Laser Doppler Flowmetry Research Articles

Impact of Hypo- and Hyper-capnia on Spreading Depolarizations in Rat Cerebral Cortex.

Patients with traumatic brain injury are typically maintained at low-normal levels of arterial partial pressure of carbon dioxide (PaCO2) to counteract the risk of elevated intracranial pressure during intensive care. However, several studies suggest that management at hypercarbic levels may have therapeutic benefit. Here we examined the impact of CO2 levels on spreading depolarizations (SD), a mechanism and marker of acute lesion development in stroke and brain trauma. In an acute preparation of mechanically ventilated (30/70 O2/N2) female rats, SDs were evoked by cortical KCl application and monitored by electrophysiology and laser doppler flowmetry; CO2 levels were adjusted by ventilator settings and supplemental CO2. During 90min of KCl application, rats were maintained at hypocapnia (end-tidal CO2 22±2mmHg) or hypercapnia (57±4mmHg) but did not differ significantly in arterial pH (7.31±0.10 vs. 7.22±0.08, p=0.31) or other variables. Surprisingly, there was no difference between groups in the number of SDs recorded (10.7±4.2 vs. 11.7±3.1; n=3 rats/group; p=0.75) nor in SD durations (64±27 vs. 69±37 sec, p=0.54). In separate experiments (n=3), hypoxia was induced by decreasing inhaled O2 to 10% and single SDs were induced under interleaved conditions of hypo-, normo-, and hypercapnia. No differences in SD duration were observed. In both normoxia and hypoxia experiments, however, mean arterial pressures were negatively correlated with SD durations (normoxia R2=-0.29; hypoxia R2=-0.61, p's<0.001). Our results suggest that any therapeutic benefit of elevated CO2 therapy may be dependent on an acidic shift in pH or may only be observed in conditions of focal brain injury.

Application of deep oscillation therapy in the treatment of peripheral arterial diseases

Intermittent claudication is a common symptom of peripheral arterial disease, affecting up to 50% of patients over the age of 50, which is characterized by pain, discomfort, and cramping in the leg muscles during physical activity. Intermittent claudication is a common symptom of lower extremity arterial disease (LEAD), which significantly impacts patients’ quality of life and drives healthcare costs. Current treatments for intermittent claudication are often inadequate, leading to a need for more effective treatments. Developing new treatments is critical to improve outcomes for patients and address the public health implications of LEAD. This study’s aim was to present the impact of comprehensive physiotherapy, conducted independently, with the supervision of a physiotherapist, for 14 weeks, on a patient with intermittent claudication caused by peripheral arterial disease. The therapy included bicycle training in a form of physical therapy at home, combined with deep oscillation therapy. Deep oscillation therapy involved the use of an electrostatic field with a frequency of 5 to 250 Hz. The field was applied following the lymphatic drainage methodology. In the discussed case, a statistically significant and favourable increase in the measured variables was observed, such as the increase of bone-brachial index from 0.65 to 0.8, the increase of tissue perfusion, measured by laser Doppler flowmetry, from 12.3% to 61%, depending on the measurement site, and the increase in pain-free walking distance by 451%. TcPO2 measurement in the affected leg increased from 31 to 48 mmHg. The use of physical therapy at home combined with deep oscillation showed improvements in pain-free walking distance, Ankle Brachial Index, and other measures in patients with peripheral arterial disease. Deep oscillation therapy demonstrated potential analgesic effects but also raised concerns about possible nerve damage. The study indicated that physical therapy at home might serve as an alternative to supervised exercise therapy, but it had limitations like a small sample size and lack of direct comparisons.

Morphological features of the photoplethysmographic signal: a new approach to characterize the microcirculatory response to photobiomodulation.

