Impaired Blood Flow Research Articles

CONGENITAL DEFECTS OF ANTERIOR ABDOMINAL WALL IN NEWBORNS: TRADITIONS AND NEW TENDENCIES

Introduction. The problem of treatment of newborns with congenital malformations of the anterior abdominal wallremains relevant due to the increasing number of malformations such as gastroschisis and omphalocele in newborns as wellas high complications and mortality.The aim of this work is to improve the effectiveness of treatment of newborns suffering from gastroschisis andomphalocele by optimizing pre-, intra- and postoperative management of patients.Material and research methods. The results of examination and treatment of 55 newborns with gastroschisis and 22 newbornswith omphalocele were analyzed for the period from 1993 to 2021. Examination algorithm included: antenatal counseling ofpregnant women, postnatal consultation and transportation of the newborn to the institution where the defect correction, clinical,laboratory and instrumental examination, bacteriological examinations, histological examination of surgical material, measurementof intra-abdominal pressure will be performed to determine adequate surgical correction of the malformation.Results and discussion. Studies in infants suffering from gastroschisis and omphalocele and viscero-abdominaldisproportion have shown an increase in the intra-abdominal pressure at all stages of correction, which significantly affectedthe mechanical properties of the lungs and manifested a decrease in lung distension, increased airway resistance andincreased inspiratory pressure. During surgical correction of viscero-abdominal disproportion at all stages of the study, themechanical properties of the newborn's lungs changed (compliance decreased, airway resistance increased), being directlydependent on the level of intra-abdominal pressure, as evidenced by the main groups of patients suffering from omphalocele.The maximum change in the mechanical properties of the lungs was observed at 24-48 hours after correction of visceroabdominal disproportion and coincided with the maximum figures for the increase in intra-abdominal pressure in newborns.Adequate lung ventilation under conditions of maximum increase in intra-abdominal pressure in newborns was achievedby increasing PIP to high numbers (up to 20-22 cm of water column) at 24-48 hours after correction of viscero-abdominaldisproportion with a gradual moderate decrease and retention of PEEP within the limits of 4-5 cm of water column.In the main groups of patients suffering from gastroschisis and omphalocele, normalization of disturbance of themechanical properties of the lungs (compliance and resistance) was faster than in the comparison groups. This was due to thefact that the level of intra-abdominal hypertension was taken into account when choosing the method of surgical correctionand infusion therapy in the mode of normovolemic hemodilution. In the study of peripheral hemodynamics (abdominal bloodflow) it was found that in the comparison groups in patients suffering from gastroschisis and omphalocele, higher indicesof resistance in the superior mesenteric and renal arteries, indicating impaired blood flow in the above vessels. In the main groups of patients suffering from gastroschisis and omphalocele, these indicators were significantly lower, which indicatesa better abdominal blood flow in patients in whom the choice of surgical correction method was taken into account whenchoosing the method of surgical correction.Intra-abdominal hypertension is one of the important reasons for the development of negative consequences when closingthe malformation of the anterior abdominal wall in newborns suffering from gastroschisis and omphalocele. Therefore,one of the main directions of improving the results of treatment of newborns with congenital malformation of the anteriorabdominal wall is the development and introduction of new methods for diagnosis of intraabdominal hypertension in practicalneonatal surgery and taking measures to prevent abdominal compartment syndrome.Depending on the condition of the child and the type of congenital malformation of the anterior abdominal wall, thetreatment tactics foresaw the following three options:1. Primary radical operation.2. Stage-by-stage surgical treatment.3. Conservative treatment followed by surgery.While analyzing the results of the study, it can be noted that a total of 26 newborns died of congenital defects of theanterior abdominal wall after surgery, including 18 children from the comparison group (1993-2004) and 8 from the mainstudy group (2005-2021), which amounted to 52,94% and 18,60% respectively. The main causes of death were neonatalsepsis, profound prematurity and severe comorbidities.Conclusions:1. Taking into account the results of treatment of newborns suffering from gastroschisis and omphalocele, it can bestated that the reduction of mortality in newborns by 3 times is primarily due to the introduction of neonatal surgery innew approaches to diagnosis, pre- and postoperative management, anesthesia and individualized surgical correction of thispathology.2. Intra-abdominal hypertension in case of congenital malformations of the anterior abdominal wall leads to a significantdeterioration of the mechanical properties of the lungs, hemodynamic disorders, oliguria, intestinal ischemia, decreasedorgan perfusion.3. Increased intra-abdominal hypertension was an indication for a change in surgical tactics - the abandonment of radicalplastic surgery of the abdominal wall and the transition to staged intervention or the use of surgical techniques that increasethe volume of the abdominal cavity.

