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British Journal of Anaesthesia Oct 2020Patients undergoing cerebral bypass surgery are prone to cerebral hypoperfusion. Currently, arterial blood pressure is often increased with vasopressors to prevent... (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND
Patients undergoing cerebral bypass surgery are prone to cerebral hypoperfusion. Currently, arterial blood pressure is often increased with vasopressors to prevent cerebral ischaemia. However, this might cause vasoconstriction of the graft and cerebral vasculature and decrease perfusion. We hypothesised that cardiac output, rather than arterial blood pressure, is essential for adequate perfusion and aimed to determine whether dobutamine administration resulted in greater graft perfusion than phenylephrine administration.
METHODS
This randomised crossover study included 10 adult patients undergoing cerebral bypass surgery. Intraoperatively, patients randomly and sequentially received dobutamine to increase cardiac index or phenylephrine to increase mean arterial pressure (MAP). An increase of >10% in cardiac index or >10% in MAP was targeted, respectively. Before both interventions, a reference phase was implemented. The primary outcome was the absolute difference in graft flow between the reference and intervention phase. We compared the absolute flow difference between each intervention and constructed a random-effect linear regression model to explore treatment and carry-over effects.
RESULTS
Graft flow increased with a median of 4.1 (inter-quartile range [IQR], 1.7-12.0] ml min) after dobutamine administration and 3.6 [IQR, 1.3-7.8] ml min after phenylephrine administration (difference -0.6 ml min; 95% confidence interval [CI], -14.5 to 5.3; P=0.441). There was no treatment effect (0.9 ml min; 95% CI, 0.0-20.1; P=0.944) and no carry-over effect.
CONCLUSIONS
Both dobutamine and phenylephrine increased graft flow during cerebral bypass surgery, without a preference for one method over the other.
CLINICAL TRIAL REGISTRATION
Netherlands Trial Register, NL7077 (https://www.trialregister.nl/trial/7077).
Topics: Adult; Arterial Pressure; Cardiac Output; Cerebral Revascularization; Cerebrovascular Circulation; Cross-Over Studies; Dobutamine; Female; Humans; Male; Middle Aged; Phenylephrine
PubMed: 32718724
DOI: 10.1016/j.bja.2020.05.040 -
American Journal of Physiology.... Apr 2022Muscle sympathetic nerve activity (MSNA) increases during hyperinsulinemia, primarily attributed to central nervous system effects. Whether peripheral vasodilation...
Muscle sympathetic nerve activity (MSNA) increases during hyperinsulinemia, primarily attributed to central nervous system effects. Whether peripheral vasodilation induced by insulin further contributes to increased MSNA via arterial baroreflex-mediated mechanisms requires further investigation. Accordingly, we examined baroreflex modulation of the MSNA response to hyperinsulinemia. We hypothesized that rescuing peripheral resistance with coinfusion of the vasoconstrictor phenylephrine would attenuate the MSNA response to hyperinsulinemia. We further hypothesized that the insulin-mediated increase in MSNA would be recapitulated with another vasodilator (sodium nitroprusside, SNP). In 33 young healthy adults (28 M/5F), MSNA (microneurography) and arterial blood pressure (BP, Finometer/brachial catheter) were measured, and total peripheral resistance (TPR, ModelFlow) and baroreflex sensitivity were calculated at rest and during intravenous infusion of insulin ( = 20) or SNP ( = 13). A subset of participants receiving insulin ( = 7) was coinfused with phenylephrine. Insulin infusion decreased TPR ( = 0.01) and increased MSNA ( < 0.01), with no effect on arterial baroreflex sensitivity or BP ( > 0.05). Coinfusion with phenylephrine returned TPR and MSNA to baseline, with no effect on arterial baroreflex sensitivity ( > 0.05). Similar to insulin, SNP decreased TPR ( < 0.02) and increased MSNA ( < 0.01), with no effect on arterial baroreflex sensitivity ( > 0.12). Acute hyperinsulinemia shifts the baroreflex stimulus-response curve to higher MSNA without changing sensitivity, likely due to insulin's peripheral vasodilatory effects. Results show that peripheral vasodilation induced by insulin contributes to increased MSNA during hyperinsulinemia. We hypothesized that elevation in muscle sympathetic nervous system activity (MSNA) during hyperinsulinemia is mediated by its peripheral vasodilator effect on the arterial baroreflex. Using three separate protocols in humans, we observed increases in both MSNA and cardiac output during hyperinsulinemia, which we attributed to the baroreflex response to peripheral vasodilation induced by insulin. Results show that peripheral vasodilation induced by insulin contributes to increased MSNA during hyperinsulinemia.
