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Current Opinion in Nephrology and... Mar 2024The transmembrane protein 16A (TMEM16A) Ca 2+ -activated Cl - channel constitutes a key depolarising mechanism in vascular smooth muscle and contractile pericytes, while... (Review)
Review
PURPOSE OF REVIEW
The transmembrane protein 16A (TMEM16A) Ca 2+ -activated Cl - channel constitutes a key depolarising mechanism in vascular smooth muscle and contractile pericytes, while in endothelial cells the channel is implicated in angiogenesis and in the response to vasoactive stimuli. Here, we offer a critical analysis of recent physiological investigations and consider the potential for targeting TMEM16A channels in vascular disease.
RECENT FINDINGS
Genetic deletion or pharmacological inhibition of TMEM16A channels in vascular smooth muscle decreases artery tone and lowers systemic blood pressure in rodent models. Inhibition of TMEM16A channels in cerebral cortical pericytes protects against ischemia-induced tissue damage and improves microvascular blood flow in rodent stroke models. In endothelial cells, the TMEM16A channel plays varied roles including modulation of cell division and control of vessel tone through spread of hyperpolarisation to the smooth muscle cells. Genetic studies implicate TMEM16A channels in human disease including systemic and pulmonary hypertension, stroke and Moyamoya disease.
SUMMARY
The TMEM16A channel regulates vascular function by controlling artery tone and capillary diameter as well as vessel formation and histology. Preclinical and clinical investigations are highlighting the potential for therapeutic exploitation of the channel in a range of maladaptive states of the (micro)circulation.
Topics: Humans; Chloride Channels; Endothelial Cells; Hypertension, Pulmonary; Myocytes, Smooth Muscle; Stroke
PubMed: 38193301
DOI: 10.1097/MNH.0000000000000967 -
Current Knowledge about Headaches Attributed to Ischemic Stroke: Changes from Structure to Function.Brain Sciences Jul 2023Headaches are common after ischemic stroke (IS). Unlike primary headaches, headaches attributed to IS have specific clinical features. This review describes the... (Review)
Review
Headaches are common after ischemic stroke (IS). Unlike primary headaches, headaches attributed to IS have specific clinical features. This review describes the epidemiology, clinical characteristics, risk factors, and influence of IS headaches. Previous reports were summarized to show the correlations between headaches and structural lesions in the cerebral cortex, subcortical white matter, deep gray matter nuclei, brainstem, and cerebellum. However, the substantial heterogeneity of IS, subjective evaluations of headaches, and inadequate cohort studies make it difficult to explore the pathophysiology of headaches attributed to IS. In our recommendation, favorable imaging techniques, such as magnetic resonance imaging and positron emission tomography, may provide new insights into mechanical studies of IS headaches from structure to function. It may also be helpful to extend the research field by targeting several shared signal transducers between headaches and IS. These markers might be neuropeptides, vasoactive substances, ion channels, or electrophysiologic changes.
PubMed: 37509047
DOI: 10.3390/brainsci13071117 -
Journal of Molecular and Cellular... May 2024The coronary circulation has the inherent ability to maintain myocardial perfusion constant over a wide range of perfusion pressures. The phenomenon of pressure-flow... (Review)
Review
The coronary circulation has the inherent ability to maintain myocardial perfusion constant over a wide range of perfusion pressures. The phenomenon of pressure-flow autoregulation is crucial in response to flow-limiting atherosclerotic lesions which diminish coronary driving pressure and increase risk of myocardial ischemia and infarction. Despite well over half a century of devoted research, understanding of the mechanisms responsible for autoregulation remains one of the most fundamental and contested questions in the field today. The purpose of this review is to highlight current knowledge regarding the complex interrelationship between the pathways and mechanisms proposed to dictate the degree of coronary pressure-flow autoregulation. Our group recently likened the intertwined nature of the essential determinants of coronary flow control to the symbolically unsolvable "Gordian knot". To further efforts to unravel the autoregulatory "knot", we consider recent challenges to the local metabolic and myogenic hypotheses and the complicated dynamic structural and functional heterogeneity unique to the heart and coronary circulation. Additional consideration is given to interrogation of putative mediators, role of K and Ca channels, and recent insights from computational modeling studies. Improved understanding of how specific vasoactive mediators, pathways, and underlying disease states influence coronary pressure-flow relations stands to significantly reduce morbidity and mortality for what remains the leading cause of death worldwide.
Topics: Humans; Coronary Circulation; Homeostasis; Animals; Blood Pressure; Coronary Vessels; Hemodynamics
PubMed: 38608928
DOI: 10.1016/j.yjmcc.2024.04.008 -
Clinical Autonomic Research : Official... Dec 2023
Recent updates in autonomic research: new insights into vagal nerve activity during exercise, cardiac autonomic neuropathy and silent myocardial infarction in diabetes, and timing of orthostatic blood pressure change and future risk of dementia.