Introduction and Objectives: Advanced analysis of the morphological features of the photoplethysmographic (PPG) waveform may provide greater understanding of mechanisms of action of photobiomodulation (PBM). Photobiomodulation is a non-ionizing, red to near-infrared irradiation shown to induce peripheral vasodilatation, promote wound healing, and reduce pain. Using laser Doppler flowmetry combined with thermal imaging we found previously in a clinical study that PBM stimulates microcirculatory blood flow and that baseline palm skin temperature determines, at least in part, why some individuals respond favorably to PBM while others do not. "Responders" (n = 12) had a skin temperature range of 33°C-37.5°C, while "non-responders" (n = 8) had "cold" or "hot" skin temperature (<33°C or >37.5°C respectively). The continuous PPG signals recorded from the index fingers of both hands in the original clinical study were subjected to advanced post-acquisitional analysis in the current study, aiming to identify morphological features that may improve the accuracy of discrimination between potential responders and non-responders to PBM. Methods: The PPG signals were detrended by subtracting the lower envelope from the raw signal. The Root Mean Square (RMS) and Entropy features were extracted as were two additional morphological features -- Smoothness and number of local extrema per PPG beat (#Extrema). These describe the signal jaggedness and were developed specifically for this study. The Wilcoxon test was used for paired comparisons. Correlations were determined by the Spearman correlation test (rs). Results: The PPG waveforms of responders to PBM had increased amplitude and decreased jaggedness (Baseline vs. 10' post-irradiation: Entropy, 5.0 ± 1.3 vs. 3.9 ± 1.1, p = 0.012; #Extrema, 4.0 ± 1.1 vs. 3.0 ± 1.6, p = 0.009; RMS, 1.6 ± 0.9 vs. 2.3 ± 1.2, p = 0.004; Smoothness, 0.10 ± 0.05 vs. 0.19 ± 0.16, p = 0.016). In addition, unilateral irradiation resulted in a bilateral response, although the response of the contralateral, non-irradiated hand was shorter in duration and lower in magnitude. Although subjects with 'cold,' or 'hot,' baseline skin temperature appeared to have morphologically distinct PPG waveforms, representing vasoconstriction and vasodilatation, these were not affected by PBM irradiation. Conclusion: This pilot study indicates that post-acquisitional analysis of morphological features of the PPG waveform provides new measures for the exploration of microcirculation responsiveness to PBM.

Effective wound healing agents based on N-alkenylimidazole zinc complexes derivatives: future prospects and opportunities

Introduction: The therapeutic effect of commercially available domestic and foreign drugs for the treatment of various skin injuries is far from optimal. These drugs have no universal effects, but cause pronounced side reactions. There is a clear demand for development of innovative wound-healing drugs with antimicrobial properties, which increase the natural protective function of the skin. Pharmaceutical compounds with zinc nanoparticles have been increasingly recognized as a promising therapeutic direction. These drugs can easily penetrate into damaged tissues and stimulate metabolic processes. Zinc complexes with imidazole derivatives are of a particular interest. Imidazole acts as a structural fragment of many natural physiologically active compounds, thus providing targeted delivery of this essential trace element into the wound for inclusion in the multicascade mechanism of wound healing. The aim of the study: to provide experimental evidence for effects of recently developed zinc complexes with N-alkenylimidazole as wound healing agents. Materials and Methods: Wound-healing effects of six 1% gels containing distinct N-alkenylimidazole zinc complexe derivatives based on the Na-carboxymethylcellulose (Na-CMC) were comparatively studied in 128 outbred white rats of both genders. The Na-CMC-based Zinc Sulfate 1% gel, Methyluracil and Solcoseryl served as reference drugs. After performing the local tolerance study of zinc complexes, linear and planar sterile wounds of comparable size were inflicted in anesthetized animals. The degree of healing was evaluated on the day 8 and day 28 after the treatment start by wound sizes and histological examination of inflammatory response, epithelization, granulation tissue, angiogenesis, and necrosis. The skin microcirculation system was evaluated using the laser Doppler Flowmetry (LDF), whereby the blood flow indicators were recorded 30 and 60 minutes after intraperitoneal administration of the trial compound. The antimicrobial activity of the zinc compounds was determined in vitro by means of their minimum inhibitory concentration suppressing the bacteria and fungi growth using the double serial dilution method in liquid culture media. The statistical data processing was performed using the Statistica 12 software package. Results and Discussion: In the linear wound model, all animals treated with either of six experimental zinc compounds showed almost complete reduction in wound size (92-100%, p&lt;0.05) on the day 8, significantly exceeding the wound healing in the control animals (reduction by 67-88 %, p&lt;0.05) and effects of the reference drugs (reduction by 83-86%, p&lt;0.05). In the planar wound model, the most significant wound healing effect was reached by using the gel containing N-isopropenylimidazole zinc diacetate (encoded as Pilim-1). The respective histological examination showed signs of complete epithelialization, absence of destructive changes in the epidermis, restoration of skin appendages and presence of mature granulation tissue. Intraperitoneal Pilim-1 administration at a dose of 20 mg/kg improved microcirculation in the rat skin, as judged by significant effects on perfusion and the amplitudes of the isolated rhythms of the LDF-gram. In addition, Pilim-1 exerted a moderate bacteriostatic and fungistatic activity, which was 2 times greater than the antimicrobial activity of Metronidazole. Conclusion: Topical application of gels containing 1% N-alkenylimidazole zinc complex derivatives accelerates the healing of uninfected linear and planar wounds in comparison with the established reference drugs. The Pilim-1 zinc compound exhibited the most pronounced therapeutic effect. The observed in vitro antimicrobial action of Pilim-1 is of further interest for potential implications in treatment of infected skin wounds. The regenerative effect of this substance opens prospects for development of new drugs with improved wound healing properties.

Hemodynamics and cutaneous microcirculation during induction of general anesthesia with and without esketamine.

