Peripheral Microvascular Function Research Articles

Abstract TP65: Evaluation Of Leg Microvascular Function In Chronic Stroke Survivors Using Near Infrared Spectroscopy And The Vascular Occlusion Technique.

Background: Chronic stroke survivors have impaired conduit artery endothelial function, but little is known about peripheral microvascular function post-stroke. Near infrared spectroscopy (NIRS) can non-invasively measure tissue oxygen saturation (StO 2 ) of skeletal muscle, and when combined with a dynamic challenge like a vascular occlusion, can indirectly evaluate tissue oxygen utilization during the occlusion period and microvascular function during the post-occlusive hyperemic period. We hypothesized that microvascular function would be impaired in the tibialis anterior (TA) muscle of the affected leg of chronic stroke survivors compared to the non-affected leg as evidenced by a slower oxygen resaturation rate post-cuff release. Methods: Fifteen chronic stroke survivors completed this study. The mean age was 57±12 years, 10 were female, and the mean time since stroke was 12±10 years. After resting for fifteen minutes a NIRS sensor was placed over either the affected or non-affected TA. The opposite leg was tested one week later. After recording five minutes of baseline StO 2 , a cuff was placed around the proximal thigh and inflated to 225 mmHg for five minutes. StO 2 was continuously measured during cuff inflation and for five minutes post-cuff release. The rate of change in StO 2 was calculated during the five-minute cuff occlusion and the first 12 seconds post-cuff release. Results: There was no difference in baseline StO 2 between the affected and non-affected TA (68±11% vs. 67±6%, respectively; p=0.60). There was also no difference in the change in StO 2 during the occlusion period (affected ΔStO 2 = -31±12 % vs. non-affected -35±19%; p=0.76), or the rate of oxygen desaturation (affected -0.15±0.11 %·s -1 vs non-affected -0.10±0.04 %·s -1 ; p=0.39). After cuff release, there was a greater oxygen resaturation rate in the non-affected leg compared to the affected leg (3.13±2.08 %·s -1 vs. 1.60±1.11 %·s -1 , respectively; p=0.01). Conclusion: There was no difference in oxygen utilization between the affected and non-affected TA during the cuff occlusion period. The oxygen resaturation response in the affected TA post-cuff release was slower compared to the non-affected TA, suggesting microvascular function is impaired in the affected muscle.

High Frequency of Microvascular Dysfunction in US Outpatient Clinics: A Sign of High Residual Risk? Data from 7,105 Patients.

Previous studies have linked peripheral microvascular dysfunction measured by arterial tonometry to high residual risk in on-statin patients. Digital thermal monitoring (DTM) of microvascular function is a new and simplified technique based on fingertip temperature measurements that has been correlated with the burden of atherosclerosis and its risk factors. Here, we report analyses of DTM data from two large US registries: Registry-I (6,084 cases) and Registry-II (1,021 cases) across 49 US outpatient clinics. DTM tests were performed using a VENDYS device during a 5-minute arm-cuff reactive hyperemia. Fingertip temperature falls during cuff inflation and rebounds after deflation. Adjusted maximum temperature rebound was reported as vascular reactivity index (VRI). VRI distributions were similar in both registries, with mean ± SD of 1.58 ± 0.53 in Registry-I and 1.52 ± 0.43 in Registry-II. In the combined dataset, only 18% had optimal VRI (≥2.0) and 82% were either poor (<1.0) or intermediate (1.0-2.0). Women had slightly higher VRI than men (1.62 ± 0.56 vs. 1.54 ± 0.47, p < 0.001). VRI was inversely but mildly correlated with age (r = −0.19, p < 0.001). Suboptimal VRI was found in 72% of patients <50 years, 82% of 50-70 years, and 86% of ≥70 years. Blood pressure was not correlated with VRI. In this largest registry of peripheral microvascular function measurements, suboptimal scores were highly frequent among on-treatment patients, possibly suggesting a significant residual risk. Prospective studies are warranted to validate microvascular dysfunction as an indicator of residual risk.

Endothelial and microvascular function in liver cirrhosis: an old concept that needs re-evaluation?

