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Heliyon Aug 2023Examination of circulatory dynamics and autonomic nerve activity in acute hemorrhage in diabetic (DM) rats revealed that despite decreased receptor sensitivity to...
Examination of circulatory dynamics and autonomic nerve activity in acute hemorrhage in diabetic (DM) rats revealed that despite decreased receptor sensitivity to arterial blood pressure, the DM rats experienced a decline in the heart rate and acceleration of the parasympathetic nerve activity at the sympathoinhibitory phase in response to bleeding (Bezold-Jarisch [B-J] reflex). To elucidate the involvement of the B-J reflex as a reaction to acute hemorrhage in DM rats by assessing -Fos-positive cell (-Fos) expression in the nucleus of the solitary tract (SolM), the primary relay nucleus of the baroreflex, Streptozotocin-induced DM and non-DM rats underwent controlled-graded bleeding or continuous phenylephrine infusion under conscious state. Changes in hemodynamics and autonomous nervous system caused by acute hemorrhage and continuous phenylephrine infusion were examined by analyzing blood pressure-heart rate variability. Furthermore, effects of hemorrhage and phenylephrine infusion on the expression of -Fos in SolM were examined. DM rats showed increased -Fos expression in response to acute blood loss in the SolM. Non-DM rats showed the same phenomenon in response to continuous phenylephrine infusion in the SolM. Significant interactions between DM and Non-DM rats were observed among hemodynamic and autonomic response to acute hemorrhage and continuous phenylephrine infusion. DM rats were sensitive to acute blood loss, and the circulatory system easily collapsed with accelerating parasympathetic activity in the form of the B-J reflex.
PubMed: 37520984
DOI: 10.1016/j.heliyon.2023.e18394 -
Intensive Care Medicine Experimental May 2024Catecholamines are commonly used as therapeutic drugs in intensive care medicine to maintain sufficient organ perfusion during shock. However, excessive or sustained...
BACKGROUND
Catecholamines are commonly used as therapeutic drugs in intensive care medicine to maintain sufficient organ perfusion during shock. However, excessive or sustained adrenergic activation drives detrimental cardiac remodeling and may lead to heart failure. Whether catecholamine treatment in absence of heart failure causes persistent cardiac injury, is uncertain. In this experimental study, we assessed the course of cardiac remodeling and recovery during and after prolonged catecholamine treatment and investigated the molecular mechanisms involved.
RESULTS
C57BL/6N wild-type mice were assigned to 14 days catecholamine treatment with isoprenaline and phenylephrine (IsoPE), treatment with IsoPE and subsequent recovery, or healthy control groups. IsoPE improved left ventricular contractility but caused substantial cardiac fibrosis and hypertrophy. However, after discontinuation of catecholamine treatment, these alterations were largely reversible. To uncover the molecular mechanisms involved, we performed RNA sequencing from isolated cardiomyocyte nuclei. IsoPE treatment resulted in a transient upregulation of genes related to extracellular matrix formation and transforming growth factor signaling. While components of adrenergic receptor signaling were downregulated during catecholamine treatment, we observed an upregulation of endothelin-1 and its receptors in cardiomyocytes, indicating crosstalk between both signaling pathways. To follow this finding, we treated mice with endothelin-1. Compared to IsoPE, treatment with endothelin-1 induced minor but longer lasting changes in cardiomyocyte gene expression. DNA methylation-guided analysis of enhancer regions identified immediate early transcription factors such as AP-1 family members Jun and Fos as key drivers of pathological gene expression following catecholamine treatment.
CONCLUSIONS
The results from this study show that prolonged catecholamine exposure induces adverse cardiac remodeling and gene expression before the onset of left ventricular dysfunction which has implications for clinical practice. The observed changes depend on the type of stimulus and are largely reversible after discontinuation of catecholamine treatment. Crosstalk with endothelin signaling and the downstream transcription factors identified in this study provide new opportunities for more targeted therapeutic approaches that may help to separate desired from undesired effects of catecholamine treatment.
PubMed: 38733526
DOI: 10.1186/s40635-024-00632-9 -
International Journal of Medical... 2023Hypothermia is common in patients undergoing urological surgery; however, no single preventative modality is completely effective. This study evaluated the effects of... (Randomized Controlled Trial)
Randomized Controlled Trial
The effect of combining prewarming with intraoperative phenylephrine infusion on the prevention of hypothermia in patients undergoing urological surgery: a prospective, randomized, and controlled trial.
