Measures of cardiovascular function suggest autonomic nervous system dysregulation after surgical induction of joint injury in the male Lewis rat

Abstract

Functional changes in the autonomic nervous system may help explain variability in the progression of knee osteoarthritis (OA). Thus, the objective of this study was to evaluate autonomic nervous system shifts, measured via heart rate response variables, in rat knee joint injury and OA models. Cardiovascular characteristics were measured at baseline and bi-weekly for 8 weeks after skin incision, medial collateral ligament transection (MCLT), or MCLT+medial meniscus transection (MCLT+MMT). Heart rate was also assessed during a mild stressor (elevated maze). At endpoint, cardiovascular responses to mechanical knee stimuli were evaluated, as well as responses to 1-phenylbiguanide, a 5HT3A receptor agonist with reported ability to stimulate vagal responses. During low activity, a slower heart rate occurred in MCLT (299±10 bpm) and MCLT+MMT (310±10 bpm) animals compared to controls (325±10 bpm). Furthermore, patellar ligament mechanical stimuli produced an immediate decrease in heart rate and blood pressure in all groups. Finally, a larger drop in heart rate was observed in MCLT (252±40 bpm) and MCLT+MMT (263±49 bpm) following administration of 1-phenylbiguanide compared to skin incision (168±45 bpm). Acute mechanical stimulation of the patellar ligament produced drops in heart rate, suggesting a possible joint-brain connection that modulates autonomic responses. With both joint injury, cardiac vagal activation was altered in response to pharmacological stimulation, with chronic longitudinal heart rate reduction. These data provide some preliminary evidence of potential functional shifts in autonomic nervous system function in models of joint injury and OA.