Microvascular Responses Research Articles

Epicardial adipose tissue attenuation on computed tomography in women with coronary microvascular dysfunction: A pilot, hypothesis generating study

BackgroundPatients with myocardial ischemia without obstructive coronary artery disease often have coronary microvascular dysfunction (CMD) and associated increased risk of cardiovascular (CV) events and anginal hospitalizations. Epicardial adipose tissue (EAT) covers much of the myocardium and coronary arteries and when dysfunctional, secretes proinflammatory cytokines and is associated with CV events. While oxidative stress and systemic inflammation are associated with CMD, the relationship between EAT and CMD in women is not well known. MethodsWomen diagnosed with CMD (n = 21) who underwent coronary computed tomography with coronary artery calcium (CAC) scoring were compared to a reference group (RG) of women referred for CAC screening for preventive risk assessment (n = 181). EAT attenuation (Hounsfield units (HU)) was measured adjacent to the proximal right coronary artery, along with subcutaneous adipose tissue (SCAT). Two-sample t-tests with unequal variances were utilized. ResultsMean age of the CMD group was 56 ± 8 years and body mass index (BMI) was 31.6 ± 6.8 kg/m2. CV risk factors in the CMD group were prevalent: 67 % hypertension, 44 % hyperlipidemia, and 33 % diabetes. Both CMD and RG had similar CAC score (25.86 ± 59.54 vs. 24.17 ± 104.6; p = 0.21. In the CMD group, 67 % had a CAC of 0. Minimal atherosclerosis (CAD-RADS 1) was present in 76 % of women with CMD. The CMD group had lower EAT attenuation than RG (−103.3 ± 6.33 HU vs. −97.9 ± 8.3 HU, p = 0.009, respectively). There were no differences in SCAT attenuation. Hypertension, smoking history, age, BMI, and CAC score did not correlate with EAT in either of the groups. ConclusionsWomen with CMD have decreased EAT attenuation compared to RG women. EAT-mediated inflammation and changes in vascular tone may be a mechanistic contributor to abnormal microvascular reactivity. Clinical trials testing therapeutic strategies to decrease EAT may be warranted in the management of CMD.

Vasoreactivity and inhaled treprostinil response in interstitial lung disease pulmonary hypertension

IntroductionDespite shared features with pulmonary arterial hypertension, acute vasoreactivity in pulmonary hypertension with interstitial lung disease (PH-ILD) is not well characterized, including its potential ability to predict therapeutic outcomes. We sought to determine if acute vasoreactivity in PH-ILD to oxygen (O2) and inhaled nitric oxide (iNO) predicts inhaled treprostinil (iTre) outcomes.Materials and MethodsIn this retrospective cohort analysis, we identified treatment-naïve PH-ILD patients with vasoreactivity testing using O2 and O2+iNO. Six-month iTre outcome was assessed. “iTre improvement” required fulfillment of criteria on objective assessment without clinical worsening. “iTre failure” was defined by lack of objective improvement or a clinical worsening event.ResultsAmong 75 PH-ILD patients, mPAP decreased by −3 mmHg (−12.6%) and PVR by −1.3WU (−23.7%) with O2+iNO. With O2+iNO, mPAP decreased ≥10 mmHg to <40 mmHg in 4 patients (5.3%), and 23 (30.7%) had ≥20% reduction in mPAP and PVR. Among 33 iTre-treated patients, there were 13 improvements and 20 failures. The microvascular response, measured by distensibility, to O2 aloneversusO2+iNO correlated with 6-month iTre outcome. Patients with 6-month iTre improvement had large relative distensibility increases with O2+ iNO (versusfailure, 76.0%versus15.3%, p=0.004). Conversely, iTre failure was associated with increased distensibility with O2 alone (versusimprovement, 26.8%versus−3.9%, p=0.045).ConclusionsIn PH-ILD, the microvascular response to O2versusO2+iNO testing was associated with six-month iTre outcome, likely reflecting the differential contributions of hypoxic vasoconstriction and remodeling. Acute vasoreactivity may inform therapeutic decision-making in PH-ILD.

Noninvasive assessment of human microvascular function in health and disease using incident dark-field microscopy.

Reduced peripheral microvascular reactivity is associated with an increased risk for major adverse cardiac events (MACEs). Tools for noninvasive assessment of peripheral microvascular function are limited, and existing technology is poorly validated in both healthy populations and patients with cardiovascular disease (CVD). Here, we used a handheld incident dark-field imaging tool (CytoCam) to test the hypothesis that, compared with healthy individuals (no risk factors for CVD), subjects formally diagnosed with coronary artery disease (CAD) or those with ≥2 risk factors for CAD (at risk) would exhibit impaired peripheral microvascular reactivity. A total of 17 participants (11 healthy, 6 at risk) were included in this pilot study. CytoCam was used to measure sublingual microvascular total vessel density (TVD), perfused vessel density (PVD), and microvascular flow index (MFI) in response to the topical application of acetylcholine (ACh) and sublingual administration of nitroglycerin (NTG). Baseline MFI and PVD were significantly reduced in the at-risk cohort compared with healthy individuals. Surprisingly, following the application of acetylcholine and nitroglycerin, both groups showed a significant improvement in all three microvascular perfusion parameters. These results suggest that, despite baseline reductions in both microvascular density and perfusion, human in vivo peripheral microvascular reactivity to both endothelial-dependent and -independent vasoactive agents remains intact in individuals with CAD or multiple risk factors for disease.NEW & NOTEWORTHY To our knowledge, this is the first study to comprehensively characterize in vivo sublingual microvascular structure and function (endothelium-dependent and -independent) in healthy patients and those with CVD. Importantly, we used an easy-to-use handheld device that can be easily translated to clinical settings. Our results indicate that baseline microvascular impairments in structure and function can be detected using the CytoCam technology, although reactivity to acetylcholine may be maintained even during disease in the peripheral microcirculation.

Interaction of macro- and microvascular function underlies brachial artery flow-mediated dilation in humans.

