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1.
Medicine (Baltimore) ; 103(10): e37454, 2024 Mar 08.
Artigo em Inglês | MEDLINE | ID: mdl-38457564

RESUMO

BACKGROUND: Phenylephrine may cause a reduction in maternal cerebral tissue oxygen saturation (SctO2) during Caesarean birth to prevent spinal hypotension; however, the effect of norepinephrine has not been assessed. We hypothesized that norepinephrine was more effective than phenylephrine in maintaining SctO2 when preventing spinal hypotension during Caesarean birth. METHODS: We conducted a randomized, double-blind, controlled study. Sixty patients were randomly assigned to prophylactic norepinephrine or phenylephrine to maintain blood pressure during spinal anesthesia for Caesarean birth. SctO2, systolic blood pressure, and heart rate were recorded. The primary outcome was the incidence of a 10% reduction of intraoperative SctO2 from baseline or more during Caesarean birth. RESULTS: The norepinephrine group had a lower incidence of more than 10% reduction of intraoperative SctO2 from baseline than that of the phenylephrine group (13.3% vs 40.0%, P = .02). The change in SctO2 after 5 minutes of norepinephrine infusion was higher than that after phenylephrine infusion (-3.4 ±â€…4.7 vs -6.2 ±â€…5.6, P = .04). The change in SctO2 after 10 minutes of norepinephrine infusion was higher than that after phenylephrine infusion (-2.5 ±â€…4.4 vs -5.4 ±â€…4.6, P = .006). The norepinephrine group showed greater left- and right-SctO2 values than the phenylephrine group at 5 to 10 minutes. However, the change in systolic blood pressure was comparable between the 2 groups. CONCLUSION: Norepinephrine was more effective than phenylephrine in maintaining SctO2 when preventing spinal hypotension during Caesarean birth. However, the changes in clinical outcomes caused by differences in SctO2 between the 2 medications warrant further studies.


Assuntos
Anestesia Obstétrica , Raquianestesia , Hipotensão , Gravidez , Feminino , Humanos , Fenilefrina/uso terapêutico , Norepinefrina/uso terapêutico , Vasoconstritores/uso terapêutico , Saturação de Oxigênio , Resultado do Tratamento , Hipotensão/etiologia , Hipotensão/prevenção & controle , Hipotensão/tratamento farmacológico , Cesárea/efeitos adversos , Raquianestesia/efeitos adversos , Método Duplo-Cego
2.
Life Sci ; 343: 122488, 2024 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-38428573

RESUMO

AIM: The present study evaluated whether topiramate (TPM) treatment during the peripubertal period affects vascular parameters of male rats and whether oxidative stress plays a role in these changes. MAIN METHODS: Rats were treated with TPM (41 mg/kg/day, gavage) or vehicle (CTR group) from the postnatal day (PND) 28 to 50. At PND 51 and 120 the rats were evaluated for: thoracic aorta reactivity to phenylephrine, in the presence (Endo+) or absence of endothelium (Endo-), to acetylcholine and to sodium nitroprusside (SNP), aortic thickness and endothelial nitric oxide synthase (eNOS) expression. In serum were analyzed: the antioxidant capacity by ferric reducing antioxidant power assay; endogenous antioxidant reduced glutathione, and superoxide anion. Results were expressed as mean ± s.e.m., differences when p < 0.05. STATISTICS: Two-way ANOVA (and Tukey's) or Student t-test. KEY FINDINGS: At PND 51, the contraction induced by phenylephrine in Endo+ ring was higher in TPM when compared to CTR. At PND 120, the aortic sensitivity to acetylcholine in TPM rats was reduced in comparison with CTR. The aortic eNOs expression and the aortic thickness were similar between the groups. At PND 51 and 120, TPM group presented a decrease in antioxidants when compared to CTR groups and at PND 120, in TPM group the superoxide anion was increased. SIGNIFICANCE: Taken together, the treatment of rats with TPM during peripubertal period promoted permanent impairment of endothelial function probably mediated by oxidative stress.


