-
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 -
The British Journal of Ophthalmology Jan 1974
Review
Topics: Cyclopentanes; Glaucoma; Gonioscopy; Humans; Intraocular Pressure; Iris; Moxisylyte; Phenylephrine; Pilocarpine; Pneumonia, Pneumococcal; Pupil
PubMed: 4276441
DOI: 10.1136/bjo.58.1.41 -
Journal of the American Heart... Dec 2023Cardiac hypertrophy (CH) is a well-established risk factor for many cardiovascular diseases and a primary cause of mortality and morbidity among older adults. Currently,...
BACKGROUND
Cardiac hypertrophy (CH) is a well-established risk factor for many cardiovascular diseases and a primary cause of mortality and morbidity among older adults. Currently, no pharmacological interventions have been specifically tailored to treat CH. OTUD7B (ovarian tumor domain-containing 7B) is a member of the ovarian tumor-related protease (OTU) family that regulates many important cell signaling pathways. However, the role of OTUD7B in the development of CH is unclear. Therefore, we investigated the role of OTUD7B in CH.
METHODS AND RESULTS
OTUD7B knockout mice were used to assay the role of OTUD7B in CH after transverse aortic coarctation surgery. We further assayed the specific functions of OTUD7B in isolated neonatal rat cardiomyocytes. We found that OTUD7B expression decreased in hypertrophic mice hearts and phenylephrine-stimulated neonatal rat cardiomyocytes. Furthermore, OTUD7B deficiency exacerbated transverse aortic coarctation surgery-induced myocardial hypertrophy, abnormal cardiac function, and fibrosis. In cardiac myocytes, OTUD7B knockdown promoted phenylephrine stimulation-induced myocardial hypertrophy, whereas OTUD7B overexpression had the opposite effect. An immunoprecipitation-mass spectrometry analysis showed that OTUD7B directly binds to KLF4 (Krüppel-like factor 4). Additional molecular experiments showed that OTUD7B impedes KLF4 degradation by inhibiting lysine residue at 48 site-linked ubiquitination and suppressing myocardial hypertrophy by activating the serine/threonine kinase pathway.
CONCLUSIONS
These results demonstrate that the OTUD7B-KLF4 axis is a novel molecular target for CH treatment.
Topics: Mice; Rats; Animals; Kruppel-Like Factor 4; Aortic Coarctation; Cardiomegaly; Phenylephrine; Mice, Knockout; Ubiquitination; Myocytes, Cardiac; Mice, Inbred C57BL; Endopeptidases
PubMed: 38084712
DOI: 10.1161/JAHA.123.029745 -
Drug Design, Development and Therapy 2022It is well-known that severe preeclamptic parturients have less vasopressor requirements than normotensive parturients; however, the exact dose difference is poorly... (Randomized Controlled Trial)
Randomized Controlled Trial
Comparative Dose-Response Study of Phenylephrine Bolus for the Treatment of the First Episode of Spinal Anesthesia-Induced Hypotension for Cesarean Delivery in Severe Preeclamptic versus Normotensive Parturients.
BACKGROUND
It is well-known that severe preeclamptic parturients have less vasopressor requirements than normotensive parturients; however, the exact dose difference is poorly documented. This study aimed to determine and compare the ED and ED of a single bolus phenylephrine for the treatment of spinal anesthesia-induced hypotension in parturients with severe preeclampsia and parturients with normotension.
METHODS
Seventy-five parturients with severe preeclampsia scheduled for cesarean delivery under combined spinal-epidural anesthesia were enrolled and randomly allocated to receive a single bolus of phenylephrine at five different doses (40, 50, 60, 70, and 80 μg), whereas 75 parturients with normotension were randomized to receive a single bolus of phenylephrine at five different doses (70, 80, 90, 100, and 110 μg) for the treatment of the first episode of hypotension. Phenylephrine dose values were log-transformed, the proportions of the successful interventions at each dose were converted to probits, and regression analysis was performed.
RESULTS
The ED and ED (95% CI) of bolus phenylephrine were 72.1 (61.7 to 79.9) μg and 107 (95.9-128.6) μg in parturients with normotension. The ED and ED values in parturients with severe preeclampsia were 47.6 (41.3-52.7) μg and 70.7 (62.9-86.7) μg. The relative median potency was 1.51 (1.16-2.61).
CONCLUSION
Under this study conditions, severe preeclamptic parturients required a 34% reduction of ED of phenylephrine dose compared with normotensive parturients.