Liver cirrhosis is characterized by significant circulatory dysregulation, related to an imbalance among several vasodilating agents, mainly nitric oxide. In contrast to portal vein and macrovascular hemodynamic alterations, which have been rather well described, the peripheral microcirculatory and endothelial structure and function in this population are less well studied. Endothelial dysfunction is characterized by an imbalance between endothelium-derived relaxing and contracting factors. A number of methods have been used to assess endothelial and microvascular function in human studies. Venous occlusion plethysmography was used for many years as the gold standard for evaluating endothelial function, but flow-mediated dilatation (FMD) of the forearm is currently the most frequently used method. In patients with cirrhosis, the few existing studies have mainly used FMD, but the relevant results are largely contradictory. In recent years, several noninvasive and easily applicable methods, such as near-infrared spectroscopy, laser speckle contrast imaging, peripheral arterial tonometry, optical coherence tomography and nailfold video-capillaroscopy, have been increasingly used to assess peripheral microvascular function and have demonstrated a number of advantages. In this review, we present functional methods to evaluate peripheral microvascular and endothelial function, and we discuss the existing evidence on circulatory dysfunction in patients with liver cirrhosis.

Peripheral microvascular dysfunction is also present in patients with ischemia and no obstructive coronary artery disease (INOCA).

In patients with ischemia and no obstructive coronary artery disease (INOCA), coronary microvascular dysfunction is associated with higher rate of major adverse cardiovascular events. To demonstrate if microvascular dysfunction present in coronary microcirculation of patients with INOCA may be detected noninvasively in their peripheral circulation. 25 patients with INOCA and 25 apparently healthy individuals (controls) were subjected to nailfold videocapillaroscopy (NVC) and venous occlusion plethysmography (VOP) to evaluate peripheral microvascular function and blood collection for biomarkers analysis, including soluble vascular cell adhesion molecule-1 (sVCAM-1), endothelin-1 (ET-1) and C-reactive protein (CRP). Red blood cell velocity (RBCV) before and after ischemia (RBCVmax) were significantly lower in patients with INOCA (p = 0.0001). Time to reach maximal red blood cell velocity (TRBCVmax) was significantly longer in INOCA group (p = 0.0004). Concerning VOP, maximal blood flow (p = 0.004) and its relative increment were significantly lower in patients with INOCA (p = 0.0004). RBCVmax showed significant correlations with sVCAM-1 (r = -0.38, p < 0.05), ET-1 (r = -0.73, p < 0.05) and CRP (r = -0.33, p < 0.05). Relative increment of maximal post-ischemic blood flow was significantly correlated with sVCAM-1 (r = -0.42, p < 0.05) and ET-1 (r = -0.48, p < 0.05). The impairment of microvascular function present in coronary microcirculation of patients with INOCA can be also detected in peripheral microcirculation.

Evidence of reduced peripheral microvascular function in young Black women across the menstrual cycle.

Black women (BLW) have a higher prevalence of cardiovascular disease (CVD) morbidity and mortality compared with White women (WHW). A racial disparity in CVD risk has been identified early in life as young adult BLW demonstrate attenuated vascular function compared with WHW. Previous studies comparing vascular function between premenopausal WHW and BLW have been limited to the early follicular (EF) phase of the menstrual cycle, which may not reflect their vascular function during other menstrual phases. Therefore, we evaluated peripheral microvascular function in premenopausal WHW and BLW using passive leg movement (PLM) during three menstrual phases: EF, ovulation (OV), and mid-luteal (ML). We hypothesized that microvascular function would be augmented during the OV and ML phases compared with the EF phase in both groups, but would be attenuated in BLW compared with WHW at all three phases. PLM was performed on 26 apparently healthy premenopausal women not using hormonal contraceptives: 15 WHW (23 ± 3 yr), 11 BLW (24 ± 5 yr). There was a main effect of race on the overall change in leg blood flow (ΔLBF) (P = 0.01) and leg blood flow area under the curve (LBF AUC) (P = 0.02), such that LBF was lower in BLW. However, there was no effect of phase on ΔLBF (P = 0.69) or LBF AUC (P = 0.65), nor an interaction between race and phase on ΔLBF (P = 0.37) or LBF AUC (P = 0.75). Despite peripheral microvascular function being unchanged across the menstrual cycle, a racial disparity was apparent as microvascular function was attenuated in BLW compared with WHW across the menstrual cycle.NEW & NOTEWORTHY This is the first study to compare peripheral microvascular function between young, otherwise healthy Black women and White women at multiple phases of the menstrual cycle. Our novel findings demonstrate a significant effect of race on peripheral microvascular function such that Black women exhibit significant attenuations in microvascular function across the menstrual cycle compared with White women.

