Angiotensin II potentiates α-adrenergic vasoconstriction in the elderly.

Aging is characterized by increased sympatho-excitation, expressed through both the α-adrenergic and RAAS (renin-angiotensin-aldosterone) pathways. Although the independent contribution of these two pathways to elevated vasoconstriction with age may be substantial, significant cross-talk exists that could produce potentiating effects. To examine this interaction, 14 subjects (n=8 young, n=6 old) underwent brachial artery catheterization for administration of AngII (angiotensin II; 0.8-25.6 ng/dl per min), NE [noradrenaline (norepinephrine); 2.5-80 ng/dl per min] and AngII with concomitant α-adrenergic antagonism [PHEN (phentolamine); 10 µg/dl per min]. Ultrasound Doppler was utilized to determine blood flow, and therefore vasoconstriction, in both infused and contralateral (control) limbs. Arterial blood pressure was measured directly, and sympathetic nervous system activity was assessed via microneurography and plasma NE analysis. AngII sensitivity was significantly greater in the old, indicated by both greater maximal vasoconstriction (-59±4% in old against -48±3% in young) and a decreased EC50 (half-maximal effective concentration) (1.4±0.2 ng/dl per min in old against 2.6±0.7 µg/dl per min in young), whereas the maximal NE-mediated vasoconstriction was similar between these groups (-58±9% in old and -62±5% in young). AngII also increased venous NE in the old group, but was unchanged in the young group. In the presence of α-adrenergic blockade (PHEN), maximal AngII-mediated vasoconstriction in the old was restored to that of the young (-43±8% in old and -39±6% in young). These findings indicate that, with healthy aging, the increased AngII-mediated vasoconstriction may be attributed, in part, to potentiation of the α-adrenergic pathway, and suggest that cross-talk between the RAAS and adrenergic systems may be an important consideration in therapeutic strategies targeting these two pathways.

A differing role of oxidative stress in the regulation of central and peripheral hemodynamics during exercise in heart failure.

This study sought to characterize the role of free radicals in regulating central and peripheral hemodynamics at rest and during exercise in patients with heart failure (HF). We examined cardiovascular responses to dynamic handgrip exercise (4, 8, and 12 kg at 1 Hz) following consumption of either a placebo or acute oral antioxidant cocktail (AOC) consisting of vitamin C, E, and α-lipoic acid in a balanced, crossover design. Central and peripheral hemodynamics, mean arterial pressure, cardiac index, systemic vascular resistance (SVR), brachial artery blood flow, and peripheral (arm) vascular resistance (PVR) were determined in 10 HF patients and 10 age-matched controls. Blood assays evaluated markers of oxidative stress and efficacy of the AOC. When compared with controls, patients with HF exhibited greater oxidative stress, measured by malondialdehyde (+36%), and evidence of endogenous antioxidant compensation, measured by greater superoxide dismutase activity (+83%). The AOC increased plasma ascorbate (+50%) in both the HF patients and controls, but significant systemic hemodynamic effects were only evident in the patients with HF, both at rest and throughout exercise. Specifically, the AOC reduced mean arterial pressure (-5%) and SVR (-12%) and increased cardiac index (+7%) at each workload. In contrast, peripherally, brachial artery blood flow and PVR (arm) were unchanged by the AOC. In conclusion, these data imply that SVR in patients with HF is, at least in part, mediated by oxidative stress. However, this finding does not appear to be the direct result of muscle-specific changes in PVR.

On the contribution of group III and IV muscle afferents to the circulatory response to rhythmic exercise in humans.