Brachial artery flow-mediated dilation (BAFMD) is induced by hyperemic wall shear rate (WSR) following forearm ischemia. In older adults, there appears to be a reduced brachial hyperemic WSR and altered stimulus-response relationship compared with young adults. However, it is unclear if an altered forearm microvascular response to ischemia influences brachial hyperemic WSR in older adults. We determined associations between brachial hyperemic WSR and forearm skeletal muscle oxygen saturation in young and older adults. Healthy young (n = 17, 29 ± 7 yr) and older (n = 32, 65 ± 4 yr) adults participated in the study. BAFMD by a multigate spectral Doppler system and forearm skeletal muscle oxygen saturation by near-infrared spectroscopy were concurrently measured. When compared with the young, older adults showed reduced oxygen extraction kinetics (OE, 0.15 [0.12-0.17] vs. 0.09 [0.05-0.12]%s-1) and magnitude (So2deficit, 3,810 ± 1,420 vs. 2,723 ± 1,240%s) during ischemia, as well as oxygen resaturation kinetics (So2slope, 2.5 ± 0.7 vs. 1.7 ± 0.7%s-1) upon reperfusion (all P < 0.05). When OE in the young and So2slope in older adults were stratified by their median values, young adults with OE above the median had greater hyperemic WSR parameters compared with those below the median (P < 0.05), but So2slope in older adults did not show clear differences in hyperemic WSR parameters between those above/below the median. This study demonstrates that, in addition to a reduced microvascular response to ischemia, there may be a dissociation between microvascular response to ischemia and brachial hyperemic WSR in older adults, which may result in a further impairment of BAFMD in this cohort.NEW & NOTEWORTHY Microvascular response to ischemia and subsequent reperfusion is diminished in older adults compared with the young. Furthermore, there appears to be a dissociation between the microvascular response to ischemia and brachial hyperemic WSR in older adults, which may further disturb the BAFMD process in this cohort. A reduced BAFMD in older adults may be a result of multiple alterations occurring both at macro- and microcirculation.

#1553 Effects of proteinuria on muscle oxygenation and microvascular reactivity in patients with pre-dialysis CKD: a post-hoc analysis

Abstract Background and Aims Vascular dysfunction is a hallmark of CKD. Previous studies showed an impaired microvascular reactivity in the skeletal muscles, which deteriorates in advanced CKD stages. This analysis aims to examine the impact of proteinuria on skeletal muscle oxygenation and microvascular reactivity at rest, during an occlusion-reperfusion maneuver, and during exercise in patients with pre-dialysis CKD. Method 66 patients with CKD stage 2-4 were included in this post-hoc analysis; 24-h urine samples were used for evaluation of proteinuria. Continuous measurement of muscle oxygenation [tissue saturation index (TSI%)] via near-infrared-spectroscopy at rest, during occlusion-reperfusion and during a 3-min handgrip exercise (at 35% of maximal-voluntary-contraction). Results The study groups were similar in terms of age (proteinuric vs nonproteinuric: 68.4 ± 10.6 vs 67.2 ± 10.8; p = 0.676), eGFR (41.3 ± 18.9 vs 46.3 ± 14.8; p = 0.248) and BMI (28.4 ± 4.9 vs 28.1 ± 4.8; p = 0.803). Resting muscle oxygenation did not differ between study groups (proteinuric vs nonproteinuric: 63.35 ± 4.09 vs 62.34 ± 3.21; p = 0.280). During occlusion, proteinuric CKD patients had marginally lower TSI occlusion magnitude (25.77 ± 7.87 vs 29.95 ± 10.34; p = 0.074) but no difference in occlusion slope (−0.09 ± .03 vs -.10 ± .04; p = 0.134). During reperfusion, the TSI reperfusion slopes were significantly lower in proteinuric CKD (slope to max 1.03 ± .45 vs 1.39 ± 0.69; p = 0.035 and 10-sec slope: 1.34 ± .63 vs 1.92 ± .75; p = 0.002); hyperemic response was numerically lower in proteinuric CKD (7.13 ± 4.27 vs 8.89 ± 4.68; p = 0.131). Finally, during exercise no differences were detected in the average muscle oxygenation between-group (10.76 ± 6.05 vs 10.65 ± 5.39; p = 0.943). Conclusion Although no differences in resting muscle oxygenation were detected, CKD patients with proteinuria showed more impaired skeletal muscle oxidative capacity (as suggested by lower TSI magnidute during occlusion), and miscrovascular reactivity during reperfusion.

Correlation of diabetic renal hypoperfusion with microvascular responses of the skeletal muscle: a rat model study using diffuse correlation spectroscopy.

Using diffuse correlation spectroscopy, we assessed the renal blood flow and thigh muscle microvascular responses in a rat model of type 2 diabetes. The blood flow index at the renal surface decreased significantly with arterial clamping, cardiac extirpation, and the progression of diabetic endothelial dysfunction. Renal blood flow measured in diabetic and nondiabetic rats also showed a significant correlation with the reactive hyperemic response of the thigh muscle. These results suggest shared microcirculatory dysfunction in the kidney and skeletal muscle and support endothelial responses in the skeletal muscle as a potential noninvasive biomarker of renal hypoperfusion.

An evaluation of the effects of localised skin cooling on microvascular, inflammatory, structural, and perceptual responses to sustained mechanical loading of the sacrum: A study protocol.

This study protocol aims to investigate how localised cooling influences the skin's microvascular, inflammatory, structural, and perceptual tolerance to sustained mechanical loading at the sacrum, evaluating factors such as morphology, physiology, and perceptual responses. The protocol will be tested on individuals of different age, sex, skin tone and clinical status, using a repeated-measure design with three participants cohorts: i) young healthy (n = 35); ii) older healthy (n = 35); iii) spinal cord injured (SCI, n = 35). Participants will complete three testing sessions during which their sacrum will be mechanically loaded (60 mmHg; 45 min) and unloaded (20 min) with a custom-built thermal probe, causing pressure-induced ischemia and post-occlusive reactive hyperaemia. Testing sessions will differ by the probe's temperature, which will be set to either 38°C (no cooling), 24°C (mild cooling), or 16°C (strong cooling). We will measure skin blood flow (via Laser Doppler Flowmetry; 40 Hz); pro- and anti-inflammatory biomarkers in skin sebum (Sebutape); structural skin properties (Optical Coherence Tomography); and ratings of thermal sensation, comfort, and acceptance (Likert Scales); throughout the loading and unloading phases. Changes in post-occlusive reactive hyperaemia will be considered as the primary outcome and data will be analysed for the independent and interactive effects of stimuli's temperature and of participant group on within- and between-subject mean differences (and 95% Confidence Intervals) in peak hyperaemia, by means of a 2-way mixed model ANOVA (or Friedman). Regression models will also be developed to assess the relationship between absolute cooling temperatures and peak hyperaemia. Secondary outcomes will be within- and between-subject mean changes in biomarkers' expression, skin structural and perceptual responses. This analysis will help identifying physiological and perceptual thresholds for the protective effects of cooling from mechanically induced damage underlying the development of pressure ulcers in individuals varying in age and clinical status.

