Venoarteriolar Response Research Articles

RETRACTION: Augmented venoarteriolar response with ageing is associated with morning blood pressure surge.

RETRACTION: Augmented venoarteriolar response with ageing is associated with morning blood pressure surge.

The effect of transdermal combined product on the state of microcirculatory blood flow in patients with chronic venous insufficiency

Introduction. Treatment of patients with severe chronic venous insufficiency of the lower extremities is complex and along with compression therapy includes transdural use of drugs. Aim. To study the microcirculatory blood flow of the tissues of the distal segments of the lower limbs in patients with severe chronic venous insufficiency and the possibility of its correction with the use of a combined product for local application.Materials and мethods. The study included 40 patients suffering from varicose vein disease with chronic venous insufficiency of C3-C5 stages according to CEAP. In the main group of patients (n = 30) the transdermal combined product Detragel® was used; patients of the comparison group (n = 10) received only basic compression therapy of functional class II. The basis for the assessment of microcirculation of the lower limbs soft tissues was the analysis of the results of laser doppler flowmetry. Results. At local use of Detragel® in combination with elastic bandage in 91% of observations, there was a statically significant decrease of basal blood flow less than 4.0 pf. units (p < 0.05). The mean basal blood flow was 2.7 ± 0.6 pf. units (1.6–3.9 pf. units, 95% CI), which was consistent with normal values. Statistically significant decrease in veno-arteriolar response to 51.5 ± 10.8% (36.0–68.8%, 95% CI) was recorded in 75% of cases after 14 days of topical treatment, although veno-arteriolar response decreased to normal in only 53% of cases. Conclusion. Correction of microcirculatory disorders in patients with varicose vein disease should include local use of medicine.

Effect of reflex and mechanical decreases in skin perfusion on thermal- and agonist-induced eccrine sweating in humans.

In humans, skin blood flux (SkBF) and eccrine sweating are tightly coupled, suggesting common neural control and regulation. This study was designed to separate these two sympathetic nervous system end-organ responses via nonadrenergic SkBF-decreasing mechanical perturbations during heightened sudomotor drive. We induced sweating physiologically via whole body heat stress using a high-density tube-lined suit (protocol 1; 2 women, 4 men), and pharmacologically via forearm intradermal microdialysis of two steady-state doses of a cholinergic agonist, pilocarpine (protocol 2; 4 women, 3 men). During sweating induction, we decreased SkBF via three mechanical perturbations: arm and leg dependency to engage the cutaneous venoarteriolar response (CVAR), limb venous occlusion to engage the CVAR and decrease perfusion pressure, and limb arterial occlusion to cause ischemia. In protocol 1, heat stress increased arm cutaneous vascular conductance and forearm sweat rate (capacitance hygrometry). During heat stress, despite decreases in SkBF during each of the acute (3 min) mechanical perturbations, eccrine sweat rate was unaffected. During heat stress with extended (10 min) ischemia, sweat rate decreased. In protocol 2, both pilocarpine doses (ED50 and EMAX) increased SkBF and sweat rate. Each mechanical perturbation resulted in decreased SkBF but minimal changes in eccrine sweat rate. Taken together, these data indicate that a wide range of acute decreases in SkBF do not appear to proportionally decrease either physiologically- or pharmacologically induced eccrine sweating in peripheral skin. This preservation of evaporative cooling despite acutely decreased SkBF could have consequential impacts for heat storage and balance during changes in body posture, limb position, or blood flow restrictive conditions.

Restless legs syndrome: prevention with Pycnogenol® and improvement of the venoarteriolar response.

The aim of this registry study was to evaluate the preventive efficacy of Pycnogenol® (French maritime pine bark, standardized extract), an anti-inflammatory and antioxidant supplement, previously used for muscular pain and cramps, in otherwise healthy subjects with restless legs syndrome (RLS). Two management groups were formed: one using the standard management (SM) and one using SM and Pycnogenol® 150 mg/day for 4 weeks. Forty-five subjects were included in the study, 21 took Pycnogenol® and 24 were in the SM group. After 4 weeks no side effects or tolerability problems were observed. Compliance was optimal. The two groups were comparable at baseline. Limb sensations were assessed with a Visual Analogue Scale Line (0 to 4). There was a statistically non-significant improvement with SM in all subjects. Improvement with Pycnogenol® supplementation was significant (P<0.05) for all assessed parameters with important clinical meanings as 19 out of 21 supplemented subjects reported a clear benefit from supplementation. Resting flux - slightly elevated at inclusion - was normalized in the supplemented group (P<0.05) as seen by a decrease in flux. The venoarteriolar response - affected at inclusion in all subjects with RLS - was improved with the supplement, indicating a better axon-axon reflex response and a lower level of subclinical neural alteration. The need for pain managements was significantly reduced (P<0.05) with supplementation after 4 weeks, as only 4/21 supplemented subjects vs. 16/24 in the SM-only group had to use analgesics. Thermography of the leg did not reveal any significant asymmetry of perfusion. Oxidative stress as plasma free radicals (PFR) was significantly improved (reduced) (P<0.05) in subjects using Pycnogenol®. Likewise, minimal edema, measured with the edema tester, was significantly decreased with Pycnogenol®. Pycnogenol® prevents or relieves symptoms associated with restless leg syndrome and positively affects the venoarteriolar response. Future studies in this condition, including more complex subjects may indicate the role of Pycnogenol® in this common and still obscure syndrome and in subclinical muscular and neurological alterations.

