Vasoconstriction during non-hypotensive hypovolemia is not associated with activation of baroreflex: A causality-based approach.

Non-hypotensive hypovolemia simulated with oscillatory lower body negative pressure in the range of -10 to -20 mmHg is associated with vasoconstriction {increase in total peripheral vascular resistance (TPVR)}. Due to the mechanical stiffening of vessels, there is a disjuncture of mechano-neural coupling at the level of arterial baroreceptors which has not been investigated. The study was designed to quantify both the cardiac and vascular arms of the baroreflex using an approach based on Wiener-Granger causality (WGC) - partial directed coherence (PDC). Thirty-three healthy human volunteers were recruited and continuous heart rate and blood pressure {systolic (SBP), diastolic (DBP), and mean (MBP)} were recorded. The measurements were taken in resting state, at -10 mmHg (level 1) and -15 mmHg (level 2). Spectral causality - PDC was estimated from the MVAR model in the low-frequency band using the GMAC MatLab toolbox. PDC from SBP and MBP to RR interval and TPVR was calculated. The PDC from MBP to RR interval showed no significant change at -10 mmHg and -15 mmHg. No significant change in PDC from MBP to TPVR at -10 mmHg and -15 mmHg was observed. Similar results were obtained for PDC estimation using SBP as input. However, a significant increase in TPVR from baseline at both levels of oscillatory LBNP (p-value <0.001). No statistically significant change in PDC from blood pressure to RR interval and blood pressure to TPVR implies that vasoconstriction is not associated with activation of the arterial baroreflex in ≤-15 mmHg LBNP. Thereby, indicating the role of cardiopulmonary reflexes during the low level of LBNP simulated non-hypotensive hypovolemia.

Coronary artery disease and its vascular associates in patients with chronic nonsurgical hypoparathyroidism.

OBJECTIVE: Patients with chronic hypoparathyroidism (cHypoPT) are prone to intracranial-calcification, cataract and nephrocalcinosis. In this study, we systematically investigated the possibility of increased coronary artery calcification (CAC) and coronary artery disease (CAD) in them. DESIGN: Cross-sectional. PATIENTS AND MEASUREMENTS: Ninety-four nonsurgical cHypoPT (M:F = 50:44; age = 45 ± 15 years) with 18.6 ± 9.3 years of illness were assessed. Those with dyspnoea, angina, syncope, abnormal electrocardiogram, echocardiography or significant CAC underwent coronary angiography or myocardial-perfusion-stress imaging. Their lipid parameters and high-sensitivity C-reactive protein (hsCRP) were compared with age-matched healthy controls (Group A, n = 101). The prevalence of CAC in cHypoPT was compared with that of subjects referred from cardiology-clinics (Group B, n = 148, age = 52 ± 11 years). RESULTS: One of 94 cHypoPT had known CAD. On screening, 17 cHypoPT required evaluation for CAD. Two of 17 had severe coronary stenosis, and 12 showed subclinical CAD. CAC and aortic-valve calcification occurred in 21.5% and 11.8%. Clinical and subclinical CAD, CAC and aortic-valve calcification in cHypoPT ≥50 years of age was 8.1%, 27.0%, 52.8% and 27.8%, respectively. Frequency of age-adjusted CAC was comparable between cHypoPT and control Group B (30.2% vs. 30.7%, p = .93). Elevated hsCRP was higher in cHypoPT than in controls A (52% vs. 32%, p < .01). Factors associated with CAD in cHypoPT were CAC and hypertension. However, CAD and CAC showed no association with long-term calcemic or phosphatemic control and intracranial-calcification in cHypoPT. CONCLUSIONS: Clinical and subclinical CAD was observed in 3.2% and 12.8% of cHypoPT patients. The increased prevalence of CAD, CAC and aortic-valve calcification in cHypoPT above 50 years of age suggested their careful cardiac evaluation during follow-up.

Effect of Yoga Based Cardiac Rehabilitation on Blood Pressure Variability and Baroreflex Sensitivity: RCT in Patients Post MI.

