Skin Microvascular Reactivity Research Articles

Evaluation of maternal skin microvascular reactivity by laser speckle contrast imaging in pregnancies complicated by preeclampsia and foetal growth restriction

Evaluation of maternal skin microvascular reactivity by laser speckle contrast imaging in pregnancies complicated by preeclampsia and foetal growth restriction

Multiscale optoacoustic assessment of skin microvascular reactivity in carotid artery disease

Microvascular endothelial dysfunction may provide insights into systemic diseases, such as carotid artery disease. Raster-scan optoacoustic mesoscopy (RSOM) can produce images of skin microvasculature during endothelial dysfunction challenges via numerous microvascular features. Herein, RSOM was employed to image the microvasculature of 26 subjects (13 patients with single carotid artery disease, 13 healthy participants) to assess the dynamics of 18 microvascular features at three scales of detail, i.e., the micro- (<100μm), meso- (≈100-1000μm) and macroscale (>1000μm), during post-occlusive reactive hyperemia challenges. The proposed analysis identified a subgroup of 9 features as the most relevant to carotid artery disease because they achieved the most efficient classification (AUC of 0.93) between the two groups in the first minute of hyperemia (sensitivity/specificity: 0.92/0.85). This approach provides a non-invasive solution to microvasculature quantification in carotid artery disease, a main form of cardiovascular disease, and further highlights the possible link between systemic disease and microvascular dysfunction.

Skin Microvascular Dysfunction in Type 2 Diabetes Mellitus Using Laser Speckle Contrast Analysis and Association with Carotid Intima-Media Thickness.

Background: It is established that diabetes mellitus (DM) is characterized by increased cardiovascular risk associated with subclinical atherosclerosis as well as microvascular alterations. Laser speckle contrast analysis (LASCA) is an innovative, non-invasive method for assessing skin microvascular function. Objectives: We sought to assess skin microvascular function in patients with type 2 DM and matched controls. Methods: Consecutive patients with DM and individuals matched for age, sex and BMI were included in the study. Skin microvascular perfusion was assessed, using LASCA, during baseline, a 5 min occlusion period and a 5 min reperfusion period. Carotid intima-media thickness (cIMT) was measured as a surrogate marker of macrocirculation. Results: In total, 18 patients with DM and 22 in the control group were enrolled. No statistically significant differences were observed in baseline flux, peak flux and percentage decrease during arterial occlusion. During reperfusion, individuals with DM exhibited a smaller peak magnitude compared to controls (147.0 ± 64.7% vs. 189.4 ± 46.0%, respectively; p < 0.05). Moreover, cIMT was higher in patients with DM compared to controls (0.68 ± 0.09 mm vs. 0.60 ± 0.08 mm, respectively, p < 0.01) and was negatively correlated with skin microvascular reactivity in the univariate analysis. In the multivariate analysis, glucose and office systolic blood pressure levels remained significant predictors of microvascular reactivity. Conclusions: Our study shows that patients with type 2 DM exhibit impaired skin microvascular function compared to controls. Furthermore, glucose levels and blood pressure play a key role in microvascular dysfunction. However, additional studies are needed to address the clinical significance of early microvascular changes in DM.

The correlation between first-trimester serum biochemical and biophysical markers and skin microvascular reactivity assessed by laser speckle contrast imaging

The correlation between first-trimester serum biochemical and biophysical markers and skin microvascular reactivity assessed by laser speckle contrast imaging

Accumulation of Microvascular Target Organ Damage in Systemic Lupus Erythematosus Patients Is Associated with Increased Cardiovascular Risk.

