Laser Doppler Flowmeter Research Articles

STUDY OF ENDOTHELIAL PROTECTIVE AND OSTEOPROTECTIVE PROPERTIES OF ROSUVASTATIN, L-NORVALINE AND THEIR COMBINATIONS IN EXPERIMENTAL OSTEOPOROSIS

Aim. Study of the effectiveness of pharmacological management of experimental osteoporosis with rosuvastatin, L-norvaline and their combination in comparison with strontium ranelate. Materials and methods. Simulation of hypoestrogenic osteoporosis was performed by bilateral oophorectomy in female Wistar rats. Four weeks after the surgery, the animals were administered study drugs during 4 weeks. After 12 weeks in the experimental animals, the parameters of intraosseous microcirculation of the proximal metaphysis of the femur were analyzed and the coefficient of endothelial dysfunction was calculated on the basis of laser Doppler flowmetry data. Calculation and registration of parameters of microcirculation were performed using the Biopac systems MP-150 laser doppler flowmeter and the TSD-144 needle sensor, and the results were processed using the AcqKnowledge version 4.1-4.2 software. For a comprehensive assessment of the formation of osteoporotic shifts and the effectiveness of therapy with the drugs studied, histomorphometry of the proximal metaphysis of the femurs was performed. When calculating the width of the bone trabecula, ImageJ version 1.39 was used. Results. It was found that L-norvaline and rosuvastatin in the doses under study in monotherapy and in combination significantly increase the parameters of regional intraosseous microcirculation of the vertex femur region. The investigated drugs and their combination, in comparison with the reference preparation, have an endothelial protective activity. This circumstance favorably affects intraosseous microcirculation, which contributes to the stable course of bone remodeling and prevents progression of osteoporotic disorders. In a morphometric study, it was established that L-norvaline, rosuvastatin, and their combination in these dosages prevented a decrease in the average width of bone trabeculae to the level of animals with experimental osteoporosis. Conclusion. L-norvaline, rosuvastatin and their combination in these dosages have a significant osteoprotective effect.

Peripheral circulation indicators in veteran trail runners.

[Purpose] Competitive sport places strict demands on the cardiovascular systems of veteran trail runners. Our research objective was to evaluate the dynamics of microcirculation parameters of veteran runners in hypoxic and mid-altitude conditions. [Subjects and Methods] Seven male runners from Russia and Italy between the ages of 50 and 60 years were examined whilst competing at mid-altitude (1,500–2,000 m above sea level). The same runners were examined in a simulated mid-altitude hypoxic environment, which was a hypoxic chamber with 16% oxygen concentration, for 720 minutes. Under both conditions, peripheral circulation was studied using a laser Doppler flowmeter attached to the distal phalange of the second finger of the subject’s right hand. All subjects had a microcirculation parameter assessed, which was the standard deviation of the erythrocytes flow vibration in peripheral circulation, under both conditions. In order to assess the intensity of vasomotor reactions of the microcirculatory vessels, the coefficient of variation was used. [Results] In the hypoxic environment, a decrease in the microcirculation parameter was noted in the short-term (360 minutes), with a subsequent compensatory increase in the long-term (720 minutes). However, the coefficient of variation showed a reverse trend with an increase in the vasomotor activity of microvessels from 12.4% to 18.2% at the stage of maximum training load within one month in the mid-altitude in the hypoxic environment, with a consequent reduction in preparation for the start. [Conclusion] In the hypoxic environment, the subjects demonstrated a two-stage change in the dynamics of the microcirculation parameter: an initial fall and a subsequent increase reaching the initial values. Similar changes were found when subjects were competing at mid-altitude. Our results show that the assessment of the peripheral circulation in a simulated mid-altitude hypoxic environment can be used to determine the readiness of veteran sportsmen for long-term trail running in mid-altitude conditions.

