Larger cell size in rabbits with heart failure increases myocardial conduction velocity and QRS duration.
BACKGROUND
Patients with heart failure (HF) have an increased QRS duration, usually attributed to decreased conduction velocity (CV) due to ionic remodeling but which may alternatively result from increased heart size or cellular uncoupling. We investigated the relationship between QRS width, heart size, intercellular coupling, and CV in a rabbit model of moderate HF and in computer simulations.


RESULTS
HF was induced by pressure-volume overload. Heart weight (21.1+/-0.5 versus 10.2+/-0.4 g, mean+/-SEM; P<0.01) and QRS duration (58+/-1 versus 50+/-1 ms; P<0.01) were increased in HF versus control. Longitudinal CV (thetaL; 79+/-2 versus 67+/-4 cm/s; P<0.01) and transversal subepicardial CV (thetaT; 43+/-2 versus 37+/-2 cm/s; P<0.05) were higher in HF than in controls. Transmural CV (thetaTM) was unchanged (25+/-2 versus 24+/-1 cm/s; P=NS). Patch-clamp experiments demonstrated that sodium current was unchanged in HF versus control. Immunohistochemical experiments revealed that connexin43 content was reduced in midmyocardium but unchanged in subepicardium. Myocyte dimensions were increased in HF by approximately 30%. Simulated strands of mammalian ventricular cells (Luo-Rudy dynamic model) revealed increased thetaL and thetaT with increased myocyte size; however, increased CV could not compensate for increased strand size of longitudinally coupled cells, and consequently, total activation time was longer.


CONCLUSIONS
Increased myocyte size combined with the observed expression pattern of connexin43 yields increased thetaL and thetaT and unchanged thetaTM in our nonischemic model of HF. A hypertrophied left ventricle together with insufficiently increased thetaL and unaltered thetaTM results in a prolonged QRS duration.
Wiegerinck
Rob F
RF
Department of Experimental Cardiology, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands. R.F.Wiegerinck@amc.uva.nl
Verkerk
Arie O
AO
Belterman
Charly N
CN
van Veen
Toon A B
TA
Baartscheer
Antonius
A
Opthof
Tobias
T
Wilders
Ronald
R
de Bakker
Jacques M T
JM
Coronel
Ruben
R
D000818:Animals; D006332:Cardiomegaly / Q000473:pathology / Q000503:physiopathology*; D002450:Cell Communication; D048429:Cell Size; D003198:Computer Simulation; D018031:Connexin 43 / Q000032:analysis; D004562:Electrocardiography; D006329:Heart Conduction System / Q000473:pathology / Q000503:physiopathology*; D006333:Heart Failure / Q000473:pathology* / Q000503:physiopathology; D017379:Hypertrophy, Left Ventricular; D066298:In Vitro Techniques; D032342:Muscle Cells / Q000473:pathology; D011817:Rabbits
D018031:Connexin 43