Relation of forward and backward traveling pressure waves with subclinical carotid artery wall remodeling and central pulse pressure.

Central pulse pressure (PP) is the sum of forward and backward traveling pressure waves that have been associated with cardiovascular disease (CVD) risk. However, previous studies have reported differential findings regarding the importance of the forward versus the backward wave for CVD risk. Therefore, we sought to determine the degree to which the forward and backward pressure waves are associated with subclinical carotid artery wall remodeling and central PP in healthy adults. Using applanation tonometry, carotid pressure waveforms were acquired in 308 healthy individuals (aged 45 ± 17 years, range 19-80 years, 61% women), from which the time integral of the forward (PfTI) and backward (PbTI) pressure waves were derived via pressure-only wave separation analysis. Common carotid artery intima-media thickness (cIMT), a biomarker of subclinical CVD risk, was derived via B-mode ultrasonography measured ∼2 cm from the carotid bulb. Both PfTI (r = 0.31, P < 0.001) and PbTI (r = 0.40, P < 0.001) were correlated with cIMT. However, further analysis revealed that PbTI mediated the relation between PfTI and cIMT (proportion mediated = 156%, P < 0.001). The association between PbTI and cIMT remained after adjusting for age, sex, body mass index, blood glucose, low-density lipoprotein cholesterol, heart rate, brachial systolic pressure, and aortic stiffness (B = 0.02, 95% confidence interval = 0.01, 2.77, P < 0.001). Both PfTI (r = -0.58, P < 0.001) and PbTI (r = -0.50, P < 0.001) were correlated with central PP, however, PfTI fully mediated the association between PbTI and central PP (proportion mediated = 124%, P < 0.001). Although PfTI is correlated with higher central PP, it is PbTI that is directly associated with carotid artery wall remodeling.NEW & NOTEWORTHY The present study contributes to the growing body of evidence highlighting the physiological and clinical insight provided by the pulsatile hemodynamic components of central artery pulse pressure. The notable findings of this study are: 1) The reflected (backward) pressure wave is associated with carotid intima-media thickness independent of traditional cardiovascular risk factors, including systolic blood pressure and aortic stiffness. 2) The incident (forward) pressure wave, and not the reflected pressure wave, is associated with greater central pulse pressure.

Low- and high-frequency spinal cord stimulation and arterial blood pressure in patients with chronic pain and hypertension: a retrospective study.

PURPOSE: Evidence suggests that traditional low-frequency spinal cord stimulation (LF-SCS) reduces arterial blood pressure (BP) in patients with chronic pain and hypertension independent of improved pain symptoms. However, it remains unclear whether high-frequency spinal cord stimulation (HF-SCS) also lowers BP in chronic pain patients with hypertension. Therefore, in a retrospective study design, we tested the hypothesis that clinic BP would be significantly reduced following implantation of HF-SCS in patients with chronic pain and hypertension. METHODS: Clinic BP within 3 months before and after surgical implantation of either a LF-SCS or HF-SCS device between 2010 and 2020 were collected from electronic medical records at The University of Kansas Health System (TUKHS). RESULTS: A total of 132 patients had available records of clinic BP (64 ± 13 years of age). Patients with hypertension (n = 32) demonstrated a significantly greater reduction in systolic BP (-8 ± 12 versus 2 ± 9 mmHg, P < 0.001) following implantation compared with normotensive patients (n = 100). Importantly, the change in BP was inversely related to baseline BP independent of age and sex following implantation of HF-SCS (n = 70, R = -0.50, P < 0.001) or LF-SCS (n = 62, R = -0.42, P = 0.001). Higher pain scores before implantation were not associated with reduction in systolic BP (R = 0.10, P = 0.43) or diastolic BP (R = -0.08, P = 0.53) (n = 69) after implantation. CONCLUSION: These findings confirm previous studies showing reduced BP following implantation of LF-SCS in patients with chronic pain and hypertension and provide novel data regarding reduced BP following implantation of newer generation HF-SCS devices.

Sex-specific associations of reservoir-excess pressure parameters with age and subclinical vascular remodeling.

