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Scientific Reports Apr 2024Although the esophageal stethoscope is used for continuous auscultation during general anesthesia, few studies have investigated phonocardiographic data as a continuous...
Although the esophageal stethoscope is used for continuous auscultation during general anesthesia, few studies have investigated phonocardiographic data as a continuous hemodynamic index. In this study, we aimed to induce hemodynamic variations and clarify the relationship between the heart sounds and hemodynamic variables through an experimental animal study. Changes in the cardiac contractility and vascular resistance were induced in anesthetized pigs by administering dobutamine, esmolol, phenylephrine, and nicardipine. In addition, a decrease in cardiac output was induced by restricting the venous return by clamping the inferior vena cava (IVC). The relationship between the hemodynamic changes and changes in the heart sound indices was analyzed. Experimental data from eight pigs were analyzed. The mean values of the correlation coefficients of changes in S1 amplitude (ΔS1amp) with systolic blood pressure (ΔSBP), pulse pressure (ΔPP), and ΔdP/dt during dobutamine administration were 0.94, 0.96, and 0.96, respectively. The mean values of the correlation coefficients of ΔS1amp with ΔSBP, ΔPP, and ΔdP/dt during esmolol administration were 0.80, 0.82, and 0.86, respectively. The hemodynamic changes caused by the administration of phenylephrine and nicardipine did not correlate significantly with changes in the heart rate. The S1 amplitude of the heart sound was significantly correlated with the hemodynamic changes caused by the changes in cardiac contractility but not with the variations in the vascular resistance. Heart sounds can potentially provide a non-invasive monitoring method to differentiate the cause of hemodynamic variations.
Topics: Animals; Swine; Heart Sounds; Dobutamine; Nicardipine; Hemodynamics; Phenylephrine; Propanolamines
PubMed: 38615106
DOI: 10.1038/s41598-024-59362-3 -
Indian Journal of Ophthalmology Jul 2024To study the pupil dynamics with premixed intracameral anesthetic mydriatic combination of phenylephrine (0.31%), tropicamide (0.02%), and lidocaine (1%) in pediatric...
PURPOSE
To study the pupil dynamics with premixed intracameral anesthetic mydriatic combination of phenylephrine (0.31%), tropicamide (0.02%), and lidocaine (1%) in pediatric cataract surgery.
METHODS
Consecutive children aged ≤12 years planned for cataract surgery were recruited. A commercially available premixed combination of phenylephrine (0.31%), tropicamide (0.02%), and lidocaine (1%) was injected at the beginning of surgery without any topical/infusion drugs for mydriasis. Pupil sizes at various points of surgery were studied.
RESULTS
We recruited 75 patients with a mean age of 24.3 ± 33.4 months (range: 1 month-11 years). Adequate mydriasis with a single injection was achieved in 93.5% (n = 73 eyes of 70 patients) without additional pharmacotherapy or intervention. The mean pupillary diameter increased from 1.8 ± 0.79 to 6.1 ± 1.4 mm after injection (mean change of 4.2 ± 1.25 mm from baseline). The mean variability in pupillary diameter was 0.73 ± 1.3 mm. In five eyes, good dilatation was not possible even after repeat injection.
CONCLUSION
Fixed-dose premixed intracameral injection is effective in pupil dilatation. It alleviates the need for any topical dilators or additional intraoperative supplementation for pediatric cataract surgery.
Topics: Humans; Mydriatics; Child, Preschool; Male; Infant; Female; Cataract Extraction; Pupil; Child; Tropicamide; Phenylephrine; Lidocaine; Anterior Chamber; Cataract; Prospective Studies; Follow-Up Studies; Ophthalmic Solutions; Dose-Response Relationship, Drug
PubMed: 38454863
DOI: 10.4103/IJO.IJO_2628_23 -
International Neurourology Journal Feb 2024Adreno-muscarinic synergy, a supra-additional contractile response to simultaneous application of α-adrenoreceptor and muscarinic receptor agonists, is a feature of...