Laser doppler flowmeter and vascular diseases

Laser doppler flowmeter and vascular diseases

Sensitive detection of hemodynamic failure during orthostatic stress in patients with diabetic polyneuropathy using a mini laser Doppler blood flowmeter

Autonomic dysfunction in diabetes is serious but often underestimated. The purpose of this study was to evaluate hemodynamics within the important initial phase just after standing, which cannot be evaluated by conventional instruments for orthostatic hypotension. Earlobe blood flow (EBF), which indirectly reflects the blood pressure response on standing, was evaluated using a mini laser Doppler flowmeter during standing from the sitting position in 58 healthy controls and 56 diabetic patients categorized as without (11), mild (27), and advanced diabetic polyneuropathy (18). The response area of the EBF waveform within 30 seconds after standing was calculated. An increased response area indicates poor recovery of EBF. Response area increased significantly with the degree of neuropathy (P < .001 for linear trend). Orthostatic hypotension was detected in two patients in the mild neuropathy group. The present approach may be sensitive and practical for detecting autonomic dysfunction not detected with the conventional orthostatic test.

The coupling between peripheral microcirculation and slow breathing

Vasomotion (rhythmic changes in arteriolar diameter) is believed to enhance tissue perfusion at low oxygenation levels. We hypothesized that slow breathing and vasomotion may correlate temporally (“coupling”), especially at low oxygenation levels. We paced down spontaneous breathing to about 5 or 6breaths/min in 14 healthy subjects using device-guided breathing (DGB), and continuously monitored respiration, transcutaneous oxygen pressure (“oxygenation”), and skin capillary blood flow ("microflow”) using a laser Doppler flowmeter. The coupling was expressed by cross-correlation calculated in 1-min time windows. Our main results illustrated that: (1) coupling increased gradually upon slowing breathing down in a subgroup, in which initial oxygenation was lower than a threshold of 30mmHg (0.3±0.2 vs. 0.07±0.2, P<10−6); (2) during DGB changes in oxygenation elicited opposite (relative) changes in microflow, with 4-fold higher sensitivity for low initial oxygenation relative to high (regression slope −0.094±0.010mmHg−1 vs. −0.020±0.002mmHg−1, P<10−6); (3) at low initial oxygenation, we observed larger coupling and (relative) microflow changes in younger subjects, and greater oxygenation changes in females (P<10−6 for all); (4) pulse pressure changes from before to after DGB were reduced by increased oxygenation changes during DGB (−5.5±7.4mmHg, r=−0.73, P<0.001). In conclusion, the present methodology can provide the variation trend of respiration–vasomotion coupling during DGB that may characterize microcirculation behavior at tissue oxygenation below a measurable threshold. The potential association of these trends and thresholds with pathologies or specific conditions of the cardiopulmonary system, and the possible role played by the neural sympathetic activity in that coupling, deserve further studies.

Levosimendan Administration in Limb Ischemia: Multicomponent Signaling Serving Kidney Protection.

Aims and ObjectivesAcute renal failure is a severe complication of lower extremity major arterial reconstructions, which could even be fatal. Levosimendan is a dual-acting positive inotropic and vasodilatory agent, which is suspected to have protective effects against cardiac ischemia. However, there is no data available on lower limb or remote organ ischemic injuries therefore the aim of the study was to investigate the effect of levosimendan on lower limb ischemia-reperfusion injury and the corollary renal dysfunction.MethodsMale Wistar rats underwent 180 min bilateral lower limb ischemia followed by 4 or 24 hours of reperfusion. Intravenous Levosimendan was administered continuously (0.2μg/bwkg/min) throughout the whole course of ischemia and the first 3h of reperfusion. Results were compared with sham-operated and ischemia-reperfusion groups. Hemodynamic monitoring was performed by invasive arterial blood pressure measurement. Kidney and lower limb muscle microcirculation was registered by a laser Doppler flowmeter. After 4h and 24h of reperfusion, serum, urine and histological samples were collected.ResultsSystemic hemodynamic parameters and microcirculation of kidney and the lower limb significantly improved in the Levosimendan treated group. Muscle viability was significantly preserved 4 and 24 hours after reperfusion. At the same time, renal functional laboratory tests and kidney histology demonstrated significantly less expressive kidney injury in Levosimendan groups. TNF-α levels were significantly less elevated in the Levosimendan group 4 hours after reperfusion.ConclusionThe results claim a protective role for Levosimendan administration during major vascular surgeries to prevent renal complications.