Augmented venoarteriolar response with ageing is associated with morning blood pressure surge.

What is the central question of this study? The venoarteriolar response (VAR) contributes substantially to the maintenance of orthostatic tolerance in humans. Despite its importance in haemodynamic homeostasis, the impact of ageing on the VAR remains understudied. What is the main finding and its importance? Older adults exhibit an augmented VAR in response to leg dependency. The age-related augmentation of the VAR might be linked with progressive increases of peripheral vascular resistance with ageing. We found a modest but significant correlation between the leg VAR and the morning blood pressure surge in older adults. Augmented leg VAR might contribute to the blood pressure elevation in the early morning. The venoarteriolar response (VAR) is a non-adrenergic, non-baroreflex-mediated mechanism of vasoconstriction, which has been proposed to contribute ∼45% of the increase in total peripheral resistance during orthostasis. Despite its importance in human cardiovascular control during orthostatic stress, there is no information available regarding the impact of age and sex on the VAR or its role in diurnal blood pressure (BP) variation. We studied 33 (15 women) young (mean± SD; 28± 4 years old) and 26 (12 women) older (71± 3 years old) healthy individuals. Brachial and femoral blood flow were measured using Doppler ultrasound. The percentage reduction in vascular conductance (blood flow/mean BP) during 4min of limb dependency (35-40cm below the heart level) was used to assess the VAR. The morning surge in BP was assessed using 24h ambulatory BP monitoring. Peak VAR in the lower limb, but not in the upper limb, was significantly higher in the older than the younger adults (33± 4versus 26± 6%, older versus young; P< 0.05). There was no sex difference in the VAR in either the young or the older group. A greater leg VAR was related to a greater morning surge in BP in older adults (r= -0.4, P= 0.02) but not in the young adults (r= -0.26, P= 0.1). Thus, advancing age enhances the VAR in the lower limb and is associated with the morning blood pressure surge in older adults. Sex does not affect this local axonal reflex in healthy humans.

Effect of reflex and mechanical decreases in skin blood flow on exogenous cholinergic‐induced eccrine sweating in humans

Human skin blood flow (SkBF) and sweating increase concurrently during increases in skin sympathetic nerve activity and subsequent neurotransmitter release to these cutaneous appendages. Previous studies have blocked sweating without affecting SkBF with the use of the muscarinic agonist atropine, but few have altered SkBF without affecting sweating because standard methods such as introducing an α‐adrenergic agonist decrease SkBF but also can engage eccrine sweat gland receptors. Thus, this study aimed to utilize non‐adrenergic mechanical perturbations to decrease SkBF during intradermal perfusion of a cholinergic agonist. Three intradermal microdialysis fibers were placed in dorsal forearm skin of 4 women and 3 men (age 24±1 yr, height 173±4 cm, weight 80±8 kg) to perfuse 2 doses of pilocarpine nitrate (0.01 and 1.66 mg/ml, corresponding to the ED50 and EMAX from previous dose‐response modeling) or the vehicle (lactated Ringer's). Forearm SkBF (laser‐Doppler flowmetry) was decreased for 3 min by engaging the venoarteriolar response (arm lowered ~30 cm from heart level; CVAR), venoarteriolar response plus decreased perfusion pressure (venous occlusion by proximal cuff inflation; CVAR with ΔPP), and ischemia (arterial occlusion by proximal cuff inflation); sweat rate was measured by perfusing anhydrous medical air through a ventilated capsule (capacitance hygrometry). Drug infusions significantly increased SkBF (+87±18 and +57±16 units) and sweating (+0.37±0.20 and +0.64±0.15 mg/ml/min, for pilocarpine ED50 and EMAX, respectively) compared to vehicle control in which SkBF minimally increased (+8±4 units) and there was no alteration in sweating (−0.02±0.09). Decreased SkBF was observed with CVAR (−26±14, −33±9, and −38±9%), CVAR with ΔPP (−62±7, −42±20 and −61±8%), and ischemia (−99±1, −92±5 and −93±2% for pilocarpine ED50, pilocarpine EMAX, and vehicle control, respectively). Despite these significant decreases in SkBF, changes in eccrine sweat rate were minimal (CVAR = −1±12, +3±3, and −2±5%; CVAR with ΔPP = +3±7, −2±4, and −3±4%; and ischemia = +5±10, +5±5, and +6±5% for pilocarpine ED50, pilocarpine EMAX, and vehicle control, respectively). These data suggest that very acute decreases in SkBF do not proportionally decrease cholinergic‐induced sweating in human forearm skin.This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.