Home-Based Heat Therapy and Vascular Function of Adults Living with Type 2 Diabetes: Preliminary Analyses of a Randomized Controlled Trial

Background: Several studies indicate that various heat exposure interventions improve peripheral endothelial function and microvascular reactivity, as well as reduce central arterial stiffness and blood pressure in various populations. Nonetheless, few studies have considered the potential therapeutic effects of heat exposure for people living with type 2 diabetes mellitus (T2DM), who are at high cardiovascular risk. In addition, all heat therapy interventions investigated to date have been laboratory-based, which may limit long-term adherence. HYPOTHESES: This study aims is to determine the effects of a 12-week home-based heat therapy intervention on markers of vascular function in adults living with T2DM. The primary hypothesis is that heat therapy improves peripheral endothelial function relative to a sham intervention. Secondary hypotheses include improved microvascular reactivity, central arterial stiffness, and 24h blood pressure. METHODS: Thirteen adults (66 ± 10 years, 28.9 ± 6.0 kg/m2, 9 men/ 4 women) living with TD2M were randomized to 12 weeks of home-based heat therapy (n=7, lower leg immersion in 42°C water) or a thermoneutral sham intervention (n=6, lower leg immersion in 36°C water). Peripheral endothelial function (brachial artery flow-mediated dilation, FMD), microvascular reactivity (post-occlusive reactive hyperemia), arterial stiffness (carotid-femoral pulse wave velocity), and 24h blood pressure (ambulatory blood pressure monitoring), were measured before and after the intervention. RESULTS: Brachial artery FMD changed by 1.72% [95%CI, 0.06; 3.37] in response to heat therapy compared to 0.41% [-1.38; +2.20] in response to the sham intervention. Peak and total reactive hyperemia changed by 0.79 mL/min/mmHg [-0.27; 1.86] and by 1.77 mL/mmHg [0.73; 2.81], respectively, in response to heat therapy compared with 0.76 mL/min/mmHg [-0.38; 1.91] and 1.68 mL/mmHg [0.56; 2.80] in response to the sham intervention. Arterial stiffness changed by 0.55 m/s [-1.62; 2.71] in response to heat therapy compared with -1.60 m/s [-3.75; 0.57] in response to the sham intervention. The 24h-systolic and diastolic blood pressure changed by 6 mmHg [-1; +12] and 2 mmHg [-3; +7], respectively, in response to heat therapy compared with -2 mmHg [-10; +6] and -3 mmHg [-9; +3] in response to the sham intervention. CONCLUSION: These preliminary results suggest that 12 weeks of home-based lower leg hot water immersion improves brachial artery FMD in adults with T2DM. In contrast, the heat therapy intervention does not appear to improve microvascular reactivity, central arterial stiffness, or 24h blood pressure. Cardiometabolic Health Diabetes and Obesity Research Network and Diabète Quebec. This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

Acute and chronic hyperglycemia blunts microvascular reactivity in postmenopausal women with type 2 diabetes

Type 2 diabetes (T2D) is strongly associated with increased risk of cardiovascular diseases via endothelial dysfunction. Hyperglycemia causes microvascular endothelial dysfunction and reduces muscle perfusion. Near-infrared spectroscopy (NIRS) measures microvascular reactivity in skeletal muscle during vascular occlusion/reperfusion. However, the impact of acute and chronic hyperglycemia on macrovascular endothelial function (brachial flow-mediated dilation, FMD) and microvascular reactivity (NIRS-derived tissue oxygen saturation index, TOI) has not been examined in postmenopausal women with and without T2D. We hypothesized that T2D women would have decreased FMD and TOI responsiveness in the fasted condition and greater vascular impairments during acute hyperglycemia compared to controls.Ten T2D (61 ± 5 years) and 10 normoglycemic postmenopausal women (CON, 62 ± 7 years) participated in the study. Hemoglobin A1C (HbA1C) and blood glucose were measured by finger prick at baseline (fasted condition). Brachial artery FMD was evaluated using ultrasound. Forearm muscle TOI magnitude and slope during arterial occlusion and reperfusion periods were measured using NIRS. An oral glucose tolerance test (OGTT) was performed to induce acute hyperglycemia. Blood glucose, FMD, and TOI were measure at baseline and 1 hour (1-h) after OGTT. Abdominal fat was assessed by waist circumference and visceral adipose tissue (VAT) obtained by a whole-body dual-energy X-ray absorptiometry scan.Fasting HbA1C and glucose, waist circumference, and VAT were higher in T2D compared to CON (all p &lt; 0.05). The increase in blood glucose at 1-h was higher in T2D (Δ143 ± 15 mg/dl) compared to CON (Δ49 ± 5 mg/dl) (p &lt; 0.01). FMD at baseline and the decreases in FMD at 1-h were similar in T2D (Δ-2.2 ± 0.2%) and CON groups (Δ-1.9 ± 0.4%) (all p &lt; 0.01). At baseline, T2D showed blunted TOI occlusion magnitude (T2D: -16 ± 1 vs. CON: -21 ± 2%), TOI occlusion slope (T2D: -0.05 ± 0.01 vs. CON: -0.07 ± 0.01), TOI reperfusion magnitude (T2D: 21 ± 2 vs. CON: 32 ± 3%), and TOI reperfusion slope (T2D: 0.79 ± 0.10 vs. CON: 1.19 ± 0.14) compared to CON (all p &lt; 0.05). At 1-h, T2D exhibited lower TOI occlusion magnitude (T2D: -17 ± 2 vs. CON: -24 ± 3%), TOI occlusion slope (T2D: -0.06 ± 0.01 vs. CON: -0.08 ± 0.01), TOI reperfusion magnitude (T2D: 23 ± 2 vs. CON: 33 ± 4%), and TOI reperfusion slope (T2D: 0.90 ± 0.19 vs. CON: 1.14 ± 0.15) compared to CON (all p &lt; 0.05). HbA1C, a measure of chronic hyperglycemia, was positively correlated with VAT (r = 0.514, p = 0.02) and TOI occlusion slope (r = 0.460, p = 0.04) and negatively correlated with TOI reperfusion magnitude (r = -0.506, p = 0.02) and slope at baseline (r = -0.493, p = 0.03). In conclusion, women with T2D exhibited blunted microvascular reactivity despite similar FMD compared with normoglycemic women in the fasted condition. Acute hyperglycemia further blunted microvascular function, but not macrovascular endothelial function, in women with T2D. Blunted microvascular reactivity was associated with chronic hyperglycemia and elevated VAT in postmenopausal women. This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

