Blood Flow Oscillations Research Articles

Assessment of blood microcirculation and oxidative metabolism of biological tissue in the limb at changing its position by methods of laser Doppler flowmetry and fluorescence spectroscopy

Introduction. Diagnostics of blood circulation in skin microvessels and oxidative metabolism of biological tissue allows predicting the presence of microcirculatory disorders in the body, assessing their severity and monitoring therapy. The use of a functional test related to the change in the position of the entire human body in space is a well-known method for studying the functions of the autonomic nervous system and diagnosing cardiovascular diseases.Purpose. To study a set of parameters characterizing oxidative metabolism and dynamics of blood microcirculation in the finger during a sequence of tests with the change in the position of the upper limb using fluorescence spectroscopy and laser Doppler flowmetry.Materials and Methods. The study was conducted on a group of volunteers consisting of 10 people aged 21–40 years. The LAZMA PF device (Russia), implementing the methods of laser Doppler flowmetry and fluorescence spectroscopy, was placed on the pad of the middle finger. Each volunteer’s microcirculation parameters were measured in two arm positions: «at heart level» and with the limb vertically raised in the «up» position. Blood flow oscillations were continuously measured during all stages: three times in two positions.Results. A change in the limb position from the «at heart level» to «up» state leads to a decrease in the average values of microcirculation indices by 12 perfusion units (p. u.) and oxidative metabolism by 7 relative units (r. u.) with a simultaneous increase in the NADH coenzyme by 3 r. u., i.e. there is a unidirectional change in the microcirculation and oxidative metabolism parameters and an oppositely directed change of the NADH coenzyme values. According to the results of NADH coenzyme measurements, based on the analysis of statistical data, a statistically significant difference was found between the «at heart level» and «up» arm positions. This difference was not revealed only in the first cycle of the study, the reliability of p was greater than 0.05, between the arm positions 1–2, when the arm was «at heart level» and then raised «up». It was also found that with each new measurement cycle, the probability value of p for NADH indicators steadily decreased with a change in the arm position, at a significance level of p<0.05. The probability value of p became statistically significant starting from the second cycle of the study. Based on the results of oxidative metabolism indicator measurements, it was found that the probability value of p had a statistical significance of p<0.05 at each change of arm position in each cycle.Conclusion. The studies have shown that in order to obtain reliable information about the results of the limb position test, it is not enough to perform one-time measurements of the microcirculation indicator or the oxidative metabolism of biological tissue using laser Doppler flowmetry. The position of the limb and its change leads to significant changes in microcirculation and oxidative metabolism indicators, which should be taken into account when conducting medical and physiological studies

Blood flow dynamics in the arterial and venous parts of the capillary.

Although there is currently sufficient information on various parameters of capillary blood flow, including the average values of blood velocity, there is no data on the dynamics of velocity and the mechanisms of its modulation in various parts of the capillary. The main idea of this work is to develop a tool and image data processing to study the characteristics of the capillary blood flow dynamics. In this study, using the developed method of high-speed videocapillaroscopy, the red blood cells (RBC) velocities in the arterial and venous parts of the nailfold capillaries were compared and a time-frequency analysis of the dynamics of the velocity signals with the calculation of phase coherence was performed. We indicated that the velocity in the arterial part is twice as high and that the ratio of velocities in the arterial and venous parts is stable regardless of the local velocity. This study also empirically confirms the similarity between the oscillations of blood flow in different parts of the capillary and the synchronization of the velocity phases. We believe that the determination of the absolute velocity characteristics of blood flow, together with the mechanisms of its regulation and the ratio of velocities in the arterial and venous parts, can act as a diagnostic approach.

Diagnosis, Pathophysiology and Management of Microvascular Dysfunction in Diabetes Mellitus.

Microcirculation is an essential system that regulates oxygen and nutrients to cells and tissues in response to various environmental stimuli and pathophysiological conditions. Diabetes mellitus can cause microvascular complications including nephropathy, neuropathy, and retinopathy. The pathogenesis of microvascular dysfunction in diabetes is associated with hyperglycemia and the result of an interplay of various factors. Research studies have demonstrated that functional microvascular dysfunction appears much earlier than structural alterations in vasculature in diabetes. This finding of the progression from microvascular dysfunction to macrovascular disease establishes a foundation for the screening and early diagnosis of diabetes by assessing the microvascular function. This comprehensive review discusses technologies (laser Doppler, transcutaneous oximetry, infrared thermography and near-infrared spectroscopy) with computational methods (linear (time and frequency domains), nonlinear and machine learning approaches) for diagnosing microvascular dysfunction in diabetes. Pathophysiological changes of microvascular dysfunction leading to impaired vasomotion and blood flow oscillations in diabetes are reviewed. Recent findings in managing microvascular dysfunction using lifestyle modifications and force-based modulations are evaluated. A consensus endorsed by the American Diabetes Association has been reached that an effective exercise program would greatly slow down the progression of microvascular dysfunction and its impact on diabetic foot ulcers, muscle fatigue and weakness and peripheral neuropathy. However, it is imperative to determine the dose-response relationship of exercise and microvascular responses in patients with diabetes. Research studies have demonstrated that local vibration and whole-body vibration can improve microcirculation in various pathological conditions, including diabetes. Due to the complex nature of microvascular regulation, various computational methods have been developed to shed light on the influence of diabetes on microvascular dysfunction. This comprehensive review will contribute to the diagnosis and management of microvascular dysfunction in diabetes.

