Effects of midodrine and L-NAME on systemic and cerebral hemodynamics during cognitive activation in spinal cord injury and intact controls

This is the published version.We previously showed that increases in mean arterial pressure (MAP) following administration of midodrine hydrochloride (MH) and nitro-L-arginine methyl ester (L-NAME) resulted in increased mean cerebral blood flow velocity (MFV) during head-up tilt in hypotensive individuals with spinal cord injury (SCI) and question if this same association was evident during cognitive activation. Herein, we report MAP and MFV during two serial subtraction tasks (SSt) given before (predrug) and after (postdrug) administration of MH; (10 mg), L-NAME (1 mg/kg) or no drug (ND) in 15 subjects with SCI compared to nine able-bodied (AB) controls. Three-way factorial analysis of variance (ANOVA) models were used to determine significant main and interaction effects for group (SCI, AB), visit (MH, L-NAME, ND), and time (predrug, postdrug) for MAP and MFV during the two SSt. The three-way interaction was significant for MAP (F = 4.262; P = 0.020); both MH (30 ± 26 mmHg; P < 0.05) and L-NAME (27 ± 22 mmHg; P < 0.01) significantly increased MAP in the SCI group, but not in the AB group. There was a significant visit by time interaction for MFV suggesting an increase from predrug to postdrug following L-NAME (6 ± 8 cm/sec; P < 0.05) and MH (4 ± 7 cm/sec; P < 0.05), regardless of study group, with little change following ND (3 ± 3 cm/sec). The relationship between change in MAP and MFV was significant in the SCI group following administration of MH (r2 = 0.38; P < 0.05) and L-NAME (r2 = 0.32; P < 0.05). These antihypotensive agents, at the doses tested, raised MAP, which was associated with an increase MFV during cognitive activation in hypotensive subjects with SCI

Prevalence of Abnormal Systemic Hemodynamics in Veterans with and without Spinal Cord Injury

Advances in the clinical management of patients with acute and chronic spinal cord injury (SCI) have contributed to extended life expectancies; however longevity in those with SCI remains below that of the general population.(1) Reduced longevity in the SCI population has been attributed to increased incidence of age-associated chronic illnesses,(2) premature cardiovascular aging,(3) and increased prevalence of heart disease, stroke (4) and diabetes mellitus, (5) compared to the general population. In fact, cardiovascular disease (CVD) is now a leading cause of morbidity and mortality in the SCI population, which may be amplified due to increased risk factors such as inactivity, chronic inflammation, and impairment in autonomic cardiovascular control.(6) The American Spinal Injury Association (ASIA) impairment scale (AIS) is used to document remaining motor and sensory function following SCI; (7, 8) however, the degree of autonomic nervous system impairment is not considered within this classification schema.(9, 10) That said, impaired autonomic control of the cardiovascular system after SCI results in measurable changes in heart rate (HR) and blood pressure (BP) that loosely reflect the level and completeness of SCI documented using the AIS classification, (11, 12) but may also reflect orthostatic positioning.(6, 12, 13) The impact of these changes in HR and BP on cardiovascular health and longevity is not fully appreciated in the SCI population; however, prior to identifying the consequences of these cardiovascular abnormalities, prevalence rates of HR and BP values which fall outside the expected normal range should be documented. The International Standards to Document Autonomic Function (post-SCI) initially established guidelines for the assessment of HR and BP abnormalities in 2009, (10) which was updated in 2012, but the thresholds remained consistent. (14) Specifically, bradycardia is defined as a HR ≤ 60 beats/minute (bpm) and tachycardia as a HR ≥ 100 bpm. (14) Hypotension is defined as a systolic BP (SBP) ≤ 90 mmHg and a diastolic BP (DBP) ≤ 60 mmHg; hypertension is SBP ≥ 140 and/or DBP ≥ 90 mmHg. (14) While these definitions comply with standards established in the non-SCI population, due to decentralized cardiovascular control, they may not be appropriate for use in the SCI population. In addition, relatively recent evidence has emerged which associates adverse outcomes in the general population using other HR (15, 16) and BP (17-21) thresholds. Beyond the clinical consequences of alterations in HR and BP, persons with SCI may experience loss of independence and life quality related to the inability to adequately maintain cardiovascular homeostasis; however, until we gain a better understanding of the prevalence of these abnormalities, the development and testing of effective treatment strategies will not be a priority. Therefore, the goal of this investigation was to assess HR and BP in veterans with (SCI) and without SCI (non SCI). Similar to a recent report, (6) we hypothesized that level of SCI (i.e., the higher the lesion level the greater the prevalence of abnormal HR and BP recordings) and orthostatic positioning (i.e., increased prevalence of abnormal HR and BP recordings in the seated versus the supine position) would influence the prevalence of HR and BP abnormalities. In addition, we hypothesized that the prevalence of comorbid cardiovascular medical conditions, current smoking status, age and use of prescription anti-hypertensive (anti-HTN) medications would influence the prevalence of HR and BP abnormalities in veterans with and without SCI

Posteroanterior Cervical Transcutaneous Spinal Cord Stimulation: Interactions with Cortical and Peripheral Nerve Stimulation

Transcutaneous spinal cord stimulation (TSCS) has demonstrated potential to beneficially modulate spinal cord motor and autonomic circuitry. We are interested in pairing cervical TSCS with other forms of nervous system stimulation to enhance synaptic plasticity in circuits serving hand function. We use a novel configuration for cervical TSCS in which the anode is placed anteriorly over ~C4–C5 and the cathode posteriorly over ~T2–T4. We measured the effects of single pulses of TSCS paired with single pulses of motor cortex or median nerve stimulation timed to arrive at the cervical spinal cord at varying intervals. In 13 participants with and 15 participants without chronic cervical spinal cord injury, we observed that subthreshold TSCS facilitates hand muscle responses to motor cortex stimulation, with a tendency toward greater facilitation when TSCS is timed to arrive at cervical synapses simultaneously or up to 10 milliseconds after cortical stimulus arrival. Single pulses of subthreshold TSCS had no effect on the amplitudes of median H-reflex responses or F-wave responses. These findings support a model in which TSCS paired with appropriately timed cortical stimulation has the potential to facilitate convergent transmission between descending motor circuits, segmental afferents, and spinal motor neurons serving the hand. Studies with larger numbers of participants and repetitively paired cortical and spinal stimulation are needed