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Am J Physiol Heart Circ Physiol 283: H372-H381, 2002; doi:10.1152/ajpheart.01091.2001
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Vol. 283, Issue 1, H372-H381, July 2002

Correlation of repolarization of ventricular monophasic action potential with ECG in the murine heart

Stephan Danik1, Candido Cabo2,3, Christine Chiello2, Sacha Kang2, Andrew L. Wit2,3, and James Coromilas1

Departments of 1 Medicine, and 2 Pharmacology, and 3 The Center for Molecular Therapeutics, College of Physicians and Surgeons of Columbia University, New York, New York 10032

Transgenic mice have become important experimental models in the investigation of mechanisms causing cardiac arrhythmias because of the ability to create strains with alterations in repolarizing membrane currents. It is important to relate alterations in membrane currents in cells to their phenotypic expression on the electrocardiogram (ECG). The murine ECG, however, has unusual characteristics that make interpretation of the phenotypic expression of changes in ventricular repolarization uncertain. The major deflection representing the QRS (referred to as "a") is often followed by a secondary slower deflection ("b") and sometimes a subtle third deflection ("c"). To determine whether the second or third deflections or both represent ventricular repolarization, we recorded the ventricular monophasic action potential (MAP) in open-chest mice and correlated repolarization with the ECG. There was no significant correlation by linear regression, between action potential duration to 50% or 90% repolarization (APD50 or APD90), respectively, of the MAP and either the interval from onset of Q to onset of b (Qb interval) or onset of c (Qc interval). Administration of 4-aminopyridine (4-AP) significantly prolonged APD50 and APD90 and the Qb interval, indicating that this deflection on the ECG represents part of ventricular repolarization. After 4-AP, the c wave disappeared, also suggesting that it represents a component of ventricular repolarization. Although it appears that both the b and c waves that follow the Q wave on the ECG represent ventricular repolarization, neither correlates exactly with APD90 of the MAP. Therefore, an accurate measurement of complete repolarization of the murine ventricle cannot be obtained from the surface ECG.

arrhythmias


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