title: Comparative evaluation of calcium-sensitizing agents, pimobendan and SCH00013, on the myocardial function of canine pacing-induced model of heart failure.
abstract: Pimobendan and SCH00013 are calcium sensitizers that possess dual action of calcium sensitization and phosphodiesterase-III inhibition. This study was conducted to comparatively evaluate the effect of these medications on the myocardial function of the canine pacing-induced heart failure model using echocardiography. Heart failure was induced in 20 dogs, to which pimobendan and two different doses of SCH00013 were administered orally to 15 dogs for 3 weeks, and the remaining 5 dogs served as the control. Cardiac evaluations were performed at baseline, week 1, week 2, and week 3. Significant thinning and dilation of the left ventricles, with systolic dysfunction, indicated by reduction of fractional shortening (FS) and strain values, were observed with a low dose of SCH00013. Whereas, although systolic dysfunction was observed with reduction of FS and radial strain, significant dilation and thinning of the left ventricles and reduction of circumferential strain were not observed with pimobendan. Pimobendan had a potent positive inotropic effect, with little effect on synchronicity, while low-dose SCH00013 had a weaker positive inotropic effect but was able to sustain synchronicity. Although, it failed to show significant statistical differences, the results of this study allow speculations that administration of pimobendan and SCH00013 may have differing effect on the myocardial function in the canine pacinginduced heart failure model.
authors.affiliation: Department of Veterinary Surgery, Tokyo University of Agriculture and Technology, Japan.
authors.forename: Lina
authors.initials: L
authors.lastname: Hamabe
authors.forename: Keisuke
authors.initials: K
authors.lastname: Kawamura
authors.forename: Soo-Min
authors.initials: SM
authors.lastname: Kim
authors.forename: Rieko
authors.initials: R
authors.lastname: Yoshiyuki
authors.forename: Toshiharu
authors.initials: T
authors.lastname: Fukayama
authors.forename: Miki
authors.initials: M
authors.lastname: Shimizu
authors.forename: Ryuji
authors.initials: R
authors.lastname: Fukushima
authors.forename: Ryo
authors.initials: R
authors.lastname: Tanaka
mesh_terms: D000284:Administration, Oral; D000818:Animals; D002118:Calcium / Q000378:metabolism*; D002316:Cardiotonic Agents / Q000008:administration & dosage / Q000494:pharmacology*; D004095:Dihydropyridines / Q000008:administration & dosage / Q000494:pharmacology*; D004108:Dilatation, Pathologic; D004195:Disease Models, Animal; D004285:Dogs; D004452:Echocardiography; D005260:Female; D006333:Heart Failure / Q000000981:diagnostic imaging / Q000188:drug therapy / Q000473:pathology / Q000503:physiopathology*; D006352:Heart Ventricles / Q000000981:diagnostic imaging / Q000473:pathology; D009200:Myocardial Contraction / Q000187:drug effects; D010726:Phosphodiesterase Inhibitors / Q000008:administration & dosage / Q000494:pharmacology*; D011724:Pyridazines / Q000008:administration & dosage / Q000494:pharmacology*; D013268:Stimulation, Chemical; D013599:Systole
chemical_list: D002316:Cardiotonic Agents; D004095:Dihydropyridines; D010726:Phosphodiesterase Inhibitors; D011724:Pyridazines; C115124:Sch 00013; C041648:pimobendan; D002118:Calcium