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To substantially reduce the risk of hospitalization and death among subjects with heart failure (HF) and reduced left ventricular ejection fraction, it is necessary to make a comprehensive approach of the different neurohormonal systems that are implied in its etiopathogenesis, including not only sympathetic nervous system, and renin-angiotensin system, but also vasoactive peptides and sodium-glucose transport protein 2. The DAPA-HF trial demonstrated that the addition of dapagliflozin to the standard treatment in HF with reduced left ventricular ejection fraction, markedly decreases the risk of cardiovascular death, HF hospitalization and overall death. In addition, dapagliflozin improves functional class and quality of life. Importantly, the prognostic benefit starts early after initiating treatment with dapagliflozin, regardless baseline therapy or the presence of diabetes. All these evidences make dapagliflozin as one of the mainstays of treatment for the management of HF with reduced left ventricular ejection fraction.

BACKGROUND Multiple sclerosis (MS) is a chronic inflammatory neurodegenerative disease of the central nervous system. Vasoactive and intestinal peptide (VIP) and pituitary adenylate cyclase-activating peptide (PACAP) are neuropeptides that play roles in anti-inflammation and neuroprotection in MS. In this study, we aimed to determine the serum levels of VIP and PACAP in MS patients versus healthy controls and to correlate them with demographics and clinical characteristics. METHODS Serum samples were collected from MS patients (n = 145) and healthy controls (n = 73) to measure serum levels VIP and PACAP. RESULTS VIP serum levels were lower in MS patients than healthy controls (p

Sex differences in behaviour partly arise from the sexual dimorphism of brain anatomy between males and females. However, the sexual dimorphism of the tree shrew brain is unclear. In the present study, we examined the detailed distribution of vasoactive intestinal polypeptide-immunoreactive (VIP-ir) neurons and fibres in the suprachiasmatic nucleus (SCN) and VIP-ir fibres in the bed nucleus of the stria terminalis (BST) of male and female tree shrews. The overall volume of the SCN in male tree shrews was comparable with that in females. However, males showed a significantly higher density of VIP-ir cells and fibres in the SCN than females. The shape of the VIP-stained area in coronal sections was arched, elongated or oval in the lateral division (STL) and the anterior part of the medial division (STMA) of the BST and oval or round in the posterior part of the medial division of the BST (STMP). The volume of the VIP-stained BST in male tree shrews was similar to that in females. The overall distribution of VIP-ir fibres was similar between the sexes throughout the BST except within the STMA, where darkly stained fibres were observed in males, whereas lightly stained fibres were observed in females. Furthermore, male tree shrews showed a significantly higher intensity of Nissl staining in the medial preoptic area (MPA) and the ventral part of the medial division of the BST than females. These findings are the first to reveal sexual dimorphism in the SCN, BST and MPA of the tree shrew brain, providing neuroanatomical evidence of sexual dimorphism in these regions related to their roles in sex differences in physiology and behaviour.

Objective. To explore the clinical application of dynamic volume CT multiparameter imaging in the observation of penile hemodynamics in patients with abnormal vascular erections. Methods. 90 patients with suspected vascular abnormal erections treated in our hospital from January 2016 to January 2020 were included in the study, and 40 patients with psychologically abnormal erections were selected for the control. The corpus cavernosum injection vasoactive drug test (ICI) and dynamic volume CT and Doppler ultrasound were used to test the hemodynamics of the corpus cavernosum of all selected patients and to analyze the changes of penile length, circumference, systolic peak flow rate, diastolic peak flow rate, and blood flow resistance index in different types of penile erection disorder patients before and after ICI test. Results. Among the 90 patients with suspected vascular abnormal erection, 34 patients had arterial abnormal erection, 25 patients had venous abnormal erection, and 31 patients had mixed vascular abnormal erection. In patients with arterial abnormal erection and mixed vascular abnormal erection, penile cavernous body diameter, PSV, and abnormal erection V are smaller than those in patients with venous abnormal erection and psychological abnormal erection, while arterial abnormal erection and psychological abnormal erection are obviously higher in RI than venous abnormal erection and mixed vascular abnormal erection, and the difference is statistically significant ( P < 0.05 ). Before the ICI test, there was no significant difference in the penis circumference and length between the four groups of patients with arterial abnormal erection, venous abnormal erection, mixed vascular abnormal erection, and psychological abnormal erection ( P > 0.05 ); after the ICI test, patients with arterial abnormal erections had significantly shorter penis perimeter and penis length than those with venous abnormal erections, mixed vascular abnormal erections, and psychological abnormal erections ( P < 0.05 ). Conclusion. Dynamic volume CT can clearly reflect the penile hemodynamic state of patients with vascular abnormal erections, provide a powerful diagnostic basis for accurately and effectively determining the classification of vascular abnormal erections, and be worthy of popularization and clinical use.

Summary Crosstalk between endothelial cells (ECs) and pericytes or vascular smooth muscle cells (VSMCs) is essential for the proper functioning of blood vessels. This balance is disrupted in several vascular diseases but there are few experimental models which recapitulate this vascular cell dialogue in humans. Here, we developed a robust multi-cell type 3D vessel-on-chip (VoC) model based entirely on human induced pluripotent stem cells (hiPSCs). Within a fibrin hydrogel microenvironment, the hiPSC-derived vascular cells self-organized to form stable microvascular networks reproducibly, in which the vessels were lumenized and functional, responding as expected to vasoactive stimulation. Vascular organization and intracellular Ca2+ release kinetics in VSMCs could be quantified using automated image analysis based on open-source software CellProfiler and ImageJ on widefield or confocal images, setting the stage for use of the platform to study vascular (patho)physiology and therapy., Graphical abstract, Highlights • 3D VoC formed by hiPSC-ECs and hiPSC-VSMCs • Vascular organization in 3D VoC formed by hiPSC-VSMC and primary mural cells • Functional responses of hiPSC-VSMCs in 3D VoC • Automated analysis of microvascular network morphology and Ca2+ release in VSMCs, In this article, Orlova and colleagues describe the generation of an entirely human induced pluripotent stem cells (hiPSC)-derived vessel-on-chip composed with endothelial cells (ECs) and vascular smooth muscle cells (VSMCs). Changes in microvascular network architecture and intracellular Ca2+ release kinetics could be quantified during vascular organization or upon drug treatment providing a useful platform to study vascular development and disease.