L-Citrulline Supplementation Improves Leg Endothelial Function and Blood Flow Responses to Plantarflexion Exercise in Hypertensive Postmenopausal Women

Menopause and hypertension are associated with macro- and microvascular endothelial dysfunction at rest. Arginine deficiency and low nitric oxide (NO) synthesis may contribute to reduced muscle blood flow (BF) and oxygen delivery to exercising muscles. Improving BF to calf muscles may enhance physical activity. L-Citrulline supplementation (CIT) has improved resting macrovascular endothelial function via increased arginine availability for NO synthesis. Thus, the purpose of this study was to examine the effects of CIT on resting microvascular endothelial function and BF responses to plantarflexion exercise (PFE) in hypertensive postmenopausal women. We hypothesized that CIT would improve microvascular function and BF responses to PFE compared to placebo (PL). Twenty-one hypertensive postmenopausal women were randomized to 4 weeks of CIT (10g/day, n=10) or PL ( n=11). Superficial femoral macro- (flow-mediated dilation; FMD) and microvascular function (5s average peak blood velocity and flow during reperfusion) were assessed by ultrasound at 0 and 4 weeks. Femoral artery BF and vascular conductance (VC) were measured via ultrasound at rest and during 3-minute stages of rhythmic PFE at 5%, 15%, and 30% of 1-repetition maximum (1RM) at 0 and 4 weeks. BF and VC responses to PFE were analyzed as the change from rest to the last minute of each stage. There were no differences between groups in FMD, 5s peak velocity and flow during reperfusion, and vascular responses to PFE at 0 weeks. CIT significantly increased FMD (CIT:Δ1.28 ± 0.42 vs PL:Δ0.01 ± 0.40%, p = 0.04) and 5s peak velocity (CIT:Δ17.44 ± 4.21 vs PL:Δ0.09 ± 4.01 cm/s, p = 0.01) and flow (CIT:Δ220 ± 54 vs PL:Δ35 ± 51 mL/min, p = 0.02) during reperfusion compared to PL. CIT had no effect on BF and VC responses to 5% PFE ( p &gt; 0.05). CIT significantly augmented BF responses to 15% PFE (CIT:Δ82 ± 16 vs PL:Δ22 ± 15 mL/min, p &lt; 0.01) and 30% PFE (CIT:Δ156 ± 33 vs PL:Δ38 ± 32 mL/min, p &lt; 0.01) and VC responses to 15% PFE (CIT:Δ0.80 ± 0.16 vs PL:Δ0.11 ± 0.15 mL*100mmHg/min, p &lt; 0.01) and 30% PFE (CIT:Δ1.49 ± 0.29 vs PL:Δ0.24 ± 0.27 mL*100mmHg/min, p &lt; 0.01) compared to PL. Improvements in FMD were not correlated with BF or VC responses to PFE ( p &gt; 0.05). Improvements in 5s peak velocity were positively correlated with BF responses to 15% PFE ( r = 0.498, p = 0.02) and 30% PFE ( r = 0.532, p = 0.01), and with VC responses to 15% PFE ( r = 0.542, p = 0.01) and 30% PFE ( r = 0.633, p &lt; 0.01). Similarly, augmented 5s flow was positively correlated with BF ( r = 0.461, p = 0.04) and VC ( r = 0.558, p = 0.01) responses to 30% PFE. These findings indicate that CIT improved superficial femoral artery macro- and microvascular endothelial function at rest. However, only improvements in microvascular endothelial function influenced vascular function during leg exercise in hypertensive postmenopausal women. This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

High Fat Feeding Blunts Skeletal Muscle Oxygen Mediated Blood Flow Responses in Healthy and Type 2 Diabetic Rats

Hypothesis: High fat diet feeding impairs microvascular blood flow responses to dynamic changes in local oxygen concentration ([O2]) in Sprague-Dawley (SD) and Zucker Diabetic Sprague-Dawley (ZDSD) rats. Methods: Seven-week-old male SD and ZDSD rats were fed either a standard chow (N = 7 SD, 5 ZDSD) or a high saturated fat diet (N = 8 SD, 6 ZDSD) for 7 weeks. At 14 weeks of age animals were anaesthetized, instrumented for systemic monitoring, and mechanically ventilated. The extensor digitorum longus muscle was blunt dissected and reflected over a gas exchange chamber imbedded in the stage of an inverted microscope. Microvascular blood flow responses to high and low [O2] challenges (7 – 12 %, and 7 – 2 %) and sequential changes in [O2] (7 – 12 – 2 – 7 %) were recorded at baseline and during hyperinsulinemic-euglycemic clamp. Gas conditions within the chamber were set at 7 % for a 1-minute baseline followed by 2 minutes at either 2 or 12 % O2. The 4-minute square wave oscillation consisted of 1 minute at each [O2] (7 – 12 – 2 – 7 %). Hyperinsulinemic-euglycemic clamp was achieved by simultaneous infusion of insulin (2 U/hr/kg) and variable rate of 50 % glucose until euglycemia was reached (5 - 7 mM blood glucose). Analysis of intravital videos was completed using custom MATLAB software. All animal protocols were approved by Memorial University’s Animal Care Committee. Results: Chow fed SD had significantly higher glucose infusion rates compared to high fat fed SD, chow fed ZDSD, and high fat fed ZDSD (28.11 ± 1.807 vs. 25.14 ± 1.18, 24.56 ± 2.78, 24.77 ± 2.43 mg/kg/min, p = 0.0429, 0.0305, 0.0323, respectively). Red blood cell (RBC) saturation significantly increased and decreased in all groups within 4 s following the increase and decrease in [O2], respectively. Chow fed SD had significant decrease in RBC supply rate (SR) in response to 12 % [O2] (10.41 ± 11.31 vs 7.44 ± 8.40 cells/s, p &lt; 0.0001, τ = 15.85 s). In response to low [O2], significant increases in SR were measured in the chow fed SD and ZDSD groups (7.10 ± 8.76 vs 11.65 ± 11.36 cells/s, p &lt; 0.0001, τ = 17.65 s, and 10.86 ± 13.62 vs 13.86 ± 14.69 cells/s, p &lt; 0.0001, τ = 85.74 s, respectively). High fat fed SD and ZDSD had significant increases in RBC SR during 2 % [O2] (8.47 ± 9.75 vs 11.84 ± 12.11 cells/s, p &lt; 0.0001, τ = 68.49 s, and 16.09 ± 18.12 vs 20.73 ± 21.92 cells/s, p &lt; 0.0001, τ = 23.98 s). High fat fed ZDSD had higher, but not significantly different, baseline RBC SR compared to the chow fed ZDSD group. Chow fed SD were the only group to have an increase in RBC SR at low [O2] during hyperinsulinemic-euglycemic clamp (13.80 ± 17.78 vs 18.07 ± 20.25 cells/s, p = 0.0003, τ = 10.88 s). Conclusions: High fat feeding impairs the capillary blood flow response to local increases in [O2] in healthy and high fat fed T2D model rats. Chow fed ZDSD rats had slower capillary blood flow dynamics than the SD control group. Hyperinsulinemic-euglycemic clamp diminishes the O2 mediated blood flow response in 14-week-old SD and ZDSD rats fed a high fat diet. This project was supported by the Canadian Institute of Health Research through a project grant to GMF. Studentships were supported by Memorial University's School of Graduate Studies and the Faculty of Medicine. This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