Effect of decreasing peripheral skin blood flow via local axon reflexes, decreases in perfusion pressure, and ischemia during systemic thermal‐induced eccrine sweating in humans

In humans, skin blood flow (SkBF) and sweating are tightly coupled, suggesting common neural control and regulation and possible interactive effects of extracellular fluid delivery and sweat secretion. This study was designed to separate these two sympathetic nervous system end‐organ responses via SkBF‐decreasing mechanical perturbations in the presence of a strong sudomotor drive. Two women and 4 men (age 26±1 yrs and BMI 24±4 kg/m2) were tested in normothermia and heat stress conditions, by pumping neutral (34°C) and hot (46–50°C) water through a high‐density tube‐lined suit to either maintain internal temperature (pill telemetry) or increase it by ~1.0°C. Arm and leg SkBF (laser‐Doppler flowmetry) was decreased for 3 min by engaging the venoarteriolar response (limb lowered ~30 cm from heart level; CVAR), venoarteriolar response plus a decrease in perfusion pressure (venous occlusion by proximal cuff inflation; CVAR with ΔPP), and ischemia (arterial occlusion by proximal cuff inflation). Decreased SkBF was observed with CVAR (30±7 and 60±15%), CVAR with ΔPP (44±12 and 86±11%), and ischemia (96±1 and 99±1% for the arm and leg, respectively) during normothermia. Despite these significant decreases in SkBF, there were no significant effects on transepidermal water loss (TEWL). Heat stress increased intestinal temperature from 37.1±0.1 to 38.0±0.1°C, heart rate (ECG) from 65±5 to 93±4 bpm, arm cutaneous vascular conductance (SkBF/mean arterial pressure*100) from 52±12 to 473±85 units, and forearm sweat rate (capacitance hygrometry) from 0.0 to 0.6±0.1 mg/ml/min. During heat stress, decreased SkBF was also observed during CVAR (20±7 and 17±6%), CVAR with ΔPP (39±9 and 52±13%), and ischemia (99±1 and 100±1% for the arm and leg, respectively). Despite these significant decreases in SkBF, eccrine sweat rate was not significantly affected. These data indicate that a wide range of acute changes in SkBF do not appear to affect TEWL or eccrine sweating in peripheral skin.This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.

Pathophysiological mechanisms of chronic venous disease and their role in C0s clinical class

The aim of this review is to provide a clear understanding of the pathophysiological mechanisms of chronic venous disease (CVD) at different clinical stages and the possible role of these mechanisms in the development of symptoms in C0s clinical class of the Clinical, Etiologic, Anatomic, and Pathophysiologic classification, which consists of symptomatic patients without any visible or palpable signs of venous disease. The prevalence of C0s class in several epidemiological studies varies between 13% and 23% of the general population. Wall remodeling and valve destruction due to white cell endothelial interaction is the main cause of primary varicose veins, while deep vein thrombosis produces secondary changes leading to the postthrombotic syndrome. The underlying mechanism of the skin changes and ulceration is venous hypertension, which is transmitted to the skin microcirculation. Over the last 10 years, an improved videocapillaroscopic technique, the orthogonal polarization spectral imaging technique demonstrated that quantitative measurements in the skin microcirculation are progressively altered from C1 to C6 patients and that values in CVD patients are significantly different from healthy individuals (P < 0.05): capillary diameter increases and capillary morphology worsens from C2 to C5; diameter of the dermal papilla and diameter of the capillary bulk increase from C3 to C5; and functional capillary density (FCD) decreases from C4 to C5. In addition, significant changes have been shown between C0a and C0s patients despite the presence of normal conventional duplex scans in the latter: a decrease of FCD and an increase in the diameter of the dermal papilla. Functional abnormalities found to be present in C0s patients by recent studies include increased compliance of the venous wall (hypotonic phlebopathy), dilatation of deep veins in the calf producing an abnormally increased venous volume, reduction in emptying of venous reservoir, reduction in the venoarteriolar response on standing, and blood reflux in small venules despite a normal conventional duplex scan. However, most of the studies are small, and their findings need to be confirmed by larger series. It remains to be seen whether functional changes and microcirculatory changes respond to venoactive medications in parallel to the relief of symptoms.

