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Journal of Cardiothoracic and Vascular... Oct 2021Inotropes and vasopressors frequently are administered in critically ill and perioperative patients. However, clinical practice is highly variable across clinicians and... (Review)
Review
Inotropes and vasopressors frequently are administered in critically ill and perioperative patients. However, clinical practice is highly variable across clinicians and institutions. The inotropic score and its upgrade "vasoactive-inotropic score" (VIS) can be used to objectively quantify the degree of hemodynamic support. Several studies demonstrated a correlation between high VIS and poor outcome. Furthermore, VIS can help compare different clinical and research experiences. Several recently developed scores include VIS in their model, although they still require independent validation. Conversely, VIS has several pitfalls, including the fact that a universally recognized version that includes all commonly used vasoactive drugs does not exist. In this review, the authors summarize all the VIS, VIS-related, and VIS-validating manuscripts, and suggest a new updated version of VIS that also includes terlipressin, methylene blue, and angiotensin II.
Topics: Angiotensin II; Cardiotonic Agents; Hemodynamics; Humans; Terlipressin; Vasoconstrictor Agents
PubMed: 33069558
DOI: 10.1053/j.jvca.2020.09.117 -
International Journal of Molecular... Jul 2023Migraine is a debilitating neurological condition affecting millions of people worldwide. Until a few years ago, preventive migraine treatments were based on molecules... (Review)
Review
Migraine is a debilitating neurological condition affecting millions of people worldwide. Until a few years ago, preventive migraine treatments were based on molecules with pleiotropic targets, developed for other indications, and discovered by serendipity to be effective in migraine prevention, although often burdened by tolerability issues leading to low adherence. However, the progresses in unravelling the migraine pathophysiology allowed identifying novel putative targets as calcitonin gene-related peptide (CGRP). Nevertheless, despite the revolution brought by CGRP monoclonal antibodies and gepants, a significant percentage of patients still remains burdened by an unsatisfactory response, suggesting that other pathways may play a critical role, with an extent of involvement varying among different migraine patients. Specifically, neuropeptides of the CGRP family, such as adrenomedullin and amylin; molecules of the secretin family, such as pituitary adenylate cyclase-activating peptide (PACAP) and vasoactive intestinal peptide (VIP); receptors, such as transient receptor potential (TRP) channels; intracellular downstream determinants, such as potassium channels, but also the opioid system and the purinergic pathway, have been suggested to be involved in migraine pathophysiology. The present review provides an overview of these pathways, highlighting, based on preclinical and clinical evidence, as well as provocative studies, their potential role as future targets for migraine preventive treatment.
Topics: Humans; Animals; Migraine Disorders; Signal Transduction; Vasoactive Intestinal Peptide; Potassium Channels; Analgesics, Opioid
PubMed: 37569648
DOI: 10.3390/ijms241512268 -
Current Opinion in Endocrinology,... Apr 2021To discuss recent advances of vasoactive intestinal peptide/pituitary adenylate cyclase-activating polypeptide (VIP/PACAP) receptors in the selected central nervous... (Review)
Review
Pituitary adenylate cyclase-activating polypeptide/vasoactive intestinal peptide (Part 2): biology and clinical importance in central nervous system and inflammatory disorders.
PURPOSE OF REVIEW
To discuss recent advances of vasoactive intestinal peptide/pituitary adenylate cyclase-activating polypeptide (VIP/PACAP) receptors in the selected central nervous system (CNS) and inflammatory disorders.
RECENT FINDINGS
Recent studies provide evidence that PACAP plays an important role in a number of CNS disorders, particularly the pathogenesis of headaches (migraine, etc.) as well as posttraumatic stress disorder and drug/alcohol/smoking addiction. VIP has important therapeutic effects in a number of autoimmune/inflammatory disorder such as rheumatoid arthritis. In some cases, these insights have advanced to therapeutic trials.
SUMMARY
Recent insights from studies of VIP/PACAP and their receptors in both CNS disorders (migraine, posttraumatic stress disorder, addiction [drugs, alcohol, smoking]) and inflammatory disorders [such as rheumatoid arthritis] are suggesting new treatment approaches. The elucidation of the importance of VIP/PACAP system in these disorders combined recent development of specific drugs acting on this system (i.e., monoclonal VIP/PACAP antibodies) will likely lead to importance novel treatment approaches in these diseases.
Topics: Biology; Central Nervous System; Humans; Pituitary Adenylate Cyclase-Activating Polypeptide; Receptors, Pituitary Adenylate Cyclase-Activating Polypeptide, Type I; Receptors, Vasoactive Intestinal Peptide, Type II; Receptors, Vasoactive Intestinal Polypeptide, Type I; Vasoactive Intestinal Peptide
PubMed: 33481421
DOI: 10.1097/MED.0000000000000621 -
Nature Mar 2020The intestinal mucosa serves both as a conduit for the uptake of food-derived nutrients and microbiome-derived metabolites, and as a barrier that prevents tissue...