Enhancing Endothelial Function with Nutrient-Enriched Table Hen Eggs: A Randomized Study in Patients Recovering from Acute Coronary Syndrome.

This study investigated the effect of consumption of table eggs enriched with n-3 polyunsaturated fatty acids (n-3 PUFA), lutein, vitamin E and selenium on microvascular function, oxidative stress and inflammatory mediators in patients after acute coronary syndrome (ACS). In a prospective, randomized, interventional, double-blind clinical trial, ACS patients were assigned to either the Nutri4 (N=15, mean age: 57.2±9.2 years), or the Control group (N=13; mean age 56.8±9.6 years). The Nutri4 group consumed three enriched hen eggs daily for three weeks, providing approximately 1.785 mg of vitamin E, 0.330 mg of lutein, 0.054 mg of selenium and 438 mg of n-3 PUFAs. Biochemical parameters, including serum lipids, liver enzymes, nutrient concentrations, serum antioxidant enzyme activity (catalase (CAT), glutathione peroxidase (GPx), superoxide dismutase (SOD)), and markers of oxidative stress (thiobarbituric acid reactive substances (TBARS) and ferric reducing ability (FRAP)), were assessed before and after the dietary interventions. Additionally, arterial blood pressure, heart rate, body composition, fluid status, anthropometric measurements, and skin microvascular blood flow responses to various stimuli (postocclusive reactive hyperemia (PORH), acetylcholine- (AchID), and sodium nitroprusside- (SNPID)) were measured using laser Doppler flowmetry (LDF) throughout the study. The intake of Nutri4 eggs led to a significant reduction in LDL cholesterol levels, while the levels of total cholesterol remained within the established reference values. Consuming Nutri4 eggs resulted in a 12.7% increase in serum vitamin E levels, an 8.6% increase in selenium levels, and demonstrated a favorable impact on microvascular reactivity, as evidenced by markedly improved PORH and ACh ID. Nutri4 eggs exerted a significant influence on the activity of GPx and SOD, with no observed changes in TBARS or FRAP values. The consumption of Nutri4 eggs positively influenced microvascular function in individuals with ACS, without eliciting adverse effects on oxidative stress.

EFFECTS OF PROTEINURIA ON MUSCLE OXYGENATION AND MICROVASCULAR REACTIVITY IN PATIENTS WITH PRE-DIALYSIS CKD: A POST-HOC ANALYSIS

Objective: Vascular dysfunction is a hallmark of CKD. Previous studies showed an impaired microvascular reactivity in the skeletal muscles, which deteriorates in advanced CKD stages. This analysis aims to examine the impact of proteinuria on skeletal muscle oxygenation and microvascular reactivity at rest, during an occlusion-reperfusion maneuver, and during exercise in patients with pre-dialysis CKD. Design and method: 66 patients with CKD stage 2-4 were included in this post-hoc analysis; 24-h urine samples were used for evaluation of proteinuria. Continuous measurement of muscle oxygenation [tissue saturation index (TSI%)] via near-infrared-spectroscopy at rest, during occlusion-reperfusion and during a 3-min handgrip exercise (at 35% of maximal-voluntary-contraction). Results: The study groups were similar in terms of age (proteinuric vs nonproteinuric: 68.4±10.6 vs 67.2±10.8; p=0.676), eGFR (41.3±18.9 vs 46.3±14.8; p=0.248) and BMI (28.4±4.9 vs 28.1±4.8; p=0.803). Resting muscle oxygenation did not differ between study groups (proteinuric vs nonproteinuric: 63,35±4,09 vs 62,34±3,21; p=0.280). During occlusion, proteinuric CKD patients had marginally lower TSI occlusion magnitude (25,77±7,87 vs 29,95±10,34; p=0.074) but no difference in occlusion slope (-0,09±.,03 vs -,10±.,04; p=0.134). During reperfusion, the TSI reperfusion slopes were significantly lower in proteinuric CKD (slope to max 1,03±.,45 vs 1,39±.0,69; p=0.035 and 10-sec slope: 1,34±.,63 vs 1,92±.,75; p=0.002); hyperemic response was numerically lower in proteinuric CKD (7,13±.4,27 vs 8,89±.4,68; p=0.131). Finally, during exercise no differences were detected in the average muscle oxygenation between-group (10,76±6,05 vs 10,65±5,39; p=0.943). Conclusions: Although no differences in resting muscle oxygenation were detected, CKD patients with proteinuria showed more impaired skeletal muscle oxidative capacity (as suggested by lower TSI magnidute during occlusion), and miscrovascular reactivity during reperfusion.

Hyperoxia and regional cerebral blood flow: Do brain regions respond differently to high-oxygen gas?

