1993 Fiscal Year Final Research Report Summary
Experimental study on the mechanisms of initaiation and prevention of proarrhythmic action induced by antiarrhythmic agents.
Project/Area Number |
04670555
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Research Category |
Grant-in-Aid for General Scientific Research (C)
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Allocation Type | Single-year Grants |
Research Field |
Circulatory organs internal medicine
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Research Institution | Showa University |
Principal Investigator |
TSUNAKAWA Hiroshi Showa Univ.Fujigaoka Hosp.Div.Cardiol.Lecturer, 医学部, 講師 (90138503)
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Co-Investigator(Kenkyū-buntansha) |
IMAI Kensuke Showa Univ.Sch.Med Assistant, 医学部, 助手 (00255837)
SHIRAI Tetsuro Showa Univ.Sch.Med Assistant, 医学部, 助手
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Project Period (FY) |
1992 – 1993
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Keywords | Antiarrhythmic agents / Proarrhythmic action / Flecainide / Anisotropic condution / Rate dependent conduction / Disparity of refractoriness / Isoproterenol / Ventricular tachycardia |
Research Abstract |
To study the mechanisms of initiation and prevention of proarrhythmic action induced by antiarrhytmic agent, the conduction characteristics and the refractoriness were investigated in the open canine myocardium under the different doses of flecainide acetate and flecainide pretreated with isoproterenol. Flecainide with therapeutic plasma levels decreased the conduction velocities in the fiber orientation-and frequency-dependent manner. It lengthned the refractory periods without an increase in disparity of refractoriness. No ventricular tachycardia was induced. Toxic doses of flecainide further decreased the orientation-and frequency-dependent conduction velocites. In addition, disparities in refractoriness as well as refractory periods were markedly increased associated with an induction of sine-wave like ventricular tachycardia in 10 of 13 dogs. On the other hand, pretreatment with isoproterenol of 1mug/min prevented the excessive reduction in conduction velocity in the logitudinal fib
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er orientation induced by toxic doses of flecainide. The refractory periods and the disparities of refractoriness were not significantly increased without an induction of ventricular tachycardia(0/9). Following the termination of isoproterenol infusion, ventricular tachycardias were induced in 6 of 9 dogs and nonsustained ventricular tachycardia in 1 dog. Conduction velocity was significantly decreased in the long axis and the refractory periods were significantly lengthned associated with marked increase in disparities of refractoriness(standard deviaton : 57.4<plus-minus>25.8%, difference between maximum and minimum refractory period : (51.3<plus-minus>18.3%). These results indicated that the pronounced reduction in fiber orientation-and frequency-dependent conduction velocity associated with significant increase in disparity of refractoriness may play a major role for the development of ventricular tachycardia induced by class Ic antiarrhythmic agent, flecainide acetate. Isoproterenol may prevent the occurrence of ventricular tachycardia induced by toxic doses of flecainide associated with reversal action against the excessive anisotropic conduction velocity depression and an increase in disparity of refractorin Less
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Research Products
(14 results)