Reduction Of Microcirculation Research Articles

A comprehensive update on the use of optical coherence tomography angiography in glaucoma.

The primary purpose of this review is to provide a comprehensive summary on the technical principles of OCTA and to enumerate vascular parameters being explicated for glaucoma diagnosis and progression with emphasis on recent studies. In addition, the authors also summarize the future clinical potentials of OCTA in glaucoma and enumerate the limitations of this imaging modality in the present-day scenario. The index study is a narrative review on OCTA in glaucoma. The authors searched the PubMed database using the key phrases ''optical coherence tomography angiography" AND "glaucoma,'' AND/OR "vascular parameters" AND/OR "ocular perfusion." Being a relatively recent development in ocular imaging, studies in which OCTA imaging had been used for glaucoma evaluation since 2012 were included until March 2022. The literature search included original studies and previous review articles, while case reports were excluded. Preliminary search was based on relevant articles with search keywords in the title and abstract. The second screening was performed by reading the full text of the literature. Recent studies indicate reduction in microcirculation in glaucomatous eyes compared to the normal subjects. The area of interest for glaucoma evaluation using OCTA varies among the different studies. Based on the literature reviewed here, (1) OCTA parameters measured in the peripapillary; ONH and macular area have been shown to differentiate between glaucoma and normal eyes with a discriminatory power comparable to OCT parameters used routinely in clinics, (2) monitoring of peripapillary and macular vessel density may provide important information to the evaluation of glaucoma progression and prediction of rates of disease worsening, (3) studies suggest strong correlation between the OCTA parameters, the OCT parameters and visual function, measured by visual field testing, in glaucomatous eyes, (4) future prospects of OCTA in glaucoma evaluations using AI predicting structural and functional features and prognosis based on early vascular findings would open up scope for early detection of high-risk suspects and fast progressors in glaucoma. OCTA can be useful in quantifying vascular parameters in the optic disc, peripapillary and the macular regions for glaucoma evaluation. OCTA shows potential to become a part of everyday glaucoma management.

Disorders of microcirculation in the mechanism of bisphosphonate osteonecrosis: preliminary study in rats.

We investigated the possibilities of angioprotection and the reduction of osteonecrosis in rats that had been given bisphosphonates. In our experiment, 27 rats were divided into three groups: Group 1 was injected with saline; Group 2 was given zoledronic acid for six weeks; and Group 3 was given zoledronic acid for six weeks, with added doses of sulodexide after three weeks. After that we constructed a model of how the teeth should be extracted. The velocity of linear blood flow in the periodontal area of an extracted tooth in rats was studied using laser and high-frequency Doppler ultrasound (with the application of the vasoactive substance acetylcholine 3% for 1min). We evaluated changes in the structure of the bony tissues of the head using computed tomography, comparing the control group with the saline group. A rapid reduction in microcirculation was detected during the use of zoledronic acid for six weeks. A smaller reduction in microcirculation was detected after three weeks of treatment with sulodexide and zoledronic acid. There was a reduction in blood flow in the mucous membranes and, to a greater extent, in bony tissue. Zoledronic acid causes significant impairment of the periosteal blood flow to the mucous membranes because of a complex of disorders, which includes both the cellular component (impaired endothelium-dependent vasodilation of the mucous membrane vessels) and by reducing the intensity of microcirculation in the mucous membranes and bony tissues. Sulodexide, however, improves the restoration of blood flow and reduces the severity of osteonecrosis.

The double edge of anti-CD40 siRNA therapy: It increases renal microcapillar density but favours the generation of an inflammatory milieu in the kidneys of ApoE\u2212/\u2212 mice

BackgroundChronic kidney disease (CKD) is associated with endothelial dysfunctions thus prompting links between microcirculation (MC), inflammation and major cardiovascular risk factors.Purpose of the studyWe have previously reported that siRNA-silencing of CD40 (siCD40) reduced atherosclerosis (ATH) progression. Here, we have deepened on the effects of the siCD40 treatment by evaluating retrospectively, in stored kidneys from the siCD40 treated ApoE−/− mice, the renal microcirculation (measured as the density of peritubular capillaries), macrophage infiltration and NF-κB activation.MethodsKidneys were isolated after 16 weeks of treatment with the anti-CD40 siRNA (siCD40), with a scrambled control siRNA (siSC) or with PBS (Veh. group). Renal endothelium, infiltrating macrophages and activated NF-κB in endothelium were identified by immunohistochemistry, while the density of stained peritubular capillaries was quantified by image analysis.ResultsATH was associated with a reduction in renal MC, an effect reversed by the anti-CD40 siRNA treatment (3.8 ± 2.7% in siCD40; vs. 1.8 ± 0.1% in siSC; or 1.9 ± 1.6% in Veh.; p < 0.0001). Furthermore, siCD40 treatment reduced the number of infiltrating macrophages compared to the SC group (14.1 ± 5.9 cells/field in siCD40; vs. 37.1 ± 17.8 cells/field in siSC; and 1.3 ± 1.7 cells/field in Veh.; p = 0.001). NF-κB activation also peaked in the siSC group, showing lower levels in the siCD40 and Veh. groups (63 ± 60 positive cells/section in siCD40; vs. 152 ± 44 positive cells/section in siSC; or 26 ± 29 positive cells/section in veh.; p = 0.014). Lastly, serum creatinine was also increased in the siCD40 (3.4 ± 3.3 mg/dL) and siSC (4.6 ± 3.0 mg/dL) groups when compared with Veh. (1.1 ± 0.9 mg/dL, p = 0.1).ConclusionsAnti-CD40 siRNA therapy significantly increased the density of peritubular capillaries and decreased renal inflammation in the ATH model. These data provide a physiological basis for the development of renal diseases in patients with ATH. Furthermore, our results also highligth renal off-target effects of the siRNA treatment which are discussed.Graphical abstract

