Reactive Hyperemic Response Research Articles

Acute Effects of 3 Neuromuscular Electrical Stimulation Waveforms on Exercising and Recovery Microvascular Oxygenation Responses.

When emphasizing muscular strength during postoperative rehabilitation it is recommended to use a neuromuscular electrical stimulation (NMES) waveform that elicits the greatest muscle force and local metabolic demand that is also well tolerated. The present investigation examined the effects that 3 different clinically used NMES waveforms had on the electrically elicited force (EEF), local metabolic demand (exercising muscle oxygen saturation [SmO2]), and the subsequent reactive hyperemia response (recovery total hemoglobin concentration [THb]) of the knee extensors. Single session repeated-measures design. EEF, local metabolic demand, and reactive hyperemia responses were measured during and subsequent to 3 NMES waveforms:Russian burst modulated alternating current (RUS), biphasic pulsed current (VMS™), and burst modulated biphasic pulsed current (VMS-Burst™). Exercising SmO2 and recovery THb were assessed noninvasively using a near-infrared spectroscopy sensor placed on the vastus lateralis. Participants completed one set of 10 repetitions of each NMES waveform and were provided with 5minutes of passive, interset recovery. Two-way, repeated-measures analysis of variance examined if NMES waveform or repetition significantly affected (P < .05) EEF or exercising SmO2. Two-way, repeated-measures analysis of variance examined if NMES waveform or recovery time affected recovery THb. VMS™ and VMS-Burst™ yielded higher EEF (F = 11.839, P < .001) and greater local metabolic stress (lower exercising SmO2, F = 13.654, P < .001) compared with RUS. Greater rate of EEF decline throughout the NMES set was observed during RUS (%Δ = -50 [6] %Rep1) compared with VMS-Burst™ (%Δ = -30 [7] %Rep1) and VMS™ (%Δ = -32 [7] %Rep1). VMS™ elicited a higher reactive hyperemia response (higher recovery THb) compared with RUS (F = 3.427, P = .048). The present findings support the use of VMS™ or VMS-Burst™ compared with RUS when promoting muscular strength. In addition, the use of VMS™ might provide a greater blood volume to the target muscle subsequent to NMES contractions compared with RUS.

Effects of regular physical exercise on skin blood flow and cardiovascular risk factors in overweight and obese subjects

Objective: it is well known that low omentin levels and reduced bioavailability of nitric oxide (NO) are outgrowth of obesity. Besides, in obese subjects, microvascular dysfunction can be an initial stage of cardiovascular diseases. This situation can be evaluated with skin laser–Doppler flowmetry (LDF).Methods: in this study we investigated the effects of 12 weeks moderate physical exercise on microvascular reactivity and plasma levels of omentin and NO in 25 overweight and obese subjects. Control group was composed of 28 sedentary participants who were neither obese nor overweight. Microvascular reactivity was handled by measurement of skin blood flow from the ring finger of the right hand with LDF, which is a non–invasive method for evaluation. With this method, it was aimed to examine the post–occlusive reactive hyperemia response of the patients. None of the participants in both groups have never followed a regular exercise schedule in their life span.Results: with regular exercise, there was a statistically significant decrease in glucose (p=0.008), cholesterol (p=0.05), and triglyceride (p=0.048) levels, while body mass index, high–density lipoprotein, and low–density lipoprotein levels did not change significantly in overweight/obese group. Also, the omentin level significantly increased (p=0.01), but NO level did not change significantly. Moreover, the amount of change in omentin and NO levels measured before and after the physical exercise were significantly correlated (r=0.57). Considering the microcirculation, rest flow (p=0.001) and peak flow value of LDF (p=0.001) increased after the physical exercise.Conclusion: our study shows that moderate physical exercise affects microvascular reactivity and plasma levels of omentin in overweight and obese subjects.

A systematic review of cardiovascular risk factors in patients with traumatic spinal cord injury.

Objective: The main risk factors for cardiac events, and particularly for the development of atherosclerosis, are diabetes mellitus, arterial hypertension, dyslipidemia and smoking. Patients with a traumatic spinal cord injury (SCI) may present with autonomic nervous system dysfunction depending on their level of spinal cord injury. Studies have found a rise in cardiovascular mortality. A systematic review was conducted that focused on this patient group's predisposition to vascular risk. Methods: We performed a PubMed and Cochrane database search. After applying specific search criteria, 42 articles were included in our analysis out of a total of 10,784 matches. The articles were selected with the aim of establishing cardiovascular risk factors in patients with traumatic spinal cord injury. Results: Patients with SCI are at an increased risk for peripheral artery disease even in the absence of cardiovascular risk factors. Major vascular changes to the arteries of patients with SCI include: a reduction in lumen size, increased vessel wall tension, higher vascular stiffness, an impaired reactive hyperemic response, and a lack of reduced vascular resistance. The findings for carotid atherosclerosis were inconclusive. This group of patients also has a higher disposition for diabetes mellitus, lipid metabolism disorders and coronary artery disease. Paraplegics are more likely to suffer from dyslipidemia, obesity and PAD, while tetraplegics are more likely to have diabetes mellitus. Conclusions: Patients with SCI are more likely to have cardiovascular risk factors and have cardiovascular disease compared to the normal population. Peripheral circulatory disorders are particularly common. Patients with SCI are now considered to be a new risk group for cardiovascular disease; however, large epidemiological studies are needed to verify in more detail the cardiovascular risk profile of this patient group.

