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F1000Research 2021: Acute mesenteric ischaemia (AMI) is a surgical emergency which has an associated high mortality. The mainstay of active treatment includes early surgical...
: Acute mesenteric ischaemia (AMI) is a surgical emergency which has an associated high mortality. The mainstay of active treatment includes early surgical intervention, with resection of non-viable bowel, and revascularisation of the ischaemic bowel where possible. Due to the physiological insult of AMI however, perioperative care often involves critical care and the use of vasoactive agents to optimise end organ perfusion. A number of these vasoactive agents are currently available with varied mechanism of action and effects on splanchnic blood flow. However, specific guidance on which is the optimal vasoactive drug to use in these settings is limited. This systematic review aimed to evaluate the current evidence comparing vasoactive drugs in AMI. : A systematic search of Ovid Medline, Ovid Embase, Cochrane CENTRAL and the Cochrane Database of Systematic Review was performed on the 5th of November 2020 to identify randomised clinical trials comparing different vasoactive agents in AMI on outcomes including mortality. The search was performed through the Royal College of Surgeons of England (RCSEng) search support library. Results were analysed using the Rayyan platform, and independently screened by four investigators. : 614 distinct papers were identified. After screening, there were no randomised clinical trials meeting the inclusion criteria. : This review identifies a gap in literature, and therefore recommends an investigation into current practice and clinician preference in relation to vasoactive agents in AMI. Multicentre randomised controlled trials comparing these medications on clinical outcomes will therefore be required to address this question.
Topics: Critical Care; England; Humans; Mesenteric Ischemia
PubMed: 34621507
DOI: 10.12688/f1000research.52782.2 -
Annals of the New York Academy of... Nov 2002Abeta peptides are thought to be critical molecules in the pathophysiology of Alzheimer's disease (AD) and are the major protein constituents of senile plaques. In most... (Review)
Review
Abeta peptides are thought to be critical molecules in the pathophysiology of Alzheimer's disease (AD) and are the major protein constituents of senile plaques. In most AD cases, Abeta peptides also form some deposits in the cerebrovasculature, leading to cerebral amyloid angiopathy and hemorrhagic stroke. Regional cerebral hypoperfusion is one of the earlier clinical manifestations in both the sporadic and familial forms of AD. In addition, a variety of vascular risk factors of different etiologies (for instance, diabetes, hypertension, high cholesterol level, atherosclerosis, and smoking) constitute risk factors for AD as well, suggesting that functional vascular abnormalities may contribute to AD pathology. We studied the effect of Abeta on constrictor responses elicited by endothelin-1 in isolated human cerebral arteries collected following rapid autopsies. We report that freshly solubilized Abeta potentiates endothelin-1-induced vasoconstriction in isolated human middle cerebral and basilar arteries. The vasoconstriction elicited by Abeta in these large human cerebral arteries appears to be completely antagonized by NS-398, a selective cyclooxygenase-2 inhibitor, or by SB202190, a specific p38 mitogen-activated protein kinase inhibitor, suggesting that Abeta vasoactivity is mediated via the stimulation of a proinflammatory pathway. In addition, a similar proinflammatory response appears to be mediated by Abeta in isolated human brain microvessels, resulting in an increased production of prostaglandin E(2) and F(2alpha). Using a scanner laser Doppler imager, we show a progressive decline with aging in cortical perfusion level in transgenic APPsw mice (line 2576) compared with age-matched control littermates. The relation between the acute proinflammatory and vasoactive properties of Abeta and the chronic progressive hypoperfusion seen in AD (and transgenic models thereof) is yet to be elucidated.
Topics: Alzheimer Disease; Amyloid beta-Peptides; Cerebrovascular Circulation; Free Radicals; Humans; Inflammation; Risk Factors; Vasoconstriction
PubMed: 12480734
DOI: 10.1111/j.1749-6632.2002.tb04799.x -
Methods in Molecular Biology (Clifton,... 2019Isolated tissue chamber bath system and wire myograph were developed for "in vitro" investigation of vasoactive responses on isolated arteries from a variety of animal...
