Gap junction modifier rotigaptide decreases the susceptibility to ventricular arrhythmia by enhancing conduction velocity and suppressing discordant alternans during therapeutic hypothermia in isolated rabbit hearts

Heart Rhythm ◽  
2016 ◽  
Vol 13 (1) ◽  
pp. 251-261 ◽  
Author(s):  
Yu-Cheng Hsieh ◽  
Jiunn-Cherng Lin ◽  
Chen-Ying Hung ◽  
Cheng-Hung Li ◽  
Shien-Fong Lin ◽  
...  
Keyword(s):  
Ventricular Arrhythmia ◽  
Gap Junction ◽  
Therapeutic Hypothermia ◽  
Conduction Velocity

Distribution, propagation, and coordination of contractile activity in lymphatics

1993 ◽  
Vol 264 (4) ◽  
pp. H1283-H1291 ◽  
Author(s):  
D. C. Zawieja ◽  
K. L. Davis ◽  
R. Schuster ◽  
W. M. Hinds ◽  
H. J. Granger
Keyword(s):  
Gap Junction ◽  
Conduction Velocity ◽  
Contractile Activity ◽  
Lymph Flow ◽  
Rat Small Intestine ◽  
Gap Junctional Communication ◽  
Junctional Communication ◽  
Gap Junctional ◽  
Flow Stream

The propagation and coordination of lymphatic contractions were studied in the mesentery of the rat small intestine using in situ microscopic observation. Indexes of lymphatic diameter were simultaneously measured at two adjacent lymphangions in spontaneously contracting lymphatics (n = 51). Diameter index, contraction frequency, and the percentage of the intersegmental contractions that were propagated and coordinated (PP) were determined at both sites. The conduction velocity of the contractile activity and the percentage of the coordinated contractions that were propagated both antegrade to the direction of lymph flow and retrograde to the flow stream were determined. The results indicate that 1) 80-90% of the lymphatic contractions in the vessels we evaluated were propagated, 2) the wave of contractile activity propagated both centrally and peripherally, and 3) the conduction velocity of the contractile activity was approximately 4-8 mm/s. We tested the hypothesis that gap junctional communication is responsible for the coordination of the contractile event. To accomplish this, we used the gap junction blockers n-heptanol and oleic acid. PP was 90 +/- 4% under normal conditions and fell to a minimum value of 55 +/- 7% during the gap junction blockade. These results indicate that gap junctional communication played an important role in the propagation and coordination of contractions that occurred in spontaneously active lymphatics.

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

Label-free conduction velocity mapping and gap junction assessment of functional iPSC-Cardiomyocyte monolayers

2020 ◽  
Vol 167 ◽  
pp. 112468 ◽  
Author(s):  
Wenkun Dou ◽  
Qili Zhao ◽  
Manpreet Malhi ◽  
Xingjian Liu ◽  
Zhuoran Zhang ◽  
...  
Keyword(s):  
Gap Junction ◽  
Conduction Velocity ◽  
Label Free ◽  
Velocity Mapping

scholarly journals Interstitial volume modulates the conduction velocity-gap junction relationship

2012 ◽  
Vol 302 (1) ◽  
pp. H278-H286 ◽  
Author(s):  
Rengasayee Veeraraghavan ◽  
Mohamed E. Salama ◽  
Steven Poelzing
Keyword(s):  
Guinea Pig ◽  
Gap Junction ◽  
Conduction Velocity ◽  
Important Determinant ◽  
Cardiac Conduction ◽  
Cell Width ◽  
Interstitial Volume ◽  
Ventricular Tachycardias ◽  
The Relationship ◽  
Isolated Cell

Cardiac conduction through gap junctions is an important determinant of arrhythmia susceptibility. Yet, the relationship between degrees of Gj uncoupling and conduction velocity (θ) remains controversial. Conflicting results in similar experiments are normally attributed to experimental differences. We hypothesized that interstitial volume modulates conduction velocity and its dependence on Gj. Interstitial volume (VIS) was quantified histologically from guinea pig right ventricle. Optical mapping was used to quantify conduction velocity and anisotropy (ARθ). Albumin (4 g/l) decreased histologically assessed VIS, increased transverse θ by 71 ± 10%, and lowered ARθ. Furthermore, albumin did not change isolated cell size. Conversely, mannitol increased VIS, decreased transverse θ by 24 ± 4%, and increased ARθ. Mannitol also decreased cell width by 12%. Furthermore, mannitol was associated with spontaneous ventricular tachycardias in three of eight animals relative to zero of 15 during control. The θ-Gj relationship was assessed using the Gj uncoupler carbenoxolone (CBX). Whereas 13 μM CBX did not significantly affect θ during control, it slowed transverse θ by 38 ± 9% during mannitol (edema). These data suggest changes in VIS modulate θ, ARθ, and the θ-Gj relationship and thereby alter arrhythmia susceptibility. Therefore, VIS may underlie arrhythmia susceptibility, particularly in diseases associated with gap junction remodeling.

scholarly journals Gap junction heterogeneity as mechanism for electrophysiologically distinct properties across the ventricular wall

