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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 -
Annals of the American Thoracic Society Jan 2021Patients undergoing cardiac surgery often require vasopressor or inotropic ("vasoactive") medications, but patterns of postoperative use are not well described. This...
Patients undergoing cardiac surgery often require vasopressor or inotropic ("vasoactive") medications, but patterns of postoperative use are not well described. This study aimed to describe vasoactive medication administration throughout hospitalization for cardiac surgery, to identify patient- and hospital-level factors associated with postoperative use, and to quantify variation in treatment patterns among hospitals. Retrospective study using the Premier Healthcare Database. The cohort included adult patients who underwent coronary artery bypass grafting or open valve repair or replacement (or in combination) from January 1, 2016, to June 30, 2018. Primary outcome was receipt of vasoactive medication(s) on the first postoperative day (POD1). We identified patient- and hospital-level factors associated with receipt of vasoactive medications using multilevel mixed-effects logistic regression modeling. We calculated adjusted median odds ratios to determine the extent to which receipt of vasoactive medications on POD1 was determined by each hospital, then calculated quotients of Akaike Information Criteria to compare the relative contributions of patient and hospital characteristics and individual hospitals with observed variation. Among 104,963 adults in 294 hospitals, 95,992 (92.2%) received vasoactive medication(s) during hospitalization; 30,851 (29.7%) received treatment on POD1, most commonly norepinephrine ( = 11,427, 37.0%). A median of 29.0% (range, 0.0-94.4%) of patients in each hospital received vasoactive drug(s) on POD1. After adjustment, hospital of admission was associated with twofold increased odds of receipt of any vasoactive medication on POD1 (adjusted median odds ratio, 2.07; 95% confidence interval, 1.93-2.21). Admitting hospital contributed more to observed variation in POD1 vasoactive medication use than patient or hospital characteristics (quotients of Akaike Information Criteria 0.58, 0.44, and <0.001, respectively). Nearly all cardiac surgical patients receive vasoactive medications during hospitalization; however, only one-third receive treatment on POD1, with significant variability by institution. Further research is needed to understand the causes of variability across hospitals and whether these differences are associated with outcomes.
Topics: Aged; Cardiac Surgical Procedures; Cardiovascular Agents; Female; Humans; Male; Medicare; Retrospective Studies; Treatment Outcome; United States
PubMed: 32926642
DOI: 10.1513/AnnalsATS.202005-465OC -
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 -
Nature Communications Nov 2022The vasoactive intestinal peptide (VIP) and pituitary adenylate cyclase-activating polypeptide (PACAP) receptors are key regulators of neurological processes. Despite...
The vasoactive intestinal peptide (VIP) and pituitary adenylate cyclase-activating polypeptide (PACAP) receptors are key regulators of neurological processes. Despite recent structural data, a comprehensive understanding of peptide binding and selectivity among different subfamily receptors is lacking. Here, we determine structures of active, Gs-coupled, VIP-VPAC1R, PACAP27-VPAC1R, and PACAP27-PAC1R complexes. Cryo-EM structural analyses and molecular dynamics simulations (MDSs) reveal fewer stable interactions between VPAC1R and VIP than for PACAP27, more extensive dynamics of VIP interaction with extracellular loop 3, and receptor-dependent differences in interactions of conserved N-terminal peptide residues with the receptor core. MD of VIP modelled into PAC1R predicts more transient VIP-PAC1R interactions in the receptor core, compared to VIP-VPAC1R, which may underlie the selectivity of VIP for VPAC1R over PAC1R. Collectively, our work improves molecular understanding of peptide engagement with the PAC1R and VPAC1R that may benefit the development of novel selective agonists.
Topics: Pituitary Adenylate Cyclase-Activating Polypeptide; Vasoactive Intestinal Peptide; Protein Binding; Molecular Dynamics Simulation
PubMed: 36385145
DOI: 10.1038/s41467-022-34629-3 -
Clinical Medicine Insights. Cardiology 2022This is a focused review looking at the pharmacological support in cardiogenic shock. There are a plethora of data evaluating vasopressors and inotropes in septic shock,... (Review)
Review
This is a focused review looking at the pharmacological support in cardiogenic shock. There are a plethora of data evaluating vasopressors and inotropes in septic shock, but the data are limited for cardiogenic shock. This review article describes in detail the pathophysiology of cardiogenic shock, the mechanism of action of different vasopressors and inotropes emphasizing their indications and potential side effects. This review article incorporates the currently used specific risk-prediction models in cardiogenic shock as well as integrates data from many trials on the use of vasopressors and inotropes. Lastly, this review seeks to discuss the future direction for vasoactive medications in cardiogenic shock.
PubMed: 35153521
DOI: 10.1177/11795468221075064 -
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 -
Frontiers in Pediatrics 2023There is a need to index important clinical characteristics in pediatric cardiac surgery that can be obtained early in the postoperative period and accurately predict...
INTRODUCTION
There is a need to index important clinical characteristics in pediatric cardiac surgery that can be obtained early in the postoperative period and accurately predict postoperative outcomes.
METHODOLOGY
A prospective cohort study was conducted in the pediatric cardiac ICU and ward on all children aged <18 years undergoing cardiac surgery for congenital heart disease from September 2018 to October 2020. The vasoactive-ventilation-renal (VVR) score was analyzed to predict outcomes of cardiac surgeries with a comparison of postoperative variables.