BACKGROUND To explore the effect mechanism of "treat the spleen" therapy on immune thrombocytopenia (ITP) based on the characteristics of vasoactive factors. METHODS The ITP mice model was established by passive immunomodeling. 120 successfully modeled BALB/c mice were randomly divided into 6 groups: normal group, model group, prednisone group, Guipi Decoction group, Jianpi Yiqi group, and Jianpi Shexue group. These mice were treated with medicine for 16 days. After treatment, the platelet (PLT) counts and the degree of bleeding were evaluated, and the serum ET-1, NO, NOS3, TXA2, PGI2, vWF, VCAM-1, and TM contents of the model mice were detected by enzyme-linked immunosorbent assay (ELISA). RESULTS The PLT counts in peripheral blood of mice in each experimental group significantly decreased compared with that in the normal group (P

Эндотелиальные клетки, выстилающие стенки сосудов, преобразовывают деформацию собственных структур, вызванную током крови, в химические сигналы, одним из которых является важный регулятор просвета сосуда - оксид азота (NO). К настоящему моменту накоплен большой объём данных о клеточных механизмах активации продукции NO, однако сведений о динамике генерации оксида азота эндотелиальными клетками в зависимости от гидродинамических условий недостаточно. В этой связи разработка микрофлюидных систем in vitro, имитирующих кровеносное русло, и изучение в них эндотелия в сложных гидродинамических условиях является актуальной задачей. В данной работе для создания контролируемых гидродинамических условий для монослоя эндотелиоцитоподобных клеток EA.hy926 была спроектирована и разработана микрофлюидная система, имитирующая линейные участки микрососудистого русла. Методом непрямого определения содержания оксида азота (II) NO с использованием флуоресцентного зонда 4,5-диаминофлуоресцеина DAF-2 впервые получены данные об увеличении продукции NO клетками EA.hy926 при механическом стрессе, создаваемом потоком ростовой среды. Представлены расчетные гидродинамические характеристики микрофлюидной системы, а также методика измерения продукции NO. Возможность исследования функциональной активности эндотелия позволяет использовать разработанную микрофлюидную модельную систему как для изучения клеточно-автономных регуляторных свойств эндотелия при действии ряда вазоактивных фармакологических препаратов и других методов воздействия на эндотелий, так и при моделируемой дисфункции эндотелия. Endothelial cells lining vascular walls transform the flow-induced deformation of their own structures into chemical signals, one of which, nitric oxide (NO), is an important regulator of the vascular lumen diameter. By present, a large amount of data on cellular mechanisms for activation of NO production has been accumulated. However, there is insufficient information on changes in endothelial NO generation under different hydrodynamic conditions. Therefore, development of microfluidic systems that model blood vessels in vitro and using them to study the endothelium under complex hydrodynamic conditions are relevant tasks. In this study, a microfluidic system was developed to create controlled hydrodynamic conditions for a monolayer of endotheliocyte-like cells EAhy.926. This system simulates linear sections of the microvasculature. By indirect measurement of NO (II) content with a fluorescent 4,5-diaminofluorescein (DAF-2) probe, we showed an increase in the NO production by EAhy.926 cells under mechanical stress generated by the medium flow. The article presents the method for measuring NO production and the calculated hydrodynamic characteristics of the microfluidic system. The results showed that the developed microfluidic model system is promising for studying cell-autonomous regulatory properties of the endothelium both under the action of vasoactive agents and in simulated endothelial dysfunction.

Background The efficiency of transdermal drug delivery may be increased by pretreating the skin with microneedles, but distinct effects of microneedles and the microneedle-enhanced delivery of vasoactive drugs on the skin microvasculature are still not well investigated. Materials and methods In eight healthy human subjects, we measured the microvascular response to microneedle-induced microtraumas in the skin microvasculature using polarized light spectroscopy imaging (Tissue Viability imaging, TiVi). The microvascular response was assessed for up to 48 hours for three microneedle sizes (300 µm, 500 µm, and 750 µm) and for different pressures and application times. Results In our results, microneedle application increased the local red blood cell (RBC) concentration for up to 24 hours dependent on the needle lengths, applied time, and force. Conclusion Optimization of microneedles size, pressure, and application time should be taken into account for future protocols for drug delivery and experimental provocations.

This chapter explores the role that sex hormones play in the development and progression of renal disease. Possible pathogenic mechanisms are described including the effects of sex hormones on cell biology and on the synthesis and release of vasoactive factors and inflammatory and profibrotic cytokines. Next, the role of sex hormones in influencing repair and regeneration following renal injury is discussed and possible pathogenic mechanisms explored. In light of the paucity of data that examine interactions between sex hormones and regeneration in the kidney, this chapter also draws on data which examine the role of sex hormones in the regeneration of nonrenal tissue to suggest avenues for future translational research involving the kidney.

Spontaneous and sensory-evoked activity propagates across varying spatial scales in the mammalian cortex, but technical challenges have limited conceptual links between the function of local neuronal circuits and brain-wide network dynamics. We present a method for simultaneous cellular-resolution two-photon calcium imaging of a local microcircuit and mesoscopic widefield calcium imaging of the entire cortical mantle in awake mice. Our multi-scale approach employs an orthogonal axis design where the mesoscopic objective is oriented above the brain and the two-photon objective is oriented horizontally, with imaging performed through a microprism. We also introduce a viral method for robust and widespread gene delivery in the mouse brain. These approaches allow us to identify the behavioral state-dependent functional connectivity of pyramidal neurons and vasoactive intestinal peptide (VIP)-expressing interneurons with long-range cortical networks. Our novel imaging system provides a powerful strategy for investigating cortical architecture across a wide range of spatial scales., Reporting summary Further information on research design is available in the Life Sciences Reporting Summary linked to this article.

The vast majority of the brain's vascular length is composed of capillaries, where our understanding of blood flow control remains incomplete. This review synthesizes current knowledge on the control of blood flow across microvascular zones by addressing issues with nomenclature and drawing on new developments from in vivo optical imaging and single-cell transcriptomics. Recent studies have highlighted important distinctions in mural cell morphology, gene expression, and contractile dynamics, which can explain observed differences in response to vasoactive mediators between arteriole, transitional, and capillary zones. Smooth muscle cells of arterioles and ensheathing pericytes of the arteriole-capillary transitional zone control large-scale, rapid changes in blood flow. In contrast, capillary pericytes downstream of the transitional zone act on slower and smaller scales and are involved in establishing resting capillary tone and flow heterogeneity. Many unresolved issues remain, including the vasoactive mediators that activate the different pericyte types in vivo, the role of pericyte-endothelial communication in conducting signals from capillaries to arterioles, and how neurological disease affects these mechanisms. Expected final online publication date for the Annual Review of Physiology, Volume 84 is February 2022. Please see http://www.annualreviews.org/page/journal/pubdates for revised estimates.