Advancing Age Is Associated with Augmented Venoarteriolar Response to Leg Dependency

BackgroundThe venoarteriolar response (VAR) is a non‐baroreflex mediated regional vasoconstriction mechanism which has been proposed to contribute to about 45% of the increase in total peripheral resistance during orthostasis. Advancing age is related to elevated total peripheral resistance and it is involved in the pathogenesis of hypertension. However, whether advancing age is associated with an enhanced VAR is not known.ObjectiveTo test the hypothesis that there are sex and age differences in the VAR among healthy individuals.Method18 (10 women) young (mean±SD; 28±4 years) and 22 (11 women) older (72±4 years) healthy normotensive adults participated in the study. Brachial and femoral artery diameter and blood flow velocity were measured using doppler ultrasound. Forearm and calf cutaneous blood flow were measured using laser‐doppler flowmetry. Assessments were performed while the arm and leg were in the horizontal position and repeated following limb dependency (35–40 cm below the heart level) for 5 min. Blood pressure (BP, SunTech) and heart rate (HR, electrocardiogram) were also measured. The percent reduction in vascular conductance (=blood flow/mean BP) during limb dependency was used to assess the VAR.ResultsThe VAR was not different between dominant and non‐dominant limbs. The VAR was more pronounced in the leg compared with the arm (24+/−7% vs. 18+/−5%; P=0.04) while it was not different between men and women. Older subjects had a greater VAR in the leg compared with their younger counterparts (29+/−8% vs. 21+/5%; P=0.04), but the VAR in the arm did not differ between the groups (17+/−6 vs. 19+/−4%, young vs. old; P=0.80). Cutaneous VAR showed similar results as those measured by doppler ultrasound. BP and HR remained unchanged prior to and during limb dependency.ConclusionAging is associated with augmented venoarteriolar response in the leg but not in the arm. The enhanced venoarteriolar response induced vasoconstriction may contribute importantly to hypertension in the older population.

A Systematic Review of the Efficacy of Centella asiatica for Improvement of the Signs and Symptoms of Chronic Venous Insufficiency.

We aimed to assess the efficacy of Centella asiatica for improvement of the signs and symptoms of chronic venous insufficiency (CVI). We searched 13 electronic databases including the Cochrane Central Register of Controlled Trials for randomised controlled trials assessing the efficacy of Centella asiatica for CVI. Two review authors independently selected studies, assessed the risks of bias of included studies and extracted data. The treatment effects of similar studies were pooled whenever appropriate. Eight studies met the inclusion criteria. The pooling of data of similar studies showed that Centella asiatica significantly improved microcirculatory parameters such as transcutaneous partial pressure of CO2 and O2, rate of ankle swelling and venoarteriolar response. Three out of the eight studies did not provide quantitative data. However, these studies reported that patients treated with Centella asiatica showed significant improvement in CVI signs such as leg heaviness, pain and oedema. Our results show that Centella asiatica may be beneficial for improving signs and symptoms of CVI but this conclusion needs to be interpreted with caution as most of the studies were characterised by inadequate reporting and thus had unclear risks of bias, which may threaten the validity of the conclusions.

Elderly Blacks Have a Blunted Sympathetic Neural Responsiveness But Greater Pressor Response to Orthostasis Than Elderly Whites