Topics: Anesthesia, Spinal; Cesarean Section; Double-Blind Method; Female; Humans; Hypotension; Hypotension, Controlled; Phenylephrine; Pre-Eclampsia; Pregnancy; Vasoconstrictor Agents
PubMed: 35837022
DOI: 10.2147/DDDT.S368480 -
Anaesthesia Feb 2015
Topics: Chemistry, Physical; Drug Compounding; Methylene Blue; Phenylephrine; Sodium Chloride
PubMed: 25583189
DOI: 10.1111/anae.12983 -
Canadian Medical Association Journal Sep 1982The possibility that intranasally administered phenylephrine might cause systemic vasoconstriction and an important increase in blood pressure if administered to... (Clinical Trial)
Clinical Trial Comparative Study
The possibility that intranasally administered phenylephrine might cause systemic vasoconstriction and an important increase in blood pressure if administered to susceptible individuals in higher doses was investigated in two groups potentially at high risk: 12 patients with chronic nasal congestion whose blood pressure was normal and 14 patients with hypertension receiving the beta-blocker metoprolol. On two separate days increasing doses (0.5 to 4 mg) of phenylephrine or a placebo of identical appearance were instilled into the nostrils at hourly intervals. The blood pressure and the heart rate were recorded every 10 minutes. The total amount of phenylephrine administered (7.5 to 15 mg) was 4 to 30 times the manufacturer's recommended dose. No significant changes in blood pressure or heart rate occurred in either group after the instillation of phenylephrine.
Topics: Administration, Intranasal; Adult; Blood Pressure; Chronic Disease; Drug Interactions; Heart Rate; Humans; Metoprolol; Middle Aged; Nasal Mucosa; Nose Diseases; Phenylephrine; Vasoconstriction
PubMed: 7104913
DOI: No ID Found -
European Journal of Biochemistry Feb 1987Electrical stimulation of perivascular nerves (20 Hz/2 ms/20 V) in perfused rat liver led to a transient increase of 14CO2 production from [1-14C]glutamate, glutathione...
Electrical stimulation of perivascular nerves (20 Hz/2 ms/20 V) in perfused rat liver led to a transient increase of 14CO2 production from [1-14C]glutamate, glutathione and thiol efflux, an increase in the lactate/pyruvate and the 3-hydroxybutyrate/acetoacetate ratio, glucose release and of portal pressure. These metabolic effects were accompanied by a Ca2+ release from the liver within the initial 2 min, being followed by Ca2+ reuptake, which lasted about 3 min. The initial Ca2+ release was 67 nmol/g liver and was smaller than that observed after phenylephrine (5 microM) addition (156 nmol/g liver). Hepatic Ca2+ release following nerve stimulation or phenylephrine was not significantly affected when the hemodynamic changes were largely prevented by sodium nitroprusside (10 microM). Although the amounts of Ca2+ released were different, the glycogenolytic responses, but not the other metabolic effects, were quantitatively similar with nerve stimulation and phenylephrine. Within the first 3 min of nerve stimulation there was a K+ uptake by the liver being followed by a K+ release over the next 5-6 min and a subsequent slow K+ uptake phase. These changes resembled those observed with phenylephrine. Phentolamine, an alpha-adrenergic antagonist, abolished the Ca2+ and K+ movements following nerve stimulation as well as glucose release and the hemodynamic changes. During continuous infusion of phenylephrine, nerve stimulation led still to an increase of portal pressure; however, the effects of nerve stimulation on Ca2+ and K+ fluxes and glucose release were largely suppressed. It is concluded that the metabolic effects of electrical nerve stimulation are mediated by a redistribution of cellular Ca2+ following alpha-receptor activation. Nerve stimulation involves Ca2+ and K+ fluxes across the plasma membrane. The metabolic effects are qualitatively similar to those induced by phenylephrine. The quantitative difference between nerve stimulation and phenylephrine is explained by a differential subacinar response, with fewer cells being reached by nerve stimulation than cells containing alpha-receptors. The hemodynamic changes of nerve stimulation point to the existence of sphincters near the inflow of the sinusoidal bed.
Topics: Animals; Calcium; Cell Membrane; Electric Stimulation; Glutamates; Glutathione; Liver; Male; Oxidation-Reduction; Perfusion; Phenylephrine; Potassium; Rats; Rats, Inbred Strains
PubMed: 3816798
DOI: 10.1111/j.1432-1033.1987.tb10755.x -
International Journal of Molecular... Sep 2022This study was designed to connect aortic stiffness to vascular contraction in young male and female Wistar rats. We hypothesized that female animals display reduced...
