Reactive Hyperemic Blood Flow Research Articles

Implementing local cooling to increase skin tolerance to ischemia during normal seating in people with spinal cord injury

The purpose of this study was to investigate the effectiveness of local cooling in reducing reactive hyperemia after ischemia at the ischial tuberosities for people with spinal cord injury (SCI) during normal seating. The degree of the reactive hyperemic response is indicative of the extent of cellular stress caused by the ischemia. We hypothesized that reactive hyperemic skin blood flow (SBF) responses will be lower when local cooling is implemented by the wheelchair seat cushion. This study used a repeated measures design, and each subject underwent two conditions: normal seating with temperature control ‘on’ (cooling) and ‘off’ (non-cooling) for 30 min. Twenty-three participants with traumatic SCI were recruited. SBF and skin temperature were collected before, during and after seating. SBF signals were processed with short-time Fourier analyses to examine the underlying vascular control mechanisms, including the following (corresponding frequency bands): metabolic (0.0095–0.02 Hz), neurogenic (0.02–0.05 Hz), and myogenic (0.05–0.15 Hz) spectral densities. Our results showed that with cooling, skin temperature decreased (range −0.4 ~ −3.1 °C, p = 0.002), and reactive hyperemia parameters (normalized peak SBF and perfusion area) were reduced (p = 0.02, p = 0.033, respectively). In addition, changes in normalized peak SBF (non-cooling – cooling) was moderately correlated with changes in normalized metabolic and neurogenic spectral densities. Our findings suggested that local cooling has a positive effect on reducing the cellular stress caused by ischemia during normal seating. Metabolic and neurogenic SBF control mechanisms may play a minor role. Further exploration of the effect of temperature control on pressure injury prevention is warranted.

Greater Forearm Blood Flow is Associated with Better Walking Economy and Gait Speed in Older Adults

Gait speed decline is a well-established predictor of disability and mortality in older adults. Compromised energetic efficiency (i.e. walking economy) is a strong contributor to gait speed decline, but the underlying mechanisms influencing walking economy are undefined. Impaired vascular function is common with aging and thus may be an important contributor to the development of compromised walking economy and slow gait speed, yet the relationships among blood flow within skeletal muscle, walking economy, and gait speed in older adults are unknown. PURPOSE: To examine the relationship between measured forearm blood flow and (i) walking economy and (ii) gait speed in older men and woman. METHODS: Resting arterial inflow and reactive hyperemic blood flow (RHBF) of the left forearm was measured in 55 participants of the Longitudinal Aging Study at Towson (LAST; 53% male, mean age 70, range 51-91 years) using venous occlusion plethysmography. Walking economy was measured as the average rate of oxygen consumption during the final 2 minutes of a 5 minute standardized treadmill-based walking test at 1.5 mile per hour. Gait speed was assessed during 2.5 minutes of normal-paced walking over a 20-meter course. The association between RHBF and walking economy and RHBF and gait speed was modeled using linear regression, adjusting for age, height, and fat-free mass. Sobel tests were used to assess possible mediating effects. RESULTS: In fully adjusted models, RHBF (mean RHBF: 18.0 ± 5.9 mL•100mL tissue-1•min-1) was negatively associated with oxygen consumption (β = -7.5, p < 0.01), indicating that walking economy was 7.5 mL/min lower for each one-unit increase in blood flow. Gait speed (mean 1.3 ± 0.2 m/s) was positively associated with blood flow (β = 0.01, p = 0.05), indicating that gait speed was 0.01 m/s faster for each one-unit increase in blood flow. Mediation analyses further suggested that blood flow may mediate the association between walking economy and gait speed (p=0.06). CONCLUSION: RHBF is a significant predictor of both walking economy and gait speed in older adults, suggesting that better overall vascular health is related to enhanced walking economy and gait speed. Therefore, interventions aimed at improving vascular health in the aging population may be beneficial in maintaining gait speed and mobility with age.

Beet the Best?