Neural control of blood pressure (BP) has been reported to differ between young blacks and whites. We hypothesized that elderly blacks have enhanced sympathetic neural responses during orthostasis compared with elderly whites. Muscle sympathetic nerve activity, arm-cuff BP, and heart rate were recorded continuously, and cardiac output, stroke volume, and total peripheral resistance were measured intermittently during supine and 5-minute 60° upright tilt in 10 blacks (65 [SD, 4] years; 4 women) and 20 whites (68 [6] years; 8 women). We found that muscle sympathetic nerve activity burst frequency was similar between blacks and whites in the supine position (44 [10] versus 42 [7] bursts per minute) and during upright tilt (59 [11] versus 60 [9] bursts per minute; P=0.846 for race, P<0.001 for posture, and P=0.622 for interaction). However, upright total muscle sympathetic nerve activity was smaller in blacks than in whites (162 [39] versus 243 [112]%; P=0.003). Systolic BP, heart rate, cardiac output, and stroke volume were not different between groups. Diastolic BP was similar in the supine position, increased in all of the subjects during tilting; upright diastolic BP was greater in blacks than in whites (80 [10] versus 71 [7] mmHg; P=0.008). Total peripheral resistance did not differ between blacks and whites in the supine position or during upright tilt (P=0.354 for race, P<0.001 for posture, P=0.825 for interaction). Thus, elderly blacks have a blunted sympathetic neural responsiveness but enhanced pressor response to orthostasis compared with elderly whites, which may be attributable to an augmented sympathetic vascular transduction and/or nonadrenergic vasoconstrictor mechanisms (ie, angiotensin II or the venoarteriolar response).

Spatial variation of the veno-arteriolar reflex (VAR) and effect of reconstructive surgery in limbs with chronic critical limb ischaemia (CLI)

Ischaemic ulcers and necrosis tend to appear first in the most distal part of the feet in patients with chronic critical limb ischaemia (CLI), indicating that derangements in local microcirculation are focally distributed. In the present study the veno-arteriolar response (VAR), as an indicator of microcirculatory regulation, was obtained in three different areas of critically ischaemic feet. Five women and seven men, mean age 75 years, with unilateral CLI were included. Two groups including young and age-matched healthy participants served as controls. Laser Doppler flux (LDF) was recorded simultaneously at the pulp of the first toe (site 1), the level of the second metatarsal body (site 2), and the anterolateral part of the ankle (site 3). LDF was recorded with the investigated limb in supine and dependent positions. Orthostatic response (OR) was calculated at all measuring sites as perfusion (LDF) in the dependent foot divided by perfusion in the supine position. There was no difference in OR between the control groups, or between sites within each group. Median OR was about 0.5, indicating that perfusion was reduced to 50% during dependency. In patients with CLI, VAR was not present in the afflicted foot and ankle, and OR at the three sites were significantly greater than in controls (p<0.0005). Median OR at site 1 was 3.7, indicating considerably increased local perfusion when the foot was lowered. At site 2 the increase was moderate, and there was no increase present at site 3 (median OR=1.0). There was a significant trend towards normal values (OR<0.8) after vascular reconstruction at all sites. Abolished VAR and increased local perfusion in ischaemic limbs assist in explaining why patients with ischaemic rest pain obtain relief of pain with dependency. The recovery of VAR following reconstructive surgery indicates that the microcirculatory derangement is reversible.

Effect of whole body heat stress on peripheral vasoconstriction during leg dependency

The venoarteriolar response (VAR) increases vascular resistance upon increases in venous transmural pressure in cutaneous, subcutaneous, and muscle vascular beds. During orthostasis, it has been proposed that up to 45% of the increase in systemic vascular tone is due to VAR-related local mechanism(s). The objective of this project was to test the hypothesis that heat stress attenuates VAR-mediated cutaneous and whole leg vasoconstriction. During normothermic conditions, measurements of cutaneous blood flow (laser-Doppler flowmetry) and femoral artery blood flow (Doppler ultrasound) were obtained from both legs during supine and leg-dependent conditions. These measurements were repeated following a whole body heat stress (increase in internal temperature of 1.4 +/- 0.2 degrees C). Before leg dependency, cutaneous (CVC) and femoral vascular conductances (FVC) were significantly elevated in both legs during heat stress relative to normothermia (P < 0.001). During leg dependency the absolute decrease in CVC was attenuated during heat stress (P < 0.01) while the absolute decrease in FVC was unaffected (P = 0.90). When CVC and FVC data were analyzed as a relative change from their respective baseline values, heat stress significantly attenuated the magnitude of vasoconstriction due to leg dependency in the cutaneous and femoral circulations (P < 0.001 for both variables). These data suggest that an attenuated local vasoconstriction, evoked via the venoarteriolar response, may contribute to reduced blood pressure control and thus reduced orthostatic tolerance that occurs in heat-stressed individuals.

