Enhanced heterogeneity of myocardial conduction and severe cardiac electrical instability in annexin A7-deficient mice

Objectives: Annexin A7 is involved in cardiomyocyte membrane organization and Ca 2+ -dependent signalling processes. We investigated theimpact of annexin A7 on cardiac electrophysiological properties using an annexin A7-deficient mouse strain (annexin A7 −/ ).Methods: Nineteen adult annexin A7 −/ and 14 wild-type mice were examined electrophysiologically in vivo by transvenous catheterization.Hearts were additionally perfused by the Langendorff method and epicardial activation mapping was performed.Results: The susceptibility to induction of atrial fibrillation was elevated in annexin A7 −/− mice. Ten deficient animals showed atrialfibrillation (AF) episodes ≥1 min and sustained AF ≥30 min was observed in 4 annexin A7 −/ mice, but in none of the wild-type mice. Theincidence of ventricular tachycardia (VT) was higher in annexin A7 −/ mice and VT duration was prolonged. Epicardial mapping showedelevated anisotropy and inhomogeneity of conduction, leading to conduction blocks in the deficient mice. Besides alterations of intracellularcalcium homeostasis, electron microscopy showed a homogeneous, electron-dense material that filled the myocardial intercellularcompartments and accumulated at the basement membranes. This led to expansion of the extracellular spaces, which was the most probablesubstrate factor responsible for the disturbances of electrical communication.Conclusions: Annexin A7 deficiency causes severe electrical instability in the murine heart, including conduction disturbances andanisotropy of impulse propagation, which is accompanied by disturbed calcium handling and intercellular deposits.© 2007 European Society of Cardiology. Published by Elsevier B.V. All rights reserved.