Topics: Adult; Baroreflex; Blood Pressure; Heart Rate; Humans; Hyperinsulinism; Insulin; Muscle, Skeletal; Phenylephrine; Sympathetic Nervous System; Vasodilator Agents
PubMed: 35187960
DOI: 10.1152/ajpendo.00391.2021 -
Journal of Physiology and Pharmacology... Apr 2020The aim of this study is to compare Mydrane (combination of tropicamide 0.02%, phenylephrine 0.31% and lidocaine 1%) and mydriatic drops (tropicamide 1% and... (Randomized Controlled Trial)
Randomized Controlled Trial
The aim of this study is to compare Mydrane (combination of tropicamide 0.02%, phenylephrine 0.31% and lidocaine 1%) and mydriatic drops (tropicamide 1% and phenylephrine 10%) used for cataract surgery in terms of efficacy in pupil dilation and impact on corneal endothelial cell density (CD) and central corneal thickness (CCT). Prospective study including 64 eyes of 64 patients that underwent phacoemulsification with intraocular lens implantation. Patients were randomized into two groups: Mydrane group received: tropicamide and phenylephrine one day preoperatively and Mydrane during the surgery. Reference group received: tropicamide and phenylephrine preoperatively. Pupil size was measured only in Mydrane group, in the same eye of the same patient one day preoperatively after mydriatic drops were given and during the surgery, after intracameral Mydrane injection. CD and CCT were evaluated one day preoperatively and one month postoperatively in all patients and compared between Mydrane and reference groups. The results show CCT and CD significantly decreased after surgery in both groups. There is no difference in this decrease between groups. In Mydrane group there was no difference in dilated pupil diameter between Mydrane and mydriatic drops. Gender, diabetes mellitus, POAG, alpha-1 blocker treatment failed to affect pupil dilation obtained with Mydrane. Cataract surgery affects CCT and CD regardless of which mydriatic protocol had been used. Pupil diameter was similar after drops instillation and after Mydrane injection in all patients from the Mydrane group.
Topics: Aged; Aged, 80 and over; Cataract; Cataract Extraction; Female; Humans; Injections, Intraocular; Lidocaine; Male; Middle Aged; Mydriatics; Phenylephrine; Prospective Studies; Tropicamide
PubMed: 32633242
DOI: 10.26402/jpp.2020.2.08 -
Scientific Reports Aug 2018Regulation of uterine contractility is an important aspect of women's health. Phenylephrine, a selective agonist of the α-adrenoceptor and a potent smooth muscle...
Regulation of uterine contractility is an important aspect of women's health. Phenylephrine, a selective agonist of the α-adrenoceptor and a potent smooth muscle constrictor, is widely used in women even during pregnancy to relieve cold-related symptoms, to treat postpartum haemorrhoid, and during routine eye exams. We performed isometric tension recordings to investigate the effect of phenylephrine on mouse uterine contractility. Phenylephrine decreased spontaneous and oxytocin-induced contractions in non-pregnant mouse uterine rings and strips with an IC of ~1 μM. Prazosin, an inhibitor of α-adrenoceptor, did not prevent phenylephrine-mediated relaxations. Conversely, ICI118551, an antagonist of β2-adrenoceptors, inhibited phenylephrine relaxation. In the presence of ICI118551, high concentrations (>30 μM) of phenylephrine caused mouse uterine contractions, suggesting that β-adrenoceptor-mediated inhibition interferes with the phenylephrine contractile potential. Phenylephrine-dependent relaxation was reduced in the uterus of pregnant mice. We used primary mouse and human uterine smooth muscle cells (M/HUSMC) to establish the underlying mechanisms. Phenylephrine stimulated large increases in intracellular cAMP in M/HUSMCs. These cAMP transients were decreased when HUSMCs were cultured in the presence of oestrogen and progesterone to mimic the pregnancy milieu. Thus, phenylephrine is a strong relaxant in the non-pregnant mouse uterus, but exhibits diminished effect in the pregnant uterus.
Topics: Animals; Caffeine; Common Cold; Cyclic AMP; Estradiol; Female; Genitalia, Female; Humans; Intracellular Space; Mice, Inbred C57BL; Muscle Relaxation; Myocytes, Smooth Muscle; Oxytocin; Peristalsis; Phenylephrine; Pregnancy; Progesterone; Receptors, Adrenergic, beta-2; Signal Transduction; Uterine Contraction
PubMed: 30076382
DOI: 10.1038/s41598-018-30094-5 -
International Journal of Surgery... Dec 2018In the past 20 years, many studies compared phenylephrine with ephedrine to prevent or treat hypotension in elective or emergency cesarean delivery and parturients with... (Meta-Analysis)
Meta-Analysis
BACKGROUND
In the past 20 years, many studies compared phenylephrine with ephedrine to prevent or treat hypotension in elective or emergency cesarean delivery and parturients with pre-eclampsia. A meta-analysis of the abovementioned trials is needed.