Red blood cell concentration influences the pulmonary vasculature via direct frictional force and vasoactive signaling, but whether the magnitude of the response is modified with duration of exposure is not known. By assessing the pulmonary vascular response to hemodilution in acute normobaric and prolonged hypobaric hypoxia in lowlanders and lifelong hypobaric hypoxemia in Andean natives, we demonstrated that a reduction in red cell concentration augments the vasoconstrictive effects of hypoxia in lowlanders. In high-altitude natives, hemodilution lowered pulmonary vascular resistance, but a compensatory increase in cardiac output following hemodilution rendered PASP unchanged.

We thank Dr. Bugnicourt and Dr. Godefroy for their comments on our article.1 We agree with their statements on the potential release of vasoactive factors during migraine aura and on the limitations around reversibility and the potentially low prevalence of an index vein. Naturally, a case series has to deal with the data given, and only 1 patient had follow-up imaging. The aim of our study was to introduce the phenomenon of the index vein. It would be of incredible value to calculate accuracy measures of the index vein for making the diagnosis of migraine aura in the emergency setting. We therefore strongly encourage using the definition of the index vein provided in our study for future studies to obtain sensitivity, specificity, and negative or positive predictive values of this finding. The question of involvement of the cerebral arteries during migraine aura for reversible vasoconstriction—although important—has not been the focus of this case series and remains to be determined. In this respect, time-of-flight MR angiography was indeed normal in all reported patients.

Hierarchy in sensory processing is reflected by the innervation balance on cortical interneurons in the corticothalamic network., Sensory processing is subjected to modulation by behavioral contexts that are often mediated by long-range inputs to cortical interneurons, but their selectivity to different types of interneurons remains largely unknown. Using rabies-virus tracing and optogenetics-assisted recording, we analyzed the long-range connections to various brain regions along the hierarchy of visual processing, including primary visual cortex, medial association cortices, and frontal cortices. We found that hierarchical corticocortical and thalamocortical connectivity is reflected by the relative weights of inputs to parvalbumin-positive (PV+) and vasoactive intestinal peptide–positive (VIP+) neurons within the conserved local circuit motif, with bottom-up and top-down inputs preferring PV+ and VIP+ neurons, respectively. Our algorithms based on innervation weights for these two types of local interneurons generated testable predictions of the hierarchical position of many brain areas. These results support the notion that preferential long-range inputs to specific local interneurons are essential for the hierarchical information flow in the brain.

Cerebrovascular reactivity (CVR) is defined as the ratio of the cerebral blood flow (CBF) response to an increase in a vasoactive stimulus. We used changes in blood oxygenation level-dependent (BOLD) MRI as surrogates for changes of CBF, and standardized quantitative changes in arterial partial pressure of carbon dioxide as the stimulus. Despite uniform stimulus and test conditions, differences in voxel-wise BOLD changes between testing sites may remain, attributable to physiologic and machine variability. We generated a reference atlas of normal CVR metrics (voxel-wise mean and SD) for each of two sites. We hypothesized that there would be no significant differences in CVR between the two atlases enabling each atlas to be used at any site. A total of 69 healthy subjects were tested to create site-specific atlases, with 20 of those individuals tested at both sites. 38 subjects were scanned at Site 1 (17F, 37.5 ± 16.8 y) and 51 subjects were tested at Site 2 (22F, 40.9 ± 17.4 y). MRI platforms were: Site 1, 3T Magnetom Skyra Siemens scanner with 20-channel head and neck coil; and Site 2, 3T HDx Signa GE scanner with 8-channel head coil. To construct the atlases, test results of individual subjects were co-registered into a standard space and voxel-wise mean and SD CVR metrics were calculated. Map comparisons of z scores found no significant differences between white matter or gray matter in the 20 subjects scanned at both sites when analyzed with either atlas. We conclude that individual CVR testing, and atlas generation are compatible across sites provided that standardized respiratory stimuli and BOLD MRI scan parameters are used. This enables the use of a single atlas to score the normality of CVR metrics across multiple sites.

The right-sided heart failure (RSHF) is a complex clinical syndrome including different pathogenic mechanisms and processes resulted from the right ventricle (RV) dysfunction and manifested with signs of heart failure (HF). Recently, there is a growing scientific interest in the right-sided acute and chronic heart abnormalities; this is due to growing knowledge in this field and development of novel diagnostic, therapeutic and pharmacological approaches to treatment of pulmonary hypertension that is a common cause of RSHF. Cardiac embryogenesis, anatomic particularities, difference and interdependence of RV and the left ventricle (LV) are described in the article in order to improve the knowledge on structure and function of both the right heart and the left heart. Discussion on pathophysiology, causes and clinical manifestations of acute RSHF (aRSHF) and chronic RSHF (cRSHF) should consider the right heart physiology. Pharmacological treatment should be targeted to ventricle pre-load, myocardial contractility and RV post-load, correction of pulmonary circulation and LV volume resulting in post-load reduction and improvement in the LV function. Patients with biventricular dysfunction should be treated according to current clinical guidelines on therapy of chronic HF. Vasoactive agents and diuretics have an important role for the treatment of RSHF as this is the basic therapy of pulmonary congestion both in aRSHF and cRSHF. Step-by-step therapeutic algorithm is given in the article.

Background: Functional pancreatic neuroendocrine tumors (f-PanNETs) are rare tumors of the pancreas that are associated with excess hormone production. A majority of literature available on these tumors is limited to case reports and small series and discusses a particular subtype. Here, we report the clinicopathological features and outcomes of all f-PanNETs from a high-volume pancreatectomy center. Methods: A prospectively maintained database was used to identify patients who underwent resection for f-PanNETs between January 1995 and December 2015. Patients were stratified by the type of f-PanNET, and their clinicopathological features and outcomes were analyzed and reported. Results: We identified 69 patients with a mean age of 52 ± 16 years, and the majority were female (62%). The most common type of f-PanNET were insulinomas (70%) followed by gastrinomas (15%), and vasoactive intestinal peptidomas (VIPomas) (10%). There was considerable heterogeneity in the presenting symptoms. Patients with insulinomas presented with smaller tumors compared to the other subtypes. Nodal disease was most frequent in patients with VIPomas (71 %), and gastrinomas (50%). The median overall survival (OS) was 7.4 years. Elevated Ki-67 and age >65 years were associated with poorer OS. Recurrence was observed in 8 patients (12%) and was most frequent in patients with VIPomas. Recurrence was associated with a poorer OS (P=.012). Conclusion: f-PanNETs are exceedingly rare and present with a wide variety of symptoms, histopathological findings, and outcomes. Surgical resection can help achieve good long-term survival. Key words: Functional tumor; Outcome; Pancreatic neuroendocrine tumor