Impaired Peripheral Microvascular Function and Risk of Major Adverse Cardiovascular Events in Patients With Coronary Artery Disease.

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Relationship between peripheral arterial reactive hyperemia and the index of myocardial resistance in patients undergoing invasive coronary angiography

BackgroundCoronary microvascular dysfunction is a powerful prognostic factor in patients with coronary artery disease. We investigated the role of reactive digital hyperemia peripheral arterial tonometry (RH-PAT) as a non-invasive tool to identify patients with impaired coronary microvasculature. MethodsPatients undergoing elective coronary angiography were consecutively assessed for peripheral microvascular endothelial function before coronary angiography: both the Reactive Hyperemic Index (RHI) and the Framingham reactive hyperemic index (Endoscore) were measured. During coronary angiography, the Index of microvascular resistance (IMR) was measured in all patients, and an IMR value > 25 identified patients with coronary microvascular impairment. ResultsA total of 47 patients with chronic coronary syndromes candidate to coronary angiography were included. Those with coronary microvascular impairment (n = 18 [38%]) presented with significantly lower RHI (1.68 ± 0.38 vs. 1.94 ± 0.93, p = 0.04) and Endoscore 0.50 ± 0.23 vs. 0.64 ± 0.23, p = 0.04) values as compared with patients with preserved coronary microvasculature. A significant relationship was observed between IMR with both RHI (r = 0.35, p = 0.02) and Endoscore (r = 0.34, p = 0.02). At the multivariable analysis, RHI and Endoscore were the only independent predictors of an IMR > 25. ConclusionsOur study demonstrates that digital reactive hyperemia indexes are lower in patients with high IMR values, suggesting a role for RH-PAT as non-invasive tool for identifying patients with coronary microvascular impairment.

Standard exercise stress testing attenuates peripheral microvascular function in patients with suspected coronary microvascular dysfunction

BackgroundThe effect of exercise on the microvasculature of patients with suspected coronary microvascular dysfunction (CMD), assessed by reactive hyperemia peripheral arterial tonometry (RH-PAT; EndoPAT), is unknown. The present study aimed to determine if standard clinical exercise stress testing (GXT) affected peripheral microvascular function, as determined by the reactive hyperemia index (RHI and LnRHI), in patients with suspected CMD.MethodsIn a cross-sectional study, patients (n = 76) were grouped based on whether the GXT was performed; 1) prior to (exercisers; n = 30), or 2) after the vascular assessment (non-exercisers; n = 46). Patients with an adenosine index of microvascular resistance > 25, adenosine coronary flow reserve (CFR) < 2.0, and/or acetylcholine CFR < 1.5 were considered to have CMD (n = 42). RHI and LnRHI quantified finger pulse amplitude hyperemia following 5 min of forearm ischemia.ResultsLnRHI was lower in patients with CMD compared to patients without CMD, while LnRHI was also lower in exercisers compared to non-exercisers (LnRHI: CMD Non-Exercisers: 0.63 ± 0.25; CMD Exercisers: 0.54 ± 0.19; No CMD Non-Exercisers: 0.85 ± 0.23; No CMD Exercisers: 0.63 ± 0.26; Condition and Exercise Main Effects: Both P < 0.01). In patients who did not exercise prior to the vascular assessment, the receiver operating characteristic curve (ROC) for LnRHI to predict CMD was 0.76 (95% CI: 0.62–0.91; P < 0.01). However, in patients who performed exercise prior to the vascular assessment, the ROC for LnRHI to predict CMD was 0.60 (95% CI: 0.40–0.81; P = 0.34).ConclusionsCMD is associated with impaired peripheral microvascular function and preceding acute exercise is associated with further reductions of LnRHI. Further, acute exercise abolished the capacity for RH-PAT to predict the presence of CMD in patients with chest pain and non-obstructive coronary arteries. RH-PAT measurements in patients with suspected CMD should not be conducted after exercise has been performed.

