Journal article
Optical mapping of propagation changes induced by elevated extracellular potassium ion concentration in genetically altered mouse hearts
Journal of electrocardiology, Vol.37, pp.128-134
2004
DOI: 10.1016/j.jelectrocard.2004.08.037
PMID: 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.
Details
- Title: Subtitle
- Optical mapping of propagation changes induced by elevated extracellular potassium ion concentration in genetically altered mouse hearts
- Creators
- Bonnie B Punske - Nora Eccles Harrison Cardiovascular Research and Training Institute, The University of Utah, Salt Lake City, UT, ItalyStefano Rossi - Department of Evolutionary and Functional Biology, University of Parma, ItalyPhilip Ershler - Nora Eccles Harrison Cardiovascular Research and Training Institute, The University of Utah, Salt Lake City, UT, ItalyIsaac Rasmussen - Division of Endocrinology, Metabolism, and Diabetes, The University of Utah, Salt Lake City, UT, ItalyE Dale Abel - Division of Endocrinology, Metabolism, and Diabetes, The University of Utah, Salt Lake City, UT, Italy
- Resource Type
- Journal article
- Publication Details
- Journal of electrocardiology, Vol.37, pp.128-134
- Publisher
- Elsevier Inc
- DOI
- 10.1016/j.jelectrocard.2004.08.037
- PMID
- 15534822
- ISSN
- 0022-0736
- eISSN
- 1532-8430
- Language
- English
- Date published
- 2004
- Academic Unit
- Roy J. Carver Department of Biomedical Engineering; Fraternal Order of Eagles Diabetes Research Center; Biochemistry and Molecular Biology; Endocrinology and Metabolism; Internal Medicine
- Record Identifier
- 9984024506202771
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