A primary goal of therapy for patients with peripheral artery disease (PAD) and intermittent claudication is increased ambulatory function. Supervised exercise rehabilitation was recently shown to confer superior walking benefits to pharmacological or surgical interventions. Increases in plasma inorganic nitrite, via oral nitrate, have been shown to increase exercise performance in both human and animal models, especially in hypoxic conditions. To determine whether a 36-session exercise rehabilitation program while consuming oral inorganic nitrate (4.2 mmol concentrated beetroot juice) would produce superior benefits over exercise plus placebo in pain-free walking and markers of increased skeletal muscle perfusion in patients with PAD and intermittent claudication. This was a randomized, double-blind, per-protocol study design. After the 12-week protocol, claudication onset time on a maximal treadmill test increased by 59.2±57.3 s for the exercise plus placebo group (n=13) and by 180.3±46.6 s for the exercise plus beetroot juice group (n=11; P≤0.05). This produced a between treatment medium to large standardized effect size (Cohen d) of 0.62 (95% CI, -0.23 to +1.44). The data for 6-minute walk distance showed a similar pattern with increases of 24.6±12.1 and 53.3±19.6 m ( P≤0.05) in the exercise plus placebo and exercise plus beetroot juice groups, respectively. Measures of gastrocnemius perfusion, including ankle-brachial index, peak reactive hyperemic blood flow, and tissue deoxygenation characteristics, during exercise (assessed my near-infrared spectroscopy) all changed significantly for the exercise plus beetroot juice group with moderate-to-large effect sizes over exercise plus placebo changes. Although it is premature to speculate on overall clinical utility of a nitrate-based therapy for PAD, this early pilot study evidence is encouraging. Specifically, our data suggests that increasing plasma nitrite before exercise may allow PAD subjects to train with less pain, at higher workloads for longer durations at each training session, thereby maximizing the beneficial peripheral vascular and skeletal muscle adaptations. URL: http://www.clinicaltrials.gov . Unique identifier: NCT01684930 and NCT01785524.

Unilateral application of an external pneumatic compression therapy improves skin blood flow and vascular reactivity bilaterally.

BackgroundWe sought to determine the effects of unilateral lower-limb external pneumatic compression (EPC) on bilateral lower-limb vascular reactivity and skin blood flow.MethodsThirty-two participants completed this two-aim study. In AIM1 (n = 18, age: 25.5 ± 4.7 years; BMI: 25.6 ± 3.5 kg/m2), bilateral femoral artery blood flow and reactivity (flow mediated dilation [FMD]) measurements were performed via ultrasonography at baseline (PRE) and immediately following 30-min of unilateral EPC treatment (POST). AIM2 (n = 14, age: 25.9 ± 4.5; BMI: 27.2 ± 2.7 kg/m2) involved 30-min unilateral EPC (n = 7) or sham (n = 7) treatment with thermographic bilateral lower-limb mean skin temperature (MST) measurements at baseline, 15-min of treatment (T15) and 0, 30 and 60-min (R0, R30, R60) following treatment.ResultsComparative data herein are presented as mean ± 95% confidence interval. AIM1: No significant effects on total reactive hyperemia blood flow were observed for the treated (i.e., compressed) or untreated (i.e., non-compressed) leg. A significant effect of time, but no time*leg interaction, was observed for relative FMD indicating higher reactivity bilaterally with unilateral EPC treatment (FMD: +0.41 ± 0.09% across both legs; p < 0.05). AIM2: Unilateral EPC treatment was associated with significant increases in whole-leg MST from baseline during (T15: +0.63 ± 0.56 °C in the visible untreated/contralateral leg, p < 0.025) and immediately following treatment (i.e., R0) in both treated (+1.53 ± 0.59 °C) and untreated (+0.60 ± 0.45 °C) legs (p < 0.0125). Across both legs, MST remained elevated with EPC at 30-min post-treatment (+0.60 ± 0.45 °C; p < 0.0167) but not at 60-min post (+0.27 ± 0.46 °C; p = 0.165). Sham treatment was associated with a significant increase in the treated leg immediately post-treatment (+1.12 ± 0.31 °C; p < 0.0167), but not in the untreated leg (−0.27 ± 0.12 °C). MST in neither the treated or untreated leg were increased relative to baseline at R30 or R60 (p > 0.05). Finally, during treatment and at all post-treatment time points (i.e., R0, R30 and R60), independent of treatment group (EPC vs. sham), there was a significant effect of region. The maximum increase in MST was observed at the R0 time point and was significantly (p < 0.05) larger in the thigh region (+1.02 ± 0.31 °C) than the lower-leg (+0.47 ± 0.29 °C) region. However, similar rates of MST decline from R0 in the thigh and lower leg regions were observed at the R30 and R60 time points.DiscussionUnilateral EPC may be an effective intervention for increasing skin blood flow and/or peripheral conduit vascular reactivity in the contralateral limb. While EPC was effective in increasing whole-leg MST bilaterally, there appeared to be a more robust response in the thigh compared to the lower-leg. Thus, proximity along the leg may be an important consideration in prospective treatment strategies.