METHODS
Several databases (PubMed, Embase, Web of Science and Cochrane Library) were searched from inception to April 2018 for trials comparing phenylephrine with ephedrine in cesarean delivery. The primary outcome is the incidence of maternal hypotension.
RESULTS
Thirty-six trials (2439 patients) with elective cesarean delivery, three trials (400 patients) with emergency cesarean delivery and three trials (192 patients) with parturients with pre-eclampsia were included and analyzed. The incidence of hypotension did not differ in the elective surgery group (relative risk 0.83, 95% CI 0.66 to 1.05), emergency surgery group (relative risk 1.02, 95% CI 0.87 to 1.19) and pre-eclamptic parturients group (relative risk 0.93, 95% CI 0.63 to 1.37). The phenylephrine group had a higher incidence of bradycardia and lower incidences of tachycardia and nausea or vomiting in all three patient groups. The phenylephrine group also had lower fetal acidosis rate, higher umbilical artery and vein pH values and less base excess in the elective surgery. The abovementioned outcomes were similar in the emergency surgery group and the pre-eclampsia group. Publication bias for hypotension was detected. However, the trim and fill method demonstrated that the publication bias had little impact on hypotension. Trial sequential analysis of hypotension in elective surgery showed that this meta-analysis lacked a sufficient cumulative sample size and that further studies should be included.
CONCLUSION
Phenylephrine and ephedrine were both effective in maintaining hemodynamic balance. Newborns benefited more from phenylephrine in elective cesarean delivery, but not in emergency cesarean delivery or in parturients with pre-eclampsia. More trials should be included to achieve more conclusive results.
Topics: Adult; Anesthesia, Spinal; Cesarean Section; Ephedrine; Female; Humans; Hypotension; Incidence; Infant, Newborn; Phenylephrine; Pregnancy; Vasoconstrictor Agents
PubMed: 30389535
DOI: 10.1016/j.ijsu.2018.10.039 -
Experimental Physiology Dec 2023What is the central question of this study? What are the biggest challenges in performing in vitro studies on isolated human umbilical arteries? What is the main finding...
NEW FINDINGS
What is the central question of this study? What are the biggest challenges in performing in vitro studies on isolated human umbilical arteries? What is the main finding and its importance? The protocols presented in this study indicate some potential outcomes important for interpretation of the vascular responsivities of human umbilical arteries and could be useful for planning future in vitro studies with human umbilical arteries.
ABSTRACT
Human umbilical artery (HUA) preparations are of particular importance for in vitro studies on isolated blood vessels because their sampling is not risky for the patient, and they can provide the closest possible impression of changes related to the uteroplacental circulation during pre-eclampsia. Using organ bath techniques, useful experimental protocols are provided for measuring some pathophysiological phenomena in the vascular responses of HUAs. Several vasoconstrictors (serotonin, prostaglandin F and phenylephrine) and vasodilators (acetylcholine and minoxidil) were seleted for determination of their vasoactivity in HUAs. The role of L-type voltage-operated calcium channels and different types of potassium channels (K , BK and K ) were assessed, as was the impact of homocysteine. Serotonin was confirmed to be the most potent vasoconstrictor, while acetylcholine and phenylephrine caused variability in the relaxation and contraction response of HUA, respectively. The observed increase in serotonin-induced contraction and a decrease in minoxidil-induced relaxation in the presence of homocysteine suggested its procontractile effect on HUA preparations. Using selective blockers, it was determined that K and K channels participate in the minoxidil-induced relaxation, while L-type voltage-dependent Ca channels play an important role in the serotonin-induced contraction. The presented protocols reveal some of the methodological challenges related to HUA preparations and indicate potential outcomes in interpreting the vascular effects of the investigated substances, both in physiological conditions and in the homocysteine-induced pre-eclampsia model.
Topics: Pregnancy; Female; Humans; Umbilical Arteries; Serotonin; Acetylcholine; Minoxidil; Pre-Eclampsia; Vasodilation; Vasoconstrictor Agents; Phenylephrine; Homocysteine; Adenosine Triphosphate
PubMed: 37837634
DOI: 10.1113/EP091374 -
Topics in Cognitive Science Jan 2017We use a spiking neural network model of working memory (WM) capable of performing the spatial delayed response task (DRT) to investigate two drugs that affect WM:... (Comparative Study)
Comparative Study
We use a spiking neural network model of working memory (WM) capable of performing the spatial delayed response task (DRT) to investigate two drugs that affect WM: guanfacine (GFC) and phenylephrine (PHE). In this model, the loss of information over time results from changes in the spiking neural activity through recurrent connections. We reproduce the standard forgetting curve and then show that this curve changes in the presence of GFC and PHE, whose application is simulated by manipulating functional, neural, and biophysical properties of the model. In particular, applying GFC causes increased activity in neurons that are sensitive to the information currently being remembered, while applying PHE leads to decreased activity in these same neurons. Interestingly, these differential effects emerge from network-level interactions because GFC and PHE affect all neurons equally. We compare our model to both electrophysiological data from neurons in monkey dorsolateral prefrontal cortex and to behavioral evidence from monkeys performing the DRT.