We investigated the role of skeletal muscle afferent feedback in circulatory control during rhythmic exercise in humans. Nine healthy males performed single leg knee-extensor exercise (15/30/45 watts, 3 min each) under both control conditions (Ctrl) and with lumbar intrathecal fentanyl impairing µ-opioid receptor-sensitive muscle afferents. Cardiac output and femoral blood flow were determined, and femoral arterial/venous blood samples were collected during the final minute of each workload. To rule out cephalad migration of fentanyl to the brainstem,we documented unchanged resting ventilatory responses to different levels of hypercapnia. There were no haemodynamic differences between conditions at rest. However, during exercise cardiac output was -2 % lower with fentanyl blockade compared to control (P < 0.05), secondary to a 6% and 13% reduction in heart rate and stroke volume, respectively. Throughout exercise mean arterial pressure (MAP) was reduced by 7% (P < 0.01) which is likely to have contributed to the 15% fall in femoral blood flow. However, MAP was not completely responsible for this peripheral haemodynamic change as vascular conductance was also attenuated (-9%). Evidence of increasing noradrenaline spillover (P = 0.09) implicated an elevation in sympathetic outflow in this response. The attenuated femoral blood flow during exercise with fentanyl was associated with a 17%reduction in leg O2 delivery (P < 0.01) and a concomitant rise in the arteriovenous O2 difference (4­9%), but leg O2 consumption remained 7­13% lower than control (P < 0.05). Our findings reveal an essential contribution of continuous muscle afferent feedback to ensure the appropriate haemodynamic and ultimately metabolic response to rhythmic exercise in humans

Impact of body position on central and peripheral hemodynamic contributions to movement-induced hyperemia: implications for rehabilitative medicine.

This study used alterations in body position to identify differences in hemodynamic responses to passive exercise. Central and peripheral hemodynamics were noninvasively measured during 2 min of passive knee extension in 14 subjects, whereas perfusion pressure (PP) was directly measured in a subset of 6 subjects. Movement-induced increases in leg blood flow (LBF) and leg vascular conductance (LVC) were more than twofold greater in the upright compared with supine positions (LBF, supine: 462 ± 6, and upright: 1,084 ± 159 ml/min, P < 0.001; and LVC, supine: 5.3 ± 1.2, and upright: 11.8 ± 2.8 ml·min⁻¹ ·mmHg⁻¹, P < 0.002). The change in heart rate (HR) from baseline to peak was not different between positions (supine: 8 ± 1, and upright: 10 ± 1 beats/min, P = 0.22); however, the elevated HR was maintained for a longer duration when upright. Stroke volume contributed to the increase in cardiac output (CO) during the upright movement only. CO increased in both positions; however, the magnitude and duration of the CO response were greater in the upright position. Mean arterial pressure and PP were higher at baseline and throughout passive movement when upright. Thus exaggerated central hemodynamic responses characterized by an increase in stroke volume and a sustained HR response combined to yield a greater increase in CO during upright movement. This greater central response coupled with the increased PP and LVC explains the twofold greater and more sustained increase in movement-induced hyperemia in the upright compared with supine position and has clinical implications for rehabilitative medicine.

Progressive handgrip exercise: evidence of nitric oxide-dependent vasodilation and blood flow regulation in humans.

In the peripheral circulation, nitric oxide (NO) is released in response to shear stress across vascular endothelial cells. We sought to assess the degree to which NO contributes to exercise-induced vasodilation in the brachial artery (BA) and to determine the potential of this approach to noninvasively evaluate NO bioavailability. In eight young (25 ± 1 yr) healthy volunteers, we used ultrasound Doppler to examine BA vasodilation in response to handgrip exercise (4, 8, 12, 16, 20, and 24 kg) with and without endothelial NO synthase blockade [intra-arterial N(G)-monomethyl-L-arginine (L-NMMA), 0.48 mg · dl(-1) · min(-1)]. Higher exercise intensities evoked significant BA vasodilation (4-12%) that was positively correlated with the hyperemic stimulus (r = 0.98 ± 0.003, slope = 0.005 ± 0.001). During NO blockade, BA vasodilation at the highest exercise intensity was reduced by ∼70% despite similar exercise-induced increases in shear rate (control, +224 ± 30 s(-1); L-NMMA, +259 ± 46 s(-1)). The relationship and slope of BA vasodilation with increasing shear rate was likewise reduced (r = 0.48 ± 0.1, slope = 0.0007 ± 0.0005). We conclude that endothelial NO synthase inhibition with L-NMMA abolishes the relationship between shear stress and BA vasodilation during handgrip exercise, providing clear evidence of NO-dependent vasodilation in this experimental model. These results support this paradigm as a novel and valid approach for a noninvasive assessment of NO-dependent vasodilation in humans.