Autologous fat injection therapy including a high concentration of adipose-derived regenerative cells in a vocal fold paralysis model: animal pilot study.

To verify the effectiveness and safety of the addition of adipose-derived regenerative cells to autologous fat injection therapy. Unilateral vocal fold paralysis models were made by cutting the right recurrent laryngeal nerve in two pigs. At day 30, 0.5 ml adipose-derived regenerative cells mixed with 1 ml autologous fat was injected into the right vocal fold of one pig, with the other receiving 0.5 ml Ringer's solution mixed with 1 ml autologous fat. At day 120, fibrescopy, laser Doppler flowmeter, computed tomography, vocal function evaluation and histological assessment were conducted. Although histological assessment revealed atrophy of the thyroarytenoid muscle fibre in both pigs, there was remarkable hypertrophy of the thyroarytenoid muscle fibre in the area surrounding the adipose-derived regenerative cells injection site. The addition of a high concentration of adipose-derived regenerative cells to autologous fat injection therapy has the potential to improve the treatment outcome for unilateral vocal fold paralysis.

Relationship of oscillating and average components of laser Doppler flowmetry signal.

Signals from laser Doppler flowmeters widely used in intravital studies of skin blood flow include, along with a slowly varying average component, an oscillating part. However, in most clinical studies, pulsations are usually smoothed by data preprocessing and only the mean blood flow is analyzed. To reveal the relationship between average and oscillating perfusion components measured by a laser Doppler flowmeter, we examined the microvascular response to the contralateral cold pressor test recorded at two different sites of the hand: dorsal part of the arm and finger pad. Such a protocol makes it possible to provide a wide range of perfusion. The average perfusion always decreases during cooling, while the oscillating component demonstrates a differently directed response. The wavelet analysis of laser Doppler flowmetry (LDF) signals shows that the pulsatile component is nonlinearly related to the average perfusion. Under low perfusion, the amplitude of pulsations is proportional to its mean value, but, as perfusion increases, the amplitude of pulsations becomes lower. The type of response is defined by the basal perfusion and the degree of vasoconstriction caused by cooling. Interpretation of the results is complicated by the nonlinear transfer function of the LDF device, the contribution of which is studied using artificial examples.

Inhibition of c-Jun N-terminal kinase signaling suppresses skin flap apoptosis in a rat ischemia and/or reperfusion model

BackgroundThe goals of this study were to validate the role of c-Jun N-terminal kinase (JNK) activation in skin flap apoptosis in a rat model of abdomen skin ischemia and/or reperfusion (IR) and to compare the protective effect of SP600125 and hydrogen-rich saline in skin IR injury. MethodsMale Sprague–Dawley rats were divided into five groups: one sham surgery group and four surgery groups. Before undergoing 3 h of IR management, the surgery groups were treated with normal saline (IR), dimethyl sulfoxide, SP600125 (SP), and hydrogen-rich saline (H). On the third postoperative day, blood perfusion of the flap was measured using Laser Doppler flowmeters. Hematoxylin and eosin staining was used to observe morphologic changes. Early apoptosis was observed using TdT-mediated dUTP-X nick end-labeling staining. pASK-1, pJNK, Bcl-2, and Bax were examined by immunodetection. Caspase-3 activity was also measured 24 h after reperfusion. ResultsCompared to the IR group and the dimethyl sulfoxide group, the SP group and the H group had larger skin flap survival area, more blood perfusion and lower levels of caspase-3 activity. The SP and the H groups had high expression levels of Bcl-2 and low expression levels of pASK-1 and pJNK. Bax was significantly decreased in the SP group. In addition, cell apoptosis was decreased in both the sham surgery and the H groups. ConclusionsIR-induced JNK phosphorylation was reduced by SP600125, indicating that JNK mediates the apoptosis pathways in rat skin. In the SP and the H groups, the apoptotic factors measured showed similar expression levels, indicating that JNK inhibition during IR may be associated with H-mediated protection against skin IR apoptosis.