Background: Delivery of oxygen-rich gas (hyperoxia) is used to treat medical emergencies as well as to prevent adverse outcomes in certain occupations that are subjected to extreme environmental conditions. While useful for mitigating acute health risks, hyperoxia has been linked to health decrements including systemic vasoconstriction, increased oxidative stress, worsened neurological outcomes, and increased mortality. Notably, hyperoxia has been found to decrease global cerebral blood flow (CBF) in humans by as much as 37%. Reductions in CBF are associated with increased risk of stroke and cognitive impairment- both of which present heterogeneously. To our knowledge, only one study has explored hyperoxia’s effect on regional CBF and there appeared to be a differential response between regions, but no between-region analysis was performed. If a differential response between regions can be identified, these regions could be monitored more closely for signs of dysfunction or dysregulation. We hypothesized that brain lobes and regions will exhibit a non-uniform reduction in CBF when given 100% oxygen (O2). Methods: Healthy, young adults (n= 15; 7 F; 22 ± 4 yr; BMI: 22 ± 2) were studied after an 8-hour fast and 24-hour abstinence from caffeine, exercise, or alcohol. Women were studied on days 1-5 of their menstrual cycle and not taking any hormonal contraception. Subjects completed a single magnetic resonance imaging (MRI, 3 Tesla) visit. Arterial spin labeling (ASL) MRI quantified microvascular CBF in six lobes and their 71 subregions during normoxia and again after ~10 min steady-state hyperoxia. Hyperoxia was achieved by breathing 100% O2 with supplemental carbon dioxide (CO2) to maintain end-tidal CO2 (ETCO2). The CAT12 toolbox extension for Statistical Parametric Mapping (SPM12) was used to process ASL data. CBF (mL/100g/min) was analyzed as absolute change (Δ), and relative change (%Δ). Two-factor and one-factor repeated measures ANOVA were performed to detect significant main effects and region-condition interactions. A Tukey test was used for post-hoc analysis and pairwise comparisons. Significance was set to P≤0.05. Results: Results are mean ± SD. Heart rate (HR) and ETCO2 remained similar from normoxia to hyperoxia, but mean arterial pressure (MAP) increased by 5 ± 6 mmHg ( P=0.013). Hyperoxia reduced CBF in all anatomical lobes (Occipital; Parietal; Frontal; Temporal; Brainstem/Cerebellum; Subcortical [ P≤0.001]), but the relative decrease was not different between lobes ( P=0.522; range= 18 ± 12% to 21 ± 9%). When examining CBF between 71 smaller brain regions, hyperoxia reduced blood flow in all regions ( P≤0.001; range= 15 ± 13% to 25 ± 13%); ANOVA indicated a region-specific effect ( P≤0.001), however post-hoc analysis did not identify which regions displayed different levels of hypoxic vasoconstriction. Conclusion: These are the first data to systematically examine the regional effects of hyperoxia on CBF. Contrary to our hypothesis, the microvascular CBF reduction to hyperoxia appears uniform across anatomical brain lobes. However, regional analysis indicated that there may be a differential microvascular vasoconstrictor response to hyperoxia between some functional regions of the brain. Funding: NIH R01 HL150361. This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

Divergent Vasodilator Mechanisms to Endothelial-Dependent Agonists with Advancing Age

Introduction: Microvascular function is maintained by a number of vasodilating factors, with nitric oxide (NO) and endothelial hyperpolarizing factors (EDHF) predominating. Advancing age is an independent risk factor in the development of cardiovascular disease, and NO-mediated vasodilation declines, or is unchanged, depending on the vascular bed examined, number of cardiovascular risk factors, or specific endothelial-dependent agonist used. Mechanisms contributing to cutaneous microvascular dysfunction with age have been attributed largely to reductions in NO signaling, but the role of EDHF-mediated dilation, particularly to acetylcholine (ACh), remains unclear. The purpose of this study was to determine the endothelial mechanisms contributing to age-induced cutaneous microvascular function and compare cutaneous microvascular function responses to those from isolated adipose arteriole preparations. We hypothesized that cutaneous microvascular vasodilation to ACh in older adults will be mediated primarily by EDHFs relative to young adults and that isolated adipose arteriole preparations will corroborate these findings. Methods: Four intradermal microdialysis fibers were placed in the skin of the ventral forearm of 9 young (3F/6M; 29±7 yrs) and 3 older adults (3F/0M; 59±11 yrs) for infusion of Ringer’s solution; L-NAME (10 mM), an NO synthase inhibitor; tetraethylammonium chloride (TEA; 50 mM), a non-specific K+ channel inhibitor; and a combination of L-NAME and TEA. Laser Doppler flowmetry and brachial mean arterial pressure were measured during infusion of ACh (10 mM and 100 mM) and in response to local heating to 39°C. Maximal vasodilation was assessed with heating to 43°C and infusion of sodium nitroprusside (28 mM). Adipose resistance arterioles for pressure myography were obtained from a gluteal biopsy or from surgical discard tissue, which were pre-constricted (ET-1), and ACh responses (10−9–10−4 M) were assessed in the presence of the above inhibitors. Cutaneous vascular conductance (CVC) and isolated arteriole responses are presented as % maximum vasodilation. Results: In response to local heating in young adults, L-NAME reduced vasodilator magnitude (Ringers 69.0±18.1% vs. L-NAME 30.3±12.1%; p&lt; 0.05) while TEA did not have any effect (69±18% vs. 49±28%; p=0.20). Combined L-NAME and TEA reduced vasodilation (69±18% vs. 19±6%; p&lt;0.05). Conversely, vasodilator magnitude to ACh was not different across the Ringers, L-NAME, or TEA sites (p=0.93-0.94), while combined inhibition of NOS and K+ channels with L-NAME and TEA, respectively, reduced vasodilator responsiveness (p&lt;0.05). In isolated resistance arterioles, there were no differences in %max dilation to ACh across inhibitor sites (p=0.19) in young adults. In older adults, neither independent nor combined inhibition of NOS or K+ channels impacted vasodilator responses to local heating, while vasodilator magnitude to ACh was most impacted by combined inhibition with L-NAME and TEA (83±14% vs. 32±15%; p&lt;0.05). Conclusion: Our data demonstrate that vasodilator plasticity in response to local heating is divergent with advancing age, relying on non-NO or K+ mechanisms relative to young adults, while NO and K+ mechanisms are suffcient to maintain ACh-mediated vasodilation. These findings further support the concept of diversity in vasodilator mechanisms within the microvasculature. NHLBI K99-HL161491 (WEH), K08-HL150340 (JJM), R01-HL160752 (JKF), R01-HL133029 (AB), and NICHD R01-HD099340 (MJD). This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

Treatment of Hypotension with Phenylephrine Increases Cerebral Microvascular Perfusion in a Rat Model of Acute Hemodilution