Assuntos
Acetilcolina , Antioxidantes , Ratos , Animais , Masculino , Antioxidantes/farmacologia , Antioxidantes/metabolismo , Topiramato/farmacologia , Acetilcolina/metabolismo , Superóxidos/metabolismo , Endotélio Vascular/metabolismo , Óxido Nítrico Sintase Tipo III/metabolismo , Estresse Oxidativo , Aorta Torácica/metabolismo , Fenilefrina/farmacologia , Óxido Nítrico/metabolismo
3.
BMC Anesthesiol ; 24(1): 88, 2024 Mar 02.
Artigo em Inglês | MEDLINE | ID: mdl-38431582

RESUMO

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).


Assuntos
Anestesia Geral , Índice de Perfusão , Humanos , Fenilefrina/farmacologia , Débito Cardíaco , Estudos Prospectivos , Volume Sistólico , Hidratação , Pressão Sanguínea
4.
Drug Des Devel Ther ; 18: 639-650, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38476203

RESUMO

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.


Assuntos
Raquianestesia , Cesárea , Hipotensão , Pré-Eclâmpsia , Feminino , Humanos , Recém-Nascido , Gravidez , Raquianestesia/efeitos adversos , Bradicardia/induzido quimicamente , Método Duplo-Cego , Hipotensão/tratamento farmacológico , Norepinefrina , Fenilefrina , Pré-Eclâmpsia/tratamento farmacológico , Vasoconstritores
5.
Pharmacol Res Perspect ; 12(2): e1180, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38421097

RESUMO

Changes in vascular biomechanics leading to increase in arterial stiffness play a pivotal role in circulatory dysfunction. Our objectives were to examine sex-specific pharmacological changes related to the biomechanics and any structural modifications in small resistance arteries of Dahl salt-sensitive male and female rats. The composite Young modulus (CYM) was determined using pressure myograph recordings, and immunohistochemistry was used for the evaluation of any structural changes in the third-order mesenteric arteries (n = 6). Animals on high-salt diet developed hypertension with significant elevation in central and peripheral blood pressures and pulse wave velocity compared to those on regular diet. There were no significant differences observed in the CYM between any of the groups (i.e., males and females) in vehicle-treated time-control studies. The presence of verapamil (0.3 µM) significantly reduced CYM in hypertensive males without changes within females compared to vehicle. This effect was abolished by phenylephrine (0.3 µM). BaCl2 (100 µM), ouabain (100 µM), and L-NAME (0.3 µM) combined significantly increased CYM in vessels from in normotensive males and females but not in hypertensive males compared to vehicle. The increase in CYM was abolished in the presence of phenylephrine. Sodium nitroprusside (0.3 µM), in the presence of phenylephrine, significantly reduced CYM in male normotensive versus hypertensive, with no differences within females. Significant differences were observed in immunohistochemical assessment of biomechanical markers of arterial stiffness between males and females. Our findings suggest sex possibly due to pressure differences to be responsible for adaptive changes in biomechanics, and varied pharmacological responses in hypertensive state.


Assuntos
Hipertensão , Análise de Onda de Pulso , Ratos , Masculino , Feminino , Animais , Ratos Endogâmicos Dahl , Fenômenos Biomecânicos , Artérias , Fenilefrina/farmacologia , Cloreto de Sódio
6.
Int J Mol Sci ; 25(4)2024 Feb 16.
Artigo em Inglês | MEDLINE | ID: mdl-38397020

