Cutaneous Microvascular Reactivity Research Articles

Impaired Microvascular Reactivity in Patients with Chronic Kidney Disease Submitted to Kidney Transplantation: A Prospective Observational Study.

The effect of kidney transplantation on endothelial dysfunction and autonomic dysfunction in uremia remains controversial, and few studies have evaluated this question. Endothelial dysfunction and autonomic dysfunction, both, be assessed noninvasively using laser Doppler flowmetry (LDF). This study evaluated cutaneous microvascular blood flow and reactivity using LDF in patients undergoing kidney transplantation. This prospective longitudinal cohort study involved 40 patients with chronic kidney disease (CKD) undergoing kidney transplantation, compared with 40 patients without kidney disease. Using LDF, post-occlusive reactive hyperemia (PORH) (resting flow [RF], peak flow, ratio between peak, and RF, hyperemic area, PORH index), and sympathetic constrictor response to inspiratory breath-hold (mean minimum inspiratory values) were evaluated. RF and sympathetic constrictor response to inspiratory breath-hold (mean minimum inspiratory values), were lower in the CKD group at 1 week and at 3 months after transplantation (p < 0.005). Mean minimum inspiratory values increase in the CKD group, 3 months after transplantation. Compared with controls with no CKD, in CKD patients undergoing kidney transplantation, microcirculation by LDF shows improvement after 3 months.

Mechanoreceptor sensory feedback is impaired by pressure induced cutaneous ischemia on the human foot sole and can predict cutaneous microvascular reactivity.

The foot sole endures high magnitudes of pressure for sustained periods which results in transient but habitual cutaneous ischemia. Upon unloading, microvascular reactivity in cutaneous capillaries generates an influx of blood flow (PORH: post-occlusive reactive hyperemia). Whether pressure induced cutaneous ischemia from loading the foot sole impacts mechanoreceptor sensitivity remains unknown. Pressure induced ischemia was attained using a custom-built-loading device that applied load to the whole right foot sole at 2 magnitudes (15 or 50% body weight), for 2 durations (2 or 10 minutes) in thirteen seated participants. Mechanoreceptor sensitivity was assessed using Semmes-Weinstein monofilaments over the third metatarsal (3MT), medial arch (MA), and heel. Perceptual thresholds (PT) were determined for each site prior to loading and then applied repeatedly to a metronome to establish the time course to return to PT upon unload, defined as PT recovery time. Microvascular flux was recorded from an in-line laser speckle contrast imager (FLPI-2, Moor Instruments Inc.) to establish PORH peak and recovery rates at each site. PT recovery and PORH recovery rate were most influenced at the heel and by load duration rather than load magnitude. PT recovery time at the heel was significantly longer with 10 minutes of loading, regardless of magnitude. Heel PORH recovery rate was significantly slower with 10minutes of loading. The 3MT PT recovery time was only longer after 10 minutes of loading at 50% body weight. Microvascular reactivity or sensitivity was not influenced with loading at the MA. A simple linear regression found that PORH recovery rate could predict PT recovery time at the heel (R2=0.184, p<0.001). In populations with degraded sensory feedback, such as diabetic neuropathy, the risk for ulcer development is heightened. Our work demonstrated that prolonged loading in healthy individuals can impair skin sensitivity, which highlights the risks of prolonged loading and is likely exacerbated in diabetes. Understanding the direct association between sensory function and microvascular reactivity in age and diabetes related nerve damage, could help detect early progressions of neuropathy and mitigate ulcer development.

A 5-Week Guided Active Play Program Modulates Skin Microvascular Reactivity in Healthy Children.

Children's poor levels of physical activity (PA) participation and early-onset vascular aging are identified as global health challenges. Children's guided activity play (GAP)-based PA programs have emerged as effective strategies to improve cardiovascular risk factors and health-related fitness. This study proposes to investigate whether GAP improves children's cutaneous microvascular reactivity and health-related fitness. Children's (n = 18; 9.8 [1.5]y) PA during a 5-week (4d/wk; 1h/d) GAP program was assessed (accelerometry) with preassessments and postassessments for anthropometric, musculoskeletal fitness, blood pressure, estimated aerobic power, and cutaneous microvascular reactivity. PA averaged 556 (132)kcal·week-1 at 34.7% (7.5%) time at moderate to vigorous intensity. Resting heart rate (-9.5%) and diastolic blood pressure (-7.8%) were reduced without changes in health-related fitness indices. Cutaneous microvascular reactivity to sodium nitroprusside iontophoresis increased the average perfusion (+36.8%), average cutaneous vascular conductance (+30%), the area under the curve (+28.8%), and a faster rise phase (+40%) of perfusion (quadratic modeling; P ≤ .05). Chi-square and crosstabulation analysis revealed significant association between children's PA levels and sodium nitroprusside average perfusion levels, where children with PA levels ≥205.1kcal.55minute-1 were overrepresented in the medium/high levels of sodium nitroprusside perfusion. A 5-week GAP modified the microvascular reactivity in children without changes in body mass, musculoskeletal fitness, or estimated aerobic power.