Assessment of Diastolic Energy Loss in Hypertensives versus Controls

Increased energy loss (EL) during transmitral filling, if present in hypertensive subjects (HYT), can potentially inhibit normal intraventricular filling patterns that contribute to generating stroke volume.1 However, the presence, timing, and magnitude of EL in hypertension remain uncertain.2 Vector flow mapping (VFM) is a validated technology using color Doppler velocities to visualize intraventricular flow velocity vectors and derive estimates of EL.3 We hypothesized that VFM would reveal that hypertension increased left ventricular (LV) EL, causing impaired intracardiac diastolic blood flow efficiency.

Toward a Better Understanding of Muscle Microvascular Perfusion During Exercise in Patients With Peripheral Artery Disease: The Effect of Lower-Limb Revascularization

Purpose: Leg muscle microvascular blood flow (perfusion) is impaired in response to maximal exercise in patients with peripheral artery disease (PAD); however, during submaximal exercise, microvascular perfusion is maintained due to a greater increase in microvascular blood volume compared with that seen in healthy adults. It is unclear whether this submaximal exercise response reflects a microvascular impairment, or whether it is a compensatory response for the limited conduit artery flow in PAD. Therefore, to clarify the role of conduit artery blood flow, we compared whole-limb blood flow and skeletal muscle microvascular perfusion responses with exercise in patients with PAD (n=9; 60±7 years) prior to, and following, lower-limb endovascular revascularization. Materials and Methods: Microvascular perfusion (microvascular volume × flow velocity) of the medial gastrocnemius muscle was measured before and immediately after a 5 minute bout of submaximal intermittent isometric plantar-flexion exercise using contrast-enhanced ultrasound imaging. Exercise contraction-by-contraction whole-leg blood flow and vascular conductance were measured using strain-gauge plethysmography. Results: With revascularization there was a significant increase in whole-leg blood flow and conductance during exercise (p<0.05). Exercise-induced muscle microvascular perfusion response did not change with revascularization (pre-revascularization: 3.19±2.32; post-revascularization: 3.89±1.67 aU.s−1; p=0.38). However, the parameters that determine microvascular perfusion changed, with a reduction in the microvascular volume response to exercise (pre-revascularization: 6.76±3.56; post-revascularization: 2.42±0.69 aU; p<0.01) and an increase in microvascular flow velocity (pre-revascularization: 0.25±0.13; post-revascularization: 0.59±0.25 s−1; p=0.02). Conclusion: These findings suggest that patients with PAD compensate for the conduit artery blood flow impairment with an increase in microvascular blood volume to maintain muscle perfusion during submaximal exercise. Clinical Impact The findings from this study support the notion that the impairment in conduit artery blood flow in patients with PAD leads to compensatory changes in microvascular blood volume and flow velocity to maintain muscle microvascular perfusion during submaximal leg exercise. Moreover, this study demonstrates that these microvascular changes are reversed and become normalized with successful lower-limb endovascular revascularization.

Endothelial G protein stimulatory α-subunit is a critical regulator of post-ischemic angiogenesis.

Post-ischemic angiogenesis is a vital pathophysiological process in diseases such as peripheral arterial disease (PAD), heart ischemia, and diabetic retinopathy. The molecular mechanisms of post-ischemic angiogenesis are complicated and not fully elucidated. The G protein stimulatory alpha subunit (Gsα) is essential for hormone-stimulated cyclic adenosine monophosphate (cAMP) production and is an important regulator for many physiological processes. In the present study, we investigated the role of endothelial Gsα in post-ischemic angiogenesis by generating adult mice with endothelial-specific Gsα deficiency (GsαECKO). GsαECKO mice had impaired blood flow recovery after hind limb ischemic injury, and reduced neovascularization in allograft transplanted tumors. Mechanically, Gsα could regulate the expression of angiogenic factor with G patch and FHA domains 1 (AGGF1) through cAMP/CREB pathway. AGGF1 plays a key role in angiogenesis and regulates endothelial cell proliferation as well as migration. Knockdown of CREB or mutation of the CRE site on the AGGF1 promoter led to reduced AGGF1 promoter activity. In addition, knockdown of AGGF1 reduced the proangiogenic effect of Gsα in endothelial cells, and overexpression of AGGF1 reversed the impaired angiogenesis in GsαECKO mice in vivo. The finding may prove useful in designing new therapeutic targets for treatments of post-ischemic angiogenesis-related diseases.