Dissociation of local and global skeletal muscle oxygen transport metrics in type 2 diabetes

AimsExercise capacity is impaired in type 2 diabetes, and this impairment predicts excess morbidity and mortality. This defect appears to involve excess skeletal muscle deoxygenation, but the underlying mechanisms remain unclear. We hypothesized that reduced blood flow, reduced local recruitment of blood volume/hematocrit, or both contribute to excess skeletal muscle deoxygenation in type 2 diabetes. MethodsIn patients with (n=23) and without (n=18) type 2 diabetes, we recorded maximal reactive hyperemic leg blood flow, peak oxygen utilization during cycling ergometer exercise (VO2peak), and near-infrared spectroscopy-derived measures of exercise-induced changes in skeletal muscle oxygenation and blood volume/hematocrit. ResultsWe observed a significant increase (p<0.05) in skeletal muscle deoxygenation in type 2 diabetes despite similar blood flow and recruitment of local blood volume/hematocrit. Within the control group skeletal muscle deoxygenation, local recruitment of microvascular blood volume/hematocrit, blood flow, and VO2peak are all mutually correlated. None of these correlations were preserved in type 2 diabetes. ConclusionsThese results suggest that in type 2 diabetes 1) skeletal muscle oxygenation is impaired, 2) this impairment may occur independently of bulk blood flow or local recruitment of blood volume/hematocrit, and 3) local and global metrics of oxygen transport are dissociated.

Acute ingestion of citrulline stimulates nitric oxide synthesis but does not increase blood flow in healthy young and older adults with heart failure.

To determine if age-associated vascular dysfunction in older adults with heart failure (HF) is due to insufficient synthesis of nitric oxide (NO), we performed two separate studies: 1) a kinetic study with a stable isotope tracer method to determine in vivo kinetics of NO metabolism, and 2) a vascular function study using a plethysmography method to determine reactive hyperemic forearm blood flow (RH-FBF) in older and young adults in the fasted state and in response to citrulline ingestion. In the fasted state, NO synthesis (per kg body wt) was ∼ 50% lower in older vs. young adults and was related to a decreased rate of appearance of the NO precursor arginine. Citrulline ingestion (3 g) stimulated de novo arginine synthesis in both older [6.88 ± 0.83 to 35.40 ± 4.90 μmol · kg body wt(-1) · h(-1)] and to a greater extent in young adults (12.02 ± 1.01 to 66.26 ± 4.79 μmol · kg body wt(-1) · h(-1)). NO synthesis rate increased correspondingly in older (0.17 ± 0.01 to 2.12 ± 0.36 μmol · kg body wt(-1) · h(-1)) and to a greater extent in young adults (0.36 ± 0.04 to 3.57 ± 0.47 μmol · kg body wt(-1) · h(-1)). Consistent with the kinetic data, RH-FBF in the fasted state was ∼ 40% reduced in older vs. young adults. However, citrulline ingestion (10 g) failed to increase RH-FBF in either older or young adults. In conclusion, citrulline ingestion improved impaired NO synthesis in older HF adults but not RH-FBF, suggesting that factors other than NO synthesis play a role in the impaired RH-FBF in older HF adults, and/or it may require a longer duration of supplementation to be effective in improving RH-FBF.

7D.04

Objective: Our previous study demonstrated that one week of salt loading significantly impaired skin microvascular reactivity without changes in blood pressure (BP) levels. The aim of this study was to evaluate whether one week of high-salt (HS) diet changes body fluid status and body composition subsequently affecting vascular reactivity. Design and method: 10 healthy women (age range 20–23) took a 7-days low-salt (LS) diet (<40mmol Na/day) and 7-days HS diet (∼240mmol of Na/day). Salt resistance, defined as a <5 mmHg change in BP determined while on the LS and HS diets was confirmed in all subjects. Skin microvascular post occlusive reactive hyperemic (PORH) blood flow (indicator of endothelial function) was assessed by laser Doppler flowmetry (LDF) before and after each diet protocol. Plasma Renin Activity (PRA), plasma aldosterone, plasma and 24h-urine sodium, potassium, urea and creatinine levels were measured before and after diets. Body composition was assessed with a four-terminal portable impedance analyzer (Maltron Bioscan 920-II). Body Mass Index (BMI), Fat Free Mass% (FFM%), Fat Mass% (FM%), Total Body Water% (TBW%), Extracellular Water% (ECW%), Intracellular Water (ICW%), ECW/ICW, Plasma Fluid (PF), Interstitial Fluid (IF) and Body Density Mass (BDM) were calculated. Results: Changes in 24 h urinary sodium, PRA and plasma aldosterone levels confirmed subjects conformed to the diet. There was no change in BP and HR before and after both diet protocols. HS diet caused significant impairment in microvascular reactivity (PORH) (R-O LS diet 156 ± 23% vs. HS diet 100 ± 12%, P = 0.040). One week HS diet did not induce any significant change in body composition parameters BMI, FFM%, FM% and BDM, compared to LS diet. Body fluid components (TBW%, ECW%, ICW%, ECW/ICW, PF and IF) were not different in LS compared to HS group. Conclusions: This study confirmed that even one week of HS diet significantly altered microvascular reactivity in young healthy normotensive and salt-resistant women, without changes in BP. Furthermore, our results indicate that vascular changes after HS diet are independent of body composition and body fluid status just as they are pressure independent, but are consequence of unique effect of HS on endothelial function.