Impaired microvascular reactivity in patients treated with 5-fluorouracil chemotherapy regimens: Potential role of endothelial dysfunction

Background5-fluorouracil (5-FU) is the second most common cancer chemotherapy associated with short- and long-term cardiotoxicity. Although the mechanisms mediating these toxicities are not well understood, patients often present with symptoms suggestive of microvascular dysfunction. We tested the hypotheses that patients undergoing cancer treatment with 5-FU based chemotherapy regimens would present with impaired microvascular reactivity and that these findings would be substantiated by decrements in endothelial nitric oxide synthase (eNOS) gene expression in 5-FU treated human coronary artery endothelial cells (HCAEC). MethodsWe first performed a cross-sectional analysis of 30 patients undergoing 5-FU based chemotherapy treatment for cancer (5-FU) and 32 controls (CON) matched for age, sex, body mass index, and prior health history (excluding cancer). Cutaneous microvascular reactivity was evaluated by laser Doppler flowmetry in response to endothelium-dependent (local skin heating; acetylcholine iontophoresis, ACh) and -independent (sodium nitroprusside iontophoresis, SNP) stimuli. In vitro experiments in HCAEC were completed to assess the effects of 5-FU on eNOS gene expression. Results5-FU presented with diminished microvascular reactivity following eNOS-dependent local heating compared to CON (P = 0.001). Iontophoresis of the eNOS inhibitor L-NAME failed to alter the heating response in 5-FU (P = 0.95), despite significant reductions in CON (P = 0.03). These findings were corroborated by lower eNOS gene expression in 5-FU treated HCAEC (P < 0.01) compared to control. Peak vasodilation to ACh (P = 0.58) nor SNP (P = 0.39) were different between groups. ConclusionsThe present findings suggest diminished microvascular function along the eNOS-NO vasodilatory pathway in patients with cancer undergoing treatment with 5-FU-based chemotherapy regimens and thus, may provide insight into the underlying mechanisms of 5-FU cardiotoxicity.

The Efficacy of Exercise Training for Cutaneous Microvascular Reactivity in the Foot in People with Diabetes and Obesity: Secondary Analyses from a Randomized Controlled Trial.

It is unclear if cutaneous microvascular dysfunction associated with diabetes and obesity can be ameliorated with exercise. We investigated the effect of 12-weeks of exercise training on cutaneous microvascular reactivity in the foot. Thirty-three inactive adults with type 2 diabetes and obesity (55% male, 56.1 ± 7.9 years, BMI: 35.8 ± 5, diabetes duration: 7.9 ± 6.3 years) were randomly allocated to 12-weeks of either (i) moderate-intensity continuous training [50–60% peak oxygen consumption (VO2peak), 30–45 min, 3 d/week], (ii) low-volume high-intensity interval training (90% VO2peak, 1–4 min, 3 d/week) or (iii) sham exercise placebo. Post-occlusive reactive hyperaemia at the hallux was determined by laser-Doppler fluxmetry. Though time to peak flux post-occlusion almost halved following moderate intensity exercise, no outcome measure reached statistical significance (p > 0.05). These secondary findings from a randomised controlled trial are the first data reporting the effect of exercise interventions on cutaneous microvascular reactivity in the foot in people with diabetes. A period of 12 weeks of moderate-intensity or low-volume high-intensity exercise may not be enough to elicit functional improvements in foot microvascular reactivity in adults with type 2 diabetes and obesity. Larger, sufficiently powered, prospective studies are necessary to determine if additional weight loss and/or higher exercise volume is required.

Effects of home-based leg heat therapy on walking performance in patients with symptomatic peripheral artery disease: a pilot randomized trial.