European Society of Cardiology/European Society of Hypertension versus the American College of Cardiology/American Heart Association guidelines on the cut-off values for early hypertension: a microvascular perspective

The aim of this study was to investigate retinal and peripheral microvascular function in asymptomatic individuals that fall into different BP groups when using either the ESC/ESH or the ACC/AHA guidelines. Retinal and peripheral microvascular function was assessed in 358 participants by means of dynamic retinal vessel analysis and digital thermal monitoring, respectively. Blood pressure and lipid panel were also evaluated. Retinal vascular function measured in all groups belonging to the ACC/ASH classifications were within the normal values for age-matched normal population. Individuals classed as grade 1 hypertension according to the ESC/ESH guidelines, however, exhibited a significantly decreased artery baseline (p = 0.0004) and MC (p = 0.040), higher slopeAD (p = 0.0018) and decreased vein MC (p = 0.0446) compared to age matched normal individuals. In addition, they also had significant lower artery baseline, artery BDF, MD and MC than individuals classed as stage 1 hypertension based on the ACC/ASH guidelines (p = 0.00022, p = 0.0179, p = 0.0409 and p = 0.0329 respectively). Peripheral vascular reactivity (aTR) was lower in ESC /ESH grade I compared to those graded ACC/ASH stage I hypertension (p = 0.0122). The conclusion of this study is that microvascular dysfunctions is present at multiple levels only in individuals with ESC/ESH grade 1 hypertension. This observation could be important when deciding personalised care in individuals with early hypertensive changes.

Vascular Aging Detected by Peripheral Endothelial Dysfunction Is Associated With ECG-Derived Physiological Aging.

BackgroundAn artificial intelligence algorithm that detects age using the 12‐lead ECG has been suggested to signal “physiologic age.” This study aimed to investigate the association of peripheral microvascular endothelial function (PMEF) as an index of vascular aging, with accelerated physiologic aging gauged by ECG‐derived artificial intelligence–estimated age.Methods and ResultsThis study included 531 patients who underwent ECG and a noninvasive PMEF assessment using reactive hyperemia peripheral arterial tonometry. Abnormal PMEF was defined as reactive hyperemia peripheral arterial tonometry index ≤2.0. Accelerated or delayed physiologic aging was calculated by the Δ age (ECG‐derived artificial intelligence–estimated age minus chronological age), and the association between Δ age and PMEF as well as its impact on composite major adverse cardiovascular events were investigated. Δ age was higher in patients with abnormal PMEF than in patients with normal PMEF (2.3±7.8 versus 0.5±7.7 years; P=0.01). Reactive hyperemia peripheral arterial tonometry index was negatively associated with Δ age after adjustment for cardiovascular risk factors (standardized β coefficient, –0.08; P=0.048). The highest quartile of Δ age was associated with an increased risk of major adverse cardiovascular events compared with the first quartile of Δ age in patients with abnormal PMEF, even after adjustment for cardiovascular risk factors (hazard ratio, 4.72; 95% CI, 1.24–17.91; P=0.02).ConclusionsVascular aging detected by endothelial function is associated with accelerated physiologic aging, as assessed by the artificial intelligence–ECG Δ age. Patients with endothelial dysfunction and the highest quartile of accelerated physiologic aging have a marked increase in risk for cardiovascular events.

Laser Doppler flowmetry to assess myocardial microcirculation.

