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.

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.

The Electrical Activity of the Radial Nerve in Diadema antillarum Philippi and Certain Other Echinoids

1968 ◽  
Vol 48 (2) ◽  
pp. 279-289
Author(s):  
N. MILLOTT ◽  
H. OKUMURA
Keyword(s):  
Electrical Activity ◽  
Conduction Velocity ◽  
Radial Nerve ◽  
Diadema Antillarum ◽  
Double Peak ◽  
Slow Potential ◽  
Refractory Periods ◽  
Spine Movement ◽  
Stimulation Of

1. The propagated massed potentials which follow stimulation of the radial nerve in Arbacia, Diadema, Echinus and Paracentrotus are described. 2. Approximate values for the averaged absolute and relative refractory periods and the conduction velocity were obtained. 3. The response of Diadema has a double peak which is shown to represent responses of nerves differing in excitability and conduction velocity. The fast potential is concerned with spine movement. The slow potential is related to inhibition of spine movements excited photically.

Abstract 591: Can Waveform Characteristics Predict Defibrillation to a Perfusing Rhythm in Short Versus Prolonged Ventricular Fibrillation in a Swine Model?

Circulation ◽  
2008 ◽  
Vol 118 (suppl_18) ◽  
Author(s):  
Julia H Indik ◽  
Mathias Zuercher ◽  
Karl B Kern ◽  
Ronald W Hilwig ◽  
Robert A Berg
Keyword(s):  
Logistic Regression ◽  
Ventricular Fibrillation ◽  
Short Duration ◽  
Important Determinant ◽  
Swine Model ◽  
Median Frequency ◽  
Chest Compressions ◽  
Long Duration ◽  
Spectral Area ◽  
Minute Duration

It is known that defibrillation of ventricular fibrillation (VF) to a perfusing rhythm (ROSC) is more likely to occur in VF of short duration. It is unknown whether ROSC can be predicted by waveform characteristics in VF of short compared to long duration, apart from a consideration of time alone. VF was untreated for 2 minutes (N=10) or 8 minutes (N=10) in normal swine, after which a defibrillation shock was applied. Chest compressions for two minutes were allowed following but not prior to the shock to achieve a perfusing rhythm (ROSC). VF was analyzed from needle electrodes prior to the shock for amplitude spectral area (AMSA), slope, median frequency and bandwidth. Predictors of ROSC were determined by logistic regression. In VF of 2 minute duration 7 out of 10 swine achieved ROSC compared to 2 out 10 swine with VF of 8 minutes (P=0.025) and time was a significant predictor of ROSC (P=0.033). AMSA was significantly higher at 2 minutes (75 ± 18 mV-Hz) compared to 8 minutes (56±11 mV-Hz, p=0.007) as was slope (3.5±1 vs 2.6±0.5 mV/s, p=0.015). Bandwidth was slightly increased from 2.2±0.6 Hz at 2 minutes to 2.8±0.8 Hz at 8 minutes,(p=0.048), while median frequency was similar. However, no waveform characteristic was a significant predictor of ROSC, with substantial overlap in distributions between animals with and without ROSC. Duration of VF is an important determinant of the likelihood of achieving ROSC with defibrillation. Particularly in VF of short duration, VF waveform characteristics do not add to the predictability of achieving ROSC even though they may demonstrate a significant time evolution.

Abstract 1087: Effects of Oral Gap Junction Conduction-Enhancing Antiarrhythmic Peptide GAP-134 on Experimental Atrial Fibrillation in Dogs

Circulation ◽  
2007 ◽  
Vol 116 (suppl_16) ◽  
Author(s):  
Gabriel Laurent ◽  
Howard Leong-Poi ◽  
Gordon Moe ◽  
Xudong Hu ◽  
Petsy Pui-Sze So ◽  
...  
Keyword(s):  
Atrial Fibrillation ◽  
Gap Junction ◽  
Electrophysiological Study ◽  
Placebo Treatment ◽  
Refractory Periods ◽  
Percent Change ◽  
Dog Model ◽  
Antiarrhythmic Peptide ◽  
The Mean ◽  
Mechanical Remodeling

Background: Abnormal intercellular communication caused by connexin dysfunction may promote atrial fibrillation (AF). Objective: To assess the effect of the gap junction conduction-enhancing antiarrhythmic peptide GAP-134 on AF inducibility and maintenance in a new dog model of atrial cardiomyopathy. Methods and Results: Twenty four dogs underwent simultaneous atrioventricular pacing (2 weeks at 220 bpm, atrioventricular delay 0 ms), and were randomly assigned to placebo treatment (PACED-PLACEBO; 12 dogs) or oral GAP-134 (PACED-GAP 134; 12 dogs) (starting at day 0). Percent change in left atrial systolic area (Δ% LASA) from baseline to 2 weeks was calculated using trans-esophageal echocardiography. At 2 weeks, animals underwent an open chest electrophysiological study; conduction velocity (CV) when pacing at 150ms cycle length (CL), effective refractory periods (ERP) and AF vulnerability were measured. The mean plasma concentration of GAP-134 was 557 ± 239 nmol/L. GAP-134 increased CV (395.1 ± 63.2 vs 307.8 ± 54.6 mm/s, p<0.01), and shortened ERP at 200ms CL (104.0 ± 8.6 vs 112.8 ± 11.5 ms, P<0.05). GAP-134 significantly reduced AF inducibility [% burst attempts inducing AF] and maintenance [mean AF duration, number of episodes >10min] in dogs with less than 100% ΔLASA (n=5). In dogs with more structural remodeling (ΔLASA ≥100%, n=7), CV increased but AF inducibility was unaffected. Conclusions: Oral GAP-134 prevents CV slowing in a dog model of atrial cardiomyopathy, but attenuates AF inducibility and maintenance only in dogs with less mechanical remodeling.

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.

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