These tools will no longer be maintained as of December 31, 2024. Archived website can be found here. PubMed4Hh GitHub repository can be found here. Contact NLM Customer Service if you have questions.


Pubmed for Handhelds

PUBMED FOR HANDHELDS

Search MEDLINE/PubMed

  • Title: Effects of OR-1896, a metabolite of levosimendan, on force of contraction and Ca2+ transients under acidotic condition in aequorin-loaded canine ventricular myocardium.
    Author: Takahashi R, Endoh M.
    Journal: Naunyn Schmiedebergs Arch Pharmacol; 2002 Nov; 366(5):440-8. PubMed ID: 12382073.
    Abstract:
    We performed experiments in canine ventricular trabeculae loaded with aequorin to elucidate the influence of acidosis on the positive inotropic effect (PIE) of OR-1896 (R)- N-[4-(4-methyl-6-oxo-1,4,5,6-tetrahydro-pyridazin-3-yl)-phenyl]-acetamide, an active metabolite of levosimendan. The concentration-response curve (CRC) for OR-1896 was biphasic in acidotic conditions (pH(o) 6.6) that was essentially the same as that in control conditions (pH(o) 7.4). The CRC for PIE of OR-1896 reached a plateau at 10(-6) M (first phase) and it became steeper again at 10(-3) M (second phase). Under acidotic conditions the efficacy of the first phase was 10% of the maximal response to isoproterenol (ISO(max)) and the PIE was associated with an increase in Ca(2+) transients of 2% of ISO(max) (P<0.05). The sensitivity of myofilaments to Ca(2+) ions was increased by OR-1896 in acidotic conditions, whereas the relationship of Ca(2+) transients and contractile force during an increase in elevation of the extracellular Ca(2+) concentration and during application of dihydroouabain was shifted prominently to the right in acidotic conditions. In conclusion, OR-1896 elicited a PIE due to an increase in the sensitivity of myofilaments to Ca(2+) ions even in acidotic conditions. The PIE of OR-1896 in acidotic conditions was much less than that in control conditions because the effect of the compound to induce an increase in intracellular Ca(2+) mobilization was markedly attenuated in acidotic conditions.
    [Abstract] [Full Text] [Related] [New Search]