Laser Doppler Flowmeter Research Articles

Neuro- and vasoprotective potential of neuropeptide Y Y2 receptor agonist, NPY13-36, against transient focal cerebral ischemia in spontaneously hypertensive rats

Numerous in vitro and in vivo experimental studies indicate that neuropeptide Y Y2 receptors (Y2R) are potential targets for neuroprotective therapy, including neuroprotection against ischemic stroke in healthy rats. Since stroke in humans is typically associated with comorbidities and long-term hypertension is the most common comorbidity leading to stroke, this study aimed to assess the neuroprotective potential of the Y2R agonist NPY13–36 in the rats with essential hypertension (SHR) subjected to 90 min middle cerebral artery suture occlusion with subsequent reperfusion (MCAOR). The cerebrocortical microflow in the ischemic focus and penumbra was continuously monitored with a Laser-Doppler flowmeter. NPY13–36 (10 μg/6 μl physiological saline solution) was administered intracerebroventricularly (i.c.v.) during ischemia or early reperfusion. The infarct area (triphenyltetrazolium chloride staining), behavioral tests (gait, mobility, and sensorimotor functions), and the response of the cerebrocortical microcirculation in the penumbra to hypercapnia and to the inhibition of the synthesis of nitric oxide were studied. Our results demonstrate that administration of NPY13-36 reduces the size of the infarct, improves motor functions, and restores microcirculatory response to the blockade of nitric oxide synthase when administered during reperfusion. The novelty of this study is a finding of the vasoprotective effect of NPY13-36 in brain ischemia/reperfusion. Moreover, this study provides evidence of the beneficial effects of NPY13-36 in animals with essential hypertension and indicates that Y2R ligands may be promising candidates for treating the ischemic brain in the case of this disease.

Electric Pulp Test Threshold Responses in Healthy Mature Permanent Teeth

Electric pulp testers assess only the neural component of pulp sensibility in dental practice, while vascular status is evaluated with laser Doppler flowmeters and pulp oximeters, which are more reliable for determining vitality in traumatic teeth. Objective: To determine the accuracy of the electric pulp test in healthy mature permanent teeth. Methods: This cross-sectional study was conducted at the Liaquat University of Medical and Health Sciences Jamshoro by consecutive sampling on 220 participants aged 18-35, who had healthy, mature permanent central incisors, canines, first premolars, and first molars, with no history of cardiac pacemakers and metallic restorations. Teeth were isolated, dried, and tested with a COXO C-Pulse electric pulp tester using toothpaste as a conducting medium. Threshold responses were recorded at increasing currents, with each tooth tested twice to determine the mean value. Accuracy was assessed using additional metrics post-therapy. Chi-square tests were employed to compare accuracy across gender and age groups, with significance set at p<0.05. Results: The mean age of the patients was 25.55 ± 5.41 years. 132 (60%) subjects were female, 88 (40%) subjects were male in this study. Accuracy of the electric pulp test in healthy mature permanent teeth was detected in 181 (82.3%) subjects in this study. Conclusion: It was concluded that the electric pulp tester method seems to be a reliable way to evaluate how sensitive the live nerve tissue inside a tooth is for healthy permanent teeth that have fully formed.

Development of modified laser Doppler flowmetry device for real-time monitoring of esophageal mucosal blood flow: a preclinical assessment with an animal model.

This study aimed to modify a laser Doppler flowmeter designed and assembled at our institute. After measuring sensitivity evaluation in ex vivo experiments, we confirmed the efficacy of this new device for monitoring real-time esophageal mucosal blood flow changes after thoracic stent graft implantation by simulating various clinical situations in an animal model. Thoracic stent graft implantation was performed in a swine model (n = 8). Esophageal mucosal blood flow decreased significantly from baseline (34.1 ± 18.8ml/min/100g vs. 16.7 ± 6.6ml/min/100g, P < 0.05) in the lower esophagus (Th6-Th8) where the stent graft covered the aorta. In the hemorrhagic shock model (shock index ≥ 1.0), esophageal mucosal blood flow showed a remarkable change from baseline in the upper esophagus (Th1-Th3), where the stent graft did not cover the aorta (20.8 ± 9.8ml/min/100g vs. 12.9 ± 8.6ml/min/100g, P < 0.01); however, it returned to the baseline value within a 30-min period. Mucosal blood flow remained stable in the esophagus, where the stent graft did not cover the aorta. After elevating the mean blood pressure to > 70mmHg with continuous intravenous noradrenaline infusion, esophageal mucosal blood flow increased significantly in both regions; however, the reaction was different between the two regions. Our newly developed laser Doppler flowmeter could measure real-time esophageal mucosal blood flow changes in various clinical situations during thoracic stent graft implantation in a swine model. Hence, this device can be applied in many medical fields by downsizing it.

