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This Article Full Text Full Text (PDF) All Versions of this Article: 294/4/H1716    most recent 00945.2007v1 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 ISI Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Google Scholar Articles by Gergs, U. Articles by Neumann, J. PubMed PubMed Citation Articles by Gergs, U. Articles by Neumann, J.

A positive inotropic effect of ATP in the human cardiac atrium

¹Institut für Pharmakologie und Toxikologie and ²Institut für Pharmakologie und Toxikologie, Universitätsklinikum, Westfälische Wilhelms-Universität, Münster; and ³Klinik für Herz- und Thoraxchirugie, Medizinische Fakultät, Martin-Luther-Universität Halle-Wittenberg, Halle, Germany

Submitted 15 August 2007 ; accepted in final form 4 February 2008

We studied contractile effects in isolated electrically driven (1 Hz) atrial preparations from patients undergoing cardiac bypass surgery. ATP concentration dependently (10, 30, and 100 µM) and rapidly decreased force of contraction (negative inotropic effect, NIE) and thereafter more slowly increased force of contraction. The maximum positive inotropic effect (PIE) at 100 µM ATP amounted to 152% of the predrug value (n = 9) and was stable and could be washed out fast and completely. The PIE did not affect time parameters of contraction (time to peak tension and time of relaxation). Moreover, a similar NIE and PIE were noted with adenosine 5'-O-(2-thiotriphosphate) (100 µM). In contrast 2-methyl-thio-ATP did not exert a NIE but only a PIE. In a second set of experiments, preparations were first incubated for 30 min with purinoreceptor antagonists and, in their continuous presence, 100 µM ATP was applied. However, the PIE and NIE of ATP could neither be blocked with suramin (100 and 500 µM), pyridoxalphosphate-6-azophenyl-2',4'-disulfonic acid (50 µM), nor reactive blue 2 (30, 100, and 500 µM), which are known blockers for subtypes of P₂ receptors, or 1,3-dipropyl-cyclopentvl-xanthine (1 and 10 µM), a subtype (A₁ adenosine) P₁ receptor blocker. Likewise, the inhibitor of phospholipase C (PLC) activity (U-73122) and the inhibitor of adenylate cyclase activity (SQ-022563) (10 µM each) failed to affect the NIE and the PIE of ATP. We tentatively suggest that the PIE of ATP might be mediated via P_2X4-like receptors. In summary, we describe a novel biphasic effect of ATP on force contraction in the isolated human atrium. It is conceivable that ATP plays a physiological role in the human heart, for instance, after cardiac injury to sustain contractility.

human heart; right atrium; adenosine 5'-triphosphate; purinoceptor; inotropy