Several different methods enable the study peripheral microcirculation. Among them, non-invasive laser Doppler flowmetry (LDF) is routinely used to assess microvascular function by quantifying rapid changes in skin blood flow in response to a given pharmacological or mechanical stimulus [1]. Owing to its accessibility, peripheral microvascular function has been proposed as a diagnostic and prognostic marker in cardiovascular disease. Importantly, it has been shown that peripheral microvascular endothelial dysfunction correlates with endothelial function in coronary microvessels suggesting that endothelial dysfunction is a globalized pathological condition [2]. However, there is still a strong need in clinical practice to develop a tool which enables heart microcirculation in vivo assessment. Although, a direct assessment of the target microvascular bed such as coronary microcirculation is technically challenging. Cardiac surgery, especially coronary artery bypass grafting (CABG), may be associated with several cardiovascular complications, including ischemia or acute myocardial infarction, arrhythmias and hemodynamic instability. Therefore, the possibility of intra- and postoperative myocardial microvascular perfusion assessment is of major clinical importance. Various studies have indicated that LDF is able to detect the real-time oscillations in myocardial perfusion in different experimental setups [3]. Of note, there is relatively little data concerning myocardial microvascular measurements in humans.

Clinical significance of endothelial vasodilatory function evaluated by EndoPAT in patients with systemic sclerosis.

Endothelial dysfunction is a hallmark of vasculopathy associated with systemic sclerosis (SSc). Reactive hyperemia peripheral arterial tonometry is a rapid and non-invasive technique to assess peripheral microvascular endothelial function by measuring changes in digital pulse volume during reactive hyperemia. Low scores of the reactive hyperemia index (RHI) imply an impaired vasodilatory response and, accordingly, impaired endothelial and vascular health. To investigate the clinical significance of the RHI in SSc patients, RHI values were measured in 43 SSc patients and 10 healthy controls. In diffuse cutaneous SSc (dcSSc) patients, RHI values were significantly decreased compared with healthy controls, and inversely correlated with disease duration. In total SSc patients, there was a significant inverse correlation between RHI values and skin score, and interstitial lung disease was associated with the decrease in RHI values. Among vascular symptoms, the current and past history of digital ulcers was seen more frequently in patients with decreased RHI values than in those with normal RHI values. Although no SSc patients had pulmonary arterial hypertension, an inverse correlation was evident between RHI values and mean pulmonary arterial pressure measured by right heart catheterization. These results indicate that the decrease in RHI values is associated with skin fibrosis, interstitial lung disease, digital ulcers and pulmonary vascular involvement leading to pulmonary arterial hypertension, supporting the canonical idea that endothelial dysfunction is a critical event underlying the development of tissue fibrosis and vascular complications in SSc.

Reactive hyperemia: a review of methods, mechanisms, and considerations.

Reactive hyperemia is a well-established technique for noninvasive assessment of peripheral microvascular function and a predictor of all-cause and cardiovascular morbidity and mortality. In its simplest form, reactive hyperemia represents the magnitude of limb reperfusion following a brief period of ischemia induced by arterial occlusion. Over the past two decades, investigators have employed a variety of methods, including brachial artery velocity by Doppler ultrasound, tissue reperfusion by near-infrared spectroscopy, limb distension by venous occlusion plethysmography, and peripheral artery tonometry, to measure reactive hyperemia. Regardless of the technique used to measure reactive hyperemia, blunted reactive hyperemia is believed to reflect impaired microvascular function. With the advent of several technological advancements, together with an increased interest in the microcirculation, reactive hyperemia is becoming more common as a research tool and is widely used across multiple disciplines. With this in mind, we sought to review the various methodologies commonly used to assess reactive hyperemia and current mechanistic pathways believed to contribute to reactive hyperemia and reflect on several methodological considerations.

Sex-related differences in forearm skin microvascular reactivity of young healthy subjects.

To assess sex-related differences in forearm skin microvascular reactivity to vascular occlusion and cardiovascular health in young healthy women and men. 203 young healthy individuals (67 men/136 women) participated in this study. Post-occlusive reactive hyperemia (PORH) in skin microcirculation following 1', 2' and 3' vascular occlusion period was assessed using laser Doppler flowmetry. Anthropometric parameters, body composition, blood pressure, heart rate and biochemical parameters were measured in all participants. Correlations between PORH and measured parameters were determined by using corresponding tests. Women had significantly higher forearm PORH following 1', 2' and 3' vascular occlusion than men. Women had lower body mass index and waist-to-hip ratio, but higher fat mass than men. Men had significantly higher blood pressure and lower heart rate than women. Also, women had lower hemoglobin, urea, creatinine and serum uric acid, but higher HDL cholesterol level than men. PORH was negatively associated with waist-to-hip ratio and systolic blood pressure only in women. Young healthy women exhibit higher skin microvascular reactivity to vascular occlusion compared to age-matched men. Increased systolic blood pressure or central obesity (waist-to-hip ratio) may pose greater risk to young healthy women than men by adversely affecting peripheral microvascular function.