Features of blood microcirculation across different age groups in relation to urban ecosystem conditions

BACKGROUND: Understanding adverse effects of environmental factors, including those associated with urbanization and high population density, are important for development of public health protection measures. The hemodynamics of the microcirculatory system plays a significant role in maintaining tissue homeostasis, with morphofunctional characteristics often present in most cases of diseases. However, there remains a lack of comprehensive research on the aging process and the effects of residing in different urban settings on microcirculation dynamics. AIM: To study the changes in the microcirculatory system across different age groups, depending on the state of urban ecosystems, including a megalopolis and a small tourist city without significant industrial activity. MATERIAL AND METHODS: The study involved volunteers from the industrial megalopolis of Nizhny Novgorod and the city of Semenov, a small tourist town without significant industrial activity. Volunteers from different areas, varying in terms of human activity and environmental conditions, were divided into three age groups: group 1: 18–44 years old, group 2: 45–59 years old, and group 3: 60–74 years old. Microcirculation was measured by laser Doppler flowmetry (LDF) using a laser capillary blood flow analyzer "LAZMA ST" (NPP LAZMA LLC, Russia). The amplitude-frequency characteristics were evaluated with a wavelet analysis of blood flow oscillations. RESULTS: A comparison of the amplitude-frequency characteristics (frequency response) of microcirculation between the 1st group of a megalopolis and a small tourist city with minimal industrial activity did not reveal any significant differences. However, upon further analysis of the amplitude-frequency spectrum of groups 2 and 3, changes in the reactivity of microcirculatory structures were observed, depending on age and urban environment. Inter-group differences based on urban ecosystems were identified through variations in endothelial rhythm amplitudes (Ae), neurogenic rhythm (An), myogenic oscillations (Am), and heart rate amplitude (Ah). The megalopolis group exhibited a decrease in An, Am, and Ah, along with an increase in Ae in groups 2 and 3. In contrast, the small city population showed a decrease in Ae, An, and As in group 2, followed by an increase in Ae, An, Am in group 3, and a further decrease in As compared to age groups 1 and 2. Furthermore, the indicator reflecting the power of blood flow into the microcirculatory bed decreased in the 3rd age group of the megalopolis. CONCLUSION: The analysis of microcirculation using the LDF method allows to identify the involvement of various mechanisms regulating microcirculation, depending on the condition of the agro-ecosystem and the presence of risk factors that reduce adaptive capacity with age and living in a megalopolis. The findings from this study can be used to develop measures to prevent tissue perfusion insufficiency in different urban environments.

Features of eyelid microcirculation in chronic mixed blepharitis and type 2 diabetes mellitus

BACKGROUND: Microcirculatory dysfunction in patients with diabetes mellitus leads to tissue trophic insufficiency, reduction of adaptation reserves. It is possible to perform lifetime assessment of structural and functional changes in the microcirculation system by laser Doppler flowmetry. The presence of microcirculatory disorders is established in eyelids in chronic blepharitis and meibomian gland dysfunction. The article presents the results of the study concerning the peculiarities of neoangiogenesis as a mechanism of development of chronic blepharitis and meibomian gland dysfunction in diabetes mellitus (DM).AIM: to reveal the peculiarities of microcirculatory disorders of the eyelid in chronic mixed blepharitis in patients with type 2 diabetes mellitus (T2DM).MATERIALS AND METHODS: The study was conducted in 57 patients: 37 patients with chronic mixed bilateral blepharitis and a verified diagnosis of T2DM (group 1, n=74 eyes, average age 69.5 ± 7.5 years; subgroup 1a, n=38 eyes — patients with T2DM and glycated hemoglobin average level (HbA1с) 6.7±1.2; subgroup 1b, n=36 eyes — patients with T2DM and HbA1с average level 8.2±1.3) and 20 patients with chronic mixed bilateral blepharitis without signs of DM (group 2, n=40 eyes, mean age 67.2±4.3 years). Laser Doppler flowmetry was performed on the device «LAZMA MC-1».RESULTS: In patients with chronic blepharitis against the background of T2DM the development of ischemia of the eyelid tissue with increasing tension of functioning of the regulatory systems of microcirculation blood flow and lymph flow was detected, and in persons without DM — venous stasis with moderate inhibition of vasomotor, respiratory and dominance of cardiac oscillations of blood flow, as well as insufficiency of neurogenic oscillations of lymph flow. In this case in 1a subgroup the dominance of neurogenic oscillations of blood flow was revealed, in 1b - myogenic. Microcirculatory changes of lymph flow in the 1b subgroup were more pronounced in comparison with the 1a subgroup.CONCLUSION: The results proves the negative influence of T2DM on the microcirculatory bed of patients with chronic mixed blepharitis. The disorders detected by laser Doppler flowmetry vary depending on the HbA1с.