Intraoperative blood loss is associated with reduced mean arterial blood pressure (MAP), which may endanger vital organ perfusion, including the brain. Phenylephrine (PE), an α1-receptor agonist, is clinically utilized to treat intraoperative hypotension through vasoconstriction of resistance arterioles. Clinical studies suggest that raising MAP with PE may decrease perfusion to vital organs such as the brain. Experimental studies suggest that lower α-receptor density in the cerebral resistance arteries may lead to preserved brain perfusion after PE administration. We hypothesize that treatment of hypotension with PE will result in preserved brain perfusion due to different microvascular blood flow and tissue oxygen tension (pO2) responses in the brain and skeletal muscle in an experimental rat model. With Animal Care and Use Committee approval in accordance with ARRIVE-2 guidelines, spontaneously breathing anesthetized rats (1.5% isoflurane) underwent hemodilution by exchanging 40-50% estimated blood volume 1:1 with saline over 10 minutes to achieve a 10-20 mmHg drop in MAP. MAP (tail artery) was measured continuously. Hypotension was treated with PE (10-20 μg/kg/min iv) to increase MAP to a target above baseline MAP. Shed blood was re-infused after stopping the PE infusion. Microvascular blood flow (Oxyflo; Oxford Optronix, Oxford, UK, n=7) or microvascular pO2 (OxyLED, Oxyphor G4, Oxygen Enterprises Ltd., Philadelphia, PA, n=6) were measured continuously in the cerebral cortex (burr hole) and biceps femoris muscle simultaneously in each rat. Results were analyzed via one or two-way ANOVA, with significance achieved at p&lt;0.05. Baseline and post-hemodilution MAP values were comparable in both groups. PE infusion increased MAP to a mean level near 100 mmHg in both groups (p&lt;0.05). Microvascular blood flow and tissue pO2 were greater in the brain as compared to the muscle at all time points (p&lt;0.01 for both). PE infusion resulted in an increase in cerebral microvascular blood flow from baseline (1465±689 vs. 687±453 blood perfusion units (BPU); p&lt;0.001) that was sustained after discontinuing PE and during blood reinfusion. No changes in muscle microvascular flow were observed after PE infusion (294±129 vs. 168±113 BPU). A sustained increase in cerebral microvascular pO2 was measured following PE infusion (50.2±8.6 vs. 40.6±4.6 mmHg; p=0.02), whereas muscle tissue pO2 did not change (22.2±5.6 vs. 25.0±2.5 mmHg). A differential blood flow and microvascular pO2 response was observed following PE infusion in brain and skeletal muscle. Both cerebral microvascular blood flow and tissue pO2 demonstrated sustained increases after PE infusion. By contrast, no changes were observed in muscle microvascular blood flow and pO2. These results suggest that treatment of hypotension with PE administration preferentially increased cerebral vs. muscle perfusion in an experimental model of acute blood loss and fluid resuscitation. Canadian Anesthesiologists’ Society and University of Toronto Merit Award Support. This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

Insulin-Mediated Capillary Recruitment Is Absent in the Cutaneous Microvasculature of Women with a History of Gestational Diabetes Mellitus

Women with a history of gestational diabetes mellitus (GDM) have a significantly greater risk of developing cardiovascular disease and type II diabetes compared to women who had an uncomplicated pregnancy (HC). Although the mechanisms underlying this increased risk are unclear, emerging evidence suggests that microvascular endothelial dysfunction, mediated via reduced nitric oxide (NO)-dependent dilation, persists after pregnancy complicated by GDM. Whether this microvascular dysfunction reduces insulin-mediated responses in these women is unexplored. We hypothesized that insulin-mediated capillary recruitment would be attenuated in women with a history of GDM via NO-dependent mechanisms. 24 women (n=12/group; HC: 35±1 years, 24±4 months post-partum; GDM: 33±1 years, 21±3 months postpartum) underwent intradermal microdialysis, which involved the placement of 2 fibers in the ventral forearm for the local delivery of 10−4M insulin alone or 10−4M insulin+15mM NG-nitro-L-arginine methyl ester (L-NAME, NO-synthase inhibitor). The cutaneous blood flow response to post-occlusive reactive hyperemia (PORH; 5 minutes) was assessed before and during insulin perfusion. Red blood cell flux was measured continuously over each microdialysis site by laser-Doppler flowmetry. Cutaneous vascular conductance was calculated (CVC=flux/mean arterial pressure), normalized to maximum (%CVCmax), and presented as PORH area under the curve (AUC, %CVCmax• sec−1). Microvascular capillary recruitment was assessed as ΔAUC (pre-insulin AUC - insulin AUC). Insulin perfusion increased PORH in HC (pre-insulin: 4066±490 vs. insulin: 7848±978 AUC; p=0.03) but had no effect in GDM (pre-insulin: 3765±293 vs. insulin: 6196±779 AUC; p=0.26). Insulin perfusion did not increase PORH at the L-NAME site in either group (p&gt;0.05). Within groups, L-NAME perfusion reduced insulin-mediated capillary recruitment in HC (control: 3781±1109 vs. L-NAME: 470±945 ΔAUC; p=0.04) but not GDM (control: 2431±796 vs. L-NAME: -41±1014 ΔAUC, p=0.11). These data suggest that insulin-mediated capillary recruitment assessed by PORH in the cutaneous circulation is mediated by NO-dependent mechanisms in healthy women with a history of uncomplicated pregnancy and attenuated in healthy women with a history of GDM. This reduction in insulin-mediated microvascular responses may contribute to the increased risk of cardiovascular disease and type II diabetes in these women. UI Fraternal Order of Eagles Diabetes Research Center Catalyst Grant; NIH HL169201. This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

Ischemic Conditioning Improves the Microvascular Hyperemic Response to Passive Limb Movement in Young Adults