Background: Systemic lupus erythematosus (SLE) is a prototype autoimmune disease associated with increased cardiovascular (CV) burden. Besides increased arterial stiffness and subclinical atherosclerosis, microvascular dysfunction is considered an important component in the pathophysiology of CV disease. However, there is a lack of data regarding the effect of multiple target organ damage (TOD) on CV health. Objectives: This study aimed to evaluate (i) the presence of microvascular changes in SLE in various vascular beds, (ii) the possible associations between the accumulation of microvascular TOD and CV risk and (iii) whether Galectin-3 represents a predictor of combined microvascular TOD. Methods: Participants underwent (i) evaluation of skin microvascular perfusion (laser speckle contrast analysis), (ii) fundoscopy (non-mydriatic fundus camera), (iii) indirect assessment of myocardial perfusion (subendocardial viability ratio) and (iv) determination of urine albumin-to-creatinine ratio (UACR). CV risk was calculated using the QResearch Risk Estimator version 3 (QRISK3). Serum Galectin-3 levels were determined. Results: Forty-seven SLE patients and fifty controls were studied. SLE patients demonstrated impaired skin microvascular reactivity (160.2 ± 41.0 vs. 203.6 ± 40.1%), retinal arteriolar narrowing (88.1 ± 11.1 vs. 94.6 ± 13.5 μm) and higher UACR levels compared to controls. Furthermore, SLE individuals had significantly higher Galectin-3 levels [21.5(6.1) vs. 6.6(6.6) ng/dL], QRISK3 scores [7.0(8.6) vs. 1.3(3.6)%] and a greater chance for microvascular dysfunction. In the SLE group, patients with multiple TOD exhibited higher QRISK3. In the multivariate analysis, the accumulation of TOD correlated with disease activity and Galectin-3 (p < 0.05). Conclusions: Our study showed for the first time that SLE patients exhibit a greater number of cases of TOD. The accumulation of TOD was associated with increased CV risk. Clinicians dealing with SLE should be aware and seek microvascular alterations.

High dietary salt intake attenuates nitric oxide mediated endothelium-dependent vasodilation and increases oxidative stress in pregnancy.

This study aimed to investigate the impact of dietary salt intake during normal pregnancy on maternal microvascular and macrovascular endothelium-dependent reactivity and oxidative stress level. In this cross-sectional study, based on their 24-h urinary sodium excretion, pregnant women (37-40 weeks of gestation) were divided into three groups: normal salt (<5.75 g/day, N = 12), high salt (5.75-10.25 g/day, N = 36), and very high salt (VHS;>10.25 g/day, N = 17). Forearm skin microvascular reactivity in response to vascular occlusion, local heating (LTH) and iontophoresis of acetylcholine (AChID), as well as brachial artery flow mediated dilation (FMD) were measured. Serum nitric oxide, endocan, 8-iso-prostaglandin F2α (8-iso-PGF2α), thiobarbituric acid reactive substances (TBARS), and ferric-reducing ability of plasma assay were measured as biomarkers of endothelial function/activation and oxidative stress. Brachial artery FMD, microvascular AChID, and LTH were significantly decreased in VHS compared with NS group, while LTH was also decreased in normal salt compared with high salt group. Nitric oxide was significantly decreased in both high salt and VHS groups compared with normal salt. Endocan, 8-iso-PGF2α, and TBARS were significantly increased in VHS compared with the normal salt group. High dietary salt intake is associated with decreased nitric oxide mediated endothelium-dependent vasodilation in peripheral microcirculation and macrocirculation of healthy pregnant women due to increased oxidative stress.

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.

The Effect of Acute Hyperglycaemia Induced by Oral Glucose Load on Heart Rate Variability and Skin Microvascular Reactivity in Young Adults.

We aimed to elucidate the effects of acute hyperglycaemia, induced by an oral glucose tolerance test (OGTT), on the autonomic nervous system (ANS) and skin microvascular reactivity at the time point of peak plasma glucose concentration (cglc) in 20 young, healthy participants. We assessed their heart rate variability (HRV) as a measure of the ANS activity and the parameters of post-occlusive reactive hyperaemia (PORH) to estimate skin microvascular reactivity as measured by laser Doppler (LD) fluxmetry. The tests were repeated 30 min after a standard OGTT (75 g glucose dissolved in 250 mL water) and, in a separate control experiment, after drinking the same amount of water. Participants had their cglc and serum insulin measured at three consecutive time-points according to the testing protocol. The low-frequency (LF) spectral power, the LF to high-frequency (LF/HF) ratio, and the diastolic blood pressure increased significantly more after water than after OGTT, and there was a trend of the peak LD flux of PORH decreasing more after OGTT than after water. Significant correlations between some PORH and all the HRV parameters and cglc increase after OGTT were found, implying diminished vascular reactivity evoked by hyperglycaemia in healthy subjects with lower glucose tolerance.