OBJECTIVE: Central artery reservoir pressure and excess pressure (XSP) are associated with cardiovascular disease (CVD) events and mortality. However, sex differences in the trajectory of central reservoir pressure and XSP with advancing age and their relations with vascular markers of subclinical CVD risk are incompletely understood. Therefore, we tested the hypothesis that central reservoir pressure and XSP would be positively associated with advancing age and vascular markers of subclinical CVD risk in men and women. METHOD: Healthy adults ( n  = 398; aged 18-80 years, 60% female individuals) had central (carotid) artery pressure waveforms acquired by applanation tonometry. Reservoir pressure and XSP peaks and integrals were derived retrospectively from carotid pressure waveforms using custom written software. Carotid artery intimal-medial thickness (IMT) was measured by ultrasonography, and aortic stiffness was determined from carotid-femoral pulse wave velocity (cfPWV). RESULTS: Reservoir pressure peak, reservoir pressure integral and XSP integral were higher with age in both men and women ( P  < 0.05), whereas XSP peak was lower with age in men ( P  < 0.05). In women, both reservoir pressure peak ( ß â€Š= 0.231, P  < 0.01) and reservoir pressure integral ( ß â€Š= 0.254, P  < 0.01) were associated with carotid artery IMT, and reservoir pressure peak was associated with cfPWV ( ß â€Š= 0.120, P  = 0.02) after adjusting for CVD risk factors. CONCLUSION: Central artery reservoir pressure and XSP were higher with advancing age in men and women, and reservoir pressure peak was associated with both carotid artery wall thickness and aortic stiffness in women but not men. Central reservoir pressure peak may provide some insight into sex differences in vascular remodeling and subclinical CVD risk with advancing age in healthy adults.

Concomitantly higher resting arterial blood pressure and transduction of sympathetic neural activity in human obesity without hypertension.

OBJECTIVE: Central (abdominal) obesity is associated with elevated adrenergic activity and arterial blood pressure (BP). Therefore, we tested the hypothesis that transduction of spontaneous muscle sympathetic nerve activity (MSNA) to BP, that is, sympathetic transduction, is augmented in abdominal obesity (increased waist circumference) and positively related to prevailing BP. METHODS: Young/middle-aged obese (32 ±â€Š7 years; BMI: 36 ±â€Š5 kg/m2, n = 14) and nonobese (29 ±â€Š10 years; BMI: 23 ±â€Š4 kg/m2, n = 14) without hypertension (24-h ambulatory average BP < 130/80 mmHg) were included. MSNA (microneurography) and beat-to-beat BP (finger cuff) were measured continuously and the increase in mean arterial pressure (MAP) during 15 cardiac cycles following MSNA bursts of different patterns (single, multiples) and amplitude (quartiles) was signal-averaged over a 10 min baseline period. RESULTS: MSNA burst frequency was not significantly higher in obese vs. nonobese (21 ±â€Š3 vs. 17 ±â€Š3 bursts/min, P = 0.34). However, resting supine BP was significantly higher in obese compared with nonobese (systolic: 127 ±â€Š3 vs. 114 ±â€Š3; diastolic: 76 ±â€Š2 vs. 64 ±â€Š1 mmHg, both P < 0.01). Importantly, obese showed greater increases in MAP following multiple MSNA bursts (P = 0.02) and MSNA bursts of higher amplitude (P = 0.02), but not single MSNA bursts (P = 0.24), compared with nonobese when adjusting for MSNA burst frequency. The increase in MAP following higher amplitude bursts among all participants was associated with higher resting supine systolic (R = 0.48; P = 0.01) and diastolic (R = 0.48; P = 0.01) BP when controlling for MSNA burst frequency, but not when also controlling for waist circumference (P > 0.05). In contrast, sympathetic transduction was not correlated with 24-h ambulatory average BP. CONCLUSION: Sympathetic transduction to BP is augmented in abdominal obesity and positively related to higher resting supine BP but not 24-h ambulatory average BP.

One-day acceptance and commitment therapy (ACT) workshop improves anxiety but not vascular function or inflammation in adults with moderate to high anxiety levels in a randomized controlled trial.