Effect of full crown preparation on pulpal blood flow in man

ObjectiveTo determine if full crown preparation causes an increase in pulpal blood flow (PBF), indicating inflammation, in human subjects. DesignThe experiments were carried out on 35 intact, mandibular posterior teeth in 13 subjects: 32 were abutments for 16 fixed bridges that replaced first molars; the other 3 were first premolars adjacent to abutment teeth that served as un-operated controls. Crown preparations were made using an air-rotor with water-spray under regional block anaesthesia (4% articaine with epinephrine 1:100,000). PBF was recorded with a laser Doppler flow meter (LDF) before and after administering the anaesthetic, with the LDF probe on the buccal enamel. PBF was then recorded from the abutment teeth with the probe on buccal dentine after preparing the buccal surfaces of both teeth, after completing the crown preparations, and after 1 and 7days. PBF was also recorded from the buccal enamel of the control teeth on each occasion. ResultsThe mean±S.D. PBF values before and after anaesthesia were 2.63±2.13 and 2.42±2.38P.U. respectively, which were not significantly different (Paired t-test). The mean values for the abutment teeth after buccal preparation, after complete crown preparation, and after 1 and 7days were 5.20±2.49, 4.53±2.52, 4.92±2.98 and 5.48±2.65P.U. respectively. The 4 values for each tooth were not significantly different (two-way RM ANOVA). In the control group, the values under all six conditions were not significantly different. ConclusionsRegional block anaesthesia produced no change in PBF, nor did full-crown preparation, neither immediately after the procedure nor 1 and 7days later.

Changes in Maxillary Canine Pulpal Blood Flow During Dentoalveolar Distraction Osteogenesis.

The aim of this study was to assess the effects of dentoalveolar distraction osteogenesis (DD) on the pulpal blood flow (PBF) of maxillary canines. A laser Doppler flowmeter (LDF) was used to measure PBF in maxillary canines of 10 patients undergoing DD (study group) and 10 nonsurgical subjects who received no orthodontic treatment (control group). PBF was measured at baseline, at 4 and 7 days postoperatively, at the end of distraction and at the end of consolidation in the study group and at similar time-points in nonsurgical control subjects. Data were analyzed using paired and Student t tests, with the significance level set at 0.05. Study findings showed that baseline PBF values did not differ significantly between groups. PBF in the control group did not vary over time; however, in the study group, an initial decrease in PBF was observed at 4 days postoperatively and was followed by a gradual increase to preoperative levels at the end of distraction. During the DD latency period, there appears to be a short-lived ischemic phase when perfusion of pulp tissue declines; however, blood-flow returns to normal by the end of distraction.

Electromyographic Threshold and Microvascular Reactivity for Assessment of Muscle Fatigue in Elderly Women [1

INTRODUCTION: To analyze muscle fatigue in elderly women using two non-invasive methods, surface electromyography and laser-Doppler flowmetry. METHODS: The sample consisted of 60 sedentary elderly women of 65 to 85 years of age, all enrolled at the Open University for the Elderly (UAMA). The women in the intervention group (n=30) participated in a strength-training program, while the women in the control group (n=30) did not. The intervention group performed a strength-training program involving two sessions a week for sixteen weeks. The muscle fatigue evaluation was conducted through electromyographic fatigue threshold (EMGFT), also using the simultaneous evaluation of the results of electromyographic activity and 30-second chair stand test (CST) and flowmetric assessment of microvascular reactivity by laser-Doppler flowmeter. RESULTS: Muscle performance was improved in the intervention group, with a significant increase in muscle strength when the 30-second CST baseline values were compared with those registered following the intervention (9.63±1.90 repetitions/30 seconds versus 15.16±3.23 repetitions/30 seconds, respectively; P<.001). In addition, there was a statistically significant reduction in peripheral muscle fatigue according to the fatigue index, an improvement in neuromotor efficacy and an increase in EMGFT. The microvascular reactivity data obtained showed significant gains in the hyperemic area in the intervention group compared to the control group. CONCLUSION/IMPLICATIONS: The EMGFT protocol used to analyze the variables from the electromyographic signal and the PORH protocol used to evaluate microcirculation by laser-Doppler flowmetry can be applied to study muscle fatigue in the elderly.