To assess the effects of 12 weeks Yoga based Cardiac Rehabilitation program on Blood Pressure Variability and Baroreflex Sensitivity in Eighty patients post myocardial infarction. Randomized controlled trial with two parallel groups. A tertiary care institution in India. The Yoga group received 13 hospital-based structured yoga sessions in adjunct to the standard care. Control Group participants received enhanced standard care involving three brief educational sessions on importance of diet and physical activity. Beat to beat arterial pressure variability and baroreflex sensitivity was determined non-invasively. Baseline measurement was done at 3 weeks post Myocardial Infarction. The measurements were repeated at 13th week and at 26th week post MI. There was no significant difference between the groups in time domain indices of SBP variability. At 26th week post MI, after normalization the Low Frequency power increased in the yoga group as compared to the decrease in the standard care group (p = 0.02). Though the High Frequency power increased in both the groups, the magnitude of increase was higher in the standard care group (p = 0.005). However, the total power increased significantly in yoga group with a concurrent decrease in standard care group (p = < 0.001). The SBP All BRS was significantly different between the groups with an increase in the yoga group and a decline in standard care group (p = 0.003) at 13th week. A short-term Yoga based cardiac rehabilitation has additive effects in improving baroreflex sensitivity and dampening blood pressure variability post myocardial infarction in patients under optimal medication.The main trial is registered in Clinical Trials Registry-India (CTRI) (Ref. No: CTRI/2012/02/002408). In addition, CTRI has also been registered for the sub-study. (Ref. No: CTRI/2017/09/009925).

The effect of Bacillus coagulans Unique IS-2 supplementation on plasma amino acid levels and muscle strength in resistance trained males consuming whey protein: a double-blind, placebo-controlled study.

PURPOSE: The aim of the present study was to assess the effect of Bacillus coagulans Unique IS-2 supplementation on absorption and utilization of protein in resistance-trained males. METHODS: In this double blind, placebo-control trial, resistance-trained males (21.08 ± 2.84 years) were randomized to consume, either 20 g of whey protein powder {80% whey protein concentrate (WPC80), amounting to 15.4 g protein} with 2 billion CFU Bacillus coagulans Unique IS-2 (supplemental group) or 20 g of whey protein powder and lactose instead of Bacillus coagulans (placebo group) once daily for 60 days with a controlled resistance exercise protocol. The whey protein concentrate (WPC-80) given to both groups had a lactose content of 6.8%. Plasma-free amino acids (PFAAs) were determined at baseline, at 30 and 60 days of supplementation. Muscle strength, hypertrophy, VO2 max, and body composition, and other biochemical parameters were assessed at baseline and end line. RESULTS: A positive effect of probiotic Bacillus coagulans Unique IS-2 supplementation was observed on protein absorption as evidenced by an increase in total PFAA by + 16.1% (p = 0.004). Branched chain amino acids (BCAA) comprising isoleucine (p = 0.016), leucine (p = 0.001), and valine (p = 0.002) were increased by + 33.1% in ITT analysis as compared to placebo after 60 days. At 30 days an increase in isoleucine by + 35% (p = 0.113), leucine by + 43% (p = 0.032), and valine by + 32% (p = 0.017) was observed in ITT analysis. Probiotic effect was shown on exercise performance as evidenced by an increase in one RM of leg press and vertical jump power by + 16.61% (p = 0.024) and + 7.86% (p = 0.007), respectively. CONCLUSION: Significantly increased absorption of BCAA with supplementation of B. coagulans Unique IS-2 along with whey protein and improvement in leg press and vertical jump power was noted indicating the positive effect of the probiotic on muscle power in the lower body. TRIAL REGISTRATION NUMBER: CTRI/2017/03/008117; Date:16.03.2017.

Student perceptions on synchronous virtual versus face-to-face teaching for leader-centered and participant-centered postgraduate activities during COVID-19.