PURPOSE
Adreno-muscarinic synergy, a supra-additional contractile response to simultaneous application of α-adrenoreceptor and muscarinic receptor agonists, is a feature of several lower urinary tract regions that have dual sympathetic and parasympathetic innervation. We tested the hypothesis that synergy is also a feature of prostate tissue obtained from men with benign prostatic enlargement.
METHODS
Isolated tissue strips were dissected from prostate 'chips', collected after transurethral prostate resection procedures for in vitro experiments, to measure isometric tension at 36°C.
RESULTS
Added separately to the superfusate, phenylephrine and carbachol generated contractions with mean pEC50 (-log10EC50) values of 5.36 and 5.58, respectively, although phenylephrine maximal responses were about six-fold greater. In the presence of carbachol, the mean phenylephrine pEC50 was significantly increased to 5.84 and maximal response increased by 28%; overall, a significant synergistic response was demonstrated. The synergistic response was reduced by muscarinic receptor antagonists, most potently by the M3-selective agent 4-DAMP (1,1-dimethyl-4-diphenylacetoxypiperidinium iodide), and less so by M2 and M1-selective inhibitors gallamine and pirenzepine, but with an overall profile indicating M3/M2 mediation of the synergistic response. The magnitude of the synergistic response was variable between prostate chips that provided isolated preparations suggesting regional heterogenicity, although their zonal origin could not be determined.
CONCLUSION
These experiments show that adreno-muscarinic contractile synergy is a feature of human hyperplastic prostate tissue. This has implications for the use of a combination therapy of α-blockers and anti-muscarinic agent to relieve secondary symptoms associated with benign prostatic hyperplasia, at least in men who can tolerate antimuscarinics without a risk of retention.
PubMed: 38461856
DOI: 10.5213/inj.2346144.122 -
BMC Chemistry Oct 2023The development and validation of the stability indicating HPLC technique has contributed to the understanding of the stability profile of ibuprofen (IBU) and...
The development and validation of the stability indicating HPLC technique has contributed to the understanding of the stability profile of ibuprofen (IBU) and phenylephrine (PHE). Stability profile was achieved for PHE; the drug was found to be liable to be influenced by stress oxidative conditions; two oxidative degradants (Deg1 & Deg2) were formed and their structures were confirmed using IR and mass spectrometry. The drugs and degradation products were successfully separated using a gradient elution method on YMC-C8 column with 0.1% hexanesulfonic acid and acetonitrile as a mobile phase at pH 6.6. The flow rate was 1.0 mL/min, and a diode array detector operating at 220 nm was used for UV detection. The retention times of degradants Deg1, Deg2, ibuprofen (IBU), and phenylephrine hydrochloride (PHE) were 2.0, 2.2, 3.2 and 7.0 min, respectively. The proposed method was validated with respect to linearity, accuracy, precision, specificity, and robustness using ICH guidelines. The linearities of ibuprofen and phenylephrine hydrochloride were in the range of 10-100 μg/mL and 0.3-10 μg/mL, respectively. The % recoveries of the two drugs were found to be 100.75 ± 1.44%, 99.67% ± 1.67, and the LOD was found to be 2.75/mL and 0.09/mL for IBU, and PHE, respectively. The method was successfully applied to the estimation of ibuprofen and phenylephrine hydrochloride combination in pharmaceutical dosage form. The proposed technique was validated using ICH guidelines and its greenness was assessed according to Analytical Eco Scale metric (AES). Molecular docking was used to assess the two drugs and PHE oxidative degradants interaction with the stationary phase and to confirm the outcomes of the proposed method with regard to the order of elution of the two drugs and PHE degradation products. Eco-friendly and environmental safety were assessed through the application of one of the most applicable greenness assessment tool; Analytical Eco Scale metric (AES).
PubMed: 37876006
DOI: 10.1186/s13065-023-01056-4 -
Pharmaceutical Biology Dec 2024The mechanisms of Traditional Chinese Medicine (TCM) Guizhi-Gancao Decoction (GGD) remain unknown.
Network pharmacology integrated with experimental validation to elucidate the mechanisms of action of the Guizhi-Gancao Decoction in the treatment of phenylephrine-induced cardiac hypertrophy.
