title: FK506 does not affect cardiac contractility and adrenergic response in vitro.
abstract: FK506 (tacrolimus) is a new immunosuppressant being used in cardiac allograft transplantation. While cyclosporine A has been shown to exert an acute negative inotropic effect on isolated heart muscle preparations, little is known of the inotropic influence of FK506. The Ca(2+) release channel of human skeletal muscle and cardiac muscle is associated with FK506 binding proteins (FKBP), FKBP12 and FKBP12.6, respectively. FKBPs can be dissociated by treatment with FK506. As a consequence of FK506 exposure, isolated skeletal muscle and cardiac muscle ryanodine receptors show altered gating characteristics. Therefore, we analyzed the direct inotropic effect of FK506 exposure to isolated, intact heart muscle preparations from the human and rabbits. Experiments were performed on isolated, electrically stimulated right atrial auricular muscle strips obtained from human myocardium during elective open heart surgery and on intact right ventricular trabeculae from rabbit hearts. The human preparations were exposed to concentrations of 8 x 10(-9), 8 x 10(-8) and 8 x 10(-6) M FK506 followed by a cumulative dose-response curve with isoprenaline as a non-selective beta-adrenoceptor agonist. Our data suggest that FK506 does not exert any positive or negative inotropic effect in either human or rabbit myocardium.
authors.affiliation: Martin-Luther-Universität Halle-Wittenberg, Clinic for Cardiothoracic Surgery, Research Laboratory, Ernst Grube Str. 40, D-06120, Halle an der Saale, Germany. hmilting@hdz-nrw.de
authors.forename: H
authors.initials: H
authors.lastname: Milting
authors.forename: P M
authors.initials: PM
authors.lastname: Janssen
authors.forename: T
authors.initials: T
authors.lastname: Wangemann
authors.forename: H
authors.initials: H
authors.lastname: Kögler
authors.forename: E
authors.initials: E
authors.lastname: Domeier
authors.forename: T
authors.initials: T
authors.lastname: Seidler
authors.forename: K
authors.initials: K
authors.lastname: Hakim
authors.forename: M
authors.initials: M
authors.lastname: Grapow
authors.forename: O
authors.initials: O
authors.lastname: Zeitz
authors.forename: J
authors.initials: J
authors.lastname: Prestle
authors.forename: H R
authors.initials: HR
authors.lastname: Zerkowski
mesh_terms: D000318:Adrenergic beta-Agonists / Q000494:pharmacology*; D000818:Animals; D016275:Atrial Function; D016572:Cyclosporine / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D006325:Heart Atria / Q000187:drug effects; D006352:Heart Ventricles / Q000187:drug effects; D006801:Humans; D007166:Immunosuppressive Agents / Q000494:pharmacology*; D066298:In Vitro Techniques; D007545:Isoproterenol / Q000494:pharmacology*; D009200:Myocardial Contraction / Q000187:drug effects*; D011817:Rabbits; D016559:Tacrolimus / Q000494:pharmacology*; D016276:Ventricular Function
chemical_list: D000318:Adrenergic beta-Agonists; D007166:Immunosuppressive Agents; D016572:Cyclosporine; D007545:Isoproterenol; D016559:Tacrolimus