APD) is accounted for by the previous diastolic interval [DI( n−1)], i.e., restitution, and the previous APD [APD( n−1)], i.e., memory. We tested the hypothesis that a characteristic of the AP upstroke, the maximum rate of depolarization ( V̇max), also helps account for its APD. A floating microelectrode was used to make transmembrane recordings at 16,000 samples/s from the anterior left ventricular wall during four 20-s episodes of VF in each of six pigs. V̇max, time from V̇max to 60% repolarization (APD60), and DI were calculated throughout all episodes. Stepwise linear regression was used to determine how well each APD60 (APD60 n) was predicted by V̇max of that AP, the four previous DIs ( n−1, n − 2, n − 3, n − 4), and the three previous APD60s ( n−1, n − 2, n − 3). V̇max entered in the regression equation significantly more often (86% of VF episodes) than either APD( n−1) (47% of episodes) or DI( n−1) (58% of episodes). When these three variables entered first or second, their coefficients were almost always positive, consistent with a longer APD associated with 1) a larger V̇max, 2) a longer APD( n−1), and 3) a longer DI( n−1). R2 of the regression for all entered variables was 0.51 ± 0.01 (mean ± SD). During the first 20 s of VF in swine, V̇max is a more important determinant of APD than the previous DI (restitution) or the previous APD (memory). All variables together account for only one-half of APD variation during VF.

P2564Levosimendan shortens action potential duration, decreases alternans threshold and prevents ventricular arrhythmia during therapeutic hypothermia in isolated rabbit hearts

2019 ◽  
Vol 40 (Supplement_1) ◽  
Author(s):  
Y C Hsieh ◽  
C H Li ◽  
Y C Liao ◽  
J C Lin ◽  
C J Weng ◽  
...  
Keyword(s):  
Ventricular Fibrillation ◽  
Action Potential ◽  
Therapeutic Hypothermia ◽  
Action Potential Duration ◽  
Ventricular Arrhythmias ◽  
Cycle Length ◽  
Novel Approach ◽  
Mapping System ◽  
K Current ◽  
Calcium Sensitizer

Abstract Background Therapeutic hypothermia (TH) increases the susceptibility to ventricular arrhythmias (VA) by prolonging action potential duration (APD) and facilitating arrhythmogenic spatially discordant alternans (SDA). The calcium sensitizer levosimendan has been reported to shorten APD by enhancing ATP-sensitive K current. We hypothesize that levosimendan might shorten the already prolonged APD during TH, decreasing SDA threshold, and prevent the occurrence of VA. Methods Langendorff-perfused isolated rabbit hearts were subjected to 15-min TH (30°C) followed by 30-min treatment with levosimendan (0.5 μM, n=9) or vehicle (n=8). Using an optical mapping system, epicardial APD was evaluated by S1 pacing. SDA threshold was defined as the longest pacing cycle length (PCL) that induced SDA phenomenon. Ventricular fibrillation (VF) inducibility was evaluated by burst pacing for 30 s using the shortest PCL that achieved 1:1 ventricular capture. Results Levosimendan shortened the ventricular APD (at PCL 300 ms, from 229±9 ms to 211±18 ms, p=0.02) and decrease the SDA threshold (from 327±88 ms to 311±68 ms, p=0.001) during TH. The VF inducibility was decreased by levosimendan from 39±30% at 30°C to 14±12% after levosimendan infusion. In control hearts, the APD (p=0.75), SDA threshold (p=ns) and VF inducibility (p=0.12) were not changed by vehicle during TH. Conclusions Levosimendan protects the hearts against VA during TH by shortening APD and decreasing SDA threshold. Enhancing ATP-sensitive K current with levosimendan might be a novel approach to prevent VA during TH.

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.

scholarly journals Idiopathic Ventricular Fibrillation Characterized by Spatial Heterogeneity of Action Potential Duration and Its Restitution Kinetics

2008 ◽  
Vol 49 (6) ◽  
pp. 733-740 ◽  
Author(s):  
Sonoko Ashino ◽  
Ichiro Watanabe ◽  
Masayoshi Kofune ◽  
Kimie Ohkubo ◽  
Yasuo Okumura ◽  
...  
Keyword(s):  
Ventricular Fibrillation ◽  
Action Potential ◽  
Spatial Heterogeneity ◽  
Action Potential Duration ◽  
Idiopathic Ventricular Fibrillation

Reverse use dependence of calcium sensitizer levosimendan on action potential duration shortening prevents ventricular arrhythmia during therapeutic hypothermia

2020 ◽  
Vol 41 (Supplement_2) ◽  
Author(s):  
Y.C Hsieh ◽  
C.H Li ◽  
J.C Lin ◽  
C.J Weng ◽  
Y.S Chien ◽  
...  
Keyword(s):  
Ventricular Arrhythmia ◽  
Action Potential ◽  
Therapeutic Hypothermia ◽  
Action Potential Duration ◽  
Heart Failure Treatment ◽  
Novel Approach ◽  
Mapping System ◽  
Diastolic Interval ◽  
K Current ◽  
Calcium Sensitizer

Abstract Background Therapeutic hypothermia (TH) increases the risk of ventricular arrhythmia (VA) by prolonging action potential duration (APD) and steepening the APD restitution (APDR). The calcium sensitizer levosimendan, a medication for heart failure treatment, has been reported to shorten APD by enhancing ATP-sensitive K current and affect the APDR. Purpose We hypothesized that levosimendan might shorten the already prolonged APD particularly at long pacing cycle length (PCL), thus decreases the maximal slope of APDR, and prevent VA during TH. Methods Langendorff-perfused isolated rabbit hearts were subjected to 15-min TH (30°C) followed by 30-min treatment with levosimendan (0.5 μM, n=9) or vehicle (n=8). Using an optical mapping system, APD was evaluated by S1 pacing and APDR curve was plotted using APD70 versus diastolic interval. Ventricular fibrillation (VF) inducibility was evaluated by burst pacing for 30 s at the shortest PCL that achieved 1:1 ventricular capture. Results The APD was shortened from 259±8 ms at TH to 241±18 ms after levosimendan infusion at long PCL of 400 ms (p=0.024). However, at short PCL of 280 ms, the APD was not changed before (194±19) and after (188±23) levosimendan during TH (p=0.61). Levosimendan decreases the maximal slope of APDR curve from 1.99±0.65 at TH to 1.41±0.32 after adding levosimendan (p=0.034). The VF inducibility was decreased by levosimendan from 39±30% at 30°C to 14±12% with levosimendan (p=0.023). In control hearts, the maximal slope of APDR (p=0.75) and VF inducibility (p=0.12) were not changed by vehicle during TH. Conclusion Levosimendan might protect the hearts against VA during TH by shortening APD at long PCL and flattening the APDR. Enhancing ATP-sensitive K current with levosimendan during TH might be a novel approach to prevent VA during TH. Funding Acknowledgement Type of funding source: None

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