Isolated tissue chamber bath system and wire myograph were developed for "in vitro" investigation of vasoactive responses on isolated arteries from a variety of animal species and vascular beds. The chapter characterizes the main principles of mechanical measurement of the changes in isometric tension of vascular smooth muscles in isolated rat thoracic aorta and superior mesenteric artery and describes several protocols on how to investigate vasoactive properties of hydrogen sulfide (HS) from the point of view of its mutual interaction with NO. Several methodological advances, results, and their interpretations in the context of the general knowledge are described. In the protocols the approach on how to study the vasoactive modulatory as well as direct action of HS and mutual interaction of HS with nitroso compounds, lipids, and endogenously produced NO is described.
Topics: Animals; Aorta, Thoracic; Hydrogen Sulfide; Mesenteric Arteries; Muscle, Smooth, Vascular; Nitric Oxide; Rats; Rats, Inbred SHR; Rats, Wistar; Vasodilation
PubMed: 31148108
DOI: 10.1007/978-1-4939-9528-8_7 -
International Journal of Molecular... Aug 2022Increased fructose consumption induces metabolic-syndrome-like pathologies and modulates vasoactivity and the participation of nitric oxide (NO) and hydrogen sulfide...
Vasoactive Effects of Chronic Treatment with Fructose and Slow-Releasing HS Donor GYY-4137 in Spontaneously Hypertensive Rats: The Role of Nitroso and Sulfide Signalization.
Increased fructose consumption induces metabolic-syndrome-like pathologies and modulates vasoactivity and the participation of nitric oxide (NO) and hydrogen sulfide (HS). We investigated whether a slow-releasing HS donor, GYY-4137, could exert beneficial activity in these conditions. We examined the effect of eight weeks of fructose intake on the blood pressure, biometric parameters, vasoactive responses, and NO and HS pathways in fructose-fed spontaneously hypertensive rats with or without three weeks of GYY-4137 i.p. application. GYY-4137 reduced triacylglycerol levels and blood pressure, but not adiposity, and all were increased by fructose intake. Fructose intake generally enhanced endothelium-dependent vasorelaxation, decreased adrenergic contraction, and increased protein expression of interleukin-6 (IL-6), tumor necrosis factor alpha (TNFα), and concentration of conjugated dienes in the left ventricle (LV). Although GYY-4137 administration did not affect vasorelaxant responses, it restored disturbed contractility, LV oxidative damage and decreased protein expression of TNFα in fructose-fed rats. While the participation of endogenous HS in vasoactive responses was not affected by fructose treatment, the expression of HS-producing enzyme cystathionine β-synthase in the LV was increased, and the stimulation of the NO signaling pathway improved endothelial function in the mesenteric artery. On the other hand, chronic treatment with GYY-4137 increased the expression of HS-producing enzyme cystathionine γ-lyase in the LV and stimulated the beneficial pro-relaxant and anti-contractile activity of endogenous HS in thoracic aorta. Our results suggest that sulfide and nitroso signaling pathways could trigger compensatory vasoactive responses in hypertensive rats with metabolic disorder. A slow HS-releasing donor could partially amend metabolic-related changes and trigger beneficial activity of endogenous HS.
Topics: Animals; Cystathionine gamma-Lyase; Fructose; Hydrogen Sulfide; Morpholines; Nitric Oxide; Organothiophosphorus Compounds; Rats; Rats, Inbred SHR; Sulfides; Tumor Necrosis Factor-alpha
PubMed: 36012477
DOI: 10.3390/ijms23169215 -
Pediatric Transplantation Jun 2023There is limited data examining donor vasopressor and/or inotrope medications (vasoactives) on pediatric orthotopic heart transplant (OHT) outcomes. We aim to evaluate...
