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November 10, 2000Circulation Research161 citations

High-Resolution Optical Mapping of the Right Bundle Branch in Connexin40 Knockout Mice Reveals Slow Conduction in the Specialized Conduction System

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HTHouman TamaddonDVDhananjay VaidyaASAlexander M. Simon

Key Result

Connexin40 knockout mice exhibited significantly slower conduction velocity in the right bundle branch compared to wild-type mice (43.7 vs 74.5 cm/s; P<0.01).

Structured PICO

P
Population
14 mice (7 wild-type and 7 Connexin40 knockout) evaluated for cardiac conduction defects.
E
Exposure
Connexin40 gene knockout
C
Comparator
Wild-type (WT) mice
O
Outcome
Conduction velocity of the right bundle branch, PR interval, and ventricular epicardial activation breakthrough timessurrogate

Connexin40 knockout mice exhibit significant conduction defects in the specialized conduction system, demonstrating the critical role of gap junctions in cardiac impulse propagation.

Main Result

Absolute Event Rate: 43.7% vs 74.5%

p-value: p=<0.01

Abstract

Connexin40 (Cx40) is a major gap junction protein that is expressed in the His-Purkinje system and thought to be a critical determinant of cell-to-cell communication and conduction of electrical impulses. Video maps of the ventricular epicardium and the proximal segment of the right bundle branch (RBB) were obtained using a high-speed CCD camera while simultaneously recording volume-conducted ECGs. In Cx40(-/-) mice, the PR interval was prolonged (47.4+/-1.4 in wild-type WT n=6 and 57.5+/-2.8 in Cx40(-/-) n=6; P<0.01). WT ventricular epicardial activation was characterized by focused breakthroughs that originated first on the right ventricle (RV) and then the left ventricle (LV). In Cx40(-/-) hearts, the RV breakthrough occurred after the LV breakthrough. Additionally, Cx40(-/-) mice showed RV breakthrough times that were significantly delayed with respect to QRS complex onset (3.7+/-0.7 ms in WT n=6 and 6.5+/-0.7 ms in Cx40(-/-) n=6; P<0.01), whereas LV breakthrough times did not change. Conduction velocity measurements from optical mapping of the RBB revealed slow conduction in Cx40(-/-) mice (74.5+/-3 cm/s in WT n=7 and 43.7+/-6 cm/s in Cx40(-/-) n=7; P<0.01). In addition, simultaneous ECG records demonstrated significant delays in Cx40(-/-) RBB activation time with respect to P time (P-RBB time; 41.6+/-1.9 ms in WT n=7 and 55.1+/-1.3 ms in n=7; P<0.01). These data represent the first direct demonstration of conduction defects in the specialized conduction system of Cx40(-/-) mice and provide new insight into the role of gap junctions in cardiac impulse propagation.

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Cite This Study

Tamaddon et al. (2000) studied Connexin40 knockout (n=14). Connexin40 knockout vs. Wild-type mice was evaluated on Conduction velocity of the right bundle branch (p=<0.01). Connexin40 knockout mice exhibited significantly slower conduction velocity in the right bundle branch compared to wild-type mice (43.7 vs 74.5 cm/s; P<0.01).

synapsesocial.com/papers/6a2090e7fdf8ac6477c64133https://doi.org/10.1161/01.res.87.10.929
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