Finger SBP measurement as a way to manage hypertension in patients with markedly calcified arteries: a case report.

Overestimation of blood pressure (BP) resulting from medial artery calcification (MAC) is a cause of pseudoresistant hypertension. In this condition, there is no noninvasive way to reliably assess the BP. We report the case of a 62-year-old man who had a four-limb MAC, hypertension despite five antihypertensive molecules, and significant orthostatic hypotension following the addition of the fifth drug. Hypotension symptoms resolved after discontinuation of two treatments. Subsequently, measurement of finger SBP (FSBP) by laser Doppler flowmeter (LDF) was used to estimate upper-limb SBP. While the brachial SBP was greater than 170 mmHg, the FSBP was always less than 140 mmHg. In the absence of upper-limb artery disease, by evidencing the discrepancy between FSBP and brachial SBP, LDF-obtained FSBP could be a reliable tool to ascertain pseudohypertension and monitor the antihypertensive treatment.

Gingivo-Periosteal Expansion of Edentulous Jaw Crest with An Osmotic Self-Inflatable Expander: A Preclinical in Vivo Study.

This study examined the biocompatibility and expansion volume of tissue expanders utilizing rabbits and beagles as experimental models. The self-inflatable expander was provided using a Tissue balloon® (Neobiotech Co., Seoul, Korea). In 9 adult rabbits, a Tissue balloon® was placed under the lateral mandibular periosteum via an extraoral approach. After 2, 3, and 4 weeks (n=3), the expanders were removed, and soft tissue and bone samples were collected for analysis. Histomorphometric analysis and measurements of expander characteristics were performed. In 5 Beagles, all premolars were extracted. Three months after extraction, tissue expanders were placed in the maxilla and mandible, adjacent to dental extraction sites, and removed after 3 weeks. Gingival parameters were measured before and after expansion. Blood perfusion in the oral mucosa was assessed using a laser Doppler flowmeter at different time points. After three weeks, dogs were euthanized, and tissue samples were collected for histologic analysis, focusing on inflammatory response, bone formation, and gingival thickness changes. In the rabbit study, measurements of size, weight, and volume showed significant increases over 4 weeks. Swelling peaked at 2 weeks postimplantation and then gradually stabilized. Histologic examination revealed no signs of inflammation, and expanders were covered by collagen-rich capsules. Some bone resorption was noted due to pressure from the expanders, but the resorption was not significant. In the beagle study, twenty tissue expanders were implanted; 1 expander was lost, and 9 wounds dehisced during soft tissue healing. However, no signs of infection were noted. Histologic evaluation showed bone atrophy, attributed to swelling pressure, at the recipient site. Gingival thickness was not decreased. Perfusion measurements indicated that expansion did not affect microvascular circulation adversely. Overall, both studies suggest that tissue expanders demonstrate biocompatibility and successful expansion volume in vivo, with minimal adverse effects on surrounding tissues and microvascular circulation.

Factor XII and prekallikrein promote microvascular inflammation and psoriasis in mice.

Psoriasis is an autoimmune inflammatory skin disease, featuring microvascular abnormalities and elevated levels of bradykinin. Contact activation of Factor XII can initiate the plasma kallikrein-kinin cascade, producing inflammation and angioedema. The role of Factor XII in psoriasis is unknown. The effects of deficiency of Factor XII or its enzymatic substrate, prekallikrein, were examined in the imiquimod-induced mouse model of psoriasis. Skin microcirculation was assessed using intravital confocal microscopy and laser Doppler flowmeter. A novel antibody blocking Factor XII activation was evaluated for psoriasis prevention. Expression of Factor XII was markedly up-regulated in human and mouse psoriatic skin. Genetic deletion of Factor XII or prekallikrein, attenuated imiquimod-induced psoriatic lesions in mice. Psoriatic induction increased skin microvascular blood perfusion, causing vasodilation, hyperpermeability and angiogenesis. It also promoted neutrophil-vascular interaction, inflammatory cytokine release and enhanced Factor XII / prekallikrein enzymatic activity with elevated bradykinin. Factor XII or prekallikrein deficiency ameliorated these microvascular abnormalities and abolished bradykinin increase. Antagonism of bradykinin B2 receptors reproduced the microvascular protection of Factor XII / prekallikrein deficiency, attenuated psoriatic lesions, and prevented protection by Factor XII / prekallikrein deficiency against psoriasis. Furthermore, treatment of mice with Factor XII antibody alleviated experimentally induced psoriasis and suppressed microvascular inflammation. Activation of Factor XII promoted psoriasis via prekallikrein-dependent formation of bradykinin, which critically mediated psoriatic microvascular inflammation. Inhibition of contact activation represents a novel therapeutic strategy for psoriasis.