Venoarteriolar Response Is Unaltered By Beta-adrenergic Blocker Or Exercise Training In Postural Orthostatic Tachycardia Syndrome

Postural Orthostatic Tachycardia Syndrome (POTS) is characterized by excessive tachycardia during orthostasis. We previously found that POTS patients have enhanced venoarteriolar response (VAR) when compared to healthy sedentary women. Whether a standard pharmacologic treatment for POTS such as beta blockers, or non-pharmacological treatment like exercise training could normalize the VAR in these patients is unknown. PURPOSE: We tested the hypothesis that short-term exercise training would attenuate cutaneous VAR to a greater extent than beta blocker treatment. METHODS: Nineteen patients (18 females, 1 male), age 15-44 years were studied. First, patients were given a random, double-blind assignment to receive either placebo (n=10) or non-selective beta blocker (n=9, propanolol, 80 mg q.d.) treatment for 4 wk, and then patients (n=17) completed a 3-mo exercise training program. Female patients were tested during mid-luteal phases of their menstrual cycles before and after medication treatment, and after exercise training. Skin blood flow (SkBF, laser-Doppler flowmetry), was measured in the calf at heart level (baseline, BL) and during leg dependency of 17-35 cm below the heart for 2 min each while supine. RESULTS: Blood pressure (BP, Portapres) and heart rate (HR, ECG) were monitored continuously. Both HR and BP were not different at BL compared to during leg dependency, except diastolic BP was slightly higher during leg dependency in the pre exercise training group [BL 62±11 (SD) mmHg vs. leg dependency 63±12, P=0.037]. HR was significantly lower after beta blocker (BL 86±16 bpm vs. 71±13, P=0.002) and after exercise training (81±14 bpm vs. 72±15, P=0.002). Only the group taking beta blocker had significant reductions in systolic and diastolic BP (P=0.013 and 0.008) after treatment. VAR, determined by the relative decrease in SkBF during leg dependency, was not different after placebo (-45±10% vs. -42±13, P=0.571), beta blocker (-42±12% vs. -38 ±14, P=0.471) or exercise training (-41±13% vs. -46±11, P=0.314). CONCLUSION: These results suggest that the enhanced VAR observed in POTS patients is not affected by beta blocker or exercise training. However, the pathophysiology for such enhanced VAR and the effective therapy still need to be determined. Supported by NIH K23 (HL0752 83) and the GCRC grant (RR00633).

Effect of whole‐body heat stress on peripheral vasoconstriction during engagement of the venoarteriolar response

The aim of this study was to test the hypothesis that whole‐body heat stress attenuates venoarteriolar response (VAR) mediated vasoconstriction of the cutaneous and whole‐leg circulations. During normothermia (NT), cutaneous blood flow (CBF) and femoral artery blood flow (FBF) were obtained during supine and leg dependent conditions. These measurements were repeated following whole‐body passive heat stress (WBH) that increased internal temperature by 1.4±0.2 °C. Cutaneous (CVC) and femoral vascular conductances (FVC) were calculated by dividing CBF and FBF by mean arterial pressure. During leg dependency, the absolute decrease in CVC (NT: 0.22 ± 0.1; WBH: 0.19 ± 0.3 arbitrary units·mmHg−1; P=0.97) and FVC (NT: 1.90 ± 1.7; WBH: 0.70 ± 2.1 ml·min−1·mmHg−1; P=0.71) were similar between thermal conditions. However, since WBH substantially increased CVC and FVC (P&lt;0.001 for both variables), the percent reduction in CVC (NT: 58 ± 9%; WBH: 9.4 ± 9.1%, P&lt;0.001) and FVC (NT: 33 ± 21%; WBH: 6.0 ± 17%; P=0.02) during leg dependency were attenuated during WBH relative to NT. These data suggest that heat stress reduces the vasoconstrictive response in the cutaneous and whole leg circulations during engagement of the VAR via leg dependency. These attenuated responses may contribute to reduced blood pressure control in hyperthermic subjects leading to impaired orthostatic tolerance.

Integrity of venoarteriolar reflex determines level of microvascular skin flow enhancement with intermittent pneumatic compression

To investigate whether intermittent pneumatic compression (IPC) augments skin blood flow through transient suspension of local vasoregulation, the veno-arteriolar response (VAR), in healthy controls and in patients with peripheral arterial disease (PAD). Nineteen healthy limbs and twenty-two limbs with PAD were examined. To assess VAR, skin blood flow (SBF) was measured using laser Doppler fluxmetry in the horizontal and sitting positions and was defined as percentage change with postural alteration [(horizontal SBF--sitting SBF)/horizontal SBF x 100]. On IPC application to the foot, the calf, or both, SBF was measured with laser Doppler fluxmetry, the probe being attached to the pulp of the big toe. Baseline VAR was higher in the controls 63.8 +/- 6.4% than in patients with PAD (31.7 +/- 13.4%, P = .0162). In both groups SBF was significantly higher with IPC than at rest (P < .0001). A higher percentage increase with IPC was demonstrated in the controls (242 +/- 85% to 788 +/- 318%) than in subjects with PAD, for each one of the three different IPC modes investigated (98 +/- 33% to 275 +/- 72%) with IPC was demonstrated. The SBF enhancement with IPC correlated with VAR for all three compression modes (r = 0.58, P = .002 for calf compression, r = 0.65, P < .0001 for foot compression alone, and r = 0.64, P = .0002 for combined foot and calf compression). The integrity of the veno-arteriolar response correlates with the level of skin blood flow augmentation generated with intermittent pneumatic compression, indicating that this may be associated with a transient suspension of the autoregulatory vasoconstriction both in healthy controls and in patients with PAD.

