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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

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Summary

We studied the effect of a new positive inotropic agent, OPC-8212 (3,4-Dihydro-6-[4-(3,4-dimethoxybenzoyl)-l-piperazinyl]-2(1H)-quinolinone), 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.

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Authors and Affiliations

  1. Department of Cardiovascular Dynamics, National Cardiovascular Center Research Institute, 5-7-1 Fujishirodai, Suita, 565, Osaka, Japan

    Shiho Futaki, Takashi Nozawa, Yoshio Yasumura, Nobuaki Tanaka & Hiroyuki Suga

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  1. Shiho Futaki
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  2. Takashi Nozawa
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  3. Yoshio Yasumura
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  4. Nobuaki Tanaka
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  5. Hiroyuki Suga
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Additional information

Partly supported by a Grant-in-Aid (61480102) for Scientific Research from the Ministry of Education, Science, and Culture, and a Research Grant (60C-3) for Cardiovascular Diseases from the Ministry of Health and Welfare of Japan.

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Futaki, S., Nozawa, T., Yasumura, Y. et al. 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. Heart Vessels 4, 153–161 (1988). https://doi.org/10.1007/BF02058428

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  • DOI: https://doi.org/10.1007/BF02058428

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