Currently, there are limited data on the effect of macrocirculatory hemodynamic changes on human microcirculation, especially during the induction of general anesthesia (GA). We performed a non-randomized observational trial on patients receiving GA for elective surgery. In the control group (CG), for GA induction sufentanil, propofol, and rocuronium was administered. Patients assigned to the esketamine group (EG) received additional esketamine for GA induction. Invasive blood pressure (IBP) and pulse contour cardiac output (CO) measurement were performed continuously. Microcirculation was assessed using cutaneous Laser Doppler Flowmetry (forehead and sternum LDF), peripheral and central Capillary Refill Time (pCRT, cCRT), as well as brachial temperature gradient (Tskin-diff) at baseline, 5, 10 and 15 minutes after induction of GA. 42 patients were included in the analysis (CG n = 22, EG n = 20). pCRT, cCRT, Tskin-diff, forehead and sternum LDF decreased following GA induction in both groups. IBP and CO were significantly more stable in esketamine group. However, the changes in the microcirculatory parameters were not significantly different between the groups. The addition of esketamine for GA induction warranted better hemodynamic stability for the first five minutes, but had no significant effect on any of the cutaneous microcirculatory parameters measured.

Assessment of the Microcirculation in Superficial and Deep Biotissue with Photobiomodulation

Background Quantitative measurement of blood flow in specific biotissue targets is crucial for photobiomodulation therapy (PBMT). PBMT has been applied on many clinical applications. However, the conclusive confirmation of its effects on microcirculation and laser wavelength dependency in superficial and deep tissues is lacking. Objective This study examines the microcirculatory response and laser wavelength dependency of red and near infrared (NIR) lasers in biotissue. Laser Doppler flowmetry (LDF) was used to assess the flux and velocity of erythrocytes in buccal tissue when exposed to 660 nm and 830 nm laser radiation. Discussion The microcirculatory response of subjects during and after laser radiation were analyzed. Each laser has an energy density of 73.17 J/cm2 . Both the 660 nm and 830 nm lasers demonstrated the capability to enhance microcirculation in both superficial and deep tissues. Furthermore, we observed that laser wavelengths at 660 nm and 830 nm respectively enhanced the microcirculatory response in superficial and deep tissues. Importantly, this cumulative effect persisted for at least 10 minutes. Conclusions The present results indicate that PBM can effectively improve local blood perfusion in specific target areas and peripheral biotissues. These findings have potential applications in enhancing wound healing and local microcirculation within the target areas.

Functional State of the Mesenteric Arteries and Vessels of the Skin Microcirculation Bed in Rats with Experimental Kidney Dysfunction

Chronic kidney disease is accompanied by cardiovascular complications, including endothelial dysfunction, arterial hypertension, and atherosclerosis. The aim of this work is to compare the reactivity of the vessels of the microcirculatory bed (MCR) of the skin, assessed by laser Doppler flowmetry (LDF) and mesenteric arteries in rats with resection of 5/6 of the mass of the kidneys, and to evaluate the possibility of using LDF analysis as a method that reflects the functional state of large resistive vessels. Wistar rats were divided into two groups: animals of the NE-group (n = 15) had 5/6 of the mass of kidney tissue removed, control animals of the SO-group (n = 15) underwent a sham operation. After 8 weeks, the reactivity of rat skin microvessels to acetylcholine (ACh) and sodium nitroprusside (NP) iontophoresis was assessed. A week later, in rats, the effect of NE on the reactivity of mesenteric arteries preconstricted with phenylephrine was evaluated in vivo using microphotographic and video recording of the diameter. It has been shown that NE does not affect the average value of perfusion in the skin of rats at rest, however, it changes the structure of the frequency range of the spectrum of fluctuations in the MCR index, increasing the value of endothelial, neurogenic, and myogenic tone. NE led to the development of endothelial dysfunction of the mesenteric arteries and MCR vessels of the skin, which was expressed in a decrease in vascular reactivity to the action of endothelium-dependent (ACh) and endothelium-independent (NP) vasodilators. Thus, the development of experimental kidney dysfunction led to changes in the spectral components of fluctuations in the MCR index in the skin, indicating an increase in tonic effects of various genesis on the vessels. NE was accompanied by a decrease in the reactivity of microvessels of the skin and mesenteric arteries, however, there was no correlation between an increase in the MCR index and dilatation of the mesenteric arteries under the action of vasodilator agonists.

