2010 Fiscal Year Final Research Report

Granulocyte-Colony Stimulating Factor Administration Reduced the Inducibility of Ventricular Tachyarrhythmias in mouse model

Research Project

Project/Area Number	21791762
Research Category	Grant-in-Aid for Young Scientists (B)
Allocation Type	Single-year Grants
Research Field	Emergency medicine
Research Institution	University of Tsukuba
Principal Investigator	SHIMOJO Nobutake University of Tsukuba, 大学院・人間総合科学研究科, 講師 (20462210)
Project Period (FY)	2009 – 2010
Keywords	致死性不整脈治療
Research Abstract	Cardiac hypertrophy is an in dependent risk factor for sudden cardiac death from ventricular tachyarrhythmias (VTa). Granulocyte-colony stimulating factor (G-CSF) has recently been reported to suppress VTa after myocardial infarction by modulating the function of gap junctions between cardiomyocytes via maintaining Connexin-43 (Cx43). We hypothesized that the G-CSF could also regress an enhanced vulnerability to VTa in the cardiac hypertrophy without ischemic fibrosis through regulating Cx43. We used Dahl salt-sensitive rats as LVH models. The inducibility of VTa by rapid ventricular burst pacing was decreased in G-CSF administration groups compared to vehicles. Expression levels of phosphorylated Cx43 was increased in G-CSF administerd rat hearts by western blotting. We demonstrated that the G-CSF administration ameliorated the electrophysiological stability in the rat model of cardiac hypertrophy by modulating the function of gap junctions through accelerating phosphorylation of Cx43. Theses results warrant carefully designed clinical studies.