OBJECTIVE: Acceptance and Commitment Therapy (ACT) is a behavioral intervention demonstrating sustained improvements in anxiety in individuals with chronic anxiety and psychological distress. Because anxiety disorders are associated with the development of cardiovascular disease (CVD), we hypothesized that a novel 1-day ACT workshop would both lower anxiety and improve vascular function in persons with moderate/high anxiety. METHODS: In a randomized controlled study, 72 adults (age 33.9 ± 8.6 (SD) years) with baseline moderate/high anxiety completed a one-day ACT intervention (n = 44, age 33.9 ± 8.7 years) or control (n = 28, age 37.1 ± 10.1 years). Pre-specified secondary outcomes were measured over 12 weeks: aortic stiffness (carotid-femoral pulse wave velocity [cfPWV]), forearm vascular endothelial function (post-ischemic peak forearm blood flow [FBF] via plethysmography), and brachial artery flow-mediated dilation (FMD). Carotid artery stiffness (ß-stiffness index), and inflammatory markers (C-reactive protein and tumor necrosis factor-alpha) were also explored. RESULTS: Although the intervention had a significant and sustained effect on the primary outcome of anxiety as measured by the Beck Anxiety Inventory, the 1-day ACT workshop was not associated with improvement in vascular or inflammatory endpoints. The intervention was unexpectedly associated with increases in ß-stiffness index that were also associated with changing trait anxiety. CONCLUSION: Anxiety improvements did not translate into improvements in any of the vascular function outcomes. This may reflect a less-than-robust effect of the intervention on anxiety, failure in design to select those with vascular dysfunction, or not intervening on a relevant causal pathway. (Trial registration NCT02915874 at www.clinicaltrials.gov).

Dissociation between reduced pain and arterial blood pressure following epidural spinal cord stimulation in patients with chronic pain: A retrospective study.

PURPOSE: Acute pain and resting arterial blood pressure (BP) are positively correlated in patients with chronic pain. However, it remains unclear whether treatment for chronic pain reduces BP. Therefore, in a retrospective study design, we tested the hypothesis that implantation of an epidural spinal cord stimulator (SCS) device to treat chronic pain would significantly reduce clinic pain ratings and BP and that these reductions would be significantly correlated. METHODS: Pain ratings and BP in medical records were collected before and after surgical implantation of a SCS device at the University of Iowa Hospitals and Clinics between 2008 and 2018 (n = 213). RESULTS: Reductions in pain rating [6.3 ± 2.0 vs. 5.0 ± 1.9 (scale: 0-10), P < 0.001] and BP [mean arterial pressure (MAP) 95 ± 10 vs. 89 ± 10 mmHg, P < 0.001] were statistically significant within 30 days of SCS. Interestingly, BP returned toward baseline within 60 days following SCS implantation. Multiple linear regression analysis showed that sex (P = 0.007), baseline MAP (P < 0.001), and taking hypertension (HTN) medications (P < 0.001) were significant determinants of change in MAP from baseline (Δ MAP) (model R2 = 0.33). After statistical adjustments, Δ MAP was significantly greater among women than among men ( - 7.2 ± 8.5 vs. - 3.9 ± 8.5 mmHg, P = 0.007) and among patients taking HTN medications than among those not taking hypertension medications ( - 10.1 ± 8.7 vs. - 3.9 ± 8.5 mmHg, P < 0.001), despite no group differences in change in pain ratings. CONCLUSIONS: Together, these findings suggest that SCS for chronic pain independently produces clinically meaningful, albeit transient, reductions in BP and may provide a rationale for studies aimed at reducing HTN medication burden among this patient population.

CORP: Standardizing methodology for assessing spontaneous baroreflex control of muscle sympathetic nerve activity in humans.