The intestinal mucosa serves both as a conduit for the uptake of food-derived nutrients and microbiome-derived metabolites, and as a barrier that prevents tissue invasion by microorganisms and tempers inflammatory responses to the myriad contents of the lumen. How the intestine coordinates physiological and immune responses to food consumption to optimize nutrient uptake while maintaining barrier functions remains unclear. Here we show in mice how a gut neuronal signal triggered by food intake is integrated with intestinal antimicrobial and metabolic responses that are controlled by type-3 innate lymphoid cells (ILC3). Food consumption rapidly activates a population of enteric neurons that express vasoactive intestinal peptide (VIP). Projections of VIP-producing neurons (VIPergic neurons) in the lamina propria are in close proximity to clusters of ILC3 that selectively express VIP receptor type 2 (VIPR2; also known as VPAC2). Production of interleukin (IL)-22 by ILC3, which is upregulated by the presence of commensal microorganisms such as segmented filamentous bacteria, is inhibited upon engagement of VIPR2. As a consequence, levels of antimicrobial peptide derived from epithelial cells are reduced but the expression of lipid-binding proteins and transporters is increased. During food consumption, the activation of VIPergic neurons thus enhances the growth of segmented filamentous bacteria associated with the epithelium, and increases lipid absorption. Our results reveal a feeding- and circadian-regulated dynamic neuroimmune circuit in the intestine that promotes a trade-off between innate immune protection mediated by IL-22 and the efficiency of nutrient absorption. Modulation of this pathway may therefore be effective for enhancing resistance to enteropathogens and for the treatment of metabolic diseases.
Topics: Animals; Circadian Rhythm; Eating; Female; Immunity, Innate; Interleukins; Intestinal Absorption; Intestines; Lymphocytes; Male; Mice; Mice, Inbred C57BL; Neurons; Postprandial Period; Receptors, CCR6; Receptors, Vasoactive Intestinal Peptide, Type II; Symbiosis; Vasoactive Intestinal Peptide; Interleukin-22
PubMed: 32050257
DOI: 10.1038/s41586-020-2039-9 -
Shock (Augusta, Ga.) Dec 2023Background: Septic shock is a distributive shock with decreased systemic vascular resistance and MAP. Septic shock contributes to the most common causes of death in the... (Meta-Analysis)
Meta-Analysis
Background: Septic shock is a distributive shock with decreased systemic vascular resistance and MAP. Septic shock contributes to the most common causes of death in the intensive care unit (ICU). Current guidelines recommend the use of norepinephrine as the first-line vasopressor, whereas adrenergic agonists and vasopressin analogs are also commonly used by physicians. To date, very few studies have synthetically compared the effects of multiple types of vasoactive medications. The aim of this study was to systemically evaluate the efficacy of vasoactive agents both individually and in combination to treat septic shock. Methods: The PubMed, MEDLINE, Embase, Web of Science, and Cochrane Central Register for Controlled Trials (CENTRAL) were searched up to May 12, 2022, to identify relevant randomized controlled trials. A network meta-analysis was performed to evaluate the effect of different types of vasopressors. The primary outcome was 28-day all-cause mortality. The secondary outcome was the ICU length of stay. Adverse events are defined as any undesirable outcomes, including myocardial infarction, cardiac arrhythmia, peripheral ischemia, or stroke and cerebrovascular events. Findings: Thirty-three randomized controlled trials comprising 4,966 patients and assessing 8 types of vasoactive treatments were included in the network meta-analysis. The surface under the cumulative ranking curve provided a ranking of vasoactive medications in terms of 28-day all-cause mortality from most effective to least effective: norepinephrine plus dobutamine, epinephrine, vasopressin, terlipressin, norepinephrine, norepinephrine plus vasopressin, dopamine, and dobutamine. Dopamine was associated with a significantly shorter ICU stay than norepinephrine, terlipressin, and vasopressin, whereas other vasoactive medications showed no definite difference in ICU length of stay. Regarding adverse events, norepinephrine was associated with the highest incidences of myocardial infarction and peripheral ischemia. Dopamine was associated with the highest incidence of cardiac arrhythmia. Epinephrine and terlipressin were associated with the highest incidences of myocardial infarction and peripheral ischemia. Interpretation: The results of this network meta-analysis suggest that norepinephrine plus dobutamine is associated with a lower risk of 28-day mortality in septic shock patients than other vasoactive medications, and the use of dopamine is associated with a higher risk of 28-day mortality due to septic shock than norepinephrine, terlipressin, and vasopressin.
Topics: Humans; Shock, Septic; Dopamine; Terlipressin; Dobutamine; Network Meta-Analysis; Vasoconstrictor Agents; Epinephrine; Norepinephrine; Vasopressins; Arrhythmias, Cardiac; Ischemia; Myocardial Infarction
PubMed: 37548686
DOI: 10.1097/SHK.0000000000002193 -
Cholecystokinin neurons in mouse suprachiasmatic nucleus regulate the robustness of circadian clock.Neuron Jul 2023The suprachiasmatic nucleus (SCN) can generate robust circadian behaviors in mammals under different environments, but the underlying neural mechanisms remained unclear....