RESUMO

Anserine, an imidazole dipeptide, is present in the muscles of birds and fish and has various bioactivities, such as anti-inflammatory and anti-fatigue effects. However, the effect of anserine on the development of heart failure remains unknown. We cultured primary cardiomyocytes with 0.03 mM to 10 mM anserine and stimulated them with phenylephrine for 48 h. Anserine significantly suppressed the phenylephrine-induced increases in cardiomyocyte hypertrophy, ANF and BNP mRNA levels, and histone H3K9 acetylation. An in vitro histone acetyltransferase (HAT) assay showed that anserine directly suppressed p300-HAT activity with an IC50 of 1.87 mM. Subsequently, 8-week-old male C57BL/6J mice were subjected to transverse aortic constriction (TAC) and were randomly assigned to receive daily oral treatment with anserine-containing material, Marine Active® (60 or 200 mg/kg anserine) or vehicle for 8 weeks. Echocardiography revealed that anserine 200 mg/kg significantly prevented the TAC-induced increase in left ventricular posterior wall thickness and the decrease in left ventricular fractional shortening. Moreover, anserine significantly suppressed the TAC-induced acetylation of histone H3K9. These results indicate that anserine suppresses TAC-induced systolic dysfunction, at least in part, by inhibiting p300-HAT activity. Anserine may be used as a pharmacological agent for human heart failure therapy.


Assuntos
Anserina , Cardiomiopatias , Insuficiência Cardíaca , Miócitos Cardíacos , Fatores de Transcrição de p300-CBP , Animais , Humanos , Masculino , Camundongos , Acetilação , Anserina/farmacologia , Cardiomegalia/genética , Cardiomiopatias/metabolismo , Inibidores Enzimáticos/farmacologia , Insuficiência Cardíaca/metabolismo , Histonas/metabolismo , Camundongos Endogâmicos C57BL , Miócitos Cardíacos/efeitos dos fármacos , Miócitos Cardíacos/metabolismo , Fenilefrina/farmacologia , Fatores de Transcrição de p300-CBP/antagonistas & inibidores
7.
Cardiovasc Toxicol ; 24(3): 321-334, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38409566

RESUMO

Cirrhotic cardiomyopathy is a myocardial disease that may go undetected in the early stages due to peripheral vasodilatation. The aim of the study was to evaluate the electrocardiogram (ECG) and heart rate variability (HRV) after raising blood pressure by phenylephrine injection in rats with liver cirrhosis. Twenty male Sprague-Dawley rats were divided into the Sham and common bile duct ligation (CBDL) groups. After 44 days, animals were anesthetized and the right femoral artery and vein catheterized. After a steady-state period, a bolus injection of phenylephrine (PHE, 10 µg/µl/IV, baroreflex maneuver) was followed by a slow injection of PHE (100 µg/ml/5 min/IV, sustained maneuver). Rapid and slow injections of PHE resulted in a greater increase in mean arterial pressure (MAP) and a weaker bradycardia response in the CBDL group than in the Sham group. ECG analysis showed increased QT, QTc, JT, and T peak to T end in the CBDL group, which remained unchanged after PHE injection. On the other hand, the parasympathetic indices of the HF band and RMSSD, and the sympathetic index of the LF band after PHE injection were lower in the CBDL group than in the Sham group.ECG data indicated prolonged ventricular depolarization and repolarization, independent of blood pressure levels in cirrhosis. On the other hand, after PHE injection, the parasympathetic and sympathetic components of HRV decreased, regardless of the duration of elevated blood pressure. We suggest that HRV analysis can provide a useful approach to assess cardiac dysfunction associated with elevated blood pressure in cirrhosis.


Assuntos
Hipertensão , Ratos , Masculino , Animais , Frequência Cardíaca , Pressão Sanguínea , Ratos Sprague-Dawley , Fenilefrina , Cirrose Hepática , Eletrocardiografia , Fibrose
8.
JAMA ; 331(9): 796-798, 2024 03 05.
Artigo em Inglês | MEDLINE | ID: mdl-38329748

RESUMO

This study examines purchasing patterns regarding oral decongestants, concerns about their efficacy, and the need for timelier postmarket evaluation.