Abstract P422: CD4+ T Cells From Preeclamptic Patients During Pregnancy Causes Cognitive Dysfunction Postpartum In A Pregnant Rat Model

Preeclampsia (PE), new onset hypertension (HTN) during pregnancy, is associated with impaired cognitive function and increased cerebral blood flow (CBF). Although we have previously shown adoptive transfer of placental CD4+ T cells from PE women into athymic nude pregnant rats causes HTN and circulating factors associated with PE, we do not know the role of CD4+ T cells in contributing to impaired cerebral blood flow and cognitive dysfunction in the postpartum period. Therefore, we hypothesize that adoptive transfer of placental CD4+ T cells from PE patients into pregnant athymic nude recipient rats will cause maternal hypertension and cognitive dysfunction and impaired CBF postpartum. Placental CD4+ T cells were isolated from normotensive (NP) and preeclamptic (PE) pregnant women at delivery. One million CD4+ T cells were injected interperitoneally (i.p.) into normal pregnant nude athymic rats on gestational day (GD) 12. Dams were allowed to deliver and aged 12-weeks after delivery. Blood pressure (MAP) was measured by carotid catheter and at 12-weeks postpartum CBF autoregulation was measured by laser Doppler flowmetry. The Barnes maze and the novel object recognition behavioral assays were used to assess cognitive function on gestational day (GD) 15-19 and 12-weeks postpartum. A student’s t-test was used for statistical analysis. MAP increased during pregnancy in PE recipient rats (115±2 mmHg, n=5) compared to NP recipient rats (99±3 mmHg, n=4, p&lt; 0.05). MAP significantly increased in the postpartum period in PE recipient rats (114±2 mmHg, n=5) compared to NP controls (98±2 mmHg, n=7, p&lt;0.05). PE recipient rats exhibited latency with errors navigating in the Barnes maze compared to NP controls during pregnancy and postpartum. Locomotor activity was decreased in PE recipient rats compared to NP controls during pregnancy (p&lt;0.05) and postpartum. PE recipient rats had increased CBF autoregulation compared to NP rat recipients in the postpartum period. Our findings indicate that rat recipients of CD4+ T cells from PE patients demonstrate maternal HTN and increased CBF and cognitive dysfunction in the postpartum period compared to recipients of NP CD4 + T cells. These data indicate long-term cognitive and cerebral dysfunction as a result of preeclampsia.

Abstract P209: Six Weeks Oral Losartan Treatment Improves Endothelium-dependent Dilation In Normotensive Women With A History Of Preeclampsia

Women with a history of preeclampsia have a 4-fold increased risk of cardiovascular disease compared to women who had a healthy pregnancy. These women demonstrate microvascular endothelial dysfunction, mediated by reduced nitric oxide (NO)-dependent dilation and increased sensitivity to angiotensin II. We hypothesized that systemic angiotensin II type 1 receptor (AT 1 R) inhibition would improve endothelium- and NO-dependent dilation in the microvasculature of women with a history of preeclampsia. Seven normotensive (seated SBP 118±6; DBP 78±6 mmHg) women (33±6 years of age, 11±7 months postpartum) with a history of preeclampsia participated in a double-blind placebo-controlled crossover study. Following 6 weeks of placebo and losartan treatment (50 mg/day), participants wore a 24-hour blood pressure monitor and completed 1 study visit in which 2 intradermal microdialysis fibers were placed in the skin of the ventral forearm for graded infusions of acetylcholine (ACh, 10 -7 -10 2 mM) or ACh + 15 mM N G nitro L-arginine methyl ester (L-NAME; NO synthase inhibitor) to assess endothelium- and NO-dependent dilation, respectively. Red blood cell flux was measured over each microdialysis site by laser-Doppler flowmetry. Cutaneous vascular conductance was calculated (CVC=Doppler flux/mean arterial pressure) and normalized to maximum (%max; 28 mM SNP + 43°C). Systemic losartan treatment augmented endothelium-dependent (losartan: 96±4 vs placebo: 70±14%max; P &lt;0.001) and NO-dependent (losartan: 35±14 vs placebo: 23±8%; P &lt;0.001) dilation. There was no effect of treatment on 24-hour systolic blood pressure (losartan: 117±4 vs placebo: 117±8 mmHg), diastolic blood pressure (losartan: 72±5 vs placebo: 71±5 mmHg) or mean arterial pressure (losartan: 92±4 vs placebo: 92±6 mmHg; all P&gt;0.05 ). Losartan treatment increased endothelium-dependent vasodilation via NO-mediated pathways in the absence of changes in blood pressure in women with a history of preeclampsia. These data suggest that systemic AT 1 R inhibition may be a viable therapeutic approach to treat persistent microvascular dysfunction in otherwise healthy women who have had preeclampsia.