Striatal Blood Flow Changes by Middle Cerebral Artery Occlusion and Its Effect on Neurological Deficits in Mice.

We attempted to record the regional cerebral blood flow (CBF) simultaneously at various regions of the cerebral cortex and the striatum during middle cerebral artery (MCA) occlusion and to evaluate neurological deficits and infarct formation. In male C57BL/6J mice, CBF was recorded in three regions including the ipsilateral cerebral cortex and the striatum with laser Doppler flowmeters, and the origin of MCA was occluded with a monofilament suture for 15-90 min. After 48 h, neurological deficits were evaluated, and infarct was examined by triphenyltetrazolium chloride (TTC) staining. CBF decrease in the striatum was approximately two-thirds of the MCA-dominant region of the cortex during MCA occlusion. The characteristic CBF fluctuation because of spontaneously occurred spreading depolarization observed throughout the cortex was not found in the striatum. Ischemic foci with slight lower staining to TTC were found in the ipsilateral striatum in MCA-occluded mice for longer than 30 min (n = 54). Twenty-nine among 64 MCA-occluded mice exhibited neurological deficits even in the absence of apparent infarct with minimum staining to TTC in the cortex, and the severity of neurological deficits was not correlated with the size of the cortical infarct. Neurological deficits might be associated with the ischemic striatum rather than with cortical infarction.

Effect of Orthognathic Surgery On Pulp Blood Flow and Pulp Sensibility: A Prospective Control Trial

IntroductionOrthognathic surgery has the potential to compromise the vitality of the teeth. This paper aims to assess changes in pulp blood flow (PBF) and pulp sensibility (PS) of the anterior dentition following orthognathic surgery and to assess the influence of the proximity of the surgical osteotomy on the PBF and/or PS. MethodsTwenty-six patients undergoing orthognathic surgery (Le Fort I or bilateral sagittal split osteotomy [BSSO]) were compared to sixteen control patients treated by fixed appliances only using Laser Doppler flowmeter (LDF) and thermal testing (CO2 snow). Surgery patients were tested at T1 (presurgery), T2 (4-5 weeks postsurgery), T3 (3 months postsurgery), and T4 (6 months postsurgery). Control patients were tested at T1 (pretreatment), T2 (6 months posttreatment), T3 (12 months posttreatment), and T4 (18 months posttreatment). Differences between the maxilla and mandible were assessed. ResultsNo differences in PBF or PS were recorded in the control group. In the surgery group, both jaws followed the same pattern after surgery, an initial decrease at T2 followed by a gradual recovery to pretreatment PBF levels with no significant difference between T1 versus T4 in both jaws. No difference in PBF was observed between the maxilla and mandible at any testing time interval. Conclusions and Clinical ImplicationsPBF and PS of the anterior dentition was severely affected immediately postsurgery, followed by a gradual increase to full recovery. This pattern of recovery was exhibited in both jaws. A negative sensibility response or discoloration should not be seen as an indication of irreversible ischemic pulp changes. Monitoring for at least 6 months or using LDF as a confirmatory test is required before any irreversible endodontic treatment is to be considered.