Assuntos
Comércio , Fenilefrina , Pseudoefedrina , Comércio/tendências , Fenilefrina/economia , Fenilefrina/uso terapêutico , Pseudoefedrina/economia , Pseudoefedrina/uso terapêutico , Estados Unidos/epidemiologia
9.
Clin Sci (Lond) ; 138(4): 137-151, 2024 Feb 21.
Artigo em Inglês | MEDLINE | ID: mdl-38299431

RESUMO

Hypercholesterolemia in pregnancy is a physiological process required for normal fetal development. In contrast, excessive pregnancy-specific hypercholesterolemia increases the risk of complications, such as preeclampsia. However, the underlying mechanisms are unclear. Toll-like receptor 4 (TLR4) is a membrane receptor modulated by high cholesterol levels, leading to endothelial dysfunction; but whether excessive hypercholesterolemia in pregnancy activates TLR4 is not known. We hypothesized that a high cholesterol diet (HCD) during pregnancy increases TLR4 activity in uterine arteries, leading to uterine artery dysfunction. Sprague Dawley rats were fed a control diet (n=12) or HCD (n=12) during pregnancy (gestational day 6-20). Vascular function was assessed in main uterine arteries using wire myography (vasodilation to methacholine and vasoconstriction to phenylephrine; with and without inhibitors for mechanistic pathways) and pressure myography (biomechanical properties). Exposure to a HCD during pregnancy increased maternal blood pressure, induced proteinuria, and reduced the fetal-to-placental weight ratio for both sexes. Excessive hypercholesterolemia in pregnancy also impaired vasodilation to methacholine in uterine arteries, whereby at higher doses, methacholine caused vasoconstriction instead of vasodilation in only the HCD group, which was prevented by inhibition of TLR4 or prostaglandin H synthase 1. Endothelial nitric oxide synthase expression and nitric oxide levels were reduced in HCD compared with control dams. Vasoconstriction to phenylephrine and biomechanical properties were similar between groups. In summary, excessive hypercholesterolemia in pregnancy impairs uterine artery function, with TLR4 activation as a key mechanism. Thus, TLR4 may be a target for therapy development to prevent adverse perinatal outcomes in complicated pregnancies.


Assuntos
Hipercolesterolemia , Hiperlipidemias , Animais , Feminino , Masculino , Gravidez , Ratos , Hipercolesterolemia/metabolismo , Hiperlipidemias/metabolismo , Cloreto de Metacolina/metabolismo , Fenilefrina/farmacologia , Fenilefrina/metabolismo , Placenta , Ratos Sprague-Dawley , Receptor 4 Toll-Like/metabolismo , Artéria Uterina/metabolismo , Vasodilatação/fisiologia
10.
Toxicol Appl Pharmacol ; 484: 116873, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38417591

RESUMO

This study analyzed how glyphosate exposure in the gestational period affects vascular function in their female offspring and whether oxidative stress is involved in this effect. To this, pregnant Wistar rats were exposed through drinking water to 0.2% of a glyphosate commercial formulation, and we analyzed the response to acetylcholine and phenylephrine in the aorta from offspring of Glyphosate-based herbicide (O-GBH) and controls (O-CON) rats at six months of age. Relaxation to acetylcholine was reduced in O-GBH than in O-CON. Acute Indomethacin and Apocynin increased relaxation to acetylcholine in O-GBH. The aorta from O-GBH was hyperactive to phenylephrine; the preincubation with N-nitro-L-arginine methyl ester (L-NAME) increased contraction to phenylephrine more in O-CON than O-GBH. TEMPOL similarly reduced phenylephrine response, and L-NAME prevented this effect. The TBARS and GSH levels were increased in O-GBH than in O-CON. Results reinforce the concept that oxidative stress during the perinatal period contributes to the development of vascular changes in adulthood. Results also reveal that oxidative stress parameters altered, and the current levels considered safe for exposure to Glyphosate deserve further investigation, especially in the female gender.


Assuntos
Herbicidas , Gravidez , Humanos , Ratos , Animais , Feminino , Herbicidas/toxicidade , Ratos Wistar , NG-Nitroarginina Metil Éster , Exposição Materna/efeitos adversos , Acetilcolina , Glicina/toxicidade , Fenilefrina/toxicidade
11.
Pregnancy Hypertens ; 35: 96-102, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38306739

