A new cardiotonic agent, OPC-8212, elevates the myocardial oxygen consumption versus pressure-volume area (PVA) relation in a similar manner to catecholamines and calcium in canine hearts.
We studied the effect of a new positive inotropic agent, OPC-8212 (3,4-Dihydro-6-[4-(3,4-dimethoxybenzoyl)-1-piperazinyl]-2(1H)-quinolinon e), on the relation between left ventricular oxygen consumption (VO2) and pressure-volume area (PVA) in excised cross-circulated dog hearts. PVA represents the total mechanical energy generated by ventricular contraction. OPC-8212 increased the contractility index, Emax, by 59% +/- 36% from 7.6 +/- 4.3 to 11.1 +/- 4.6 mmHg/(ml/100 g LV [leftventricle]). OPC-8212 elevated the VO2-PVA relation without a significant change in its slope. Namely, OPC-8212 did not affect the mechanical efficiency of the contractile machinery from the PVA-dependent fraction of VO2 to PVA, but increased the PVA-independent fraction of VO2 which is related with non-mechanical processes of contraction. This effect suggested an increased energy expenditure for excitation-contraction coupling. These results associated with the enhanced contractile state by OPC-8212 were both qualitatively and quantitatively similar to those obtained with catecholamines and calcium in our previous study. This suggests that OPC-8212, catecholamines, and calcium have similar effects on intracellular Ca2+ concentration and enhanced ventricular contractility.
Futaki
S
S
Department of Cardiovascular Dynamics, National Cardiovascular Center Research Institute, Osaka, Japan.
Nozawa
T
T
Yasumura
Y
Y
Tanaka
N
N
Suga
H
H
D000818:Animals; D002118:Calcium / Q000494:pharmacology; D002316:Cardiotonic Agents / Q000494:pharmacology*; D002395:Catecholamines / Q000494:pharmacology; D004285:Dogs; D004734:Energy Metabolism / Q000187:drug effects; D009200:Myocardial Contraction / Q000187:drug effects*; D009206:Myocardium / Q000378:metabolism*; D010101:Oxygen Consumption / Q000187:drug effects*; D011719:Pyrazines; D011804:Quinolines / Q000494:pharmacology*
D002316:Cardiotonic Agents; D002395:Catecholamines; D011719:Pyrazines; D011804:Quinolines; C041667:vesnarinone; D002118:Calcium