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Publication
Optical Mapping of Propagation Changes Induced by Elevated Extracellular
Potassium Ion Concentration in Genetically Altered Mouse Hearts
Authors
Bonnie B. Punske, Stefano Rossi, Philip Ershler, Isaac Rasmussen and E. Dale
Abel
Submitted By
E. Dale Abel on 7/25/2005
Status
Published
Journal
Journal of electrocardiology
Year
2004
Date Published
1/1/2005
Volume : Pages
37 : 128 - 134
PubMed Reference
15534822
Abstract
Diabetes is associated with high rates of cardiovascular disease and
sudden death. Therefore, dissecting specific mechanisms, such as the effects of
impaired insulin signaling on cardiac electrophysiology may lead to better
diagnosis and treatment. Lack of insulin receptors in mouse myocytes has been
shown to reduce repolarizing potassium currents and prolong action potential
duration. We hypothesized that these changes would manifest as rate-related
effects on electrical propagation in the intact heart. This study employed
optical
mapping to characterize propagation changes in intact mouse hearts with
cardiomyocyte-restricted knock out of insulin receptors (CIRKO). Methods:
Fluorescent signals emitted from excited Di-4-ANEPPS in isolated Langendorff
perfused mouse hearts were recorded from the left ventricular epicardium
using an 8 by 8 photo diode array. The study included hearts from 8 CIRKO
mice and 8 wild type (WT) littermate controls. Hearts were stimulated from the
right atrium or the left ventricle at basic cycle lengths ranging from 160 to
280
ms under normal conditions and then after 5 minutes of perfusion with
elevated potassium ion concentration (9.4 mM). Results: None of the 8 CIRKO
hearts maintained regular responses to atrial stimulation at the 160 ms cycle
length under normal conditions; however, all of the WT hearts were captured
at this rate. Total activation time for a 4 mm by 4 mm area was longer for
CIRKO hearts when compared with WT. Average epicardial conduction
velocity was slower for the CIRKO when compared to WT. Propagation delay
due to the presence of high [K]e was significant in both CIRKO and WT mice,
but significantly longer for the CIRKO hearts. Conclusions: These results show
that in addition to reducing repolarization currents, impaired myocardial
insulin signaling leads to impaired electrical impulse propagation particularly
at increased heart rates. These data suggest a link between impaired myocardial
insulin signaling and the increased risk of arrhythmia and sudden death in
patients with diabetes.
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Please acknowledge all posters, manuscripts or scientific materials that were generated in part or whole using funds from the Diabetic Complications Consortium(DiaComp) using the following text:
Financial support for this work provided by the NIDDK Diabetic Complications Consortium (RRID:SCR_001415, www.diacomp.org), grants DK076169 and DK115255
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