Comparative Evaluation of Calcium-Sensitizing Agents, Pimobendan and SCH00013, on the Myocardial Function of Canine Pacing–Induced Model of Heart Failure

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...

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Main Authors: Lina Hamabe, Keisuke Kawamura, Soo-min Kim, Rieko Yoshiyuki, Toshiharu Fukayama, Miki Shimizu, Ryuji Fukushima, Ryo Tanaka
Format: Article
Language:English
Published: Elsevier 2014-01-01
Series:Journal of Pharmacological Sciences
Online Access:http://www.sciencedirect.com/science/article/pii/S1347861319301896
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spelling doaj-ff02727745e4490287ed3e6d47ff9e942020-11-25T02:20:56ZengElsevierJournal of Pharmacological Sciences1347-86132014-01-011243386393Comparative Evaluation of Calcium-Sensitizing Agents, Pimobendan and SCH00013, on the Myocardial Function of Canine Pacing–Induced Model of Heart FailureLina Hamabe0Keisuke Kawamura1Soo-min Kim2Rieko Yoshiyuki3Toshiharu Fukayama4Miki Shimizu5Ryuji Fukushima6Ryo Tanaka7Department of Veterinary Surgery, Faculty of Veterinary Medicine, Tokyo University of Agriculture and Technology, Saiwaicho 3-5-8, Fuchu, Tokyo 183-8509, Japan; Corresponding author. linahamabe@vet.ne.jpDepartment of Veterinary Surgery, Faculty of Veterinary Medicine, Tokyo University of Agriculture and Technology, Saiwaicho 3-5-8, Fuchu, Tokyo 183-8509, JapanDepartment of Veterinary Surgery, Faculty of Veterinary Medicine, Tokyo University of Agriculture and Technology, Saiwaicho 3-5-8, Fuchu, Tokyo 183-8509, JapanDepartment of Veterinary Surgery, Faculty of Veterinary Medicine, Tokyo University of Agriculture and Technology, Saiwaicho 3-5-8, Fuchu, Tokyo 183-8509, JapanDepartment of Veterinary Surgery, Faculty of Veterinary Medicine, Tokyo University of Agriculture and Technology, Saiwaicho 3-5-8, Fuchu, Tokyo 183-8509, JapanVeterinary Diagnostic Imaging, Faculty of Veterinary Medicine, Tokyo University of Agriculture and Technology, Saiwaicho 3-5-8, Fuchu, Tokyo 183-8509, JapanDepartment of Veterinary Surgery, Faculty of Veterinary Medicine, Tokyo University of Agriculture and Technology, Saiwaicho 3-5-8, Fuchu, Tokyo 183-8509, JapanDepartment of Veterinary Surgery, Faculty of Veterinary Medicine, Tokyo University of Agriculture and Technology, Saiwaicho 3-5-8, Fuchu, Tokyo 183-8509, JapanPimobendan 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 pacing-induced heart failure model. Keywords:: animal model, calcium sensitizer, echocardiography, heart failure, inotropic agenthttp://www.sciencedirect.com/science/article/pii/S1347861319301896
collection DOAJ
language English
format Article
sources DOAJ
author Lina Hamabe
Keisuke Kawamura
Soo-min Kim
Rieko Yoshiyuki
Toshiharu Fukayama
Miki Shimizu
Ryuji Fukushima
Ryo Tanaka
spellingShingle Lina Hamabe
Keisuke Kawamura
Soo-min Kim
Rieko Yoshiyuki
Toshiharu Fukayama
Miki Shimizu
Ryuji Fukushima
Ryo Tanaka
Comparative Evaluation of Calcium-Sensitizing Agents, Pimobendan and SCH00013, on the Myocardial Function of Canine Pacing–Induced Model of Heart Failure
Journal of Pharmacological Sciences
author_facet Lina Hamabe
Keisuke Kawamura
Soo-min Kim
Rieko Yoshiyuki
Toshiharu Fukayama
Miki Shimizu
Ryuji Fukushima
Ryo Tanaka
author_sort Lina Hamabe
title Comparative Evaluation of Calcium-Sensitizing Agents, Pimobendan and SCH00013, on the Myocardial Function of Canine Pacing–Induced Model of Heart Failure
title_short Comparative Evaluation of Calcium-Sensitizing Agents, Pimobendan and SCH00013, on the Myocardial Function of Canine Pacing–Induced Model of Heart Failure
title_full Comparative Evaluation of Calcium-Sensitizing Agents, Pimobendan and SCH00013, on the Myocardial Function of Canine Pacing–Induced Model of Heart Failure
title_fullStr Comparative Evaluation of Calcium-Sensitizing Agents, Pimobendan and SCH00013, on the Myocardial Function of Canine Pacing–Induced Model of Heart Failure
title_full_unstemmed Comparative Evaluation of Calcium-Sensitizing Agents, Pimobendan and SCH00013, on the Myocardial Function of Canine Pacing–Induced Model of Heart Failure
title_sort comparative evaluation of calcium-sensitizing agents, pimobendan and sch00013, on the myocardial function of canine pacing–induced model of heart failure
publisher Elsevier
series Journal of Pharmacological Sciences
issn 1347-8613
publishDate 2014-01-01
description 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 pacing-induced heart failure model. Keywords:: animal model, calcium sensitizer, echocardiography, heart failure, inotropic agent
url http://www.sciencedirect.com/science/article/pii/S1347861319301896
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