Laser flowmetry of microcirculation of the finger depending on the external temperature and the limb position

Introduction. The use of laser Doppler flowmetry (LDF) makes it possible to assess the condition and disorders of blood microcirculation, improving the quality of diagnosis of various cardiovascular diseases. Additional functional tests with laser flowmetric measurements are used to assess the state of the mechanisms that regulate the tissue blood flow. Objective. To identify patterns of blood flow changes in the microcirculatory bed when combining a postural test and a change in air temperature. Materials and methods. The study was conducted on a group of 20 subjects, which included an equal number of girls and boys aged 21–23 years, who were considered healthy and did not have cardiovascular diseases. The experiment was carried out in two stages: first in a room with an air temperature of 201 °C, then at 301 °C. To assess the difference in data between arm positions within the same study phase at the same temperature, the Student’s t-test was used to compare quantitative variables in two dependent samples. The Wilcoxon test was used to assess statistical differences in data for the same hand position but at different air temperatures. Changes were considered statistically significant at p&lt;0.05. The subjects were measured the microcirculation of peripheral blood vessels on the phalanx of the finger in three positions relative to the level of the heart using a portable laser Doppler flowmeter LAZMA PF (Russia). Results. It is shown that an increase in ambient temperature leads to an increase in the difference in microcirculation of peripheral vessels when the arm position changes relative to the level of the heart. When a person is in a room with a temperature of 301 °C, dilation of blood vessels and changes in their tone occur, which explains the increase in microcirculation values in relative perfusion units. Conclusions. The results of the study showed an increase in statistically significant differences according to the Student’s t-test between the different hand positions with increasing room temperature (p&lt;0.0001). In a comparative sample between the first stage (at an air temperature of 20±1 °C) and the second stage of the study (at an air temperature of 30±1 °C), statistically significant results (p&lt;0.001) were obtained according to the Wilcoxon test for the hand position at the heart level and the raised arm.

Studying Erythromelalgia Using Doppler Flowmetry Perfusion Signals and Wavelet Analysis-An Exploratory Study.

Erythromelalgia (EM) is a rare disease, which is still poorly characterized. In the present paper, we compared the hand perfusion of one female EM patient, under challenges, with a healthy control group. Using a laser Doppler flowmeter (LDF) with an integrated thermal probe, measurements were taken in both hands at rest (Phase I) and after two separate challenges-post-occlusive hyperemia (PORH) in one arm (A) and reduction of skin temperature (cooling) with ice in one hand (B) (Phase II). The final measurement periods corresponded to recovery (Phases III and IV). The control group involved ten healthy women (27.3 ± 7.9 years old). A second set of measurements was taken in the EM patient one month after beginning a new therapeutic approach with beta-blockers (6.25 mg carvedilol twice daily). Z-scores of the patient's LDF and temperature fluctuations compared to the control group were assessed using the Wavelet transform (WT) analysis. Here, fluctuations with |Z| > 1.96 were considered significantly different from healthy values, whereas positive or negative Z values indicated higher or lower deviations from the control mean values. Cooling elicited more measurable changes in LDF and temperature fluctuations, especially in higher frequency components (cardiac, respiratory, and myogenic), whereas PORH notably evoked changes in lower frequency components (myogenic, autonomic, and endothelial). No significant Z-score deviations were observed in the second measurement, which might signify a stabilization of the patient's distal perfusion following the new therapeutic approach. This analysis involving one EM patient, while clearly exploratory, has shown significant deviations in WT-derived physiological components' values in comparison with the healthy group, confirming the interest in using cold temperature as a challenger. The apparent agreement achieved with the clinical evaluation opens the possibility of expanding this approach to other patients and pathologies in vascular medicine.

Early hemodynamics after tibial transverse transport in patients with nonarterial stenosis and arterial stenosis diabetic foot.

