![[Feedback]](/icons/banner/feedbackACT.gif){kind=icon}
![[For Subscribers]](/icons/banner/subscriberACT.gif){kind=icon}
![[Archive]](/icons/banner/archiveACT.gif){kind=icon}
![[Search]](/icons/banner/searchACT.gif){kind=icon}
![[Contents]](/icons/banner/tocACT.gif){kind=icon}
|
|
|
|
|
||
K Todaka, J Wang, GH Yi, R Stennett, M Knecht, M Packer and D Burkhoff
Department of Medicine, College of Physicians and Surgeons, Columbia University, New York, New York, USA.
Levosimendan is hypothesized to be primarily a calcium sensitizer in vitro. Therefore, its inotropic action may be similar in both the normal and the congestive heart failure (CHF) state, and it may be associated with a decreased energetic cost of inotropism in vivo. To test these hypotheses, we gave levosimendan to cross-circulated isolated hearts from normal (n = 11) and CHF (n = 7, 4-week rapid pacing) dogs. Peak isovolumic left ventricular pressure at an end- diastolic pressure of 5 mm Hg (Pmax,5) measured by an intraventricular balloon was 120 +/- 15 mm Hg in normal dogs, and it was increased by approximately 40% in response to approximately 0.63 microM levosimendan. In CHF dogs, base-line Pmax,5 was only 60 +/- 12 mm Hg (P < .01 compared to normals), and approximately 8.4 microM levosimendan (P < .05) was required to increase Pmax,5 by approximately 40%. The inotropic actions were associated with increases in unloaded myocardial oxygen consumption by comparable amounts in normal and falling hearts. The blunted inotropic response in CHF and the energetic cost of inotropism were also comparable to those obtained with isoproterenol. In other studies, there was no significant inotropic action of levosimendan in Langendorff-perfused rat hearts (n = 5), and intracellular calcium concentration, estimated by macroinjected aequorin, in ferret hearts (n = 2) increased dose-dependently. These findings suggest that inotropic actions of levosimendan in vivo may be mediated in part by factors other than calcium sensitization.
This article has been cited by other articles:
|
|
 |
|
  S. Masutani, H.-J. Cheng, M. Hyttila-Hopponen, J. Levijoki, A. Heikkila, A. Vuorela, W. C. Little, and C.-P. Cheng Orally Available Levosimendan Dose-Related Positive Inotropic and Lusitropic Effect in Conscious Chronically Instrumented Normal and Heart Failure Dogs J. Pharmacol. Exp. Ther., April 1, 2008; 325(1): 236 - 247. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. A. Kass and R. J. Solaro Mechanisms and Use of Calcium-Sensitizing Agents in the Failing Heart Circulation, January 17, 2006; 113(2): 305 - 315. [Full Text] [PDF]
|
|
|
|
 |
|
 H. Tachibana, H.-J. Cheng, T. Ukai, A. Igawa, Z.-S. Zhang, W. C. Little, and C.-P. Cheng Levosimendan improves LV systolic and diastolic performance at rest and during exercise after heart failure Am J Physiol Heart Circ Physiol, February 1, 2005; 288(2): H914 - H922. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
G. S. Nelson, R. D. Berger, B. J. Fetics, M. Talbot, J. C. Spinelli, J. M. Hare, and D. A. Kass Left Ventricular or Biventricular Pacing Improves Cardiac Function at Diminished Energy Cost in Patients With Dilated Cardiomyopathy and Left Bundle-Branch Block Circulation, December 19, 2000; 102(25): 3053 - 3059. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H. Senzaki, T. Isoda, N. Paolocci, U. Ekelund, J. M. Hare, and D. A. Kass Improved Mechanoenergetics and Cardiac Rest and Reserve Function of In Vivo Failing Heart by Calcium Sensitizer EMD-57033 Circulation, March 7, 2000; 101(9): 1040 - 1048. [Abstract] [Full Text] [PDF]
|
|
 |
 |
 |
|
 |
 |
 |