Consequent to the unprecedented COVID-19 pandemic, pedagogic changes were introduced in postgraduate courses in Physiology, where face-to-face teaching was replaced with synchronous virtual mode for leader-centered (seminar, symposium) and participant-centered (journal club, group discussion) academic activities. We hypothesized that the effectiveness of virtual and face-to-face modes as perceived by postgraduate students in terms of facilitating their overall learning may differ across the spectrum of leader-centered and participant-centered activities. To assess the same, we designed and administered a comprehensive, structured, and validated feedback questionnaire. Postgraduate students (n = 29) rated virtual sessions significantly more convenient, but less attentive and comprehensible, and reported better audiovisual experience during face-to-face sessions. Students rated flexibility to attend, self-paced learning, ability to revise, lookup for information in real time, and accessibility to distant expertise as important features of virtual sessions and instant feedback, eye-to-eye contact, and ability to interact in the group for face-to-face sessions. Virtual and face-to-face sessions were perceived as equally effective in facilitating their overall learning for the conduct of leader-centered seminars and symposia. However, face-to-face sessions were considered more effective for the conduct of participant-centered group discussions and journal clubs. During the pandemic, students perceive the synchronous virtual mode as an equally effective alternative for the conduct of leader-centered academic activities, but face-to-face teaching is still preferred for the conduct of participant-centered academic activities.

Adaptive strategies to conduct participant-centric structured virtual group discussions for postgraduate students in the wake of the COVID-19 pandemic.

In the wake of COVID-19, the postgraduate activities in physiology were shifted from live (face-to-face teaching) to virtual mode. This transition posed a challenge to postgraduate students and faculty moderators, especially for participant-centric group discussion, wherein face-to-face interaction contributes significantly to active learner engagement. To bridge the gap between live group discussion (GD) and virtual GD in the conventional format (VGD), we implemented an innovative yet feasible multistep approach of conducting structured virtual group discussion (sVGD). It involved priming of students during the preparatory phase and incorporation of the Tuckman model of group dynamics, which consists of sequential substages of forming, storming, norming, and performing into the virtual format. Unsupervised synchronous and asynchronous, as well as supervised synchronous interactions within and in between the minigroups in a structured way, led to active engagement of students with one another and the moderator, despite the constraints imposed by the virtual format. After establishing the feasibility of the approach during the first GD (sVGD-1), sVGD-2 was conducted, further refining the approach, and feedback was obtained from the postgraduate students. Pre-GD feedback revealed that the live session was preferred over virtual for the conduct of GD, whereas both live GD and sVGD were perceived to be more effective than VGD in the post-GD feedback. Such pedagogical innovations may also help to address the challenges posed in traditional teaching across the undergraduate and postgraduate courses in medical education and beyond during such unforeseeable circumstances.

IUPS Physiology Education Workshop series in India: organizational mechanics, outcomes, and lessons.

Active learning promotes the capacity of problem solving and decision making among learners. Teachers who apply instructional processes toward active participation of learners help their students develop higher order thinking skills. Due to the recent paradigm shift toward adopting competency-based curricula in the education of healthcare professionals in India, there is an emergent need for physiology instructors to be trained in active-learning methodologies and to acquire abilities to promote these curriculum changes. To address these issues, a series of International Union of Physiological Sciences (IUPS) workshops on physiology education techniques in four apex centers in India was organized in November 2018 and November 2019. The "hands-on" workshops presented the methodologies of case-based learning, problem-based learning, and flipped classroom; the participants were teachers of basic sciences and human and veterinary medicine. The workshop series facilitated capacity building and creation of a national network of physiology instructors interested in promoting active-learning techniques. The workshops were followed by a brainstorming meeting held to assess the outcomes. The aim of this report is to provide a model for implementing a coordinated series of workshops to support national curriculum change and to identify the organizational elements essential for conducting an effective Physiology Education workshop. The essential elements include a highly motivated core organizing team, constant dialogue between core organizing and local organizing committees, a sufficient time frame for planning and execution of the event, and opportunities to engage students at host institutions in workshop activities.

Contribution of systemic vascular reactivity to variability in pulse volume amplitude response during reactive hyperemia.

