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American Journal of Health-system... Sep 2022The pathophysiology and hemodynamic management of acute spinal cord injuries, including the use of intravenous and enteral vasoactive agents, are reviewed. (Review)
Review
PURPOSE
The pathophysiology and hemodynamic management of acute spinal cord injuries, including the use of intravenous and enteral vasoactive agents, are reviewed.
SUMMARY
Spinal cord injuries are devastating neurological insults that in the acute setting lead to significant hemodynamic disturbances, including hypotension and bradycardia, that are influenced by the level of injury. High thoracic (usually defined as at or above T6) and cervical injuries often manifest with hypotension and bradycardia due to destruction of sympathetic nervous system activity and unopposed vagal stimulation to the myocardium, whereas lower thoracic injuries tend to result in hypotension alone due to venous pooling. Initial management includes maintaining euvolemia with crystalloids and maintaining or augmenting mean arterial pressure with the use of intravenous vasoactive agents to improve neurological outcomes. Choice of vasopressor should be based on patient-specific factors, particularly level of injury and presenting hemodynamics. This review includes the most recent literature on intravenous vasopressors as well as the limited evidence supporting the use of enteral vasoactive agents. Enteral vasoactive agents may be considered, when clinically appropriate, as a strategy to wean patients off of intravenous agents and facilitate transfer outside of the intensive care unit.
CONCLUSION
The hemodynamic management of acute spinal cord injuries often requires the use of vasoactive agents to meet mean arterial pressure goals and improve neurological outcomes. Patient-specific factors must be considered when choosing intravenous and enteral vasoactive agents.
Topics: Bradycardia; Hemodynamics; Humans; Hypotension; Spinal Cord Injuries; Vasoconstrictor Agents
PubMed: 35677966
DOI: 10.1093/ajhp/zxac164 -
Frontiers in Pediatrics 2021We aimed to determine the association of vasoactive-inotropic score (VIS) and vasoactive-ventilation-renal (VVR) score with in-hospital mortality and functional outcomes...
We aimed to determine the association of vasoactive-inotropic score (VIS) and vasoactive-ventilation-renal (VVR) score with in-hospital mortality and functional outcomes at discharge of children who receive ECMO. A sub-analysis of the multicenter, prospectively collected data by the Collaborative Pediatric Critical Care Research Network (CPCCRN) for Bleeding and Thrombosis on ECMO (BATE database) was conducted. Of the 514 patients who received ECMO across eight centers from December 2012 to February 2016, 421 were included in the analysis. Patients > 18 years of age, patients placed on ECMO directly from cardiopulmonary bypass or as an exit procedure, or patients with an invalid or missing VIS score were excluded. Higher VIS (OR = 1.008, 95% CI: 1.002-1.014, = 0.011) and VVR (OR: 1.006, 95% CI: 1.001-1.012, = 0.023) were associated with increased mortality. VIS was associated with worse Pediatric Cerebral Performance Category (PCPC) (OR = 1.027, 95% CI: 1.010-1.044, = 0.002) and Pediatric Overall Performance Category (POPC) score (OR = 1.023, 95% CI: 1.009-1.038, = 0.002) at discharge. No association was found between VIS or VVR and Functional Status Score (FSS) at discharge. Using multivariable analyses, controlling for ECMO mode, ECMO location, ECMO indication, primary diagnosis, and chronic diagnosis, extremely high VIS and VVR were still associated with increased mortality.
PubMed: 34917562
DOI: 10.3389/fped.2021.769932 -
Annals of Palliative Medicine Mar 2021Vasoactive intestinal peptide (VIP) is an important neurotransmitter involved in the modulation of gastrointestinal function through the stimulation of VIP receptors....
BACKGROUND
Vasoactive intestinal peptide (VIP) is an important neurotransmitter involved in the modulation of gastrointestinal function through the stimulation of VIP receptors. However, the expression of VPAC1R, VPAC2R and PAC1R in the human Lower esophageal sphincter (LES) has not been fully clarified. Therefore, the purpose of this study is to explore the expression of these receptors in the human Lower esophageal sphincter, the responses of the Lower esophageal sphincter to Vasoactive intestinal peptide, and the role of Vasoactive intestinal peptide receptors in the responses.
