title: Hindlimb unloading results in increased predisposition to cardiac arrhythmias and alters left ventricular connexin 43 expression.
abstract: Hindlimb unloading (HU) is a well-established animal model of cardiovascular deconditioning. Previous data indicate that HU results in cardiac sympathovagal imbalance. It is well established that cardiac sympathovagal imbalance increases the risk for developing cardiac arrhythmias. The cardiac gap junction protein connexin 43 (Cx43) is predominately expressed in the left ventricle (LV) and ensures efficient cell-to-cell electrical coupling. In the current study we wanted to test the hypothesis that HU would result in increased predisposition to cardiac arrhythmias and alter the expression and/or phosphorylation of LV-Cx43. Electrocardiographic data using implantable telemetry were obtained over a 10- to 14-day HU or casted control (CC) condition and in response to a sympathetic stressor using isoproterenol administration and brief restraint. The arrhythmic burden was calculated using a modified scoring system to quantify spontaneous and provoked arrhythmias. In addition, Western blot analysis was used to measure LV-Cx43 expression in lysates probed with antibodies directed against the total and an unphosphorylated form of Cx43 in CC and HU rats. HU resulted in a significantly greater total arrhythmic burden during the sympathetic stressor with significantly more ventricular arrhythmias occurring. In addition, there was increased expression of total LV-Cx43 observed with no difference in the expression of unphosphorylated LV-Cx43. Specifically, the increased expression of LV-Cx43 was consistent with the phosphorylated form. These data taken together indicate that cardiovascular deconditioning produced through HU results in increased predisposition to cardiac arrhythmias and increased expression of phosphorylated LV-Cx43.
authors.affiliation: Department of Physiology and Pharmacology, Des Moines University, 3200 Grand Ave., Des Moines, IA 50312, USA. moffitt.julie@gmail.com
authors.forename: Julia A
authors.initials: JA
authors.lastname: Moffitt
authors.forename: Matthew K
authors.initials: MK
authors.lastname: Henry
authors.forename: Kathryn C
authors.initials: KC
authors.lastname: Welliver
authors.forename: Amanda J
authors.initials: AJ
authors.lastname: Jepson
authors.forename: Emily R
authors.initials: ER
authors.lastname: Garnett
mesh_terms: D000818:Animals; D000906:Antibodies / Q000494:pharmacology; D001145:Arrhythmias, Cardiac / Q000175:diagnosis / Q000209:etiology* / Q000503:physiopathology*; D001794:Blood Pressure / Q000502:physiology; D018031:Connexin 43 / Q000276:immunology / Q000378:metabolism*; D004195:Disease Models, Animal; D004562:Electrocardiography; D006339:Heart Rate / Q000502:physiology; D006352:Heart Ventricles / Q000378:metabolism; D019417:Hindlimb Suspension / Q000502:physiology*; D008297:Male; D009206:Myocardium / Q000378:metabolism; D010766:Phosphorylation / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley; D013564:Sympathetic Nervous System / Q000503:physiopathology; D013617:Tachycardia, Supraventricular / Q000175:diagnosis / Q000209:etiology / Q000503:physiopathology; D017180:Tachycardia, Ventricular / Q000175:diagnosis / Q000209:etiology / Q000503:physiopathology; D014630:Vagus Nerve / Q000503:physiopathology; D014693:Ventricular Fibrillation / Q000175:diagnosis / Q000209:etiology / Q000503:physiopathology
chemical_list: D000906:Antibodies; D018031:Connexin 43; C580592:Gja1 protein, rat