Limitation of the Current AF Research Methods

Most electrophysiologic (EP) studies of AF are performed in a surgical, laboratory setting on sedated animal models. This type of experimental method is most frequently used and advantageous, because it is easy to set up, various data acquisition equipment can be used, and the experiment can be performed in a controlled setting. However, there are many factors that may influence the accuracy of the experimental result when an acute animal model is used.

Effects of Anesthesia

Effects of anesthesia on the atria are complex. These effects include depression of sinus node automaticity, increased atrial refractoriness and decreased atrio-ventricular nodal conduction, which could either be anti-fibrillatory or arrhythmogenic on AF. For example, isoflurane is commonly used as a maintenance anesthesia in EP studies and has been shown to have an anti-fibrillatory effect on the atria. In a study which a new AF treatment is being evaluated and when isoflurane is used to anesthetize the animal model, it might be difficult to assess the treatment efficacy accurately because isoflurane might have contributed to the treatment efficacy favorably. As a result, conclusion made from a sedated animal model may not be fully applicable to the same model in a conscious state.

Effects of the Autonomic Nervous System

Autonomic nervous system (ANS) tone also has a major impact on the electrophysiologic state of the heart, and is more difficult to control and study in a laboratory setting. Sudden cardiac death and myocardial infarction are shown to be related to ANS tone and it has been postulated that a change in ANS tone may contribute to cardiac instability. In an experiment performed on sedated animal model, the natural ANS tone is compromised. Also, ANS tone varies in a 24-hour period, and its effects are difficult to examine in a laboratory setting when experiments are only performed for a finite time period. An AF treatment could be more effective under certain ANS tone, however it would be difficult to verify in a surgical setting. To take into account the effects of ANS tone on the heart in a study, it is important that the experimental model has to be conscious, mobile and in its natural environment throughout the study. In addition, it is preferred that the experimental data is acquired in a non-invasive manner. By limiting the amount of interference of the experimental model, the natural ANS tone can be conserved.

Lack of Long-Term AF Study

AF is progressive in nature and it is widely believed that ``AF begets AF''. To be able to continuously observe the development of AF by making systematic measurement from initiation, and to frequently monitor the effectiveness of a given therapy in the same model will provide a tremendous amount of information about AF and its time course. However, it is unrealistic to do so in a surgical setting.

In research, several groups have been successful in following AF development using animal models. Wijffels et al. monitored changes in AERP and CV, as AF developed and also after cardioversion for a 4-week period in goat model. Garret and Todd et al. studied the inducibility and cumulative effects of AF in goats over a repetitive 5-days and 1-month period of sustained AF, respectively. These studies provided valuable information on the remodeling process. However, these experiments were limited by tethering of the animals, and by the short experimental periods.

Limited Types and Amount of Collected Data

In most studies of AF, both on humans and on animals, long-term, continuous monitoring of the heart is done using commercial implantable cardioverter-defibrillators (ICDs) or pacemakers. It is one of the best experimental methods because it monitors the course of AF most naturally. Data can be downloaded repeatedly by placing a ``programming magnet'' over an ICD or a pacemaker. However, a disadvantage with this method is that only a limited amount of data can be stored in an ICD or a pacemaker due to limited memory space. Usually, only the number and duration of arrhythmic episodes, a limited number of ECGs, along with several statistical values are recorded. To add more data acquisition capabilities to these devices, further modification is required. Unfortunately, ICD manufacturers are usually reluctant to share design details of their devices with research groups due to proprietary reasons. As a result, custom modification of ICDs is difficult, and only limited types and amount of data can be collected with commercial ICDs.

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