Abstract P217: The Role Of Angiotensin-(1-7) In Regulating Vascular Endothelial Function In Postmenopausal Women

Postmenopausal women (PMW) have reduced endothelial function, however, the mechanisms contributing to this decline remain unclear. Angiotensin-(1-7) [Ang-(1-7)] is a vasoactive peptide of the vasodilatory arm of the Renin-Angiotensin system and increasing bioavailable Ang-(1-7) enhances endothelial function in young women (YW) with pre-clinical cardiovascular disease. Circulating Ang-(1-7) decreases with aging and may be impacted by menopause. However, whether increasing bioavailable Ang-(1-7) improves endothelial function in PMW is unknown. The purpose of this study was to test the hypothesis that increasing bioavailable Ang-(1-7) improves endothelial function in PMW. We assessed skin blood flow responses to local heating in 8 healthy YW (27±9 yrs) and 5 healthy PMW (56±4 yrs). Cutaneous vasodilation was measured using laser-Doppler flowmetry directly over microdialysis perfusions of lactated Ringer’s (control) in YW and PMW, and in PMW only, 100 μM Ang-(1-7). Following 45 minutes of perfusion of lactated Ringer’s and Ang-(1-7), skin was heated to 42°C (0.1°C·sec -1 ) until laser-Doppler flux reached a stable plateau, indicative of endothelium-dependent dilation. Following the plateau, 28mM sodium nitroprusside was perfused while skin was heated to 43°C to achieve maximal vasodilation. Cutaneous vascular conductance (CVC) was calculated as laser-Doppler flux/MAP, and normalized to maximal dilation (%CVC max ). Women were normotensive (MAP: YW 86±7 mmHg; PMW 85±9 mmHg) and not obese (BMI: YW 23±3 kg/m 2 ; PMW 23±4 kg/m 2 ). YW had greater dilation during local heating (control: YW 94.54±5.4 vs. PMW 82.59±10.72 %CVC max ; P=0.021). Contrary to our hypothesis, Ang-(1-7) did not enhance heating-induced vasodilation in PMW (80.10±9.43 %CVC max ; P=0.69). These preliminary results suggest that increasing bioavailable Ang-(1-7) may not improve endothelial function in PMW. Additional studies are needed to understand if these findings are due to estrogen deficiency in PMW.

Idiopathic cervical dystonia and non-motor symptoms: a pilot case-control study on autonomic nervous system

PurposeNon-motor symptoms, such as sleep disturbances, fatigue, neuropsychiatric manifestations, cognitive impairment, and sensory abnormalities, have been widely reported in patients with idiopathic cervical dystonia (ICD). This study aimed to clarify the autonomic nervous system (ANS) involvement in ICD patients, which is still unclear in the literature.MethodsWe conducted a pilot case-control study to investigate ANS in twenty ICD patients and twenty age-sex-matched controls. The Composite Autonomic System Scale 31 was used for ANS clinical assessment. The laser Doppler flowmetry quantitative spectral analysis, applied to the skin and recorded from indices, was used to measure at rest, after a parasympathetic activation (six deep breathing) and two sympathetic stimuli (isometric handgrip and mental calculation), the power of high-frequency and low-frequency oscillations, and the low-frequency/high-frequency ratio.ResultsICD patients manifested higher clinical dysautonomic symptoms than controls (p < 0.05). At rest, a lower high-frequency power band was detected among ICD patients than controls, reaching a statistically significant difference in the age group of ≥ 57-year-olds (p < 0.05). In the latter age group, ICD patients showed a lower low-frequency/high-frequency ratio than controls at rest (p < 0.05) and after mental calculation (p < 0.05). Regardless of age, during handgrip, ICD patients showed (i) lower low-frequency/high-frequency ratio (p < 0.05), (ii) similar increase of the low-frequency oscillatory component compared to controls, and (iii) stable high-frequency oscillatory component, which conversely decreased in controls. No differences between the two groups were detected during deep breathing.ConclusionICD patients showed ANS dysfunction at clinical and neurophysiological levels, reflecting an abnormal parasympathetic-sympathetic interaction likely related to abnormal neck posture and neurotransmitter alterations.

Clinical effectiveness of comprehensive evaluation of soft tissue inflammation during preparation and treatment by dental implantation: A case report

At the Department of Orthopedic Dentistry and Orthodontics of the Ryazan State Medical University, one patient (A.) underwent after tooth extraction at the orthopedic rehabilitation using immediate prosthetics, and another patient (B.) was cured after extraction proceeded naturally. Both patients underwent dental implantation 4 months later. After tooth extraction and implantation, both patients underwent complex diagnostic observations on days 7, 20, and 30 through objective, instrumental, and laboratory follow-up of inflammation using the SchillerPisarev test, laser Doppler flowmetry (LDF), and assessment of the level of pro-inflammatory cytokines interleukin 6 (IL-6) and tumor necrosis factor (TNF-) and C-reactive protein (CRP). After tooth extraction on day 30, the clinical picture of both patients indicated complete subsidence of inflammation and stabilization of repair. The IL, CRP, and TNF- levels were 1.36 and B. 1.75 pg/mL, 0.68 and 0.88 mg/L, and 17.8 and 21.3 pg/mL in patients A and B, respectively. LDF indicators were 18.47 conventional units in patient A, and the microcirculation parameter was 11.46 conventional units in patient B. Thirty days after implantation, the levels of IL-6, CRP, and TNF- were 1.39 and 1.78 pg/mL, 0.74 and 0.92 mg/mL, and 18.9 and 20.2 pg/mL, respectively. The LDF values were 20.35 units in patient A, and the microcirculation parameter was 19.62 units in patient B. Comprehensive analysis of inflammation is necessary because of its high information content and ability to identify possible complications.