Doppler Ultrasound Testing Suggests Hemorrhoids in Females may be a Consequence of Impaired Blood Flow Associated with Pelvic Organ Prolapse

Abstract Background It has been observed that there is a high incidence of hemorrhoids in female patients with pelvic organ prolapse. Also, in these patients, hemorrhoidal disease improves after the surgical correction of the pelvic organ prolapse. Objective Our hypothesis was that a cause-effect relationship between pelvic organ prolapse, and hemorrhoids might be the key. The objective of this study was to find an element which connects these two conditions. Study Design We conducted a pilot study which consisted of two parts. An initial part, in which we asked several patients with grades III and IV pelvic organ prolapse and hemorrhoids, who have undergone surgery for prolapse, to determine the impact of the surgical restoration of the prolapsed organs on their hemorrhoidal disease. For the second part, on several patients with uncorrected uterine prolapse grades III and IV, we determined the resistive index of the hemorrhoidal branches within the rectal wall before and after manual reduction of the prolapse. Results First, more than 50% of patients who underwent uterine prolapse correction described an improvement of their hemorrhoidal disease of over 50%. Second, the resistive index of the hemorrhoidal branches was significantly lower after manual reduction of the prolapse. We consider that obstructed veins due to pelvic organ prolapse might induce the dilation of the hemorrhoids. The direct measurement of the resistive index of the hemorrhoidal branches allows us to directly assess the increased resistance in the rectal vascular system. Conclusion Venous stasis and impaired vascular flow might be the pathophysiological explanation for the association between pelvic organ prolapse and hemorrhoids. In these patients, the pathogenic treatment should aim at the restoration of a normal blood flow (prolapse surgical cure) instead of focusing on hemorrhoids only.

MicroRNA therapeutic targets in neonatal hypoxic-ischemic brain injury: a narrative review.

Neonatal hypoxic-ischemic brain injury (HIBI) is a devastating injury resulting from impaired blood flow and oxygen delivery to the brain at or around the time of birth. Despite the use of therapeutic hypothermia, more than one in four survivors suffer from major developmental disabilities-an indication of the critical need for more effective therapies. MicroRNAs (miRNA) have the potential to act as biomarkers and/or therapeutic targets in neonatal HIBI as a step toward improving outcomes in this high-risk population. This review summarizes the current literature around the use of cord blood and postnatal circulating blood miRNA expression for diagnosis or prognosis in human infants with hypoxic-ischemic encephalopathy, as well as animal studies assessing endogenous brain miRNA expression and potential for therapeutic targeting of miRNA expression for neuroprotection. Ultimately, the lack of knowledge regarding brain specificity of circulating miRNAs and the temporal variability in expression currently limit the use of miRNAs as biomarkers. However, given their broad effect profile, ease of administration, and small size allowing for effective blood-brain barrier crossing, miRNAs represent promising therapeutic targets for improving brain injury and reducing developmental impairments in neonates after HIBI. IMPACT: The high morbidity and mortality of neonatal hypoxic-ischemic brain injury (HIBI) despite current therapies demonstrates a need for developing more sensitive biomarkers and superior therapeutic options. MicroRNAs have been evaluated both as biomarkers and therapeutic options after neonatal HIBI. The limited knowledge regarding brain specificity of circulating microRNAs and temporal variability in expression currently limit the use of microRNAs as biomarkers. Future studies comparing the neuroprotective effects of modulating microRNA expression must consider temporal changes in the endogenous expression to determine appropriate timing of therapy, while also optimizing techniques for delivery.

Clinical and Histological Effects of Partial Blood Flow Impairment in Vascularized Lymph Node Transfer.