CONTEXT
The mechanisms of Traditional Chinese Medicine (TCM) Guizhi-Gancao Decoction (GGD) remain unknown.
OBJECTIVE
This study explores the mechanisms of GGD against cardiac hypertrophy.
MATERIALS AND METHODS
Network pharmacology analysis was carried out to identify the potential targets of GGD. experiments, C57BL/6J mice were divided into Con, phenylephrine (PE, 10 mg/kg/d), 2-chloroadenosine (CADO, the stable analogue of adenosine, 2 mg/kg/d), GGD (5.4 g/kg/d) and GGD (5.4 g/kg/d) + CGS15943 (a nonselective adenosine receptor antagonist, 4 mg/kg/d). experiments, primary neonatal rat cardiomyocytes (NRCM) were divided into Con, PE (100 µM), CADO (5 µM), GGD (10 g/mL) and GGD (10 g/mL) + CGS15943 (5 µM). Ultrasound, H&E and Masson staining, hypertrophic genes expression and cell surface area were conducted to verify the GGD efficacy. Adenosine receptors (ADORs) expression were tested real-time polymerase chain reaction (PCR), western blotting and immunofluorescence analysis.
RESULTS
Network pharmacology identified ADORs among those of the core targets of GGD. experiments demonstrated that GGD attenuated PE-induced increased surface area (with an EC of 5.484 × 10 g/mL). data shown that GGD attenuated PE-induced ventricular wall thickening. and data indicated that GGD alleviated PE-induced hypertrophic gene expression (e.g., ANP, BNP and MYH7/MYH6), A1AR over-expression and A2aAR down-expression. Moreover, CADO exerts effects similar to GGD, whereas CGS15943 eliminated most effects of GGD.
DISCUSSION AND CONCLUSIONS
Our findings suggest the mechanism by which GGD inhibits cardiac hypertrophy, highlighting regulation of ADORs as a potential therapeutic strategy for HF.
Topics: Animals; Drugs, Chinese Herbal; Phenylephrine; Cardiomegaly; Mice, Inbred C57BL; Mice; Male; Rats; Myocytes, Cardiac; Network Pharmacology; Rats, Sprague-Dawley; Cells, Cultured; Disease Models, Animal; Medicine, Chinese Traditional
PubMed: 38773737
DOI: 10.1080/13880209.2024.2354335 -
Tuberkuloz Ve Toraks Dec 2023Iatrogenic bleeding during bronchoscopy may lead to early termination, insufficient sample collection, decreased diagnostic accuracy, and even death. Unlike rigid...
Iatrogenic bleeding during bronchoscopy may lead to early termination, insufficient sample collection, decreased diagnostic accuracy, and even death. Unlike rigid bronchoscopy, the management of bleeding during flexible fiberoptic bronchoscopy does not allow the use of methods such as cautery, direct pressure, etc. and is usually limited to the application of liquids. The management of endobronchial bleeding usually depends on two main mechanisms: 1) vasoconstriction; 2) enhancing coagulation to form fibrin clots. The data on cold saline, the most widely recognized agent, is based on case reports and the experience of centers, not randomized controlled trials. Vasoconstrictor agents consist of adrenaline, vasopressin analogues, phenylephrine, and xylometazoline hydrochloride. However, there are only a limited number of randomized controlled trials on adrenaline, and information on the remaining substances is limited to retrospective studies, case reports, and expert opinions. The endobronchial administration of tranexamic acid, which inhibits fibrin degradation, has been the subject of very few studies. Despite its documented efficacy, information regarding its dosage, frequency of use, and safety is lacking. Although Ankaferd Blood Stopper, which binds erythrocytes to the vascular endothelium, has been shown to be effective in controlling bleeding related to dental procedures, the gastrointestinal tract, and operations, only one retrospective study found it to be effective against endobronchial bleeding that could not be controlled with cold saline and adrenaline. Although there are a variety of agents that centers use in their routine procedures, there is not yet a consensus on the efficacy, dose, frequency, and safety of any of them.
