scholarly journals B-PO02-024 ATP-SENSITIVE POTASSIUM CURRENT OPENER LEVOSIMENDAN MODULATES ACTION POTENTIAL DURATION ALTERNANS PROPERTIES AND PREVENTS VENTRICULAR ARRHYTHMIA DURING THERAPEUTIC HYPOTHERMIA

Heart Rhythm ◽  
2021 ◽  
Vol 18 (8) ◽  
pp. S105
Author(s):  
Yu-Cheng Hsieh ◽  
Cheng-Hung Li ◽  
Jiunn-cherng Lin ◽  
Chi-Jen Weng ◽  
Yu-Shan Chien ◽  
...  
Keyword(s):  
Ventricular Arrhythmia ◽  
Action Potential ◽  
Therapeutic Hypothermia ◽  
Action Potential Duration ◽  
Potassium Current

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

Concurrent increases in post-pacing action potential duration and contractility predict occurrence of ventricular arrhythmia

2020 ◽  
Vol 472 (12) ◽  
pp. 1783-1791
Author(s):  
Chih-Min Liu ◽  
Feng-Zhi Lin ◽  
Yao-Chang Chen ◽  
Yung-Kuo Lin ◽  
Yen-Yu Lu ◽  
...  
Keyword(s):  
Ventricular Arrhythmia ◽  
Action Potential ◽  
Action Potential Duration

Effects of moderate hypoxia on premature action potentials of rabbit papillary muscle

1984 ◽  
Vol 62 (5) ◽  
pp. 596-599
Author(s):  
Julio Alvarez ◽  
Francisco Dorticós ◽  
Jesús Morlans
Keyword(s):  
Action Potential ◽  
Action Potential Duration ◽  
Action Potentials ◽  
Potassium Current ◽  
Maximum Rate ◽  
Resting Potential ◽  
Papillary Muscles ◽  
Premature Response ◽  
Coupling Interval ◽  
Control Response

Experiments were performed to study the effects of hypoxia on the characteristics of premature action potentials of rabbit papillary muscles. At normal resting potential, the duration of the premature action potential at the shortest coupling intervals was always greater than that of the control response. As the coupling interval was increased beyond 150 ms, the duration of the premature action potential regained control values. In cells depolarized to −70 mV by KCl, early lengthening of the premature response was attenuated. After 60 min of hypoxia, recovery of action potential duration at normal and reduced resting potentials was accelerated. The maximum rate of depolarization and its reactivation time constant were not affected by 60 min of hypoxia. It is suggested that intracellular free Ca is important in the control of action potential duration via the outward background potassium current.

Epac activator critically regulates action potential duration by decreasing potassium current in rat adult ventricle

2013 ◽  
Vol 57 ◽  
pp. 96-105 ◽  
Author(s):  
Fabien Brette ◽  
Erick Blandin ◽  
Christophe Simard ◽  
Romain Guinamard ◽  
Laurent Sallé
Keyword(s):  
Action Potential ◽  
Action Potential Duration ◽  
Potassium Current

Action potential duration in ventricular muscle during selective metabolic block

1987 ◽  
Vol 253 (2) ◽  
pp. H373-H379 ◽  
Author(s):  
H. Hayashi ◽  
T. Watanabe ◽  
T. F. McDonald
Keyword(s):  
Action Potential ◽  
Action Potential Duration ◽  
Calcium Current ◽  
Potassium Current ◽  
Glucose Solution ◽  
Cardiac Action Potential ◽  
Atp Content ◽  
Cardiac Action ◽  
Metabolic Block ◽  
Action Potential Shortening

We have examined whether maintenance of the cardiac action potential duration depends exclusively on energy from glycolysis. Oxidative phosphorylation in guinea pig papillary muscles was inhibited by superfusion with hypoxic solutions. After 60 min in 50 mM glucose solution, the action potential duration was 85% of aerobic control, but ATP content was only 25%; after 60 min in 0 mM glucose, both the duration and ATP content had declined to 15% control. When the glucose concentration of hypoxic solution was raised from 0 to 50 mM, there was nearly full recovery of the action potential duration but ATP only increased to about 25% control. We attribute action potential shortening during metabolic inhibition to suppression of calcium current and activation of potassium current; the latter are graded in intensity and expressed only at low ATP. When normoxic muscle was treated with 20 mM 2-deoxy-D-glucose (2-DG) to inhibit glycolysis, there was an early transient shortening of the action potential. This was attributed to ATP consumption related to early rapid 2-DG influx and phosphorylation. After the transient, the action potential duration was maintained for several hours in oxygenated 2-DG solution. The duration was also maintained in oxygenated muscle depleted of glycolytic substrate. Thus we found no evidence of an exclusive relation between action potential duration and glycolysis.

Intravenous Anesthetic Propofol Inhibits Multiple Human Cardiac Potassium Channels

2015 ◽  
Vol 122 (3) ◽  
pp. 571-584 ◽  
Author(s):  
Lei Yang ◽  
Hui Liu ◽  
Hai-Ying Sun ◽  
Gui-Rong Li
Keyword(s):  
Potassium Channels ◽  
Action Potential ◽  
Action Potential Duration ◽  
Potassium Current ◽  
Open Channels ◽  
Atrial Myocytes ◽  
Hek 293 ◽  
Human Atrial Myocytes ◽  
Hek 293 Cells ◽  
293 Cells

Abstract Background: Propofol is widely used clinically for the induction and maintenance of anesthesia. Clinical case reports have shown that propofol has an antiatrial tachycardia/fibrillation effect; however, the related ionic mechanisms are not fully understood. The current study investigates the effects of propofol on human cardiac potassium channels. Methods: The whole cell patch voltage clamp technique was used to record transient outward potassium current (Ito) and ultrarapidly activating delayed rectifier potassium current (IKur) in human atrial myocytes and hKv1.5, human ether-à-go-go-related gene (hERG), and hKCNQ1/hKCNE1 channels stably expressed in HEK 293 cells. Current clamp mode was used to record action potentials in human atrial myocytes. Results: In human atrial myocytes, propofol inhibited Ito in a concentration-dependent manner (IC50 = 33.5 ± 2.0 μM for peak current, n = 6) by blocking open channels without affecting the voltage-dependent kinetics or the recovery time constant; propofol decreased IKur (IC50 = 35.3 ± 1.9 μM, n = 6) in human atrial myocytes and inhibited hKv1.5 current expressed in HEK 293 cells by preferentially binding to the open channels. Action potential duration at 90% repolarization was slightly prolonged by 30 μM propofol in human atrial myocytes. In addition, propofol also suppressed hERG and hKCNQ1/hKCNE1 channels expressed in HEK 293 cells. Conclusion: Propofol inhibits multiple human cardiac potassium channels, including human atrial Ito and IKur, as well as hKv1.5, hERG, and hKCNQ1/hKCNE1 channels stably expressed in HEK 293 cells, and slightly prolongs human atrial action potential duration, which may contribute to the antiatrial tachycardia/fibrillation effects observed in patients who receive propofol.

Sign in / Sign up

Export Citation Format

Share Document