Regarding vascularized lymph node transfer (VLNT) for lymphedema, partial blood flow impairment in transferred lymph node (LN) flaps may adversely affect the therapeutic results. We investigated the clinical and histological effects of partial blood flow impairment in LN flaps. In upper extremity lymphedema cases, based on ultrasonographic examination at 2 weeks after VLNT, we compared the treatment results depending on whether the postoperative blood flow in transferred LNs was good (Group G) or poor (Group P). Novel partial ischemia and congestion of LN flap mouse models were developed to determine their histological features. In 42 cases, significant differences were observed between Group G (n = 37) and Group P (n = 5) based on the amount of volume reduction (136.7 ± 91.7 mL and 55.4 ± 60.4 mL, respectively; p = 0.04) and lymph flow recanalization rate in indocyanine green fluorescent lymphography (67.6% and 0%, respectively; p = 0.0007). In mouse models, thrombi formation in the marginal sinus and numerous Myl9/12-positive immunocompetent cells in follicles were observed in congested LNs. Blood flow maintenance in the transferred LNs is an essential factor influencing the therapeutic effect of VLNT. Postoperatively, surgeons should closely monitor blood flow in the transferred LNs, particularly in cases of congestion.

Elevated endothelin-1 levels as risk factor for an impaired ocular blood flow measured by OCT-A in glaucoma

The purpose of this study was to ascertain whether a correlation exists between glaucoma-associated alteration of ocular vascular haemodynamics and endothelin-1 (ET-1) levels exist. Eyes of patients with cataract (n = 30) or glaucoma (n = 68) were examined with optical coherence tomography (OCT) and OCT-angiography (OCT-A; AngioVue™-RTVue-XR; Optovue, Fremont, California, USA). The peripapillary and the macular vessel density (VD) values were measured. Inferior and superior retinal nerve fibre layer (RNFL) thickness loss was used for further OCT staging. Aqueous humour of the examined eye and plasma were sampled during cataract or glaucoma surgery and analysed by means of ELISA to determine their ET-1 level. Glaucoma eyes are characterised by reductions in RNFL thickness and VD that correlate significantly with the OCT GSS score. Peripheral and ocular ET-1 level were significantly elevated in patients with glaucoma and correlate positively with the OCT-GSS score of the entire study population. Peripapillary and macula VD of glaucoma patients correlates negatively with plasma ET-1 levels. Multivariable analysis showed a subordinate role of intraocular pressure predictive factor for impaired retinal blood flow compared with plasma ET-1 level in glaucoma. Peripheral ET-1 level serves as risk factor for detection of ocular blood flow changes in the optic nerve head region of glaucomatous eyes.

The state of blood flow of the main arteries of the head in children with neurocirculatory dysfunction and connective tissue dysplasia

BACKGROUND: The article studies the relationship between connective tissue dysplasia and neurocirculatory dysfunction. They are united by a systematic and multi-organ nature of complaints and violations. The frequency of occurrence of neurocirculatory dysfunction in connective tissue dysplasia depends on the severity of phenotypic signs and is 23.531.1%.&#x0D; AIM: The aim of this study is to evaluate the significance of the method of duplex scanning of the main cerebral vessels, as well as to evaluate the relationship of the obtained parameters with the data of neurosonography, radiography of the cervical spine in children with signs of neurocirculatory dysfunction and connective tissue dysplasia.&#x0D; MATERIALS AND METHODS: The duplex scanning method was used to study the main vessels of the neck that provide blood supply to the brain: common and internal carotid, vertebral arteries in 240 children hospitalized for somatic various diseases.&#x0D; RESULTS: The presence of diagnostically significant changes in the cervical spine was found in 111 of them (46.3%): hypoplasia of the CI or СII vertebrae with cranial subluxations, instability of the cervical spine, and juvenile osteochondrosis. In children diagnosed with neurocirculatory dysfunction without signs of connective tissue dysplasia, disturbances in the form of asymmetry of blood flow along the entire vertebral artery prevail in comparison with the comparison group. In patients with more pronounced signs of connective tissue dysplasia, structural features of the cervical spine (hypoplasia of the CI or СII vertebrae with cranial subluxations, instability, juvenile osteochondrosis) and impaired blood flow of the main arteries are significantly more common.&#x0D; CONCLUSIONS: According to the data of duplex scanning of the main arteries of the neck, disorders in the form of hemodynamically significant asymmetry of blood flow in the vertebral arteries at different levels are significantly more common. In patients with pronounced signs of connective tissue dysplasia, structural features of the cervical spine and impaired blood flow of the main arteries of the neck are significantly more common. The presence of connective tissue dysplasia may be one of the causes of the above disorders.

