Combined effects of reduced connexin 43, depressed active generator properties and energetic stress on conduction disturbances in canine failing myocardium.
To show that reductions in connexin43 (Cx43) can contribute, in association with electrophysiological alterations identified from unipolar recordings, to conduction disturbances in a realistic model of heart failure, canines were subjected to chronic rapid pacing (240/min for 4 weeks) and progressive occlusion of the left coronary circumflex artery (LCx) by an ameroid constrictor. Alterations identified from 191 epicardial recordings included abrupt activation delay, functional block, ST segment potential elevation, and reduced maximum negative slope (-dV/dt (max)). The LCx territory was divided into apical areas with depressed conduction velocity (LCx1: 0.06 +/- 0.04 m/s, mean +/- SD) and basal areas with relatively preserved conduction (LCx2: 0.28 +/- 0.01 m/s). Subepicardial Cx43 immunoblot measurements (percent of corresponding healthy heart measurements) were reduced in LCx1 ( approximately 40%) and LCx2 ( approximately 60%). In addition, -dV/dt (max) was significantly depressed (-3.8 +/- 3.3 mV/ms) and ST segment potential elevated (23.3 +/- 14.6 mV) in LCx1 compared to LCx2 (-9.5 +/- 3.4 mV/ms and 0.3 +/- 1.4 mV). Anisotropic conduction, Cx43 and ST segment potential measurements from the left anterior descending coronary artery territory, and interstitial collagen from all regions were similar to the healthy. Thus, moderate Cx43 reduction to "clinically relevant" levels can, in conjunction with regional energetic stress and depression of sarcolemmal active generator properties, provide a substrate for conduction disturbances.
Falcao
Stéphanie
S
Centre de recherche, Hôpital du Sacré-Coeur de Montréal, 5400 Gouin Blvd. West, Montréal, H4J 1C5, Québec, Canada.
Rousseau
Guy
G
Baroudi
Ghayath
G
Vermeulen
Michel
M
Bouchard
Caroline
C
Jones
Douglas L
DL
Cardinal
René
R
D000818:Animals; D001145:Arrhythmias, Cardiac / Q000503:physiopathology; D015153:Blotting, Western; D002304:Cardiac Pacing, Artificial; D018031:Connexin 43 / Q000037:antagonists & inhibitors / Q000502:physiology*; D003331:Coronary Vessels / Q000502:physiology; D003627:Data Interpretation, Statistical; D004285:Dogs; D004562:Electrocardiography; D004594:Electrophysiology; D004734:Energy Metabolism / Q000502:physiology*; D045604:Extracellular Fluid / Q000378:metabolism; D005260:Female; D006329:Heart Conduction System / Q000503:physiopathology*; D006333:Heart Failure / Q000503:physiopathology*; D066298:In Vitro Techniques; D008297:Male
D018031:Connexin 43