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The effects of TA-064, dopamine and isoproterenol on the acutely ischemic myocardium Eiichi Tokutake 1 , Ichiro Watanabe 1 , Tomoaki Saito 1 , Kazuhira Hibiya 1 , Nobuhiro Takahasi 1 , Toshitsugu Ogura 1 , Sei Yumikura 1 , Masaki Nagasawa 1 , Satoshi Saito 1 , Yukio Ozawa 1 , Michinobu Hatano 1 1The 2nd Department of Internal Medicine, Nihon University School of Medicine pp.897-902
Published Date 1985/7/15
DOI https://doi.org/10.11477/mf.1404204710

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  • Abstract
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 The use of positive inotropic agents in patients with acute myocardial infarction in the early stage remains controversial. The increase in myocardial oxygen demands induced by positive inotropic agents may cause deleterious effects. We studied comparative effects of TA-064, dopamine andisoproterenol on the acutely ischemic myocardium in 24 mongrel dogs.

 Method : Left anterior descending artery was ligated for 10 minutes as a control occlusion. Acute ischemic injury was evaluated by measurements of interstitial K+ and ΔST. TA-064 (1.0 1.5μg/kg/min), Dopamine (5μg/kg/min) and Isoproterenol (0.03μg/kg/min), which caused similar inotropic effects (Max dp/dt ; 30% increase, cardiac output ; 20% increase) were tested.

 Results : 1) TA-064 and dopamine increased HR by 4.3% and 4.1% respectively (N.S.), but isoproterenol increased it by 9.0% (p<0.01). TA-064 and dopamine increased mean BP by 7.0% and 6.0% respectively (N.S.), but isoproterenol, decreased it by 0.5% (N.S.). 2) Interstitial K+ rose from 3.9±0.1mM to 8.1±0.6mM in control coronary artery occlusion (CAO). Interstitial K+ increasedto 9.1±0.4mM after TA-064, to 9.3±0.5mM after dopamine and to 10.1±0.4mM after isoproterenol (p<0.01). 3) ΔST was 6.4±0.9mV in the control CAO, but TA-064 increased ΔST by 24.6% (N.S.), dopamine increased it by 29.0% (N.S.) and isoproterenol increased it by 51.8% (p<0.01).

 Conclusion : These three inotropic agents potentiated the rise of interstitial K+ and ΔST in the ischemic zone, but such deleterious effects on ischemic myocardium are less pronounced than isoproterenol at similar inotropic action. Thus TA-064 might be a favorable inotropic agent to be used orally in patient with CHF after AMI, especially catecholamine dependent refractory heart failure and CHF with bradycardia and/or AV block in which digitalis was relatively contraindicated.


Copyright © 1985, Igaku-Shoin Ltd. All rights reserved.

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