METHODS
Sling and clasp fiber samples of LES were acquired from patients undergoing subtotal esophagectomy, while circular muscle bundles from the esophagus and gastric fundus were used as control groups. Western blotting and RT-PCR technology were performed to determine the expression of the three VIP receptor subtypes. The isometric tension responses of the muscle sample strips to Ro25-1553 and PG99-465, and the effect of electrical field stimulation (EFS) on the sling and clasp fibers were studied.
RESULTS
We found that VPAC2R messenger RNA (mRNA) and protein were expressed in the sling and clasp fibers of human LES. However, no VPAC1R or PAC1R mRNA and protein expressions were found in the LES samples. The sling and clasp fibers of the LES produced significant concentration-dependent relaxation following exposure to Ro25-1553 and EFS could induce them to produce frequency-dependent relaxation. Furthermore, the relaxation responses of the LES were inhibited by PG99-465 and induced by EFS and Ro25-1553.
CONCLUSIONS
VPAC2R, but not VPAC1R or PAC1R, is expressed by the human LES. The relaxation responses of the LES generated by the VIP receptor agonist Ro25-1553 and EFS could be inhibited by the selective VPAC2 receptor antagonist PG99-465. VPAC2R may be important for the generation of relaxation and functional regulation of the LES.
Topics: Electric Stimulation; Esophageal Sphincter, Lower; Esophagectomy; Humans; Neurotransmitter Agents; Receptors, Vasoactive Intestinal Peptide
PubMed: 33849096
DOI: 10.21037/apm-21-193 -
Contrast Media & Molecular Imaging 2022Cardiovascular disease (CVD) is a common human disease with a large number of patients. Vasoactive drugs have a good effect on the contraction and expansion of blood...
Cardiovascular disease (CVD) is a common human disease with a large number of patients. Vasoactive drugs have a good effect on the contraction and expansion of blood vessels, which can provide certain help for the management of cardiovascular diseases. However, the clinical care of cardiovascular disease has always been based on the superficial resistance level of body fat, weight, and so on, which is unfavorable for the real recovery of patients with cardiovascular disease. This article aims to quantitatively evaluate the effects of clinical care based on vasoactive drug therapy and intrinsic factors of cardiovascular disease. For the treatment of vasoactive drugs, this paper selects the principle of action of the adrenal hormone to judge and analyze the expansion and contraction of the cardiovascular disease. For the clinical nursing of patients with cardiovascular disease, based on multivariate logistic regression, this paper selects internal factors such as age and blood pressure to model the nursing effect. Experiments have shown that the logistic regression model established in this paper can evaluate well the recovery effect of patients with cardiovascular disease. The AUC value of the model reached around 0.9. This showed that the clinical care of patients with cardiovascular disease can not only rationally judge the recovery effect through the model but also adjust the physical and mental conditions of patients with cardiovascular disease according to the coefficients of the model to achieve the best recovery effect.
Topics: Cardiovascular Diseases; Hormones; Humans; Logistic Models
PubMed: 36213559
DOI: 10.1155/2022/5659513 -
Pediatric Emergency Care Jan 2022The aim of the study was to describe patterns of initiation (and factors associated with delayed initiation) of vasoactive agents among pediatric emergency patients with...
OBJECTIVE
The aim of the study was to describe patterns of initiation (and factors associated with delayed initiation) of vasoactive agents among pediatric emergency patients with septic shock.
METHODS
Patients with septic shock from November 2013 to September 2016 who had a vasoactive agent initiated for documented hypotension were classified as "guideline adherent" (hypotensive following the final fluid bolus and had vasoactive agents initiated within 60 minutes) or "delayed initiation" (hypotensive after the final bolus and were initiated on vasoactive agents after >60 minutes). Patient-level factors (demographics, presence of underlying condition including central venous catheter, and markers of disease severity) and outcomes (mortality, length of stay) were compared between groups.
RESULTS
Of the 37 eligible patients, 17 received vasoactive agents within "guideline adherent" timelines and 10 were "delayed initiation." An additional group was identified as "transient responders"; these patients were normotensive after a final fluid bolus but developed hypotension and were initiated on a vasoactive agent within 2 hours after admission (n = 10). We found no significant difference between the "guideline adherent" and "delayed initiation" groups according to patient-level factors or outcomes; "transient responders" were more likely than other groups to have a central venous catheter and had longer lengths of stay.