Protective Mechanism of Electroacupuncture on Peripheral Neurotoxicity Induced by Oxaliplatin in Rats.

To study the effect of electroacupuncture (EA) on oxaliplatin-induced peripheral neuropathy (OIPN) in rats. Male Sprague-Dawley rats were equally divided into 3 groups using a random number table: the control group, the OIPN group, and the EA (OIPN + EA) group, with 10 rats in each. The time courses of mechanical, cold sensitivity, and microcirculation blood flow intensity were determined. The morphology of the dorsal root ganglion (DRG) was observed by electron microscopic examination. The protein levels of nuclear factor E2-related factor 2 (Nrf2), heme oxygenase-1 (HO-1), and the transient receptor potential (TRP) protein family in DRGs were assayed by Western blot. EA treatment significantly reduced mechanical allodynia and cold allodynia in OIPN rats (P<0.01). Notably, oxaliplatin treatment resulted in impaired microcirculatory blood flow and pathomorphological defects in DRGs (P<0.01). EA treatment increased the microcirculation blood flow and attenuated the pathological changes induced by oxaliplatin (P<0.01). In addition, the expression levels of Nrf2 and HO-1 were down-regulated, and the TRP protein family was over-expressed in the DRGs of OIPN rats (P<0.01). EA increased the expression levels of Nrf2 and HO-1 and decreased the level of TRP protein family in DRG (P<0.05 or P<0.01). EA may be a potential alternative therapy for OIPN, and its mechanism may be mainly mediated by restoring the Nrf2/HO-1 signaling pathway.

The nNOS and NeuN expression aspects in the cerebral cortex of rats with different cognitive abilities in cerebral hypoperfusion with short-term physical exercise

Introduction. Physical activity is often used in rehabilitation to restore cognitive function after cerebral blood flow impairment and typological features like baseline cognitive ability may alter their effectiveness.The aim was to evaluate the expression of nNOS and NeuN in the large hemisphere cortex in the cerebral hypoperfusion occurrence in rats having different scores in the Morris maze.Materials and methods. Cerebral hypoperfusion was simulated by bilateral ligation of the common carotid arteries. Before surgery, Wistar rats were divided into equal subgroups with high (HCA) and low levels of cognitive ability (LCA) according to the results of Morris maze testing. Animals were removed from the experiment at 8, 21, 35, 60, and 90 days after surgery, a total of 184 rats, 24 formed the control group and 80 formed the cerebral hypoperfusion subgroup with 80 animals undergoing short-term swimming daily starting on day 7 of the experiment.Results. We revealed the earlier changes in HCA animals (8th day of the experiment) induced by cerebral hypoperfusion accompanied by a more intense nNOS-positive neurons density reduction to 47 % of control values, the length of their processes, and an increase in pericarion area. In LCA the decrease of density was only 75 % of control values and pericarion area does not differ from control values. At later periods on the 60 and 90 days of the experiment LCA demonstrates the preservation of the neurons density and greater length of their processes (67 % of the control subgroup values).Conclusion. HCA is a risk factor for damage of nNOS-positive neurons in cerebral hypoperfusion. Physical exercise more effectively decreases nNOS expression in animals with HCA, which may be one of the sanogenetic mechanisms of this factor.

