Effects of levosimendan on myocardial contractility and oxygen consumption

Koji Todaka, Jie Wang, Geng Hua Yi, Richard Stennett, Mathias Knecht, Milton Packer, Daniel Burkhoff

研究成果: ジャーナルへの寄稿記事

47 引用 (Scopus)

抄録

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 (P(max,5)) measured by an intraventricular balloon was 120 ± 15 mm Hg in normal dogs, and it was increased by ~40% in response to ~0.63 μM levosimendan. In CHF dogs, base- line P(max,5)) was only 60 ± 12 mm Hg (P < .01 compared to normals), and ~8.4 μM levosimendan (P < .05) was required to increase P(max,5)) by ~40%. The inotropic actions were associated with increases in unloaded myocardial oxygen consumption by comparable amounts in normal and failing 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.

元の言語英語
ページ(範囲)120-127
ページ数8
ジャーナルJournal of Pharmacology and Experimental Therapeutics
279
発行部数1
出版物ステータス出版済み - 10 1 1996
外部発表Yes

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Oxygen Consumption
Heart Failure
Dogs
Muscle Contraction
Calcium
Aequorin
Costs and Cost Analysis
Ferrets
Ventricular Pressure
Isoproterenol
simendan
Blood Pressure

All Science Journal Classification (ASJC) codes

  • Molecular Medicine
  • Pharmacology

これを引用

Todaka, K., Wang, J., Yi, G. H., Stennett, R., Knecht, M., Packer, M., & Burkhoff, D. (1996). Effects of levosimendan on myocardial contractility and oxygen consumption. Journal of Pharmacology and Experimental Therapeutics, 279(1), 120-127.

Effects of levosimendan on myocardial contractility and oxygen consumption. / Todaka, Koji; Wang, Jie; Yi, Geng Hua; Stennett, Richard; Knecht, Mathias; Packer, Milton; Burkhoff, Daniel.

:: Journal of Pharmacology and Experimental Therapeutics, 巻 279, 番号 1, 01.10.1996, p. 120-127.

研究成果: ジャーナルへの寄稿記事

Todaka, K, Wang, J, Yi, GH, Stennett, R, Knecht, M, Packer, M & Burkhoff, D 1996, 'Effects of levosimendan on myocardial contractility and oxygen consumption', Journal of Pharmacology and Experimental Therapeutics, 巻. 279, 番号 1, pp. 120-127.
Todaka, Koji ; Wang, Jie ; Yi, Geng Hua ; Stennett, Richard ; Knecht, Mathias ; Packer, Milton ; Burkhoff, Daniel. / Effects of levosimendan on myocardial contractility and oxygen consumption. :: Journal of Pharmacology and Experimental Therapeutics. 1996 ; 巻 279, 番号 1. pp. 120-127.
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abstract = "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 (P(max,5)) measured by an intraventricular balloon was 120 ± 15 mm Hg in normal dogs, and it was increased by ~40{\%} in response to ~0.63 μM levosimendan. In CHF dogs, base- line P(max,5)) was only 60 ± 12 mm Hg (P < .01 compared to normals), and ~8.4 μM levosimendan (P < .05) was required to increase P(max,5)) by ~40{\%}. The inotropic actions were associated with increases in unloaded myocardial oxygen consumption by comparable amounts in normal and failing 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.",
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