Abstract 14754: Role Of The Cardiac Conduction System In Pathophysiology Of Congestive Heart Failure
A proportion of heart failure patients die of bradyarrhythmias, presumably from dysfunction of the cardiac conduction system. Here we studied the cardiac conduction system in rabbits with congestive heart failure (CHF) induced by left ventricular (LV) volume and pressure overload over 8 weeks. At this time there was significant LV hypertrophy, diminished LV fractional shortening and increased LV internal dimension. High-fidelity ECG recording after autonomic blockade showed that the intrinsic heart rate was lower in the CHF group. The RR interval was inversely related to fractional shortening and was slower in sicker hearts (R2=0.680; P<0.05) - this is evidence of dysfunction of the sinoatrial node in the CHF group. In the CHF group, there were significant increases in the PR interval (by 22%; P=0.001) and QRS duration (by 26%; P=0.02) and this is evidence of dysfunction of the atrioventricular node and His-Purkinje system. Expression of ion channels and related proteins at the mRNA level, measured by quantitative PCR, was markedly affected: mRNA for 48%, 80% and 33% of 33 ion channels etc. studied was significantly decreased in the sinoatrial node, left Purkinje fibres and right Purkinje fibres, respectively, during CHF. Ion channel expression in the working myocardium, however, was less affected. Significant alterations in mRNA expression in the LV muscle, right ventricular muscle and right atrial muscle occurred in only 21%, 3% and 6%, respectively, of the ion channels studied. For example, in the sinoatrial node, there were marked reductions in the expression of funny channels (HCN1 and HCN4 by 36 and 87%), Ca2+ channels (Cav1.2 and Cav1.3 by 51% and 56%) and K+ channels (Kv1.5, Kir2.1, Kir2.2, ERG and KvLQT1 by 50-86%). In addition, there were significant reductions in Ca2+-handling proteins in the sinoatrial node (NCX1, RYR3 and SERCA2 by 46-67%). These changes are likely to cause a slowing of the intrinsic pacemaker activity of the sinoatrial node. In conclusion, our study shows widespread remodelling of ion channels in the cardiac conduction system in CHF, which may contribute to bradyarrhythmic death in heart failure patients.
- © 2011 by American Heart Association, Inc.