FACTORS RELATED TO SKIN MICROVASCULAR DYSFUNCTION IN INDIVIDUALS WITH DIFFERENT RANGE OF GLUCOSE LEVELS

Objective: Existing data confirm the presence of microvascular dysfunction in hypertension and diabetes mellitus (DM). Prediabetes is recognized as a significant metabolic status, being a key factor in the occurrence of DM and there is increasing evidence concerning microvascular complications in prediabetes. Laser speckle contrast analysis (LASCA) is a non-invasive technique that can be used to evaluate skin microvascular function. The aim of our study was to assess cardiovascular factors that are possibly associated with microvascular reactivity in a population from normoglycaemia to DM. Design and method: Individuals with normoglycemia, prediabetes and diabetes without established cardiovascular disease were included in the study. In all participants, forearm skin blood flow was recorded under standardized conditions using a laser speckle contrast imager (PeriCam PSI NR System, Perimed). Post-occlusive reactive hyperaemia (PORH) was assessed following a standardized protocol and data were analyzed with a signal processing software (PIMSoft, Perimed). Skin microvascular reactivity was expressed as a percentage increase between baseline and peak perfusion (%). Office BP was measured in each participant according to a standard methodology and aortic blood pressure was assessed using the Sphygmocor device. Results: Fifty individuals (18 patients with prediabetes, 16 patients with DM and 16 controls) were included in the study. In the univariate model both glucose levels and aortic systolic blood pressure (aSBP) correlated inversely with microvascular reactivity (r = -0.382 and r = -0.349, p&lt;0.01 for both comparisons) However, in the multivariate model only the association with aSBP remained statistically significant (beta = -0.363, p&lt;0.05). Conclusions: Only central SBP, but not glucose predicted skin microvascular dysfunction in individuals with normoglycemia, prediabetes and diabetes and without established cardiovascular disease.

Skin microvascular reactivity in patients with diabetic retinopathy.

Early detection of microangiopathic complications of diabetes mellitus (DM) is necessary to analyze the patient's condition and prevent disease progression. The study was aimed to investigate the relationship between the presence of retinopathy and decreased reactivity of the microcirculatory bed in patients with diabetes. The study involved 130 subjects: healthy volunteers (n=48), DM patients without retinopathy (n=53) and with retinopathy (n=29). Skin microvascular reactivity was assessed on the forearm using laser Doppler flowmetry with a local heating test combined with occlusion. The slope of local thermal hyperemia curve (Slope-120) and other parameters of microvascular reactivity showed difference in pairwise comparisons between the groups. Slope-120 had the highest sensitivity (0.759) and specificity (0.717) in detection of diabetic retinopathy. The decrease of Slope-120 was associated with retinopathy (odds ratio (OR) - 8.3 (2.9-24.1), p<0.001), even after adjusting for other factors (OR - 11.0 (1.6-77.2), p=0.016). Thus, assessment of skin microvascular reactivity may be a useful test for detecting signs of microangiopathic complications and for screening patients in risk group. Decreased microvascular reactivity has been shown to be prospective as an independent indicator of retinopathy in type 1 DM.

Impaired peripheral microvascular reactivity in patients with nonobstructive coronary artery disease

This study aimed to determine whether peripheral microvascular reactivity is impaired in patients with nonobstructive coronary artery disease (NOCAD). Stable patients presenting with angina were recruited and, based on results from coronary angiography, were categorized into OCAD (coronary stenosis of ≥50%) and NOCAD (stenosis <50%) groups. A control group with no history of angina was also recruited. Forearm skin microvascular reactivity was measured using the laser Doppler blood perfusion monitor and the process of postocclusive skin reactive hyperemia (PORH). Patients were categorized into OCAD (n = 42), NOCAD (n = 40), and control (n = 39) groups. Compared with the control group, the PORH perfusion percent change (PORH% change) was significantly lower in the OCAD and NOCAD groups. No significant differences were noted between the OCAD and NOCAD groups. Additionally, the NOCAD group without any coronary obstruction takes a longer time to reach peak perfusion and had lower PORH% change compared with the nonangina control group. Angina patients with NOCAD have microvascular dysfunction as demonstrated by reduced magnitude of reperfusion with an ischemic stimulus. NOCAD patients without coronary obstruction also displayed a slower response to reperfusion.