The therapeutic effect of curcumin in male albino rats and its putative mechanisms on cerebral microvascular flow

The present study aimed to investigate the therapeutic effect of curcumin on hypertension and its putative mechanisms in the cerebral microcirculation. The surgical preparation was made to generate a cranial window for observation of the capillary network in the cerebral cortex region. Digital image processing, intravital videomicroscopy, and laser Doppler flow meter were used in this investigation. The number of open capillaries, arterial blood pressure, red cell velocity, microvascular diameter, circulating endothelial cells, relative blood flow and frequency were determined. Control rats showed severe dysfunction in the microcirculation with increased blood pressure. In curcumin treated mice, the blood pressure significantly reduced compared to their respective controls. Curcumin significantly increased blood velocity and LDF flow in hypertensive and normotensive rats. Curcumin significantly altered the circulating endothelial cells and open capillaries number in the male albino rats. Our results suggested that the curcumin exerts its therapeutic effect in male albino rats by regulating vasomotion function, increasing blood perfusion, releasing the peripheral resistance and opening efficiently capillaries. Taking all these data together, it is concluded that the curcumin might be useful in the regulation of the cerebral microcirculatory function and hypertension.

Quantification of the Blood Platelet Reactivity in the ADP-Induced Model of Non-Lethal Pulmonary Thromboembolism in Mice with the Use of Laser Doppler Flowmetry.

IntroductionThe paper describes an alternative method for quantification of in vivo ADP-induced thromboembolism. The aim of the studies was to develop a method of quantification which would not require either extravasation or labelling of platelets. Our proposed approach is based on the monitoring of changes of blood flow with the use of laser Doppler flowmetry.Materials and MethodsMice of C57Bl strain were used in the study. ADP was injected to the vena cava and blood flow was monitored with the use of a laser Doppler flowmeter in the mesentery. Measurements in platelet-depleted mice, mice pretreated with cangrelor, an ADP receptor antagonist, and eptifibatide, a blocker of fibrinogen binding to GPIIbIIIa, were conducted as the proof-of-concept in the performed experiments. Intravital microscopy and ex vivo imaging of organs was performed to identify the sites of aggregate formation resulting from ADP injection.ResultsThe injection of ADP resulted in a dose-dependent reduction of the blood flow in the mesentery. These responses were fully attributable to blood platelet aggregation, as shown by the lack of the effect in platelet-depleted mice, and significantly reduced responses in mice pretreated with cangrelor and eptifibatide. No platelet aggregate formation in mesenteric vessels was revealed by intravital microscopy, while ex vivo imaging showed accumulation of fluorescent labelled platelets in the lung.ConclusionsInjection of ADP to the venous system results in the formation of platelet aggregates predominantly in the lung. This results in reversible blood flow cessation in peripheral blood vessels. The measurement of this blood flow cessation in the mesentery allows indirect measurement of ADP-induced pulmonary thromboembolism. We suggest that this approach can be useful for in vivo screening for antiplatelet drug candidates.

Improvements in tissue blood flow and lumbopelvic stability after lumbopelvic core stabilization training in patients with chronic non-specific low back pain.

[Purpose] This study investigated the effects of lumbopelvic stabilization training on tissue blood flow changes in the lumbopelvic region and lumbopelvic stability compared to placebo treatment and controlled intervention among patients with chronic non-specific low back pain. [Subjects and Methods] A total of 25 participants (7 males, 18 females; mean age, 33.3 ± 14.4 years) participated in this within-subject, repeated-measures, double-blind, placebo-controlled comparison trial. The participants randomly underwent three types of interventions that included lumbopelvic stabilization training, placebo treatment, and controlled intervention with 48 hours between sessions. Lumbopelvic stability and tissue blood flow were measured using a pressure biofeedback device and a laser Doppler flow meter before and after the interventions. [Results] The repeated-measures analysis of variance results demonstrated a significant increase in tissue blood flow over the lumbopelvic region tissues for post- versus pre-lumbopelvic stabilization training and compared to placebo and control interventions. A significant increase in lumbopelvic stability before and after lumbopelvic stabilization training was noted, as well as upon comparison to placebo and control interventions. [Conclusion] The current study supports an increase in tissue blood flow in the lumbopelvic region and improved lumbopelvic stability after core training among patients with chronic non-specific low back pain.

