Optical mapping reveals conduction slowing and impulse block in iron-overload cardiomyopathy.
Cardiac disease with arrhythmia or heart failure is the leading cause of death in patients with thalassemia major and a major complication of other forms of iron overload. Current antiarrhythmic treatment does not appear to alter the clinical course. Using a gerbil model of iron-overload cardiomyopathy, we previously observed a reduction in the fast inward sodium current in isolated cardiomyocytes. Electrocardiograms (ECGs) in the same gerbil model indicate PR-interval prolongation, QRS-interval widening, and arrhythmias. We hypothesize that such changes in the ECG in this model are the result of abnormal action-potential conduction at the level of the whole heart. To test this hypothesis, we took ECGs and recorded action potentials using high-resolution optical mapping from the anterior surface of 9 iron-overloaded and 9 age-matched control ventricular-paced, Langendorff-perfused gerbil hearts. The iron-overloaded gerbils received weekly iron-dextran injections of 800 mg/kg for 14 to 18 weeks. ECGs showed QRS- and PR-interval prolongation in iron-treated gerbils compared with that in controls. In addition, atrioventricular block was observed in 2 of 6 iron-treated gerbils but not in controls. Conduction velocity was significantly slower in iron-treated gerbils than in controls. At normal pacing rates, abnormal activation patterns caused by stable regions of conduction block were observed in iron-overloaded gerbils (33%) but not in controls. Such abnormal impulse conduction may be a mechanism of increased arrhythmia vulnerability in iron-overload cardiomyopathy.
Laurita
Kenneth R
KR
Heart and Vascular Research Center and Center for cell signaling MetroHealth Campus, Case Western Reserve university, Cleveland, OH 44109-1998, USA. klaurita@metrohelath.org
Chuck
Emil Thomas
ET
Yang
Tianen
T
Dong
Wei-Qiang
WQ
Kuryshev
Yuri A
YA
Brittenham
Gary M
GM
Rosenbaum
David S
DS
Brown
Arthur M
AM
D000200:Action Potentials; D000818:Animals; D009202:Cardiomyopathies / Q000209:etiology / Q000503:physiopathology*; D004562:Electrocardiography; D005260:Female; D005849:Gerbillinae; D006329:Heart Conduction System / Q000503:physiopathology*; D019190:Iron Overload / Q000150:complications / Q000503:physiopathology*; D055095:Optics and Photonics