-
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 -
Current Opinion in Cardiology Jul 2018Hypertension (HTN) is a widespread and growing disease, with medication intolerance and side-effect present among many. To address these obstacles novel pharmacotherapy... (Review)
Review
PURPOSE OF REVIEW
Hypertension (HTN) is a widespread and growing disease, with medication intolerance and side-effect present among many. To address these obstacles novel pharmacotherapy is an active area of drug development. This review seeks to explore future drug therapy for HTN in the preclinical and clinical arenas.
RECENT FINDINGS
The future of pharmacological therapy in HTN consists of revisiting old pathways to find new targets and exploring wholly new approaches to provide additional avenues of treatment. In this review, we discuss the current status of the most recent drug therapy in HTN. New developments in well trod areas include novel mineralocorticoid antagonists, aldosterone synthase inhibitors, aminopeptidase-A inhibitors, natriuretic peptide receptor agonists, or the counter-regulatory angiotensin converting enzyme 2/angiotensin (Ang) (1-7)/Mas receptor axis. Neprilysin inhibitors popularized for heart failure may also still hold HTN potential. Finally, we examine unique systems in development never before used in HTN such as Na/H exchange inhibitors, vasoactive intestinal peptide agonists, and dopamine beta hydroxylase inhibitors.
SUMMARY
A concise review of future directions of HTN pharmacotherapy.
Topics: Antihypertensive Agents; Cytochrome P-450 CYP11B2; Dopamine beta-Hydroxylase; Glutamyl Aminopeptidase; Humans; Hypertension; Mineralocorticoid Receptor Antagonists; Neprilysin; Receptors, Atrial Natriuretic Factor; Receptors, Vasoactive Intestinal Peptide; Renin-Angiotensin System; Sodium-Hydrogen Exchanger 3
PubMed: 29702500
DOI: 10.1097/HCO.0000000000000529 -
Advances in Protein Chemistry and... 2015Neuropeptides are potentially valuable tools for clinical applications as they offer many distinct advantages over other bioactive molecules like proteins and monoclonal... (Review)
Review
Neuropeptides are potentially valuable tools for clinical applications as they offer many distinct advantages over other bioactive molecules like proteins and monoclonal antibodies due to their reduced side effects and simple chemical modifications. Despite such advantages, the difficulty with neuropeptides often relies on their poor metabolic stability and reduced biological activity intervals. Among the neuropeptides, VIP has been identified as a potentially bioactive agent for inflammatory, neurodegenerative, and cancer-related diseases. However, the effective translation of preclinical studies related to VIP to clinical realities faces several major challenges, most of which are commonplace for other neuropeptides. Here, we present recent studies aimed at developing nanostructured organic and inorganic systems either for the appropriate delivery of VIP or for VIP targeting. These technologies stand as an alternative starting point for chemical manipulations of the neuropeptides in order to improve potency, selectivity, or pharmacokinetic parameters.
Topics: Antineoplastic Agents; Drug Delivery Systems; Gene Expression; Humans; Hydrophobic and Hydrophilic Interactions; Molecular Targeted Therapy; Nanoparticles; Neoplasms; Protein Binding; Receptors, Vasoactive Intestinal Peptide; Static Electricity; Translational Research, Biomedical; Vasoactive Intestinal Peptide
PubMed: 25819279
DOI: 10.1016/bs.apcsb.2014.11.006 -
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 -
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 -
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 -
Animals : An Open Access Journal From... May 2019Vascular endothelium plays a key role in regulating cardiovascular homeostasis by controlling the vascular tone. Variations in sex hormones during the reproductive cycle... (Review)
Review
Vascular endothelium plays a key role in regulating cardiovascular homeostasis by controlling the vascular tone. Variations in sex hormones during the reproductive cycle of females affect the homeostasis of the cardiovascular system. Also, the evidence shows that estrogens show a cardioprotective effect. On this basis, this study describes some vascular responses induced by vasoactive substances during the estrous cycle in rats. We obtained the information available on this topic from the online databases that included scientific articles published in the Web of Science, PubMed, and Scielo. Many investigations have evaluated the vasoactive response of substances such as acetylcholine and norepinephrine during the estrous cycle. In this review, we specifically described the vascular response to vasoactive substances in rats during the estrous cycle, pregnancy, and in ovariectomized rats. In addition, we discussed the existence of different signaling pathways that modulate vascular function. The knowledge of these effects is relevant for the optimization and development of new treatments for some vascular pathologies.
PubMed: 31146394
DOI: 10.3390/ani9060288 -
Pediatric Critical Care Medicine : a... Aug 2017To assess the validity of Vasoactive-Inotropic Score as a scoring system for cardiovascular support and surrogate outcome in pediatric sepsis.