CONCLUSIONS
Although there are perceived barriers to vasoactive agent initiation, we found no significant difference in patient-level factors between the timely and delayed groups. This study also identified a group of patients labeled as transient responders, who initially appeared volume responsive but who required vasoactive support within several hours. This cohort requires further study.
Topics: Child; Cohort Studies; Emergency Service, Hospital; Fluid Therapy; Humans; Hypotension; Shock, Septic
PubMed: 32941359
DOI: 10.1097/PEC.0000000000002219 -
International Journal of Molecular... Apr 2022Multiple sclerosis (MS) is a chronic neuroinflammatory and demyelinating disease of the central nervous system (CNS), characterised by the infiltration of peripheral... (Review)
Review
Multiple sclerosis (MS) is a chronic neuroinflammatory and demyelinating disease of the central nervous system (CNS), characterised by the infiltration of peripheral immune cells, multifocal white-matter lesions, and neurodegeneration. In recent years, microglia have emerged as key contributors to MS pathology, acting as scavengers of toxic myelin/cell debris and modulating the inflammatory microenvironment to promote myelin repair. In this review, we explore the role of two neuropeptides, pituitary adenylate cyclase-activating polypeptide (PACAP) and vasoactive intestinal peptide (VIP), as important regulators of microglial functioning during demyelination, myelin phagocytosis, and remyelination, emphasising the potential of these neuropeptides as therapeutic targets for the treatment of MS.
Topics: Humans; Microglia; Multiple Sclerosis; Pituitary Adenylate Cyclase-Activating Polypeptide; Vasoactive Intestinal Peptide
PubMed: 35563181
DOI: 10.3390/ijms23094788 -
Science (New York, N.Y.) Oct 2021Context controls the activity of sensory neurons.
Context controls the activity of sensory neurons.
Topics: Animals; Mice; Neural Inhibition; Neural Pathways; Neurons; Retina; Sensory Receptor Cells; Somatostatin; Vasoactive Intestinal Peptide; Visual Cortex; Visual Perception
PubMed: 34709912
DOI: 10.1126/science.abl7124 -
International Journal of Molecular... Dec 2019The neuroendocrine and immune systems are coordinated to maintain the homeostasis of the organism, generating bidirectional communication through shared mediators and... (Review)
Review
The neuroendocrine and immune systems are coordinated to maintain the homeostasis of the organism, generating bidirectional communication through shared mediators and receptors. Vasoactive intestinal peptide (VIP) is the paradigm of an endogenous neuropeptide produced by neurons and endocrine and immune cells, involved in the control of both innate and adaptive immune responses. Exogenous administration of VIP exerts therapeutic effects in models of autoimmune/inflammatory diseases mediated by G-protein-coupled receptors (VPAC1 and VPAC2). Currently, there are no curative therapies for inflammatory and autoimmune diseases, and patients present complex diagnostic, therapeutic, and prognostic problems in daily clinical practice due to their heterogeneous nature. This review focuses on the biology of VIP and VIP receptor signaling, as well as its protective effects as an immunomodulatory factor. Recent progress in improving the stability, selectivity, and effectiveness of VIP/receptors analogues and new routes of administration are highlighted, as well as important advances in their use as biomarkers, contributing to their potential application in precision medicine. On the 50th anniversary of VIP's discovery, this review presents a spectrum of potential clinical benefits applied to inflammatory and autoimmune diseases.
Topics: Animals; Autoimmune Diseases; Diabetes Mellitus, Type 1; Humans; Inflammation; Inflammatory Bowel Diseases; Receptors, Vasoactive Intestinal Peptide, Type II; Receptors, Vasoactive Intestinal Polypeptide, Type I; Rheumatic Diseases; Sjogren's Syndrome; Vasoactive Intestinal Peptide
PubMed: 31861827
DOI: 10.3390/ijms21010065 -
ELife Aug 2022The neocortex is organized around layered microcircuits consisting of a variety of excitatory and inhibitory neuronal types which perform rate- and oscillation-based...