Machine-learning-based diabetes classification method using blood flow oscillations and Pearson correlation analysis of feature importance

Abstract Diabetes is a global health issue affecting millions of people and is related to high morbidity and mortality rates. Current diagnostic methods are primarily invasive, involving blood sampling, which can lead to infection and increased patient stress. As a result, there is a growing need for noninvasive diabetes diagnostic methods that are both accurate and fast. High measurement accuracy and fast measurement time are essential for effective noninvasive diabetes diagnosis; these can be achieved using diffuse speckle contrast analysis (DSCA) systems and artificial intelligence algorithms. In this study, we use a machine learning algorithm to analyze rat blood flow signals measured using a DSCA system with simple operation, easy fabrication, and fast measurement for helping diagnose diabetes. The results confirmed that the machine learning algorithm for analyzing blood flow oscillation data shows good potential for diabetes classification. Furthermore, analyzing the blood flow reactivity test revealed that blood flow signals can be quickly measured for diabetes classification. Finally, we evaluated the influence of each blood flow oscillation data on diabetes classification through feature importance and Pearson correlation analysis. The results of this study should provide a basis for the future development of hemodynamic-based disease diagnostic methods.

An alternative instrumental method for studying the morphofunctional state of eyelids in chronic blepharitis

Background: To date, the assessment of morphofunctional changes within eyelids is performed using laser scanning confocal microscopy, which has extensive diagnostic capabilities. Identification of the indicators equivalence of this method and laser Doppler flowmetry will confirm the existence of an alternative, objective and economical method of eyelid examination in chronic blepharitis. Aim: To prove the possibility of laser Doppler flowmetry application as an alternative method of eyelid morphofunctional state assessment. Materials and methods: The study included 62 patients (124 eyes) with an established diagnosis of chronic mixed demodecticosis blepharitis, including 46 women and 16 men, mean age 65.8 ± 3.2 years, randomly assigned into two groups with identical age and gender composition. Group 1 patients (31 patients, 62 eyes) were treated with cosmeceuticals containing terpenes and terpenoids 2 times a day and tear substitute 3 times a day for 1.5 months. Group 2 patients (31 patients, 62 eyes) used an eyelid care gel containing sulphur medicaments 2 times a day and a tear substitute 3 times a day for 1.5 months. In addition to standard ophthalmological examination, laser Doppler flowmetry and laser scanning confocal microscopy were performed. Dynamic follow-up was performed after 1.5 and 3 months. Results: The analysis of laser scanning confocal microscopy and laser Doppler flowmetry parameters revealed a high inverse correlation between the density of inflammatory cells of the eyelids tarsal conjunctiva and neurogenic oscillations of blood flow, as well as high direct correlation with the index of blood flow shunting. A marked direct correlation between the density index of meibomian gland acinuses and the parameters of myogenic oscillations of blood flow and neurogenic oscillations of lymph flow was established. Conclusions: Pearson’s correlation analysis performed on laser scanning confocal microscopy and laser Doppler flowmetry parameters assessing the morphofunctional state of the eyelids demonstrated the presence of equivalence in both study groups with high statistical reliability. The obtained data confirm the possibility of using laser Doppler flowmetry method for objective assessment of eyelid condition and allow the parameters of this method to serve as criteria for choosing pathogenetically oriented therapy of chronic blepharitis with evaluation of its effectiveness.

A digital twin approach for stroke risk assessment in Atrial Fibrillation Patients

Atrial fibrillation (AF) is associated with a fivefold increased risk of cerebrovascular events, contributing to 15-18% of all strokes. Stroke prevention in clinical practice is typically guided by the CHA2DS2-VASc score, which depends on general clinical risk factors but falls short in predicting risk at an individual patient level. In this study, we introduce a digital twin model of the left atrium (LA) combined with computational fluid dynamics (CFD) simulations to enhance personalized stroke risk assessment. Simulations were performed on patient-specific dynamic LA models in sinus rhythm (SR) across three patient groups: 10 controls (CTRL), 10 with paroxysmal AF (PAR-AF), and 10 with persistent AF (PER-AF). Blood flow velocity and areas susceptible to thrombogenesis, based on several factors including endothelial damage, were identified in the left atrial appendage (LAA). In general, control subjects exhibited higher average blood velocity in both the LAA and its ostium (0.11±0.03m/s and 0.28±0.05m/s, respectively) compared to those with AF. In the AF groups, the velocities were lower (LAA: PAR-AF 0.05±0.02m/s, PER-AF 0.04±0.02m/s; LAA ostium: PAR-AF 0.14±0.03m/s, PER-AF 0.11±0.04m/s). CFD analysis revealed that endothelial cell activation potential (ECAP) was significantly higher in AF patients (PAR-AF: 3.96±3.28Pa⁻1, PER-AF: 4.77±2.08Pa⁻1) compared to controls (0.93±0.63Pa⁻1). These findings suggest that AF patients experience slower and more oscillatory blood flow in the LAA, increasing their risk of thrombosis. Additionally, blood tends to stagnate within the LAA, further raising the likelihood of clot formation. This proposed method could be used to enhance stroke risk stratification in AF patients by incorporating an index that integrates blood velocity-derived parameters.