PP.02.38

The aim of our study was to valuate: 1) how chronic exercise (CEX) modulate body composition components, 2) how CEX affects microvascular reactivity of skin microcirculation (indicator of endothelial function) and 3) is there an association between body composition components and microvascular reactivity in young healthy men. Young healthy lean sedentary subjects (SS) (N = 8) and trained athletes (TR) (N = 16) participated in this study. Blood pressure, heart rate, body mass index (BMI), waist to hip ratio (WHR), fasting lipid panel, plasma glucose and C reactive protein (CRP) were measured in all subjects. Body composition was measured with a four-terminal portable impedance analyzer (Maltron Bioscan 920-II). Empirically derived formulas were used to calculate estimated Fat Mass, Muscle Mass, Total Body Water (TBW), Intra-Cellular Water (ICW) and Extra-Cellular Water (ECW). Skin microvascular post occlusive reactive hyperemic (PORH) blood flow was assessed by laser Doppler flowmetry (LDF). All subjects were normotensive, lean, age-matched males, with no difference in BMI, WHR, arterial blood pressure and heart rate, just as in fastig lipid panel, plasma glucose and CRP between SS and TR. Fat Mass% was significantly higher in SS than in TR (Fat Mass% SS 13.8 ± 4.2 vs. TR 8.7 ± 1.2, P=0.012), while Muscle Mass% was significantly higher in TR than in SS (Muscle Mass% SS 45.8 ± 1.5 vs. TR 48.4 ± 1.4, P=0.022). TBW% was significantly higher in TR when compared to SS (TBW% SS 61.6 ± 3.3 vs. TR 65.8 ± 1.6, P=0.017), without the difference in specific water compartments (ECW% and ICW%) between groups. Skin microvascular PORH was significantly higher in TR compared with SS (R-O SS 85.5 ± 19.2% vs. TR 125.1 ± 37.4%, P=0.005). Multiple linear regression results indicate that among body composition parameters only TBW% is significantly assocciated with skin microvascular PORH (P=0.035). There was no correlation between arterial blood pressure and TBW% in normotensive normaly hydrated subjects. The principle findings of our study are: 1) when trained athletes exibits significantly better skin microvasular reactivity compared to age-matched and physical constitution-matched sedentary subjects, which presupposes better endothelial function ; and 2) TBW% may be a associated with vascular reactivity in normaly hydrated normotensive subjects.

Trial‐to‐Trial and Day‐to‐Day Variability in Forearm Blood Flow During Reactive Hyperemia

Reactive hyperemia (RH) following the release of a brief limb occlusion is commonly used to assess resistance vessel function. The purpose of this study was to examine the impact of repeated trials on the within subject day‐to‐day variability of forearm blood flow during RH. Ten young, healthy, non‐smoking subjects (6 female, 4 male) were examined in the fasted state. Brachial artery diameter and blood velocity were assessed with Echo and Doppler ultrasound, respectively. Subjects visited the lab twice and performed four RH trials each visit. The RH protocol was performed on the left arm and included 5 minutes of forearm cuff occlusion at a pressure of 250 mmHg, followed by release. Within subjects trial‐to‐trial and day‐to‐day variability was assessed by the coefficient of variation (CV = (Standard Deviation/Mean) x 100). The Day‐to‐day CV was calculated using 1) Trial 1 from each day and 2) a 4‐Trial average. Peak forearm blood flow did not differ significantly between trials or days (p &gt; 0.05). Within subject trial‐to‐trial variability was consistent between visits (CV, 9.39 ± 7.78% and 10.1 ± 3.19%; p = 0.737). The within subject day‐to‐day CV determined from the first trial on each day was not significantly different from the CV determined from the four trial average (CV, 14.9± 15.1% and 12.0± 9.62%; p = 0.240). In conclusion, averaging over repeated trials on each visit did not significantly reduce the day‐to‐day variability in peak reactive hyperemia blood flow.

Brachial artery characteristics and micro-vascular filtration capacity in rock climbers