Topics: Humans; Blood Pressure; Heart; Vagus Nerve; Diabetes Mellitus; Myocardial Infarction; Dementia; Autonomic Nervous System Diseases; Diabetic Neuropathies
PubMed: 37924394
DOI: 10.1007/s10286-023-00999-x -
Canadian Journal of Anaesthesia =... Sep 2023Abrupt hemodynamic changes or life-threatening arrhythmias are frequently observed in individuals receiving anesthesia for cardiac arrhythmia ablation. Remimazolam is a... (Review)
Review
Effects of remimazolam on hemodynamic changes during cardiac ablation for atrial fibrillation under general anesthesia: a propensity-score-matched retrospective cohort study.
PURPOSE
Abrupt hemodynamic changes or life-threatening arrhythmias are frequently observed in individuals receiving anesthesia for cardiac arrhythmia ablation. Remimazolam is a novel ultra-short-acting benzodiazepine that has been associated with better hemodynamic stability than conventional anesthetic agents do. This study aimed to investigate whether remimazolam reduces vasoactive agent use compared with desflurane in individuals undergoing ablation for atrial fibrillation under general anesthesia.
METHODS
In a retrospective cohort study, we reviewed electronic medical records of adult patients who underwent ablation for atrial fibrillation under general anesthesia between July 2021 and July 2022. We divided patients into remimazolam and desflurane groups according to the principal agent used for anesthesia. The primary endpoint was the overall incidence of vasoactive agent use. We compared the groups using propensity-score matching (PSM) analysis.
RESULTS
A total of 177 patients were included-78 in the remimazolam group and 99 in the desflurane group. After PSM, 78 final patients were included in each group. The overall incidence of vasoactive agent use was significantly lower in the remimazolam group than in the desflurane group (41% vs 74% before PSM; 41% vs 73% after PSM; both, P < 0.001). The incidence rate, duration, and maximum dose of continuous vasopressor infusion were also significantly lower in the remimazolam group (P < 0.001). Use of remimazolam was not associated with increased complications after the ablation procedures.
CONCLUSIONS
General anesthesia using remimazolam vs desflurane was associated with significantly reduced vasoactive agent requirement and better hemodynamic stability without increased postoperative complications in patients undergoing ablation for atrial fibrillation.
Topics: Adult; Humans; Atrial Fibrillation; Desflurane; Retrospective Studies; Anesthesia, General; Benzodiazepines; Hemodynamics
PubMed: 37430181
DOI: 10.1007/s12630-023-02514-2 -
Anatomical Record (Hoboken, N.J. : 2007) Aug 2024The amygdaloid complex, also known as the amygdala, is a heterogeneous group of distinct nuclear and cortical pallial and subpallial structures. The amygdala plays an...
The amygdaloid complex, also known as the amygdala, is a heterogeneous group of distinct nuclear and cortical pallial and subpallial structures. The amygdala plays an important role in several complex functions including emotional behavior and learning. The expression of calcium-binding proteins and peptides in GABAergic neurons located in the pallial and subpallial amygdala is not uniform and is sometimes restricted to specific groups of cells. Vasoactive intestinal polypeptide (VIP) is present in specific subpopulations of GABAergic cells in the amygdala. VIP immunoreactivity has been observed in somatodendritic and axonal profiles of the rat basolateral and central amygdala. However, a comprehensive analysis of the distribution of VIP immunoreactivity in the various pallial and subpallial structures is currently lacking. The present study used immunohistochemical and morphometric techniques to analyze the distribution and the neuronal localization of VIP immunoreactivity in the rat pallial and subpallial amygdala. In the pallial amygdala, VIP-IR neurons are local inhibitory interneurons that presumably directly and indirectly regulate the activity of excitatory pyramidal neurons. In the subpallial amygdala, VIP immunoreactivity is expressed in several inhibitory cell types, presumably acting as projection or local interneurons. The distribution of VIP immunoreactivity is non-homogeneous throughout the different areas of the amygdaloid complex, suggesting a distinct influence of this neuropeptide on local neuronal circuits and, consequently, on the cognitive, emotional, behavioral and endocrine activities mediated by the amygdala.
Topics: Animals; Vasoactive Intestinal Peptide; Rats; gamma-Aminobutyric Acid; Male; Amygdala; Rats, Wistar; GABAergic Neurons; Immunohistochemistry; Interneurons; Rats, Sprague-Dawley
PubMed: 38263752
DOI: 10.1002/ar.25390 -
Deutsche Medizinische Wochenschrift... Oct 2023Today, peripheral artery disease (PAD) is treated with the most modern endovascular and open surgical revascularisation procedures. But the short and long-term success...