Microcirculatory Dysfunction in Patients With Diabetes Mellitus Detected by a Distributed System of Wearable Laser Doppler Flowmetry Analysers.

The paper is devoted to the study of perfusion and amplitude-frequency spectra of laser Doppler flowmetry (LDF) signals in patients with diabetes mellitus (DM) in different skin areas of the upper and lower extremities using a distributed system of wearable LDF analysers. LDF measurements were performed in the areas of the fingers, toes, wrists and shins. The mean perfusion values, the amplitudes of blood flow oscillations in endothelial, neurogenic, myogenic, respiratory and cardiac frequency ranges, and the values of nutritive blood flow were analysed. The results revealed a decrease in tissue perfusion and nutritive blood flow in the lower extremities and an increase in these parameters in the upper extremities in patients with DM. A decrease in the amplitudes of endothelial and neurogenic oscillations was observed. The obtained results confirm the possibility of using wearable LDF analysers to detect differences in the blood flow regulation in normal and pathological conditions.

Using Wavelet Analysis of Blood Flow Oscillations to Investigate Differences in Skin Blood Flow Regulations Between the Upper and Lower Limbs.

The objective of this study was to investigate the differences in skin blood flow regulations between the upper and lower limbs in healthy adults using wavelet analysis of skin blood oscillations. To the best of our knowledge, this is the first study investigating the dominant skin blood flow control of the upper and lower limbs in healthy adults. Skin blood flow of the forearm and leg was simultaneously measured by laser Doppler flowmetry (LDF) in 17 healthy adults. Skin blood flow oscillations were analyzed using wavelet analysis to assess the dominant control among the metabolic endothelial (0.0095-0.02Hz), neurogenic (0.02-0.05Hz), myogenic (0.05-0.15Hz), respiratory (0.15-0.4Hz), and cardiac (0.4-2Hz) origins. Skin blood flow in the leg (11.13 ± 4.90 perfusion unit) was significantly higher than in the forearm (6.90 ± 2.50 perfusion unit, p < 0.001). The metabolic endothelial control is more dominant in the forearm (1.19 ±0.51 au) compared to the leg (0.73 ± 0.41 au, p < 0.01). The myogenic control is more dominant in the leg (1.18 ± 0.28 au) compared to the forearm (0.96±0.18 au, p < 0.05). Through wavelet analysis of skin blood flow oscillations, the results indicate that metabolic endothelial control is more dominant in the forearm (upper limbs) and myogenic control is more dominant in the leg (lower limbs).

Induced blood flow oscillations at 0.1 Hz protects oxygenation of severely ischemic tissue in humans.

Generating 10-s (∼0.1 Hz) fluctuations or "oscillations" in arterial pressure and blood flow blunts reductions in cerebral tissue oxygenation in response to 15%-20% reductions in cerebral blood flow. To examine the effect of 0.1 Hz hemodynamic oscillations on tissue oxygenation during severe ischemia, we developed a partial limb ischemia protocol targeting a 70%-80% reduction in blood flow. We hypothesized that 0.1 Hz hemodynamic oscillations would attenuate reductions in tissue oxygenation during severe ischemia. Thirteen healthy humans (6 M and 7 F; 27.3 ± 4.2 yr) completed two experimental protocols separated by ≥48 h. In both conditions, an upper arm cuff was used to decrease brachial artery (BA) blood velocity by ∼70%-80% from baseline. In the oscillation condition (0.1 Hz), 0.1 Hz hemodynamic oscillations were induced by intermittently inflating and deflating bilateral thigh cuffs every 5 s during forearm ischemia. In the control condition (0 Hz), the thigh cuffs were inactive. BA blood flow, forearm tissue oxygenation (SmO2), and arterial pressure were measured continuously. The initial reduction in BA blood velocity was tightly matched between protocols (0 Hz: -76.9 ± 7.9% vs. 0.1 Hz: -75.5 ± 7.4%, P = 0.49). Although 0.1 Hz oscillations during forearm ischemia had no effect on the reduction in BA velocity (0 Hz: -73.0 ± 9.9% vs. 0.1 Hz: -73.3 ± 8.2%, P = 0.91), the reduction in SmO2 was attenuated (0 Hz: -35.7 ± 8.6% vs. 0.1 Hz: -27.2 ± 8.9%, P = 0.01). These data provide further evidence for the use of 0.1 Hz hemodynamic oscillations as a potential therapeutic intervention for conditions associated with severe tissue ischemia (e.g., hemorrhage and stroke).NEW & NOTEWORTHY We investigated the effects of induced 10-s (0.1 Hz) oscillations in blood flow on forearm tissue oxygenation during severe ischemia. Intermittent inflation of bilateral thigh cuffs was used as a clinically applicable method to drive blood flow oscillations. In support of our hypothesis, 0.1 Hz oscillations in blood flow blunted reductions in forearm tissue oxygenation. These results further support the potential use of oscillatory hemodynamics as a therapeutic intervention for ischemic conditions.