Few noninvasive therapies currently exist to improve functional capacity in people with lower extremity peripheral artery disease (PAD). The goal of the present study was to test the hypothesis that unsupervised, home-based leg heat therapy (HT) using water-circulating trousers perfused with warm water would improve walking performance in patients with PAD. Patients with symptomatic PAD were randomized into either leg HT (n = 18) or a sham treatment (n = 16). Patients were provided with water-circulating trousers and a portable pump and were asked to apply the therapy daily (7 days/wk, 90 min/session) for 8 wk. The primary study outcome was the change from baseline in 6-min walk distance at 8-wk follow-up. Secondary outcomes included the claudication onset-time, peak walking time, peak pulmonary oxygen consumption and peak blood pressure during a graded treadmill test, resting blood pressure, the ankle-brachial index, postocclusive reactive hyperemia in the calf, cutaneous microvascular reactivity, and perceived quality of life. Of the 34 participants randomized, 29 completed the 8-wk follow-up. The change in 6-min walk distance at the 8-wk follow-up was significantly higher (P = 0.029) in the group exposed to HT than in the sham-treated group (Sham: median: -0.9; 25%, 75% percentiles: -5.8, 14.3; HT: median: 21.3; 25%, 75% percentiles: 10.1, 42.4, P = 0.029). There were no significant differences in secondary outcomes between the HT and sham group at 8-wk follow-up. The results of this pilot study indicate that unsupervised, home-based leg HT is safe, well-tolerated, and elicits a clinically meaningful improvement in walking tolerance in patients with symptomatic PAD.NEW & NOTEWORTHY This is the first sham-controlled trial to examine the effects of home-based leg heat therapy (HT) on walking performance in patients with peripheral artery disease (PAD). We demonstrate that unsupervised HT using water-circulating trousers is safe, well-tolerated, and elicits meaningful changes in walking ability in patients with symptomatic PAD. This home-based treatment option is practical, painless, and may be a feasible adjunctive therapy to counteract the decline in lower extremity physical function in patients with PAD.

Comparison of Cortical and Cutaneous Vascular Hemodynamic Changes in Hypoxia by Usingin VivoSkull and Skin Optical Clearing Techniques

Hypoxia occurs in various pathophysiological conditions. Especially, brain can be seriously affected by the oxygen deficiency. However, challenges exist in optically monitoring cerebral hemodynamics with high resolution. As an easily-detected vessel bed, peripheral skin is a potential target for predicting cerebrovascular hemodynamic changes. However, the similarities and differences between cerebral and cutaneous hemodynamics during hypoxia are still unclear. One of the main reasons is that optical imaging techniques are fundamentally depth/resolution-limited due to high scattering properties of turbid tissue. Fortunately, in vivo tissue optical clearing techniques can efficiently overcome these problems, and avoid the side-effects of surgical windows. In this work, we simultaneously monitor the changes in cortical and cutaneous microvascular blood oxygen and blood flow under the assistance of in vivo skull and skin optical clearing techniques, and quantitatively compared the differences between cerebral and cutaneous arteriovenous functional responses to the hypoxic stimulus. The results indicated that the variation tendency of blood oxygen response might be more similar, and cutaneous vascular blood oxygen response has the potential to serve as an accessible indicator for revealing cerebrovascular dysfunction. Moreover, it provides a feasible approach to realize visualization of in vivo monitoring cerebral and cutaneous microvascular reactivity with minimal invasiveness.

Dietary supplementation with whey protein improves systemic microvascular function in heart failure patients: a pilot study

Endothelial dysfunction is a well-known component of the pathophysiology of heart failure (HF), with proven prognostic value. Dietary supplementation with whey protein (WP) has been widely used to increase skeletal muscle mass, but it also has vascular effects, which are less understood. This study aimed to evaluate the effects of WP supplementation on the systemic microvascular function of HF patients. This was a blinded, randomized, placebo-controlled clinical trial that evaluated the effects of 12-week WP dietary supplementation on systemic microvascular function, in patients with HF New York Heart Association (NYHA) classes I/II. Cutaneous microvascular flow and reactivity were assessed using laser speckle contrast imaging, coupled with pharmacological local vasodilator stimuli. Fifteen patients (aged 64.5±6.2 years, 11 males) received WP supplementation and ten patients (aged 68.2±8.8 years, 8 males) received placebo (maltodextrin). The increase in endothelial-dependent microvascular vasodilation, induced by skin iontophoresis of acetylcholine, was improved after WP (P=0.03) but not placebo (P=0.37) supplementation. Moreover, endothelial-independent microvascular vasodilation induced by skin iontophoresis of sodium nitroprusside, was also enhanced after WP (P=0.04) but not placebo (P=0.42) supplementation. The results suggested that dietary supplementation with WP improved systemic microvascular function in patients with HF.