Topics: Animals; Guanfacine; Haplorhini; Humans; Memory, Short-Term; Models, Neurological; Neurons; Phenylephrine; Prefrontal Cortex
PubMed: 28001002
DOI: 10.1111/tops.12247 -
Eye (London, England) Oct 2018Unpreserved phenylephrine is often used as an off-licence intracameral surgical adjunct during cataract surgery to assist with pupil dilation and/or stabilise the iris...
PURPOSE
Unpreserved phenylephrine is often used as an off-licence intracameral surgical adjunct during cataract surgery to assist with pupil dilation and/or stabilise the iris in floppy iris syndrome. It can be delivered as a neat 0.2 ml bolus of either 2.5 or 10% strength, or in a range of ad-hoc dilutions. We wished to assess the accuracy of intracameral phenylephrine preparation in clinical practice.
METHODS
Phenylephrine 0.2 ml was analysed both neat (2.5 and 10%) and in diluted form (ratio of 1:1 and 1:3). Samples were analysed using the validated spectrophotometric method.
RESULTS
A total of 36 samples were analysed. The standard curve showed linearity for phenylephrine (R = 0.99). Wide variability was observed across all dilution groups. There was evidence of significant differences in the percentage deviations from intended results between dilutions (p < 0.001). Mean percentage deviation for 1:3 dilution was significantly greater than neat (p = 0.003) and 1:1 dilution (p = 0.001). There was no evidence of a significant difference between 1:1 and neat (p = 0.827).
CONCLUSIONS
Current ad-hoc dilution methods used to prepare intracameral phenylephrine are inaccurate and highly variable. Small volume 1 ml syringes should not be used for mixing or dilution of drug. Commercial intracameral phenylephrine products would address dosage concerns and could improve surgical outcomes in cases of poor pupil dilation and/or floppy iris syndrome.
Topics: Analysis of Variance; Cataract Extraction; Drug Compounding; Humans; Intraoperative Complications; Mydriatics; Phenylephrine
PubMed: 29907787
DOI: 10.1038/s41433-018-0143-y -
Naunyn-Schmiedeberg's Archives of... Jul 2022The β-agonist mirabegron is thought to induce relaxation of the detrusor muscle, contributing to the improvement of overactive bladder symptoms. There has been recent...
The β-agonist mirabegron is thought to induce relaxation of the detrusor muscle, contributing to the improvement of overactive bladder symptoms. There has been recent interest in purposing mirabegron as a medical expulsive therapy drug to improve the passage of smaller kidney stones by relaxing the ureteral smooth muscles. The aim of this study was to determine the effects of mirabegron on the activity of the ureter. Additionally, we investigated the receptor and mechanisms through which mirabegron exerts these effects. In vitro agonist-induced responses of isolated porcine distal ureteral tissues were measured in the absence and presence of mirabegron in organ bath experiments. The responses were expressed as frequency, area under the curve and maximum amplitude. Mirabegron at concentrations of 100 nM and lower failed to suppress phenylephrine- or 5-HT-induced contractions in the porcine ureteral strip. Mirabegron at 1 μM and 10 μM produced a rightward shift of phenylephrine concentration-response curves in these tissues. This effect of mirabegron (10 μM) was not present in 5-HT concentration-response curves. The mirabegron effect on phenylephrine-induced contractions was also not abolished by β-adrenoceptor antagonist SR 59230A (10 μM), β-adrenoceptor antagonist propranolol (10 μM), α-adrenoceptor antagonist yohimbine (30 nM), and nitric oxide synthase inhibitor L-NNA (10 μM). The present results show that mirabegron suppresses ureteral contractile responses in the porcine ureter via α-adrenoceptor antagonism, since their effects were not present when the tissues were contracted with 5-HT. Furthermore, the inhibitory effects by mirabegron were not affected by β-adrenoceptor antagonists.
Topics: Acetanilides; Adrenergic beta-Antagonists; Animals; Muscle Contraction; Phenylephrine; Receptors, Adrenergic, alpha-1; Serotonin; Swine; Thiazoles
PubMed: 35445849
DOI: 10.1007/s00210-022-02244-0 -
Journal of Clinical Monitoring and... Jun 2019
Topics: Animal Experimentation; Animals; Hemodynamics; Phenylephrine; Stroke Volume; Veins
PubMed: 30478524
DOI: 10.1007/s10877-018-0225-1