Analysis of phase shift between pulse oscillations of macro- and microvascular cerebral blood flow in patients with traumatic brain injury

PurposeAfter a traumatic brain injury (TBI), monitoring of both macrovascular and microvascular blood circulation can potentially yield a better understanding of pathophysiology of potential secondary brain lesions. We investigated the changes in phase shift (PS) between cardiac-induced oscillations of cerebral blood flow (CBF) measured at macro (ultrasound Doppler) and microvascular (laser Doppler) level. Further we assessed the impact of intracranial pressure (ICP) on PS in TBI patients. A secondary aim was to compare PS to TCD-derived cerebral arterial time constant (τ), a parameter that reflects the circulatory transit time.MethodsTCD blood flow velocities (FV) in the middle cerebral artery, laser Doppler blood microcirculation flux (LDF), arterial blood pressure (ABP), and ICP were monitored in 29 consecutive patients with TBI. Eight patients were excluded because of poor-quality signals. For the remaining 21 patients (median age = 23 (Q1: 20–Q3: 33); men:16,) data were retrospectively analysed. PS between the fundamental harmonics of FV and LDF signals was determined using spectral analysis. τ was estimated as a product of cerebrovascular resistance and compliance, based on the mathematical transformation of FV and ABP, ICP pulse waveforms.ResultsPS was negative (median: −26 (Q1: −38–Q3: −15) degrees) indicating that pulse LDF at a heart rate frequency lagged behind TCD pulse. With rising mean ICP, PS became more negative (R = −0.51, p < 0.019) indicating that delay of LDF pulse increases. There was a significant correlation between PS and cerebrovascular time constant (R = −0.47, p = 0.03).ConclusionsPulse divergence between FV and LDF became greater with elevated ICP, likely reflecting prolonged circulatory travel time.

Tumor-Derived Exosomes Promote Tumor Growth Through Modulating Microvascular Hemodynamics in a Human Ovarian Cancer Xenograft Model.

Abnormal tumor vascular network contributes to aberrant blood perfusion and reduced oxygenation in tumors, which lead to poor efficacy of chemotherapy and radiotherapy. We aimed to explore the effects of the tumor-derived exosomes (TDEs) and C188-9 (a small molecule inhibitor of signal transducer and activator of transcription 3, STAT3) on tumor microvascular hemodynamics and determine which blood flow oscillations for various frequency intervals are responsible for these changes. Microvascular hemodynamics parameters were recorded using a PeriFlux 6000 EPOS system in tumor surface in a nude mouse subcutaneous xenograft model. Oscillations of laser Doppler flowmetry (LDF) signal were investigated by wavelet transform analysis. TDEs facilitated tumor growth at least partially was associated with increasing blood flow in smaller vessels with lower speed and decreasing the blood flow at larger vessels with higher speed. Lower oxyhemoglobin saturation (SO2) on tumor surface was aggravated by TDEs, and C188-9 treatment significantly alleviated this decrease. Wavelet transform spectral analysis revealed that TDEs increased the amplitude of oscillations in four frequency intervals related to endothelial (NO-dependent and -independent), myogenic and neurogenic activities, and C188-9 had no effect on this increase. TDEs facilitated tumor growth partially was associated with increasing blood flow in distributing vessels, reducing blood perfusion in larger vessels, and lowering SO2 on tumor surface. Enhanced vascular smooth muscle, endothelial and neurogenic activities occurred in tumor superficial zone.

