Effects of OPC-18790, a new positive inotropic agent, on energetics in the ischaemic canine heart: a 31P-MRS study

Cardiovasc Res. 1995 Aug;30(2):299-306.

Abstract

Objective: Effects of OPC-18790, a novel positive inotropic agent, on cardiohaemodynamics and cardiac energetics were assessed simultaneously in dogs with cardiac ischaemia using phosphorus-31 magnetic resonance spectroscopy (31P-MRS) and compared with those of amrinone, a pure cGMP-inhibited PDE inhibitor.

Methods: Cardiac ischaemia was produced by partial stenosis of the coronary artery. Dogs with cardiac ischaemia were instrumented for the determination of regional coronary blood flow (non-radioactive coloured microsphere method), regional contractile function (sonomicrometry), and haemodynamics. Myocardial phosphate compounds were measured simultaneously by 31P-MRS.

Results: Coronary stenosis produced regional dyskinesis, a slight decrease in cardiac output (CO), intracellular acidosis, an increase in the inorganic phosphate (Pi)/creatine phosphate (PCr) ratio concomitantly with a decrease in regional coronary blood flow (CBF) in the ischaemic region. OPC-18790 dose-dependently produced an increase in contractility (measured by peak LVdP/dt) and CO, with only slight changes in heart rate (HR) and mean blood pressure (mBP). OPC-18790 did not change regional dyskinesis, but improved the Pi/PCr ratio at the high dose compared with ischaemic values (before drug administration). Amrinone produced an increase in CO comparable to that of OPC-18790; however, the increase in peak LVdP/dt was smaller while the increase in HR and decrease in mBP were larger than those seen with OPC-18790. Amrinone worsened the Pi/PCr ratio and intracellular acidosis only at the high dose.

Conclusion: These observed differences in energy metabolism between OPC-18790 and amrinone at the high dose may be due to the ability of OPC-18790 to increase CBF in the ischaemic region and which may attributed to its differing effect on overall haemodynamics. Thus, OPC-18790 may be useful in the management of ischaemic heart failure.

Publication types

  • Comparative Study

MeSH terms

  • Amrinone / pharmacology
  • Animals
  • Blood Pressure / drug effects
  • Cardiotonic Agents / pharmacology*
  • Coronary Circulation / drug effects
  • Dogs
  • Dose-Response Relationship, Drug
  • Energy Metabolism / drug effects*
  • Female
  • Heart Rate / drug effects
  • Magnetic Resonance Imaging
  • Male
  • Myocardial Contraction / drug effects*
  • Myocardial Ischemia / metabolism*
  • Myocardium / metabolism
  • Quinolones / pharmacology*

Substances

  • Cardiotonic Agents
  • Quinolones
  • toborinone
  • Amrinone