OBJECTIVES
There is limited data examining donor vasopressor and/or inotrope medications (vasoactives) on pediatric orthotopic heart transplant (OHT) outcomes. We aim to evaluate the effects of vasoactives on pediatric OHT outcomes.
METHODS
The United Network for Organ Sharing database was retrospectively reviewed from January 2000 to March 2018 for donor hearts. Exclusion criteria included multiorgan transplants and recipient age >18. Donors receiving vasoactives at the time of procurement were compared to donors not on vasoactives, including the number of vasoactives and the type. End-points of interest were survival at 30 days and 1 year as well as post-transplant rejection at 1 year. Logistic and Cox models were used to quantify survival end-points.
RESULTS
Of 6462 donors, 3187 (49.3%) were receiving at least one vasoactive. Comparing any vasoactive medication versus none, there was no difference in 30-day survival (p = .27), 1 year survival (p = .89), overall survival (p = .68), or post-transplant rejection (p = .98). There was no difference in 30-day survival for donors receiving 2 or more vasoactive infusions (p = .89), 1 year survival (p = .53), overall survival (p = .75), or post-transplant rejection at 1 year (p = .87). Vasopressin was associated with decreased 30-day mortality (OR = 0.22; p = .028), dobutamine with decreased 1-year mortality (OR = 0.37; p = .036), overall survival (HR = 0.51; p = .003), and decreased post-transplant rejection (HR = 0.63; p = .012).
CONCLUSIONS
There is no difference in pediatric OHT outcomes when the cardiac donor is treated with vasoactive infusions at procurement. Vasopressin and dobutamine were associated with improved outcomes. This information can be used to guide medical management and donor selection.
Topics: Humans; Child; Tissue Donors; Heart Transplantation; Tissue and Organ Procurement; Retrospective Studies; Dobutamine; Graft Survival
PubMed: 36898843
DOI: 10.1111/petr.14500 -
Birth Defects Research Aug 2020Amniotic band syndrome (ABS) includes limb deficiencies accompanied by fibrous strands originating from the amniotic lining. Terminal transverse limb deficiencies (TTLD)...
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.
Topics: Amniotic Band Syndrome; Humans; Infant, Newborn; Odds Ratio; Smoking
PubMed: 32573119
DOI: 10.1002/bdr2.1740 -
Peritoneal Dialysis International :... 2008Conventional peritoneal dialysis (PD) solutions elicit vasodilation, which is implicated in the variable rate of solute transport during the dwell. The components...
BACKGROUND
Conventional peritoneal dialysis (PD) solutions elicit vasodilation, which is implicated in the variable rate of solute transport during the dwell. The components causing such vasoactivity are still controversial. This study was conducted to define the vasoactive components of conventional and new PD solutions.
METHODS
Three visceral peritoneal microvascular levels were visualized by intravital video microscopy of the terminal ileum of anesthetized rats. Anesthesia-free decerebrate conscious rats served as control. Microvascular diameter and blood flow by Doppler measurements were conducted after topical peritoneal exposure to 4 clinical PD solutions and 6 prepared solutions designed to isolate potential vasoactive components of the PD solution.
RESULTS
All clinically available PD solutions produced a rapid and generalized vasodilation at all intestinal microvascular levels, regardless of the osmotic solute. The pattern and magnitude of this dilation was not affected by anesthesia but was determined by arteriolar size, the osmotic solute, and the solution's buffer anion system. The greatest dilation occurred in the small precapillary arterioles and was elicited by conventional PD solution and heat re-sterilized solution containing low glucose degradation products (GDPs). Hypertonic mannitol solutions produced a dilation that was approximately 50% less than the dilation obtained with glucose solutions with identical osmolarity and buffer. Increasing a solution's osmolarity did not produce a parallel increase in the magnitude of dilation, suggesting a nonlinear relationship between the two variables. Lactate dissolved in an isotonic solution was completely non-vasoactive unless the solution's H(+) concentration was increased. At low pH, isotonic lactate produced a rapid but transient vasodilation. This vascular reactivity was similar in magnitude and pattern to that obtained with the isotonic 7.5% icodextrin solution (Extraneal; Baxter Healthcare, Deerfield, Illinois, USA).