Is metabolically healthy obesity indeed healthy at the microvascular level?

Abstract Background In the current “obesity epidemic”, obese individuals without insulin resistance, lipid disorders, or hypertension, have been called “metabolically healthy” (MHO) and considered to have intermediate cardiovascular risk, between that of healthy nonobese (HNO) individuals and of metabolically unhealthy obese (MUO). Nonetheless, this is controversial, as MHO may have subclinical abnormalities, and indeed may be a transitory state in the way to the unhealthy phenotype. Purpose To evaluate systemic microvascular reactivity in MHO, MUO and HNO. Methods Ten MHO, 10 MUO and 20 HNO individuals were studied. Obesity was considered as a BMI ≥30 kg/m2. The NCEP/ATPIII criteria, excluding waist circumference, were used to define the metabolically healthy phenotype (absence of all criteria) or unhealthy phenotype (presence of any of the criteria). Laser speckle contrast imaging coupled with skin acetylcholine (Ach) iontophoresis was employed to study cutaneous microvascular reactivity (endothelial-dependent vasodilatation), as a surrogate for systemic microvascular function, and cutaneous vascular conductance [CVC in arbitrary perfusion units of microvascular flow (APU)/mean arterial pressure (mmHg)] was measured. Results Mean age was 34.8, 36.7 and 32.3 years (P=0.17, ANOVA) and BMI was 20.7, 32.2 and 33.3 kg/m2 (P&amp;lt;0.0001) for HNO, MHO and MUO, respectively. Both MHO and MUO had significantly decreased microvascular vasodilation in comparison to HNO (Figure 1). Of note, there was no significant difference between MHO and MUO regarding CVC (both similarly decreased when compared to the healthy controls). Conclusions This study underscores that MHO is not a “benign” condition, as it has adverse effects on microvascular function, similarly to those found in MUO. The study of cutaneous microvascular function may be useful to identify subclinical abnormalities in obese individuals who might deserve more intensive management. Figure 1 Funding Acknowledgement Type of funding source: Public Institution(s). Main funding source(s): FAPERJ - Fundação de Amparo à Pesquisa do Estado do Rio de Janeiro - Brazil

Leg heat therapy improves perceived physical function but does not enhance walking capacity or vascular function in patients with peripheral artery disease.

A single session of leg heat therapy (HT) has been shown to elicit increases in leg blood flow and reduce blood pressure (BP) and the circulating levels of endothelin-1 (ET-1) in patients with symptomatic peripheral artery disease (PAD). We assessed whether 6 wk of supervised leg HT (3 times/wk) with water-circulating trousers perfused with water at 48°C improved 6-min walk distance in individuals with PAD compared with a sham treatment. Secondary outcomes included the assessment of leg vascular function, BP, quality of life, and serum ET-1 and nitrite plus nitrate (NOx) levels. Of 32 PAD patients randomized, 30 [age: 68 ± 8 yr; ankle-brachial index (ABI): 0.6 ± 0.1] completed the 3- and 6-wk follow-ups. Participants completed 98.7% of the treatment sessions. Compared with the sham treatment, exposure to HT did not improve 6-min walk distance, BP, popliteal artery reactive hyperemia, cutaneous microvascular reactivity, resting ABI, or serum NOx levels. The change from baseline to 6 wk in scores of the physical functioning subscale of the 36-item Short Form Health Survey was significantly higher in the HT group (control -6.9 ± 10 vs. HT 6.8 ± 15; 95% confidence interval: 2.5-24.3, P = 0.017). Similarly, the change in ET-1 levels after 6 wk was different between groups, with the HT group experiencing a 0.4 pg/mL decrease (95% confidence interval: -0.8-0.0, P = 0.03). These preliminary results indicate that leg HT may improve perceived physical function in symptomatic PAD patients. Additional, larger studies are needed to confirm these findings and determine the optimal treatment regimen for symptomatic PAD patients.NEW & NOTEWORTHY This is the first sham-controlled study to investigate the effects of leg heat therapy (HT) on walking performance, vascular function, and quality of life in patients with peripheral artery disease (PAD). Adherence to HT was high, and the treatment was well tolerated. Our findings revealed that HT applied with water-circulating trousers evokes a clinically meaningful increase in perceived physical function and reduces the serum concentration of the potent vasoconstrictor endothelin-1 in patients with PAD.