PURPOSE: The aim of the present study was to investigate why the magnitude of reactive hyperemia (RH) observed by pulse volume amplitude (PVA) after arm occlusion differs greatly among study subjects. METHODS: Healthy subjects (n = 12) in the age range of 22-30 years participated in this study. Vascular reactivity was assessed by measuring the changes in finger PVA simultaneously in the test (occluded arm) and control arm (contralateral non-occluded arm) using two separate Photoplethysmographic sensors. Short-term HRV was computed from simultaneously acquired lead II ECG signal to monitor the changes in cardiac sympathetic nervous activity. RESULTS: The observed coefficient of variation for inter-subject variability in PVA response in test arm during second minute of RH was 115.3%. In the control arm, significantly reduced PVA was observed during the period of occlusion as well as RH. This observation was corroborated by simultaneously acquired short-term HRV which showed a significant rise in total power (p value < 0.005) and low-frequency (LF) power (p value < 0.05) during release of occlusion when compared to the baseline. A significant positive correlation (Spearman r = 0.33; p = 0.02) was observed between % change in PVA in the control arm and in the test arm for first 3 min of RH. CONCLUSIONS: Sympathetic activation possibly plays an important role in mediating the inter-subject variability of vascular responses during reactive hyperemia which warrants simultaneous recording of both the test and the control arm responses during RH to accurately assess endothelial function.

Planning, implementation, and evaluation of multicomponent, case-based learning for first-year Indian medical undergraduates.

Didactic lecture is an effective method to quickly pass on a high volume of information to a large number of students. However, if not well designed, lectures can be monotonous and provide only passive learning, with little scope for higher order learning skills. To address this drawback of lectures, we supplemented it with case-based learning (CBL), which has been shown to promote self-learning. After giving an overview of gastrointestinal physiology through lectures, CBL on peptic ulcer disease was implemented for first-year Bachelor of Medicine, Bachelor of Surgery students. The present study aimed to evaluate the students' and teachers' opinions on the notion of supplementing lectures with CBL. In previous reports, discussion using clinical cases was primarily employed as the solitary component for conducting CBL. In the present study, three different but mutually exclusive components, such as case discussion, concept map, and critical thinking exercise on a specific topic in gastrointestinal pathophysiology, were integrated to form the multicomponent CBL (MC-CBL). Students reported that MC-CBL could promote application of the knowledge learned in lectures in a more appropriate context (92.42% positive response), enhance their learning efficiency (98.46% positive response), promote their active participation in the learning process (98.48% positive response), and help them in integrating physiological concepts with clinical science (98.46% positive response). Teachers observed that MC-CBL could promote active learning, analytic, and problem-solving skills of students. In conclusion, MC-CBL appeared to be an effective supplement for the lectures, providing an opportunity for the students to relate the knowledge learned during lectures.

Waist Circumference Rather than Body Mass Index is Better Indicator of Insulin Resistance in Type 2 Diabetes Mellitus in North Indian Population.

Obesity and insulin resistance (IR) are associated with type 2 diabetes mellitus (DM). Obesity can be quantified by body mass index (BMI) and waist circumference (WC). Similarly, IR is commonly quantified by fasting-plasma-insulin (FPI) and Homeostatic model assessment (HOMA-IR). We aimed our study to find correlation between obesity-parameters and IR especially in the Indian population where despite lower BMI there is more prevalence of type 2 DM. In 34 uncomplicated patients of type 2 DM weight and WC were measured and BMI was calculated. HOMA-IR and FPI level were estimated to assess IR. Significant correlation was found between HOMA-IR and WC (r = +0.368, P = 0.0324) but it was non-significant between HOMAIR and BMI. Correlations were also not significant between FPI and WC or BMI. In conclusion, HOMA-IR and WC are better measures of IR and obesity as compared to FPI and BMI, respectively in type 2 DM.

A Novel Practical to Demonstrate Systemic and Local Regulation of Circulation in a Human Subject.