Passive leg movement: A novel method to assess vascular function during passive leg heating?

Passive leg movement: A novel method to assess vascular function during passive leg heating?

Microcirculation Disorders in Patients with Severe COVID-19

Impaired microcirculation due to endothelial dysfunction in COVID-19 is considered to be the most important link in the pathogenesis of this disease. However, due to the complexity of its instrumental assessment in critically ill patients, the data available in the literature on specific manifestations of endothelial dysfunction are very contradictory.The objective: to determine the most characteristic capillaroscopic signs of microvascular disorders and to assess the state of microcirculation regulation in patients with severe COVID-19.Subjects and Methods. When admitted to the intensive care unit, 60 patients with COVID-19 and 12 patients with chronic cardiovascular pathology without COVID-19 (Comparison Group) were examined. All patients underwent microscopy of the microcirculatory bed of finger nail bed; the following parameters were assessed: diameters of the venous, arterial and transitional parts of capillaries, height of capillary loops, density of capillaries per 1 mm of the length of the perivascular zone, the average linear velocity of capillary blood flow (LVCBF), and thickness of the perivascular zone. The presence of avascular zones, the number of capillaries in the visualized field with circulating aggregates in the lumen, and the shape of capillaries were taken into account. In addition, an occlusion test using laser Doppler flowmetry was performed in 32 patients with COVID-19. The maximum post-occlusive increase in blood flow at the moment of cuff deflation was assessed, as well as changes in the mean value of post-occlusive blood flow relative to the baseline within 3 minutes after cuff deflation.Results. In 53 (88.3%) patients with COVID-19, abnormalities corresponding to chronic microcirculatory changes in the form of predominance of pathological capillary forms were detected. Microaggregates in the lumen of capillaries and decreased linear velocity of blood flow were revealed in 100% of cases. When comparing groups of patients with different outcomes, statistically significant differences were revealed between the LVCBF parameters (in the survivors - 354.35 ± 44.78 pm/sec, in the deceased - 278.4 ± 26.59 pm/sec), as well as between the values of the perivascular zones thickness (95.35 ± 15.96 microns versus 159.93 ± 19.90 microns). The results of the post-occlusion test revealed a significant difference between the groups in terms of the maximum post-occlusion gain (39.42 ± 3.85 BPU in the group with a favorable outcome, 27.69 ± 3.19 BPU in the group with an unfavorable outcome, 47.23 ± 1.78 BPU in the control group). In both groups, there was no increase in this parameter relative to the initial blood flow. At the same time, in the control group, the average index of post-occlusive blood flow was higher than the initial level.Conclusions. Acute microcirculation disorders with decreased linear velocity of capillary blood flow, circulation of aggregates, increased thickness of the perivascular zone were detected in all patients with severe COVID-19 but especially in those with unfavorable outcomes. Vascular tone regulation disorders were manifested by the absence of reactive hyperemia in response to acute ischemia, as well as a decrease in maximal flow-induced increase. These changes fit into the concept of endothelial dysfunction. Signs of chronic microcirculation disorders in most patients increase the risk of severe COVID-19.

Indices Of Resistance Artery Function In Upper And Lower Limbs Are Related In Young Women

