This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Song, Y. Articles by Belardinelli, L. Search for Related Content PubMed PubMed Citation Articles by Song, Y. Articles by Belardinelli, L. Pubmed/NCBI databases Compound via MeSH Substance via MeSH Medline Plus Health Information Arrhythmia Related Collections Contractile function Arrythmias-basic studies Ischemic biology - basic studies

(Circulation. 2002;105:118.)
© 2002 American Heart Association, Inc.

Basic Science Reports

Selective Attenuation of Isoproterenol-Stimulated Arrhythmic Activity by a Partial Agonist of Adenosine A₁ Receptor

Yejia Song, MD; Lin Wu, MD; John C. Shryock, PhD; Luiz Belardinelli, MD

Department of Medicine, University of Florida, Gainesville (Y.S., L.W., J.C.S.), and CV Therapeutics, Palo Alto, Calif (L.B.).

Correspondence to Yejia Song, PO Box 100277, Department of Medicine, University of Florida, 1600 SW Archer Rd, Gainesville, FL 32610. E-mailsongy{at}medicine.ufl.edu

Background— The goal of this study was to examine the hypothesis that a partial agonist of the adenosine A₁ receptor (A₁AdoR) may cause a greater attenuation of catecholamine-induced ventricular arrhythmic activity than of contractility.

Methods and Results— The effects of CVT-2759 and adenosine, a partial and a full agonist of the A₁AdoR, on isoproterenol-stimulated arrhythmic activity and contractility of guinea pig isolated ventricular myocytes were determined. CVT-2759 (10 µmol/L) and adenosine (10 µmol/L) significantly inhibited isoproterenol-induced arrhythmic activity (aftercontraction and transient inward current) but did not reduce the amplitudes of twitch shortening and L-type Ca²⁺ current. Increasing the concentration of the full agonist adenosine from 10 to 100 µmol/L, however, caused significant attenuation of twitch shortening as well as aftercontractions, whereas increasing the concentration of the partial agonist CVT-2759 from 10 to 100 µmol/L did not. CVT-2759 also significantly inhibited isoproterenol-induced spontaneous ventricular beats in isolated hearts. In contrast to adenosine, CVT-2759 neither activated adenosine-sensitive K⁺ current nor shortened the duration of the atrial APD.

Conclusions— The present results support the hypothesis and suggest a potential role for a partial agonist of the A₁AdoR in the treatment of cardiac arrhythmias.

Key Words: adenosine • arrhythmia • contractility • myocytes

This article has been cited by other articles:

				P. Bartholoma, E. Gorjup, D. Monz, A. Reininger-Mack, H. Thielecke, and A. Robitzki Three-Dimensional In Vitro Reaggregates of Embryonic Cardiomyocytes: A Potential Model System for Monitoring Effects of Bioactive Agents J Biomol Screen, December 1, 2005; 10(8): 814 - 822. [Abstract] [PDF]

				L. Fabritz, P. Kirchhof, L. Fortmuller, J. A Auchampach, H. A Baba, G. Breithardt, J. Neumann, P. Boknik, and W. Schmitz Gene dose-dependent atrial arrhythmias, heart block, and brady-cardiomyopathy in mice overexpressing A3 adenosine receptors Cardiovasc Res, June 1, 2004; 62(3): 500 - 508. [Abstract] [Full Text] [PDF]

				P. Kirchhof, L. Fabritz, L. Fortmuller, G. P. Matherne, A. Lankford, H. A. Baba, W. Schmitz, G. Breithardt, J. Neumann, and P. Boknik Altered sinus nodal and atrioventricular nodal function in freely moving mice overexpressing the A1 adenosine receptor Am J Physiol Heart Circ Physiol, June 5, 2003; 285(1): H145 - H153. [Abstract] [Full Text] [PDF]