2010 ◽  
Vol 298 (3) ◽  
pp. H787-H794 ◽  
Author(s):  
Maria Strom ◽  
Xiaoping Wan ◽  
Steven Poelzing ◽  
Eckhard Ficker ◽  
David S. Rosenbaum
Keyword(s):  
Left Ventricle ◽  
Gap Junction ◽  
Conduction Velocity ◽  
Velocity Dispersion ◽  
Expression Patterns ◽  
Fold Increase ◽  
Ventricular Wall ◽  
Cx43 Expression ◽  
Electrophysiological Properties ◽  
Junction Protein

Gap junctions are critical to maintaining synchronized impulse propagation and repolarization. Heterogeneous expression of the principal ventricular gap junction protein connexin43 (Cx43) is associated with action potential duration (APD) dispersion across the anterior ventricular wall. Little is known about Cx43 expression patterns and their disparate impact on regional electrophysiology throughout the heart. We aimed to determine whether the anterior and posterior regions of the heart are electrophysiologically distinct. Multisegment, high-resolution optical mapping was performed in canine wedge preparations harvested separately from the anterior left ventricle (aLV; n = 8) and posterior left ventricle (pLV; n = 8). Transmural APD dispersion was significantly greater on the aLV than the pLV (45 ± 13 vs. 26 ± 8.0 ms; P < 0.05). Conduction velocity dispersion was also significantly higher ( P < 0.05) across the aLV (39 ± 7%) than the pLV (16 ± 3%). Carbenoxolone perfusion significantly enhanced APD and conduction velocity dispersion on the aLV (by 1.53-fold and 1.36-fold, respectively), but not the pLV (by 1.27-fold and 1.2-fold, respectively), and produced a 4.2-fold increase in susceptibility to inducible arrhythmias in the aLV. Confocal immunofluorescence microscopy revealed significantly ( P < 0.05) greater transmural dispersion of Cx43 expression on the aLV (44 ± 10%) compared with the pLV wall (8.3 ± 0.7%), suggesting that regional expression of Cx43 expression patterns may account for regional electrophysiological differences. Computer simulations affirmed that localized uncoupling at the epicardial-midmyocardial interface is sufficient to produce APD gradients observed on the aLV. These data demonstrate that the aLV and pLV differ importantly with respect to their electrophysiological properties and Cx43 expression patterns. Furthermore, local underexpression of Cx43 is closely associated with transmural electrophysiological heterogeneity on the aLV. Therefore, regional and transmural heterogeneous Cx43 expression patterns may be an important mechanism underlying arrhythmia susceptibility, particularly in disease states where gap junction expression is altered.

scholarly journals Enhancement of Gap Junction Function During Acute Myocardial Infarction Modifies Healing and Reduces Late Ventricular Arrhythmia Susceptibility

2016 ◽  
Vol 2 (5) ◽  
pp. 574-582 ◽  
Author(s):  
Fu Siong Ng ◽  
Jeremy M. Kalindjian ◽  
Simon A. Cooper ◽  
Rasheda A. Chowdhury ◽  
Pravina M. Patel ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Acute Myocardial Infarction ◽  
Ventricular Arrhythmia ◽  
Gap Junction

Regional gap junction inhibition increases defibrillation thresholds

2003 ◽  
Vol 285 (1) ◽  
pp. H10-H16 ◽  
Author(s):  
J. Jason Sims ◽  
Kell L. Schoff ◽  
Jennifer M. Loeb ◽  
Nicholas A. Wiegert
Keyword(s):  
Ventricular Fibrillation ◽  
Gap Junction ◽  
Conduction Velocity ◽  
Velocity Dispersion ◽  
Important Determinant ◽  
Refractory Periods ◽  
Regional Gap ◽  
Junction Conductance ◽  
Regional Infusion ◽  
Gap Junction Inhibition

It is clear that ischemia inhibits successful defibrillation by altering regional electro-physiology. However, the exact mechanisms are unclear. This study investigated whether regional gap junction inhibition increases biphasic shock defibrillation thresholds (DFT). Sixteen swine were instrumented with a mid-left anterior descending (LAD) perfusion catheter for regional infusion of 0.5 mM/h heptanol ( n = 8) or saline ( n = 8). DFT values and effective refractory periods (ERP) at five myocardial sites were determined. Regional conduction velocity (CV) was determined in an LAD drug-perfused and nondrug-perfused region in an additional seven swine. Regional heptanol infusion increased 50% DFT values by 33% ( P = 0.01) and slowed CV by 42–59% ( P < 0.01) but did not affect ERP. Regional heptanol also increased CV dispersion by ∼270% ( P < 0.05) but did not change ERP dispersion. Regional placebo did not alter any of these parameters. Furthermore, regional heptanol infusion induced spontaneous ventricular fibrillation in eight of eight animals. Increasing spatial conduction velocity dispersion by impairing regional gap junction conductance increased DFT values. Dispersion in conduction velocity slowing during regional ischemia may be an important determinant of defibrillation efficacy.

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