Brachial artery flow-mediated dilation (FMD) has long been used to assess conduit artery (macrovascular) function. Additionally, the reactive hyperemic (RH) response following FMD cuff occlusion can function as an assessment of upper limb downstream resistance artery (microvascular) function. Passive leg movement (PLM) is a newer assessment of lower limb downstream resistance artery function that has been previously validated against the vasodilatory response to FMD (FMD%), but only in men. PURPOSE: Therefore, the purpose of this study was to compare lower limb resistance artery function, assessed by PLM, to upper limb conduit artery and resistance artery function, respectively assessed by FMD% and FMD RH, in healthy young women. We hypothesized that PLM would be positively related to both FMD% and FMD RH. METHODS: PLM and FMD were performed on 63 healthy premenopausal women (ages 18-35 years) during the early follicular phase of the menstrual cycle. Blood flow velocity and arterial diameter were assessed using Doppler ultrasound. Pearson correlation coefficients were used to evaluate associations between PLM and FMD%/RH. PLM indices included change in leg blood flow (∆LBF) and leg blood flow area under the curve (LBF AUC) and FMD RH indices included change in brachial artery blood flow (∆BABF) and brachial artery blood flow area under the curve (BABF AUC). RESULTS: ∆LBF was significantly positively related to ∆BABF (r = 0.32, P = 0.01). LBF AUC was significantly positively related to BABF AUC (r = 0.33, P = 0.01). However, contrary to our hypothesis, FMD% was not related to ∆LBF (r = 0.10, P = 0.45) or LBF AUC (r = 0.15, P = 0.23). CONCLUSIONS: PLM and FMD RH indices were positively related in young women, suggesting overlap of microvascular physiological responses in the upper and lower limbs. However, upper limb conduit artery function assessed by FMD% was not related to any PLM indices in these healthy young women, suggesting that they are capturing different aspects of vascular function and should not be used interchangeably. Supported, in part, by NIH grant P20 GM113125

Blood flow restriction in the presence or absence of muscle contractions does not preserve vasculature structure and function following 14-days of limb immobilization.

Limb immobilization causes local vasculature to experience detrimental adaptations. Simple strategies to increase blood flow (heating, fidgeting) successfully prevent acute (≤ 1day) impairments; however, none have leveraged the hyperemic response over prolonged periods (weeks) mirroring injury rehabilitation. Throughout a 14-day unilateral limb immobilization, we sought to preserve vascular structure and responsiveness by repeatedly activating a reactive hyperemic response via blood flow restriction (BFR) and amplifying this stimulus by combining BFR with electric muscle stimulation (EMS). Young healthy adults (M:F = 14:17, age = 22.4 ± 3.7years) were randomly assigned to control, BFR, or BFR + EMS groups. BFR and BFR + EMS groups were treated for 30min twice daily (3 × 10min ischemia-reperfusion cycles; 15% maximal voluntary contraction EMS), 5 days/week (20 total sessions). Before and after immobilization, artery diameter, flow-mediated dilation (FMD) and blood flow measures were collected in the superficial femoral artery (SFA). Following immobilization, there was less retrograde blood velocity (+ 1.8 ± 3.6cms-1, P = 0.01), but not retrograde shear (P = 0.097). All groups displayed reduced baseline and peak SFA diameter following immobilization (- 0.46 ± 0.41mm and - 0.43 ± 0.39mm, P < 0.01); however, there were no differences by group or across time for FMD (% diameter change, shear-corrected, or allometrically scaled) nor microvascular function assessed by peak flow capacity. Following immobilization, our results reveal (1) neither BFR nor BFR + EMS mitigate artery structure impairments, (2) intervention-induced shear stress did not affect vascular function assessed by FMD, and (3) retrograde blood velocity is reduced at rest offering potential insight to mechanisms of flow regulation. In conclusion, BFR appears insufficient as a treatment strategy for preventing macrovascular dysfunction during limb immobilization.

Agreement Between MRI and NIRS Based Assessments of Skeletal Muscle Oxygenation During Reactive Hyperemia

Skeletal muscle oxygenation is a commonly reported variable in human physiology research, and is often assessed using near-infrared spectroscopy (NIRS). In recent years, a novel magnetic resonance imaging (MRI) sequence, termed PIVOT (Perfusion, IntraVenous Oxygenation, and T2*) has been used to quantify skeletal muscle oxygenation during reactive hyperemia protocols. While the skeletal muscle oxygenation responses appear to be similar between investigations using the MRI PIVOT sequence and NIRS, the agreement between these two indices has yet to be explicitly reported. Purpose The purpose of this study was to determine the level of agreement between MRI PIVOT and NIRS based assessments of the skeletal muscle oxygenation (SmO2) response to a reactive hyperemia protocol. Methods Fifteen subjects (6 males, 25 ± 3 yrs, 170.8 ± 11.9 cm, 73.6 ± 11.3 kg, 24.8 ± 1.9 kg/m2) participated in a single laboratory visit, which was divided into two separate experiments. In one experiment, three consecutive reactive hyperemia protocols (2 min baseline, 5 min arterial occlusion, 5 min reactive hyperemia) were performed on the dominant leg, each separated by ~10 minutes of rest. Arterial occlusion was applied to the upper thigh with a pneumatic pressure cuff, and SmO2 was recorded from the medial gastrocnemius (MG) and tibalis anterior (TA) via NIRS. Next, subjects were transitioned to the MRI facility, where the experiment was repeated inside the bore of a 3T MRI scanner. In this experiment, SmO2 was collected using an adaptation of the MRI PIVOT sequence, and was represented as the intensity of the T2* signal. The order of experiments (MRI vs. NIRS) were counterbalanced between subjects, and the three reactive hyperemia trials within each experiment were averaged into a single response curve. From those response curves, a Pearson's correlation analysis was used to examine the linear relationship between the NIRS Tissue Saturation Index (TSI) response and the MRI T2* response during reactive hyperemia. Likewise, the areas under the curve (AUC; 2 min) for TSI and T2* were calculated for each subject and were compared between experiments using Bland-Altman Plots. Linear Regression Analyses were also used to assess any potential measurement bias. Results Pearson's correlation analyses indicated a significant and moderate relationship between the reactive hyperemic responses collected via NIRS and MRI (R=0.760, P<0.001 and R=0.537, P<0.001 for the MG and TA, respectively). Bland Altman plots demonstrated a strong agreement between the TSI and T2* AUC values (data fell within the 95% confidence interval limits), and linear regression analyses were non-significant (b= -0.753, P=0.068 and b=0.089, P=0.75 for the MG and TA, respectively), indicating no significant measurement bias. Conclusions These data suggest that there is a moderate level of agreement between the MRI PIVOT and NIRS based assessments of the SmO2 response to reactive hyperemia.