The use of spontaneous bursts of muscle sympathetic nerve activity (MSNA) to assess arterial baroreflex control of sympathetic nerve activity has seen increased utility in studies of both health and disease. However, methods used for analyzing spontaneous MSNA baroreflex sensitivity are highly variable across published studies. Therefore, we sought to comprehensively examine methods of producing linear regression slopes to quantify spontaneous MSNA baroreflex sensitivity in a large cohort of subjects (n = 150) to support a standardized procedure for analysis that would allow for consistent and comparable results across laboratories. The primary results demonstrated that 1) consistency of linear regression slopes was considerably improved when the correlation coefficient was above -0.70, which is more stringent compared with commonly reported criterion of -0.50, 2) longer recording durations increased the percentage of linear regressions producing correlation coefficients above -0.70 (1 min = 15%, 2 min = 28%, 5 min = 53%, 10 min = 67%, P < 0.001) and reaching statistical significance (1 min = 40%, 2 min = 69%, 5 min = 78%, 10 min = 89%, P < 0.001), 3) correlation coefficients were improved with 3-mmHg versus 1-mmHg and 2-mmHg diastolic blood pressure (BP) bin size, and 4) linear regression slopes were reduced when the acquired BP signal was not properly aligned with the cardiac cycle triggering the burst of MSNA. In summary, these results support the use of baseline recording durations of 10 min, a correlation coefficient above -0.70 for reliable linear regressions, 3-mmHg bin size, and importance of properly time-aligning MSNA and diastolic BP. Together, these findings provide best practices for determining spontaneous MSNA baroreflex sensitivity under resting conditions for improved rigor and reproducibility of results.

Beat-to-Beat Blood Pressure Variability in the First Trimester Is Associated With the Development of Preeclampsia in a Prospective Cohort: Relation With Aortic Stiffness.

Women with preeclampsia, a hypertensive disorder of pregnancy, exhibit greater beat-to-beat blood pressure variability (BPV) in the third trimester after clinical onset of the disorder. However, it remains unknown whether elevated BPV precedes the development of preeclampsia. A prospective study cohort of 139 women (age 30.2±4.0 years) were enrolled in early pregnancy (<14 weeks gestation). BPV was quantified by time domain analyses of 10-minute continuous beat-to-beat blood pressure recordings via finger photoplethysmography in the first, second, and third trimesters. Aortic stiffness (carotid-femoral pulse wave velocity) and spontaneous cardiovagal baroreflex sensitivity were also measured each trimester. Eighteen women (13%) developed preeclampsia. Systolic BPV was higher in all trimesters among women who developed versus did not develop preeclampsia (first: 4.8±1.3 versus 3.7±1.2, P=0.001; second: 5.1±1.8 versus 3.8±1.1, P=0.02; third: 5.2±0.8 versus 4.0±1.1 mm Hg, P=0.002). Elevated first trimester systolic BPV was associated with preeclampsia (odds ratio, 1.94 [95% CI, 1.27-2.99]), even after adjusting for risk factors (age, body mass index, systolic blood pressure, history of preeclampsia, and diabetes mellitus) and was a significant predictor of preeclampsia (area under the receiver operator characteristic curve=0.75±0.07; P=0.002). Carotid-femoral pulse wave velocity was elevated in the first trimester among women who developed preeclampsia (5.9±0.8 versus 5.2±0.8 m/s; P=0.002) and was associated with BPV after adjustment for mean blood pressure (r=0.26; P=0.005). First trimester baroreflex sensitivity did not differ between groups (P=0.23) and was not related to BPV (P=0.36). Elevated systolic BPV is independently associated with the development of preeclampsia as early as the first trimester, possibly mediated in part by higher aortic stiffness.

Aortic stiffness is associated with changes in retinal arteriole flow pulsatility mediated by local vasodilation in healthy young/middle-age adults.

