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Cardiovascular Research Advance Access [Accepted Manuscript] published online on November 9, 2007
Cardiovascular Research, doi:10.1093/cvr/cvm060
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Spatial heterogeneity of myocardial perfusion predicts local potassium channel expression and action potential duration

Marion Stoll, PhD, Michael Quentin, Andrej Molojavyi, MD, Volker Thämer, MD and Ulrich K.M. Decking, MD

Dept. of Cardiovascular Physiology, Heinrich-Heine-University, Düsseldorf, Germany

Correspondence to: Ulrich Decking, M.D., Dept. of Cardiovascular Physiology, Heinrich-Heine-University Düsseldorf, Universitätsstr. 1, Building 22.03, 40225 Düsseldorf, Germany. Fax: +49.211.81.12672, Phone: +49.211.81.12651, E-mail: decking{at}uni-duesseldorf.de

Aims: In the heart, there is not only a transmural gradient of left ventricular perfusion and action potential duration (APD), but also spatial heterogeneity within each myocardial layer, where local blood flow and energy turnover vary more than 3-fold between individual regions. We analyzed at high spatial resolution whether a corresponding heterogeneity also extends to ion channel gene expression and APD.

Methods: In the open-chest beagle dog, left ventricular 300 µl samples of very low or high flow were identified by radioactive microspheres and expression levels determined by quantitative PCR. The distribution of epicardial APD was assessed by mapping local activation repolarisation intervals (ARI) and QT.

Results: ERG, the potassium channel mediating IKr, and KChIP2, the interacting protein modulating Ito, were increased in Low flow (3.3- resp. 2.5-fold, p < 0.001 resp. <0.05; n = 6 hearts, 30-31 samples each) as compared to High flow areas. This suggested enhanced repolarizing currents in Low flow areas, and in consequence, mathematical model analysis predicted a shorter local APD upon enhanced ERG and IKr. Epicardial mapping revealed a patchy, temporally stable APD pattern (n = 11), a small apico-basal gradient and an APD prolongation induced by the ERG blocker dofetilide predominantly in areas of short basal ARI or QT resp. (n = 9). In addition, in Short QT areas, ERG expression was 3-fold increased (p < 0.05, n = 4).

Conclusion: The spatial pattern of perfusion is matched by the novel patterns of K+ channel expression and APD. Whenever this newly recognized intramural dispersion of APD increases, it may contribute to arrhythmogenesis.

KEYWORDS ion channels; blood flow; mapping; microspheres

Time for primary review: 26


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