The essential role of executive control is to select the most appropriate behavior among other candidates depending on the sensory information (exogenous information) and on the subject's internal state (endogenous information). Here I review series of the evidence implicating that the rodent prefrontal cortex (PFC) evaluates and compares the expected outcome for candidate actions that are automatically primed by exogenous and endogenous information, and selects the most appropriate action while inhibiting the others, with different PFC subregions contributing to distinct aspects of the computation via differential recruitments of the distributed networks. The recurrent nature of the PFC networks further facilitates the computation by integrating bottom-up signals over a long timescale. I also overview the local circuit organization in the PFC, where vasoactive intestinal peptide-positive (VIP) GABAergic interneurons are tightly linked with the cholinergic system and play significant roles in regulating executive control signals. The empirical evidence inspires the disinhibitory module hypothesis of the PFC organization that a group of pyramidal neurons and interneurons forms a disinhibitory module with similar task-variable selectivity in the PFC, and long-range inputs and neuromodulations in these modules exert a distributed gain modulation of the ongoing executive control signals by adjusting VIP neuron activity.

Complex regional pain syndrome (CRPS) is a perplexing painful syndrome of the extremities usually following a harmful event. It is distinguished in two types, mainly depending on the presence of nerve injury. Although its prevalence may vary depending on social and ethnic factors, middle-aged women seem to suffer most often and the upper limb is the most commonly affected extremity. Apart from pain, which is the dominating feature, the clinical picture unfolds across several domains: sensory, motor, autonomic and trophic. This syndrome develops in two phases, the acute (warm) phase, with the classic symptoms of inflammation, and the chronic (cold) phase, often characterized by trophic changes of the soft tissues and even bones. Although the syndrome has been studied for over two decades, no imaging or laboratory test has been established for the diagnosis and recently proposed diagnostic criteria have not yet been validated and are only occasionally applied. Its pathophysiology is still quite obscure, although the most likely mechanisms involve the classic and neurogenic paths of inflammation mediated by cytokines and neuropeptides, intertwined with changes of the autonomic and central nervous system, psychological mechanisms and, perhaps, autoimmunity. Although plenty of treatment modalities have been tried, none has been proven unequivocally efficacious. Apart from information and education, which should be offered to all patients, the most effective pharmacological treatments seem to be bisphosphonates, glucocorticoids and vasoactive mediators, while physical therapy and rehabilitation therapy also make part of the treatment.

Background/objective: A prospective cohort study aimed to evaluate the clinical efficacy of a specific vasoactive herbal formula, Huo Xue Tong Luo capsule (HXTL capsule), for the treatment of patients with asymptomatic osteonecrosis of femoral head (ONFH). Methods: We evaluated a clinical trial of 55 patients (59 hips) with asymptomatic ONFH (no joint collapse) evaluated by Steinberg staging system and necrosis range classification criteria. Then, they were given HXTL capsule under specific protocol. Among them, 39 males and 16 females with an average age of 36.4 ± 10.1 years were followed up for an average of 4.38 years during treatment. The aggravation of clinical and imaging results was assessed by initial pain and joint collapse. The clinical and imaging outcomes of these patients were compared with those of a historical control group from the literature under critical inclusion criteria. Results: At the latest follow-up, initial pain occurred in five of 59 (8.5%) hips of patients taking HXTL capsule compared with 31 of 81 (38.3%) controls (p

Movement has a prominent impact on activity in sensory cortex, but has opposing effects on visual and auditory cortex. Both cortical areas feature a vasoactive intestinal peptide-expressing (VIP) disinhibitory circuit, which in visual cortex contributes to the effect of running. In auditory cortex, however, the role of VIP circuitry in running effects remains poorly understood. Running and optogenetic VIP activation are known to differentially modulate sound-evoked activity in auditory cortex, but it is unknown how these effects vary across cortical layers, and whether laminar differences in the roles of VIP circuitry could contribute to the substantial diversity that has been observed in the effects of both movement and VIP activation. Here we asked whether VIP neurons contribute to the effects of running, across the layers of auditory cortex. We found that both running and optogenetic activation of VIP neurons produced diverse changes in the firing rates of auditory cortical neurons, but with distinct effects on spontaneous and evoked activity and with different patterns across cortical layers. On average, running increased spontaneous firing rates but decreased evoked firing rates, resulting in a reduction of the neuronal encoding of sound. This reduction in sound encoding was observed in all cortical layers, but was most pronounced in layer 2/3. In contrast, VIP activation increased both spontaneous and evoked firing rates, and had no net population-wide effect on sound encoding, but strongly suppressed sound encoding in layer 4 narrow-spiking neurons. These results suggest that VIP activation and running act independently, which we then tested by comparing the arithmetic sum of the two effects measured separately to the actual combined effect of running and VIP activation, which were closely matched. We conclude that the effects of locomotion in auditory cortex are not mediated by the VIP network.

Coronavirus SARS-CoV-2 is responsible for the COVID-19 pandemic, and headache is reported in 6.5% to 34% of all cases. There is little published evidence on the pharmacological treatment of COVID-19 headache. This case series presents six COVID-19 infected patients with refractory headache, in which intranasal bedside Sphenopalatine Ganglion Block was performed for analgesia. All patients had a reduction in headache intensity from severe pain to mild or no pain after the procedure with minor transient side effects. Proposed mechanisms of action include reduction of local autonomic stimuli, intracranial vasoconstriction, and reduction of vasoactive substances release in the pterygopalatine fossa.

Neuroendocrine tumours while rare, need to be considered in patients with chronic diarrhoea. Reported herein is a case of vasoactive intestinal peptideoma in a patient with refractory diarrhoea following a diagnosis of coeliac disease., Neuroendocrine tumours while rare, are an important cause of to consider among patients with chronic diarrhoea. Reported herein is a case of vasoactive intestinal peptideoma in a patient with refractory diarrhoea following a diagnosis of coeliac disease.