Today, peripheral artery disease (PAD) is treated with the most modern endovascular and open surgical revascularisation procedures. But the short and long-term success of these interventions is decisively determined by the conservative therapy of PAD, which therefore represents the absolute basic therapy of every PAD. Conservative treatment addresses the "Big Five" of atherosclerosis risk factors: smoking, lack of exercise and overweight, diabetes, hypertension, and hyperlipidemia. Despite the knowledge that PAD as a peripheral manifestation of the systemic atherosclerosis needs the same risk factor management as e.g., coronary heart disease, not even every second PAD patient in Germany receives the required therapy. This paper presents the spectrum of both drug and non-drug strategies and focuses on aspects such as platelet inhibition and anticoagulation regimes, lipid-lowering options as well as the benefits and necessity of exercise programs to promote collaterals and improve quality of life by extending the pain-free walking distance. Proven strategies to overcome smoking addiction, use and purpose of vasoactive substances are highlighted as well as the potential risks of diabetic foot syndrome for limb salvage and prevention of wounds.
Topics: Humans; Conservative Treatment; Secondary Prevention; Quality of Life; Peripheral Arterial Disease; Atherosclerosis
PubMed: 37757889
DOI: 10.1055/a-2017-7742 -
Medicine Oct 2023Vitamin C has been used as an adjuvant in the treatment of sepsis and septic shock; however, its role remains controversial. This study aimed to assess the effectiveness... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Vitamin C has been used as an adjuvant in the treatment of sepsis and septic shock; however, its role remains controversial. This study aimed to assess the effectiveness of intravenous high-dose vitamin C in sepsis and septic shock patients by meta-analysis.
METHODS
The PubMed, Embase, and Cochrane Library electronic databases were searched to identify relevant studies. The primary outcome was defined as the short-term all-cause mortality rate. Secondary outcomes included duration of vasoactive drug use, intensive care unit length of stay, sequential organ failure assessment scores up to 96 hours after treatment and 90-day mortality. Review Manager version 5.4 was used to perform the meta-analysis. Relative risk and mean differences (MD) with 95% confidence intervals were determined using fixed- or random-effects models.
RESULTS
Eight randomized controlled trials (RCTs) comprising 1394 patients were eligible for assessment. Overall, the pooled results showed that high-dose vitamin C decreased short-term all-cause mortality in patients with sepsis, but no significant differences were observed in patients with septic shock. Additionally, high-dose vitamin C was associated with decreased duration of vasoactive drug use in patients with sepsis, but not in patients with septic shock. However, it did not significantly affect the duration of intensive care unit stay in RCTs of patients with sepsis and septic shock. Additionally, it did not significantly affect sequential organ failure assessment scores 96 hours post-treatment or 90-day mortality.
CONCLUSION
These results suggest that intravenous high-dose vitamin C may improve outcomes in patients with sepsis, but do not benefit patients with septic shock. Further RCTs and other studies should be conducted to determine whether vitamin C should be recommended as an adjunctive sepsis treatment.
Topics: Humans; Shock, Septic; Randomized Controlled Trials as Topic; Sepsis; Intensive Care Units; Ascorbic Acid; Antineoplastic Agents
PubMed: 37861551
DOI: 10.1097/MD.0000000000035648 -
Nursing Children and Young People Nov 2023Group A Streptococcus bacteria can cause various pyogenic infections such as tonsillitis, pharyngitis, scarlet fever, impetigo, erysipelas, cellulitis and pneumonia....
Group A Streptococcus bacteria can cause various pyogenic infections such as tonsillitis, pharyngitis, scarlet fever, impetigo, erysipelas, cellulitis and pneumonia. Most group A Streptococcus infections in children are mild and respond positively to treatment with antibiotics. However, some children develop severe infection accompanied by complications such as sepsis and will require urgent treatment, which may include non-invasive or invasive ventilation and the administration of fluids and vasoactive agents. In some instances, for example if there are no beds available in the paediatric intensive care unit, these interventions may be undertaken in a ward setting. This article gives an overview of group A Streptococcus infection, including two rare but severe complications, streptococcal toxic shock syndrome and necrotising fasciitis. It uses a fictionalised case study to examine the management of the deteriorating child with suspected group A Streptococcus infection, including respiratory support, haemodynamic support and symptom management.
Topics: Child; Humans; Streptococcal Infections; Scarlet Fever; Streptococcus pyogenes; Anti-Bacterial Agents
PubMed: 37599641
DOI: 10.7748/ncyp.2023.e1467