title: Survival benefit of ghrelin in the heart failure due to dilated cardiomyopathy.
abstract: Although ghrelin has been demonstrated to improve cardiac function in heart failure, its therapeutic efficacy on the life expectancy remains unknown. We aim to examine whether ghrelin can improve the life survival in heart failure using a mouse model of inherited dilated cardiomyopathy (DCM) caused by a deletion mutation ΔK210 in cardiac troponin T (cTnT). From 30 days of age, ghrelin (150 μg/kg) was administered subcutaneously to DCM mice once daily, control mice received saline only. The survival rates were compared between the two groups for 30 days. After 30-day treatment, functional and morphological measurements were conducted. Ghrelin-treated DCM mice had significantly prolonged life spans compared with saline-treated control DCM mice. Echocardiography showed that ghrelin reduced left ventricular (LV) end-diastolic dimensions and increased LV ejection fraction. Moreover, histoanatomical data revealed that ghrelin decreased the heart-to-body weight ratio, prevented cardiac remodeling and fibrosis, and markedly decreased the expression of brain natriuretic peptide. Telemetry recording and heart rate variability analysis showed that ghrelin suppressed the excessive cardiac sympathetic nerve activity (CSNA) and recovered the cardiac parasympathetic nerve activity. These results suggest that ghrelin has therapeutic benefits for survival as well as for the cardiac function and remodeling in heart failure probably through suppression of CSNA and recovery of cardiac parasympathetic nerve activity.
authors.affiliation: Department of Cardiac Physiology, National Cerebral and Cardiovascular Center Research Institute Osaka, Japan.
authors.forename: Cheng-Kun
authors.initials: CK
authors.lastname: Du
authors.affiliation: Department of Cardiac Physiology, National Cerebral and Cardiovascular Center Research Institute Osaka, Japan.
authors.forename: Dong-Yun
authors.initials: DY
authors.lastname: Zhan
authors.affiliation: Department of Clinical Pharmacology, Graduate School of Medical Sciences, Kyushu University Fukuoka, Japan.
authors.forename: Sachio
authors.initials: S
authors.lastname: Morimoto
authors.affiliation: Department of Cardiac Physiology, National Cerebral and Cardiovascular Center Research Institute Osaka, Japan.
authors.forename: Tsuyoshi
authors.initials: T
authors.lastname: Akiyama
authors.affiliation: Department of Physiology, University of Otago Otago, New Zealand.
authors.forename: Daryl O
authors.initials: DO
authors.lastname: Schwenke
authors.affiliation: Department of Regenerative Medicine and Tissue Engineering, National Cerebral and Cardiovascular Center Research Institute Osaka, Japan.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Hosoda
authors.affiliation: Department of Biochemistry, National Cerebral and Cardiovascular Center Research Institute Osaka, Japan.
authors.forename: Kenji
authors.initials: K
authors.lastname: Kangawa
authors.affiliation: Department of Cardiac Physiology, National Cerebral and Cardiovascular Center Research Institute Osaka, Japan.
authors.forename: Mikiyasu
authors.initials: M
authors.lastname: Shirai
keywords: Ghrelin; heart failure; inherited dilated cardiomyopathy; knock-in mouse; sudden cardiac death; survival