Analysis of the efficacy of the new cardiotonic agent TA-064.
TA-064 is a new cardiotonic agent which is also effective orally, according to investigations conducted in Japan. We analyzed computer-assisted alterations of pressure-volume relationships serially and of indirect myocardial oxygen consumption (MVO2) estimations on line during TA-064 influence in 16 patients with congestive cardiomyopathy: left ventricular function was moderately decreased in seven patients (group A) and drastically decreased in nine (group B). Results showed that TA-064, 8 micrograms/kg/min intravenously, exerted positive inotropic effects in both groups and induced mean maximal delta percentage changes at about 5 minutes of infusion as follows: left ventricular stroke work index +65% and +47%; dP/dtmax +61% and 59%; left ventricular efficiency +62% and 53%; MVO2 +31% and +11% (p less than 0.05). TA-064, 20 mg by mouth induced serum levels (group A = 23.8 +/- 12ng/ml and group B = 26.4 +/- 20 ng/ml) corresponding to the effects with dosages of 1 to 2 ng/kg/min intravenously (p greater than 0.05), thus implying that significant changes in left ventricular function require higher oral dosages. We conclude that TA-064 improves left ventricular function, primarily via a contractility increase, also in group B patients without toxic side effects. On-line indirect MVO2 assessment and analysis of serial pressure-volume relationships helped to provide a more complex definition of the mechanism and efficiency of the cardiotonic agent under study.
D000284:Administration, Oral; D000328:Adult; D002306:Cardiac Volume / Q000187:drug effects; D009202:Cardiomyopathies / Q000503:physiopathology*; D002316:Cardiotonic Agents / Q000008:administration & dosage / Q000097:blood / Q000494:pharmacology*; D004983:Ethanolamines / Q000008:administration & dosage / Q000097:blood / Q000494:pharmacology*; D006352:Heart Ventricles / Q000000981:diagnostic imaging / Q000187:drug effects; D006439:Hemodynamics / Q000187:drug effects*; D006801:Humans; D007263:Infusions, Parenteral; D008297:Male; D008875:Middle Aged; D009200:Myocardial Contraction / Q000187:drug effects; D009206:Myocardium / Q000378:metabolism; D009862:Online Systems; D010101:Oxygen Consumption / Q000187:drug effects; D011312:Pressure; D011859:Radiography; D013318:Stroke Volume / Q000187:drug effects
D002316:Cardiotonic Agents; D004983:Ethanolamines; C037293:denopamine