CONCLUSIONS
(1) Hyperosmolarity is the major vasoactive component of PD solution. (2) Hyperosmolarity and active intracellular glucose uptake account together for approximately 75% of PD solution-induced dilation, whereas GDPs contribute to approximately 25%. (3) Lactate is vasoactive only at low pH (high [H(+)]). (4) The magnitude of PD solution-mediated vasodilation is partially dependent on the nature of the osmotic solute, the GDP contents, and the [H(+)], which determine the vasoactivity of the lactate-buffer anion system. Studies are required to define the molecular mechanisms of PD-induced vasodilation and to determine the vasoactive properties of these solutions after chronic infusion.
Topics: Animals; Biological Transport; Buffers; Dialysis Solutions; Glucans; Glucose; Icodextrin; Lactates; Male; Microcirculation; Osmolar Concentration; Peritoneal Cavity; Peritoneal Dialysis; Peritoneum; Random Allocation; Rats; Rats, Sprague-Dawley; Rats, Wistar; Regional Blood Flow; Vasodilation
PubMed: 18474922
DOI: No ID Found -
Congenital Heart Disease Nov 2019The main goal of this study is to examine the variation in vasoactive agent prescription patterns across a large cohort of patients. In addition, we sought to determine... (Comparative Study)
Comparative Study
OBJECTIVE
The main goal of this study is to examine the variation in vasoactive agent prescription patterns across a large cohort of patients. In addition, we sought to determine the association between the number of vasoactive agents used during admissions and characteristics of admissions utilizing varying numbers of vasoactive agents.
METHODS
This was a multi-institutional, cross-sectional study of the pediatric health information system database of patients who underwent congenital heart surgery and received vasoactive agents from 2004 to 2015. The international classification of disease-9 (ICD-9) codes were used to select admissions to those only pertaining to cardiac patients. The vasoactive agents investigated included epinephrine, norepinephrine, dopamine, dobutamine, milrinone, and vasopressin.
RESULTS
A total of 43 441 postoperative pediatric cardiac admissions were identified and included in the final analyses. Of these, a majority used at least one vasoactive agent at some point during the admissions with the median being three vasoactives. Each vasoactive was utilized with decreasing frequency throughout the study period except for vasopressin which increased in frequency of use. After adjusting for multiple confounding factors, only milrinone was associated with decreased inpatient mortality in any postoperative subset, while the rest of the vasoactive were associated with increased inpatient mortality in some of the postoperative subsets.
CONCLUSION
Vasoactive agents have decreased in frequency of use in postoperative pediatric cardiac admissions, except for vasopressin. Only milrinone was found to be associated with decreased inpatient mortality in any subset of these patients, while all other vasoactive agents were found to be associated with increased inpatient mortality at least in one of the subsets.
Topics: Age Factors; Cardiac Surgical Procedures; Cardiotonic Agents; Cross-Sectional Studies; Databases, Factual; Drug Utilization; Hospital Mortality; Humans; Patient Admission; Postoperative Care; Practice Patterns, Physicians'; Risk Factors; Time Factors; Treatment Outcome; United States; Vasoconstrictor Agents
PubMed: 31454161
DOI: 10.1111/chd.12837 -
Pediatric Critical Care Medicine : a... Aug 2017Pediatric shock represents a major cause of morbidity and mortality in the United States. Standardization of treatment such as volume resuscitation and vasoactive...