Rock climbers perform repeated isometric forearm muscle contractions subjecting the vasculature to repeated ischaemia and distorted haemodynamic signals. This study investigated forearm vascular characteristics in rock climbers compared to healthy untrained controls. Eight climbers (CLIMB) (BMI; 22.3, s = 2.0 kg/m2, isometric handgrip strength; 46, s = 8 kg) were compared against eight untrained controls (CON) (BMI; 23.8, s = 2.6 kg/m2, isometric handgrip strength; 37, s = 9 kg). Brachial artery diameter and blood flow were measured, using Doppler ultrasound, at rest and following 5-mins ischaemia (peak diameter) and ischaemic exercise (maximal dilation) to calculate flow mediated dilation (FMD) and dilatory capacity (DC). Capillary filtration capacity was assessed using venous occlusion plethysmography. Resting (4.30, s = 0.26 vs. 3.79, s = 0.39 mm), peak (4.67, s = 0.31 vs. 4.12, s = 0.45 mm) and maximal (5.14, s = 0.42 vs. 4.35, s = 0.47 mm) diameters were greater (P < 0.05) in CLIMB than CON, respectively, despite no difference in FMD (9.2, s = 2.6 vs. 8.7, s = 2.9%). Peak reactive hyperaemic blood flow (1136, s = 504 vs. 651, s = 221 ml/min) and capillary filtration capacity (3.8, s = 0.9 vs. 5.2, s = 0.7 ml.min−1.mmHg−1.100 ml tissue−1 × 10−3) were greater (P < 0.05) in CLIMB compared to CON, respectively. Rock climbers exhibit structural vascular adaptation compared to untrained control participants but have similar vascular function. This may contribute to the enhanced ability of climbers to perform repeated isometric contractions.

Effects of isometric handgrip training dose on resting blood pressure and resistance vessel endothelial function in normotensive women

Isometric handgrip (IHG) training lowers resting blood pressure (BP) in both hypertensives and normotensives, yet the effect of training dose on the magnitude of reduction and the mechanisms associated with the hypotensive response are elusive. We investigated, in normotensive women, the effects of two different doses of IHG training on resting BP, and explored improved resistance vessel endothelial function and heart rate variability (HRV) as potential mechanisms of BP reduction. Resting BP, HRV, and resistance vessel endothelial function (venous strain-gauge plethysmography with reactive hyperemia) were assessed in 32 women before and after 4 and 8 weeks of 3×/week (n = 12) or 5×/week (n = 11) IHG training (four, 2-min unilateral contractions at 30 % maximal voluntary contraction), or 0×/week control (n = 9). IHG training decreased systolic BP in the 3×/week (94 ± 6 to 91 ± 6 to 88 ± 5 mmHg, pre- to mid- to post-training; P < 0.01) and 5×/week (97 ± 11 to 90 ± 9 to 91 ± 9 mmHg, P < 0.01) groups, concomitant with increased forearm reactive hyperemic blood flow (26 ± 7 to 30 ± 8 to 36 ± 9 mL/min/100 mL tissue, P < 0.01; and 26 ± 7 to 29 ± 7 to 38 ± 13 mL/min/100 mL tissue, P < 0.01, respectively), yet both remained unchanged in the control group. No changes were observed in diastolic BP, mean arterial BP, or any indices of HRV in any group (all P > 0.05). In conclusion, IHG training lowers resting systolic BP and improves resistance vessel endothelial function independent of training dose in normotensive women.

P68: Laser Doppler perfusion imaging for non-invasive assessment of vascular responses in living mice

Background Methods for the assessment of vascular functions in mice are largely limited to ex vivo organ bath methods particularly the aortic ring assay. We aimed at establishing an easy to perform, sensitive, and valid method for the non-invasive measurement of vascular responses to pharmacological and physiological stimuli in vivo using laser Doppler perfusion imaging (LDPI). Methods Male C57Bl/6, 8–10 week old mice were anesthetized with isoflurane and tissue perfusion of the hindlimb was assessed by LDPI (Perimed, Stockholm, Sweden). The changes in tissue perfusion in response to vasodilators and vasoconstrictors was assessed by acute intraperitoneal (i.p) application of nitroglycerin, intravenous (i.v.) application of acethylcholine, and i.p application of epinephrine. Reactive hyperemic blood flow was induced by occluding the vessels of the hindlimb using an inflatable cuff until the perfusion signal reached the zero level. After 1–5 min of ischemia the cuff pressure was released. We determined intra-individual variability by measuring the same mouse on three consecutive days ( n = 4) and inter-individual variability by comparing the coefficient of variation (CV) of 11 mice. The effect of acute and chronic inhibition of nitric oxide synthase (NOS) or cyclooxygenase (COX) on the hyperemic response was achieved by administration of l -NNA or indometacin i.p or for 6 days in drinking water ad libitum, respectively. Results Application of nitroglycerin increased the perfusion of the hindlimb within approximately 100 s by 127% (191 ± 36 vs. 435 ± 23 perfusion units, PU), while epinephrine (209 ± 59 vs. 90 ± 18 PU:) resulted in a maximum decrease of 57% of the mean perfusion ( n = 5). I.v. administration of adenosine elevated the perfusion by 41% (224 ± 34 vs. 316 ± 43 PU). Reactive hyperemia progressively increased after 1, 3 and 5 min ischemia with the maximal response achieved after 5 min ischemia. Time to maximum reperfusion and the ratio of maximum/baseline perfusion values (perfusion reserve) showed the smallest variation, while the area under the perfusion curve exhibited a CV of 40–50%. Generally, intra-individual variability was lower as compared to inter-individual variability. Chronic oral treatment with l -NNA significantly prolonged the time to maximal perfusion (36 ± 5 vs. 77 ± 18 s), while acute NOS inhibition ( l -NNA i.P) reduced the perfusion reserve (2.5 ± 0.1 vs. 1.8 ± 0.0). In addition, chronic inhibition of COX resulted in a 16 s longer reperfusion (48 ± 5 vs. 64 ± 5 s) but had no effect on the other parameters. Conclusion Taken together, LDPI can be used as a valid and reproducible method for measuring vascular responses to physiological and pharmacological stimuli in the hindlimb of living mice. This may be a valuable experimental model that is similar to methodologies applied in humans enabling a translation of basic science findings. Disclosure Nothing to disclose.