Attenuated exercise induced hyperaemia with age: mechanistic insight from passive limb movement.

The influence of age on the central and peripheral contributors to exercise-induced hyperaemia is unclear. Utilizing a reductionist approach, we compared the peripheral and central haemodynamic responses to passive limb movement (exercise without an increase in metabolism) in 11 old (71 ± 9 years of age S.D.) and 11 young (24 ± 2 years of age) healthy subjects. Cardiac output (CO), heart rate (HR), stroke volume (SV), mean arterial pressure (MAP), and femoral blood flow of the passively moved and control legs were evaluated second-by-second during 2 min of passive knee extension at a rate of 1 Hz. Compared to the young, the old group exhibited a significantly attenuated increase in HR (7 ± 4% vs. 13 ± 7% S.D.), CO (10 ± 6% vs. 18 ± 8%) and femoral blood flow in the passively moved (123 ± 55% vs. 194 ± 57%) and control legs (47 ± 43% vs. 77 ± 96%). In addition, the change in vascular conductance in the passively moving limb was also significantly attenuated in the old (2.4 ± 1.2 ml min(-1) mmHg(-1)) compared to the young (4.3 ± 1.7 ml min(-1) mmHg(-1)). In both groups all main central and peripheral changes that occurred at the onset of passive knee extension were transient, lasting only 45 s. In a paradigm where metabolism does not play a role, these data reveal that both central and peripheral haemodynamic mechanisms are likely to be responsible for the 30% reduction in exercise-induced hyperaemia with age.

Understanding exercise-induced hyperemia: central and peripheral hemodynamic responses to passive limb movement in heart transplant recipients.

To better characterize the contribution of both central and peripheral mechanisms to passive limb movement-induced hyperemia, we studied nine recent (<2 yr) heart transplant (HTx) recipients (56 ± 4 yr) and nine healthy controls (58 ± 5 yr). Measurements of heart rate (HR), stroke volume (SV), cardiac output (CO), and femoral artery blood flow were recorded during passive knee extension. Peripheral vascular function was assessed using brachial artery flow-mediated dilation (FMD). During passive limb movement, the HTx recipients lacked an HR response (0 ± 0 beats/min, Δ0%) but displayed a significant increase in CO (0.4 ± 0.1 l/min, Δ5%) although attenuated compared with controls (1.0 ± 0.2 l/min, Δ18%). Therefore, the rise in CO in the HTx recipients was solely dependent on increased SV (5 ± 1 ml, Δ5%) in contrast with the controls who displayed significant increases in both HR (6 ± 2 beats/min, Δ11%) and SV (5 ± 2 ml, Δ7%). The transient increase in femoral blood volume entering the leg during the first 40 s of passive movement was attenuated in the HTx recipients (24 ± 8 ml) compared with controls (93 ± 7 ml), whereas peripheral vascular function (FMD) appeared similar between HTx recipients (8 ± 2%) and controls (6 ± 1%). These data reveal that the absence of an HR increase in HTx recipients significantly impacts the peripheral vascular response to passive movement in this population and supports the concept that an increase in CO is a major contributor to exercise-induced hyperemia.

Limb movement-induced hyperemia has a central hemodynamic component: evidence from a neural blockade study.

The purpose of this investigation was to partially remove feedback from type III/IV skeletal muscle afferents and determine how this feedback influences the central and peripheral hemodynamic responses to passive leg movement. Heart rate (HR), stroke volume (SV), cardiac output (CO), mean arterial pressure, leg vascular conductance (LVC), and leg blood flow (LBF) were measured during 2 min of passive knee extension in eight young men before and after intrathecal fentanyl injection. Passive movement increased HR by 14 beats/min from baseline to maximal response during control (CON) (65 ± 4 to 79 ± 5 beats/min, P < 0.05), whereas HR did not significantly increase with the fentanyl block (BLK). LBF and LVC increased in both conditions; however, these increases were attenuated and delayed during BLK [%change from baseline to maximum, LBF: CON 295 ± 109 vs. BLK 210 ± 86%, (P < 0.05); LVC: CON 322 ± 40% vs. BLK 231 ± 32%, (P < 0.04)]. In CON, HR, SV, CO, and LVC increased contributing to the hyperemic response. However, under BLK conditions, statistically insignificant increases in HR and SV combined to yield a small, but significant, increase in CO and an attenuated hyperemic response. Therefore, partially blocking skeletal muscle afferent feedback blunts the central hemodynamic response due to passive limb movement, which then results in an attenuated and delayed movement-induced hyperemia. In combination, these findings provide evidence that limb movement-induced hyperemia has a significant central hemodynamic component induced by peripheral nerve activation.