Purpose of the study: Systemic and local regulation of peripheral circulation is a vital concept to be taught to undergraduate medical students. There is lack of an effective practical module to demonstrate and reinforce the theoretical understanding of this concept. Methodology: We designed a simple feasible novel practical using finger pulse recording coupled with hand grip test and reactive hyperemia protocol to elicit systemic and local regulation of peripheral circulation respectively. Main findings: The reduction in finger pulse amplitude during hand grip contralateral to the exercising hand demonstrates systemic regulation while the isolated ipsilateral increase in finger pulse amplitude during reactive hyperemia demonstrates local regulation. Conclusion: : Here we propose a simple novel practical for effective demonstration of systemic and local regulation of circulation for under-graduate teaching in physiology.

Vascular Responses to Post Occlusive Reactive Hyperemia and Systemic Inflammation in Overlap Syndrome of Chronic Obstructive Pulmonary Disease and Obstructive Sleep Apnea.

BACKGROUND: Post-occlusive reactive hyperemia (RH) is impaired in Chronic Obstructive Pulmonary Disease (COPD) and Obstructive Sleep Apnea (OSA). The aim of the present study was to examine systemic vascular response and endothelial function in patients of Overlap Syndrome (OS) of COPD and OSA and also to investigate whether OS has any additional effect on endothelial dysfunction when compared to dysfunction caused by COPD alone. METHODS: 31 COPD patients and 13 healthy controls participated in the study. Overnight Polysomnogra was done to classify the patients into COPD only group (Apnea-Hypopnea Index <5) (n=15) and OS group (AHI >5) (n=16). Peripheral pulse waveform changes during reactive hyperemia were assessed using digital Photoplethysmography (PPG) technique in which pulse wave amplitude (PWA), Maximum slope of upstroke and Pulse Transit Time (PTT) were measured. C - reactive protein was assessed as marker of inflammation by ELISA. RESULTS: Maximum percentage changes in PWA during RH were significantly lower in the both COPD group [20.34(12.02-34.07)] (p<0.001) and Overlap Syndrome group [10.96(6.21-21.49)] (p<0.0001) as compared to Controls [49.79(46.03-65.32)], whereas amplitude responses were not significantly different in the COPD and OS group (p>0.05). Maximum percentage change in slope of upstroke showed similar responses in the three groups. CRP levels (mg/) were raised in COPD [11.60(1.75-15.00] (p<0.001) and OS group [12.52(5.28- 15.70))](p<0.0001) as compared to controls [0.59(0.58-0.91)]. Maximum percentage change in amplitude negatively correlated with serum CRP levels in COPD group (r=-0.557, p=0.03) and in OS group (r=-O.552, p= 0.02). FEV1% predicted positively correlated with maximum percentage change in amplitude in OS group(r=0.579, p=0.018). No correlation of AHI was found with any of the vascular function parameter in Overlap group. CONCLUSION: The patients with Overlap Syndrome have systemic inflammation and impaired reactive hyperaemia response. However, no additive effect of OSA was observed on impaired RH in patients with co-existing COPD.

Correction for blood pressure improves correlation between cerebrovascular reactivity assessed by breath holding and 6% CO(2) breathing.

BACKGROUND: Changes in cerebral blood flow velocity to hypercapnia are associated with changes in systemic blood pressure (BP). These confounding BP-dependent changes in cerebral blood flow velocity cause misinterpretation of cerebrovascular reactivity (CVR) results. The objective of the study was to determine the relationship between CVR assessed by breath holding and 6% CO2 breathing after correcting for BP-dependent changes in cerebral blood flow velocity. METHODS: In 33 patients of uncomplicated type 2 diabetes mellitus, CVR was assessed as percentage changes in cerebral blood flow velocity and cerebrovascular conductance index. RESULTS: Percentage change in cerebral blood flow velocity during breath holding was positively correlated with that of during 6% CO2 breathing (r = .35; P = .0448). CVR during breath holding and 6% CO2 breathing were better correlated when expressed as percentage changes in cerebrovascular conductance index (r = .49; P = .0040). Similarly, breath-holding test results expressed as percentage changes in cerebral blood flow velocity correctly identified only 37.5% of the poor reactors to 6% CO2 breathing. However, when the breath-holding test results were expressed as percentage changes in cerebrovascular conductance index, 62.5% of the poor reactors to 6% CO2 breathing were correctly identified indicating a better agreement between the test results obtained by the 2 methods. CONCLUSION: Cerebrovascular response to breath holding is better correlated with that of 6% CO2 breathing when changes in cerebral blood flow velocity were corrected for associated changes in BP.