The diagnosis of peripheral arteriopathy in the diabetic foot is complicated by diabetes and its advanced complications. It has been found that diabetic foot can be categorized into arterial stenosis and non-arterial stenosis, both of which have significant differences in hemodynamic characteristics. To evaluate the early hemodynamic changes in diabetic foot patients with nonarterial stenosis and arterial stenosis treated by tibial transverse transport (TTT) using high-frequency color Doppler ultrasonography (HFCDU) and a laser Doppler flowmeter. Twenty-five patients with Wagner grades 3-5 diabetic foot ulcers were treated with TTT, and the wound healing time and rate were recorded. Patients were grouped according to the results of preoperative lower-extremity ultrasonography. Cases with ≥ 50% stenosis in any of the femoral, popliteal, posterior tibial, anterior tibial, and peroneal arteries of the affected limb were classified as the arterial stenosis group (n = 16); otherwise, they were classified as the nonarterial stenosis group (n = 9). Before and one month after surgery, HFCDU was used to evaluate the degree of lower limb artery lesions and hemodynamic changes in patients. The degree of femoral-popliteal atherosclerotic stenosis, the degree of vascular stenosis and occlusion of the lower-knee outflow tract, and the degree of medial arterial calcification were scored; the three scores were added together to obtain the total score of lower extremity arteriopathy. PeriScanPIM3, a laser Doppler flowmeter system, was used to detect alterations in plantar microcirculation before and 1 mo after surgery. Wound healing and hemodynamic indices were compared between the two groups. The wound healing time of the diabetic foot was significantly shorter in the nonarterial stenosis group than in the arterial stenosis group (47.8 ± 13 vs 85.8 ± 26, P < 0.05), and the wound healing rate of both groups was 100%. The preoperative total lower extremity arteriopathy scores were lower in the nonarterial stenosis group than those in the arterial stenosis group (18.89 ± 8.87 vs 24.63 ± 3.52, P < 0.05). The nonarterial stenosis group showed higher preoperative popliteal artery (POA) blood flow than the arterial stenosis group (204.89 ± 80.76 cc/min vs 76.75 ± 48.49 cc/min, P < 0.05). Compared with the baseline (before surgery), the postoperative POA blood flow of the affected limb in the nonarterial stenosis group decreased one month after surgery (134.11 ± 47.84 cc/min vs 204.89 ± 80.76 cc/min, P < 0.05), while that in the arterial stenosis group increased (98.44 ± 30.73 cc/min vs 61.69 ± 21.70 cc/min, P < 0.05). Although the POA blood flow in the arterial stenosis group was obviously improved one month after surgery, it was still lower than that in the nonarterial stenosis group (98.44 ± 30.73 cc/min vs 134.11 ± 47.84 cc/min, P < 0.05). The nonarterial stenosis group had higher preoperative plantar microcirculation than the arterial stenosis group (56.1 ± 9.2 vs 33.2 ± 7.5, P < 0.05); compared with the baseline, the plantar microcirculation in the arterial stenosis group was significantly improved one month after surgery (51.9 ± 7.2, P < 0.05), while that in the nonarterial stenosis group was reduced (35.9 ± 7.2, P < 0.05). Based on preoperative HFCDU findings, diabetic foot patients can be divided into two categories: Those with nonarterial stenosis and those with arterial stenosis, with obvious differences in hemodynamic changes in the early postoperative period between them. In the early stage after TTT, the blood flow volume and velocity and the plantar microcirculation perfusion of the affected limb of the diabetic foot with nonarterial stenosis decreased compared with the baseline, while those of the diabetic foot with arterial stenosis improved significantly compared with the baseline, although both had smoothly healed diabetic foot ulcers.

Functional state of the endothelium in men after mine-explosive injury during the war in Ukraine

Mine-explosive trauma (MET) is the most common trauma type and one of the main disability causes of the able-bodied contingent. Among the mechanisms of the cardiovascular and cerebrovascular disorders development after MET, endothelial dysfunction (ED) plays an important role. The study aims - to assess the functional state of the microvessels and large arteries endothelium in men after a mine-explosive injury. Materials and methods: the functional state of the skin microvessels endothelium was determined using a two-channel laser Doppler flowmeter BLF-21D "Transonic Systems Inc" (USA) during the test with the creation of reactive hyperemia. The function of the large arteries endothelium was determined using the D.S. Celermajer test, with post-occlusion reactive hyperemia according to the generally accepted method on the Nemio XG device, SSA-580A (Toshiba) with a high-frequency linear sensor with a central frequency of 7 MHz. We examined men with mild MET (average age 37.7 ± 1.5 years). The control group was represented by 43 practically healthy men without MET (average age 41.8 ± 2.1 years). Results: dysfunction of the microvessels endothelium was found in most persons with MET (69.1%), compared to men without MET (41.9%). Dysfunction of the large vessels endothelium was found in 40.4% of examined persons with MET. Persons with MET have a combination of large and small vessel endothelial dysfunction in 23.4% of cases, at the same time persons without MET have a higher proportion of isolated microvessel endothelial dysfunction (34.9%). Conclusions: men with MET often have arterial endothelial dysfunction with microvascular endothelial dysfunction together, whereas men without MET have predominantly isolated microvascular endothelial dysfunction. ________________________________________________________________________________________ Keywords: mine-explosive injury; functional state of the endothelium; microcirculation.

Determination of Scalp Vascular Topography by Laser Doppler Flowmetry and Comparison of Vascular Damage by Different Blades in Hair Transplantation.