Reversible skin microvascular hyporeactivity in patients with immune-mediated thrombocytopenic thrombotic purpura

BackgroundImmune-mediated thrombotic thrombocytopenic purpura (iTTP) is a rare disease characterized by arteriolar and capillary microthrombosis precipitating organ failure. However, the contribution of endothelial dysfunction on impaired microvascular blood flow in iTTP patients has been poorly explored. This pilot observational study aimed to explore endothelial-mediated vasoreactivity in iTTP patients at admission and its changes after plasma exchange therapy (PE).MethodsWe conducted a prospective observational study in patients (> 18-year old) admitted in ICU for iTTP. Using laser Doppler flowmetry and acetylcholine (Ach) iontophoresis in the forearm, we recorded the skin microvascular blood flow and the endothelium-mediated vasoreactivity at admission and after PE. Demographics, biological, clinical courses, and outcomes were also collected. As a control group, we used a previously published cohort of young diabetic patients after correction of ketoacidosis.ResultsEighteen confirmed iTTP patients and 34 controls were included in the study, mainly female (72%) aged 43 ± 16-year-old. At admission, 55% had neurological abnormalities, 50% cardiac issues and 27.8% an acute kidney injury. Median platelet count was 19 G/mL [10–37]. Baseline microvascular blood flow was decreased in iTTP patients when compared to controls (5.97 ± 4.5 vs. 10.1 ± 6.3 PU, P = 0.03), associated with markedly impaired endothelial-mediated skin microvascular reactivity (AUC: 9627 ± 8122 vs. 16,475 ± 11,738, P = 0.03). Microvascular reactivity improved after the first PE session (AUC: 9627 ± 8122 vs 16,558 ± 10,699, P = 0.007, respectively, baseline and post-PE1) and much more after the second session (26,431 ± 23,181, P = 0.04 post-PE1 vs post-PE2). Hemolysis biomarkers (LDH and bilirubin) negatively correlated with skin microvascular flow and vasoreactivity.ConclusionWe highlighted a marked yet reversible skin endothelium-mediated microvascular hyporeactivity in iTTP patients that could participate in organ injury pathophysiology.

Microvascular reactivity using laser Doppler measurement in type 2 diabetes with subclinical atherosclerosis

Microangiopathy should be noted in diabetes with subclinical vascular diseases. Little is known about whether various surrogate markers of systemic arterial trees exacerbate simultaneously in preclinical atherosclerosis. To clarify the association of skin microvascular reactivity with arterial stiffness is essential to elucidating early atherosclerotic changes. The post-occlusive reactive hyperemia of skin microcirculation was evaluated in 27 control and 65 type 2 diabetic subjects, including 31 microalbuminuria (MAU) and 34 normoalbuminuria (NAU) patients. The laser Doppler skin perfusion signals were transformed into three frequency intervals for the investigation of endothelial, neurogenic, and myogenic effects on basal and reactive flow motion changes. The analysis of spectral intensity and distribution provided insight into potential significance of microvascular regulation in subclinical atherosclerotic diseases. Systemic arterial stiffness was studied by the brachial ankle pulse wave velocity (baPWV). Following occlusive ischemia, the percent change of endothelial flow motion was lower in MAU than in NAU and control groups. The MAU group revealed a relative increase in myogenic activity and a decrease in endothelial activity in normalized spectra. The baPWV showed more significant associations with reactive endothelial change (r = - 0.48, P < 0.01) and normalized myogenic value (r = - 0.37, P < 0.05) than diabetes duration and HbA1c. By multivariate regression analysis, only endothelial vasomotor changes independently contributed to the decreased baPWV (OR 3.47, 95% CI 1.63-7.42, P < 0.05). Impaired microcirculatory control is associated with increased arterial stiffness in preclinical atherosclerosis. To identify the early manifestations is necessary for at-risk patients to prevent from further vascular damage.

