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Cardiovascular Research 1995 30(2):299-306; doi:10.1016/S0008-6363(95)00057-7
© 1995 by European Society of Cardiology
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Copyright © 1995, European Society of Cardiology

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

Makoto Ishikawab, Toyoki Mori*,b, Shuji Itoha, Hiroyuki Fujikia, Keiko Kogab, Michiaki Tominagaa and Youichi Yabuuchib

a2nd Tokushima Institute of New Drug Research, Otsuka Pharmaceutical Co. Ltd., 463-10 Kagasuno, Kawauchi-cho, Tokushima 771-01, Japan
bTokushima Research Institute, Otsuka Pharmaceutical Co. Ltd., 463-10 Kagasuno, Kawauchi-cho, Tokushima 771-01, Japan

* Corresponding author. Tel. (+81-886)-65-2126, ext. 2934; Fax (+81-886)-65-7628.

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.

KEYWORDS Cardiac energetics; Systemic hemodynamics; Myocardial ischemia; Coronary blood flow; OPC-18790; Amrinone; NMR


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