OBJECTIVES
To assess the validity of Vasoactive-Inotropic Score as a scoring system for cardiovascular support and surrogate outcome in pediatric sepsis.
DESIGN
Secondary retrospective analysis of a single-center sepsis registry.
SETTING
Freestanding children's hospital and tertiary referral center.
PATIENTS
Children greater than 60 days and less than 18 years with sepsis identified in the emergency department between January 2012 and June 2015 treated with at least one vasoactive medication within 48 hours of admission to the PICU.
INTERVENTIONS
None.
MEASUREMENTS AND MAIN RESULTS
Vasoactive-Inotropic Score was abstracted at 6, 12, 24, and 48 hours post ICU admission. Primary outcomes were ventilator days and ICU length of stay. The secondary outcome was a composite outcome of cardiac arrest/extracorporeal membrane oxygenation/in-hospital mortality. One hundred thirty-eight patients met inclusion criteria. Most common infectious sources were pneumonia (32%) and bacteremia (23%). Thirty-three percent were intubated and mortality was 6%. Of the time points assessed, Vasoactive-Inotropic Score at 48 hours showed the strongest correlation with ICU length of stay (r = 0.53; p < 0.0001) and ventilator days (r = 0.52; p < 0.0001). On multivariable analysis, Vasoactive-Inotropic Score at 48 hours was a strong independent predictor of primary outcomes and intubation. For every unit increase in Vasoactive-Inotropic Score at 48 hours, there was a 13% increase in ICU length of stay (p < 0.001) and 8% increase in ventilator days (p < 0.01). For every unit increase in Vasoactive-Inotropic Score at 12 hours, there was a 14% increase in odds of having the composite outcome (p < 0.01).
CONCLUSIONS
Vasoactive-Inotropic Score in pediatric sepsis patients is independently associated with important clinically relevant outcomes including ICU length of stay, ventilator days, and cardiac arrest/extracorporeal membrane oxygenation/mortality. Vasoactive-Inotropic Score may be a useful surrogate outcome in pediatric sepsis.
Topics: Adolescent; Child; Child, Preschool; Combined Modality Therapy; Critical Care; Female; Hospital Mortality; Humans; Infant; Intensive Care Units, Pediatric; Length of Stay; Male; Prognosis; Respiration, Artificial; Retrospective Studies; Sepsis; Severity of Illness Index; Vasoconstrictor Agents
PubMed: 28486385
DOI: 10.1097/PCC.0000000000001191 -
PloS One 2022Vasoactive treatment is a cornerstone in treating hypoperfusion in cardiogenic shock following acute myocardial infarction (AMICS). The purpose was to compare the...
BACKGROUND
Vasoactive treatment is a cornerstone in treating hypoperfusion in cardiogenic shock following acute myocardial infarction (AMICS). The purpose was to compare the achievement of treatment targets and outcome in relation to vasoactive strategy in AMICS patients stratified according to the Society of Cardiovascular Angiography and Interventions (SCAI) shock classification.
METHODS
Retrospective analysis of patients with AMICS admitted to cardiac intensive care unit at two tertiary cardiac centers during 2010-2017 with retrieval of real-time hemodynamic data and dosages of vasoactive drugs from intensive care unit databases.
RESULTS
Out of 1,249 AMICS patients classified into SCAI class C, D, and E, mortality increased for each shock stage from 34% to 60%, and 82% (p<0.001). Treatment targets of mean arterial blood pressure > 65mmHg and venous oxygen saturation > 55% were reached in the majority of patients; however, more patients in SCAI class D and E had values below treatment targets within 24 hours (p<0.001) despite higher vasoactive load and increased use of epinephrine for each severity stage (p<0.001). In univariate analysis no significant difference in mortality within SCAI class D and E regarding vasoactive strategy was observed, however in SCAI class C, epinephrine was associated with higher mortality and a significantly higher vasoactive load to reach treatment targets. In multivariate analysis there was no statistically association between individually vasoactive choice within each SCAI class and 30-day mortality.
CONCLUSION
Hemodynamic treatment targets were achieved in most patients at the expense of increased vasoactive load and more frequent use of epinephrine for each shock severity stage. Mortality was high regardless of vasoactive strategy; only in SCAI class C, epinephrine was associated with a significantly higher mortality, but the signal was not significant in adjusted analysis.
Topics: Angiography; Epinephrine; Humans; Myocardial Infarction; Retrospective Studies; Shock, Cardiogenic
PubMed: 35925990
DOI: 10.1371/journal.pone.0272279