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This Article Full Text Full Text (PDF) All Versions of this Article: 293/4/H2148    most recent 00074.2007v1 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 Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Birkenmeier, K. Articles by Felix, S. B. Search for Related Content PubMed PubMed Citation Articles by Birkenmeier, K. Articles by Felix, S. B.

COX-2-dependent and potentially cardioprotective effects of negative inotropic substances released after ischemia

¹Innere Klinik B, Ernst-Moritz-Arndt-Universität, Greifswald, Germany; ²Max-Delbrück-Zentrum, Berlin, Germany; ³Medizinische Klinik mit Schwerpunkt Kardiologie und Angiologie, Charité Campus Mitte, Universitätsmedizin Berlin, Berlin, Germany

Submitted 18 January 2007 ; accepted in final form 18 July 2007

During reperfusion, cardiodepressive factors are released from isolated rat hearts after ischemia. The present study analyzes the mechanisms by which these substances mediate their cardiodepressive effect. After 10 min of global stop-flow ischemia, rat hearts were reperfused and coronary effluent was collected over a period of 30 s. We tested the effect of this postischemic effluent on systolic cell shortening and Ca²⁺ metabolism by application of fluorescence microscopy of field-stimulated rat cardiomyocytes stained with fura-2 AM. Cells were preincubated with various inhibitors, e.g., the cyclooxygenase (COX) inhibitor indomethacin, the COX-2 inhibitors NS-398 and lumiracoxib, the COX-1 inhibitor SC-560, and the potassium (ATP) channel blocker glibenclamide. Lysates of cardiomyocytes and extracts from whole rat hearts were tested for expression of COX-2 with Western blot analysis. As a result, in contrast to nonischemic effluent (control), postischemic effluent induced a reduction of Ca²⁺ transient and systolic cell shortening in the rat cardiomyocytes (P < 0.001 vs. control). After preincubation of cells with indomethacin, NS-398, and lumiracoxib, the negative inotropic effect was attenuated. SC-560 did not influence the effect of postischemic effluent. The inducibly expressed COX-2 was detected in cardiomyocytes prepared for fluorescence microscopy. The effect of postischemic effluent was eliminated with applications of glibenclamide. Furthermore, postischemic effluent significantly reduced the intracellular diastolic and systolic Ca²⁺ increase (P < 0.01 vs. control). In conclusion, the cardiodepressive effect of postischemic effluent is COX-2 dependent and protective against Ca²⁺ overload in the cells.

cyclooxygenase; potassium adenosine 5'-triphosphate channels