This study was designed to connect aortic stiffness to vascular contraction in young male and female Wistar rats. We hypothesized that female animals display reduced intrinsic media-layer stiffness, which associates with improved vascular function. Atomic force microscopy (AFM)-based nanoindentation analysis was used to derive stiffness (Young's modulus) in biaxially (i.e., longitudinal and circumferential) unloaded aortic rings. Reactivity studies compatible with uniaxial loading (i.e., circumferential) were used to assess vascular responses to a selective α1 adrenergic receptor agonist in the presence or absence of extracellular calcium. Elastin and collagen levels were indirectly evaluated with fluorescence microscopy and a picrosirius red staining kit, respectively. We report that male and female Wistar rats display similar AFM-derived aortic media-layer stiffness, even though female animals withstand higher aortic intima-media thickness-to-diameter ratio than males. Female animals also present reduced phenylephrine-induced aortic force development in concentration-response and time-force curves. Specifically, we observed impaired force displacement in both parts of the contraction curve (Aphasic and Atonic) in experiments conducted with and without extracellular calcium. Additionally, collagen levels were lower in female animals without significant elastin content and fragmentation changes. In summary, sex-related functional differences in isolated aortas appear to be related to dissimilarities in the dynamics of vascular reactivity and extracellular matrix composition rather than a direct response to a shift in intrinsic media-layer stiffness.
Topics: Adrenergic Agonists; Animals; Calcium; Carotid Intima-Media Thickness; Collagen; Elastin; Female; Male; Phenylephrine; Rats; Rats, Wistar; Vascular Stiffness
PubMed: 36232616
DOI: 10.3390/ijms231911314 -
Anaesthesia Dec 2005
Topics: Acidosis; Anesthesia, Obstetrical; Ephedrine; Female; Fetal Diseases; Humans; Maternal-Fetal Exchange; Phenylephrine; Pregnancy
PubMed: 16288624
DOI: 10.1111/j.1365-2044.2005.04443.x -
Acta Ophthalmologica Scandinavica Oct 2000To investigate the influence of protein concentration in the anterior chamber, measured by laser flare meter, on pain sensation after phenylephrine instillation in... (Comparative Study)
Comparative Study
PURPOSE
To investigate the influence of protein concentration in the anterior chamber, measured by laser flare meter, on pain sensation after phenylephrine instillation in patients with iridocyclitis.
METHODS
Twenty-five consecutive patients with iridocyclitis were included. Patients with cataract, exfoliation syndrome, diabetes mellitus, glaucoma or any other previous ocular diseases or ocular surgery were excluded. Patients were divided into two groups: Group 1--without fibrinoid reaction (FR) in the anterior chamber (18 patients), and Group 2--with FR (7 patients). Protein concentration in the anterior chamber was measured with laser flare meter (FC 500, Kowa Co., Japan). Pupil size was measured by Alcon Tilo Scale, and pain sensation was estimated by Visual Analogue Scale (VAS, Kabi Pharmacia). All measurements were done before and 1 hour after topical instillation of 10% phenylephrine hydrochloride into the subconjunctival sac of the inflamed eyes.
RESULTS
Eyes with iridocyclitis and fibrinoid reaction (FR) have a higher flare intensity compared to those without FR (p<0.05). Pupil size was significantly increased after phenylephrine instillation in both study groups (Wilcoxon test, p<0.05). The VAS pain and flare intensity were significantly decreased in group without FR after phenylephrine instillation (Group 1) compared to values before treatment (Wilcoxon test, p<0.05). In eyes with FR (Group 2), no significant influence of phenylephrine instillation was found on VAS pain and flare intensity.
CONCLUSIONS
After phenylephrine instillation, flare intensity and pain were significantly decreased only in eyes with iridocyclitis and without FR. The decreasing level of flare intensity, and paralysis of the pupil after phenylephrine instillation seem to alleviate pain in those eyes.
Topics: Adult; Aged; Aged, 80 and over; Anterior Chamber; Aqueous Humor; Diagnostic Techniques, Ophthalmological; Eye Proteins; Female; Humans; Iridocyclitis; Male; Middle Aged; Mydriatics; Ophthalmic Solutions; Pain; Pain Measurement; Phenylephrine; Prospective Studies; Pupil
PubMed: 11037905
DOI: 10.1034/j.1600-0420.2000.078005516.x