Although necrosis is a rare complication in hair transplantation, it is extremely traumatic for both the patient and surgeon and also has potential medicolegal consequence. Studies have shown that ischemia in the recipient bed is related to tissue damage caused by the instruments used and the number of grafts per cm². We aimed to measure the effects of different instruments on circulation by dividing the recipient area of hair grafts of the same person into 2 sides as right and left. Sapphire percutaneous blade was used on the right side, and a handmade razor slit was used on the left side in 12 male patients with consent. Subsequently, vascularity was evaluated with laser Doppler flowmetry. Scalp vascularity has so far only been evaluated with macroanatomic studies in the literature. First, the authors evaluated the effect of local anesthesia and adrenaline-containing swelling fluids on vascularity with a Laser Doppler Flowmeter. Afterward, the tissue damage caused by sapphire percutaneous blades and handmade blades (obtained from razor blades) were quantitatively analyzed and compared with each other. Our results showed that handmade razor blades caused significantly less tissue damage.

Laser Doppler Flowmeter as a Periodontal Evaluation Method: A Clinical Pilot Study

Background and objectives: Periodontal disease, as an inflammatory pathology, induces hemodynamic changes that can be evaluated by different unbiased methods such as laser Doppler flowmetry. This clinical investigation assesses laser Doppler as a non-invasive procedure to monitor gingival vascularization and its potential relationship with the response to treatment of periodontal disease. Materials &amp; methods: 45 sites of white Spanish patients with active periodontitis undertake a complete periodontal analysis. This included periodontal pathogens identification along with the monitoring of the gingival margin microvascularization using a Doppler laser at the points exhibiting the most periodontal damage. All assessments were performed before and after periodontal combined treatment PCT (scaling, root planing, and antibiotic therapy prescription) (n = 45 sites). Results: Parameters of periodontal disease showed a positive correlation with pathogen levels. Blood flow readings decreased significantly after PCT (p &lt; 0,05), although this parameter was not statistically correlated with periodontal nor microbial assessments in a significant range. Conclusion: Laser Doppler is a complementary method of monitoring periodontal inflammation to traditional techniques of clinical periodontal evaluation. Further studies are necessary to determine its usefulness as a predictive method of periodontal disease evolution.

Videocapillaroscopic monitoring of microcirculation in rats during photodynamic therapy

The proposed approach to microcirculation assessment is non-invasive, informative, and can be implemented during photoactivation, and thus is perspective both for research tasks and clinical practice. The functional principles of the vasculature response to photodynamic exposure, identified using this technique, also foster the efficiency and safety of photodynamic therapy. The developed setup allows simultaneous photodynamic exposure and studying the microcirculation parameters by videocapillaroscopy and photoplethysmography techniques. Photodynamic action is carried out by 662 nm laser radiation with a power density of 15 mW/cm2 in continuous and pulsed modes. The imaging system of the setup consists of a large working distance microscope, an optical filter, and a monochrome camera. The illumination system is based on LED with a central wavelength of 532 nm. The acquired images were processed in order to obtain morphometric and hemodynamic microcirculation data in the inspected skin area. To compare the proposed approach with existing methods, we measured blood flow parameters by a laser Doppler flowmeter. We tested the developed setup on rats injected with a photosensitizer and obtained active vessel maps, photoplethysmograms, and skin vessel density values before, during, and after photoactivation in both generation modes. The proposed approach allows to reveal differences in the microcirculation response to photodynamic effects of low power densities in different modes, in particular, the discrepancy between the time from the start of exposure to the cessation of blood flow and the start of the recovery period.

Remodeling of the cardiovascular hemodynamic environment by lower limb heat exposure: A computational fluid dynamic study

BackgroundLower limb heat exposure (LLHE) is a promising strategy for the daily management of cardiovascular health because of its non-pharmaceutical advantages. To support the application of this strategy in cardiovascular protection, we examined its impact on the global hemodynamic environment. MethodsSkin blood flow (SBF) of eight locations on the lower limbs was measured before and after LLHE (40 °C and 44 °C) in ten healthy subjects by using a laser Doppler flowmeter. A closed-loop model of circulation uses changes in SBF to quantify the influence of LLHE on the blood flow of the arterial trunk (from ascending aorta to the femoral artery) and visceral branches (coronary, celiac, renal, and mesenteric arteries). ResultsThe SBF in all locations tested on the lower limbs increased significantly (p<0.001) with LLHE and a 3.39-fold and 7.40-fold increase in mean SBF were observed under 40 °C and 44 °C conditions, respectively. In the model, the peak (3.9–25.1%), end-diastolic (13.7–107.3%), and mean blood flow (8.5–86.5%) in the arterial trunk increased with the increase in temperature, but the retrograde flow in the thoracic aorta and abdominal aorta Ⅰ increased at least twice in the diastolic period. Furthermore, LLHE also increased the blood flow of the visceral branches (2.5–20.7%). ConclusionThese findings suggest that LLHE is expected to be a daily strategy for enhancing the functions of both the arterial trunk and visceral arteries, but the increased blood flow reversal in the thoracic and abdominal aortas warrants further investigation.