Visualizing and quantifying cutaneous microvascular reactivity in humans by use of optical coherence tomography: impaired dilator function in diabetes.

The pathophysiology and time course of impairment in cutaneous microcirculatory function and structure remain poorly understood in people with diabetes, partly due to the lack of investigational tools capable of directly imaging and quantifying the microvasculature in vivo. We applied a new optical coherence tomography (OCT) technique, at rest and during reactive hyperemia (RH), to assess the skin microvasculature in people with diabetes with foot ulcers (DFU, n = 13), those with diabetes without ulcers (DNU, n = 9), and matched healthy controls (CON, n = 13). OCT images were obtained from the dorsal part of the foot at rest and following 5 min of local ischemia induced by inflating a cuff around the thigh at suprasystolic level (220 mmHg). One-way ANOVA was used to compare the OCT-derived parameters (diameter, speed, flow rate, and density) at rest and in response to RH, with repeated-measures two-way ANOVA performed to analyze main and interaction effects between groups. Data are means ± SD. At rest, microvascular diameter in the DFU (84.89 ± 14.84 µm) group was higher than CON (71.25 ± 7.6 µm, P = 0.012) and DNU (71.33 ± 12.04 µm, P = 0.019) group. Speed in DFU (65.56 ± 4.80 µm/s, P = 0.002) and DNU (63.22 ± 4.35 µm/s, P = 0.050) were higher than CON (59.58 ± 3.02 µm/s). Microvascular density in DFU (22.23 ± 13.8%) was higher than in CON (9.83 ± 2.94%, P = 0.008), but not than in the DNU group (14.8 ± 10.98%, P = 0.119). All OCT-derived parameters were significantly increased in response to RH in the CON group (all P < 0.01) and DNU group (all P < 0.05). Significant increase in the DFU group was observed in speed (P = 0.031) and density (P = 0.018). The change in density was lowest in the DFU group (44 ± 34.1%) compared with CON (199.2 ± 117.5%, P = 0.005) and DNU (148.1 ± 98.4, P = 0.054). This study proves that noninvasive OCT microvascular imaging is feasible in people with diabetes, provides powerful new physiological insights, and can distinguish between healthy individuals and patients with diabetes with distinct disease severity.

Editorial

Editorial

Effects of chronic type 5 phosphodiesterase inhibition on penile microvascular reactivity in hypertensive patients with erectile dysfunction: a randomized crossover placebo-controlled trial.

This randomized crossover and placebo-controlled trial evaluated the effects of daily use of sildenafil citrate (SIL, 1-month 50 mg twice daily) on penile and systemic endothelial microvascular function in hypertensive patients presenting with erectile dysfunction. The effects of SIL on arterial pressure were evaluated using ambulatory blood pressure monitoring (ABPM). Fifty patients diagnosed with primary arterial hypertension and erectile dysfunction (aged 57.4 ± 5.6 years), recruited in a tertiary public hospital, were treated with SIL (50 mg twice daily) or placebo (PLA) for two 30-day periods with a 30-day washout between them. Laser speckle contrast imaging coupled with acetylcholine skin iontophoresis was used to evaluate penile and systemic (forearm) cutaneous microvascular reactivity. SIL treatment increased penile basal microvascular flow (P = 0.002) and maximal endothelial-dependent peak response to skin iontophoresis of acetylcholine (ACh, P = 0.006). The area under the curve of microvascular vasodilation induced by ACh was also significantly increased (P = 0.02). Lastly, SIL treatment did not modify systemic microvascular reactivity. Twenty-four-hour ABPM (P = 0.0002) and daytime (P = 0.002) and nighttime (P = 0.001) mean diastolic blood pressure values were significantly reduced after SIL treatment. The scores of the Simplified International Index of Erectile Function (P < 0.0001) and the number of patients with positive responses to Sexual Encounter Profile question 3 (P < 0.0001) also increased after SIL treatment. Penile endothelium-dependent microvascular reactivity improved after continuous use of sildenafil in hypertensive patients with erectile dysfunction; the treatment also reduced blood pressure, suggesting that, in addition to improving erectile function, daily use of sildenafil could improve blood pressure control.

Participant experiences in a feasibility trial of supervised exercise training in adults with venous leg ulcers: A qualitative study.

