| Co-Investigator(Kenkyū-buntansha) |
KUBOTA Hiroshi Kyorin University, Department of Medicine, Associate Professor, 医学部, 助教授 (00262006)
NAKAZAWA Kazuo National Cardiovascular Center Research Institute, Head, 室長 (50198058)
NAMBA Tsunetoyo Kagawa Prefectural College of Heath Sciences, Associate Professor, 保健医療学部, 助教授 (70331866)
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| Budget Amount *help |
¥1,200,000 (Direct Cost: ¥1,200,000)
Fiscal Year 2005: ¥500,000 (Direct Cost: ¥500,000)
Fiscal Year 2004: ¥700,000 (Direct Cost: ¥700,000)
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| Research Abstract |
Introduction : It has been reported that electrical stimulation can control spiral wave (SW) reentry. However, the underlying mechanistic basis of the SW control with respect to virtual electrode polarization (VEP) interaction is undetermined. The aim of the present study is to test numerically our hypothesis that the cathode-break (CB) excitation following localized stimulus-induced VEP can control SW reentry and to assess the effects of pilsicainide, a pure sodium channel blocker, on electrophysiological action and wavefront dynamics during atrial fibrillation (AF). Methods : (1)We conducted altogether 3,168 simulations of localized stimulus during SW reentry in a bidomain sheet. Unipolar cathodal 2-msec stimuli of strengths 4, 8, 16, and 24 mA were delivered at 99 locations in the sheet. (2)In a newly developed model of isolated, perfused and superfused canine atria (n=12), the right and left endocardium were simultaneously mapped using a computerized mapping system. AF was induced
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with 1-5μM acetylcholine. The antifibrillatory actions of pilsicainide on AF cycle length (AFCL), refractory period (RP), conduction velocity (CV), excitable gap (EG), and the core of mother rotor were studied. The RP was defined as the shortest coupling interval that could capture the fibrillating atrium. The EG was estimated as difference between the AFCL and RP. At baseline, multiple wavefronts were observed. Results : (1)The interaction between the localized stimulus-induced VEP and the original SW reentry resulted in one of three consequent outcomes : SW shift, SW breakup, and no response. Stimulus timing, site, and strength were the important factors for the VEP-mediated SW control. CB excitation following the strong VEP initially propagated through the excitable gap deexcited by the virtual anode. Therefore, even though the stimulus was delivered during the refractory period at a distance from the SW core center, there was a possibility that the CB excitation following strong stimulus reached the original SW core and shifted its reentrant center. Furthermore, we found that the episode numbers of SW shift across the fibers were more sensitive to the stimulus strength than those of SW shift along the fibers. (2)After 2.5μg/mL infusion of pilsicainide, all preparations showed irregular activity and AF was terminated in 2 preparations. The AFCL and RP were prolonged and CV was decreased significantly. EG was widened (147% ; P<0.01) and the core perimeter was increased (100% ; P<0.01). Increasing the dosage either terminated AF (6 preparations) or converted to organized activity (i.e., atypical atrial flutter)(4 preparations). On the maps, all "unorganized" AFs were terminated with the excitation of the core of mother rotor by an outside wavefront, whereas in preparations with atrial flutter, pilsicainide did not terminate its activity. Conclusions : (1)The simulations would support our hypothesis. This study may provide new mechanistic insight into the control of cardiac fibrillation, based on SW reentry. (2)Widening of the EG by pilsicainide facilitates the excitation of the core of mother rotor, leading to the termination of AF. In some experiments, pilsicainide converts AF to persistent atrial flutter. Less
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