Mitochondrial dysfunction underlies impaired neurovascular coupling following traumatic brain injury

Traumatic brain injury (TBI) involves an acute injury (primary damage), which may evolve in the hours to days after impact (secondary damage). Seizures and cortical spreading depolarization (CSD) are metabolically demanding processes that may worsen secondary brain injury. Metabolic stress has been associated with mitochondrial dysfunction, including impaired calcium homeostasis, reduced ATP production, and elevated ROS production. However, the association between mitochondrial impairment and vascular function after TBI is poorly understood. Here, we explored this association using a rodent closed head injury model. CSD is associated with neurobehavioral decline after TBI. Craniotomy was performed to elicit CSD via electrical stimulation or to induce seizures via 4-aminopyridine application. We measured vascular dysfunction following CSDs and seizures in TBI animals using laser doppler flowmetry. We observed a more profound reduction in local cortical blood flow in TBI animals compared to healthy controls. CSD resulted in mitochondrial dysfunction and pathological signs of increased oxidative stress adjacent to the vasculature. We explored these findings further using electron microscopy and found that TBI and CSDs resulted in vascular morphological changes and mitochondrial cristae damage in astrocytes, pericytes and endothelial cells. Overall, we provide evidence that CSDs induce mitochondrial dysfunction, impaired cortical blood flow, and neurobehavioral deficits in the setting of TBI.

Diabetic Foot Ulcer Imaging: An Overview and Future Directions.

Diabetic foot ulcers (DFUs) affect one in every three people with diabetes. Imaging plays a vital role in objectively complementing the gold-standard visual yet subjective clinical assessments of DFUs during the wound treatment process. Herein, an overview of the various imaging techniques used to image DFUs is summarized. Conventional imaging modalities (e.g., computed tomography, magnetic resonance imaging, positron emission tomography, single-photon emitted computed tomography, and ultrasound) are used to diagnose infections, impact on the bones, foot deformities, and blood flow in patients with DFUs. Transcutaneous oximetry is a gold standard to assess perfusion in DFU cases with vascular issues. For a wound to heal, an adequate oxygen supply is needed to facilitate reparative processes. Several optical imaging modalities can assess tissue oxygenation changes in and around the wounds apart from perfusion measurements. These include hyperspectral imaging, multispectral imaging, diffuse reflectance spectroscopy, near-infrared (NIR) spectroscopy, laser Doppler flowmetry or imaging, and spatial frequency domain imaging. While perfusion measurements are dynamically monitored at point locations, tissue oxygenation measurements are static two-dimensional spatial maps. Recently, we developed a spatio-temporal NIR-based tissue oxygenation imaging approach to map for the extent of asynchrony in the oxygenation flow patterns in and around DFUs. Researchers also measure other parameters such as thermal maps, bacterial infections (from fluorescence maps), pH, collagen, and trans-epidermal water loss to assess DFUs. A future direction for DFU imaging would ideally be a low-cost, portable, multi-modal imaging platform that can provide a visual and physiological assessment of wounds for comprehensive wound care intervention and management.

Peculiarities of paravulvar microcirculation in skin and muscle in blast wound in variants of early local injection of reparative active agent