The influence of obesity on falls and quality of life.

OBJECTIVE: To determine (1) whether obese older adults had higher prevalence of falls and ambulatory stumbling, impaired balance and lower health-related quality of life (HRQL) than their normal weight counterparts, and (2) whether the falls and balance measures were associated with HRQL in obese adults. METHODS: Subjects who had a body mass index (BMI) greater than 30 kg/m2 were classified into an obese group (n = 128) while those with BMI between 18.5 and 24.9 kg/m2 were included into a normal weight group (n = 88). Functional tests were performed to assess balance, and questionnaires were administered to assess history of falls, ambulatory stumbling, and HRQL. RESULTS: The obese group reported a higher prevalence of falls (27% vs. 15%), and ambulatory stumbling (32% vs. 14%) than the normal weight group. Furthermore, the obese group had lower HRQL, (p < or = 0.05) for physical function (63 +/- 27 vs. 75 +/- 26; mean +/- SD), role-physical (59 +/- 40 vs. 74 +/- 37), vitality (58 +/- 23 vs. 66 +/- 20), bodily pain (62 +/- 25 vs. 74 +/- 21) and general health (64 +/- 19 vs. 70 +/- 18). In the obese group, a history of falls was related (p < or = 0.05) to lower scores in 4 domains of HRQL, and ambulatory stumbling was related (p < or = 0.01) to 7 domains. CONCLUSION: In middle-aged and older adults, obesity was associated with a higher prevalence of falls and stumbling during ambulation, as well as lower values in multiple domains of HRQL. Furthermore, a history of falls and ambulatory stumbling were related to lower measures of HRQL in obese adults.

The relationship between arterial elasticity and metabolic syndrome features.

The purpose of this study was to examine the effects of metabolic syndrome (MS) features on arterial elasticity of the large and small arteries in apparently healthy adults, to examine the effect of clustered features of MS, and to determine which features are most predictive of large and small artery elasticity. The subjects for this study consisted of 126 men and women, age 45 years and older. The subjects rested supine while pulse contour analysis was measured from the radial artery by using an HDI/Pulsewave CR-2000 instrument (Hypertension Diagnostic, Inc) to assess arterial elasticity in the large and small arteries. Medical history was obtained along with body mass index, waist circumference, body surface area, and blood pressure. Large artery elasticity was lower (p = 0.002) in subjects with hypertension (12.7 -/+ 4.3 mL/mm Hg x 10) than in those with normotension (15.0 -/+ 4.2 mL/mm Hg x 10; mean -/+ SD), and small artery elasticity was lower (p = 0.001) as well (3.9 -/+2.3 mL/mm Hg x 100 vs 5.3 -/+ 2.5 mL/mm Hg x 100). Large artery elasticity was lower (p = 0.02) in obese subjects (12.2 -/+ 4.9 mL/mm Hg x 10) than in nonobese subjects (14.2 -/+ 4.5 mL/mm Hg x 10), and large artery elasticity was lower (p = 0.04) in subjects with abdominal obesity (12.2 -/+ 4.5 mL/mm Hg x 10) than in those without (14.5 -/+ 4.8 mL/mm Hg x 10). Large artery elasticity decreased as the number of features of MS increased (p < 0.01). Multiple regression showed that body mass index and the presence of hypertension were predictors of large artery elasticity (R = 0.61, R2 = 0.37, p = 0.003, SEE = 3.60 mL/mm Hg x 10), and hypertension was a predictor of small artery elasticity (R = 0.53, R2 = 0.28, p = 0.001, SEE = 2.12 mL/mm Hg x 100). Hypertension and obesity are the features of MS that are most predictive of impairment in large and small artery elasticity in apparently healthy middle-aged and older adults. Furthermore, impairment in large artery elasticity is more evident in subjects with at least three features of MS.