Chronic statin therapy is associated with enhanced cutaneous vascular responsiveness to sympathetic outflow during passive heat stress.

Impairments in both central sympathetic and peripheral microvascular function contribute to blunted reflex cutaneous vasodilatation during heat stress in healthy older adults. Hypercholesterolaemia is associated with decrements in neurovascular function; however, little is known about the impact of hypercholesterolaemia on the integrated responses to heat stress. Further, whether chronic statin therapy alters skin sympathetic outflow or its relation to cutaneous vascular conductance during heat stress is unknown. We demonstrate that reflex cutaneous vasodilatation is impaired in older hypercholesterolaemic adults but not in formerly hypercholesterolaemic adults currently treated with a statin compared to age-matched controls. Additionally, chronic statin treatment-induced improvements in reflex vasodilatation are mediated, in part, by increases in end-organ responsiveness to efferent sympathetic outflow during whole-body heating. These data add to the growing body of literature substantiating the beneficial pleiotropic neurovascular effects of chronic statin treatment and provide further support for the use of statins to confer additional cardioprotective benefits in older adults. Attenuated reflex cutaneous vasodilatation in healthy human ageing is mediated by alterations in both central (sympathetic outflow) and peripheral (microvascular endothelial) function. Hypercholesterolaemia is associated with further impairments in neurovascular function. HMG-CoA reductase inhibitors (statins) improve cutaneous endothelium-dependent dilatation; however, whether statin therapy alters skin sympathetic nervous system activity (SSNA) or its relation to cutaneous vascular conductance (CVC) during passive heat stress is unknown. We hypothesized that (1) hypercholesterolaemic older adults would demonstrate blunted increases in both SSNA and CVC during passive heating and (2) chronic statin treatment would improve the response range and sensitivity of the SSNA:CVC relation. Reflex vasodilatation in response to a 1.0°C rise in oral temperature (Tor ; water perfused suit) was induced in 13 healthy normocholesterolaemic adults (62±2years; LDL=113±7mg/dl), 10 hypercholesterolaemic adults (60±1years; LDL=183±2mg/dl), and 10 previously hypercholesterolaemic adults (64±1years; LDL=102±2mg/dl) treated with lipophilic statin (10-40mg daily). SSNA (peroneal microneurography) and red cell flux (laser-Doppler flowmetry) in the innervated dermatome (dorsum of foot) were continuously measured. Reflex vasodilatation was blunted in hypercholesterolaemic adults, but not in statin-treated adults, compared to normocholesterolaemic adults (at ∆Tor =1.0°C: normal=36±1%CVCmax , high=32±1%CVCmax , statin=38±1%CVCmax ; P<0.01). ∆SSNA was not different (at ∆Tor =1.0°C: normal: ∆=393±96%, high: ∆=311±120%, statin: ∆=256±90%; P=0.11). The slope of the SSNA:CVC relation was blunted in hypercholesterolaemic adults (0.02±0.03%CVCmax /%baseline ) compared to both normocholesterolaemic (0.09±0.02%CVCmax /%baseline ; P=0.024) and statin-treated (0.12±0.05%CVCmax /%baseline ; P=0.03) adults. Chronic statin treatment improves reflex cutaneous vasodilatation in formerly hypercholesterolaemic older adults by increasing end-organ responsiveness to sympathetic outflow during passive heat stress.