Introduction. A promising method of correcting microcirculatory disorders in the area of soft tissue injury is the use of agents with antihypoxant action, which include deproteinized calf-blood hemoderivate.The aim of the work was to reveal the peculiarities of subcutaneous and intramuscular local injection of deproteinized calfblood hemoderivate on the changes of microcirculation in the skin and muscles in the experimental blast wound area.Materials and methods. The experiments were performed on 90 male Wistar rats weighing (320±20) g in compliance with international rules of work with laboratory animals. Modeling of an explosive wound of the soft tissues of the femur with mild degree of blood loss was carried out according to the original author’s method (Patent RU No. 2741238 dated 22.01.2021). After primary surgical treatment was performed paravulnarly, deproteinized calf-blood hemoderivate was injected intramuscularly, intramuscularly and subcutaneously (Actovegin drug) once in six points with an insulin syringe. Microcirculation in the skin and muscles of the injured area was assessed by laser Doppler flowmetry using the device LAKK-M (Russia). To determine the normal values of microcirculation, data obtained from healthy animals were used.Results. Local intramuscular injection into the paravular area resulted in an increase of the constant perfusion component (M) by 24.1−35.9 % (p &lt; 0.05) and by 18.0−56.4 % (p &lt; 0.05) in the skin and muscles during all periods of observation, an increase of the variable perfusion component (σ) in the skin by 31.4−38.0 % (p &lt; 0.05) during 28 days and in muscles by 8.8−58.7 % (p &lt; 0.05) during the first 14 days only, increase of Kv ratio in skin by 12.4 % (p = 0.01) early after injury (7 days) and decrease in muscles by 18.3−20.8% (p &lt; 0.05) at 14−28 days. Local combined administration (intramuscularly and subcutaneously) of the drug around the wound promoted the increase of the constant perfusion component (M) in the skin by 23.8 % (p = 0.005) and 6.9 % (p = 0.01) at the 7th and 28th days of observation, increase of σ index in skin by 14.2−45.1 % (p &lt; 0.007) on the 7−14 days and its decrease in muscles by 15.7 % (p = 0.009) by the end of the 7th day of observation in comparison with animals after only intramuscular injection only. Also, the coefficient of variation (Kv) with the combined route of injection was increased in the skin by 8.8−23.8 % (p &lt; 0.009) in the first 14 days and decreased in the muscles by 15.7 % (p = 0.008) in the early period after injury (7 days) relative to its values in animals with intramuscular injection.Discussion. The results of the study allow noting the stimulating effect of deproteinized calf-blood hemoderivate on neovasculogenesis in the damaged tissues, which can be judged by the increase in the constant perfusion component (M). In addition, we can conclude that the direct endothelium-protective effect of the drug consists in the modulation of microcirculatory flow, which confirms the significant increase in the variable perfusion component (σ) throughout the experiment.Conclusion. Local paravular administration of deproteinized calf-blood hemoderivate in experimental blast wound promotes microcirculation increase in the soft tissues of the injury area. Combined (intramuscular and subcutaneous) local paravular injection of the drug allows more effective stimulation of microcirculation in the skin and muscles of the injury area.

Effects of a Mitochondrial Targeted Ubiquinol (MitoQ) on Vascular Function and Exercise Capacity in Chronic Kidney Disease: A Randomized Controlled Pilot Study.

Mitochondrial derived oxidative stress is implicated in vascular and skeletal muscle abnormalities in chronic kidney disease (CKD). The purpose of this study was to investigate the effects of a mitochondrial targeted ubiquinol (MitoQ) on vascular function and exercise capacity in CKD. In this randomized controlled trial, 18 patients with CKD (Mean±SEM: Age, 62±3years; eGFR, 45±3ml/min/1.732) received 4 weeks of 20mg/day MitoQ (MTQ) or placebo (PLB). Outcomes assessed at baseline and follow up included macrovascular function measured by flow mediated dilation; microvascular function assessed by laser Doppler flowmetry combined with intradermal microdialysis; aortic hemodynamics assessed by oscillometery; and exercise capacity by cardiopulmonary exercise testing. Compared to PLB, MTQ improved flow mediated dilation (baseline vs follow up: MTQ, 2.4±0.3 vs. 4.0±0.9%; PLB, 4.2±1.0 vs. 2.5±1.0%; p=0.04). MTQ improved microvascular function (DCVC: MTQ, 4.50 ± 2.57 vs. PLB -2.22 ± 2.67%; p=0.053). Central aortic systolic and pulse pressures were unchanged, however, MTQ prevented increases in augmentation pressures that were observed in the PLB group (p=0.026). MTQ did not affect exercise capacity. This study demonstrates potential for a mitochondrial targeted ubiquinol to improve vascular function in CKD. The findings hold promise for future investigations of mitochondrial targeted therapies in CKD.

Estrogen-Related Receptor Gamma Gene Therapy Promotes Therapeutic Angiogenesis and Muscle Recovery in Preclinical Model of PAD.

Background Peripheral arterial disease and critical limb ischemia are cardiovascular complications associated with vascular insufficiency, oxidative metabolic dysfunction, and myopathy in the limbs. Estrogen-related receptor gamma (ERRγ) has emerged as a dual regulator of paracrine angiogenesis and oxidative metabolism through transgenic mouse studies. Here our objective was to investigate whether postischemic intramuscular targeting of ERRγ via gene therapy promotes ischemic recovery in a preclinical model of peripheral arterial disease/critical limb ischemia. Methods and Results Adeno-associated virus 9 (AAV9) Esrrg gene delivery vector was developed and first tested via intramuscular injection in murine skeletal muscle. AAV9-Esrrg robustly increased ERRγ protein expression, induced angiogenic and oxidative genes, andboosted capillary density and succinate dehydrogenase oxidative metabolic activity in skeletal muscles of C57Bl/6J mice. Next, hindlimb ischemia was induced via unilateral femoral vessel ligation in mice, followed by intramuscular AAV9-Esrrg (or AAV9-green fluorescent protein) gene delivery 24 hours after injury. ERRγ overexpression increased ischemic neoangiogenesis and markers of endothelial activation, and significantly improved ischemic revascularization measured using laser Doppler flowmetry. Moreover, ERRγ overexpression restored succinate dehydrogenase oxidative metabolic capacity in ischemic muscle, which correlated with increased mitochondrial respiratory complex protein expression. Most importantly, myofiber size to number quantification revealed that AAV9-Esrrg restores myofibrillar size and mitigates ischemia-induced myopathy. Conclusions These results demonstrate that intramuscular AAV9-Esrrg delivery rescues ischemic pathology after hindlimb ischemia, underscoring that Esrrg gene therapy or pharmacological activation could be a promising strategy for the management of peripheral arterial disease/critical limb ischemia.