Elucidating mechanisms of attenuated skin vasodilation during passive heat stress in persons with spinal cord injury

Objective Persons with spinal cord injury (SCI) are unable to efficiently dissipate heat via thermoregulatory vasodilation as efficiently as able-bodied persons during whole body passive heat stress (PHS). Skin blood flow (SkBF) is controlled by dual sympathetic vasomotor systems: noradrenergic vasoconstrictor (VC) nerves and cholinergic vasodilator (VD) nerves. Thus, impaired vasodilation could result from inappropriate increases in noradrenergic VC tone that compete with cholinergic vasodilation or diminished cholinergic tone. To address this issue, we used bretylium (BR) which selectively blocks neural release of norepinephrine, thereby reducing noradrenergic VC tone. If impaired vasodilation during PHS is due to inappropriate increase in VC tone, BR treatment will improve SkBF responses during PHS. Design Prospective interventional trial. Setting laboratory. Participants 22 veterans with SCI. Interventions Skin surface areas with previously defined intact vs. impaired thermoregulatory vasodilation were treated with BR iontophoresis with a nearby untreated site serving as control/CON. Participants underwent PHS until core temperature rose 1°C. Outcome Measures Laser doppler flowmeters measured SkBF over BR and CON sites in areas with impaired and intact thermoregulatory vasodilation. Cutaneous vascular conductance (CVC) was calculated for all sites. Peak-PHS CVC was normalized to baseline (BL): (CVC peak-PHS/CVC BL) to quantify SkBF change. Results CVC rise in BR sites was significantly less than CON sites in areas with intact (P = 0.03) and impaired (P = 0.04) thermoregulatory vasodilation. Conclusion Cutaneous blockade of neural release of noradrenergic neurotransmitters affecting vasoconstriction did not enhance thermoregulatory vasodilation during PHS in persons with SCI; rather BR attenuated the response. Cutaneous blockade of neural release of noradrenergic neurotransmitters affecting vasoconstriction did not restore cutaneous active vasodilation during PHS in persons with SCI.

High antioxidant load impairs cutaneous microvascular function in healthy women

PURPOSE: Human cutaneous circulation is used as an in vivo bioassay to examine mechanisms of systemic vascular dysfunction in cohorts of patients with accelerated cardiovascular disease risk. Local drug infusions, including atorvastatin (statin; LOX inhibitor) and systemic interventions to investigate anti-inflammatory mechanisms (e.g., oral salsalate) have been used to elucidate mechanisms underlying microvascular dysfunction. However, in healthy cohorts, high antioxidant load can attenuate total vasodilation and nitric oxide (NO)-dependent vasodilation. Thus, we aimed to examine endothelial function during high antioxidant load from these localized and systemic treatments in healthy control groups. We hypothesized that combined localized and systemic treatments will attenuate endothelial function in healthy women. METHODS: In a randomized placebo control design, oral salsalate (1500mg/twice daily/5 days) was used to assess the impact of systemic inflammation on cutaneous vascular function. Four intradermal microdialysis fibers were placed into the intradermal space of the ventral forearm of six healthy women (32±7 years). Laser-Doppler flowmeter probes, used to measure cutaneous blood flow, were placed in local heating units set to 33°C. Increasing concentrations of acetylcholine (ACh; endothelium-dependent vasodilator) from 10 -10 to 10 -1 M were co-perfused with one of the following: Lactated Ringer’s (control), 0.02 mM statin, 15 mM N G -nitro-L-arginine methyl ester (L-NAME; nitric oxide synthase inhibitor), and statin + L-NAME (COMBO) sequentially for 5 min each. Following the dose-response protocol, maximal cutaneous vasodilation was induced by increasing local skin temperature to 43°C and perfusing 28 mM sodium nitroprusside. Cutaneous vascular conductance (CVC) was calculated as the quotient of red blood cell flux and mean arterial pressure and normalized as a percentage of the site-specific maximum (%CVC max ). Data at each intervention were compared with control using a two-way (dose x site) analysis of variance. Responses at each dosage were compared using paired t-tests and corrected for multiple comparisons. RESULTS: Following oral salsalate, there was no difference in the %CVC max response to ACh with local L-NAME (p=0.896) or COMBO interventions (p=0.617) as compared to the placebo. However, following oral salsalate, there was a significant reduction in %CVC max in the statin treated site at higher ACh concentrations (10 -5 M, 10 -4 M, 10 -3 M; all p&lt;0.01). CONCLUSION: Endothelial function was attenuated when subjects were introduced to a combination of oral salsalate and statin localized treatments. Five-day oral salsalate intake and local statin may result in high antioxidant load in healthy women creating a shift in redox balance, thus leading to impaired endothelial function. Supported by NIH Grant R01 HL161000 This is the full abstract presented at the American Physiology Summit 2023 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.