Topics: Humans; Bronchoscopy; Retrospective Studies; Hemorrhage; Stroke; Epinephrine; Fibrin; Iatrogenic Disease
PubMed: 38152010
DOI: 10.5578/tt.20239608 -
RSC Advances Apr 2024Cucurbiturils (CB) are known to establish stable host-guest complexes with a variety of drug molecules. Herein, the supramolecular complexation between cucurbit[7]uril...
Cucurbiturils (CB) are known to establish stable host-guest complexes with a variety of drug molecules. Herein, the supramolecular complexation between cucurbit[7]uril (CB7) and phenylephrine hydrochloride is reported in aqueous solution. Phenylephrine forms inclusion complex with CB7 with high binding affinity ( = 4.0 × 10 M), which allows for the development of a fluorescence-based sensing assay applying the dye displacement strategy. The structure of the host-guest inclusion complex is investigated by H NMR spectroscopy, in which complexation-induced chemical shifts indicate the immersion of the aromatic ring inside the hydrophobic cavity of CB7. Density functional theory (DFT) calculations support the H NMR results, and reveal that the complex is stabilized through intermolecular interactions between the polar groups on the phenylephrine and the carbonyl rims of CB7, as well as the hydrophobic effect. Moreover, preferential binding of phenylephrine in its protonated over the neutral form results in a complexation-induced p shift.
PubMed: 38655473
DOI: 10.1039/d4ra01910e -
Brazilian Journal of Medical and... 2024Arthritis has important cardiovascular repercussions. Phenylephrine-induced vasoconstriction is impaired in rat aortas in the early phase of the adjuvant-induced...
Arthritis has important cardiovascular repercussions. Phenylephrine-induced vasoconstriction is impaired in rat aortas in the early phase of the adjuvant-induced arthritis (AIA), around the 15th day post-induction. Therefore, the present study aimed to verify the effects of AIA on hyporesponsiveness to phenylephrine in rat aortas. AIA was induced by intradermal injection of Mycobacterium tuberculosis (3.8 mg/dL) in the right hind paw of male Wistar rats (n=27). Functional experiments in isolated aortas were carried out 15 days after AIA induction. Morphometric and stereological analyses of the aortas were also performed 36 days after the induction of AIA. AIA did not promote structural modifications in the aortas at any of the time points studied. AIA reduced phenylephrine-induced contraction in endothelium-intact aortas, but not in endothelium-denuded aortas. However, AIA did not change KCl-induced contraction in either endothelium-intact or denuded aortas. L-NAME (non-selective NOS inhibitor), 1400W (selective iNOS inhibitor), and ODQ (guanylyl cyclase inhibitor) reversed AIA-induced hyporesponsiveness to phenylephrine in intact aortas. 7-NI (selective nNOS inhibitor) increased the contraction induced by phenylephrine in aortas from AIA rats. In summary, the hyporesponsiveness to phenylephrine induced by AIA was endothelium-dependent and mediated by iNOS-derived NO through activation of the NO-guanylyl cyclase pathway.
Topics: Animals; Male; Phenylephrine; Rats, Wistar; Arthritis, Experimental; Nitric Oxide; Vasoconstriction; Endothelium, Vascular; Vasoconstrictor Agents; Rats; Aorta
PubMed: 38775546
DOI: 10.1590/1414-431X2024e13304 -
International Journal of Molecular... Dec 2023Quantum pharmacology introduces theoretical models to describe the possibility of ultra-high dilutions to produce biological effects, which may help to explain the...