Prototype of multi-channel Laser Doppler flowmeter

Prototype of multi-channel Laser Doppler flowmeter

Variable hyperemia of biological tissue as a noise source in the input optical signal of a medical laser Doppler flowmeter

As applied to the problems of medical laser Doppler flowmetry and based on a modified Kubelka–Munk two-flow model, analytic expressions have been obtained for the radiation power backscattered by biological tissue, taking into account the variable hyperemia of its microvasculature. An estimate is made of the power contribution of the Doppler component of the flow to the overall backscattered-radiation signal recorded by the device, which appears when light is scattered at moving erythrocytes. It is shown that the power contribution of the Doppler component to the overall backscattered radiation flux is no greater than 5% on average. The variable hyperemia that results from various physiological processes causes the radiation flux recorded by the Doppler flowmeter to be amplitude modulated. The power of the amplitude-modulated component can be of the same order of magnitude as, and in certain cases even greater than, the power of the useful Doppler signal, creating noise in the input signal of the device.

Protective effects of (6R)-5,6,7,8-tetrahydro-l-biopterin on local ischemia/reperfusion-induced suppression of reactive hyperemia in rat gingiva.

We herein investigated the regulatory mechanism in the circulation responsible for rat gingival reactive hyperemia (RH) associated with ischemia/reperfusion (I/R). RH was analyzed using a laser Doppler flowmeter. RH and I/R were elicited by gingival compression and release with a laser Doppler probe. RH increased in a time-dependent manner when the duration of compression was between 30 s and 20 min. This increase was significantly suppressed by Nω-nitro-l-arginine-methyl-ester (l-NAME), 7-nitroindazole (7-NI), and 2,4-diamino-6-hydroxypyrimidine (DAHP). However, RH was markedly inhibited following 60 min of compression. This inhibition was significantly decreased by treatments with superoxide dismutase (SOD), (6R)-5,6,7,8-tetrahydro-l-biopterin (BH4), and sepiapterin. The luminescent intensity of superoxide anion (O2•−)-induced 2-methyl-6-(4-methoxyphenyl)-3,7-dihydroimidazo-[1,2-a] pyrazine-3-one (MCLA) was markedly decreased by SOD and BH4, but only slightly by sepiapterin. BH4 significantly decreased O2•− scavenging activity in a time-dependent manner. These results suggested that nitric oxide (NO) secreted by the nitrergic nerve played a role in regulating local circulation in rat gingiva. This NO-related regulation of local circulation was temporarily inhibited in the gingiva by the I/R treatment. The decrease observed in the production of NO, which was caused by suppression of NO synthase (NOS) activity subsequent to depletion of the NOS co-factor BH4 by O2•−, played a partial role in this inhibition.

Thermal Pain and Pain Anticipation Induce a Decrease in Microvascular Perfusion in Sickle Cell and Normal Subjects