Hypothermia is common in patients undergoing urological surgery; however, no single preventative modality is completely effective. This study evaluated the effects of combining prewarming with intraoperative phenylephrine infusion for the prevention of hypothermia in patients undergoing urological surgery. This prospective study enrolled 58 patients scheduled for urological surgery under general anesthesia. The patients were randomized into two groups (n = 29). Patients in the experimental (prewarming and phenylephrine infusion) group (PP group) received prewarming for 20 min and intraoperative phenylephrine infusion, whereas those in the control group (C group) received no active prewarming with only intermittent administration of vasoactive agents. The patient's sublingual temperatures before and after anesthesia and nasopharyngeal temperature during anesthesia were recorded as core temperatures. The incidence of intraoperative hypothermia was higher in the C group than in the PP group (57.7% [15/26] vs. 23.1% [6/26], = 0.01). The severity of intraoperative hypothermia was higher in the C group than in the PP group ( = 0.004). The nasopharyngeal temperature at the end of surgery was lower in the C group than in the PP group (35.8 ± 0.6°C vs. 36.3 ± 0.4°C, = 0.002). The trend of core temperature decline during the first hour after anesthesia induction differed between the two groups ( = 0.003; its decline was more gradual in the PP group). The combination of prewarming for 20 min and intraoperative phenylephrine infusion reduced the incidence and severity of intraoperative hypothermia and modified the trend of decreasing core temperatures in patients undergoing urological surgery.
Topics: Humans; Hypothermia; Prospective Studies; Phenylephrine; Body Temperature; Perioperative Care
PubMed: 37928872
DOI: 10.7150/ijms.89671 -
Cureus Mar 2024This study delves into the prevalence of spinal anesthesia-induced hypotension during cesarean (c-section) childbirth, focusing on existing treatments and their... (Review)
Review
This study delves into the prevalence of spinal anesthesia-induced hypotension during cesarean (c-section) childbirth, focusing on existing treatments and their efficacy. Currently, neuraxial analgesia is the most efficient method for alleviating pain during c-sections, but its major side effect, hypotension, necessitates a thorough understanding of the available treatment options. A scoping review was conducted using PubMed and Rayyan, with inclusion criteria being English peer-reviewed articles from the last five years, involving nulligravida/primigravida women under 35 years old in the United States. The research reveals various treatments to mitigate spinal anesthesia-induced hypotension. Norepinephrine and epinephrine have demonstrated effectiveness in maintaining blood pressure while reducing adverse maternal outcomes following delivery. When comparing fixed-rate infusions of norepinephrine to phenylephrine, norepinephrine demonstrated lower rates of bradycardia (=0.004), thereby reducing the necessity for bolus atropine rescue (=0.01). Furthermore, the use of colloid solutions during c-sections significantly decreased the incidence of hypotension when compared to crystalloid solutions (<0.00001). Non-pharmacological methods, such as lower extremity wrapping and elevation, exhibited higher systolic and diastolic blood pressures, along with higher usage of ephedrine when compared to control groups. Pharmacological treatments proved more effective than non-pharmacological interventions in preventing maternal hypotension during c-sections. Notably, colloid preloading emerged as the most effective approach, helping to maintain maternal blood pressure, cardiac output, and heart rate while also minimizing the amount of ephedrine required and reducing anesthesia-related adverse effects. However, the study suggests the need for further investigations to determine the optimal dosage for colloid preloading. This research provides valuable insights into enhancing maternal well-being during c-sections by addressing the issue of neuraxial anesthesia-induced hypotension.
PubMed: 38633922
DOI: 10.7759/cureus.56340 -
Frontiers in Veterinary Science 2023A 7-year-old castrated male American Shorthair cat presented with left-side Horner's syndrome and voice change. The overall clinical presentation included dysphagia,...
