Antiarrhythmic effect of ACE inhibitors infarcted myocardium
| Project/Area Number |
07670805
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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 |
Circulatory organs internal medicine
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| Research Institution | Keio University |
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Principal Investigator |
MITAMURA Hideo Keio University Cardiology Associate Professor, 医学部, 助教授 (70129675)
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| Co-Investigator(Kenkyū-buntansha) |
TAKATSUKI Seiji Keio University Cardiology Assistant, 医学部, 助手 (60245470)
SUEYOSHI Koichiro Keio University Cardiology Assistant, 医学部, 助手 (00235839)
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| Project Period (FY) |
1995 – 1996
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| Project Status |
Completed (Fiscal Year 1996)
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| Budget Amount *help |
¥2,000,000 (Direct Cost: ¥2,000,000)
Fiscal Year 1996: ¥1,100,000 (Direct Cost: ¥1,100,000)
Fiscal Year 1995: ¥900,000 (Direct Cost: ¥900,000)
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| Keywords | myocardial infarction / ventricular arrhythmias / ACE inhibitor / beta adrenergic blocker |
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| Research Abstract |
This study was designed to evaluate the antiarrhythmic effect of angiotensin converting enzyme inhibitors (ACEI) in a canine model of myocardial infarction. In order to achieve this goal, the study was devided into 2 protocols which were serially carried out over the 2 years from 1995 to 1996.
A preliminary study to evaluate the arrhythmogenic substrate in this model was started in 1995. Using mongrel dogs, myocardial infarction was created by coronary artery ligation. One week later, under anesthesia with chest open, an electrophysiologic study was done with a 47 channel mapping electrode placed on the epicardial surface of the infarcted myocardium and a pacing electrode in the right ventricular outflow tract. During constant ventricular pacing at 300msec, local QT intervals were measured at these 47 points to evaluate dispersion of refractoriness in the surviving epicardial muscle. Induction of ventricular tachyarrhythmias was attempted by programd stimulation. These dogs had reproduc
… More
ibly inducible ventricular tachyarrhythmias with ventricular refractoriness heterogenously distributed over the surviving epicardial muscle.
Since the autonomic tone is known to affect susceptibility to these arrhythmias, we studied the effect of isoproterenol and ONO1101 (a ultrashortacting beta blocker) on dispersion of refractoriness and inducibility of arrhythmias. It was shown that isoproterenol increased dispersion of refractoriness and arrhythmia inducibility while ONO1101 reversed these effect. Since angiotensin II promotes norepinephrin release from sympathetic nerve gterminal, ACEI will exhibit antiadrenergic action, which may be antiarrhythmic.
The effect of ACEI,enalapril, was studied in 1996 in a similar canine model of myocardial infarction except that the electrophysiologic test was carried out while the dog was awake with chest closed. Dogs were randomly allocated to receive enalapril 10mg p.o. or no drug, the latter serving as control. And the electrophysiologic tests were done 1 and 2 weeks after myocardial infarction. Although the control animals had dispersion of refractoriness and inducibility of ventricular tachyarrhythmias similar to what we observed earlier, these features waned by the second week. Since the arrhythmogenic substrate in this model changes after myocardial infarction and only a few dogs had inducible sustained ventricular tachyarrhythmias at 2 weeks, the demonstration of the antiarrhythmic effects of ACEI was considered to be impossible. Less
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Report
(3 results)
Research Products
(21 results)
