Heart rate and blood pressure responses to head‐up tilt following autonomic blockade in persons with SCI and intact controls
Authors: Wecht Jill Maria , Weir Joseph P , Nhuquynh Nguyen , Schilero Gregory J , Bauman William A 
Published: November 2023

Objective

To determine the contribution of cholinergic withdrawal and adrenergic activation on the heart rate (HR) and systolic blood pressure (SBP) responses to head‐up tilt (HUT) in persons with spinal cord injury (SCI), categorized by the level of sympathetic cardiac innervation.

Participants/methods

Fifteen individuals with chronic SCI (13±12years) and 13 age‐matched controls (41±11 vs. 38±12 years, respectively) participated in the study; the SCI group included 8 individuals with high cord lesions (HIGH: C4‐T3) and 7 individuals with low cord lesions (LOW: T5‐L2). All subjects underwent a HUT maneuver to 70° following randomized‐blinded IV administration of: 1) placebo (NS: normal saline), 2) an anticholinergic agent (AntiCh: glycopyrrolate [0.4 mg/kg])and 3) glycopyrrolate in combination with a selective beta‐1 antagonist (AntiCh + BB: glycopyrrolate + esmolol [1.0 mg/kg + maintenance dose of 50 mcg/kg/min]) on separate laboratory visits. We hypothesized that the increase in HR during HUT would be augmented following administration of AntiCh compared to placebo in all 3 groups, and that this response would be attenuated with AntiCh + BB in the controls and individuals with LOW SCI, but not in those with HIGH SCI. Further, the change in SBP with HUT would not be significantly altered by autonomic cardiac blockade, regardless of group.

Design

Supine inter‐beat‐interval (IBI msec) of HR (Impedance Pneumograph, model RESP 1: UFI) and beat‐to‐beat SBP, assessed at the finger arteriole using photoplethysmography (Finometer PRO, Finapres Medical Systems B.V.), were recorded for 5 minutes prior to administration of the study drugs. The HUT maneuver was initiated 7 minutes after drug infusion and IBI and SBP were recorded continuously for 5‐minutes in the HUT position. General linear models (SPSS Version 21.0; IBM Corporation) were constructed to determine significant main (group and drug) and interaction (group × drug) effects for the change in average IBI and SBP from the supine to the HUT position.

Results

The interaction effect for IBI was not significant (p=0.71) reflecting a similar pattern of response among the groups across the three drug conditions. As expected, the main effect for drug was significant (p<0.001, partial eta^2 = 0.53). Subsequent Bonferroni corrected pairwise comparisons indicate a significant increase in HR compared to placebo (10±9 bpm) with AntiCh (33±15 bpm; p<0.0001), which was attenuated by AntiCh + BB (22±11 bpm; p<0.0001). The interaction effect was marginally significant for SBP (p=0.053); therefore, we performed separate analyses to compare each drugs' effect on the SBP response to HUT among the groups. There were no group differences for the change in SBP following placebo or AntiCh administration; however, Tukey post hoc analyses demonstrated a significantly augmented fall in orthostatic SBP following AntiCh + BB administration in the HIGH SCI group (−28.6±28.1 mmHg) compared to the control(5.7±21.5 mmHg; p<0.01) and LOW SCI (−4.3±17.2 mmHg; p<0.05) groups.

Conclusion

Contrary to our hypothesis, we report a similar IBI response to placebo, AntiCh and AntiCh + BB among the groups, suggesting active cholinergic and adrenergic influences on HR during HUT, regardless of the level of SCI. The differential effect of AntiCh + BB on SBP in those with HIGH SCI compared to controls and LOWSCI suggests cardiac cholinergic and adrenergic influences may be important in the maintenance of orthostatic SBP in individuals with lesions above T4.

Support or Funding Information

VA RR&D Service grant # B9212C