Exercise training can improve lower-limb cutaneous microvascular reactivity in adults with venous leg ulceration; however, there is a lack of research on patients' views about the acceptability and feasibility of exercise interventions. The aim of this study was to explore participants' experiences of the trial "Exploring the Feasibility of Implementing a Supervised Exercise Training and Compression Hosiery Intervention in Patients with Venous Ulceration" (FISCU). Semi-structured face-to-face and telephone interviews were used to investigate participants' experiences (n = 16) of taking part in the FISCU trial. Data were analysed using thematic analysis. Three overarching themes were identified, along with 11 sub-themes: (a) sedentary cautious living (because of pain and reduced mobility, treatment and perceived control, and advice to rest and be careful), (b) key components of the exercise trial (including motivation, an individualised intervention supervised by a specialist exercise professional, and satisfaction with the intervention), and (c) benefits of exercise (physical benefits and healing, psychological well-being, positive impact on comorbidities, and an improved self-management strategy). This study found that an exercise intervention was viewed by participants as positive, acceptable, and feasible while living with a venous leg ulcer. An individualised and supervised exercise programme was key to build confidence to exercise.

EFFECTS OF RADIATION ON CUTANEOUS MICROVASCULAR FUNCTION IN THE INTACT HUMAN CIRCULATION

Radiation is a commonly used treatment for various types of cancer, however it is often associated with an increased risk of cardiovascular disease (CVD). Previous animal studies have shown a significant decreased relaxation in irradiated arteries in response to Acetylcholine. However, there is a paucity of knowledge on the effects of radiation within the intact human circulation. Given that changes vascular function occurs early in the progression of numerous cardiovascular and metabolic diseases characterization of the microvascular responses to radiation treatment is critical. Therefore, the primary was to determine the effects of cancer treatment radiation on cutaneous microvascular reactivity in breast cancer patients.METHODSThe present study utilized a longitudinal study design in breast cancer patients receiving radiation therapy. Cutaneous microvascular reactivity to Acetylcholine (ACh) was evaluated following radiation exposure in breast cancer patients at the site of radiation treatment and at a control non‐irradiated site. Briefly, red blood cell flux was measured as an index of cutaneous blood flow via laser Doppler flowmetry with ACh mediated vasodilation determined by iontophoresis drug delivery. Data are expressed as cutaneous vascular conductance.RESULTSTo date, 4 patients have completed the study (planned enrollment of 15 patients). Cutaneous vascular conductance to ACh was significantly attenuated following a total cumulative dose of 1950 ± 719 cGy. Similarly, the total ACh response was decreased in the radiated tissue. The forth coming patients will provide additional insight into the effects of radiation exposure on microvascular reactivity. Furthermore, we will be able to provide insight into the role coexisting risk factors of metabolic syndrome and preexisting atherosclerosis on radiation‐induced vascular dysfunction.CONCLUSIONThis study demonstrates that low doses of radiation for cancer treatment attenuate cutaneous microvascular function, which may have long‐term implications for cardiovascular health in these patients.Support or Funding InformationN/AThis abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.

Evaluation of systemic microvascular reactivity in adults with congenital heart disease.

Adults with congenital heart disease share some features with those with chronic heart failure. Although microvascular endothelial dysfunction has been described in chronic heart failure, evaluation of the microcirculation in adults with congenital heart disease is lacking. The present study aimed to investigate systemic microvascular reactivity in adults with congenital heart disease. The patients initially underwent cardiopulmonary exercise testing. Then, the cutaneous microvascular reactivity was evaluated in these patients using a laser speckle contrast imaging system coupled with skin iontophoresis of endothelial-dependent (acetylcholine) or -independent (sodium nitroprusside) vasodilators and postocclusive reactive hyperemia (PORH) and compared with healthy controls matched for age and sex. Thirty-one patients and 29 healthy controls were evaluated. The basal microvascular flow (P<.0001) and area under the curve in response to acetylcholine (P<.0001) were higher in the patients than in the healthy volunteers. The increase in cutaneous vascular conductance in response to sodium nitroprusside was reduced in the patients compared to the healthy volunteers (P=.0031). No difference in the microvascular response was observed during postocclusive reactive hyperemia. The basal microvascular flow of patients with peak oxygen consumption below 16.0mL kg-1 min-1 was superior to that of patients with values greater than 16.0mL kg-1 min-1 (P=.0046). Adults with congenital heart disease present a higher baseline cutaneous microvascular blood flow than healthy controls and do not present systemic microvascular endothelial dysfunction. Nevertheless, endothelium-independent microvascular reactivity is blunted, suggesting an altered vascular smooth muscle response or vascular structural alterations. Finally, patients with a lower functional capacity presented a greater microvascular basal blood flow than subjects with a higher functional capacity.