Aortic stiffness is associated with augmented pressure pulsatility in large conduit arteries and remodeling of the microcirculation. However, studies in humans examining the relation between aortic stiffness and end-organ microvascular flow pulsatility are limited. Therefore, we used the retinal microvasculature as an end-organ in vivo model to examine the hypothesis that aortic stiffness would be positively associated with microvascular flow pulsatility index (PI) (flow pulse amplitude/mean flow) in humans. In 40 young/middle-age healthy adults (25-60 yr old, 50% women), aortic stiffness (carotid-femoral pulse wave velocity, CFPWV) and retinal arteriole flow (laser speckle flowgraphy) were examined at rest and during metabolic vasodilation (light flicker). CFPWV and related increases in central pulse pressure (PP) were inversely correlated with arteriole lumen diameter independent of age (CFPWV: R = -0.52, P = 0.001; Central PP: R = -0.39, P = 0.014). Accordingly, microvascular resistance was positively related to CFPWV independent of age (R = 0.35, P = 0.031). Multiple linear regression showed that CFPWV was not a significant determinant of resting arteriole flow PI (ß = -0.10, P = 0.64). However, during reduced retinal microvascular resistance using light flicker (P < 0.001), CFPWV was a significant determinant of the percent change in arteriole flow PI (ß = 0.58, P = 0.046), but not mean flow (ß = -0.17, P = 0.54), where reductions in arteriole flow PI were associated with lower CFPWV. In summary, our findings suggest that higher aortic stiffness and the related increase in central PP in healthy young/middle-age adults are associated with retinal arteriole narrowing and smaller reductions in arteriole flow pulsatility in response to dynamic conditions such as local metabolic vasodilation.NEW & NOTEWORTHY By using the human retinal microvasculature as an end-organ in vivo model, we confirm that aortic stiffness and related increases in central pulse pressure are inversely correlated with retinal arteriole lumen diameter and increased microvascular resistance among heathy young/middle-age adults. Additionally, higher aortic stiffness is not associated with excessive flow pulsatility in the retinal microvasculature under tonic conditions but may be related to limited reductions in retinal arteriole flow pulsatility in response to local vasodilation.

Augmented pressor and sympathoexcitatory responses to the onset of isometric handgrip in patients with type 2 diabetes.

Patients with type 2 diabetes (T2D) exhibit greater daytime blood pressure (BP) variability, increasing their cardiovascular risk. Given the number of daily activities that incorporate short-duration isometric muscle contractions (e.g., carrying groceries), herein we investigated BP and muscle sympathetic nerve activity (MSNA) responses at the onset of isometric handgrip (HG). We tested the hypothesis that, relative to control subjects, patients with T2D would exhibit exaggerated pressor and MSNA responses to the immediate onset of HG. Mean arterial pressure (MAP) and MSNA were quantified during the first 30 s of isometric HG at 30% and 40% of maximal voluntary contraction (MVC) and during a cold pressor test (CPT), a nonexercise sympathoexcitatory stimulus. The onset of 30% MVC HG evoked similar increases in MAP between groups (P = 0.17); however, the increase in MSNA was significantly greater in patients with T2D versus control subjects with the largest group difference at 20 s (P < 0.001). At the onset of 40% MVC HG, patients with T2D demonstrated greater increases in MAP (e.g., 10 s, T2D: 9 ± 1 mmHg, controls: 5 ± 2 mmHg; P = 0.04). MSNA was also greater in patients with T2D at 40% MVC onset but differences were only significant at the 20-30 s timepoint (T2D: 15 ± 3 bursts/min, controls: -2 ± 4 bursts/min; P < 0.001). Similarly, MAP and MSNA responses were augmented during the onset of CPT in T2D patients. These findings demonstrate exaggerated pressor and MSNA reactivity in patients with T2D, with rapid and robust responses to both isometric contractions and cold stress. This hyper-responsiveness may contribute to daily surges in BP in patients with T2D, increasing their short-term and long-term cardiovascular risk.

Sex and age differences in the association between sympathetic outflow and central elastic artery wall thickness in humans.