Commentary on Viewpoint: The human cutaneous circulation as a model of generalized microvascular function

VIEWPOINTCommentary on Viewpoint: The human cutaneous circulation as a model of generalized microvascular functionJulian StewartJulian StewartPublished Online:01 Jul 2008https://doi.org/10.1152/japplphysiol.00159.2008MoreSectionsPDF (27 KB)Download PDF ToolsExport citationAdd to favoritesGet permissionsTrack citations ShareShare onFacebookTwitterLinkedInEmailWeChat to the editor: Can we use skin as a surrogate for generalized microvascular function (3)? If only it were unambiguously true. I wish to inject a note of caution. On the one hand, skin contains the most easily accessed and manipulated microvasculature. Also, cutaneous microvascular abnormalities are invariably found in generalized systemic illnesses such as diabetes, heart disease, and aging, which affect all microvessels. This argues in favor of using skin microvessels as a surrogate for other microvasculature. On the other hand, it remains unclear whether cutaneous pathophysiology during generalized illness is caused by the actual mechanisms of disease or whether it is an end organ effect depending on disease presence. Each regional microcirculation has specific structures and functions: the skin is highly specialized in anatomy (1) and autonomic physiology, which combine to optimize its primary thermoregulatory function. Specialization makes for special physiology. For example, autonomic physiology forms an essential framework for vascular control and is unique in the skin, which has a potent active vasodilation mechanism. The skin has a limited response to baroreflex mediated input (5), diminished β2-adrenergic response (4), contributes little to systemic arterial resistance during euthermia, but has a most potent venoarteriolar response (2). Local vasoregulation by autocrine and paracrine mechanisms may be shared among microvascular circulations and thus, cutaneous endothelial mechanisms share many features with other microcirculations. Even here caveats are warranted: for example, cutaneous reactive hyperemia appears to be nitric oxide independent (6). So, is the skin a useful surrogate for other microvasculature? Depends.REFERENCES1 Braverman IM. The cutaneous microcirculation. J Investig Dermatol Symp Proc 5: 3–9, 2000.Crossref | PubMed | Google Scholar2 Henriksen O, Nielsen SL, Paaske WP, Sejrsen P. Autoregulation of blood flow in human cutaneous tissue. Acta Physiol Scand 89: 538–543, 1973.Crossref | PubMed | Google Scholar3 Holowatz LA, Thompson-Torgerson CS, Kenney WL. Viewpoint: The human cutaneous circulation as a model of generalized microvascular function. J Appl Physiol; doi:10.1152/japplphysiol.00858.2007.Link | ISI | Google Scholar4 Koss MC. Characterization of adrenoceptor subtypes in cat cutaneous vasculature. J Pharmacol Exp Ther 254: 221–227, 1990.ISI | Google Scholar5 Wilson TE, Cui J, Crandall CG. Absence of arterial baroreflex modulation of skin sympathetic activity and sweat rate during whole-body heating in humans. J Physiol 536: 615–623, 2001.Crossref | PubMed | ISI | Google Scholar6 Zhao JL, Pergola PE, Roman LJ, Kellogg DL Jr. Bioactive nitric oxide concentration does not increase during reactive hyperemia in human skin. J Appl Physiol 96: 628–632, 2004.Link | ISI | Google ScholarAUTHOR NOTESAddress for reprint requests and other correspondence: J. Steward, Suite 3050, 19 Bradhurst Ave., Hawthorne, NY 10532 (e-mail: [email protected]) Download PDF Previous Back to Top Next FiguresReferencesRelatedInformationCited ByDo peripheral and/or central chemoreflexes influence skin blood flow in humans?24 October 2014 | Physiological Reports, Vol. 2, No. 10 More from this issue > Volume 105Issue 1July 2008Pages 384-384 Copyright & PermissionsCopyright © 2008 the American Physiological Societyhttps://doi.org/10.1152/japplphysiol.00159.2008PubMed18641226History Published online 1 July 2008 Published in print 1 July 2008 Metrics