Retinal and peripheral vascular function in healthy individuals with low cardiovascular risk

ObjectiveTo assess retinal and peripheral microvascular function in individuals with low cardiovascular risk. Methods and resultsRetinal microvascular function was assessed using the dynamic vessel analyser (DVA) and peripheral vascular reactivity was measured using the digital thermal monitor (DTM) in 136 healthy participants. In addition, systemic blood pressure (BP) profiles, blood analyses for glucose and lipid metabolism markers (CHOL, HDL-c, LDL-c), as well as the Framingham Risk Score (FRS) were assessed in all participants.Based on peripheral vascular reactivity scores, participants were separated into 3 groups: high, intermediate and low risk. Participants with high risk showed a significant higher retinal arteriolar time to reach maximum dilation (tMD) than those with intermediate and low risk (p < 0.001). In addition, retinal arterial dilation amplitude (DA), and constriction slope (SlopeAC) were higher in subjects with low risk (p = 0.006, p = 0.019). Only in high risk participants, peripheral vascular reactivity parameters correlated with retinal arterial functional parameters DA, (r = 0.3800, p = 0.029) and tMD (r = −0.5904, p < 0.001). ConclusionWe conclude that signs of abnormal vascular function are similarly present and detectable in various microvascular beds, despite existing differences in their anatomical and physiological properties.

Peripheral Microvascular Function Reflects Coronary Vascular Function.

Objectives- Coronary endothelial dysfunction is a precursor of atherosclerosis and adverse outcomes. Whether endothelial dysfunction is a localized or generalized phenomenon in humans remains uncertain. We simultaneously measured femoral and coronary vascular function with the hypothesis that peripheral vascular endothelial function will be reflective of coronary endothelial function. Approach and Results- Eighty-five subjects underwent coronary angiography for evaluation of chest pain or abnormal stress tests. Endothelium-dependent and -independent vascular function were measured using intracoronary and intrafemoral infusions of acetylcholine and sodium nitroprusside, respectively. Coronary flow reserve was assessed using intracoronary adenosine infusion. Flow velocity was measured in each circulation using a Doppler wire (FloWire, EndoSonics). Coronary vascular resistance and femoral vascular resistance were calculated as mean arterial pressure (mm Hg)/coronary blood flow (mL/min) and mean arterial pressure (mm Hg)/femoral average peak velocity (cm/s), respectively. Mean age was 53±11 years, 37% were female, 44% had hypertension, 12% had diabetes mellitus, and 38% had obstructive coronary artery disease. There was a correlation between the change in femoral vascular resistance with acetylcholine and acetylcholine-mediated changes in both the coronary vascular resistance ( r=0.27; P=0.014) and in the epicardial coronary artery diameter ( r=-0.25; P=0.021), indicating that subjects with normal endothelial function in the femoral circulation had normal endothelial function in the coronary epicardial and microcirculation and vice versa. The coronary vasodilator response to adenosine also correlated with the femoral vasodilatation with acetylcholine ( r=0.4; P=0.0002). There was no correlation between the coronary and femoral responses to sodium nitroprusside. Conclusions- Endothelial functional changes in the peripheral and coronary circulations were modestly correlated. Thus, peripheral microvascular endothelial function reflects endothelium-dependent coronary epicardial and microvascular function and the coronary flow reserve. Visual Overview- An online visual overview is available for this article.

Aerobic Exercise Improves Microvascular Function in Older Adults.