RESUMO

Early diagnosis and efficient treatment of preeclampsia remains a medical challenge and etiological factors converge in a deficient placentation that triggers oxidative stress. There is evidence that statins show antioxidant effects that can improve endothelial function without adverse perinatal effects. We aimed to compare early vs. late pravastatin treatment on the oxidative stress and cardiovascular features of an experimental model of preeclampsia. Female Wistar rats were randomly divided into preeclampsia phenotype rats (PEP) developed by sub renal aortic coarctation (SRAC) and healthy pregnant rats (C). Each group received pravastatin (5 mg/Kg) p.o. either for one week before and during the first week or during the last two weeks of gestation. Blood pressure was determined using the plethysmographic method. Phenylephrine (Phe)-induced contractility was evaluated in isolated thoracic and abdominal aortic rings with or without endothelium. Blood samples were obtained to determine anion superoxide concentration as indicator of NADPH activity. Two-way ANOVA and Bonferroni post hoc tests were used to define statistical significance. Early or late pravastatin treatment decreased hypertension of PEP animals but did not change BP of the healthy pregnant group. Thoracic and abdominal aorta from PEP rats showed increased contractility that was reverted by pravastatin early treatment in endothelium intact rings. Pravastatin did not significantly change contractility neither in the thoracic nor in the abdominal aorta segments from healthy pregnant control rats (C), and decrease anion superoxide concentration by NADPH activity. We conclude pravastatin can improve both blood pressure and endothelium-dependent Phe-induced contractility in an experimental model of preeclampsia by reducing oxidative stress.


Assuntos
Pravastatina , Pré-Eclâmpsia , Gravidez , Humanos , Ratos , Feminino , Animais , Pravastatina/farmacologia , Pravastatina/uso terapêutico , Pré-Eclâmpsia/tratamento farmacológico , Superóxidos/farmacologia , NADP/farmacologia , Ratos Wistar , Estresse Oxidativo , Fenilefrina/farmacologia , Endotélio Vascular
12.
Physiol Rep ; 12(1): e15911, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-38212292

RESUMO

Wire myography to test vasomotor functions of blood vessels ex-vivo are well-established for the systemic circulation, however, there is no consensus on protocols for pulmonary arteries. We created a standardized wire myography protocol for healthy rat PAs and validated this in a pulmonary hypertension (PH) model. Vessels stretched to higher initial tensions (5.0, 7.5 and 10.0 mN) exhibited a uniform response to phenylephrine, a larger dynamic range, and lower EC50 values. The endothelium-mediated relaxation showed that moderate tensions (7.5 and 10.0 mN) produced robust responses with higher maximum relaxation and lower EC50 values. For endothelium independent responses, the higher initial tension groups had lower and more consistent EC50 values than the lower initial tension groups. Pulmonary arteries from rats with PH were more responsive to vasoactive drugs when subjected to a higher initial tension. Notably, vessels in the PH group subjected to 15.0 mN exhibited high dynamic ranges in contractile and relaxation responses without tearing. Lastly, we observed attenuated cholinergic responses in these vessels-consistent with endothelial dysfunction in PH. Therefore, a moderate initial tension of 7.5-10.0 mN is optimal for healthy rat pulmonary arteries and a higher initial tension of 15.0 mN is optimal for pulmonary arteries from animals with PH.


Assuntos
Hipertensão Pulmonar , Artéria Pulmonar , Ratos , Masculino , Animais , Fenilefrina , Miografia/métodos , Vasodilatação
14.
Anatol J Cardiol ; 28(1): 55-64, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-38167793

