Correlation of repolarization of ventricular monophasic action potential with ECG in the murine heart.
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 (APD(50) or APD(90)), 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 APD(50) and APD(90) 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 APD(90) of the MAP. Therefore, an accurate measurement of complete repolarization of the murine ventricle cannot be obtained from the surface ECG.
Danik
Stephan
S
Department of Medicine, College of Physicians and Surgeons of Columbia University, New York, New York 10032, USA.
Cabo
Candido
C
Chiello
Christine
C
Kang
Sacha
S
Wit
Andrew L
AL
Coromilas
James
J
D000200:Action Potentials / Q000502:physiology*; D000818:Animals; D004562:Electrocardiography / Q000379:methods; D004566:Electrodes; D022062:Electrophysiologic Techniques, Cardiac; D006339:Heart Rate / Q000502:physiology; D016014:Linear Models; D051379:Mice; D016276:Ventricular Function