The endothelium of arteries and veins has long been studied by doctors and researchers who deal with cardiovascular diseases. However, a global view of endothelial function was not possible until the past two decades that witnessed the discovery of prostacyclin production, the subsequent discovery of endothelium-derived nitric oxide (NO), and other vasoactive factors. There are three known endothelium-dependent vasodilation mechanisms: (1) dependent on the cGMP system (NO – nitric oxide); (2) dependent on the adenosine 3′5′-cyclic monophosphate (cAMP) system (PGI2 – prostacyclin); and (3) hyperpolarization (EDHF – hyperpolarizing factor of the endothelium still unknown or nonexistent). These mechanisms are synergistic with each other, with NO being the most important factor, because in addition to being an endogenous vasodilator, it is also an antiplatelet factor. These basic concepts are fundamental to understand the vasoplegic endothelium dysfunction.

El tumor carcinoide primario de ovario es una entidad poco frecuente que se caracteriza por la producción de sustancias vasoactivas que pasan directamente al torrente circulatorio y producen el llamado síndrome carcinoide. Estas sustancias también son las causantes de la formación de placas de fibrosis en las válvulas cardiacas, principalmente las derechas. Presentamos un caso de tumor carcinoide primario de ovario con afectación de la válvula tricúspide, que fue diagnosticado a partir de la lesión cardiaca. En la literatura están descritos casos clínicos aislados y revisiones de casos que nos pueden ayudar en el diagnóstico y en la toma de decisiones terapéuticas. Debemos conocer la existencia de estos tumores; la clínica debe alertarnos sobre su presencia. Es primordial un manejo multidisciplinar junto con endocrinólogos, cardiólogos, oncólogos, anatomo-patólogos, anestesistas, ginecólogos y cirujanos cardiacos, para ofrecer un tratamiento completo.

Urticaria is one of the common ailments of skin which may be considered as an extremely disabling and difficult-to-treat condition. Urticaria is the fourth-most prevalent allergic disease which occurs due to the release of histamine, bradykinin, kallikrein, and other vasoactive substances from mast cells and basophils in the superficial dermis. It is appropriate to not call it one disease, instead it can be considered as a reaction pattern of the skin which involves the upper dermis, characterized by localized edema and represented by the development of wheals. Treatment forms widely used in modern medicine for this condition are non-sedative anti histamines and corticosteroids. A complementary and integrative approach for urticaria is the need of the hour, wherein, various single or combination of herbs and extracts can be used independently as well as along with allopathic drugs. In Unani literature, disease has been described by the name of Sharā. The aim of the present paper was to explore the different aspects of urticaria with special reference to Unani and modern medicine.

Background Previous studies reported changes in the local vasoactive substance production within the endometrium with a subsequent increase in vascularity as a possible mechanism of intrauterine contraceptive device (IUCD)-induced heavy menstrual bleeding. This research investigates the role of power Doppler velocimetries of the uterine arteries, endometrium, and sub-endometrium vascularization as a predictor of IUCD-induced heavy menstrual bleeding. Results Endometrium flow index (FI) and vascularization flow index (VFI) significantly increased in both groups: women with heavy menstrual bleeding (group A) and women without heavy menstrual bleeding (group B), with significantly higher increase in group A. Endometrium VFI ≥ 0.18 had the highest significant diagnostic characteristics in the prediction of heavy menstrual bleeding, followed by sub-endometrium VI ≥ 3.75. Conclusion The results of this study suggest an increase in uterine blood flow in women with IUCD-induced menorrhagia. Endometrial and sub-endometrial Doppler vascular indices can be used for the prediction of IUCD-induced heavy menstrual bleeding.

Vasoactive intestinal peptide-expressing (VIP) interneurons in the cortex regulate feedback inhibition of pyramidal neurons through suppression of somatostatin-expressing (SST) interneurons and, reciprocally, SST neurons inhibit VIP neurons. Although VIP neuron activity in the primary visual cortex (V1) of mouse is highly correlated with locomotion, the relevance of locomotion-related VIP neuron activity to visual coding is not known. Here we show that VIP neurons in mouse V1 respond strongly to low contrast front-to-back motion that is congruent with self-motion during locomotion but are suppressed by other directions and contrasts. VIP and SST neurons have complementary contrast tuning. Layer 2/3 contains a substantially larger population of low contrast preferring pyramidal neurons than deeper layers, and layer 2/3 (but not deeper layer) pyramidal neurons show bias for front-to-back motion specifically at low contrast. Network modeling indicates that VIP-SST mutual antagonism regulates the gain of the cortex to achieve sensitivity to specific weak stimuli without compromising network stability.

The hypothalamic suprachiasmatic (SCN) clock contains several neurochemically defined cell groups that contribute to the genesis of circadian rhythms. Using cell-specific and genetically targeted approaches we have confirmed an indispensable role for vasoactive intestinal polypeptide-expressing SCN (SCNVIP) neurons, including their molecular clock, in generating the mammalian locomotor activity (LMA) circadian rhythm. Optogenetic-assisted circuit mapping revealed functional, di-synaptic connectivity between SCNVIP neurons and dorsomedial hypothalamic neurons, providing a circuit substrate by which SCNVIP neurons may regulate LMA rhythms. In vivo photometry revealed that while SCNVIP neurons are acutely responsive to light, their activity is otherwise behavioral state invariant. Single-nuclei RNA-sequencing revealed that SCNVIP neurons comprise two transcriptionally distinct subtypes, including putative pacemaker and non-pacemaker populations. Altogether, our work establishes necessity of SCNVIP neurons for the LMA circadian rhythm, elucidates organization of circadian outflow from and modulatory input to SCNVIP cells, and demonstrates a subpopulation-level molecular heterogeneity that suggests distinct functions for specific SCNVIP subtypes., Cell groups in the hypothalamic suprachiasmatic clock contribute to the genesis of circadian rhythms. The authors identified two populations of vasoactive intestinal polypeptide-expressing neurons in the suprachiasmatic nucleus which regulate locomotor circadian rhythm in mice.

Cardiorenal syndrome is a complex interplay of dysregulated heart and kidney interaction that leads to multiorgan system dysfunction, which is not an uncommon occurrence in the setting of right heart failure. The traditional concept of impaired perfusion and forward flow recently has been modified to include the recognition of systemic venous congestion as a contributor, with direct and indirect mechanisms, including elevated renal venous pressure, reduced renal perfusion pressure, increased renal interstitial pressure, tubular dysfunction, splanchnic congestion, and neurohormonal and inflammatory activation. Treatment options beyond diuretics and vasoactive drugs remain limited and lack supportive evidence.