Случай осложненного течения перелома дистального метаэпифиза лучевой кости

INTRODUCTION: Zudek syndrome (neuroreflex algodystrophy, accompanied by osteoporosis, limited range of motion in the wrist and interphalangeal joints, impaired blood flow and associated trophic alterations) accounts for up to 62% of complications of fracture of the distal metaepiphysis of the radius. It may be a consequence of primary action of pathological factors (I type), or may result from compression of peripheral nerves (II type). The article describes a clinical case illustrating occurrence of almost all critical errors in the treatment process (non-performance of local anesthesia of the fracture and of reposition of fragments; fixation of the hand in a vicious (for this type of fracture) flexion position for up to 3 weeks; lack of local physiotherapy, anti-inflammatory and kinesitherapeutic treatment; use of “aggressive” mechanotherapy in passive restoration of the volume of movements and of “hard” massage against the background pain syndrome) that contributed to the development of the given II type complication. As a result, a surgical correction was required — corrective osteotomy of the radius to eliminate the cause of compression of the ulnar and median nerves and restore the interrelations between the articular surfaces in the wrist joint. CONCLUSION: Non-observance of the principles of treatment of a fracture of the radius in a “typical place” (emergency care; adequate anesthesia; immediate sparing reposition; subsequent clinical and radiological control, functional management; sufficient period of immobilization; early physiotherapy and kinesitherapy; etc.) may provoke such a threatening complication as Zudek syndrome characterized by a prolonged disability and inflicting physical and moral suffering. Besides, it is associated with a high cost of treatment and restoration of the function of the damaged limb, significantly exceeding the economic standard.

Endothelial Autophagy in Coronary Microvascular Dysfunction and Cardiovascular Disease.

Coronary microvascular dysfunction (CMD) refers to a subset of structural and/or functional disorders of coronary microcirculation that lead to impaired coronary blood flow and eventually myocardial ischemia. Amid the growing knowledge of the pathophysiological mechanisms and the development of advanced tools for assessment, CMD has emerged as a prevalent cause of a broad spectrum of cardiovascular diseases (CVDs), including obstructive and nonobstructive coronary artery disease, diabetic cardiomyopathy, and heart failure with preserved ejection fraction. Of note, the endothelium exerts vital functions in regulating coronary microvascular and cardiac function. Importantly, insufficient or uncontrolled activation of endothelial autophagy facilitates the pathogenesis of CMD in diverse CVDs. Here, we review the progress in understanding the pathophysiological mechanisms of autophagy in coronary endothelial cells and discuss their potential role in CMD and CVDs.

Relations of impaired blood flow and cerebrospinal fluid flow with damage of strategic for cognitive impairment brain regiones in cerebral small vessel disease

Introduction. Cerebral small vessel disease (CSVD), associated with age and vascular risk factors, as well as the main cause of vascular and degenerative mixed cognitive impairment (CI). Previously established microstructural predictors of CI (axial diffusion in normal-appearing periventricular white matter of the posterior left frontal lobe, the right midcingulate cortex, and the middle posterior part of the corpus callosum) can be used to calculate an integrative factor, exceeding the threshold value for which indicates the presence of CI. The use of this factor in the diagnosis of CI in CSVD is supported by the fact that leading mechanisms of CSVD are involved in the damage to areas of the brain that are strategic for CI. The aim of this study was to clarify the link between the known microstructural predictors of CI in CSVD and MRI findings that correspond to the main mechanisms of CSVD. Materials and methods. Patients (n = 74; including 48 women; average age 60.6 6.9 years) with CSVD and CI of varying severity underwent phase-contrast MRI and voxel-based morphometry (3T) to assess arterial, venous and CSF flow, as well as atrophy. Results. The established microstructural predictors of CI correlated with measures of arterial and venous blood flow, as well as atrophy. Linear regression models allow us to estimate cognitive impairment (CI) predictors in cerebral small vessel disease (CSVD), based on increased arterial velocity pulse index, CSF flow at the level of the cerebral aqueduct, cerebral aqueduct area and lateral ventricles volume, when there is reduced blood flow in the superior sagittal sinus and the overall arterial blood flow. Conclusion. The ability to calculate microstructural predictors of CI due to CSVD, based on MRI findings, indicates the validity of using an integrative measure of microstructural predictors of CI as a diagnostic tool of CI in CSVD.

Long COVID: Association of Functional Autoantibodies against G-Protein-Coupled Receptors with an Impaired Retinal Microcirculation.

