Department of Veterinary Surgery, Tokyo University of Agriculture and Technology, Japan.
J Pharmacol Sci. 2014;124(3):386-93. doi: 10.1254/jphs.13196fp. Epub 2014 Mar 4.
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.
匹莫苯丹和 SCH00013 是钙增敏剂，具有钙增敏和磷酸二酯酶-III 抑制的双重作用。本研究旨在通过超声心动图比较评价这两种药物对犬起搏诱导心力衰竭模型心肌功能的影响。将 20 只犬诱导心力衰竭，其中 15 只犬口服匹莫苯丹和两种不同剂量的 SCH00013，持续 3 周，其余 5 只犬作为对照。在基线、第 1 周、第 2 周和第 3 周进行心脏评估。结果发现，低剂量 SCH00013 可导致左心室明显变薄和扩张，收缩功能障碍，表现为缩短分数（FS）和应变值降低。而匹莫苯丹虽然观察到收缩功能障碍，FS 和径向应变降低，但左心室扩张和变薄以及环向应变降低不明显。匹莫苯丹具有强大的正性肌力作用，对同步性影响较小，而低剂量 SCH00013 的正性肌力作用较弱，但能维持同步性。尽管结果没有显示出显著的统计学差异，但本研究的结果推测，匹莫苯丹和 SCH00013 可能对犬起搏诱导心力衰竭模型的心肌功能有不同的作用。
