Why do different people with Spinal Cord Injury have differing severity of symptoms with Autonomic Dysreflexia? Exploring relationships of vascular alpha-1 adrenoreceptor and baroreflex sensitivity after SCI.

Introduction: Individuals with spinal cord injury (SCI) commonly have autonomic dysreflexia (AD) with increased sympathetic activity. After SCI, individuals have decreased baroreflex sensitivity and increased vascular responsiveness. Objective: To evalate relationship between baroreflex and blood vessel sensitivity with autonomic dysreflexia symptoms. Design: Case control. Setting: Tertiary academic center. Patients: 14 individuals with SCI, 17 matched uninjured controls. Interventions: All participants quantified AD symptoms using the Autonomic Dysfunction Following SCI (ADFSCI)-AD survey. Participants received three intravenous phenylephrine boluses, reproducibly increasing systolic blood pressure (SBP) 15-40 mmHg. Continuous heart rate (R-R interval, ECG), beat-to-beat blood pressures (finapres), and popliteal artery flow velocity were recorded. Vascular responsiveness (α1 adrenoreceptor sensitivity) and heart rate responsiveness to increased SBP (baroreflex sensitivity) were calculated. Main outcome measures: Baroreflex sensitivity after increased SBP; Vascular responsiveness through quantified mean arterial pressure (MAP) 2-minute area under the curve and change in vascular resistance. Results: SCI and control cohorts were well-matched with mean age 31.9 and 29.6 years (p=0.41), 21.4% and 17.6% female respectively. Baseline MAP (p=0.83) and R-R interval (p=0.39) were similar. ADFSCI-AD scores were higher following SCI (27.9+/-22.9 vs 4.2+/-2.9 in controls, p=0.002).To quantify SBP response, MAP area under the curve was normalized to dose/bodyweight. Individuals with SCI had significantly larger responses (0.26+/-0.19 mmHg*s/kg*ug) than controls (0.06+/-0.06 mmHg*s/kg*ug, p=0.002). Similarly, leg vascular resistance increased after SCI (24% vs 6% to a normalized dose, p=0.007). Baroreflex sensitivity was significantly lower after SCI (15.0+/-8.3 vs 23.7+/-9.3 ms/mmHg, p=0.01). ADFSCI-AD subscore had no meaningful correlation with vascular responsiveness (R Conclusions: While this confirms smaller previous studies suggesting increased α1 adrenoreceptor sensitivity and lower baroreflex sensitivity in individuals with SCI, these differences lacked correlation to increased symptoms of AD. Further research into physiologic mechanisms to explain why some individuals with SCI develop symptoms is needed.