Lower cutaneous microvascular reactivity in adult cancer patients receiving chemotherapy.

Cancer patients with a history of anticancer chemotherapy are at an increased cardiovascular disease risk compared with cancer-free populations. Therefore, we tested the hypothesis that cancer patients receiving adjuvant chemotherapy would have a lower cutaneous microvascular reactivity and lower endothelium-dependent flow-mediated dilation (FMD) of the brachial artery compared with matched cancer-free control subjects. To test this hypothesis, we performed a case control study with seven cancer patients receiving adjuvant chemotherapy and seven matched healthy reference control subjects. Red blood cell flux was measured as an index of cutaneous blood flow via laser Doppler flowmetry. Acetylcholine (ACh)-mediated vasodilation was determined by iontophoresis. Data were expressed as percent increase in cutaneous vascular conductance. Endothelium-dependent FMD of the brachial artery via ultrasonography was determined as an index of macrovessel endothelial function. Cutaneous microvascular reactivity was attenuated in cancer patients compared with control subjects [cancer: 959.9 ± 187.3%, control: 1,556.8 ± 222.2%; P = 0.03, effect size (ES) = 1.1]. Additionally, cancer patients demonstrated a significantly lower area under the curve response to ACh iontophoresis compared with healthy control subjects. Brachial artery FMD was also significantly lower in cancer patients compared with control subjects (cancer: 2.2 ± 0.6%, control: 6.6 ± 1.4%; P = 0.006, ES = 1.6), which was significantly associated with measurements of microvascular reactivity. These findings suggest that decreases in vascular reactivity can occur during cancer chemotherapy, which may have implications for the long-term risk of cardiovascular disease morbidity and mortality. NEW & NOTEWORTHY Cancer survivors treated with chemotherapy experience an increased risk of cardiovascular events, linked to both cardiac and vascular toxicity. The major finding of this study is that microvascular reactivity and macrovascular endothelium-dependent flow-mediated dilation are lower in cancer patients currently receiving adjuvant chemotherapy compared with healthy counterparts.

Seven Consecutive Days of Remote Ischemic Preconditioning Improved Cutaneous Vascular Reactivity Induced by Post Occlusive Reactive Hyperemia

ObjectiveRemote ischemic preconditioning (RIPC), induced by brief periods of ischemia followed by reperfusion, elicits strong cardioprotection from ischemia reperfusion injury in animal models. However, recent clinical trials in humans have yielded mixed results that may be explained by coexisting conditions and other experimental factors. Using human skin as an alternative model to study RIPC, we hypothesized that cutaneous vascular reactivity to post‐occlusive reactive hyperemia (PORH) will be increased following repeated RIPC.MethodsYoung healthy participants (26 ± 1 years; 4 male, 5 female) performed RIPC for seven consecutive days. Each daily RIPC session consisted of 4 repetitions of 5 minutes of upper arm blood flow occlusion interspersed by 5 minutes non‐occlusion. Pre‐ and 24 hours post‐RIPC training, an index of skin microvascular blood flow (i.e., cutaneous red blood cell flux) was measured from the ventral forearm using laser speckle contrast imaging. Flux was measured continuously during baseline, 5 minutes of arm blood flow occlusion with 200 mmHg of cuff pressure, and during 5 minutes of PORH. Peak flux during hyperemia, Max (peak after subtracting baseline), Time to peak (Tp) (index of vascular resistance), Max/Tp (indicator of early vascular changes), and area under curve (AUC) were analyzed from collected data. Data are presented as cutaneous vascular conductance (CVC), which was calculated as flux/mean arterial pressure.ResultsSeven consecutive days of RIPC increased Max/Tp (Pre: 0.10 ± 0.02 vs. Post: 0.12 ± 0.02 CVC/sec, p&lt;0.05). Although not statistically different, other indices of PORH were increased; AUC (Pre: 89.7 ± 13.5 vs. Post: 107.2 ± 10.4 CVC·sec, p=0.10), Peak (Pre: 2.18 ± 0.02 vs. Post: 2.28 ± 0.20 CVC, p=0.33), Max (Pre: 1.68 ± 0.20 vs. Post: 1.79 ± 0.20 CVC, p=0.18), and Time to peak (Tp) (Pre: 18.6 ± 1.1 vs. Post: 17.0 ± 1.3 sec, p=0.11).ConclusionsSeven consecutive days of RIPC augmented cutaneous microvascular reactivity to PORH. Collectively, these data support repeated RIPC as a means to improve microvascular function in humans.All experimental procedures were approved by the Institutional Review Board at Des Moines University and conformed to the standards set by the Declaration of Helsinki (IRB#: 08‐15‐05)Support or Funding InformationFunding source: Des Moines University, IOER #03‐14‐01 (PI: J. Lang)This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.