Improvement of Microcirculation and Healing of Venous Hypertension and Ulcers With Crystacide ®: Evaluation With a Microcirculatory Model, Including Free Radicals, Laser Doppler Flux, and PO2/PCO2 Measurements

In 32 patients with chronic venous insufficiency and venous hypertension associated with ulcerations, the effects of the local application of a hydrogen peroxide cream (Crystacide) applied onto the skin was evaluated using a complex, proportional, microcirculatory model to assess and quantify venous microangiopathy after local treatment. A comparative group treated without Crystacide was included. Laser Doppler flowmetry was used to assess skin perfusion (flux and venoarteriolar response) in association with transcutaneous PO2 and PCO2 measurements. Local plasma free radicals were evaluated in the area surrounding the venous ulcer using the D-Roms test. Crystacide was applied around and on the ulcer for 10 days. Crystacide was more effective than the control treatments. PO2 was increased (improved, P < .05), and plasma free radicals, PCO2, and laser Doppler flowmetry were decreased (improving toward normal values, P < .05). Also, the ulcerated area was significantly smaller at 10 days in the Crystacide group in comparison with controls (P < .05). In the proportional microcirculatory model, all parameters indicated an important level of improvement significantly larger than in controls. In conclusion, in chronic venous insufficiency and venous ulcerations, local treatment with Crystacide (10 days) improves the microcirculation and decreases skin free radicals, thus improving healing.

Gender but not the menstrual cycle affects the cutaneous venoarteriolar response in humans

We tested the hypothesis that human cutaneous venoarteriolar response (VAR) is different between genders and affected by the menstrual cycle. Ten healthy males and 11 young females were studied. Females were tested twice: early follicular phase (EFP) and luteal phase (LP). Skin blood flow (SkBF) was measured via laser-Doppler flowmetry in the calf at heart level and during leg dependency in supine. Calf cutaneous vascular conductance (CVC) was calculated. Basal SkBF in males was greater than females [84±42 vs. 51±25 (EFP, P=0.039) and 59±23 AU (LP, P=0.099)]. The VAR, assessed as a relative decrease in SkBF from baseline, was greater in males than females, while it was not different between phases (42±21 vs. 31±16 during EFP and 30±11% during LP; P=0.017 and 0.846 for genders and phases). There was a positive relation between basal SkBF and VAR (r=0.592, P<0.001). The reduction in CVC during leg dependency was greater in males than females (49±15 vs. 32±18 during EFP and 30±11% during LP; P=0.033 and 0.005). Blood pressure and heart rate remained unchanged. These results suggest that gender but not the menstrual cycle influences cutaneous venoarteriolar response. The smaller response in women appears to be related to the lower basal skin blood flow which may be attributable to an increase in sympathetic tone rather than a local structural or functional difference in the cutaneous circulation. Supported by NIH K23 (HL0752 83)

Long-term effects of endovascular angioplasty on orthostatic vasocutaneous autoregulation in patients with peripheral atherosclerosis

To test the hypothesis that endovascular revascularization of femoropopliteal lesions improves the impaired venoarteriolar response (VAR) in patients with atherosclerosis. We prospectively compared VARs in 15 healthy controls (18 legs) and 14 patients (17 legs) with mild to moderate peripheral arterial disease before and after successful peripheral endovascular angioplasty of femoropopliteal lesions. In all subjects, foot skin blood flow was assessed by laser Doppler flowmetry in the horizontal (HBF) and sitting (SBF) positions. VAR was calculated as (HBF - SBF)/HBF x 100. In patients with peripheral arterial disease, mean HBF (in arbitrary units [AU]; mean +/- SD) was similar before (25.6 +/- 15.3 AU) and after (27.0 +/- 16.4 AU) angioplasty (P = .67), whereas SBF was significantly lower after than before the endovascular procedure (11.6 +/- 7.7 AU to 18.4 +/- 14.1 AU; P < .05). Intragroup differences between SBF and HBF were significant before and after angioplasty (P < .001). VAR was higher after angioplasty (55.1% +/- 21.2%) compared with VAR before intervention (33.4% +/- 20.2%; P = .015). Although VAR increased after the intervention, VAR was still lower than in healthy controls (68.4% +/- 20.5%; P = .025). During the 6 months of follow-up, the ankle-brachial index and VAR remained unchanged (P > .05). Patients with mild to moderate peripheral arterial disease have an impaired orthostatic autoregulation that improves after successful endovascular revascularization of femoropopliteal obstructive lesions. The effect on VAR is sustained in the absence of restenosis.