Exploring the relationship between capillary refill time, skin blood flow and microcirculatory reactivity during early resuscitation of patients with septic shock: a pilot study.

Capillary refill time (CRT), a costless and widely available tool, has emerged as a promising target to guide septic shock resuscitation. However, it has yet to gain universal acceptance due to its potential inter-observer variability. Standardization of CRT assessment may minimize this problem, but few studies have compared this approach with techniques that directly assess skin blood flow (SBF). Our objective was to determine if an abnormal CRT is associated with impaired SBF and microvascular reactivity in early septic shock patients. Twelve septic shock patients were subjected to multimodal perfusion and hemodynamic monitoring for 24h. Three time-points (0, 1, and 24h) were registered for each patient. SBF was measured by laser doppler. We performed a baseline SBF measurement and two microvascular reactivity tests: one with a thermal challenge at 44°C and other with a vascular occlusion test. Ten healthy volunteers were evaluated to obtain reference values. The patients (median age 70years) exhibited a 28-day mortality of 50%. Baseline CRT was 3.3 [2.7-7.3] seconds. In pooled data analysis, abnormal CRT presented a significantly lower SBF when compared to normal CRT [44 (13.3-80.3) vs 193.2 (99.4-285) APU, p = 0.0001]. CRT was strongly associated with SBF (R2 0.76, p < 0.0001). An abnormal CRT also was associated with impaired thermal challenge and vascular occlusion tests. Abnormal CRT values observed during early septic shock resuscitation are associated with impaired skin blood flow, and abnormal skin microvascular reactivity. Future studies should confirm these results.

Blunted Microvascular Reactivity in Psoriasis Patients in the Absence of Cardiovascular Disease, as Assessed by Laser Speckle Contrast Imaging.

Psoriasis is associated with accelerated rates of cardiovascular disease (CVD). Laser Speckle Contrast Imaging (LSCI) is a novel, non-interventional technique for the dynamic assessment of microvascular endothelial dysfunction, which represents an early precursor of CVD. We investigated whether skin microvascular reactivity is impaired in psoriasis and whether an association exists with large artery stiffening. Skin microvascular reactivity was assessed with LSCI combined with post-occlusive reactive hyperaemia protocol in psoriasis patients and controls in the absence of established CVD. Arterial stiffness and central hemodynamics were assessed throughout a whole 24 h period with the Mobil-O-Graph device. Most LSCI indices of microvascular reactivity were impaired in psoriasis patients (n = 90) compared to controls (n = 45) [baseline flux; occlusion flux; peak-to-baseline magnitude; baseline cutaneous vascular conductance (CVC); percentage increase in CVC, p &lt; 0.001 for all comparisons]. In multivariate analysis, psoriatic disease predicted the above markers independently of classical CVD risk factors. Augmentation index, peripheral pulse pressure, and central systolic/diastolic blood pressure correlated with LSCI microvascular responses in the study population (n = 135). Pulse wave velocity significantly correlated with nearly all LSCI parameters, while the association with baseline flux was independent of CVD risk factors and psoriatic disease in multivariate analysis (beta = 0.096, p = 0.039). This study provides evidence of altered skin microvascular responses in psoriasis by use of LSCI, and interaction with macrovascular dysfunction, before the establishment of overt CVD. A non-interventional approach of skin microcirculation with LSCI might be used as an early indicator of vascular health in psoriasis.

Skin microcirculation dynamics are impaired in patients with rheumatoid arthritis and no cardiovascular comorbidities.

