Circulation, Vol 86, 1945-1954, Copyright © 1992 by American Heart Association
PP de Tombe, D Burkhoff and WC Hunter
BACKGROUND. Most positive inotropic agents increase cardiac contractility
by increasing the amount of Ca2+ cycled with each beat. The additional
amount of oxygen that is consumed by the heart to cycle this additional
Ca2+ is believed to reduce myocardial efficiency. On the other hand, it has
been suggested that the agent EMD-53998 increases the Ca2+ sensitivity of
the contractile proteins without affecting the intracellular Ca2+ transient
in cardiac muscle. Therefore, application of this agent may increase
cardiac contractility without decreasing myocardial efficiency. The purpose
of the present study was to test this hypothesis. METHODS AND RESULTS. We
measured myocardial oxygen consumption (MVO2) in six isolated,
isovolumically beating blood-perfused canine hearts. The hearts were paced
at 120 beats per minute. Contractility was varied in each heart by infusion
of either CaCl2 or EMD-53998. With infusion of either agent, MVO2 was a
linearly proportional function of contractility. No significant difference
between CaCl2 and EMD-53998 could be detected in the interrelation between
contractility and MVO2. CONCLUSIONS. We conclude that the
"calcium-sensitizing agent" EMD-53998 is a potent positive inotropic agent
in the isolated, blood-perfused canine heart. However, EMD-53998 does not
provide an energetic advantage over currently used positive inotropic
agents.
ARTICLES
Effects of calcium and EMD-53998 on oxygen consumption in isolated canine hearts
Department of Biomedical Engineering, Johns Hopkins University, School of Medicine, Baltimore, Md. 21205.
This article has been cited by other articles:
 |
|
 |
|
  H.-P. Hermann, O. Zeitz, S. E Lehnart, B. Keweloh, N. Datz, G. Hasenfuss, and P. M.L Janssen Potentiation of beta-adrenergic inotropic response by pyruvate in failing human myocardium Cardiovasc Res, January 1, 2002; 53(1): 116 - 123. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. A.I.P. Trines, C. J. Slager, T. A.M. Onderwater, J. M.J. Lamers, P. D. Verdouw, and R. Krams Oxygen wastage of stunned myocardium in vivo is due to an increased oxygen cost of contractility and a decreased myofibrillar efficiency Cardiovasc Res, July 1, 2001; 51(1): 122 - 130. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 H.-P. Hermann, O. Zeitz, B. Keweloh, G. Hasenfuss, and P. M. L. Janssen Pyruvate potentiates inotropic effects of isoproterenol and Ca2+ in rabbit cardiac muscle preparations Am J Physiol Heart Circ Physiol, August 1, 2000; 279(2): H702 - H708. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. Korvald, O. P. Elvenes, L. M. Ytrebo, D. G. Sorlie, and T. Myrmel Oxygen-wasting effect of inotropy in the "virtual work model" Am J Physiol Heart Circ Physiol, April 1, 1999; 276(4): H1339 - H1345. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. Onishi, K. Sekioka, R. Ishisu, Y. Abe, H. Tanaka, M. Nakamura, Y. Ueda, and T. Nakano MCI-154, a Ca2+ sensitizer, decreases the oxygen cost of contractility in isolated canine hearts Am J Physiol Heart Circ Physiol, October 1, 1997; 273(4): H1688 - H1695. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J.A Lee and D.G Allen Calcium sensitisers: mechanisms of action and potential usefulness as inotropes Cardiovasc Res, October 1, 1997; 36(1): 10 - 20. [Full Text] [PDF]
|
|
|
|
 |
|
 Y. Koiwa, H. Honda, T. Takagi, J.-i. Kikuchi, N. Hoshi, and T. Takishima Modification of Human Left Ventricular Relaxation by Small-Amplitude, Phase-Controlled Mechanical Vibration on the Chest Wall Circulation, January 7, 1997; 95(1): 156 - 162. [Abstract] [Full Text]
|
|
|
|
|
|
A. Hgashiyama, M. W. Watkins, Z. Chen, and M. M. LeWinter Effects of EMD 57033 on Contraction and Relaxation in Isolated Rabbit Hearts Circulation, November 15, 1995; 92(10): 3094 - 3104. [Abstract] [Full Text]
|
|