Cardiovascular Autonomic Deficits in Different Types of Achalasia.

Background and objective Achalasia cardia is a primary esophageal motility disorder, and the etiopathology of this disease's progression is not known. Moreover, autonomic dysfunction has not been studied in different types of achalasia. In light of this, we aimed to address this lack of data in this study. Methods The diagnosis of achalasia was done using high-resolution esophageal manometry (HRM)-based Chicago classification v4.0. Autonomic function tests (AFT) such as the head-up tilt test, deep breathing test (DBT), Valsalva maneuver (VM), handgrip test (HGT), and cold pressor test (CPT), as well as the heart rate variability (HRV) test, were performed among the cohort and the results were compared with those of 39 age- and sex-matched healthy controls. Results AFT and HRV tests were done on 62 patients (30 achalasia type I, 28 type II, and 4 type III) and compared with 39 age- and sex-matched healthy controls. The mean duration of symptoms, high Eckardt score, and dysphagia were most common in type I achalasia, followed by type II and III. The results of AFT showed a generalized loss of parasympathetic and baroreflex-independent sympathetic reactivity in all types of achalasia. However, baroreflex-dependent cardiovascular adrenergic reactivity was normal. Regarding cardiac autonomic tone, there was a loss of parasympathetic and sympathetic influence, but sympathovagal balance was maintained. The severity of the loss of autonomic functions was higher in type I, followed by type II. Conclusions In all types of achalasia, parasympathetic reactivity, baroreflex-independent sympathetic reactivity, and cardiac autonomic tone were lower compared to healthy controls, and the severity of dysfunction increased during the progression of the disease from type II to type I.

Decreased autonomic modulation of heart rate and altered cardiac sympathovagal balance in patients with Cushing's syndrome: role of endogenous hypercortisolism.

BACKGROUND/AIMS: Endogenous Cushing's syndrome is associated with a higher risk of cardiovascular morbidity and mortality. Previous literature suggested multiple possible links by which hypercortisolism may alter the autonomic control of cardiovascular functions. We investigated the impact of chronic endogenous hypercortisolism on the autonomic regulation of cardiac functions by short-term heart rate variability analysis. METHODS: Eighteen patients with endogenous Cushing's syndrome and 20 age-, gender- and BMI-matched controls participated in the study. ECG signal was acquired in lead II configuration for 5 min and heart rate variability assessment was made in both time and frequency domain using the extracted RR interval data. RESULTS: All time and frequency domain measures of heart rate variability were significantly (p < 0.05) lower in the patient group compared to the control group. The patient group had an altered sympathovagal balance with low frequency/high frequency band ratio significantly higher than the control group [1.857 (0.6747-2.610) vs. 0.8581 (0.4779-1.352); p = 0.0253]. A significant negative correlation was obtained between normalized high frequency power of heart rate variability and basal cortisol levels (r = -0.6594; p = 0.0029). Multiple linear regression analysis identified age, disease duration (in months), basal cortisol levels and systolic blood pressure as independent predictors of normalized high frequency power. CONCLUSION: Findings of the study clearly portrayed the diminished autonomic modulation of heart rate in endogenous Cushing's syndrome and its possible relationship with hypercortisolism as the main causative factor. Diminished heart rate variability may be an indicator of the increased risk of cardiac mortality in these patients.

Differential role of central and peripheral arterial stiffness in determining brachial artery resting retrograde flow in patients with ischemic heart disease vs healthy subjects.