The neocortex is organized around layered microcircuits consisting of a variety of excitatory and inhibitory neuronal types which perform rate- and oscillation-based computations. Using modeling, we show that both superficial and deep layers of the primary mouse visual cortex implement two ultrasensitive and bistable switches built on mutual inhibitory connectivity motives between somatostatin, parvalbumin, and vasoactive intestinal polypeptide cells. The switches toggle pyramidal neurons between high and low firing rate states that are synchronized across layers through translaminar connectivity. Moreover, inhibited and disinhibited states are characterized by low- and high-frequency oscillations, respectively, with layer-specific differences in frequency and power which show asymmetric changes during state transitions. These findings are consistent with a number of experimental observations and embed firing rate together with oscillatory changes within a switch interpretation of the microcircuit.
Topics: Animals; Mice; Neocortex; Neurons; Parvalbumins; Pyramidal Cells; Vasoactive Intestinal Peptide
PubMed: 35994330
DOI: 10.7554/eLife.77594 -
International Immunopharmacology Sep 2023Loss and dysfunction of articular chondrocytes, which disrupt the homeostasis of extracellular matrix formation and breakdown, promote the onset of osteoarthritis (OA)....
Loss and dysfunction of articular chondrocytes, which disrupt the homeostasis of extracellular matrix formation and breakdown, promote the onset of osteoarthritis (OA). Targeting inflammatory pathways is an important therapeutic strategy for OA. Vasoactive intestinal peptide (VIP) is an immunosuppressive neuropeptide with potent anti-inflammatory effects; however, its role and mechanism in OA remain unclear. In this study, microarray expression profiling from the Gene Expression Omnibus database and integrative bioinformatics analyses were performed to identify differentially expressed lncRNAs in OA samples. qRT-PCR validation of the top ten different expressed lncRNAs indicated that the expression level of intergenic non-protein coding RNA 2203 (LINC02203, also named LOC727924) was the highest in OA cartilage compared to normal cartilage. Hence, the LOC727924 function was further investigated. LOC727924 was upregulated in OA chondrocytes, with a dominant sub-localization in the cytoplasm. In OA chondrocytes, LOC727924 knockdown boosted cell viability, suppressed cell apoptosis, reactive oxygen species (ROS) accumulation, increased aggrecan and collagen II, decreased matrix metallopeptidase (MMP)-3/13 and ADAM metallopeptidase with thrombospondin type 1 motif (ADAMTS)-4/5 levels, and reduced the levels of tumor necrosis factor alpha (TNF-α), interleukin 1 beta (IL-1β), and interleukin 6 (IL-6). LOC727924 could interact with the microRNA 26a (miR-26a)/ karyopherin subunit alpha 3 (KPNA3) axis by competitively targeting miR-26a for KPNA3 binding, therefore down-regulating miR-26a and upregulating KPNA3; in OA chondrocytes, miR-26a inhibition partially abolished LOC727924 knockdown effects on chondrocytes. miR-26a inhibited the nuclear translocation of p65 through targeting KPNA3 and p65 transcriptionally activated LOC727924, forming a p65-LOC727924-miR-26a/KPNA3-p65 regulatory loop to modulate OA chondrocyte phenotypes. In vitro, VIP improved OA chondrocyte proliferation and functions, down-regulated LOC727924, KPNA3, and p65 expression, and upregulated miR-26a expression; in vivo, VIP ameliorated destabilization of the medial meniscus (DMM)-induced damages on the mouse knee joint, down-regulated KPNA3, inhibited the nuclear translocation of p65. In conclusion, the p65-LOC727924-miR-26a/KPNA3-p65 regulatory loop modulates OA chondrocyte apoptosis, ROS accumulation, extracellular matrix (ECM) deposition, and inflammatory response in vitro and OA development in vivo, being one of the mechanisms mediating VIP ameliorating OA.
Topics: Mice; Animals; MicroRNAs; Chondrocytes; Vasoactive Intestinal Peptide; RNA, Long Noncoding; Reactive Oxygen Species; Cartilage, Articular; Osteoarthritis; Interleukin-1beta; Apoptosis
PubMed: 37392568
DOI: 10.1016/j.intimp.2023.110518