The influence of obesity on calf blood flow and vascular reactivity in older adults.

OBJECTIVE: To determine whether differences in vascular reactivity existed among normal weight, overweight, and obese older men and women, and to examine the association between abdominal fat distribution and vascular reactivity. METHODS: Eighty-seven individuals who were 60 years of age or older (age = 69 +/- 7 yrs; mean +/- SD) were grouped into normal weight (BMI < 25; n = 30), overweight (BMI > or = 25 and < 30; n = 28), or obese (BMI > or = 30; n = 29) categories. Calf blood flow (BF) was assessed by venous occlusion strain-gauge plethysmography at rest and post-occlusive reactive hyperemia. RESULTS: Post-occlusive reactive hyperemia BF was lower (p = 0.038) in the obese group (5.55 +/- 4.67%/min) than in the normal weight group (8.34 +/- 3.89%/min). Additionally, change in BF from rest to post-occlusion in the obese group (1.93 +/- 2.58%/min) was lower (p = 0.001) than in the normal weight group (5.21 +/- 3.59%/min), as well as the percentage change (75 +/- 98% vs. 202 +/- 190%, p = 0.006, respectively). After adjusting for age, prevalence in hypertension and calf skinfold thickness, change in BF values remained lower (p < 0.05) in obese subjects compared to the normal weight subjects. Lastly, the absolute and percentage change in BF were significantly related to BMI (r = -0.44, p < 0.001, and r = -0.37, p < 0.001, respectively) and to waist circumference (r = -0.36, p = 0.001, and r = -0.32, p = 0.002). CONCLUSION: Obesity and abdominal adiposity impair vascular reactivity in older men and women, and these deleterious effects on vascular reactivity are independent of conventional risk factors.

Large and small arterial elasticity in healthy active and sedentary premenopausal women.

The purpose of this study was to compare large and small arterial elasticity in apparently healthy sedentary and recreationally active adult women, and to examine if age affects large and small arterial elasticity. This cross-sectional study consisted of 43 premenopausal women without overt cardiovascular disease (age = 43.4 ± 4.7 yrs; mean ± SD). The subjects were grouped into a sedentary group or a leisurely active group (30 min, 3d wk of low intensity) in addition to the following age groups: 35-40 years, n = 13; 41-45 years, n = 14; 46-54 years, n = 16. Subjects rested supine while pulse contour analysis was measured from the radial artery using an HDI/Pulsewave CR-2000 instrument (Hypertension Diagnostic, Inc.) to examine arterial elasticity in the large and small arteries. Activity level and menopausal status was based on self-report. There were no differences in large (14.5 ± 1.0 ml/mmHg x 10; 14.9 ± 0.9 ml/mmHg x 10; mean ± SD) and small (5.5 ± 0.5 ml/mmHg x 100; 6.4 ± 0.4 ml/mmHg x 100) arterial elasticity between the sedentary group and the recreationally active group, respectively. Large (12.8 ± 0.9 ml/mmHg x 10) arterial elasticity was lower in the oldest group (p = 0.008) compared to the youngest group (17.6 ± 5.9 ml/mmHg x 10). After adjusting for body mass index, large arterial elasticity (p = 0.022) remained lower in the oldest group. There was a trend for small arterial elasticity to be lower in the older group compared to the young group (p = 0.063). There was no difference in large and small arterial elasticity between healthy sedentary and recreationally active premenopausal women. This suggests that more strenuous physical activity may be necessary to gain beneficial effects on the vasculature. Large arterial elasticity is decreasing with advancing age independent of body mass index. Key pointsThere was no difference in large and small artery elasticity between healthy sedentary and recreationally active women.Large artery elasticity decreases with advancing age.Subjects with the highest systolic blood pressure had the largest decrease in large artery elasticity.

Physical activity is related to quality of life in older adults.