Introduction Amniotic band syndrome (ABS) includes limb deficiencies accompanied by fibrous strands originating from the amniotic lining. Terminal transverse limb deficiencies (TTLD) appear to be similar but lack fibrous strands. Both are hypothesized to result from vascular disruption. For ABS, limb deficiencies are considered secondary to amnion rupture. We explored an alternative possibility-that TTLD is the primary defect and ABS is secondary. Methods Using data from the National Birth Defects Prevention Study, we expanded on a previous study. We examined smoking, alcohol, and medications categorized by indicated vasoactivity as markers of vascular disruption. Logistic regression models with Firth's penalized likelihood were used to estimate adjusted odds ratios (aORs) and 95% confidence intervals (CIs). Results Use of bronchodilators and aspirin appeared to increase the risk of ABS, while decongestants and nonaspirin NSAIDs increased the risk of TTLD. The risk of ABS was markedly increased in cases reporting combinations of vasoactive exposures, particularly alcohol and aspirin (aOR 3.7, 95% CI 1.6, 7.8), and alcohol and bronchodilators (aOR 3.4, 95% CI 1.4, 7.5). Increased risk of TTLD due to combinations of vasoactive exposures was only observed for smoking and decongestants (aOR 2.3, 95% CI 1.4, 3.6). Conclusions Exposures associated with increased risk of ABS had no apparent association with TTLD, supporting previous evidence that these may be distinct phenotypes. ABS appears to be associated with combined exposures with vasodilation properties, such as alcohol and bronchodilators, while increased risk of TTLD may be associated with smoking and decongestants, both vasoconstrictive exposures.

Indications, selection and duration of inotropic support during and following cardiac surgery remain variable and controversial. Nevertheless, it is employed frequently for anticipated or manifest hemodynamic instability ranging from low cardiac output to established shock stages. This chapter provides a background, justification and overview of inotropic and vasopressor therapy with a strong clinical rather than molecular and pharmacological focus. Current treatment strategies and principles of crucial aspects of medical management are discussed. The main clinical classification of inotropes and to a lesser degree vasoactive agents is included as well as clinical utilities of the most frequently used agents are described. Due to the significance of right ventricular dysfunction a section is dedicated to the right ventricle and pulmonary circulation. Finally, a summary of treatment strategies for the most common clinical scenarios is provided.

Calcific aortic valve stenosis (CAVS), the most common heart valve disease, is characterized by the slow progressive fibro-calcific remodeling of the valve leaflets, leading to progressive obstruction to the blood flow. CAVS is an increasing health care burden and the development of an effective medical treatment is a major medical need. To date, no effective pharmacological therapies have proven to halt or delay its progression to the severe symptomatic stage and aortic valve replacement represents the only available option to improve clinical outcomes and to increase survival. In the present report, the current knowledge and latest advances in the medical management of patients with CAVS are summarized, placing emphasis on lipid-lowering agents, vasoactive drugs, and anti-calcific treatments. In addition, novel potential therapeutic targets recently identified and currently under investigation are reported.

Despite the significant development and advancement in antibiotic therapy, life-threatening complication of infective diseases cause hundreds of thousands of deaths world. This paper updates some of the issues regarding the etiology and treatment of abdominal sepsis and summaries the latest guidelines as recommended by the Intra-abdominal Infection (IAI) Consensus (2017). Prognostic scores are currently used to assess the course of peritonitis. Irrespective of the initial cause, there are several measures universally accepted as contributing to an improved survival rate, with the early recognition of IAI being the critical matter in this respect. Immediate correction of fluid balance should be undertaken with the use of vasoactive agents being prescribed, if necessary, to augment and assist fluid resuscitation. The WISS study showed that mortality was significantly affected by sepsis irrespective of any medical and surgical measures. A significant issue is the prevalence of extended-spectrum β-lactamase (ESBL)-producing Enterobacteriaceae in the clinical setting, and the reported prevalence of ESBLs intra-abdominal infections has steadily increased in Asia. Europe, Latin America, Middle East, North America, and South Pacific. Abdominal cavity pathology is second only to sepsis occurring in a pulmonary site. Following IAI (2017) guidelines, antibiotic therapy should be initiated as soon as possible after a diagnosis has been verified.

Sepsis-induced cardiogenic shock is a lethal condition and the management of it is challenging. Cardiogenic shock in the septic patient involves myocardial systolic and diastolic dysfunction. The limited ability of the ventricles to contract effectively results in a decrease in oxygen delivery to the organs and tissues. Supportive therapy is provided to patients with sepsis and no specific drug can reverse the myocardial dysfunction. Rapid diagnosis, prompt antibiotic therapy, cautious protocol-driven fluid resuscitation and vasoactive agents, control of infectious source, and expeditious coronary artery revascularization is recommended to achieve a positive outcome.

In the present work modern approaches to investigation of isolated vessel's vasoactive properties with myography method were described. Authors give detailed illustrated description to the vessels preparation technique and order of actions during myography based on own experience and published data. Authors described approaches to investigate mechanical properties of vessel wall and vasoactive properties with wire myography method.

Background Both obstructive sleep apnea (OSA) and altered cerebrovascular reactivity (CVR) are associated with increased stroke risk. Nevertheless, the incidence of abnormal CVR in patients with OSA is uncertain due to the high variability in the way CVR is measured both within and between studies. We hypothesized that a standardized CVR with a consistent vasoactive stimulus and cerebral blood flow (CBF) measure would be reduced in patients with severe OSA compared with healthy controls. Methods This was a prospective study in which subjects with and without OSA were administered a standardized hypercapnic stimulus, and CBF was monitored by blood oxygen level-dependent magnetic resonance signal changes, a high space and time resolved surrogate for CBF. Results Twenty-four subjects with OSA (mean age 45.9 years, apnea–hypopnea index [AHI] 26.8 per hour) and 6 control subjects (mean age 42.8 years, AHI 2.4 per hour) were included. Compared with controls, subjects with OSA had a significantly greater whole brain (.1565 versus .1094, P = .013), gray matter (.2077 versus .1423, P = .009), and white matter (.1109 versus .0768, P = .024) CVR, respectively. Conclusions Contrary to expectations, subjects with OSA had greater CVR compared with control subjects.

