2005 Fiscal Year Final Research Report Summary
A New Pharmacologically Induced Arrhythmia Model of Brugada Syndrome : Role in M Cells.
| Project/Area Number |
16590188
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
General pharmacology
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| Research Institution | Hirosaki University |
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Principal Investigator |
MOTOMURA Shigeru Hirosaki University, School of Medicine, Professor, 医学部, 教授 (40091756)
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| Co-Investigator(Kenkyū-buntansha) |
HIGUMA Takumi Hirosaki University, School of Medicine, Assistant, 医学部, 助手 (40361018)
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| Project Period (FY) |
2004 – 2005
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| Keywords | Brugada syndrome / a canine isolated, blood-per fused right ventricular preparation / pinacidil / pilsicainide / ventricular fibrillation / sex difference / M cell / functional block |
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| Research Abstract |
We developed an experimental Brugada syndrome model using a canine isolated right ventricular preparation cross-circulated with arterial blood of a support dog and examined the VT mechanism. Two plaque electrodes containing 96 bipolar electrodes were attached to the endocardium and epicardium and transmural ECG were recorded simultaneously.
In transmural ECG, pinacidil, a KATP channel opener itself did not induced any ST change. However, when pinacidil was administered in the presence of pilsicainide, a pure sodium channel blocker, saddleback and coved types of ST elevation were induced and the degree of ST elevation became greater as the dose of pinacidil was increased.
At baseline, no ventricular arrhythmia occurred spontaneously or was induced by premature stimulation. However, 18 polymorphic VT episodes were recorded in 9 of the 12 preparations associated with ST elevation. Fourteen episodes spontaneously developed in 5 preparations after an extrasystole during basic drive pacing. An
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alysis of local recovery times revealed increased dispersion especially in epicardium, and the extrasystole originated from a site with a short recovery time, suggesting that phase 2 reentry was its mechanism. The other 4 VTs were induced by a single premature stimulus. Nine occurred associated with saddleback-type ST elevation, and the other 9 occurred with coved-type ST elevation. ALL VT was sustained until the drugs were withdrawn.
Analysis of the activation sequences during VT revealed reentry between epicardium and endocardium or reentry around an arc of a functional block confined to epicardium or endocardium with bystander activation of the other, resulting in sustained VT.
In the present study, the monophasic action potentials (MAP) were recorded from the middle layer in the myocardium of the right ventricle and obtained the MAP with approximately 15-20% longer MAP duration than those of epicardium and endocaudium, suggesting to be the M cells.. However, no functional block and phase 2 reentry associated with M cells were observed during the VT episodes. Less
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Research Products
(4 results)