Microcirculation indicators in children with bronchial asthma

In pediatric practice, non-invasive methods are relevant that allow one to study the state of blood microflow. One such method is laser Doppler flowmetry.Purpose. To evaluate the state of blood microcirculation in children with bronchial asthma by laser Doppler flowmetry during periods of exacerbation and remission of the disease.Material and methods. 40 healthy children aged 9–17 years (13.7 ± 1.8) were examined, which made up the control group. The main group of the examined were children with moderate and severe bronchial asthma (n=60) during the period of exacerbation (n=29) and remission (n=31) of similar age. To diagnose the general condition, the microcirculation of blood used a system of portable blood microcirculation LAZMA PF. From the LAZMA PF analyzers, a distributed system consisting of four devices was organized: two analyzers for simultaneous research on the 3rd finger of the hands and on the 1st toes. The record of indicators from 4 analyzers was carried out simultaneously in the position of the subject sitting for 10 minutes.Results. When studying the indicator of the microcirculatory-tissue system in children with bronchial asthma of moderate and severe severity who are in remission, we did not reveal significant differences from the indicators in healthy children. When assessing active regulation mechanisms affecting the state of microcirculation, a reliable decrease in the amplitudes of vibrations of endothelial regulation in patients with bronchial asthma compared to healthy children (p&lt;0.05) was revealed. When comparing passive oscillations of blood flow in patients with bronchial asthma, a significant decrease in the amplitudes of oscillations in the cardiac range was revealed in comparison with the control group (p&lt;0.05). Scope of results: medicine, pediatrics, therapy, pulmonology, allergology.Conclusion. The laser Doppler flowmetry can be used as an additional criterion for the diagnosis and control of the therapy of bronchial asthma in children.

Using wavelet phase coherence of heart rate variability and blood flow oscillations to compare mechanisms of action between Tai Chi mind-body exercise and brisk walking aerobic exercise

Using wavelet phase coherence of heart rate variability and blood flow oscillations to compare mechanisms of action between Tai Chi mind-body exercise and brisk walking aerobic exercise

The Effect of 0.1 Hz Blood Flow Oscillations on Microvascular Blood Flow Responses Following Severe Ischemia

Background: We have shown that inducing 10 second (0.1 Hz) oscillations in arterial pressure and blood flow protects against reductions in tissue oxygenation during ischemia, independent of changes in macrovascular blood flow. However, it is unknown whether 0.1 Hz hemodynamic oscillations impacts microvascular function and vasodilatory capacity following severe ischemia. To examine this question, we assessed the reactive hyperemic response following a prolonged peripheral limb ischemia protocol with and without induced 0.1 Hz hemodynamic oscillations. Hypothesis: 0.1 Hz oscillations in blood pressure and blood flow will increase microvascular blood flow, assessed via reactive hyperemia following a 10-min period of ischemia. Methods: Thirteen healthy human participants (6M, 7F; 27.3 ± 4.2 y) completed two experimental protocols separated by ≥48 h. In both conditions, ischemia of the forearm was induced with a pneumatic cuff on the upper arm to decrease brachial artery blood velocity by ~70-80% from baseline. In the oscillation condition (OSC), 0.1 Hz oscillations in mean arterial pressure (MAP) and brachial artery blood flow were induced by inflating and deflating bilateral thigh cuffs every 5-s (10-s cycles; 0.1 Hz) throughout the forearm ischemia period. In the control condition (CON), the thigh cuffs were in place, but were inactive throughout the forearm ischemia period. Beat to beat arterial pressure was measured via finger photo plethysmography, and brachial artery diameter and blood velocity were measured via duplex Doppler ultrasound during baseline, ischemia, and the reperfusion period. The maximum mean brachial artery blood velocity, and 3-min area under the curve (AUC) of mean brachial artery blood velocity were used to determine the reactive hyperemia response. Results: The magnitude of forearm ischemia, indexed by the reduction in brachial artery conductance, was matched between conditions (CON: -74.8 ± 10.4% vs. OSC: -75.6 ± 6.7%, p=0.39). Reactive hyperemia was not different between conditions as indexed by maximum mean brachial artery blood velocity (CON: 36.4 ± 12.4 cm/s vs. OSC: 39.3 ± 11.2 cm/s, p=0.53) or 3-min brachial artery blood velocity AUC (CON: 1495 ± 744 (cm/s)2 vs. OSC: 1596 ± 804 (cm/s)2, p=0.74). Conclusion: Inducing 0.1 Hz hemodynamic oscillations during severe ischemia does not affect microvascular function, indexed by reactive hyperemia following release of the ischemic stimulus. A more direct measure of microvascular blood flow is needed to examine whether 0.1 Hz hemodynamic oscillations improves microvascular perfusion during ischemia. NIH Neurobiology of Aging &amp; Alzheimer’s Disease Training Grant (T32 AG02049; KAD); American Heart Association Transformational Project Award (19TPA34910743; CAR); American Heart Association Predoctoral Fellowship (23PRE1018469; KAD); UNTHSC Physiology and Anatomy Seed Grant 2021 (CAR). 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.

