title: Effects of rotigaptide (ZP123) on connexin43 remodeling in canine ventricular fibrillation.
abstract: The present study investigated the effects of rotigaptide (ZP123) on the expression, distribution and phosphorylation of connexin43 (Cx43) in myocardial cell membranes in cardioversion of ventricular fibrillation (VF). A model of prolonged VF (8, 12 and 30 min) was established in mongrel dogs (n=8/group), following treatment with ZP123 or normal saline (NS control). A sham control was included. Cardiopulmonary resuscitation was begun at the start of VF followed by defibrillation. Animals received a maximum of three defibrillations of increasing energy (70, 100 and 150 J biphasic shock) as required. The average defibrillation energy, defibrillation success rate, return of spontaneous circulation and survival rate were recorded. Cx43 and phosphorylated (p-)Cx43 expression in cardiomyocyte membranes was detected by western blot and immunofluorescence analyses. Compared with the NS-treated control groups, the success defibrillation rate in the 8-min and 12-min ZP123 groups was significantly higher (P<0.05), while the average defibrillation energy was significantly lower (P<0.05). Cx43 expression in the VF groups was significantly lower than that in the sham control group (P<0.05). Cx43 expression was higher in the 12-min and 30-min ZP123 groups than that in the NS control group (P<0.05), while p-Cx43 expression decreased, although the levels were significantly higher than those in the control groups (P<0.05). Cx43 expression was positively correlated with the defibrillation success rate (r=0.91; P<0.01) and negatively with the mean defibrillation energy (r=-0.854; P<0.01), while p-Cx43 expression was positively correlated with the success rate of the previous three defibrillations (r=0.926; P<0.01).In conclusion, ZP123 reduced Cx43 remodeling through regulating the expression, distribution and phosphorylation of Cx43, thereby reducing the defibrillation energy required for successful cardioversion.
authors.affiliation: Key Laboratory of Cardiovascular Remodeling and Function Research, Chinese Ministry of Education and Chinese Ministry of Health, Department of Cardiology, Qilu Hospital of Shandong University, Jinan, Shandong 250012, P.R. China.
authors.forename: Guo-Ying
authors.initials: GY
authors.lastname: Su
authors.affiliation: Key Laboratory of Cardiovascular Remodeling and Function Research, Chinese Ministry of Education and Chinese Ministry of Health, Department of Cardiology, Qilu Hospital of Shandong University, Jinan, Shandong 250012, P.R. China.
authors.forename: Jing
authors.initials: J
authors.lastname: Wang
authors.affiliation: Key Laboratory of Cardiovascular Remodeling and Function Research, Chinese Ministry of Education and Chinese Ministry of Health, Department of Cardiology, Qilu Hospital of Shandong University, Jinan, Shandong 250012, P.R. China.
authors.forename: Zhen-Xing
authors.initials: ZX
authors.lastname: Xu
authors.affiliation: Department of Cardiology, Jinan Central Hospital Affiliated to Shandong University, Jinan, Shandong 250012, P.R. China.
authors.forename: Xiao-Jun
authors.initials: XJ
authors.lastname: Qiao
authors.affiliation: Key Laboratory of Cardiovascular Remodeling and Function Research, Chinese Ministry of Education and Chinese Ministry of Health, Department of Cardiology, Qilu Hospital of Shandong University, Jinan, Shandong 250012, P.R. China.
authors.forename: Jing-Quan
authors.initials: JQ
authors.lastname: Zhong
authors.affiliation: Key Laboratory of Cardiovascular Remodeling and Function Research, Chinese Ministry of Education and Chinese Ministry of Health, Department of Cardiology, Qilu Hospital of Shandong University, Jinan, Shandong 250012, P.R. China.
authors.forename: Yun
authors.initials: Y
authors.lastname: Zhang
mesh_terms: D000818:Animals; D000889:Anti-Arrhythmia Agents / Q000494:pharmacology*; D016887:Cardiopulmonary Resuscitation; D018031:Connexin 43 / Q000235:genetics* / Q000378:metabolism; D003971:Diastole; D004285:Dogs; D004554:Electric Countershock; D004562:Electrocardiography; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects*; D006352:Heart Ventricles / Q000187:drug effects / Q000378:metabolism / Q000503:physiopathology; D006439:Hemodynamics / Q000187:drug effects; D008297:Male; D032383:Myocytes, Cardiac / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D009842:Oligopeptides / Q000494:pharmacology*; D010766:Phosphorylation; D013599:Systole; D014693:Ventricular Fibrillation / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism / Q000503:physiopathology
chemical_list: D000889:Anti-Arrhythmia Agents; D018031:Connexin 43; D009842:Oligopeptides; C477643:rotigaptide