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.

Hindlimb unloading (HU) in rats, a model of cardiovascular deconditioning, has been found to result in cardiac sympathovagal imbalance. Previous data indicate that derangement in circadian control of heart rate may lead to increased risk for acute cardiac events via alterations in autonomic function. We hypothesized that attenuated circadian control of HR and increased incidence of spontaneous premature ventricular complexes (PVC) would occur over the course of 10–14 days of HU vs casted control (CC) condition. Radiotelemetry probes for electrocardiographic analysis were implanted in male, Sprague‐Dawley rats 10 days prior to manipulations. Data were collected for 5 consecutive minutes at the top of each hour, separated into light and dark cycles and statistically compared. Circadian differences in HR in CC (n=4) and HU (n=6) rats were similar and significantly different over 48h of baseline and 72h of HU adaptation. While loss of this difference and tachycardia occurred initially in both groups, HR and circadian control returned to baseline levels by 6 days in CC rats but not in HU rats. In addition, 27 spontaneous PVCs and one run of salvo were observed in a subset of HU rats (n=3) as compared to only 4 spontaneous PVCs in a subset of CC (n=2) rats. These data indicate that deconditioning leads to loss of circadian control of HR and increased incidence of ventricular arrhythmias, likely due to autonomic dysfunction.