Cutaneous Microvascular Blood Flow and Reactivity in Hypoxia.

As is known, hypoxia leads to an increase in microcirculatory blood flow of the skin in healthy volunteers. In this pilot study, we investigated microcirculatory blood flow and reactive hyperemia of the skin in healthy subjects in normobaric hypoxia. Furthermore, we examined differences in microcirculation between hypoxic subjects with and without short-term acclimatization, whether or not skin microvasculature can acclimatize. Fourty-six healthy persons were randomly allocated to either short-term acclimatization using intermittent hypoxia for 1 h over 7 days at an FiO2 0.126 (treatment, n = 23) or sham short-term acclimatization for 1 h over 7 days at an FiO2 0.209 (control, n = 23). Measurements were taken in normoxia and at 360 and 720 min during hypoxia (FiO2 0.126). Microcirculatory cutaneous blood flow was assessed with a laser Doppler flowmeter on the forearm. Reactive hyperemia was induced by an ischemic stimulus. Measurements included furthermore hemodynamics, blood gas analyses and blood lactate. Microcirculatory blood flow increased progressively during hypoxia (12.3 ± 7.1–19.0 ± 8.1 perfusion units; p = 0.0002) in all subjects. The magnitude of the reactive hyperemia was diminished during hypoxia (58.2 ± 14.5–40.3 ± 27.4 perfusion units; p = 0.0003). Short-term acclimatization had no effect on microcirculatory blood flow. When testing for a hyperemic response of the skin's microcirculation we found a diminished signal in hypoxia, indicative for a compromised auto-regulative circulatory capacity. Furthermore, hypoxic short-term acclimatization did not affect cutaneous microcirculatory blood flow. Seemingly, circulation of the skin was unable to acclimatize using a week-long short-term acclimatization protocol. A potential limitation of our study may be the 7 days between acclimatization and the experimental test run. However, there is evidence that the hypoxic ventilatory response, an indicator of acclimatization, is increased for 1 week after short-term acclimatization. Then again, 1 week is what one needs to get from home to a location at significant altitude.

Tempol augments the blunted cutaneous microvascular thermal reactivity in healthy young African Americans.

What is the central question of this study? The purpose was to determine whether there is a difference between African Americans and Caucasians in cutaneous microvascular function and whether this difference is attributable to elevated oxidative stress. What is the main finding and its importance? The main finding is that African Americans have an attenuated cutaneous vasodilatation during local heating relative to Caucasians that is restored with local infusion of the superoxide dismutase mimetic, tempol. This suggests that superoxide mediates microvascular dysfunction and might contribute to the greater prevalence of cardiovascular disease in this population. African Americans (AA) have elevated risk for cardiovascular disease relative to other populations. We hypothesized that the cutaneous hyperaemic response to local heating is reduced in young AA relative to Caucasian Americans (CA) and that this is attributable to elevated oxidative stress. As such, ascorbic acid (a global antioxidant) and tempol (a superoxide dismutase mimetic) would improve this response in AA. Microdialysis fibres received lactated Ringer solution (control), 10mm ascorbic acid or 10μm 4-hydroxy-2,2,6,6-tetramethylpiperidine-1-oxyl (tempol) at a rate of 2.0μlmin-1 . Cutaneous vascular conductance (CVC) was calculated as the red blood cell flux divided by mean arterial pressure. Data were presented as a percentage of maximal CVC (%CVCmax ) induced by 44°C heating plus sodium nitroprusside. Twenty-four (12 AA, 12 CA) young (23±4years old) subjects participated. During 39°C heating, the %CVCmax was lower in AA at the control (CA, 65±20% versus AA, 47±15%; P<0.05) and ascorbic acid sites (CA, 73±14% versus AA: 49±17%; P<0.01). At the tempol site, there were no differences between groups. This was followed by infusion of 10mm l-NAME at all sites to assess the contribution of nitric oxide to vasodilatation during local heating. The contribution of nitric oxide was lower in AA relative to CA at 39°C; however, this was restored with tempol. These data suggest that: (i)cutaneous vasodilatation in response to local heating is blunted in AA relative to CA; and (ii)elevated superoxide generation attenuates nitric oxide-mediated cutaneous vasodilatation in AA.