Aging is characterized by increased wall thickness of the central elastic arteries (i.e., aorta and carotid arteries), although the mechanisms involved are unclear. Evidence suggests that age-related increases in muscle sympathetic nerve activity (MSNA) may be a contributing factor. However, studies in humans have been lacking. Therefore, we tested the hypothesis that age-related increases in MSNA would be independently associated with carotid artery intima-media thickness (IMT) but not in young women given the reduced influence of MSNA on the vasculature in this group. In 93 young and middle-age/older (MA/O) adults (19-73 yr, 41 women), we performed assessments of MSNA (microneurography) and common carotid IMT and lumen diameter (ultrasonography). Multiple regression that included MSNA and other cardiovascular disease risk factors indicated that MSNA (P = 0.002) and 24-h systolic blood pressure (BP) (P = 0.024) were independent determinants of carotid IMT-to-lumen ratio (model R2 = 0.38, P < 0.001). However, when examining only young women (<45 yr), no correlation was observed between MSNA and carotid IMT-to-lumen ratio (R = -0.01, P = 0.963). MSNA was significantly correlated with IMT-to-lumen ratio while controlling for 24-h systolic BP among young men (R = 0.49, P < 0.001) and MA/O women (R = 0.59, P = 0.022). However, among MA/O men, controlling for 24-h systolic BP attenuated the association between MSNA and carotid IMT-to-lumen ratio (R = 0.50, P = 0.115). Significant age differences in IMT-to-lumen ratio between young and MA/O men (P = 0.047) and young and MA/O women (P = 0.023) were removed when adjusting for MSNA (men: P = 0.970; women: P = 0.152). These findings demonstrate an association between higher sympathetic outflow and carotid artery wall thickness with a particular exception to young women.NEW & NOTEWORTHY Increased wall thickness of the large elastic arteries serves as a graded marker for cardiovascular disease risk and progression of atherosclerosis. Findings from the present study establish an independent association between higher sympathetic outflow and carotid artery wall thickness in adults with an exception to young women and extend findings from animal models that demonstrate hypertrophy of vascular smooth muscle following chronic sympathetic-adrenergic stimulation.

Sympathetic Transduction in Type 2 Diabetes Mellitus.

Approximately 60% of patients with type 2 diabetes mellitus (T2D) develop hypertension. Recent work also indicates greater blood pressure (BP) excursions throughout the day in T2D. Collectively, these findings suggest altered BP control in T2D. Although muscle sympathetic nerve activity (MSNA) recordings in T2D have provided equivocal results, quantification of MSNA alone does not account for ensuing vasoconstriction and BP responses elicited by MSNA. Thus, we tested the hypothesis that patients with T2D exhibit enhanced sympathetic transduction to BP. MSNA (microneurography) and beat-to-beat BP (Finometer) were measured at rest in 21 T2D and 13 age-matched and body mass index-matched control subjects and, signal-averaging was performed to quantify the mean arterial pressure and total vascular conductance responses to spontaneous bursts of MSNA. The peak mean arterial pressure and total vascular conductance responses to spontaneous MSNA were similar between T2D and control (both P>0.05). However, further analysis, separating T2D into those taking statins (n=13, T2D +statin) and not taking statins (n=8, T2D -statin), indicated that T2D -statin patients (4.2±0.6 mm Hg) exhibited greater peak mean arterial pressure responses compared with both T2D +statin patients (2.5±0.3 mm Hg, P=0.01) and control (control: 2.8±0.3 mm Hg, P=0.02). Likewise, nadir total vascular conductance responses to spontaneous MSNA bursts were greater in T2D -statin patients (T2D -statin: -3.3±0.6 mL/(min·mm Hg), T2D +statin: -1.6±0.3 mL/(min·mm Hg), P=0.03; control -2.2±0.3 mL/(min·mm Hg), P=0.08). Notably, T2D +statin patients exhibited similar peak mean arterial pressure and total vascular conductance responses to MSNA compared with control. Collectively, these findings demonstrate, for the first time, that patients with T2D exhibit augmented sympathetic transduction and this effect seems to be offset by statin therapy.

Elevated Muscle Sympathetic Nerve Activity Contributes to Central Artery Stiffness in Young and Middle-Age/Older Adults.