RESULTS
A total of 199 children underwent cardiac surgery during the study period. The median (interquartile range) age was 2 (0.8-5) years, and the median weight was 9.3 (6-16) kg. The most common diagnoses were ventricular septal defect (46.2%) and tetralogy of Fallot (37.2%). At the 48th h, area under the curve (AUC) (95% CI) values were higher for the VVR score than those for other clinical scores measured. Similarly, at the 48th h, AUC (95% CI) values were higher for the VVR score than those for the other clinical scores measured for the length of stay and mechanical ventilation.
DISCUSSION
The VVR score at 48 h postoperation was found to best correlate with prolonged pediatric intensive care unit (PICU) stay, length of hospitalization, and ventilation duration, with the greatest AUC-receiver operating characteristic (0.715, 0.723, and 0.843, respectively). The 48-h VVR score correlates well with prolonged ICU, hospital stay, and ventilation.
PubMed: 36891234
DOI: 10.3389/fped.2023.1086626 -
Circulation Research Sep 2023The phrase complete vagal withdrawal is often used when discussing autonomic control of the heart during exercise. However, more recent studies have challenged this...
BACKGROUND
The phrase complete vagal withdrawal is often used when discussing autonomic control of the heart during exercise. However, more recent studies have challenged this assumption. We hypothesized that cardiac vagal activity increases during exercise and maintains cardiac function via transmitters other than acetylcholine.
METHODS
Chronic direct recordings of cardiac vagal nerve activity, cardiac output, coronary artery blood flow, and heart rate were recorded in conscious adult sheep during whole-body treadmill exercise. Cardiac innervation of the left cardiac vagal branch was confirmed with lipophilic tracer dyes (DiO). Sheep were exercised with pharmacological blockers of acetylcholine (atropine, 250 mg), VIP (vasoactive intestinal peptide; [4Cl-D-Phe6,Leu17]VIP 25 µg), or saline control, randomized on different days. In a subset of sheep, the left cardiac vagal branch was denervated.
RESULTS
Neural innervation from the cardiac vagal branch is seen at major cardiac ganglionic plexi, and within the fat pads associated with the coronary arteries. Directly recorded cardiac vagal nerve activity increased during exercise. Left cardiac vagal branch denervation attenuated the maximum changes in coronary artery blood flow (maximum exercise, control: 63.5±5.9 mL/min, n=8; cardiac vagal denervated: 32.7±5.6 mL/min, n=6, 2.5×10), cardiac output, and heart rate during exercise. Atropine did not affect any cardiac parameters during exercise, but VIP antagonism significantly reduced coronary artery blood flow during exercise to a similar level to vagal denervation.
CONCLUSIONS
Our study demonstrates that cardiac vagal nerve activity actually increases and is crucial for maintaining cardiac function during exercise. Furthermore, our findings show the dynamic modulation of coronary artery blood flow during exercise is mediated by VIP.
Topics: Animals; Sheep; Acetylcholine; Heart; Coronary Vessels; Cardiac Output; Atropine
PubMed: 37641938
DOI: 10.1161/CIRCRESAHA.123.323017 -
Systematic Reviews Jan 2024The objective of this study is to conduct a systematic review and meta-analysis examining the relationship between the vasoactive-inotropic score (VIS) and patient... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
The objective of this study is to conduct a systematic review and meta-analysis examining the relationship between the vasoactive-inotropic score (VIS) and patient outcomes in surgical settings.
METHODS
Two independent reviewers searched PubMed, Web of Science, EMBASE, Scopus, Cochrane Library, Google Scholar, and CNKI databases from November 2010, when the VIS was first published, to December 2022. Additional studies were identified through hand-searching the reference lists of included studies. Eligible studies were those published in English that evaluated the association between the VIS and short- or long-term patient outcomes in both pediatric and adult surgical patients. Meta-analysis was performed using RevMan Manager version 5.3, and quality assessment followed the Joanna Briggs Institute (JBI) Critical Appraisal Checklists.
RESULTS
A total of 58 studies comprising 29,920 patients were included in the systematic review, 34 of which were eligible for meta-analysis. Early postoperative VIS was found to be associated with prolonged mechanical ventilation (OR 5.20, 95% CI 3.78-7.16), mortality (OR 1.08, 95% CI 1.05-1.12), acute kidney injury (AKI) (OR 1.26, 95% CI 1.13-1.41), poor outcomes (OR 1.02, 95% CI 1.01-1.04), and length of stay (LOS) in the ICU (OR 3.50, 95% CI 2.25-5.44). The optimal cutoff value for the VIS as an outcome predictor varied between studies, ranging from 10 to 30.
CONCLUSION
Elevated early postoperative VIS is associated with various adverse outcomes, including acute kidney injury (AKI), mechanical ventilation duration, mortality, poor outcomes, and length of stay (LOS) in the ICU. Monitoring the VIS upon return to the Intensive Care Unit (ICU) could assist medical teams in risk stratification, targeted interventions, and parent counseling.
SYSTEMATIC REVIEW REGISTRATION
PROSPERO CRD42022359100.
Topics: Adult; Child; Humans; Acute Kidney Injury; Checklist; Databases, Factual; Intensive Care Units; Length of Stay; General Surgery; Patient Outcome Assessment
PubMed: 38184601
DOI: 10.1186/s13643-023-02403-1