Modulation of cAMP level by tedisamil in guinea pig heart

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 examine the effect of tedisamil on cAMP level in gu...

Full description

Saved in:
Bibliographic Details
Published in:Molecular and cellular biochemistry 2000-07, Vol.210 (1-2), p.75-80
Main Authors: Tribulova, N, Ravingerova, T, Okruhlicova, L, Gabauer, I, Fickova, M, Pancza, D, Slezak, J, Manoach, M
Format: Article
Language:English
Subjects:
Animals
Anti-Arrhythmia Agents - pharmacology
Bridged Bicyclo Compounds, Heterocyclic - pharmacology
Cyclic AMP - metabolism
Cyclopropanes - pharmacology
Guinea Pigs
Heart - drug effects
In Vitro Techniques
Ischemia
Male
Myocardial Ischemia - metabolism
Myocardium - metabolism
Citations: Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary: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 examine 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 x 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 vivo 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.
ISSN:0300-8177
1573-4919
DOI:10.1023/A:1007133322295