Rheumatoid arthritis (RA) is associated with increased cardiovascular disease (CVD) risk. Microvascular endothelial dysfunction contributes to the development of vascular injury and subsequent CVD. We hypothesised that RA patients exhibit blunted microvascular reactivity regardless of CVD risk factors and investigated potential associations with coronary microvascular perfusion and surrogate markers of CVD. This case-control study recruited RA patients and non-RA individuals in the absence of cardiovascular comorbidities. Skin microvascular reactivity was dynamically assessed using laser speckle contrast imaging coupled with post-occlusive reactive hyperaemia protocol. Applanation tonometry was applied to assess subendocardial viability ratio, an index of myocardial microvascular perfusion, and central arterial stiffness [carotid-femoral pulse wave velocity (PWV), augmentation index]. Peripheral arterial stiffness (carotid PWV, β-stiffness index) and carotid atherosclerosis (intima-media thickness) were assessed with carotid ultrasound software. Skin microvascular responses before and following reperfusion [baseline flux, occlusion flux, time-to-peak, peak magnitude, peak-to-baseline magnitude, baseline cutaneous vascular conductance (CVC), and percentage increase in CVC] were significantly impaired in RA patients (n=35) compared to controls (n=35). Presence of RA independently predicted altered microvascular reactivity in multivariate analysis. Skin microcirculation dynamics significantly correlated with coronary microvascular perfusion and peripheral arterial stiffness, yet not carotid atherosclerosis, even after adjustment for CVD risk factors. Patients with RA present impaired microvascular reactivity regardless of CVD risk factors at a preclinical stage preceding CVD. Assessment of skin microvascular dysfunction may reflect a state of generalised vasculopathy, including myocardial microvascular abnormalities, and serve as a non-invasive surrogate indicator of CVD risk in RA.

CORRELATION OF COGNITIVE STATUS WITH IMPAIRED SKIN MICROVASCULAR REACTIVITY IN NEWLY DIAGNOSED UNTREATED HYPERTENSIVES

Objective: Untreated hypertension (HT) in the early midlife is strongly correlated with mild cognitive impairment (MCI) later on, in the elderly. HT is also associated with significant microvascular alterations in several vascular beds including skin. Skin microcirculation has been correlated with microvascular alterations in other beds and has been proposed as a model of generalized microvascular dysfunction. We sought to estimate the prevalence of MCI in newly diagnosed untreated hypertensive patients (UHTs) and compare it to normotensive healthy individuals (NTs). We also investigated possible associations between MCI and parameters of skin microvascular reactivity by using a novel laser technique, namely Laser Speckle Contrast Imaging (LSCI). Design and method: We consecutively enrolled 51 individuals including 31 UHTs and 20 NTs. All patients were free from diabetes mellitus or any cardiovascular disease. Diagnosis of HT was based on conventional office BP and 24h-Ambulatory Blood Pressure Measurement (24h-ABPM) criteria, according to standard guidelines. The Montreal Cognitive Assessment test (MoCA test) was used to assess cognitive function with a score equal to or lower than 26 being suggestive of MCI for all participants. The LSCI technique combined with post-occlusive reactive hyperemia (PORH) protocol was used to assess skin microvascular reactivity. Skin microvascular results are expressed as percentage increase of cutaneous perfusion from baseline to peak condition (base to peak flux, %). Results: Base to peak flux was significantly lower in UHTs compared to NTs (211.0 ± 53.1 vs 154.0 ± 53.0 %, p &lt; 0.01). Although the prevalence of MCI did not differ between UHTs and NTs, there was also a significant positive correlation between the MoCA test score and base to peak flux in the UHTs group (r = 0.491, p = 0.02). Conclusions: Although UHTs did not present impaired cognitive status compared to NTs, they do present impaired skin microvascular reactivity which is strongly correlated with their cognitive status from the very early stages of hypertension. Early and effective treatment of essential hypertension may contribute to the prevention of MCI and the improvement of skin microvascular function in hypertensive patients.