Sex‐differences in the effects of isometric handgrip training on resting blood pressure and resistance vessel function

Isometric handgrip (IHG) training lowers resting blood pressure (BP) in normotensive and hypertensive populations, yet potential sex‐differences and mechanisms associated with the hypotensive response remain unclear. We studied, in normotensives, sex‐differences in the effects of IHG training on resting BP and resistance vessel function (RVF), a hypothesized mechanism of post‐training BP reduction. Resting BP (brachial artery oscillometry) and RVF (venous strain gauge plethysmography with reactive hyperaemia) were assessed in 12 females (23 ± 4 yrs; mean ± SD) and 9 males (21 ± 2 yrs), pre‐ and post‐ 8 wks of IHG training (Four, 2 min unilateral contractions at 30% of maximal effort, 3 d•wk−1). IHG training reduced resting systolic BP in both females and males (Females: 94 ± 6 to 88 ± 5 mmHg; Males: 105 ± 10 to 96 ± 7 mmHg, all P &lt; 0.05), but the magnitude of BP reduction was similar between sexes (P &gt;; 0.05). Diastolic BP remained unchanged in both females and males (Females: 57 ± 7 to 54 ± 6 mmHg; Males: 57 ± 5 to 56 ± 5 mmHg, all P &gt;; 0.05). In each sex, systolic BP reductions occurred concomitant to increases in forearm reactive hyperaemic blood flow (Females: 26 ± 7 to 36 ± 9 mL•min−1•100 mL−1; Males: 35 ± 11 to 38 ± 13 mL•min−1•100 mL−1, all P &lt; 0.05). In conclusion, IHG training effectively lowers resting BP in both females and males, and improved RVF may mediate the post‐training BP response in both sexes. Supported by University of Windsor.

Acute impact of intermittent pneumatic leg compression frequency on limb hemodynamics, vascular function, and skeletal muscle gene expression in humans

The mechanisms by which intermittent pneumatic leg compression (IPC) treatment effectively treats symptoms associated with peripheral artery disease remain speculative. With the aim of gaining mechanistic insight into IPC treatment, the purpose of this study was to investigate the effect of IPC frequency on limb hemodynamics, vascular function, and skeletal muscle gene expression. In this two study investigation, healthy male subjects underwent an hour of either high-frequency (HF; 2-s inflation/3-s deflation) or low-frequency (LF; 4-s inflation/16-s deflation) IPC treatment of the foot and calf. In study 1 (n = 11; 23.5 ± 4.7 yr), subjects underwent both HF and LF treatment on separate days. Doppler/ultrasonography was used to measure popliteal artery diameter and blood velocity at baseline and during IPC treatment. Flow-mediated dilation (FMD) and peak reactive hyperemia blood flow (RHBF) were determined before and after IPC treatment. In study 2 (n = 19; 22.0 ± 4.6 yr), skeletal muscle biopsies were taken from the lateral gastrocnemius of the treated and control limb at baseline and at 30- and 150-min posttreatment. Quantitative PCR was used to assess mRNA concentrations of genes associated with inflammation and vascular remodeling. No treatment effect on vascular function was observed. Cuff deflation resulted in increased blood flow (BF) and shear rate (SR) in both treatments at the onset of treatment compared with baseline (P < 0.01). BF and SR significantly diminished by 45 min of HF treatment only (P < 0.01). Both treatments reduced BF and SR and elevated oscillatory shear index compared with baseline (P < 0.01) during cuff inflation. IPC decreased the mRNA expression of cysteine-rich protein 61 from baseline and controls (P <0 .01) and connective tissue growth factor from baseline (P < 0.05) in a frequency-dependent manner. In conclusion, a single session of IPC acutely impacts limb hemodynamics and skeletal muscle gene expression in a frequency-dependent manner but does not impact vascular function.

Impact of endovascular treatment of atherosclerotic renal artery stenosis on endothelial function and arterial blood pressure.