Dentin hypersensitivity treatment with Nd:YAG laser: A systematic review

Objective: To compare the efficacy of Nd:YAG laser to other chemical agents in the treatment of dentin hypersensitivity.&#x0D; Methods: Pubmed, EbscoHost, ProQuest, and Google Scholar were searched for articles published between 2012 to 2022 in English, reporting randomized clinical trials, completed and with results. This systematic review was performed following the Preferred Reporting Items for Systematic Reviews (PRISMA) guidelines with PROSPERO CRD42022325046, and a critical appraisal of the literature was assessed by using JBI’s Checklist for Randomized Controlled Trials.&#x0D; Results: From 5536 articles found in the search based on keywords, 354 were filtered based on study design and desired period range, and six randomized clinical trials were eligible for the systematic review, reporting patients from 18 to 65 years old, with clinical diagnosis of dentin hypersensitive, that evaluate the efficacy of Nd:YAG laser, compared to pre-treatment using visual analog scale, yeaple probe scale, verbal rating scale and laser doppler flowmetry (LDF). These studies evaluated 159 patients and at least 402 hypersensitive teeth. Follow-up periods were considered from immediate to six months post-treatment. All active ingredients and laser treatment effectively reduce dentin hypersensitive and can maintain its efficacy over time. Only one study suggested treatment with Nd:YAG laser is not significant compared to Er,Cr:YSGG laser.&#x0D; Conclusion: Nd:YAG presents a significant immediate reduction of dentin hypersensitive and shows promising results in the long time effects. More standardized evaluation protocols should be implemented to increase the robustness of the results.&#x0D; Keywords: Dentin hypersensitivity, tooth sensitivity, dentin hypersensitivity treatment, laser, Nd:YAG, dentin desensitizing agent

Changes in Microcirculation in the Brain, Heart, and Liver in Female Rats with Translational Model of Alcoholic Cardiomyopathy.

We studied some features of blood and lymph microcirculation in the brain, heart, and liver of female rats with developed alcoholic cardiomyopathy. In female rats after 24-week forced consumption of 10% ethanol solution, the size and inotropic function of the heart were measured by echocardiography. Microcirculation in the brain, myocardium, and liver was assessed by laser Doppler flowmetry using LAKK-OP2 and LAZMA-D computerized laser analyzers. Using spectral wavelet analysis, we determined the absolute and normalized to total perfusion amplitudes of microcirculation oscillations reflecting various regulatory mechanisms. Intact animals served as controls. In rats of the experimental group, alcoholic cardiomyopathy completely developed. Under these conditions, the index of microcirculation in the brain, myocardium, and liver significantly decreased. At the same time, there was a redistribution in the brain between shunting and nutritive blood flow in favor of the latter. In the myocardium and liver, this ratio did not change.

Negative Pressure Wound Therapy in Free Muscle Flaps-Risk or Benefit?

Application of negative pressure wound therapy (NPWT) on free flaps not only reduces edema but also increases the pressure from outside. The impact of these opposite effects on flap perfusion remains elusive. This study evaluates the NPWT system's influence on macro- and microcirculation of free flaps and edema reduction to better assess the clinical value of this therapy in microsurgical reconstructions. In this open-label, prospective cohort study, a total of 26 patients with free gracilis muscle flaps for distal lower extremity reconstruction were included. Flaps were covered with an NPWT (13 patients) or a conventional, fatty gauze dressing (13 patients) for 5 postoperative days (PODs). Changes in flap perfusion were analyzed by laser Doppler flowmetry, remission spectroscopy, and an implanted Doppler probe. Flap volume as a surrogate parameter for flap edema was evaluated by three-dimensional (3D) scans. No flap showed clinical evidence of circulatory disturbances. The groups showed significant differences in the dynamic of macrocirculatory blood flow velocity with an increase in the NPWT group and a decelerated flow in the control group from PODs 0 to 3 and PODs 3 to 5. No significant differences in microcirculation parameters were observed. 3D scans for estimation of edema development demonstrated significant differences in volume dynamics between the groups. Flap volume of the controls increased, while the volume in the NPWT group decreased during the first 5 PODs. The volume of NPWT-treated flaps decreased even further after NPWT removal from PODs 5 to 14 and significantly more than the flap volume in the control group. NPWT is a safe form of dressing for free muscle flaps that enhances blood flow and results in a sustainable edema reduction. The use of NPWT dressings for free flaps should therefore be considered not only as a pure wound covering but also as a supportive therapy for free tissue transfer.