The suprachiasmatic nucleus (SCN) can generate robust circadian behaviors in mammals under different environments, but the underlying neural mechanisms remained unclear. Here, we showed that the activities of cholecystokinin (CCK) neurons in the mouse SCN preceded the onset of behavioral activities under different photoperiods. CCK-neuron-deficient mice displayed shortened free-running periods, failed to compress their activities under a long photoperiod, and developed rapid splitting or became arrhythmic under constant light. Furthermore, unlike vasoactive intestinal polypeptide (VIP) neurons, CCK neurons are not directly light sensitive, but their activation can elicit phase advance and counter light-induced phase delay mediated by VIP neurons. Under long photoperiods, the impact of CCK neurons on SCN dominates over that of VIP neurons. Finally, we found that the slow-responding CCK neurons control the rate of recovery during jet lag. Together, our results demonstrated that SCN CCK neurons are crucial for the robustness and plasticity of the mammalian circadian clock.
Topics: Animals; Mice; Cholecystokinin; Circadian Clocks; Circadian Rhythm; Mammals; Neurons; Photoperiod; Suprachiasmatic Nucleus; Vasoactive Intestinal Peptide
PubMed: 37172583
DOI: 10.1016/j.neuron.2023.04.016 -
Frontiers in Allergy 2023Angioedema is characterized by swelling localized to the subcutaneous and submucosal tissues. This review provides an overview of angioedema, including the different... (Review)
Review
Angioedema is characterized by swelling localized to the subcutaneous and submucosal tissues. This review provides an overview of angioedema, including the different types, triggers, and underlying pathophysiologic mechanisms. Hereditary and acquired angioedema are caused by dysregulation of the complement and kinin pathways. In contrast, drug-induced and allergic angioedema involve the activation of the immune system and release of vasoactive mediators. Recent advances in the understanding of the pathophysiology of angioedema have led to the development of targeted therapies, such as monoclonal antibodies, bradykinin receptor antagonists, and complement inhibitors, which promise to improve clinical outcomes in patients with this challenging condition. To accurately diagnose and manage angioedema, an understanding of this condition's complex and varied pathophysiology is both necessary and critical.
PubMed: 37920409
DOI: 10.3389/falgy.2023.1263432 -
Current Opinion in Endocrinology,... Feb 2020To summarize the use of gastrointestinal peptides in the management of portal hypertension. (Review)
Review
PURPOSE OF REVIEW
To summarize the use of gastrointestinal peptides in the management of portal hypertension.
RECENT FINDINGS
Vasoactive peptides are commonly used in the management of acute variceal hemorrhage and hepatorenal syndrome, which are portal hypertensive complications of cirrhosis. The main vasoactive peptides that are used are somatostatin and its long-acting analogue octreotide, and vasopressin and its analogue terlipressin. Early initiation of vasoactive peptides in the management of acute variceal hemorrhage and hepatorenal syndrome is associated with improved outcomes. Octreotide is the available vasoactive peptide in the Unites States. Recent developments and ongoing clinical trials may improve our understanding of hepatorenal syndrome and influence the use of vasoactive peptides, particularly terlipressin.
SUMMARY
Here, we review the literature on the use of vasoactive peptides in the management of acute variceal hemorrhage and hepatorenal syndrome.
Topics: Esophageal and Gastric Varices; Gastrointestinal Hemorrhage; Hepatorenal Syndrome; Humans; Hypertension, Portal; Liver Cirrhosis; Lypressin; Octreotide; Peptide Fragments; Somatostatin; Terlipressin
PubMed: 31815783
DOI: 10.1097/MED.0000000000000528 -
Oxidative Medicine and Cellular... 2022Vascular aging is a specific type of organic aging that plays a central role in the morbidity and mortality of cardiovascular and cerebrovascular diseases among the... (Review)
Review
Vascular aging is a specific type of organic aging that plays a central role in the morbidity and mortality of cardiovascular and cerebrovascular diseases among the elderly. It is essential to develop novel interventions to prevent/delay age-related vascular pathologies by targeting fundamental cellular and molecular aging processes. Endogenous vasoactive peptides are compounds formed by a group of amino acids connected by peptide chains that exert regulatory roles in intercellular interactions involved in a variety of biological and pathological processes. Emerging evidence suggests that a variety of vasoactive peptides play important roles in the occurrence and development of vascular aging and related diseases such as atherosclerosis, hypertension, vascular calcification, abdominal aortic aneurysms, and stroke. This review will summarize the cumulative roles and mechanisms of several important endogenous vasoactive peptides in vascular aging and vascular aging-related diseases. In addition, we also aim to explore the promising diagnostic function as biomarkers and the potential therapeutic application of endogenous vasoactive peptides in vascular aging-related diseases.
Topics: Aged; Aging; Amino Acids; Atherosclerosis; Biomarkers; Humans; Peptides; Vascular Diseases
PubMed: 36225176
DOI: 10.1155/2022/1534470