BACKGROUND Drug delivery to treat neurologic disease and cancers of the central nervous system (CNS) is severely limited by the blood-brain barrier (BBB). Vasoactive peptides (VAPs) such as regadenoson, adenosine, and labradimil have been shown in animal studies to transiently open the BBB, and regadenoson is currently under investigation in humans to determine if it might improve CNS drug delivery. There is currently limited information regarding the potential for other VAPs to open the BBB transiently. METHODS We performed a review of the literature evaluating the physiologic effects of vasoactive peptides on the vasculature of the brain and systemic organs. To assess the likelihood that a vasoactive peptide might transiently disrupt the BBB, we devised a four-tier classification system to organize data available in the literature which factors in alterations in BBB integrity and effects on normal brain vasculature and systemic blood vessels. This data was further sorted based on whether it comes from humans, animals, or in vitro systems. RESULTS We identified 38 VAPs with potential BBB permeability-altering properties. To date, none of these has been shown to open the BBB in humans. Thirteen VAPs increased BBB permeability in rodents. The remaining 25 had favorable physiologic effects on blood vessels but lack specific information on permeability changes to the BBB. We ranked VAPs in a four-tier ranking system related to their known physiologic actions. CONCLUSION Rodent studies document that analogs of bradykinin and adenosine transiently disrupt the BBB leading to higher chemotherapy concentrations in the CNS. VAPs remain an understudied class of drugs with the potential to increase drug delivery to the CNS. Dozens of VAPs have yet to be formally evaluated for this important clinical effect. This retrospective review summarizes the available data on VAPs highlighting agents that deserve further in vitro and in vivo investigations.

Vascular theories of migraine and cluster headache have dominated for many years the pathobiological concept of these disorders. This view is supported by observations that trigeminal activation induces a vascular response and that several vasodilating molecules trigger acute attacks of migraine and cluster headache in susceptible individuals. Over the past 30 years, this rationale has been questioned as it became clear that the actions of some of these molecules, in particular, calcitonin gene-related peptide and pituitary adenylate cyclase-activating peptide, extend far beyond the vasoactive effects, as they possess the ability to modulate nociceptive neuronal activity in several key regions of the trigeminovascular system. These findings have shifted our understanding of these disorders to a primarily neuronal origin with the vascular manifestations being the consequence rather than the origin of trigeminal activation. Nevertheless, the neurovascular component, or coupling, seems to be far more complex than initially thought, being involved in several accompanying features. The review will discuss in detail the anatomical basis and the functional role of the neurovascular mechanisms relevant to migraine and cluster headache.

Pulmonary hypertension (PH) is characterized by severe exercise limitation mainly attributed to the impairment of right ventricular function resulting from a concomitant elevation of pulmonary vascular resistance and pressure. The unquestioned cornerstone in the management of patients with pulmonary arterial hypertension (PAH) is specific vasoactive medical therapy to improve pulmonary hemodynamics and strengthen right ventricular function. Nevertheless, evidence for a beneficial effect of exercise training (ET) on pulmonary hemodynamics and functional capacity in patients with PH has been growing during the past decade. Beneficial effects of ET on regulating factors, inflammation, and metabolism have also been described. Small case-control studies and randomized clinical trials in larger populations of patients with PH demonstrated substantial improvements in functional capacity after ET. These findings were accompanied by several studies that suggested an effect of ET on inflammation, although a direct link between this effect and the therapeutic benefit of ET in PH has not yet been demonstrated. On this background, the aim of the present review is to describe current concepts regarding the effects of exercise on the pulmonary circulation and pathophysiological limitations, as well as the clinical and mechanistic effects of exercise in patients with PH.

The endothelium is an established modulator of vascular tone; however, the recent discovery of the anti-contractile nature of perivascular adipose tissue (PVAT) suggests that the fat, which surrounds many blood vessels, can also modulate vascular tone. Both the endothelium and PVAT secrete vasoactive substances, which regulate vascular function. Many of these factors are common to both the endothelium and PVAT; therefore, this review will highlight the potential shared mechanisms in the modulation of vascular tone. Endothelial dysfunction is a hallmark of many vascular diseases, including hypertension and obesity. Moreover, PVAT dysfunction is now being reported in several cardio-metabolic disorders. Thus, this review will also discuss the mechanistic insights into endothelial and PVAT dysfunction in order to evaluate whether PVAT modulation of vascular contractility is similar to that of the endothelium in health and disease. Linked Articles This article is part of a themed section on Molecular Mechanisms Regulating Perivascular Adipose Tissue – Potential Pharmacological Targets? To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v174.20/issuetoc

We presented the anesthesia management in the case of off-pump surgical intervention for right coronary artery to right atrium fistula with an associated huge right coronary aneurysmal mass. Careful preoperative evaluation is essential for anesthesia management due to the variable pathology of coronary fistula. The surgical process of coronary fistula is flexible, and TEE can provide rich information such as drainage site location, dilated coronary artery, helping surgeons to complete atrial or ventricular septal defect occluder placement and evaluate the outcome. Timely feedback to surgeons is conducive to detect complications in time, whereas using vasoactive drugs would cover it up.

Influenza infection is a known cause of global morbidity and mortality. Most cases of influenza A (H1N1) influenza infection are mild and do not require hospitalization. Although the most common presentation is with upper respiratory tract symptoms, hemodynamic instability requiring vasoactive drugs and ventilatory support use is unusual. We present a case of acute fulminant myocarditis that presented with dyspnea, which was confirmed with laboratory tests, chest X-ray, and echocardiogram. The test for H1N1 in nasopharyngeal secretions was positive. The patient evolved to refractory cardiogenic shock despite the clinical measures applied.

Background Cerebrovascular reactivity (CVR) is an important aspect of brain function, and as such it is important to understand relationship between CVR and functional connectivity. Methods This research studied the role of CVR, or the brain's ability to react to vasoactive stimuli on brain functional connectivity by scanning subjects with blood‐oxygenation‐level‐dependent (BOLD) functional magnetic resonance imaging (fMRI) while they periodically inhale room air and a CO 2‐enriched gas mixture. We developed a new metric to measure the effect of CVR on each intrinsic connectivity network (ICN), which contrasts to voxel‐wise CVR. We also studied the changes in whole‐brain connectivity patterns using both static functional network connectivity (sFNC) and dynamic FNC (dFNC). Results We found that network connectivity is generally weaker during vascular dilation, which is supported by previous research. The dFNC analysis revealed that participants did not return to the pre‐CO 2 inhalation state, suggesting that one‐minute periods of room‐air inhalation is not enough for the CO 2 effect to fully dissipate. Conclusions Cerebrovascular reactivity is one tool that the cerebrovascular system uses to ensure the constant, finely‐tuned flow of oxygen to function properly. Understanding the relationship between CVR and brain dynamism can provide unique information about cerebrovascular diseases and general brain function. We observed that CVR has a wide, but consistent relationship to connectivity patterns between functional networks., We analyzed the effect of CO2 on both static and dynamic functional network connectivity. In addition, we measure the cerebrovascular reactivity of connectivity networks.