Renovascular disease may cause arterial hypertension and decreases renal function, which both impair endothelial function. Endothelial function, a surrogate marker for cardiovascular risk, can be assessed non-invasively by ultrasound. The aim of this study was to investigate the impact of percutaneous transluminal renal artery angioplasty (PTRA) with stenting on endothelial function and arterial blood pressure in patients with renal artery stenosis (RAS). Flow mediated dilatation of the brachial artery, flow velocities and shear stress were measured with high resolution ultrasound in 24 hypertensive patients with renal artery stenosis prior and one day after revascularization by PTRA with stenting. Endothelial-independent brachial dilatation was measured after application of nitroglycerin. Endothelial-dependent dilatation improved from 2.4±0.9% to 6.1±1.4% (P=0.03), whereas endothelial-independent dilatation did not change after PTRA. Endothelial-dependent reactive hyperemic blood flow increased from 195±40 mL/min to 536±94 mL/min (P=0.0008), whereas endothelial-independent hyperemia did not increase after revascularization. After PTRA, shear stress at rest decreased from 37±11 to 23±3 dyne/cm² (P<0.0001), and reactive hyperemic shear stress increased from 89±29 to 107±12 dyne/cm² (P=0.014). The impact of PTRA on arterial blood pressure resulted in a mean decrease of 21±5 mmHg in systolic pressure (P<0.0001), of 9±2 mmHg in diastolic pressure (P=0.03), and of 14±5 mmHg in peripheral pulse pressure (P=0.0003), respectively. Endovascular treatment of renovascular disease improves endothelial function and decreases in resting shear stress.

Effects of limb posture on reactive hyperemia

To examine the role of limb posture on vascular conductance during rapid changes in vascular transmural pressure, we determined brachial (n = 10) and femoral (n = 10) artery post-occlusive reactive hyperemic blood flow (RHBF, ultrasound/Doppler) and vascular conductance in healthy humans with each limb at three different positions-horizontal, up and down. Limb posture was varied by raising or lowering the arm or leg from the horizontal position by 45°. In both limbs, peak RHBF and vascular conductance were highest in the down or horizontal position and lowest in the up position (arm up 338 ± 38, supine 430 ± 52, down 415 ± 52 ml/min, P < 0.05; leg up 1,208 ± 88, supine 1,579 ± 130, down 1,767 ± 149 ml/min, P < 0.05). In contrast, the maximal dynamic fall in blood flow following peak RHBF (in ml/s/s) in both limbs was highest in the limb-down position and lowest with the limb elevated (P < 0.05). These data suggest that the magnitude and temporal pattern of limb reactive hyperemia is in part related to changes in vascular transmural pressure and independent of systemic blood pressure and sympathetic control.

Impaired Leg Vasodilatory Function After Stroke

Resting and reactive hyperemic leg blood flows are significantly reduced in the paretic compared with the nonparetic limb after disabling stroke. Our objective was to compare the effects of regular treadmill exercise (TM) with an active control regimen of supervised stretching (CONTROL) on peripheral hemodynamic function. This intervention study used a randomized, controlled design, in which participants were randomized with stratification according to age and baseline walking capacity to ensure approximate balance between the 2 groups. Fifty-three chronic, ischemic stroke participants (29 TM and 24 CONTROL) with mild to moderate hemiparetic gait completed bilateral measurements of lower leg resting and reactive hyperemic blood flow using venous occlusion strain gauge plethysmography before and after the 6-month intervention period. Participants also underwent testing to track changes in peak aerobic fitness across time. Resting and reactive hyperemic blood flows were significantly reduced in the paretic compared with the nonparetic limb at baseline before any intervention (-28% and -34%, respectively, P<0.01). TM increased both resting and reactive hyperemic blood flow in the paretic limb by 25% compared with decreases in CONTROL (P<0.001, between groups). Similarly, nonparetic leg blood flow was significantly improved with TM compared with controls (P<0.001). Peak aerobic fitness improved by 18% in TM and decreased by 4% in CONTROL (P<0.01, between groups), and there was a significant relationship between blood flow change and peak fitness change for the group as a whole (r=.30, P<0.05). Peripheral hemodynamic function improves with regular aerobic exercise training after disabling stroke.

