Effects of relaxin on cardiac fibrosis, apoptosis, and tachyarrhythmia in rats with myocardial infarction.
Relaxin is safe and efficient to use for treating acute heart failure. However, the electrophysiological and arrhythmogenic effects of relaxin in an experimental healing infarction model remain unknown. In this study, a rat model with myocardial infarction (MI) received relaxin (0.5mg/kg per day) or vehicle (sodium acetate) infusion via implantable mini-pumps for 2 weeks. Thereafter, hemodynamic measurement, electrophysiological study, histological examination, and immunofluorescence labeling were performed. Relaxin treatment significantly attenuated tachyarrhythmia inducibility and cardiac dysfunction in healing infarcted heart. Epicardial monophasic action potentials showed that relaxin significantly reduced the dispersion of action potential duration in postinfarcted hearts. Histological study revealed that relaxin significantly reduced myocardial apoptosis and cardiac fibrotic collagen deposition. Western blot revealed that relaxin treatment significantly suppressed the protein expression levels of TGFβ1, α-SMA, and type I collagen. Furthermore, abnormal alterations of Connexin 43, including reduction and lateralization, were significantly attenuated by relaxin treatment at the infarcted border zone. This study provides strong evidence that continuous relaxin intervention ameliorates cardiac fibrosis and apoptosis, attenuates remodeling of gap junction and focal heterogeneity of repolarization, and reduces vulnerability to tachyarrhythmias.
Department of Gerontology, Yijishan Hospital Affiliated to Wannan Medical College, Wuhu 241001, PR China. Electronic address: Wangdeguo@medmail.com.cn.
Deguo
D
Wang
Department of Cardiology, Anhui Provincial Hospital Affiliated to Anhui Medical University, Hefei 230001, PR China.
Hongjun
H
Zhu
Department of Gerontology, Yijishan Hospital Affiliated to Wannan Medical College, Wuhu 241001, PR China.
Qing
Q
Yang
Department of Gerontology, Yijishan Hospital Affiliated to Wannan Medical College, Wuhu 241001, PR China.
Yirun
Y
Sun
D000200:Action Potentials / Q000187:drug effects; D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D018031:Connexin 43 / Q000378:metabolism; D004562:Electrocardiography; D005355:Fibrosis; D006439:Hemodynamics / Q000187:drug effects; D006801:Humans; D008297:Male; D009203:Myocardial Infarction / Q000000981:diagnostic imaging / Q000188:drug therapy* / Q000473:pathology* / Q000503:physiopathology; D009206:Myocardium / Q000473:pathology; D032383:Myocytes, Cardiac / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D017207:Rats, Sprague-Dawley; D012065:Relaxin / Q000494:pharmacology* / Q000627:therapeutic use*; D016019:Survival Analysis; D013610:Tachycardia / Q000000981:diagnostic imaging / Q000188:drug therapy* / Q000473:pathology* / Q000503:physiopathology
D018031:Connexin 43; D012065:Relaxin
Apoptosis; Connexin; Fibrosis; Gap junction; Relaxin; Ventricular arrhythmia