Interactions Between Carotid Arterial Stiffness, Amplitude of Cerebral Blood Flow Oscillations, and Cerebral Tissue Oxygenation During Simulated Hemorrhage in Humans

Introduction: Inducing 0.1 Hz (10-s cycle) oscillations in cerebral blood flow attenuates the reduction in cerebral tissue oxygenation during simulated hemorrhage in humans. It is unknown, however, how stiffness of the cerebral feed arteries influences the magnitude of cerebral blood flow oscillations, and/or the protection of cerebral tissue oxygenation. When 0.1 Hz oscillations are induced during simulated hemorrhage, we hypothesize that: 1) arterial stiffness of the internal carotid artery (ICA) will increase from rest; 2) the amplitude of 0.1 Hz oscillations in cerebral blood flow will be higher in individuals with stiffer arteries, and; 3) the reduction in cerebral tissue oxygenation will be smaller with higher amplitude of cerebral blood flow oscillations. Methods: 8 healthy human participants (age: 30.1±7.6 y) underwent a 10-min hypovolemic oscillatory lower body negative pressure (OLBNP) protocol, where chamber pressure oscillated every 5-s between -30 mmHg and -90 mmHg (i.e., 0.1 Hz). ICA beta stiffness index was calculated from measurements of ICA diameter (via ultrasound imaging), and arterial pressure (via finger photoplethysmography). Middle cerebral artery velocity (MCAv) was measured using transcranial doppler ultrasound, and cerebral tissue oxygenation (ScO2) was measured with near infrared spectroscopy. Fast Fourier transformation was used to quantify oscillations in mean MCAv at ~0.1 Hz. Results: While Mean MCAv 0.1 Hz oscillations increased from baseline to OLBNP (N=8, 34.0±33.9 (cm/s)2 vs. 104.7±58.1 (cm/s)2, p=0.01), ICA beta stiffness did not increase (N=5, 6.1±0.7 au vs. 8.2±2.7 au, p=0.21). There was no relationship between baseline ICA beta stiffness and the percent change in mean MCAv 0.1 Hz oscillations (N=5; r=0.44, p=0.46). ScO2 decreased from baseline to OLBNP (N=8, 66.5±2.9 % vs. 64.8±2.9 %, p=0.03), but there was also no relationship between the percent change in mean MCAv 0.1 Hz oscillations and the decrease in ScO2 (r=0.28, p=0.50). Conclusions: Based on these data, 0.1 Hz OLBNP does not affect ICA stiffness, and there is no relationship between ICA stiffness, amplitude of induced 0.1 Hz cerebral blood flow oscillations, and the reduction in cerebral tissue oxygenation during simulated hemorrhage. However, as this analysis was performed retrospectively, and arterial stiffness was not initially an outcome measure, there was limited data available for analysis. This limitation will be addressed in a project currently in progress in our laboratory. American Heart Association Grant in Aid. 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.

Pulsatile Perfusion Therapy at 0.1 Hz Improves Survival Following Severe Hemorrhage in Rats

Oscillations in arterial pressure and blood flow at 0.1 Hz are associated with protection of tissue oxygenation during conditions of reduced tissue perfusion. Pulsatile Perfusion Therapy (PPT) is a method we have developed to induce these oscillations, and has been associated with increased tolerance to simulated hemorrhage via lower body negative pressure in humans. However, it is unknown how effective this therapy would be in an actual hemorrhage model. The aim for this study was to test the effcacy of PPT in a rat model of severe hemorrhage. We hypothesized that PPT at 0.1 Hz would protect arterial pressure and cerebral blood flow following severe hemorrhage in rats, subsequently improving survival. Eleven adult Sprague-Dawley rats (six female, five male) were anesthetized via isoflurane, then underwent bilateral carotid artery catheterization for assessment of arterial pressure and carotid artery blood flow, while heart rate was assessed via lead II ECG. Following a 15-min baseline period, all animals were hemorrhaged to 50% of their estimated blood volume over 30-min. Rats were then randomly assigned to the PPT group (3 female, 3 male) or the control group (CON; 3 female, 2 male). PPT was administered via inflatable cuffs attached to both hind limbs, oscillating between 0 mmHg and 250 mmHg every 5-s (10-s cycles or 0.1 Hz) for 30-min immediately following hemorrhage. For the CON group, the leg cuffs were also attached but were not inflated for this 30-min period. All animals were then monitored for an additional 150-min recovery period post-hemorrhage, or until death — defined as the absence of ventricular function on the ECG. Survival time and peak mean arterial pressure (MAP), carotid blood flow, and heart rate were assessed to determine the effectiveness of PPT in protecting hemodynamic responses following hemorrhage. PPT increased survival time ( P = 0.02), with 3 of 6 (50%) rats in the PPT group and 0 of 5 (0%) rats in the CON group surviving the entire 180-min recovery period following hemorrhage. During recovery, PPT protected MAP (PPT: −46.5 ± 12.9% vs. CON: −72.6 ± 19.5% from baseline; P = 0.07) and carotid blood flow (PPT: −61.5 ± 17.7% vs. CON: −83.7 ± 6.7% from baseline; P = 0.04), but did not affect heart rate (PPT: 0.11 ± 6.58% vs. CON: −18.70 ± 29.34% from baseline, P = 0.20), although responses were highly variable between subjects. PPT protected arterial pressure and carotid blood flow in rats following severe hemorrhage, subsequently improving survival. These data add further evidence for the use of 0.1 Hz hemodynamic oscillations as a therapeutic intervention for the treatment of hemorrhage. Physiology and Anatomy Department Seed Grant. 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.