Adenosine A 2A Receptor and Vascular Response: Role of Soluble Epoxide Hydrolase, Adenosine A 1 Receptor and Angiotensin‐II

Previously, we reported that the coronary reactive hyperemic response (CRH) was reduced in adenosine A2A receptor-null (A2AAR-/-) mice, and reversed by soluble epoxide hydrolase (sEH) inhibitor. However, this is unknown in aortic vascular response; therefore, we hypothesized that A2AAR-gene deletion in mice (A2AAR-/-) affects adenosine-induced vascular response by increasing sEH and adenosine A1 receptor (A1AR) activities. A2AAR-/- mice showed an increase in sEH, AI AR and CYP450-4A protein expression but decrease in CYP450-2C compared to C57Bl/6 mice. NECA (adenosine-analog) and CCPA (adenosine A1 receptor-agonist)-induced dose-dependent vascular response was tested with t-AUCB (sEH-inhibitor) and angiotensin-II (Ang-II) in A2AAR-/- vs. C57Bl/6 mice. In A2AAR-/-, NECA and CCPA-induced increase in dose-dependent vasoconstriction compared to C57Bl/6 mice. However, NECA and CCPA-induced dose-dependent vascular contraction in A2AAR-/- was reduced by t-AUCB with NECA. Similarly, dose-dependent vascular contraction in A2AAR-/- was reduced by t-AUCB with CCPA. In addition, Ang-II enhanced NECA and CCPA-induced dose-dependent vascular contraction in A2AAR-/- with NECA. Similarly, the dose-dependent vascular contraction in A2AAR-/- was also enhanced by Ang-II with CCPA. Furthermore, t-AUCB reduced Ang-II-enhanced NECA and CCPA-induced dose-dependent vascular contraction in A2AAR-/-mice. Our data suggest that the dose-dependent vascular contraction in A2AAR-/- mice depends on increase in sEH, A1AR and CYP4A protein expression.

Effects of compression stockings on lower-limb venous and arterial system responses to prolonged sitting: A randomized cross-over trial.

Exposure to prolonged sitting increases blood pooling and the risk of lower-extremity vascular arterial and venous complications, including deep vein thrombosis. Compression garment stockings (CGS) may prevent pooling, thereby mitigating the associated vascular complications. Three aims were addressed: (i) does use of CGS help to prevent blood pooling; (ii) does blood pooling correlate with decreased stroke volume; and (iii) does use of CGS preserve leg arterial flow-mediated dilation and reactive hyperemia response. Twenty inactive participants (22 ± 4 years, 30% female, 22.1 ± 2.0 kg/m2) were randomized to sit for 3 hours with (CGS) and without use of CGS. Blood pooling was determined using medial gastrocnemius total hemoglobin. Stroke volume was estimated using finger photoplethysmography, respectively. Macrovascular and microvascular function were measured using popliteal artery flow-mediated dilation and reactive hyperemia, respectively. In response to 3 hours of sitting: (i) there was an interaction effect for total hemoglobin (p < 0.001); the condition without use of CGS increased 10.5% (95% CI: 6.7 to 14.3) and CGS increased 4.3% (95% CI: 0.1 to 7.7); (ii) blood pooling was negatively associated with stroke volume (r = -0.58, 95% CI: -0.68 to -0.45); (iii) reactive hyperemia and flow-mediated arterial dilation was impaired after prolonged sitting, and use of CGS was not associated with attenuation of this impairment. Use of CGS decreases blood pooling but does not preserve arterial macrovascular and microvascular responses to prolonged sitting. Further study is warranted to determine whether CGS has additive benefits when combined with sitting interruption strategies.