A 7-year-old castrated male American Shorthair cat presented with left-side Horner's syndrome and voice change. The overall clinical presentation included dysphagia, intermittent coughing, unilateral miosis, and third eyelid protrusion of the left eye. A topical 1% phenylephrine was applied, and miosis and protrusion of the third eyelid disappeared within 20 min which suggested a post-ganglionic lesion. Laryngoscopy showed left-sided laryngeal paralysis. Computed tomography (CT) identified a mass lesion invading outside of the left tympanic bulla with osteolysis. Endoscopically assisted ventral bulla osteotomy was performed for tumor resection and definitive diagnosis. Middle ear adenocarcinoma was diagnosed based on histopathology. It appears that these neurological signs occurred due to adenocarcinoma in the tympanic bulla, penetrating the jugular foramen and the hypoglossal canal and damaging the cranial nerve IX (glossopharyngeal nerve), X (vagus nerve), XI (accessory nerve), and XII (hypoglossal nerve) and the sympathetic nerve. To the best of our knowledge, this is the first case report of Villaret's syndrome associated with middle ear adenocarcinoma affecting the nerves passing through the jugular foramen and hypoglossal canal in cats.
PubMed: 37576831
DOI: 10.3389/fvets.2023.1225567 -
Biomedicines Aug 2023(1) Background: Obesity is associated with hypertension because of endocrine dysregulation of the adrenergic and the renin-angiotensin-aldosterone systems. The epidermal...
(1) Background: Obesity is associated with hypertension because of endocrine dysregulation of the adrenergic and the renin-angiotensin-aldosterone systems. The epidermal growth factor receptor (EGFR) is an important signaling hub in the cardiovascular system. In this study, we investigate the role of smooth muscle cell (VSMC) and endothelial cell (EC) EGFRs for blood pressure homeostasis and acute vascular reactivity in vivo. (2) Methods: Mice with deletion of the EGFR in the respective cell type received either a high-fat (HFD) or standard-fat diet (SFD) for 18 weeks. Intravascular blood pressure was measured via a Millar catheter in anesthetized animals upon vehicle load, angiotensin II (AII) and phenylephrine (PE) stimulation. (3) Results: We confirmed that deletion of the EGFR in VSMCs leads to reduced blood pressure and a most probably compensatory heart rate increase. EC-EGFR and VSMC-EGFR had only a minor impact on volume-load-induced blood pressure changes in lean as well as in obese wild-type animals. Regarding vasoactive substances, EC-EGFR seems to have no importance for angiotensin II action and counteracting HFD-induced prolonged blood pressure increase upon PE stimulation. VSMC-EGFR supports the blood pressure response to adrenergic and angiotensin II stimulation in lean animals. The responsiveness to AII and alpha-adrenergic stimulation was similar in lean and obese animals despite the known enhanced activity of the RAAS and the sympathetic nervous system under a high-fat diet. (4) Conclusions: We demonstrate that EGFRs in VSMCs and to a lesser extent in ECs modulate short-term vascular reactivity to AII, catecholamines and volume load in lean and obese animals.
PubMed: 37626737
DOI: 10.3390/biomedicines11082241 -
BMC Anesthesiology Mar 2024Tracking preload dependency non-invasively to maintain adequate tissue perfusion in the perioperative period can be challenging.The effect of phenylephrine on stroke... (Observational Study)
Observational Study
BACKGROUND
Tracking preload dependency non-invasively to maintain adequate tissue perfusion in the perioperative period can be challenging.The effect of phenylephrine on stroke volume is dependent upon preload. Changes in stroke volume induced by phenylephrine administration can be used to predict preload dependency. The change in the peripheral perfusion index derived from photoplethysmography signals reportedly corresponds with changes in stroke volume in situations such as body position changes in the operating room. Thus, the peripheral perfusion index can be used as a non-invasive potential alternative to stroke volume to predict preload dependency. Herein, we aimed to determine whether changes in perfusion index induced by the administration of phenylephrine could be used to predict preload dependency.
METHODS
We conducted a prospective single-centre observational study. The haemodynamic parameters and perfusion index were recorded before and 1 and 2 min after administering 0.1 mg of phenylephrine during post-induction hypotension in patients scheduled to undergo surgery. Preload dependency was defined as a stroke volume variation of ≥ 12% before phenylephrine administration at a mean arterial pressure of < 65 mmHg. Patients were divided into four groups according to total peripheral resistance and preload dependency.
