Comparative study of toborinone (OPC-18790) and milrinone on energy metabolism in microembolized guinea pig hearts.
The effects of toborinone (OPC-18790) and milrinone on cardiac function and energetics were compared in microembolized guinea pig hearts. Male guinea pig hearts were perfused according to the Langendorff method and microembolization was induced by injecting microspheres. The hearts were then treated with toborinone (10 microM), milrinone (4 microM), and vehicle. Energy metabolism in hearts was assessed by 31-phosphorus magnetic resonance spectroscopy (31P-MRS). Microembolization produced a decrease in coronary perfusion flow (CPF), left ventricular developed pressure (LVP), and peak LVdP/dt by about 50% concomitantly with a decrease in creatine phosphate (PCr) and ATP and an increase in inorganic phosphate (Pi) and Pi/PCr ratio. Toborinone and milrinone increased peak LVdP/dt, an index of contractility, by 15 +/- 2% and 18 +/- 3%, respectively. Milrinone increased heart rate (HR) by 22 +/- 4% but toborinone did not change HR. Toborinone did not change PCr, ATP, Pi, Pi/PCr, and intracellular pH (pHi) compared with the vehicle. On the other hand, milrinone decreased PCr and increased Pi and Pi/PCr compared with toborinone or vehicle. These results suggest that the different effects between toborinone and milrinone on energy metabolism in microembolized hearts may be due to the difference of chronotropic action between these drugs. Thus toborinone, a positive inotropic agent without chronotropic action, may be effective in acute treatment of ischemic heart failure.
Ishikawa
M
M
Tokushima Research Institute, Otsuka Pharmaceutical Co., Ltd., Japan.
Koga
K
K
Fujiki
H
H
Mori
T
T
Yabuuchi
Y
Y
D000818:Animals; D002316:Cardiotonic Agents / Q000494:pharmacology*; D004734:Energy Metabolism / Q000187:drug effects*; D006168:Guinea Pigs; D006321:Heart / Q000187:drug effects* / Q000503:physiopathology; D008297:Male; D020105:Milrinone; D017202:Myocardial Ischemia / Q000378:metabolism*; D011728:Pyridones / Q000494:pharmacology*; D015363:Quinolones / Q000494:pharmacology*
D002316:Cardiotonic Agents; D011728:Pyridones; D015363:Quinolones; C077543:toborinone; D020105:Milrinone