Long COVID (LC) describes the clinical phenotype of symptoms after infection with the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Diagnostic and therapeutic options are limited, as the pathomechanism of LC is elusive. As the number of acute SARS-CoV-2 infections was and is large, LC will be a challenge for the healthcare system. Previous studies revealed an impaired blood flow, the formation of microclots, and autoimmune mechanisms as potential factors in this complex interplay. Since functionally active autoantibodies against G-protein-coupled receptors (GPCR-AAbs) were observed in patients after SARS-CoV-2 infection, this study aimed to correlate the appearance of GPCR-AAbs with capillary microcirculation. The seropositivity of GPCR-AAbs was measured by an established cardiomyocyte bioassay in 42 patients with LC and 6 controls. Retinal microcirculation was measured by OCT–angiography and quantified as macula and peripapillary vessel density (VD) by the Erlangen-Angio Tool. A statistical analysis yielded impaired VD in patients with LC compared to the controls, which was accentuated in female persons. A significant decrease in macula and peripapillary VD for AAbs targeting adrenergic β2-receptor, MAS-receptor angiotensin-II-type-1 receptor, and adrenergic α1-receptor were observed. The present study might suggest that a seropositivity of GPCR-AAbs can be linked to an impaired retinal capillary microcirculation, potentially mirroring the systemic microcirculation with consecutive clinical symptoms.

Brain-Derived Neurotrophic Factor And Coronary Artery Disease

Coronary artery disease (CAD) is defined as myocardial damage developing as a result of its organic and functional changes, and leading to impaired blood flow through the coronary arteries. An important pathogenetic component of CAD is atherosclerosis. Currently, key aspects of the molecular relationship between inflammation and atherosclerosis are being actively studied, the immunometabolic theory of atherosclerosis is being discussed, along with an involvement of perivascular adipose tissue in the pathogenesis of this pathology, due to its ability to respond to atherogenic stimuli via developing inflammatory reactions. Evidence has been accumulated that in patients with CAD, both in their blood and perivascular adipose tissue, the level of neurotrophic factors (in particular, brain-derived neurotrophic factor, BDNF) changes, which may be a promising area of research from the standpoint of studying this factor as a therapeutic target for atherosclerosis in CAD. Neurotrophic growth factors control the functioning of both immune and nervous systems, and the balance of energy metabolism and innervation of adipose tissue. They affect vascular homeostasis, and are also involved in causing and stopping inflammation. Currently, there are data on the role of BDNF in the pathogenesis of cardiovascular, neurodegenerative and metabolic diseases, and on the effect of polyunsaturated fatty acids and eicosanoids on the level of BDNF and, accordingly, the development and progression of coronary artery atherosclerosis. Our review summarizes published data (2019-2021) on the pathophysiological and pathogenetic mechanisms of the relationship between BDNF and CAD (atherosclerosis).

Additional effects of diosmin in the treatment of arterial hypertension in patients with impaired renal venous blood flow

Objective: to estimate of the effect of diosmin in complex antihypertensive therapy on renal function in patients with hypertension and impaired renal venous blood flow.Materials and methods: we observed 147 patients with hypertension aged 40.86±8.27 with signs of bilateral impairment of venous blood flow in the kidneys, which, depending on the amount of therapy, were divided into 2 groups and 2 subgroups. The comparison group consisted of 57 AH patients with unchanged venous blood flow in both kidneys.Results: in the presence of impaired venous blood flow in the renal veins, the use of additional administration of diosmin allows maintaining or improving the filtration capacity of the kidneys. Additional monitoring of patients with impaired venous blood flow in the kidneys is required to assess the effectiveness of antihypertensive therapy with individual drugs with and without venoactive agents.Conclusion: the additional inclusion of diosmin in the complex antihypertensive therapy of patients with arterial hypertension and impaired venous blood flow to the kidneys can preserve and improve kidney function with normalization of GFR.

Impaired postprandial adipose tissue microvascular blood flow responses to a mixed-nutrient meal in first-degree relatives of adults with type 2 diabetes.