Изменения микроциркуляции в области пародонта крыс под воздействием золедроновой кислоты

There is a rather high prevalence of oncological complications in the world, in particular, the development of osteonecrosis while using bisphosphonate drugs. There are several reasons for their development. We had a task to evaluate microcirculation in the development of medication-related osteonecrosis in an experimental model of rats. We administered the Zoledronic acid for 3 weeks to rats, and studied the line rate of blood flow using laser and high-frequency Doppler ultrasound in the periodontal area of an extracted tooth in rats with application of vasoactive substance Acetylcholine 3% for 1 min. The changes in the bone structure were assessed using computer tomography of the head of the examined rats. The results revealed a quick decrease in microcirculation against the background of the use of Zoledronic acid for 3 weeks. A decrease in blood flow in the mucous membrane and bone tissue was detected. The obtained data correlated with different hypotheses of the effect of bisphosphonates on the blood flow. Zoledronic acid causes a statistically significant impairment of the periosteal blood flow, the mucous membrane due to a complex of disorders, which includes the cellular component (impaired endothelium-dependent vasodilation of the mucous membrane vessels) and the reduction of microcirculation in the mucous membrane and bone tissue.

Combined Pharmacological Correction of Experimental Frostbite

Relevance Increased knowledge of the pathogenesis of frostbite and new pharmacological agents make it possible to improve the treatment results of local cold injury. This can be achieved, in particular, through the introduction of drug combination - the selective agonist of the delta-opioid receptors (DSLET) and the serotonergic agent (serotonin adipinate) which possesses analgesic, immunomodulatory, antioxidant and anti-inflammatory activity. The purpose of the study To investigate the effect of combined pharmacological treatment by DSLET and serotonin adipinate in experimental local frostbite. Materials and methods The study was conducted on 200 male Wistar rats. The local frostbite was inflicted with a preliminary cooled in liquid nitrogen metal plummet size 3.5-3.0 cm pressing against the shaved skin of the back during 3 min. Alongside with the standard antibiotic therapy (control) animals of the experimental groups were treated DSLET (10 mkg/kg intra-peritoneally (IP), serotonin adipinate (4.5 mg/kg IP) or its combination in indicated doses. Using the method of laser Doppler flowmetry the level of microcirculation was assessed as well as the biochemical changes in serum (malondialdehyde (MDA), interleukin-6 (IL-6), tumor necrosis factor alpha (TNF-α), superoxide dismutase (SOD), catalase) in all animals at 1, 3, 7 and 14 days after cold injury. Results and their discussion The model of local frostbite in control group resulted in reduction of microcirculation in necrosis boundary area at 1, 3, 7 and 14 days compared to the intact animals. The local frostbite injury induced oxidative stress and inflammation that were confirmed by typical dynamics of serum biochemical markers of non-treated rats while the significant increase the concentration of MDA, IL-6, TNF-α and decrease SOD activity were recognized. Also compensatory enhancement of catalase activity – one of the major antioxidant enzymes was observed. As well additional administration of drug combination DSLET (10 mkg/kg) with serotonin adipinate (4.5 mg/kg) to antibacterial treatment by cefotaxime in dose 0.085 g/kg increased the microcirculation by 27.2% compared to the non-treated group (р<0.05) at day 14 after damage due to frostbite injury in rats. A curative beneficial effect caused by combined pharmacological treatment of local frostbite was also confirmed by decrease of MDA concentration and pro-inflammatory cytokines IL-6 level at 1, 3, 5 and 7 days and by enhance of catalase and SOD activities at day 7 and 14 following experimentally induced frostbite. Conclusion Compared to monotherapy, combined usage of DSLET and serotonin adipinate provides a better pharmacological treatment efficiency in experimental model of local frostbite.

Comparative Evaluation of Enalapril and Losartan in Pharmacological Correction of Experimental Osteoporosis and Fractures of its Background

In the experiment on the white Wistar female rats (222 animals), the osteoprotective effect of enalapril and losartan was studied on experimental models of osteoporosis and osteoporotic fractures. It was revealed, that in rats after ovariectomy the endothelial dysfunction of microcirculation vessels of osteal tissue develops, resulting in occurrence of osteoporosis and delay of consolidation of experimental fractures. Enalapril and losartan prevented the reduction of microcirculation in bone, which was reflected in slowing the thinning of bone trabecules and in preventing the occurrence of these micro-fractures, as well as increasing quality of experimental fractures healing.

The management of septic shock.

Septic shock is a common emergency, most often caused by gram-negative bacteremia. Appearance of gram-negative endotoxin in the systemic circulation sets off a complex reaction involving many physiologic systems. The resultant reduction in microcirculation and subsequent organ dysfunction often lead to death. Early therapy to support the cardiovascular system and rational antibiotic therapy may improve the chance of survival. Careful monitoring of disease and drug effect parameters is essential to therapy.