Novel in vivo optogenetic tools reveal autonomous pacemaker control of renal hemodynamics by macula densa cells

Macula densa (MD) cells, the tubular component of the juxtaglomerular apparatus (JGA) are generally considered as sensor cells detecting tubular salt (NaCl) concentration and based on this information provide feedback control of glomerular hemodynamics (tubuloglomerular feedback, TGF). However, the neuron-like differentiation and activity as non-traditional MD functions are emerging. This study addressed the paradigm-shifting hypothesis that rather than being simply the sensory arm of TGF, MD cells function as the nephron’s autonomous pacemaker and the primary driver and oscillator of glomerular hemodynamics. Single cell MD Ca2+ signaling was analyzed in vivo using intravital multiphoton microscopy (MPM) of MD-GT mice that selectively express the ratiometric Ca2+ reporter GCaMP6f/tdTomato in MD cells. Optogenetic MD stimulation was induced in vivo by blue light (470nm) exposure of MD-Ai27 mouse kidneys that express the depolarizing channelrhodopsin ChR2 specifically in MD cells. Conversely, MD inhibition was induced by yellow light (560nm) exposure of MD-Ai39 mouse kidneys that selectively express the hyperpolarizing halorhodopsin NpHR in MD cells. Cell membrane expression of ChR2 (in MD-Ai27 mice) and NpHR (in MD-Ai39 mice) only in the MD among all renal cell types was confirmed using immunohistochemistry. Pacemaker-like regular Ca2+ oscillations (4-fold elevations in baseline Ca2+ and average frequency of 0.03 Hz) and their cell-to-cell propagation within the MD plaque via long cell processes were observed in MD-GT mice. These Ca2+ oscillations were MD cell autonomous, as they were preserved in freshly dissected single MD cells and in the in vitro dissected and microperfused JGA, and were exclusively confined to the MD area. Bulk and scRNA seq and MD transcriptome analysis identified the high MD expression of genes related to pacemaker function, cell membrane depolarization, voltage-dependent ion channels, Ca2+ signaling and synaptic transmission that was validated by immunohistochemistry. Blue light exposure of single glomeruli/JGAs using ROI scan in MD-Ai27 mouse kidneys that previously underwent superficial corticotomy (open loop nephrons) acutely and reversibly increased capillary and afferent (AA)/efferent arteriole (EA) blood flow by approx. 50% in the light-exposed glomerulus but not in adjacent glomeruli. In contrast, yellow light exposure of single glomeruli/JGAs in MD-Ai39 mouse kidneys acutely and reversibly decreased blood flow but increased glomerular capillary diameter (suggesting preferential EA vs AA vasoconstriction) in the exposed but not in adjacent single nephrons. In addition, yellow light stimulation of single glomeruli in MD-Ai39 mouse kidneys augmented the spontaneous glomerular blood flow oscillations in these open-loop nephrons (frequency of 0.03 Hz), but not in adjacent control nephrons. Altogether, these studies identified MD cells as the nephron’s central pacemaker and oscillator of single nephron blood flow, and emphasized the importance of MD cell membrane potential and Ca2+-dependent vasodilator release as a major driver of nephron function. DK064234 DK123564 DK135290. 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.

THE IMPACT OF WINTER SWIMMING ON FUNCTIONAL MICROVASCULAR CHANGES

Objective: Microcirculation plays an important role in the development of cardiovascular control. Therefore, the aim of our study was to investigate the impact of winter swimming on functional changes in cutaneous microcirculation Flow-mediated skin fluorescence (FMSF) is a novel and non-invasive technique assessing microvascular function based on the measurements of nicotinamide adenine dinucleotide hydrogen (NADH) fluorescence intensity in the epidermis and post occlusive reactive hyperemia test. NADH intensity changes in response to blockage and release of blood flow in the brachial artery, which corresponds to microvascular function. Design and method: FMSF examinations were performed before and after the winter swimming period lasting from November 2022 to April 2023 in 37 subjects (mean age 46±4,0 years, 65% women). The mean frequency of winter swimming activity was 1,3 times per week. We analysed the following variables: the ischemic response (IRmax and IRindex) – the ratio of relative to baseline maximal increase in fluorescence intensity during cuff occlusion and the hyperaemic response after cuff release (HRmax and HRindex). Flowmotion, measured at baseline (FM) and at reperfusion (FM(R)), reflects flow oscillations. Normoxia oscillatory index (NOI) represents the proportion of endothelial and neurogenic blood flow oscillations in relation to all oscillations detected in low frequency range. The hypoxia sensitivity (HS), measured during reperfusion, reflects the intensity of flowmotion related to myogenic oscillations. Results: The statistical analysis revealed following results according to the winter swimming: Conclusions: Increase in microvascular oscillations denoted by NOI and HS suggests a beneficial impact of winter swimming on cutaneous microcirculation. Improvement in microcirculation performance may partly explain lowering of cardiovascular risk in regular winter swimmers.