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J Cardiovasc Pharmacol. 1999 Feb;33(2):237-42.

Calcium sensitivity and the effect of the calcium sensitizing drug pimobendan in the alcoholic isolated rat atrium.

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  • 1Department of Medical-Surgical Nursing, University of Illinois at Chicago, 60612, USA.

Abstract

We compared the effect of inotropic interventions (isoproterenol and pimobendan) and the relation between Ca2+ and isometric twitch force in atrial muscle from control rats and rats that had consumed alcohol for 2 months. At extracellular Ca2+ concentrations of 1-4 mM, alcohol atria developed less force than the controls. The median effective concentration (EC50) for extracellular Ca2+ was 3.2 +/- 0.01 mM for the alcohol group and 2.8 +/- 0.001 mM for the control group, whereas at maximal Ca2+, developed force was the same in both groups. To test whether the myofilament response to Ca2+ is altered with chronic alcohol consumption, we measured the relation between Ca2+ and force of atrial fiber bundle preparations extracted with Triton X-100. The Ca2+-force relation of alcohol atria (EC50 = 2.4 +/- 0.001 microM) was significantly shifted to the right of that of the control atria (EC50 = 1.94 +/- 0.001 microM Ca2+). Compared with controls, the alcohol atria demonstrated a significant depression in the inotropic effect of the beta-adrenergic agonist isoproterenol over a broad concentration range (10(-9)-10(-6) M). We also tested the effect of pimobendan, an inotropic agent with both phosphodiesterase-inhibiting and myofilament Ca2+-sensitizing actions. Developed force at concentrations of pimobendan <75 microM was similar between groups. However, at concentrations of pimobendan >75 microM, the developed force in alcohol atria was significantly less than control. Our results indicate that 2 months of alcohol consumption is associated with decreases in myofilament Ca2+ sensitivity and altered responsiveness to different inotropic agents.

PMID:
10028931
[PubMed - indexed for MEDLINE]
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