The Effect of Exercise on Haemodynamics in Intermittent Claudication

Changes in lower limb haemodynamics such as arterial pressure and/or flow have often been, and continue to be, cited as possible mechanisms for the improvement in walking performance that occurs with exercise training in individuals with peripheral arterial disease (PAD), but data are conflicting in this regard. There are a small number of literature reviews examining the effects of exercise on PAD, however, there has been insufficient analysis synthesizing possible mechanisms of effect, overall benefits and limitations of these trials. Our objective was therefore to systematically review the evidence for the effect of exercise on lower limb haemodynamic measures of resting and post-exercise ankle brachial index (ABI), resting toe pressure, and resting and reactive hyperaemic calf blood flow in PAD. A systematic search of studies published between 1934 and March 2010 was conducted using MEDLINE, EMBASE, AMED, SportDiscus, CINAHL, PEDro, Premedline, Google Scholar and Web of Knowledge databases. Eligible studies included randomized controlled trials using an exercise intervention for the treatment of intermittent claudication with haemodynamic measures of disease severity as outcomes. Relative effect sizes (ESs) and 95% confidence intervals were calculated for outcomes. Correlation and regression analyses were performed to establish relationships between symptoms and haemodynamic outcomes. Thirty-three trials including 1237 subjects with mild to moderate claudication met the eligibility criteria. Exercise did not significantly change lower extremity haemodynamics in most trials; nor were clinical improvements related to changes in resting ABI (mean ES 0.09 +/- 0.26; r = 0.02; p = 0.94), post-exercise ABI (mean ES 0.18 +/- 0.3; r = -0.33; p = 0.52) or reactive hyperaemic calf blood flow (mean ES 0.38 +/- 0.67; r = 0.35; p = 0.26). A relationship may exist between a change in symptoms and changes in resting toe pressure (mean ES 0.22 +/- 0.22; r = 0.75; p = 0.25) and resting calf blood flow (mean ES 0.09 +/- 0.16; r = 0.59; p = 0.22). Changes in resting and post-exercise ABI and reactive hyperaemic calf blood flow do not appear to explain the clinical benefits of exercise in PAD. More study is required in the areas of resting toe pressure and resting calf blood flow.

Effects of Smoking and Smoking Cessation on Endothelial Function: 1-Year Outcomes From a Randomized Clinical Trial

The purpose of this study was to determine whether smoking cessation improves flow-mediated dilation (FMD) of the brachial artery. The long-term effects of continued smoking and smoking cessation on endothelial function have not been described previously. This was a 1-year, prospective, double-blind, randomized, placebo-controlled clinical trial of the effects of 5 smoking cessation pharmacotherapies. FMD was measured by B-mode ultrasonography before and 1 year after the target smoking cessation date. Cessation was verified by exhaled carbon monoxide levels. DeltaFMD was compared among study arms and between subjects who successfully quit smoking and those who continued to smoke. Predictors of baseline FMD and DeltaFMD were identified by multivariable regression. The 1,504 current smokers (58% female, 84% white) were 44.7 +/- 11.1 years of age and smoked 21.4 +/- 8.9 cigarettes/day. Baseline FMD was similar in each treatment arm (p = 0.499) and was predicted by BA diameter (p < 0.001), reactive hyperemia blood flow (p < 0.001), high-density lipoprotein cholesterol (p = 0.001), and carbon monoxide (p = 0.012) levels. After 1 year, 36.2% quit smoking. FMD increased by 1% (6.2 +/- 4.4% to 7.2 +/- 4.2%) after 1 year (p = 0.005) in those who quit, but did not change (p = 0.643) in those who continued to smoke. Improved FMD among quitters remained significant (p = 0.010) after controlling for changes in brachial artery diameter, reactive hyperemia, low-density lipoprotein cholesterol, and the presence of a home smoking ban. Despite weight gain, smoking cessation leads to prolonged improvements in endothelial function, which may mediate part of the reduced cardiovascular disease risk observed after smoking cessation. (Smoking Cessation Medications: Efficacy, Mechanisms and Algorithms; NCT00332644).

Rapid vascular modifications to localized rhythmic handgrip training and detraining

Despite the evidence describing the rapid vascular function modifications to commencement and cessation of large muscle exercises (i.e. cycling), no studies examined the time-course vascular modifications to localized training and detraining. This study aimed to examine the effects of 4-week rhythmic handgrip exercise training and 2-week detraining on reactive hyperemic forearm blood flow and vascular resistance in 11 young men. Rhythmic handgrip exercise was performed in the non-dominant forearm for 20 min/day, 5 days/week, at 60% of maximum voluntary contraction for 4 weeks, followed by 2 weeks of no training. Forearm blood flow and vascular resistance were evaluated, in both arms, at rest and following arterial occlusion. These vascular function indices were obtained in five visits; before, after 1 and 4 week(s) of training as well as after 1 and 2 week(s) of training cessation. Resting cardiovascular measures were not altered during the study period. A 2 (arms) x 5 (visits) ANOVA revealed significant arms-by-visits interactions for reactive hyperemic forearm blood flow (p = 0.02) and vascular resistance (p = 0.02). Subsequent comparison demonstrated increased trained forearm reactive hyperemic blood flow 1 week after training, then returned to pre-training values 1 week following training cessation. In contrast, vascular resistance decreased 1 week after training commencement, only to return to pretraining level 1 week after training cessation. These results indicate a rapid, unilateral improvement in regional reactive hyperemic blood flow and vascular resistance following localized exercise-training. However, the improvements are transient and return to pretraining levels 1 week after detraining.