Adenosine A2A receptor and vascular response: role of soluble epoxide hydrolase, adenosine A1 receptor and angiotensin-II.

Previously, we have reported that the coronary reactive hyperemic response was reduced in adenosine A2A receptor-null (A2AAR-/-) mice, and it was reversed by the soluble epoxide hydrolase (sEH) inhibitor. However, it is unknown in aortic vascular response, therefore, we hypothesized that A2AAR-gene deletion in mice (A2AAR-/-) affects adenosine-induced vascular response by increase in sEH and adenosine A1 receptor (A1AR) activities. A2AAR-/- mice showed an increase in sEH, AI AR and CYP450-4A protein expression but decrease in CYP450-2C compared to C57Bl/6 mice. NECA (adenosine-analog) and CCPA (adenosine A1 receptor-agonist)-induced dose-dependent vascular response was tested with t-AUCB (sEH-inhibitor) and angiotensin-II (Ang-II) in A2AAR-/- vs. C57Bl/6 mice. In A2AAR-/-, NECA and CCPA-induced increase in dose-dependent vasoconstriction compared to C57Bl/6 mice. However, NECA and CCPA-induced dose-dependent vascular contraction in A2AAR-/- was reduced by t-AUCB with NECA. Similarly, dose-dependent vascular contraction in A2AAR-/- was reduced by t-AUCB with CCPA. In addition, Ang-II enhanced NECA and CCPA-induced dose-dependent vascular contraction in A2AAR-/- with NECA. Similarly, the dose-dependent vascular contraction in A2AAR-/- was also enhanced by Ang-II with CCPA. Further, t-AUCB reduced Ang-II-enhanced NECA and CCPA-induced dose-dependent vascular contraction in A2AAR-/- mice. Our data suggest that the dose-dependent vascular contraction in A2AAR-/- mice depends on increase in sEH, A1AR and CYP4A protein expression.

Using reactive hyperemia to investigate the effect of cupping sizes of cupping therapy on skin blood flow responses.

Various cupping sizes of cupping therapy have been used in managing musculoskeletal conditions; however, the effect of cupping sizes on skin blood flow (SBF) responses is largely unknown. The objective of this study was to compare the effect of three cupping sizes of cupping therapy on SBF responses. Laser Doppler flowmetry (LDF) was used to measure SBF on the triceps in 12 healthy participants in this repeated measures study. Three cup sizes (35, 40 and 45mm in diameter) were blinded to the participants and were tested at -300 mmHg for 5minutes. Reactive hyperemic response to cupping therapy was expressed as a ratio of baseline SBF. All three sizes of cupping cups resulted in a significant increase in peak SBF (p< 0.001). Peak SBF of the 45mm cup (9.41 ± 1.32 times) was significantly higher than the 35mm cup (5.62 ± 1.42 times, p< 0.05). Total SBF of the 45mm cup ((24.33 ± 8.72) × 103 times) was significantly higher than the 35mm cup ((8.05 ± 1.63) × 103 times, p< 0.05). Recovery time of the 45mm cup (287.46 ± 39.54 seconds) was significantly longer than the 35mm cup (180.12 ± 1.42 seconds, p< 0.05). Our results show that all three cup sizes can significantly increase SBF. The 45mm cup is more effective in increasing SBF compared to the 35mm cup.

Optical coherence tomography for the investigation of skin adaptation in lower limb prosthesis users.

Mechanically induced skin breakdown is a significant problem for many lower-limb prosthesis users. It is known that skin can adapt to the mechanical stresses of prosthesis use thereby reducing the risk of breakdown, yet little is understood about the biology behind skin adaptation. This is a proof-of-concept study for the use of novel, noninvasive optical coherence tomography (OCT) imaging techniques to investigate skin adaptation. Two OCT imaging-based tests were used to evaluate features of the skin that may be involved in adaptation to limb-socket interface stresses. The tests were used to assess the function and structure of the cutaneous microvasculature, respectively. Epidermal thickness was also quantified. Tests were run on three lower-limb prosthesis users in a region of the residual limb believed to be highly stressed within the prosthetic socket. The measurements were compared with measurements taken at a location-matched site on the contralateral limb. Two of three participants demonstrated a faster time-to-peak and larger peakmagnitude reactive hyperemia response in their residual limb compared with their contralateral limb. Two of three participants also demonstrated a larger magnitude vessel density at maximum dilation in their residual limb versus contralateral limb. The epidermal thickness was greater in the residual limb versus contralateral limb for all participants. This study demonstrated the utility of two novel OCT imaging techniques for investigating skin adaptation in users of lower-limb prostheses. If we are able to confirm these findings on a larger subject population, we will better understand the biology behind mechanically induced skin adaptation. These findings, along with the noninvasive OCT imaging methods introduced here, would have the potential to improve clinical practice by enabling the development of rehabilitation techniques and therapeutics to better strengthen skin, thereby reducing the incidence of harmful skin breakdown.

