What is a monophasic action potential?

See article by Kondo et al.[6](pages 635–644) in this issue.

One approach to developing better pharmacologic therapy for arrhythmias is to define the electrophysiologic mechanism for clinical rhythm disturbances. However, this approach is problematic, because extracellular electrograms do not provide precise information regarding the dispersion of repolarization or after-depolarizations. Floating microelectrodes have limitations in an experimental laboratory and are not widely applicable clinically. Thus, the ability to record monophasic action potentials (MAPs) using contact catheter electrodes in both experimental and clinical situations has raised the hope that cellular properties that are important in arrhythmogenesis can be identified reliably [1,2]. Indeed, several studies have suggested that the mechanism of clinical arrhythmias, such as right ventricular outflow tract tachycardia, can be determined based on monophasic action potential recordings [3,4]. However, there have been some basic questions regarding the mechanism of generation of MAPs that have not been resolved, and this has hampered the ability to fully interpret MAP recordings. The initial description of MAP was based on an in vivo contact electrode catheter, in which a recording is made between a distal tip that inactivates myocardium due to pressure and an indifferent electrode located several milliliters proximally on the catheter. Nesterenko and Antzelevitch [5] have developed an alternative technique for monophasic action potential recording. Using this technique, potassium is injected to inactivate myocardium and used to create the tissue damage that leads to the recording of the monophasic action potential. Although never explicitly claimed by Antzelevitch, it had been assumed that recordings using this potassium injection catheter provided similar information to classic contact monophasic action potential recordings.

A second area that needs further investigation is even more fundamental. Two hypotheses have been advanced to explain the generation of monophasic action potential recordings. One hypothesis suggests that MAPs record local electrical activity flowing from the active to inactive regions near the tip of the inactivating electrode. An alternative hypothesis suggests that the monophasic action potential “indifferent electrode” actually records active myocardial tissue from a wide field-of-view.

In a series of elegant experiments performed in Dr. Antzelevitch's laboratory, Kondo et al. [6] examined the mechanism of generation of monophasic action potential using both contact catheters and potassium injection. Because of the difference in the design of the two types of monophasic action potential recordings, a separate series of experiments was conducted to determine (A) where the electrical activity that creates the MAP originates from and (B) the ability of the MAP to record differences in action potential durations and after-depolarizations. The experiments have resolved many of the questions regarding recording MAPs. The authors conclusively show that MAP recordings change when myocardial activation near the “indifferent” electrode is altered, rather than when the action potential is altered at the inactivating electrode. In addition, the authors demonstrate that the contact catheter MAP electrode has a wide field-of-view, and that dispersion of depolarization can produce after-depolarization-like deflections on the contact MAP. There are some experiments that could have provided additional information. For example, varying location of the “indifferent electrode” on the contact catheter in a horizontal rather than vertical direction and producing true after-depolarizations in vitro could have clarified some additional issues. However, the results overall are quite convincing and support the authors' hypothesis that activation near the “indifferent electrode” generates the monophasic action potential, and that interpreting contact electrode monophasic action potential is fraught with danger. It should also be noted that the authors did not study after-depolarization, and thus do not claim that triggered activity cannot be detected on MAP recordings, only that other phenomena can simulate after-depolarizations.

What are the implications of Kondo et al.'s study? Based on their results, it would seem that the terminology referring to MAP's recording needs to be drastically reworked. Currently, the MAP paradox leads to statements such as those made by Kondo: “It is not the contact or MAP electrode that records the MAP but rather the indifferent electrode.” It would seem that a better way to refer to the electrodes is an “inactivating electrode” and an “active electrode.” This more simplistic terminology would allow better interpretation of the results. Secondly, the crucial feature in interpreting results of monophasic action potential seems not to be the type of inactivating electrode but rather the orientation of the “active” electrode relative to the myocardium. When this electrode is displaced from the myocardium, a wide field-of-view and potential inaccuracies in MAP recordings appear. However, the implications of Kondo's study are more than semantic. They strongly suggest that monophasic action potential recording electrodes that are based on the contact principle should be used only to estimate action potential duration in situations where APD is relatively uniform [7] and not to conclusively study after-depolarizations or local dispersion of repolarization. It may even be that activation recovery times, recorded from unipolar electrograms, will prove to be more accurate than any MAPs. In addition, Kondo et al. state that there is no way to “improve” on the contact MAP electrode to allow more accurate recordings. It is not immediately obvious that this is the case. Indeed, because it appears that it is the geometric orientation of the active and inactive electrodes on the MAP catheter rather than the mode of tissue inactivation that introduces the inaccuracies. Thus, there is no reason that a contact MAP electrode cannot be redesigned. In such a design, the active and inactive electrodes on the MAP catheter or probe would be oriented horizontally rather than vertically. A large inactivating electrode would produce the contact recording, and a small circular electrode, made of smooth, nondamaging material, could provide the active recording electrode. Depending on the tissue surface needed to generate this combination of potentials, one could still conceive of a surface probe or catheter that could record accurate contact epicardial MAP recordings. However, Kondo et al. [6] have shown us that until additional development is done, in vivo MAP recordings using contact catheters have substantial limitations and should be interpreted with caution.