| Budget Amount *help |
¥3,000,000 (Direct Cost: ¥3,000,000)
Fiscal Year 1998: ¥1,400,000 (Direct Cost: ¥1,400,000)
Fiscal Year 1997: ¥1,600,000 (Direct Cost: ¥1,600,000)
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| Research Abstract |
To determine the pathophysiological roles of the atrial multicentric pacemakers for heart rate of the dog heart, we first investigated the conditions to induce the multicentric pacemaker sites in the atrial pacemaker complex in the dog heart. To find the conditions, we studied (1) the effects of sympathetic and parasympathetic nerve stimulation on the pacemaker location and rate in the rate-related parasympathetic nerve intact or denervated heart, (2) the effects of a Ca2+ channel antagonist (verapamil), a hyperpolarization activated inward current inhibitor (zatebradine), and a blocker of the rapid type of the delayed rectifier K+ current (E-4031 ) on the pacemaker location and rate, and (3) the effects of those antagonists on the pacemaker location and rate in response to sympathetic or parasympathetic nerve stimulation in the heart of the anesthetized dog. We developed the isochronal activation sequence mapping method to determine the pacemaker location and rate in the heart of the
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open-chest anesthetized dog. In our project, we have observed and reported the following results. (1) Sympathetic nerve stimulation shifts the pacemaker location from the sinoatrial (SA) node region to the superior pacemaker region, parasympathetic nerve stimulation shifts the pacemaker location to the low right atrial pacemaker region and during simultaneous sympathetic and parasympathetic stimulation a pacemaker site exists in the SA node or low right atrial pacemaker region. After rate-related parasympathetic nerves were denervated, pacemaker location is differentially changed by autonomic stimulation. (2) When zatebradine, verapamil and E-4031 decrease atrial rate similarly, those blockers differentially affect the atrial pacemaker complex. (3) Zatebradine, verapamil and E- 4031 differentially affect the pacemaker location and rate in response to sympathetic and parasympathetic nerve stimulation in the heart of the anesthetized dog. However, we are still investigating the conditions to induce the multicentric pacemakers in the dog heart. Less
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