BACKGROUND: Physical activity is associated with health-related quality of life (HRQL) in clinical populations, but less is known whether this relationship exists in older men and women who are healthy. Thus, this study determined if physical activity was related to HRQL in apparently healthy, older subjects. METHODS: Measures were obtained from 112 male and female volunteers (70 +/- 8 years, mean +/- SD) recruited from media advertisements and flyers around the Norman, Oklahoma area. Data was collected using a medical history questionnaire, HRQL from the Medical Outcomes Survey short form-36 questionnaire, and physical activity level from the Johnson Space Center physical activity scale. Subjects were separated into either a higher physically active group (n = 62) or a lower physically active group (n = 50) according to the physical activity scale. RESULTS: The HRQL scores in all eight domains were significantly higher (p < 0.05) in the group reporting higher physical activity. Additionally, the more active group had fewer females (44% vs. 72%, p = 0.033), and lower prevalence of hypertension (39% vs. 60%, p = 0.041) than the low active group. After adjusting for gender and hypertension, the more active group had higher values in the following five HRQL domains: physical function (82 +/- 20 vs. 68 +/- 21, p = 0.029), role-physical (83 +/- 34 vs. 61 +/- 36, p = 0.022), bodily pain (83 +/- 22 vs. 66 +/- 23, p = 0.001), vitality (74 +/- 15 vs. 59 +/- 16, p = 0.001), and social functioning (92 +/- 18 vs. 83 +/- 19, p = 0.040). General health, role-emotional, and mental health were not significantly different (p > 0.05) between the two groups. CONCLUSION: Healthy older adults who regularly participated in physical activity of at least moderate intensity for more than one hour per week had higher HRQL measures in both physical and mental domains than those who were less physically active. Therefore, incorporating more physical activity into the lifestyles of sedentary or slightly active older individuals may improve their HRQL.

Use of Accelerometers to Measure Real-Life Physical Activity in Ambulatory Individuals with Multiple Sclerosis: A Pilot Study.

BACKGROUND: Multiple sclerosis (MS) may negatively affect individuals' participation in physical activity (PA). We used accelerometers to determine PA level in individuals with MS with varying degrees of disability as measured by the Expanded Disability Status Scale (EDSS) during regular daily activities. METHODS: Participants wore an accelerometer from 8 a.m. to 9 p.m. for 7 consecutive days. Activity counts recorded during this period were analyzed in 1-minute epochs and categorized into one of four PA levels: light, moderate, hard, and very hard. RESULTS: The study cohort comprised 13 patients with MS and 12 controls. There were significant negative correlations for minutes spent in PA and EDSS measures on weekdays (r = -0.61), weekend (r = -0.64), and full week (r = -0.61) and number of steps taken on weekdays (r = -0.56), weekend (r = -0.80), and full-week average (r = -0.68). Significant positive correlations were found for minutes spent in light PA and EDSS score (r = 0.69). Significant negative correlations were found for minutes spent in moderate and hard PA and EDSS score. No significant difference was seen between the MS group and controls on any parameters (P > .05). CONCLUSIONS: This study showed that accelerometers can be used to objectively quantify PA levels in individuals with MS with different disability levels. This cohort demonstrated that the amount of PA is inversely proportional to the degree of physical disability. Collected data revealed not only the amount but also the intensity of PA performed in real-life circumstances.

Retinal nerve fiber layer sector-specific compromise in relapsing and remitting multiple sclerosis.

OBJECTIVE: To evaluate quadrant and sector retinal nerve fiber layer (RNFL) thickness and total macular volume (TMV) in relapsing-remitting multiple sclerosis (RR-MS) patients. METHODS: Optical coherence tomography measures of RNFL and TMV were studied in 321 eyes without prior optic neuritis (ON) (MS unaffected), 151 eyes with prior ON (MS affected), and 148 healthy control eyes. RESULTS: Mean RNFL thickness was significantly lower in the MS affected and MS unaffected groups relative to the control group (p < 0.0001). RNFL thicknesses in the superior, inferior, and temporal quadrants were significantly reduced in MS unaffected (113 ± 15 µm, 119 ± 17 µm, 63 ± 13 µm) (p < 0.001) and MS affected groups (99 ± 19 µm, 103 ± 21 µm, 51 ± 13 µm) (p < 0.0001) compared with that in controls (120 ± 14 µm, 128 ± 15 µm, 69 ± 8 µm, respectively). TMV was significantly reduced in both the MS affected and MS unaffected groups compared with that in the controls (p < 0.0001). CONCLUSION: Quadrant, sector, and PMB RNFL thicknesses are significant individual measures in RR-MS for both affected and unaffected eyes and may prove valuable in future investigations including biomarker and outcomes research.

