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          Institute: MPI für Herz- und Lungenforschung (W. G. Kerckhoff Institut)     Collection: Publikationen des W. G. Kerckhoff-Instituts     Display Documents



ID: 428375.0, MPI für Herz- und Lungenforschung (W. G. Kerckhoff Institut) / Publikationen des W. G. Kerckhoff-Instituts
Negative inotropic effect of rapamycin on isolated human cardiomyocytes
Authors:Mollmann, H.; Nef, H. M.; Kahlert, P.; Kostin, S.; Mollmann, S.; Weber, M.; Troidl, C.; Hamm, C. W.; Holubarsch, C. J.; Elsasser, A.
Date of Publication (YYYY-MM-DD):2008
Title of Journal:J Int Med Res
Volume:36
Issue / Number:4
Start Page:810
End Page:814
Audience:Not Specified
Abstract / Description:Rapamycin is an increasingly important immunosuppressive drug and reduces restenosis after coronary stenting, but its effects on cardiac contractility are largely unknown. We investigated the acute inotropic effects of rapamycin on isolated human cardiomyocytes. Cardiomyocytes were enzymatically isolated from right atrial appendages obtained during routine coronary artery bypass surgery. Cell morphology was examined by confocal microscopy. Cell contraction was recorded after electrical stimulation. Rapamycin elicited a concentration-dependent decrease in fractional cell shortening ranging from 14.3 +/- 2.6% at 10(-8) M rapamycin to 26.4 +/- 4.2% at 10(-5) M. Rapamycin also caused a concentration-dependent decrease in diastolic cell length. Contractile performance of isolated cardiomyocytes was well preserved, as evidenced by the profound positive inotropic effects of high extracellular calcium concentration and the beta-adrenoreceptor agonist isoproterenol. The acute negative inotropic effect of rapamycin on human cardiomyocytes might be due to altered calcium homeostasis through the binding of rapamycin to FKBP12.6 and its regulatory function on the ryanodine receptor, with increased calcium leakage from the sarcoplasmic reticulum.
Free Keywords:Calcium/metabolism Cell Shape Cells, Cultured Dose-Response Relationship, Drug Humans Immunosuppressive Agents/*pharmacology Myocardial Contraction/*drug effects/physiology Myocytes, Cardiac/cytology/*drug effects/metabolism Sirolimus/*pharmacology
External Publication Status:published
Document Type:Article
Communicated by:N. N.
Affiliations:MPI für physiologische und klinische Forschung
Identifiers:URL:http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=...
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