Background: Passive limb movement (PLM) of the lower extremity is a simple and clinically relevant approach to measure peripheral microvascular health. PLM causes an acute increase in hyperemic leg blood flow (LBF) without an increase in skeletal muscle metabolism, and the hyperemic response is ~80% nitric oxide-mediated. A known therapeutic stimulus to increase large conduit artery vascular health is ischemic conditioning (IC). Whether a single session of IC can improve the hyperemic response to PLM remains unknown. Objective: To quantify the microvascular response to PLM after a single session of IC in young adults. Hypothesis: The hyperemic response to PLM, measured as a change in peak femoral artery blood flow, will be greater following IC vs. sham-IC. Methods: This was a prospective, cross-over, blinded clinical trial (NCT05935670). Young adults aged 18-30 years who were free of cardiovascular disease were recruited, and study participants completed two study visits. Participants were seated in a Biodex dynamometer and superficial femoral artery resting blood flow and diameter were measured in the dominant leg using ultrasonography. The dynamometer then passively moved the knee 90 degrees at a frequency of 1 Hz for a single PLM while blood flow was continuously measured. The ΔLBF was calculated as the absolute (ml/min) and relative (% change) difference in LBF from rest to peak. Participants were then randomized to receive either IC or sham-IC, and the vascular assessor was blinded to the condition. For IC, the cuff was placed around the proximal dominant thigh and repetitively inflated to 225 mmHg for 5 min then deflated for 5 min, for a total of 5 cycles. For sham-IC, the thigh cuff was inflated to only 25 mmHg. Fifteen minutes after IC or sham-IC the hyperemic response to PLM was re-assessed. The pre-/post- change in the PLM hyperemic response was calculated as the difference from pre- vs. post-IC or sham-IC. Statistical analysis included one-sided paired t-tests. Results: Seven individuals (3 female, age 26 ± 4 years old) completed the study. Compared to pre-IC, the relative peak hyperemic response to PLM was augmented post-IC (%ΔLBF = 89 ± 42% pre- vs. 136 ± 49% post-IC, p=0.001). Conversely, there was no change in the relative peak hyperemic response in the sham-IC condition (%ΔLBF = 108 ± 61% pre- vs. 108 ± 77% post-sham-IC, p=0.50). The pre-/post- change score of absolute peak hyperemic response to PLM was also higher after IC vs. sham-IC (change in ΔLBF = 50 ± 78 IC ml/min vs. -44 ± 127 ml/min sham-IC, p = 0.03). Conclusion: These results show an improvement in the peripheral microvascular response to PLM following IC. Future studies should examine the mechanistic pathways responsible for an improved PLM response as well as the potential benefits of IC on microvascular health in clinical populations with underlying peripheral microvascular dysfunction. AAW was supported by the National Heart, Lung and Blood Institute (T32HL13464) and Cardiovascular Center’s A.O. Smith Fellowship Scholars Program. Research was supported by the Eunice Kennedy Shriver National Institute of Child Health &amp; Human Development R01-HD099340 (ASH and MJD) and R01-HD112258 (MJD and ASH). This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

Racial Disparities in Cardio-Oncology: Contributions of Anti-Cancer Therapy Induced Endothelial Dysfunction

Background: Major adverse cardiovascular (CV) events (MACE) related to anti-cancer therapy (CTx) represent the leading cause of non-cancer related mortality among breast cancer (BC) survivors. Most preclinical studies have focused on the heart, but increasing evidence suggests decreased endothelial function is predictive of CTx induced cardiac events. To date, the role of microvascular endothelial (dys)function, a well-established predictor of MACE, has been mostly ignored and few mechanistic studies exist in human subjects. CV disease in general, and CTx induced adverse events specifically, are significantly more prevalent in Black (B) relative to non-Hispanic White (NHW) patients. Despite the overwhelming clinical evidence supporting these health disparities, the underlying causes are poorly understood. Our lab and others have demonstrated that isolated vessels from human tissue samples can be used to understand the mechanisms contributing to CV disease. The overall goal of this study is to determine the effect of anti-cancer therapy on microvascular function and identify possible racial disparities. Hypothesis: Ex vivo treatment with CTx leads to impaired endothelial function, which is augmented in healthy donor vessels from B compared to NHW patients. Methods: Human adipose arterioles obtained from de-identified surgical discarded specimens of healthy B and NWH patients were used for video-microscopy. Vessels were incubated ex vivo 16–20 h with CTx (trastuzumab-TZM, doxorubicin-Dox, or paclitaxel-PTX). Response to endothelial dependent flow mediated dilation (FMD 5-100 cmH2O pressure gradient), acetylcholine (ACh; 10−9 to 10−5 M), and the endothelial independent dilator papaverine (Pap 10-4 M) were evaluated. Data are presented as %Max diameter ± SEM, N. Statistical significance was established with 2-way ANOVA RM *p&lt;0.05. Results: Exposure to Dox decreased FMD equally in vessels from B (19±3, n=8) vs. NHW patients (29±5 n=8). The TZM induced endothelial dysfunction in vessels from B patients (37±8*, n=11) was augmented compared to NHW patients (57±15, n=6). PTX did not impair FMD in NHW patients (93±0.9, n=7) but showed a significant reduction in vessels from B patients (49±10*, n=10). Similar results were observed with ACh dilation, but Max dilator capacity to papaverine was unchanged in either group (not shown). Conclusion: Our findings suggest that racial disparities may contribute to differences in microvascular function and clinical outcomes of BC patients. Since dysfunction of the microcirculation is a common predecessor to heart failure and other MACE, novel strategies designed to predict, manage, and treat these adverse effects are needed and should be tailored to individual patient populations. To date, we cannot differentiate between biological/genetic vs. social/environmental contributors to the observed microvascular responses to CTx; that will be the focus of future studies. This work was supported by the American Heart Association Scientific Focused Research Network grant (SFRN.). This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

Noninvasive estimation of skeletal muscle oxygen consumption rate and microvascular reactivity in chronic stroke survivors using near-infrared spectroscopy.

Understanding post-stroke changes in skeletal muscle oxidative metabolism and microvascular reactivity could help create therapeutic targets that optimize rehabilitative interventions. Due to disuse atrophy, we hypothesized that basal muscle oxygen consumption rate and microvascular endothelial function would be impaired in the tibialis anterior (TA) muscle of the affected leg of chronic stroke survivors compared with the nonaffected leg and versus matched controls. Fifteen chronic stroke survivors (10 females) and 15 matched controls (9 females) completed this study. A near-infrared spectroscopy oximeter measured tissue oxygen saturation (StO2) of the TA in both legs of stroke survivors and the dominant leg of controls. A cuff was placed around the thigh and inflated to 225 mmHg for 5 min while StO2 was continuously measured. The rate of change in StO2 was calculated during cuff occlusion and immediately post-cuff release. The rate of oxygen desaturation was similar between the legs of the stroke survivors (paretic -0.12 ± 0.04%·s-1 vs. nonparetic -0.16 ± 011%·s-1; P = 0.49), but the paretic leg had a reduced desaturation rate versus controls (-0.25 ± 0.18%·s-1; P = 0.007 vs. paretic leg). After cuff release, there was a greater oxygen resaturation rate in the nonparetic leg compared with the paretic leg (3.13 ± 2.08%·s-1 vs. 1.60 ± 1.11%·s-1, respectively; P = 0.01). The control leg had a similar resaturation rate versus the nonparetic leg (control = 3.41 ± 1.79%·s-1; P = 0.69) but was greater than the paretic leg (P = 0.003). The TA in the paretic leg had an impaired muscle oxygen consumption rate and reduced microvascular endothelial function compared with controls.NEW & NOTEWORTHY Secondary consequences of stroke are not well described. In this study, we show that basal muscle oxidative consumption and microvascular endothelial function are reduced in the paretic tibialis anterior muscle of chronic stroke survivors compared with matched controls using near-infrared spectroscopy and the vascular occlusion technique. There was a moderately strong correlation between microvascular endothelial function and paretic leg strength.