OBJECTIVE
Pediatric shock represents a major cause of morbidity and mortality in the United States. Standardization of treatment such as volume resuscitation and vasoactive administration has resulted in improved patient outcomes. Vasoactives have been anecdotally associated with peripheral IV infiltration and extravasation. There is a paucity of evidence in pediatrics to determine the ideal route of vasoactive infusions and what, if any, risk factors and harm are associated with peripheral IV infiltration and extravasation. We aim to assess the frequency of and risk factors for peripheral IV infiltration and extravasation during peripheral IV vasoactive infusions in children admitted to the PICU.
DESIGN
A retrospective, cohort study of all children admitted to a PICU from January 2012 to June 2014.
SETTING
Forty-four-bed PICU at Children's National Health System.
PATIENTS
All children 0-18 years old receiving a vasoactive infusion through a peripheral IV for a minimum of 1 hour.
INTERVENTIONS
None.
MEASUREMENTS AND MAIN RESULTS
The primary outcomes of this study were incidence of peripheral IV infiltration and extravasation and resultant tissue injury. Secondary outcomes were peripheral IV characteristics and vasoactive infusion data. One hundred two patients met inclusion criteria. Sixty-two percent (63/102) were admitted with the diagnosis of septic shock. The most commonly used vasoactive agent was dopamine. The median peak Vasoactive Infusion Score was 10 (6-14). Peripheral IV infiltration and extravasation incidence was 2% (2/102) and neither event resulted in injury requiring medical or surgical intervention.
CONCLUSIONS
Vasoactive infusions through peripheral IV in children admitted to the PICU with shock were observed to have a low incidence of peripheral IV infiltration and extravasation and resultant tissue injury. Short-term delivery of vasoactives via peripheral IV catheter in a highly monitored PICU setting appears to be safe.
Topics: Adolescent; Catheterization, Peripheral; Child; Child, Preschool; Drug Administration Schedule; Extravasation of Diagnostic and Therapeutic Materials; Female; Humans; Incidence; Infant; Infant, Newborn; Infusions, Intravenous; Male; Retrospective Studies; Risk Factors; Shock, Septic; Vasoconstrictor Agents
PubMed: 28617763
DOI: 10.1097/PCC.0000000000001230 -
European Journal of Pharmaceutical... Apr 2019Ischemic heart conditions are among the main causes of sudden cardiac death worldwide. One of the strategies for avoiding myocardial infarction is the low-dose,...
Ischemic heart conditions are among the main causes of sudden cardiac death worldwide. One of the strategies for avoiding myocardial infarction is the low-dose, prophylactic use of acetylsalicylic acid (ASA), an inhibitor of platelet aggregation. To avoid the gastrointestinal damage, ASA prodrugs bearing nitric oxide (NO)-donating moiety covalently conjugated to ASA have been synthesized and evaluated extensively worldwide. Herein the synthesis of a new hybrid ASA ester covalently attached to the NO donor linsidomine, an active metabolite of molsidomine (MOL) is reported. Cell viability assay and hemolysis tests were performed in H9c2 cells and rat erythrocytes, respectively. Our new compound, the ERJ-500 not affected negatively the viability of living cells in the concentration range of 100 nM to 100 μM. Using the ex vivo Langendorff method on hearts originated from female rats, compound ERJ-500 displayed a dose-dependent, outwashable vasodilative effect in coronary arteries. Vasodilation was observed on isolated working heart model as well, with elevated stroke volume in hearts treated with ERJ-500. Furthermore, a decreased infarct size was also noticed in ERJ-500 treated hearts after ischemia/reperfusion. Based on these observations it can be expected that our new hybrid ASA may contribute to new pharmacological tool in the therapy of ischemic heart conditions and associated syndromes.
Topics: Animals; Aspirin; Cell Line; Coronary Circulation; Erythrocytes; Female; Heart; Heart Rate; Hemolysis; Molsidomine; Nitric Oxide; Rats, Sprague-Dawley; Vasodilation; Vasodilator Agents
PubMed: 30779982
DOI: 10.1016/j.ejps.2019.02.020