Muscle sympathetic nerve activity (MSNA) influences the mechanical properties (ie, vascular smooth muscle tone and stiffness) of peripheral arteries, but it remains controversial whether MSNA contributes to stiffness of central arteries, such as the aorta and carotids. We examined whether elevated MSNA (age-related) would be independently associated with greater stiffness of central (carotid-femoral pulse wave velocity [PWV]) and peripheral (carotid-brachial PWV) arteries, in addition to lower carotid compliance coefficient, in healthy men and women (n=88, age: 19-73 years, 52% men). We also examined whether acute elevations in MSNA without increases in mean arterial pressure using graded levels of lower body negative pressure would augment central and peripheral artery stiffness in young (n=15, 60% men) and middle-age/older (MA/O, n=14, 43% men) adults. Resting MSNA burst frequency (bursts·min-1) was significantly correlated with carotid-femoral PWV ( R=0.44, P<0.001), carotid-brachial PWV ( R=0.32, P=0.004), and carotid compliance coefficient ( R=0.28, P=0.01) after controlling for sex, mean arterial pressure, heart rate, and waist-to-hip ratio (central obesity), but these correlations were abolished after further controlling for age (all P>0.05). In young and MA/O adults, MSNA was elevated during lower body negative pressure ( P<0.001) and produced significant increases in carotid-femoral PWV (young: Δ+1.3±0.3 versus MA/O: Δ+1.0±0.3 m·s-1, P=0.53) and carotid-brachial PWV (young: Δ+0.7±0.3 versus MA/O: Δ+0.7±0.5 m·s-1, P=0.92), whereas carotid compliance coefficient during lower body negative pressure was significantly reduced in young but not MA/O (young: Δ-0.04±0.01 versus MA/O: Δ0.001±0.008 mm2·mm Hg-1, P<0.01). Collectively, these data demonstrate the influence of MSNA on central artery stiffness and its potential contribution to age-related increases in stiffness of both peripheral and central arteries.

Femoral vascular conductance and peroneal muscle sympathetic nerve activity responses to acute epidural spinal cord stimulation in humans.

NEW FINDINGS: What is the central question of this research? Does acute spinal cord stimulation increase vascular conductance and decrease muscle sympathetic nerve activity in the lower limbs of humans? What is the main finding and its importance? Acute spinal cord stimulation led to a rapid rise in femoral vascular conductance, and peroneal muscle sympathetic nerve activity demonstrated a delayed reduction that was not associated with the initial increase in femoral vascular conductance. These findings suggest that neural mechanisms in addition to attenuated muscle sympathetic nerve activity might be involved in the initial increase in femoral vascular conductance during acute spinal cord stimulation. ABSTRACT: Clinical cases have indicated an increase in peripheral blood flow after continuous epidural spinal cord stimulation (SCS) and that reduced muscle sympathetic nerve activity (MSNA) might be a potential mechanism. However, no studies in humans have directly examined the effects of acute SCS (<60 min) on vascular conductance and MSNA. In study 1, we tested the hypothesis that acute SCS (<60 min) of the thoracic spine would lead to increased common femoral vascular conductance, but not brachial vascular conductance, in 11 patients who previously underwent surgical SCS implantation for management of neuropathic pain. Throughout 60 min of SCS, common femoral artery conductance was elevated and significantly different from brachial artery conductance [in millilitres per minute: 15 min, change (Δ) 26 ± 37 versus Δ-2 ± 19%; 30 min, Δ28 ± 45 versus Δ0 ± 26%; 45 min, Δ48 ± 43 versus Δ2 ± 21%; 60 min, Δ36 ± 61 versus Δ1 ± 24%; and 15 min post-SCS, Δ51 ± 64 versus Δ6 ± 33%; P = 0.013]. A similar examination in a patient with cervical SCS revealed minimal changes in vascular conductance. In study 2, we examined whether acute SCS reduces peroneal MSNA in a subset of SCS patients (n = 5). The MSNA burst incidence in response to acute SCS gradually declined and was significantly reduced at 45 and 60 min of SCS (in bursts per 100 heart beats: 15 min, Δ-1 ± 12%; 30 min, Δ-14 ± 12%; 45 min, Δ-19 ± 16%; 60 min, Δ-24 ± 18%; and 15 min post-SCS: Δ-11 ± 7%; P = 0.015). These data demonstrate that acute SCS rapidly increases femoral vascular conductance and reduces peroneal MSNA. The gradual reduction in peroneal MSNA observed during acute SCS suggests that neural mechanisms in addition to attenuated MSNA might be involved in the acute increase in femoral vascular conductance.