Perturbed and spontaneous regional cerebral blood flow responses to changes in blood pressure after high-level spinal cord injury: the effect of midodrine

Abstract

Individuals with spinal cord injury (SCI) above the T6 spinal segment suffer from orthostatic intolerance. How cerebral blood flow (CBF) responds to orthostatic challenges in SCI is poorly understood. Furthermore, it is unclear how interventions meant to improve orthostatic tolerance in SCI influence CBF. This study aimed to examine 1) the acute regional CBF responses to rapid changes in blood pressure (BP) during orthostatic stress in individuals with SCI and able-bodied (AB) individuals; and 2) the effect of midodrine (alpha1-agonist) on orthostatic tolerance and CBF regulation in SCI. Ten individuals with SCI >T6, and 10 age- and sex-matched AB controls had beat-by-beat BP and middle and posterior cerebral artery blood velocity (MCAv, PCAv, respectively) recorded during a progressive tilt-test to quantify the acute CBF response and orthostatic tolerance. Dynamic MCAv and PCAv to BP relationships were evaluated continuously in the time domain and frequency domain (via transfer function analysis). The SCI group was tested again after administration of 10 mg midodrine to elevate BP. Coherence (i.e., linearity) was elevated in SCI between BP-MCAv and BP-PCAv by 35% and 22%, respectively, compared with AB, whereas SCI BP-PCAv gain (i.e., magnitudinal relationship) was reduced 30% compared with AB (all P < 0.05). The acute (i.e., 0-30 s after tilt) MCAv and PCAv responses were similar between groups. In individuals with SCI, midodrine led to improved PCAv responses 30-60 s following tilt (10 ± 3% vs. 4 ± 2% decline; P < 0.05), and a 59% improvement in orthostatic tolerance (P < 0.01). The vertebrobasilar region may be particularly susceptible to hypoperfusion in SCI, leading to increased orthostatic intolerance.

Keywords: alpha-1 agonist; cerebral autoregulation; orthostatic tolerance.

Figures

Fig. 1.

Illustration of study procedures. A: order of testing; B: tilt-testing protocol.

Fig. 2.

Steady-state hemodynamic responses to tilt: change in mean arterial pressure (MAP), systolic BP (SBP), heart rate (HR), partial pressure of end-tidal carbon dioxide (PetCO2), mean cerebral blood flow velocity of the middle cerebral artery (MCAvmean), mean cerebral blood flow velocity of the posterior cerebral artery (PCAvmean), cerebrovascular conductance of the middle cerebral artery (MCAcvc) and cerebrovascular conductance of the posterior cerebral artery (PCAcvc) in individuals with spinal cord injury (SCI; thin black line), individuals with SCI after midodrine administration (SCImido; thick black line), and able-bodied individuals (AB; thick gray line). Values are expressed as means ± SE. Markers denote significant differences between groups according to independent (SCI vs. AB) and paired samples (SCI vs. SCImido) t-tests (P < 0.05). aSCI supine vs. SCI upright; bSCImido supine vs. SCImido upright; cAB supine vs. AB upright; *SCI vs. SCImido; †AB vs. SCI; ctrend in AB supine vs. AB upright (P < 0.05).

Fig. 3.

Time-domain dynamic responses to tilt: change in MAP, HR, PetCO2, MCAvmean, PCAvmean, MCAcvc, and PCAcvc for 15 s before and 60 s after tilt in SCI (thin black line), SCImido (thick black line), and AB (thick gray line). Values are expressed as means ± SE. Markers denote significant differences between groups according to independent (SCI vs. AB) and paired (SCI vs. SCImido) sample t-tests (P < 0.05). *SCI vs. SCImido; †AB vs. SCI; #AB vs. SCImido. Note: for statistical purposes the 60-s period was binned into two 30-s periods, and the initial 30 s was binned in six 5-s periods of duration. For clarity, the largest SE is presented at the point of occurrence.

Fig. 4.

Orthostatic tolerance in SCI and SCImido. Left: self-reported symptoms of presyncope (0–10 scale) (au, arbitrary units). Note: people who developed presyncope were given a 10/10 for symptom severity at subsequent stages. Right: calculated orthostatic tolerance index (OTi). Significant main effect of midodrine *Significant differences from post hoc t-tests before and after midodrine administration; P < 0.01. Data are presented as means ± SE.