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Modulation of cAMP level by tedisamil in guinea pig heart

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Abstract

Tedisamil is antiarrhythmic class III drug with antifibrillating/defibrillating potency linked to enhancement of intermyocyte gap junctional electrical coupling most likely via its sympathomimetic cAMP-related mechanisms. This study was designed to examin the effect of tedisamil on cAMP level in guinea pig hearts in vivo and in vitro in Langendorff preparation. The drug was administered either as a bolus into vena jugularis in dosage 1.0 and 1.5 mg/kg or into the perfusion solution at a concentration of 1.5 × 10-6 mol/l. In additional experiments, this period was followed by brief 10 min global ischemia, induced by clamping of the aorta or perfusion. After 10 min from the onset of tedisamil administration as well as after 10 min of ischemia the ventricular tissue was immediately frozen for cAMP immunoassay Tedisamil caused in normal heart small but significant dose-dependent increase of myocardial cAMP (pmol/mg) level in vivo 1.8 and 2.5 vs. 1.4 as well as in vitro 1.1 vs. 0.8 (p < 0.05) conditions. Ischemia itself induced accumulation of cAMP in both, in vitro and in vitro experiments, 2.6 vs. 1.4 and 1.3 vs. 0.8, respectively. The preischemic elevation of cAMP by tedisamil was not potentiated by following ischemia, on the contrary, decline of the cyclic nucleotide was detected comparing to ischemia itself. In conclusion, tedisamil increased cAMP level in normal heart and prevented additional ischemia-related elevation of this nucleotide. The results indicate modulation of myocardial cAMP level by tedisamil, which may account for its protective effect on gap junctional electrical coupling.

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Authors and Affiliations

  1. Institute for Heart Research, Slovak Academy of Sciences, Bratislava, Slovak Replublic

    Narcis Tribulova, Tanya Ravingerova, Ludmila Okruhlicova, Ivan Gabauer, Dezider Pancza & Jan Slezak

  2. Institute of Endocrinology, Slovak Academy of Sciences, Bratislava, Slovak Replublic

    Maria Fickova

  3. Department of Physiology, Sackler School of Medicine, Tel Aviv, Israel

    Mordechai Manoach

Authors
  1. Narcis Tribulova
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  2. Tanya Ravingerova
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  3. Ludmila Okruhlicova
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  4. Ivan Gabauer
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  5. Maria Fickova
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  6. Dezider Pancza
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  7. Jan Slezak
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  8. Mordechai Manoach
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Tribulova, N., Ravingerova, T., Okruhlicova, L. et al. Modulation of cAMP level by tedisamil in guinea pig heart. Mol Cell Biochem 210, 75–80 (2000). https://doi.org/10.1023/A:1007133322295

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