RESULTS
Forty-two patients were included in this study. The stroke volume in patients with preload dependency (n = 23) increased after phenylephrine administration. However, phenylephrine administration did not impact the stroke volume in patients without preload dependency (n = 19). The perfusion index decreased regardless of preload dependency. The changes in the perfusion index after phenylephrine administration exhibited low accuracy for predicting preload dependency. Based on subgroup analysis, patients with high total peripheral resistance tended to exhibit increased stroke volume following phenylephrine administration, which was particularly prominent in patients with high total peripheral resistance and preload dependency.
CONCLUSION
The findings of the current study revealed that changes in the perfusion index induced by administering 0.1 mg of phenylephrine could not predict preload dependency. This may be attributed to the different phenylephrine-induced stroke volume patterns observed in patients according to the degree of total peripheral resistance and preload dependency.
TRIAL REGISTRATION
University Hospital Medical Information Network (UMIN000049994 on 9/01/2023).
Topics: Humans; Phenylephrine; Cardiac Output; Prospective Studies; Perfusion Index; Stroke Volume; Anesthesia, General; Fluid Therapy; Blood Pressure
PubMed: 38431582
DOI: 10.1186/s12871-024-02478-w -
JVS-vascular Science 2023Arterial ring testing is the gold standard for measuring arterial function. Increased arterial tone through arterial contraction and impaired endothelial relaxation...
OBJECTIVE
Arterial ring testing is the gold standard for measuring arterial function. Increased arterial tone through arterial contraction and impaired endothelial relaxation (endothelial dysfunction) are key metrics of impaired arterial health in peripheral arterial disease (PAD). To allow for comparative testing of arteries during standard laboratory hours, storage buffers and conditions have been used to extend the functional life of arteries. Various storage conditions have been compared, but there has not been a robust comparison or validation in human arteries. The objective of this work is to optimize storage of arterial segments for endothelial cell (EC) testing in a murine model and to test EC function in human PAD arteries. We hypothesized that certain storage conditions would be superior to others.
METHODS
Healthy murine aortas were harvested from 10- to 14-week-old C57/Bl6J male and female mice and compared under different storage protocols (24 hours) to immediate arterial testing. The storage conditions tested were: Opti-MEM (37°C or 4°C), Krebs-HEPES with 1.8 mmol/L or 2.5 mmol/L calcium (4°C), or Wisconsin (WI) solution at 4°C. Vascular function was evaluated by isometric force testing. Endothelium-dependent and -independent relaxation were measured after precontraction with addition of methacholine or sodium nitroprusside, respectively. Arterial contraction was stimulated with potassium chloride or phenylephrine. Analysis of variance was used to determine significance compared with immediate testing with < .05. Under institutional review board approval, 28 PAD arteries were collected at amputation and underwent vascular function testing as described. Disturbed flow conditions were determined by indirect (upstream occlusion) flow to the harvested tibial arteries. Stable flow arteries had in-line flow. Arterial calcification was quantified manually as present or not present.
RESULTS
We found that 4°C WI and 37°C Opti-MEM best preserved endothelium-dependent relaxation and performed similarly to immediately testing aortas (termed fresh for freshly tested) ( > .95). Other storage conditions were inferior to freshly tested aortas ( < .05). Vascular smooth muscle function was tested by endothelial-independent relaxation and contractility. All storage conditions preserved endothelial-independent relaxation and contractility similar to freshly tested arteries. However, 4°C WI and 37°C Opti-MEM storage conditions most closely approximated the maximum force of contraction of freshly tested arteries in response to potassium chloride ( > .39). For human arterial testing, 28 tibial arteries were tested for relaxation and contraction with 16 arteries with peripheral artery occlusive disease (PAD with disturbed flow) and 12 without peripheral artery occlusive disease (PAD with stable flow), of which 14 were calcified and 14 were noncalcified. Endothelial-dependent relaxation data was measurable in 9 arteries and arterial contraction data was measurable in 14 arteries. When comparing flow conditions, arteries exposed to disturbed flow (n = 4) had significantly less relaxation (2% vs 59%; = .03) compared with stable flow conditions (n = 5). In contrast, presence the (n = 6) or absence of calcification (n = 3) did not impact arterial relaxation. Arterial contraction was not different between groups in either comparison by flow (n = 9 disturbed; n = 5 stable) or calcification (n = 6 present; n = 8 absent).