Reduced effect of ischemic preconditioning against endothelial ischemia-reperfusion injury with cardiovascular risk factors in humans.

The extent that clustered CVD risk factors interfere with ischemic preconditioning (IPC) to protect against microvascular endothelial dysfunction with ischemia-reperfusion (I/R) injury in humans is unclear. We hypothesized that adults with a clustered burden of ≥3 CVD risk factors would demonstrate a reduced capacity of IPC to protect endothelial function with I/R injury. Twenty-two (age: 45 ± 14 year) adults [12 healthy controls; 10 raised risk (10-year FRS risk score ~3%)] were studied using a 2 × 2 randomized cross-over design. Pulse arterial tonometry was used to assess microvascular endothelium-dependent vasodilation during reactive hyperemia in response to endothelial I/R injury (20 min brachial artery occlusion/45 min reperfusion) that was preceded by remote IPC (3 × 5 min ischemia/reperfusion) or mock IPC. In both groups, microvascular reactive hyperemia was reduced ~20% (both P < 0.01) after endothelial I/R injury without remote IPC. However, in control subjects remote IPC prevented endothelial I/R injury (from baseline reactive hyperemic ratio: 2.1 ± 0.4 AU to post I/R injury: 2.5 ± 0.5 AU; P = 0.09). In contrast, the reactive hyperemia ratio in raised risk subjects was significantly reduced from 2.2 ± 0.6 AU to 1.9 ± 0.5 AU (P = 0.0087) despite attempts to induce protection by remote IPC, with the magnitude of reduction similar to their mock IPC trial. The magnitude of remote IPC-mediated endothelial protection against I/R injury was inversely related to the number of risk factors. CVD risk factors diminish the effect of IPC to protect the microvasculature from I/R injury in humans. Translating IPC to clinical practice for vasculoprotection will continue to be challenging in patients with increased CVD risk.

Cortisol level after dexamethasone suppression test in patients with non-functioning adrenal incidentaloma is positively associated with the duration of reactive hyperemia response on microvascular bed.

Data on endothelial derangements in patients with non-functioning adrenal incidentaloma (NFAI) are scarce. We investigated if NFAI patients present clinical, biochemical and endothelial alterations compared to individuals without an adrenal lesion and also the associations among these variables. Forty-two NFAI and 40 controls were evaluated. NFAI diagnosis and controls were defined according to the current guidelines and based on a normal adrenal imaging exam, respectively. Body composition was evaluated by dual emission X-ray absorptiometry. Endothelial reactivity was assessed by two methods: tonometry (Endo-PAT®) and laser speckle contrast imaging (LSCI). There were no differences between groups regarding age, gender, ethnicity, smoking status, and statin use. The frequency of metabolic syndrome according to the International Diabetes Federation criteria was 69% and 57.9%, respectively in NFAI and controls (p = 0.36), whereas the atherosclerotic cardiovascular disease (ASCVD) risk was 63.4% and 66.7% (p = 0.81). The clinical, laboratory, and anthropometric characteristics, as well as body composition, were similar between the groups. Additionally, any differences between groups were observed on endothelial reactivity tests. Nevertheless, we noted an association between cortisol levels after 1mg-dexamethosone suppression test (1mg-DST) and the duration of post-occlusive reactive hyperemia tested on microcirculation (r = 0.30; p = 0.03). NFAI patients require more antihypertensive drugs to achieve blood pressure control (p = 0.04). The number of antihypertensive drugs used to control blood pressure correlated with cortisol levels after 1mg-DST (r = 0.29; p = 0.03). Since both groups herein investigated had a high frequency of metabolic syndrome and ASCVD risk, it might explain similarities observed on endothelial reactivity. Nevertheless, prolonged reactive hyperemia response on microcirculation was correlated with cortisol levels under suppression.

Chronic antioxidant administration restores macrovascular function in patients with heart failure with reduced ejection fraction.