Adipose tissue microvascular blood flow (MBF) is stimulated postprandially to augment delivery of nutrients and hormones to adipocytes. Adipose tissue MBF is impaired in type 2 diabetes (T2D). Whether healthy individuals at-risk of T2D show similar impairments is unknown. We aimed to determine whether adipose tissue MBF is impaired in apparently healthy individuals with a family history of T2D. Overnight-fasted individuals with no family history of T2D for two generations (FH-, n = 13), with at least one parent with T2D (FH+, n = 14) and clinically diagnosed T2D (n = 11) underwent a mixed meal challenge (MMC). Metabolic responses [blood glucose, plasma insulin, plasma nonesterified fatty acids (NEFAs), and fat oxidation] were measured before and during the MMC. MBF in truncal subcutaneous adipose tissue was assessed by contrast ultrasound while fasting and 60 min post-MMC. FH+ had normal blood glucoses, increased adiposity, and impaired post-MMC adipose tissue MBF (Δ0.70 ± 0.22 vs. 2.45 ± 0.60 acoustic intensity/s, P = 0.007) and post-MMC adipose tissue insulin resistance (Adipo-IR index; Δ45.5 ± 13.9 vs. 7.8 ± 5.1 mmol/L × pmol/L, P = 0.007) compared with FH-. FH+ and T2D had an impaired ability to suppress fat oxidation post-MMC. Fat oxidation incremental area under the curve (iAUC) (35-55 min post-MMC, iAUC) was higher in FH+ and T2D than in FH- (P = 0.005 and 0.009, respectively). Postprandial MBF was negatively associated with postprandial fat oxidation iAUC (P = 0.01). We conclude that apparently healthy FH+ individuals display blunted postprandial adipose tissue MBF that occurs in parallel with adipose tissue insulin resistance and impaired suppression of fat oxidation, which may help explain their heightened risk for developing T2D.NEW & NOTEWORTHY Adipose tissue blood flow plays a key role in postprandial nutrient storage. People at-risk of type 2 diabetes have impaired postmeal adipose tissue blood flow. Impaired adipose tissue blood flow is associated with altered fat oxidation. Risk of type 2 diabetes may be elevated by poor adipose tissue blood flow.

Acute occurrence and rupture of a dissecting basilar artery aneurysm in a patient with SARS-CoV-2

The article describes a clinical case of a dissecting basilar artery aneurysm in a patient with SARS-CoV-2. The patient was treated in the infectious diseases hospital for bilateral polysegmental pneumonia on the background of COVID-19. Suddenly, a focal neurological deficit occurred and grew in dynamics in the form of abducens nerve paresis, bulbar disorders, and right-sided hemiparesis. MSCT and MSCT-angiography were performed in dynamics. During the first examination, the pathology of the cerebral vessels was not revealed, but 10 days later, there was detected a fusiform aneurysm of the basilar artery with a diverticulum, the rupture of which led to massive hemorrhage and an unfavorable treatment outcome. The patient's primary symptomatology could be due to impaired blood flow in the perforating branches in the area of the started dissection of the basilar artery.

Abstract 5979: Evaluating therapeutic strategies against lung cancer using multispectral optoacoustic tomography

Abstract Tumor hypoxia is an important feature of the microenvironment in various types of tumors. The leaky and compressed vessels in the tumor lead to impaired blood flow and oxygen delivery and cause hypoxia. Significant tumor hypoxia exists in non-small cell lung cancer (NSCLC) and is closely associated with radiation-resistant and poor survival. Recently, we have identified a new class of antitumor drugs, cyclopamine tartrate (CycT) and heme-sequestering peptide 2 (HeSP2). They are heme-targeting agents that effectively inhibit NSCLC oxidative metabolism, oxygen consumption, and ATP generation, which lead to the suppression of tumor progression. By using multispectral optoacoustic tomography (MSOT), an advanced noninvasive imaging modality that monitors the changes in blood oxygen saturation and vascular function in real-time, we observed the effect of heme-targeting agents in normalizing tumor vasculature and alleviating tumor hypoxia. To investigate the impact of heme-targeting agent on mediating the lung cancer radiotherapy response, we characterized the vasculature and antigenic profile of NSCLC growth during the treatment of CycT in combination with radiotherapy by performing MSOT, together with other imaging approaches including bioluminescence imaging (BLI) and immunohistochemistry (IHC). We demonstrated that the heme-targeting agents increased tumor radiation sensitivity by regulating tumor vasculature and oxygenation. Our novel combination therapy can be a powerful strategy in improving the treatment of lung cancer and potentially other radiation-resistant cancers. Citation Format: Tianyuan Wang, Hashini Wanniarachchi, Lorena Arango, Li Zhang, Li Liu. Evaluating therapeutic strategies against lung cancer using multispectral optoacoustic tomography [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 5979.