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.