What is the central question of this study? We aimed to examine oxidative stress, antioxidant capacity and macro- and microvascular function in response to 30 days of oral antioxidant administration in patients with heart failure with reduced ejection fraction. What is the main finding and its importance? We observed an approximately twofold improvement in macrovascular function, assessed via brachial artery flow-mediated dilatation, and a reduction in oxidative stress after antioxidant administration in patients with heart failure with reduced ejection fraction. The improvement in macrovascular function was reversed 1week after treatment cessation. These findings have identified the potential of oral antioxidant administration to optimize macrovascular health in this patient group. Heart failure with reduced ejection fraction (HFrEF) is characterized by macrovascular dysfunction and elevated oxidative stress that may be mitigated by antioxidant (AOx) administration. In this prospective study, we assessed flow-mediated dilatation (FMD) and reactive hyperaemia responses in 14 healthy, older control participants and 14 patients with HFrEF, followed by 30days of oral AOx administration (1g vitaminC, 600I.U. vitaminE and 0.6g α-lipoic acid) in the patient group. Blood biomarkers of oxidative stress (malondialdehyde) and AOx capacity (ferric reducing ability of plasma) were also assessed. Patients with HFrEF had a lower %FMD (2.63±1.57%) than control participants (5.62±2.60%), and AOx administration improved %FMD in patients with HFrEF (30days, 4.90±2.38%), effectively restoring macrovascular function to that of control participants. In a subset of patients, we observed a progressive improvement in %FMD across the treatment period (2.62±1.62, 4.23±2.69, 4.33±2.24 and 4.97±2.56% at days 0, 10, 20 and 30, respectively, n=12) that was abolished 7days after treatment cessation (2.99±1.78%, n=9). No difference in reactive hyperaemia was evident between groups or as a consequence of the AOx treatment. Ferric reducing ability of plasma levels increased (from 6.08±2.80 to 6.70±1.59mm, day0versus 30) and malondialdehyde levels decreased (from 6.81±2.80 to 6.22±2.84μm, day 0versus 30) after treatment. These findings demonstrate the efficacy of chronic AOx administration in attenuating oxidative stress, improving AOx capacity and restoring macrovascular function in patients with HFrEF.

Impaired Microvascular Response to Muscle Stretching in Chronic Smokers With Type 2 Diabetes

ObjectiveCigarette smoking promotes endothelial dysfunction and is a prominent catalyst for vascular disease. This study employed laser doppler flowmetry (LDF) and spectral analysis to investigate the skin microvascular response to relatively mild stimulus of stretching in diabetic smokers.MethodsThe study population consisted of thirty type 2 diabetic male patients (15 smokers vs. 15 non-smokers) and 15 normal non-smoking subjects. The cutaneous blood flow of the calf at both lower limbs was measured by LDF at a supine position throughout and after muscle stretching by passive dorsiflexion of the ankle.ResultsFollowing the stretch, post-stretch reactive hyperemia (PSRH) responses were found in all subjects. However, the diabetic non-smokers had relatively higher reactive blood flow than that of the diabetic smokers. The PSRH sustained for a longer time in both diabetic non-smokers and non-diabetic non-smokers in the time domain analysis. By spectral analysis, an observed discrepancy between that of diabetic smokers and diabetic non-smokers was statistically significant. Specifically, the frequency intervals corresponded to a nitric oxide dependent endothelial activity. In addition, an excessive response induced by stretching in frequency intervals of neurogenic activity, when compared with the non-smoking control, was found on diabetic non-smokers.ConclusionAll subjects expressed the PSRH effect in cutaneous microcirculation after a 10-s stretch stimulus; however, this effect was observed at a significantly lower intensity in chronic smokers with diabetes. The spectral analysis of the skin blood flow signals provides a pathological index for the assessment of the endothelial dysfunction induced by cigarette smoking. Furthermore, the discrepancy of neurovascular function between that of diabetic non-smokers and normal subjects could also be distinguished via the variations of the spectrum related to neurogenic activity.

Enhanced coronary vasodilation in isolated Langendorff‐perfused hearts of asthmatic mice

Clinical studies have shown that asthma is associated with high risk of cardiovascular diseases. We previously demonstrated that asthmatic mice have impaired vascular reactivity and endothelial function in aorta. However, little is known regarding coronary vascular reactivity in asthmatic mice. This study aims to examine the coronary flow response to vasodilators and to short period of ischemia in isolated hearts of asthmatic mice. Asthmatic mice were induced by I.P. injection of ovalbumin (OVA, 0.2 μg) on days 1 and 6, followed by 5% OVA aerosol challenges on days 11–13. Hearts were isolated and perfused on day 14 to examine the coronary flow (CF) response. CF was measured using Langendorff system. Baseline CF was comparable between normal and sensitized mice. However, peak CF and repayment/debt ratio following a 15‐s occlusion were significantly higher (~1.14 and 1. 55 folds increase, respectively, p&lt;0.05) in sensitized versus control mice. In lines with the enhanced reactive hyperemic response, acetylcholine (ACH, 10−9‐105.5M) induced an augmented flow increase (Emax=2.8 ± 0.16 and 2.4 ± 0.14 times the baseline in sensitized versus control mice, respectively, p&lt;0.05) which was not affected by L‐NAME (nitric oxide synthase inhibitor). Additionally, sodium nitroprusside (SNP, 10−5 M) induced a ~25% more coronary flow increase (p&lt;0.05) in sensitized mice. Our data suggest that during early stage of sensitized asthmatic mouse model, the coronary circulation demonstrates an enhanced flow reserve though the baseline flow is unchanged. The changes in coronary flow reserve in asthmatic mice indicate one of the potential protective mechanisms against hypoxia/ischemia–induced heart injury in asthmatic patients. Supported by HL 027339 (SJM) and WVCTSI Pilot Grant NIH/NIGMS U54GM104942 (DSP)