INTRODUCTION: Sickle cell disease is an inherited blood disorder characterized by vaso-occlusive crises (VOC). HbS in red blood cells (RBC) polymerizes rapidly after it releases oxygen to tissues, causing RBC to become rigid. Anything that decreases flow in the microvasculature increases the chance that this flexible-to-rigid transformation occurs causing the rigid blood cell to lodge in the microvasculature, therefore increasing the chance of vaso-occlusion and the risk of VOC. Although hypoxia and stress are known risk factors for crises, the exact mechanism that initiates VOC events is not well known. We have previously shown that transient hypoxia causes parasympathetic withdrawal and sighs cause vasoconstriction more frequently in SCD subjects than in normal controls. Pain is the hallmark of SCD and is a consequence of VOC but has not been considered as a possible trigger of vasoconstriction that may lead to VOC.OBJECTIVES: To determine if heat induced pain causes decrease in peripheral blood flow (PBF) in SCD.METHODS: 30 SCD and 30 control subjects (healthy and sickle cell traits) were recruited at Children's Hospital Los Angeles (CHLA). Quasi-periodic pulses of pain were induced on the right forearm using TSA-II neuro analyzer heating thermode.We implemented a technique using cross correlation analysis to detect changes in complex microvascular flow signals measured bilaterally on the hands, using laser-Doppler flowmeter (LDF), Peripheral Arterial Tonometer (PAT) and photo-plethysmography (PPG).We also measured the average drop from baseline in the microvascular flow during the heat pain. Data were analyzed using one- and two- sample Student t-test.RESULTS: Data on 53 subjects were analyzed. There was a significant correlation between heat pain pulses and PBF responses, as well as a significant drop in blood flow in all study participants (PPG signal, both p<0.001), indicating that heat pain pulses lead to vasoconstriction.Males had higher correlation (p<0.005) and stronger vasoconstriction (p<0.05) during heat stimuli compared to females. Other Signals (LDF and PAT) had a similar pattern but were less significant.The vasoconstriction response consisted of two components, the first one occurred prior to administration of the painful stimulus indicating that anxiety or anticipation of pain causes significant vasoconstriction. Application of the painful stimulus causes further vasoconstriction.CONCLUSIONS: The findings demonstrate a significant decrease in PBF in both SCD and controls in response to heat pain and possibly to pain anticipation. The decrease in PBF could play a critical role in the genesis of VOC in SCD by markedly prolonging microvascular transit time, increasing the likelihood of red cell entrapment when sickle red cells transform from flexible to rigid. Furthermore, the potent vasoconstriction response to pain in SCD means that pain resulting from VOC could potentially trigger a cascade effect in which vasoconstriction could lead to even more serious VOC. Since regional blood flow is regulated by the autonomic nervous system (ANS), which has been described to be dysfunctional in SCD, our study calls attention to the ANS as a factor in the genesis of crisis in this disorder. [Display omitted] DisclosuresNo relevant conflicts of interest to declare.

Protective effect of histamine microinjected into cerebellar fastigial nucleus on stress gastric mucosal damage in rats

In the study, we investigated the effect of histamine microinjected into cerebellar fastigial nucleus (FN) on stress gastric mucosal damage (SGMD), and its mechanisms in rats. The model of SGMD was established by restraining and water (21±1°C)-immersion for 3h. The gastric mucosal damage index (GMDI) indicated the severity of gastric mucosal damage. Histamine or receptor antagonist was microinjected into the FN. The decussation of superior cerebellar peduncle (DSCP) and the lateral hypothalamic area (LHA) were destroyed, respectively. The pathological changes of gastric mucosa were evaluated using biological signal acquisition system, Laser-Doppler flowmeter, and western blotting. We found that the microinjection of histamine (0.05, 0.5, and 5μg) into FN significantly attenuated the SGMD, in a dose-dependent manner, whereas, the microinjection of histamine H2 receptor antagonist, ranitidine, and glutamic acid decarboxylase antagonist, 3-mercaptopropionic acid (3-MPA) exacerbated the SGMD. The protective effect of histamine on SGMD was abolished by electrical lesion of DSCP or chemical ablation of LHA. The microinjection of histamine decreased the discharge frequency of the greater splanchnic nerve, and the gastric mucosal blood flow was increased. In addition, the cellular proliferation was enhanced, but the cellular apoptosis was reduced in the gastric mucosa. Also the pro-apoptosis protein, Bax, and caspase-3 were down-regulated, and the anti-apoptosis protein, Bcl-2 was up-regulated following microinjection of histamine. In conclusion, the FN participated in the regulation of SGMD after histamine microinjected into FN, and cerebellar–hypothalamic circuits (include: DSCP, LHA) contribute to the process, which may provide a new therapeutic strategy for SGMD.