CONCLUSIONS
In healthy murine aortas, arterial storage for 24 hours in 4°C WI or 37°C Opti-MEM both preserved endothelium-dependent relaxation and maximum force of contraction. In human PAD arteries stored in 4° WI, flow conditions before arterial harvest, but not arterial calcification, led to differences in arterial relaxation in human PAD arteries. Arterial contractility was more robust (11/28 arteries) compared with arterial relaxation (7/28 arteries), but was not significantly different under flow or calcification parameters. This work defines ideal storage conditions for arterial ring testing and identifies that EC dysfunction from disturbed flow may persist in delayed ex vivo arterial testing.
PubMed: 37649473
DOI: 10.1016/j.jvssci.2023.100122 -
Journal of Critical Care Dec 2023The primary objective was to determine the proportion of hospitals that administered norepinephrine peripheral vasopressor infusions (PVIs) in critically ill adult...
PURPOSE
The primary objective was to determine the proportion of hospitals that administered norepinephrine peripheral vasopressor infusions (PVIs) in critically ill adult patients. Secondary objectives were to describe how norepinephrine is used such as the maximum duration, infusion rate and concentration, and to determine the most common first-line PVI used by country.
MATERIALS AND METHODS
An international multi-centre cross-sectional survey study was conducted in adult intensive care units in Australia, US, UK, Canada, and Saudi Arabia.
RESULTS
Critical care pharmacists from 132 institutions responded to the survey. Norepinephrine PVIs were utilised in 86% of institutions (n = 113/132). The median maximum duration of norepinephrine PVIs was 24 h (IQR 24-24) (n = 57/113). The most common maximum norepinephrine PVI rate was between 11 and 20 μg/min (n = 16/113). The most common maximum norepinephrine PVI concentration was 16 μg/mL (n = 60/113). Half of the institutions had a preference to administer another PVI over norepinephrine as a first-line agent (n = 66/132). The most common alternative PVI used by country was: US (phenylephrine 41%, n = 37/90), Canada (dopamine 31%, n = 5/16), UK (metaraminol 82%, n = 9/11), and Australia (metaraminol 89%, n = 8/9).
CONCLUSIONS
There is variability in clinical practice regarding PVI administration in critically ill adult patients dependent on drug availability and local institutional recommendations.
Topics: Adult; Humans; Metaraminol; Critical Illness; Cross-Sectional Studies; Vasoconstrictor Agents; Norepinephrine; Critical Care; Pharmacy
PubMed: 37536012
DOI: 10.1016/j.jcrc.2023.154376 -
Journal of Clinical Medicine Apr 2024: Sulodexide (SDX) is a drug known for restoring the glycocalyx, thereby offering endothelial protection and regulating permeability. Additionally, it has antithrombotic...
: Sulodexide (SDX) is a drug known for restoring the glycocalyx, thereby offering endothelial protection and regulating permeability. Additionally, it has antithrombotic and anti-inflammatory properties and has shown arterial vasodilatory effects. Endothelial cells play a crucial role in maintaining homeostasis, with their dysfunction being a key contributor to loss in vasodilatory response, especially in arterial pathologies. The aim of this study was to investigate the effects of SDX on stimulated vascular tonus in human arterial samples and to assess the function of the endothelial layer as a source of nitric oxide (NO). : A total of 16 internal mammary artery remnants from coronary artery bypass graft surgeries were dissected into endothelium-intact and endothelium-denuded groups (n = 8 each). The arterial rings were equilibrated under tension, with their basal tonus recorded before and after phenylephrine stimulation. SDX's impact on arterial contraction was assessed through cumulative dose-response curves. NO synthase inhibitor (Nω-nitro-L-arginine methyl ester) was used to assess SDX's vasodilatory effect over the NO pathway. : SDX application resulted in concentration-dependent vasorelaxation in both endothelium-intact and endothelium-denuded groups at certain doses. However, the inhibitory effect of SDX was more pronounced in endothelium-intact rings at higher doses compared to endothelium-denuded rings ( < 0.05). Similar inhibition of contraction curves was achieved for both endothelium-intact and endothelium-denuded rings after L-NAME pre-incubation, suggesting a necessity for NO-related endothelial pathways. : SDX exerts a concentration-dependent inhibition on arterial contraction, emphasizing the critical role of an intact endothelium and NO-mediated pathways in this process. This underscores SDX's potential in treating endothelial dysfunction-related pathologies.
PubMed: 38673605
DOI: 10.3390/jcm13082332