Optical coherence tomography for the investigation of skin adaptation to mechanical stress.

Skin breakdown due to limb-socket interface stress is a significant problem for lower limb prosthesis users. While it is known that skin can adapt to stress to become more resistant to breakdown, little is understood about skin adaptation and few methods exist to noninvasively investigate it. In this study, we present novel, noninvasive imaging methods using Optical Coherence Tomography (OCT) to assess key features of the cutaneous microvasculature that may be involved in skin adaptation. Eight able-bodied participants wore a modified below-knee prosthetic socket for two weeks to stress the skin of their lower limb. Two OCT-based imaging tests were used to assess the function and structure, respectively, of the cutaneous microvasculature at multiple time points throughout the socket wear protocol. A measurable reactive hyperemia response was reliably induced in the skin of study participants in the vascular function assessment test. The vascular structure assessment demonstrated excellent field-of-view repeatability, providing rich data sets of vessel structure. No statistically significant differences were found in any of the measurements when compared between time points of the adaptation protocol. The participants' limbs were likely not stressed enough by the able-bodied socket to induce measurable skin adaptation. This study introduced new techniques to investigate skin adaptation to mechanical stress. If the key limitations are addressed, these methods have the potential to provide insight into the function and structure of the cutaneous microvasculature that previously could not be attained noninvasively.

Abstract P432: Racial Differences In Endothelial Function And Insulin Sensitivity

Racial disparities in health outcomes continue to be a significant public health concern and African Americans (AA) are disproportionately burdened by several risk factors for cardiovascular disease. Endothelial dysfunction has been shown to be a predictor of CVD and metabolic factors, including insulin resistance, are associated with endothelial dysfunction. Compared to EA, AA have impaired endothelial function and are more insulin resistant (less insulin sensitive). However, it remains unclear how insulin resistance may contribute to endothelial dysfunction in AA and EA. The purpose of the present study was to evaluate the relationship between insulin sensitivity and endothelial function in AA and EA. It was hypothesized that insulin sensitivity would be associated with endothelial function in both AA and EA. Skeletal muscle insulin sensitivity was measured by hyperinsulinemic-euglycemic glucose clamp technique in 112 lean, overweight, and obese AA and EA adults without diabetes. Insulin was infused at 120 mU/m 2 /min for 3 hours and an infusion of 20% dextrose was adjusted to maintain blood glucose at the fasting level. Insulin sensitivity (10 -4 .dL.kg -1 .min -1 /(μU/mL)) was defined as M/(G x ΔI), where M is steady state glucose infusion rate, G is steady state serum glucose concentration, and ΔI is the difference between basal and steady state serum insulin concentrations. M was adjusted for total lean body mass which was measured by dual-energy X-ray absorptiometry (DXA). Endothelial function was assessed by percent change in flow-mediated brachial artery dilatation (FMD). Changes in brachial artery diameter during reactive hyperemia were measured using ultrasound. Increased blood flow was induced via blood pressure cuff around the forearm, with a 5-minute inflation at 50 mmHg above the subject’s systolic blood pressure. Brachial arterial flow was determined using a pulsed-Doppler signal at baseline and 10-15 seconds after cuff release. Arterial diameter was measured at end-diastolic phase from super-VHS recordings. For reactive hyperemia response, measurements with the 5 largest diameters were averaged and the percent increase from baseline was determined as FMD. A total of 55 AA and 57 EA were included in the analysis. Mean insulin sensitivity was 4.89 in AA and 7.97 in EA (p &lt; .0001) and mean FMD was 10.69 in AA and 10.14 in EA (p = .595). Linear regression analysis indicated a significant relationship between insulin sensitivity and endothelial function in AA but not in EA (p= .005 and p= .5, respectively). These results suggest that insulin sensitivity may play a role in determining endothelial function in AA.