Association of vitamin D deficiency with RNFL thickness in MS individuals without history of optic neuritis.

UNLABELLED: Vitamin D deficiency has been associated with both increased risk and severity of Multiple Sclerosis (MS) as it has a modulating effect on the immune process that causes inflammation/demyelination and axonal damage. Optical Coherence Tomography (OCT) offers a quick, reliable and non-invasive way to assess the Retinal Nerve Fiber Layer (RNFL) and identifies axonal loss generated by either direct inflammation or from neurodegeneration. OBJECTIVE: To determine the association of vitamin D and RNFL in MS patients without a history of Optic Neuritis (ON) by comparing RNFL thickness in patients that are vitamin D deficient with those having normal serum levels. METHOD: The cohort of 76 MS patients underwent OCT testing to assess the RNFL thickness and macular volume, and measurement of serum 25-OH Vitamin D level. Vitamin D deficiency was defined as <30ng/ml and sufficiency as ≥30ng/ml. RESULTS: A total of 131 eyes were divided in two groups: vitamin D deficient (n=86 eyes, mean=17.7ng/ml) and vitamin D sufficient (n=45 eyes, mean=40.3ng/ml). Twenty one eyes had previous ON and were excluded from this analysis. Vitamin D deficiency was identified in 66% of the participants. RNFL thickness was similar for the vitamin D deficient and sufficient groups (85.5 vs 86µm respectively, p=0.89). Significant differences were present for age with the deficient group being younger (42 years vs 51 years, p=0.005) and having shorter disease duration (7.5 years vs 11.4 years, p=0.006). CONCLUSION: Vitamin D deficiency is not associated with thinning of RNFL or macular volume in MS eyes unaffected by ON. This finding suggests the role of vitamin D in modulating the severity of MS is not exerted through an influence on neurodegeneration.

Vascular dysfunction and chronic obstructive pulmonary disease: the role of redox balance.

Chronic obstructive pulmonary disease (COPD) is characterized by low pulmonary function, inflammation, free radical production, vascular dysfunction, and subsequently a greater incidence of cardiovascular disease. By administering an acute oral antioxidant cocktail to patients with COPD (n=30) and controls (n=30), we sought to determine the role of redox balance in the vascular dysfunction of these patients. Using a double-blind, randomized, placebo-controlled, crossover design, patients with COPD and controls were ingested placebo or the antioxidant cocktail (vitamin C, vitamin E, α-lipoic acid) after which brachial artery flow-mediated dilation and carotid-radial pulse wave velocity were assessed using ultrasound Doppler. The patients exhibited lower baseline antioxidant levels (vitamin C and superoxide dismutase activity) and higher levels of oxidative stress (thiobarbituic acid reactive species) in comparison with controls. The patients also displayed lower basal flow-mediated dilation (P<0.05), which was significantly improved with antioxidant cocktail (3.1±0.5 versus 4.7±0.6%; P<0.05; placebo versus antioxidant cocktail), but not controls (6.7±0.6 versus 6.9±0.7%; P>0.05; placebo versus antioxidant cocktail). The antioxidant cocktail also improved pulse wave velocity in patients with COPD (14±1 versus 11±1 m·s(-1); P<0.05; placebo versus antioxidant cocktail) while not affecting controls (11±2 versus 10±1 m·s(-1); P>0.05; placebo versus antioxidant). Patients with COPD exhibit vascular dysfunction, likely mediated by an altered redox balance, which can be acutely mitigated by an oral antioxidant. Therefore, free radically mediated vascular dysfunction may be an important mechanism contributing to this population's greater risk and incidence of cardiovascular disease.

Advances in the management of neurogenic detrusor overactivity in multiple sclerosis.