The study aimed to assess changes in peripheral microvascular function in sedentary older adults after aerobic exercise training. Twenty-three sedentary older adults (67 ± 5 yr, body mass index = 29 ± 5, mean ± SD) successfully completed a randomized 12-wk graded treadmill walking intervention. The exercise group (EX) performed 40 min of uphill walking 4 d·wk at 70% heart rate reserve. The control group (CON) maintained a sedentary lifestyle for 12 wk. Blood oxygen level-dependent (BOLD) responses of the soleus measured by magnetic resonance imaging were used to evaluate microvascular function; brief (1 s) maximal plantarflexion contractions were performed. Separately, blood flow in the popliteal artery was measured by ultrasound after brief contraction. Phosphorus magnetic resonance spectroscopy of the calf was used to examine muscle oxidative capacity, and whole-body peak oxygen consumption (V˙O2peak) was used to confirm training-induced cardiorespiratory adaptations. Peak postcontraction BOLD response increased by 33% in EX (PRE, 3.3% ± 1.0%; POST, 4.4% ± 1.4%) compared with CON (PRE, 3.0% ± 1.3%; POST, 3.2% ± 1.5%), P < 0.05. EX with hypertension tended to show a blunted peak BOLD increase (n = 6, 15%) compared with EX normotensive (n = 7, 50%), P = 0.056. Peak postcontraction blood flow increased by 39% in EX (PRE, 217 ± 88 mL·min; POST, 302 ± 167 mL·min) compared with CON (PRE, 188 ± 54 mL·min; POST, 184 ± 44 mL·min), P < 0.05. EX muscle oxidative capacity (kPCr) improved by 40% (PRE, 1.60 ± 0.57 min; POST, 2.25 ± 0.80 min) compared with CON (PRE, 1.69 ± 0.28 min; POST, 1.76 ± 0.52 min), P < 0.05. V˙O2peak increased by 9% for EX (PRE, 19.0 ± 3.1 mL·kg·min; POST, 20.8 ± 2.9 mL·kg·min) compared with a 7% loss in CON (PRE, 21.9 ± 3.6 mL·kg·min; POST, 20.4 ± 3.5 mL·kg·min), P < 0.05. Moderate aerobic exercise significantly improved microvascular function of the leg in older adults.

Light Emitting Diodes based Photoacoustic Imaging and Potential Clinical Applications

Using low cost and small size light emitting diodes (LED) as the alternative illumination source for photoacoustic (PA) imaging has many advantages, and can largely benefit the clinical translation of the emerging PA imaging technology. Here, we present our development of LED-based PA imaging integrated with B-mode ultrasound. To overcome the challenge of achieving sufficient signal-to-noise ratio by the LED light that is orders of magnitude weaker than lasers, extensive signal averaging over hundreds of pulses is performed. Facilitated by the fast response of the LED and the high-speed driving as well as the high pulse repetition rate up to 16 kHz, B-mode PA images superimposed on gray-scale ultrasound of a biological sample can be achieved in real-time with frame rate up to 500 Hz. The LED-based PA imaging could be a promising tool for several clinical applications, such as assessment of peripheral microvascular function and dynamic changes, diagnosis of inflammatory arthritis, and detection of head and neck cancer.

Microvascular Dysfunction Following Multiwalled Carbon Nanotube Exposure Is Mediated by Thrombospondin-1 Receptor CD47.

Pulmonary exposure to multiwalled carbon nanotubes (MWCNTs) disrupts peripheral microvascular function. Thrombospondin-1 (TSP-1) is highly expressed during lung injury and has been shown to alter microvascular reactivity. It is unclear exactly how TSP-1 exerts effects on vascular function, but we hypothesized that the TSP-1 receptor CD47 may mediate changes in vasodilation. Wildtype (WT) or CD47 knockout (CD47 KO) C57B6/J-background animals were exposed to 50 µg of MWCNT or saline control via pharyngeal aspiration. Twenty-four hours postexposure, intravital microscopy was performed to assess arteriolar dilation and venular leukocyte adhesion and rolling. To assess tissue redox status, electron paramagnetic resonance and NOx measurements were performed, while inflammatory biomarkers were measured via multiplex assay.Vasodilation was impaired in the WT + MWCNT group compared with control (57 ± 9 vs 90 ± 2% relaxation), while CD47 KO animals showed no impairment (108 ± 8% relaxation). Venular leukocyte adhesion and rolling increased by >2-fold, while the CD47 KO group showed no change. Application of the antioxidant apocynin rescued normal leukocyte activity in the WT + MWCNT group. Lung and plasma NOx were reduced in the WT + MWCNT group by 47% and 32%, respectively, while the CD47 KO groups were unchanged from control. Some inflammatory cytokines were increased in the CD47 + MWCNT group only. In conclusion, TSP-1 is an important ligand mediating MWCNT-induced microvascular dysfunction, and CD47 is a component of this dysregulation. CD47 activation likely disrupts nitric oxide (•NO) signaling and promotes leukocyte-endothelial interactions. Impaired •NO production, signaling, and bioavailability is linked to a variety of cardiovascular diseases in which TSP-1/CD47 may play an important role.