Retrograde flow in endothelial cell cultures has been shown to induce a pro-atherogenic phenotype. Despite its potential role as a pathophysiological link between cardiovascular risk factors and atherosclerotic disease, resting retrograde flows between patients with cardiovascular disease and healthy subjects have not been compared. Further, the vascular characteristics governing retrograde flow in human arteries have not been systematically investigated. Association of central and peripheral vascular characteristics with retrograde flow profile was investigated in 32 healthy subjects and 47 patients with ischemic heart disease. Endothelial dysfunction was assessed by brachial ultrasound-based calculation of flow-mediated dilation (FMD) and sub-clinical atherosclerosis was estimated from carotid-intima media thickness (CIMT). Retrograde blood flow velocity (RBFV) and shear rate were comparable between the two groups (RBFV 1.82(0.97-3.32) vs 1.78(1.24-2.65) cm/s p = 0.79). Augmentation index was a significant determinant of retrograde flow in both patients and healthy subjects. Carotid artery incremental elastic modulus was an independent determinant of retrograde flow patterns in healthy subjects while ejection fraction, cf/cr PWV ratio and forearm vascular conductance emerged as independent determinants in patients. Retrograde flow patterns were also associated with FMD (RBFV r = -0.43, p = 0.004) and CIMT (r = 0.30, p = 0.041) in patients. The results of the study suggest a difference in the determinants of retrograde flow in patients and healthy subjects, with central arterial stiffness being a major contributor in healthy subjects while interaction between central, peripheral, and cardio-arterial factors influence retrograde flow in patients with ischemic heart disease.

Assessment of Endothelial Reactivity by Measurement of Vascular Material Response to Shear Stress: A Feasibility Study.

Flow-mediated dilation (FMD) evaluates the relative change in arterial diameter during hyperemia to assess the endothelial response due to a shear stimulus. However, conventional FMD measures diameter response alone and the alterations in the arterial wall's material properties during reactive hyperemia, which also influence dilation, go unaddressed. In this work, we examine the material response (MR) of the artery during reactive hyperemia using clinically relevant stiffness markers for the assessment of endothelial reactivity (ER). For this, we have developed an in-house brachial cuff control (BCC) system to continuously acquire brachial pressure which can be integrated with simultaneous measurement of brachial diameter and used to quantify the relative changes in wall property during hyperemia non-invasively. The assessment of endothelial reactivity using material response (ERAMR) was conducted on 20 healthy participants (12M/8F) and the results were compared with conventional FMD (FMD%). The mean pressure response gave an inverse trend to that of diameter response with varying magnitudes during reactive hyperemia (18.71% from baseline for diameter and 2.45% for pressure), there was a significant difference in the measurement of FMD and ERAMR (P < 0.05). The larger distribution of ERAMR compared to FMD% in box-plots further implies the inclusion of within-subject variations. Hence, ERAMR can be a potential estimate of ER, given the need for intensive validations in this line on larger cohorts.Clinical Relevance- This study demonstrates the independent role of arterial wall material properties to quantify endothelial reactivity in response to a shear stimulus.

Normalization of Flow-mediated Dilation to Brachial Artery Material Property: A Feasibility Study.

Endothelial reactivity (ER) is widely measured using flow-mediated dilation (FMD) of brachial artery. Conventional measurement of FMD is influenced by factors such as input shear stress, arterial transmural pressure, diameter and thereby arterial material properties (ε). Thus, for a reliable interpretation of FMD, it has to be normalized with respect to the above confounding factors. Normalization of FMD with shear stress at the time of measurement has been reported to reduce measurement variability. However, its widespread usage among the research community is limited. In this work, we examine the feasibility of normalizing the brachial FMD index (FMD%) to ε : extrema (εp), baseline (εb) and extrema change (∆ε) post-ischemia using its inter-day variability against FMD. In-vivo measurements were performed on 10 participants for 2 consecutive days and simultaneous pressure-diameter cycles were collected to estimate the material properties during reactive hyperemia (RH). The box-whisker plot reveals differences in the mean and deviation of FMD to FMD|εb. A significant value for repeatability (ICC ≥ 0.6) was obtained for normalized FMD (FMD|εb) for specific stiffness index (ß), pressure-strain elastic modulus (Ep), and local pulse wave velocity (PWV) as compared to FMD. Hence, normalization of FMD% to arterial ε can potentially improve the measurement reliability of ER assessment.Clinical Relevance- This pilot study demonstrates the feasibility of brachial artery stiffness assessment during FMD and its potential use for normalizing the standard FMD measurement.