Quantum pharmacology introduces theoretical models to describe the possibility of ultra-high dilutions to produce biological effects, which may help to explain the placebo effect observed in hypertensive clinical trials. To determine this within physiology and to evaluate novel ARBs, we tested the ability of known angiotensin II receptor blockers (ARBs) (candesartan and telmisartan) used to treat hypertension and other cardiovascular diseases, as well as novel ARBs (benzimidazole--biphenyl tetrazole (ACC519T), benzimidazole--,'-biphenyl tetrazole (ACC519T(2)) and 4-butyl-N,N0-bis[[20-2Htetrazol-5-yl)biphenyl-4-yl]methyl)imidazolium bromide (BV6(K)), and nirmatrelvir (the active ingredient in Paxlovid) to modulate vascular contraction in iliac rings from healthy male New Zealand White rabbits in responses to various vasopressors (angiotensin A, angiotensin II and phenylephrine). Additionally, the hemodynamic effect of ACC519T and telmisartan on mean arterial pressure in conscious rabbits was determined, while the ex vivo ability of BV6(K) to activate angiotensin-converting enzyme-2 (ACE2) was also investigated. We show that commercially available and novel ARBs can modulate contraction responses at ultra-high dilutions to different vasopressors. ACC519T produced a dose-dependent reduction in rabbit mean arterial pressure while BV6(K) significantly increased ACE2 metabolism. The ability of ARBs to inhibit contraction responses even at ultra-low concentrations provides evidence of the existence of quantum pharmacology. Furthermore, the ability of ACC519T and BV6(K) to modulate blood pressure and ACE2 activity, respectively, indicates their therapeutic potential against hypertension.
Topics: Rabbits; Male; Animals; Angiotensin II Type 1 Receptor Blockers; Telmisartan; Angiotensin-Converting Enzyme 2; Angiotensin Receptor Antagonists; Iliac Artery; Angiotensin-Converting Enzyme Inhibitors; Benzimidazoles; Tetrazoles; Hypertension; Blood Pressure
PubMed: 38139391
DOI: 10.3390/ijms242417559 -
Drug Design, Development and Therapy 2024Norepinephrine has fewer negative effects on heart rate (HR) and cardiac output (CO) for treating postspinal hypotension (PSH) compared with phenylephrine during... (Randomized Controlled Trial)
Randomized Controlled Trial Clinical Trial
Randomized Double-Blinded Comparison of Intermittent Boluses Phenylephrine and Norepinephrine for the Treatment of Postspinal Hypotension in Patients with Severe Pre-Eclampsia During Cesarean Section.
BACKGROUND
Norepinephrine has fewer negative effects on heart rate (HR) and cardiac output (CO) for treating postspinal hypotension (PSH) compared with phenylephrine during cesarean section. However, it remains unclear whether fetuses from patients with severe pre-eclampsia could benefit from the superiority of CO. The objective of this study was to compare the safety and efficacy of intermittent intravenous boluses of phenylephrine and norepinephrine used in equipotent doses for treating postspinal hypotension in patients with severe pre-eclampsia during cesarean section.
METHODS
A total of 80 patients with severe pre-eclampsia who developed PSH predelivery during cesarean section were included. Eligible patients were randomized at a 1:1 ratio to receive either phenylephrine or norepinephrine for treating PSH. The primary outcome was umbilical arterial pH. Secondary outcomes included other umbilical cord blood gas values, Apgar scores at 1 and 5 min, changes in hemodynamic parameters including CO, mean arterial pressure (MAP), HR, stroke volume (SV), and systemic vascular resistance (SVR), the number of vasopressor boluses required, and the incidence of bradycardia, hypertension, nausea, vomiting, and dizziness.
RESULTS
No significant difference was observed in umbilical arterial pH between the phenylephrine and norepinephrine groups (7.303±0.38 vs 7.303±0.44, respectively; P=0.978). Compared with the phenylephrine group, the overall CO (P=0.009) and HR (P=0.015) were greater in the norepinephrine group. The median [IQR] total number of vasopressor boluses required was comparable between the two groups (2 [1 to 3] and 2 [1 to 3], respectively; P=0.942). No significant difference was found in Apgar scores or the incidence of maternal complications between groups.
CONCLUSION
A 60 µg bolus of phenylephrine and a 4.5 µg bolus of norepinephrine showed similar neonatal outcomes assessed by umbilical arterial pH and were equally effective when treating PSH during cesarean section in patients with severe pre-eclampsia. Norepinephrine provided a higher maternal CO and a lower incidence of bradycardia.
Topics: Female; Humans; Infant, Newborn; Pregnancy; Anesthesia, Spinal; Bradycardia; Cesarean Section; Double-Blind Method; Hypotension; Norepinephrine; Phenylephrine; Pre-Eclampsia; Vasoconstrictor Agents
PubMed: 38476203
DOI: 10.2147/DDDT.S446657