Vitamin C improves microvascular reactivity and peripheral tissue perfusion in septic shock patients

BackgroundVitamin C has potential protective effects through antioxidant and anti-inflammatory properties. However, the effect of vitamin C supplementation on microvascular function and peripheral tissue perfusion in human sepsis remains unknown. We aimed to determine vitamin C effect on microvascular endothelial dysfunction and peripheral tissue perfusion in septic shock patients.MethodsPatients with septic shock were prospectively included after initial resuscitation. Bedside peripheral tissue perfusion and skin microvascular reactivity in response to acetylcholine iontophoresis in the forearm area were measured before and 1 h after intravenous vitamin C supplementation (40 mg/kg). Norepinephrine dose was not modified during the studied period.ResultsWe included 30 patients with septic shock. SOFA score was 11 [8–14], SAPS II was 66 [54–79], and in-hospital mortality was 33%. Half of these patients had vitamin C deficiency at inclusion. Vitamin C supplementation strongly improved microvascular reactivity (AUC 2263 [430–4246] vs 5362 [1744–10585] UI, p = 0.0004). In addition, vitamin C supplementation improved mottling score (p = 0.06), finger-tip (p = 0.0003) and knee capillary refill time (3.7 [2.6–5.5] vs 2.9 [1.9–4.7] s, p < 0.0001), as well as and central-to-periphery temperature gradient (6.1 [4.9–7.4] vs 4.6 [3.4–7.0] °C, p < 0.0001). The beneficial effects of vitamin C were observed both in patients with or without vitamin C deficiency.ConclusionIn septic shock patients being resuscitated, vitamin C supplementation improved peripheral tissue perfusion and microvascular reactivity whatever plasma levels of vitamin C.ClinicalTrials.gov Identifier: NCT04778605 registered 26 January 2021.

Skin microvascular reactivity and subendocardial viability ratio in relation to dyslipidemia and signs of insulin resistance in non-diabetic hypertensive patients.

The aim of this study was to evaluate the influence of dyslipidemia and insulin resistance for the development of microvascular dysfunction in non-diabetic primary hypertension. Seventy-one patients with untreated primary hypertension were included. Skin microvascular reactivity was evaluated by laser Doppler fluxmetry with iontophoresis (acetylcholine, ACh and sodium nitroprusside, SNP) and heat-induced hyperemia. Myocardial microvascular function was estimated by the subendocardial viability ratio (SEVR) calculated from pulse wave analysis and applanation tonometry. Triglyceride x glucose (TyG index) and triglyceride/HDL cholesterol ratio were used as measurements of insulin resistance. Skin microvascular dysfunction was associated with low HDL cholesterol, where Ach-mediated peak flux (r=.27, p=.025) and heat-induced peak flux (r=.29, p=.017) related to HDL cholesterol levels. ACh peak flux was inversely related to TG/HDL ratio (r=-.29, p=.016), while responses to local heating and SNP did not. SEVR did not relate to HDL and was unrelated to markers of insulin resistance. These findings were confirmed by multivariable analyses, including potential confounders. Early microvascular dysfunction can be detected in non-diabetic hypertensive patients and is related to dyslipidemia and to signs of insulin resistance, thus predicting future cardiovascular risk.

Iontophoresis of treprostinil promotes wound healing in a murine model of scleroderma-related ulcers.

Systemic sclerosis (SSc) is a rare, chronic disease characterized by fibrosis, vascular alterations and digital ulcerations. Few drugs have shown efficacy to enhance wound healing of existing SSc-related ulcers. Local delivery of treprostinil, a prostacyclin analogue, may improve wound healing. The present work aimed first at developing a mouse model of SSc-related ulcerations and second at assessing the effect of iontophoresis of treprostinil on wound healing. We used two murine models of SSc: chemically induced with HOCl, and urokinase-type plasminogen activator receptor (uPAR)-deficient. Excisional wounding was performed on the dorsal midline with a biopsy punch. Animals were randomized into three groups: treated with electrostimulation alone, with treprostinil iontophoresis or untreated. We assessed wound healing over time, as well as skin microvascular reactivity, inflammation, microvessel density and collagen distribution, before wounding and after re-epithelialization. uPAR-/- mice, but not HOCl-treated mice, showed impaired wound healing and decreased microvascular reactivity compared with their controls. Treprostinil iontophoresis improved wound healing and microvascular density and decreased inflammation in uPAR-/- mice, while electro-stimulation did not. However, treprostinil had no effect on microvascular reactivity and collagen distribution. This study suggests that excisional wounds in uPAR-/- mice are a relevant model of SSc-related ulcers. In addition, treprostinil iontophoresis enhances wound healing in this model. Further work in now needed to show whether this effect translates in humans.