Allyl isothiocyanate, an activator of TRPA1, increases gastric mucosal blood flow through calcitonin gene-related peptide and adrenomedullin in anesthetized rats

Allyl isothiocyanate (AITC) activates transient receptor potential ankyrin 1 (TRPA1) channel, which is involved in the control of intestinal mucosal blood flow. However, the mechanism underlying the increased gastric mucosal blood flow (GMBF) in response to AITC remains unknown. We examined the effect of AITC on GMBF in the ex vivo stomachs of normal and sensory deafferented rats using a laser Doppler flowmeter. Mucosal application of AITC increased GMBF in a concentration-dependent manner. Repeated AITC exposure resulted in a marked desensitization. The increased GMBF response induced by AITC was entirely blocked by co-application of TRPA1 channel blockers HC-030031 or AP-18. Increased GMBF in response to AITC was significantly attenuated by chemical deafferentation following systemic capsaicin injections (total dose: 100 mg/kg). In contrast, increased GMBF responses to capsaicin, a transient receptor potential vanilloid 1 (TRPV1) activator, were completely abolished by chemical deafferentation. The increased GMBF response to AITC was markedly inhibited by BIBN 4096, a calcitonin gene-related peptide receptor (CGRP) antagonist, or AGP-8412, an adrenomedullin receptor antagonist. These results suggest that AITC-stimulated TRPA1 activation results in the increased GMBF through the release of CGRP and adrenomedullin.

Soybean isoflavones alleviate cerebral ischemia/reperfusion injury in rats by inhibiting ferroptosis and inflammatory cascade reaction

To explore the mechanism that mediates the effect of soybean isoflavones (SI) against cerebral ischemia/reperfusion (I/R) injury in light of the regulation of regional cerebral blood flow (rCBF), ferroptosis, inflammatory response and blood-brain barrier (BBB) permeability. A total of 120 male SD rats were equally randomized into sham-operated group (Sham group), cerebral I/R injury group and SI pretreatment group (SI group). Focal cerebral I/R injury was induced in the latter two groups using a modified monofilament occlusion technique, and the intraoperative changes of real-time cerebral cortex blood flow were monitored using a laser Doppler flowmeter (LDF). The postoperative changes of cerebral pathological morphology and the ultrastructure of the neurons and the BBB were observed with optical and transmission electron microscopy. The neurological deficits of the rats was assessed, and the severities of cerebral infarction, brain edema and BBB disruption were quantified. The contents of Fe2+, GSH, MDA and MPO in the ischemic penumbra were determined with spectrophotometric tests. Serum levels of TNF-α and IL-1βwere analyzed using ELISA, and the expressions of GPX4, MMP-9 and occludin around the lesion were detected with Western blotting and immunohistochemistry. The rCBF was sharply reduced in the rats in I/R group and SI group after successful insertion of the monofilament. Compared with those in Sham group, the rats in I/R group showed significantly increased neurological deficit scores, cerebral infarction volume, brain water content and Evans blue permeability (P < 0.01), decreased Fe2+ level, increased MDA level, decreased GSH content and GPX4 expression (P < 0.01), increased MPO content and serum levels of TNF-α and IL-1β (P < 0.01), increased MMP-9 expression and lowered occludin expression (P < 0.01). All these changes were significantly ameliorated in rats pretreated with IS prior to I/R injury (P < 0.05 or 0.01). SI preconditioning reduces cerebral I/R injury in rats possibly by improving rCBF, inhibiting ferroptosis and inflammatory response and protecting the BBB.