Bladder dysfunction in multiple sclerosis (MS) can be socially disabling, have negative psychological and economic consequences, and impair patients' quality of life. Knowledge of the functional anatomy and physiology of the urinary tract is essential to understand the symptoms associated with central nervous system lesions and the pharmacotherapies used to treat them. Treatments for neurogenic detrusor overactivity (NDO) have consisted mainly of administration of anticholinergic drugs, which have been shown to provide suboptimal clinical benefits and be poorly tolerated. The US Food and Drug Administration (FDA) approval of intravesicular botulinum toxin therapy provides a second-line option for MS patients with NDO not responsive to anticholinergic drugs. We performed a review of key literature pertaining to the intravesicular application of botulinum toxin. In the management of NDO, administration of intravesicular botulinum toxin using clean intermittent catheterization decreases the incidence of urinary tract infections, promotes urinary continence, and improves quality of life for 9 months after a single injection; moreover, those benefits are maintained with repeated injections over time.

Bison meat has a lower atherogenic risk than beef in healthy men.

The rearing method of bison and the nutrient content of the meat may make bison a healthier alternative to beef. We hypothesized that the acute and chronic effects of bison consumption, in comparison to beef, will result in a less perturbed blood lipid panel and a reduced inflammatory and oxidative stress response which will minimize the detrimental effect on vascular function. A double-blind, cross-over randomized trial was employed to examine the consequence of a single 12 oz serving (n = 14) and 7 weeks of chronic consumption (n = 10) (12 oz/d, 6 d/wk) of each meat. Measurements included blood lipids, interleukin-6, plasminogen activator inhibitor 1, C-reactive protein, oxidized low-density lipoprotein, protein carbonyl, hydroperoxides, flow-mediated dilation (FMD) and FMD/shear rate. Following a single beef meal, triglycerides and oxidized low-density lipoprotein were elevated (67% ± 45% and 18% ± 17% respectively); there was a tendency for hydroperoxides to be elevated (24% ± 37%); and FMD/shear rate was reduced significantly (30% ± 38%). Following a single meal of bison: there was a smaller increase in triglycerides (30% ± 27%), and markers of inflammation and oxidative stress and FMD/shear rate were unchanged. Chronic consumption of either meat did not influence body weight, % body fat, or blood lipids. Protein carbonyl (24% ± 45%), plasminogen activator inhibitor 1 (78% ± 126%), interleukin-6 (59% ± 76%) and C-reactive protein (72% ± 57%) were significantly elevated and FMD/shear rate was significantly reduced (19% ± 28%) following 7 weeks of beef consumption, but not bison consumption. Based on our findings, the data suggest that bison consumption results in a reduced atherogenic risk compared to beef.

Vascular function and the role of oxidative stress in heart failure, heart transplant, and beyond.

Using flow-mediated vasodilation (FMD), reactive hyperemia, and an acute oral antioxidant cocktail (AOC; vitamins C and E and α-lipoic acid), this study aimed to provide greater insight into altered vascular function and the role of oxidative stress in chronic heart failure patients with reduced ejection fraction (HFrEF) and at several time points beyond heart transplantation (HTx). A total of 61 age-matched subjects (12 healthy controls, 14 New York Heart Association class II and III HFrEF, and 35 HTx recipients [<3 years post-HTx, 5-10 years post-HTx, and >14 years post-HTx]) ingested either placebo (PL) or an AOC before FMD and reactive hyperemia testing of the brachial artery. Vascular function, as measured by FMD, was not different among the controls (6.8±1.9%), recent <3-year post-HTx group (8.1±1.2%), and the 5- to 10-year post-HTx group (5.5±1.0%). However, PL FMD was lower in the HFrEF (4.5±0.7%) and in the >14-year post-HTx group (2.9±0.8%). The AOC increased plasma ascorbate levels in all of the groups but only increased FMD in the controls (PL, 6.8±1.9%; AOC, 9.2±1.0%) and >14-year post-HTx recipients (PL, 2.9±0.8%; AOC, 4.5±1.3%). There were no differences in reactive hyperemia in any of the groups with PL or AOC. This cross-sectional study reveals that, compared with controls, vascular function is blunted in HFrEF, is similar soon after HTx, but is decreased with greater time post-HTx with free radicals implicated in this progression.