The segregation of figures from the background is an important step in generating a visual percept. In primary visual cortex (V1), figures evoke stronger neural firing than backgrounds but it is unknown how this figure-ground modulation (FGM) arises and whether it is necessary for perception. Here we show, using optogenetic silencing in mice, that FGM in V1 is necessary for figure-ground segregation. We find that the source of this enhanced activity is feedback from cortical higher visual areas. Neurons in higher areas also exhibit FGM and optogenetic silencing of higher areas strongly reduced FGM in V1. In V1, figures enhanced the activity of vasoactive intestinal peptide-expressing interneurons and suppressed somatostatin-positive interneurons, causing an increased activation of the cortical column. Our results provide new insight in how lower and higher areas of the visual cortex interact with each other to shape visual perception.

Neurotensin (NTS) is a 13-amino acid neuropeptide with neuroendocrine and vasoactive functions that is widely expressed in the central nervous system and gastrointestinal tract. NTS is sensed by a multiple cell surface proteins including two G protein-coupling receptors (GPCRs): NTS receptors 1 and 2 (NTSR1 and NTSR2). Crystal structures of NTSR1 have successfully elucidated agonist binding within the orthosteric pocket of receptor but have not revealed the full activation state of the receptor. Recent studies have attempted to address this challenge by improving NTSR1 crystal formation via thermostable mutants; unfortunately, these mutations exhibit functional defects in the G protein coupling of NTSR1. Here, we have used molecular dynamics simulations to gain greater insights into how the amino acid substitutions used in these thermostable mutants (E166A, L310A and F358A) impact receptor activation. Our simulations indicate that wild-type NTSR1 in complex with NTS8-13 shows more active-like features including a 17.7 Å shift in TM6, reflecting a network of polar and aromatic interactions orchestrating agonist-induced receptor conformational changes. We also provide evidence indicating that F358 is a precursor to the rotamer change observed in W321, and our collective analysis also suggests that mutations E166A and F358A are less impactful to G protein coupling than L310A. Furthermore, we believe that our findings can be used to design future NTSR1 mutants that do not interfere with agonist-induced conformational changes and downstream G protein coupling and thus produce structures that will allow visualization of the fully activated receptor conformation. Communicated by Ramaswamy H. Sarma Communicated by Ramaswamy H. Sarma

In the perfect world—an ideal laboratory grown vascular graft must be composed of viable tissue elements with potentials for repair and regeneration, an acceptable range of resistance to thrombosis—infections, sensitivity to vasoactive mediators, secretory and contractile properties, mimicking natural blood vessels. Three key components of generating such custom-made vessels are biocompatible polymer of natural structural proteins for building a scaffold, healthy primary vascular cells grown in the scaffold maintaining close anatomical and functional integrity, and provision for a microenvironment for providing balanced metabolic support. In addition, maintenance of a pulsatile flow of nutrients and polarization of cellular components in the synthetic vessels are also important. Obtaining decellularized vascular grafts from cadaveric donors or xenografts, populating with recipient’s primary vascular cells, and maintaining them in bioreactors or recipients own body tissue are other potential alternative approaches. Here, we will discuss some central aspects and updated information on authentic artificial blood vessel.

Background: The cost of treatments for cardiovascular diseases, in particular for populations in developing countries such as Senegal, requires an alternative which consists in developing research into new therapeutic approaches with the use of plants from the traditional pharmacopoeia. On the other hand, many of these plants have not been the subject of scientific studies. Aims and Objectives: In our study, we set out to study the effects on the vasomotricity of a plant from an in vitro model. As specific objectives, research of the vasorelaxant effects of the hydroethanolic extract of the leaves of Oxytenanthera abyssinica, on a model of pig coronary artery. Materials and Methods: The coronary artery rings were incubated with O. abyssinica (FOA) leaf extract at different concentrations (10–4 mg/ml, 5.10–4 mg/ml, 10–3 mg/ml, 5.10–3 mg/ml, 10–2 mg/ml, 5.10–2 mg/ml, 10–1 mg/ml, and 5.10–1 mg/ml) in an isolated organ system. The device comprises a set of devices including isometric tension sensors. The vessel rings to be studied are mounted on these. They are connected to metal rods that develop isometric tension. These sensors make it possible to measure the intensity of the voltage developed which reflects the vascular reactivity. After incubation, the rings are contracted with U46619 to produce a concentration-contraction curve with and without endothelium. The measured voltages are collected and represented in the form of a curve using the GraphPad software Prism version 6.01®. The results are expressed as means ± SEM of 08 experiments. The analysis of variance test (ANOVA) was used to compare the means. P < 0.05 was considered statistically significant. Results: The results obtained in this study showed that on isolated pig coronary artery rings, contracted at U46619, the hydroethanolic extract of O. abyssinica (FOA) leaves induces vascular relaxation. This vasorelaxation is obtained at concentrations ranging from 10−4 to 5.10−1 mg/ml with a relaxation percentage of approximately 100%. This percentage of relaxation is obtained both in the presence and in the absence of functional endothelium. These results suggest that the hydroethanolic extract of leaves of O. abyssinica possesses dose-dependent vasodilator properties on isolated pig coronary artery rings with endothelium-independent character. It thus appears that the raw extract of leaves of O. abyssinica can act on two ways. Conclusion: The results of our study made it possible to demonstrate a vascular relaxing effect of the hydroethanolic extract of the leaves of O. abyssinica. This vasorelaxant effect is dose dependent and endothelium independent.

Transcatheter aortic valve implantation (TAVI) is widely used in high-risk patients with severe symptomatic aortic valve stenosis (AS). The use of traditional surgical aortic valve replacement (SAVR) significantly increases the risk of complications in chronic liver failure with the release of many vasoactive and cytotoxic substrates. In patients with ischemic hepatitis or liver dysfunction along with the severe AS, TAVI may be advantageous due to its minimally invasive nature. However, there is limited information about the outcome of TAVI in a patient with both hepatic and multisystem dysfunction. We report this case demonstrating dramatic result of TAVI in a patient in extremely poor clinical condition due to ischemic hepatitis and hyperbilirunemia.