RESUMO

BACKGROUND: The aim of this study was to examine the effect of myricetin on cardiac dysfunction caused by high fructose intake. METHODS: Fructose was given to the rats as a 20% solution in drinking water for 15 weeks. Myricetin was administered by oral gavage for the last 6 weeks. Systolic blood pressure was measured by tail-cuff method. The effects of isoprenaline, phenylephrine, and acetylcholine on cardiac contractility and rhythmicity were recorded in the isolated right atrium and left ventricular papillary muscles. In addition to biochemical measurements, the cardiac expressions of cellular stress-related proteins were determined by western blotting. RESULTS: Myricetin improved systolic blood pressure but did not affect body weight, plasma glucose, and triglyceride levels in fructose-fed rats. The impairment of isoprenaline- and phenylephrine-mediated increases in atrial contraction and sinus rate in fructose-fed rats was restored by myricetin treatment. Isoprenaline, phenylephrine, and acetylcholine-mediated papillary muscle contractions were not changed by fructose or myricetin administration. The expression of the mitochondrial fission marker dynamin-related protein 1 and the mitophagic marker PTEN-induced kinase 1 (PINK1) was enhanced in the fructose-fed rat, and myricetin treatment markedly attenuated PINK1 expression. High-fructose intake augmented phosphorylation of the proinflammatory molecule Nuclear factor kappa B (NF-κB) and the stress-regulated kinase JNK1, but myricetin only reduced NF-κB expression. Moreover, myricetin diminished the elevation in the expression of the pro-apoptotic Bax. CONCLUSION: Our results imply that myricetin has a protective role in cardiac irregularities induced by a high-fructose diet through reducing systolic blood pressure, improving cardiac adrenergic responses, suppressing PINK1, NF-κB, and Bax expression, and thus reflecting a potential therapeutic value.


Assuntos
Cardiopatias , NF-kappa B , Ratos , Animais , Pressão Sanguínea , NF-kappa B/metabolismo , Acetilcolina/farmacologia , Frutose , Isoproterenol , Proteína X Associada a bcl-2/farmacologia , Fenilefrina/farmacologia , Proteínas Quinases/farmacologia
15.
Orthop Nurs ; 43(1): 41-44, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38266263

RESUMO

Priapism is a disorder where the penis without sexual stimulation maintains a prolonged rigid erection lasting 4 or more hours. There are two classifications of priapism, ischemic (low flow) or nonischemic high flow, and each have specific etiologies, diagnostic criteria, and management. This presented case study involved a 58-year-old male who experienced an ischemic priapism more than 24 hours after an anterior lumbar interbody fusion (ALIF). A flaccid penis was achieved after the patient received two 400 µg of phenylephrine HCL into the corpora cavernosum. Review of the literature suggests anesthetic medications given during the surgical procedure may have caused the priapism. Lessons that can be learned from this case study highlight that even though the nurse may not expect to see a priapism after an ALIF, the nurse must always be diligent and not become complacent with unexpected findings or assessments that may cause irreparable harm to the patient.


Assuntos
Priapismo , Masculino , Humanos , Pessoa de Meia-Idade , Priapismo/etiologia , Aprendizagem , Região Lombossacral , Fenilefrina
16.
J Neurosci ; 44(9)2024 Feb 28.
Artigo em Inglês | MEDLINE | ID: mdl-38242697

RESUMO

Cardiovascular homeostasis is maintained, in part, by neural signals arising from arterial baroreceptors that apprise the brain of blood volume and pressure. Here, we test whether neurons within the nodose ganglia that express angiotensin type-1a receptors (referred to as NGAT1aR) serve as baroreceptors that differentially influence blood pressure (BP) in male and female mice. Using Agtr1a-Cre mice and Cre-dependent AAVs to direct tdTomato to NGAT1aR, neuroanatomical studies revealed that NGAT1aR receive input from the aortic arch, project to the caudal nucleus of the solitary tract (NTS), and synthesize mechanosensitive ion channels, Piezo1/2 To evaluate the functionality of NGAT1aR, we directed the fluorescent calcium indicator (GCaMP6s) or the light-sensitive channelrhodopsin-2 (ChR2) to Agtr1a-containing neurons. Two-photon intravital imaging in Agtr1a-GCaMP6s mice revealed that NGAT1aR couple their firing to elevated BP, induced by phenylephrine (i.v.). Furthermore, optical excitation of NGAT1aR at their soma or axon terminals within the caudal NTS of Agtr1a-ChR2 mice elicited robust frequency-dependent decreases in BP and heart rate, indicating that NGAT1aR are sufficient to elicit appropriate compensatory responses to vascular mechanosensation. Optical excitation also elicited hypotensive and bradycardic responses in ChR2-expressing mice that were subjected to deoxycorticosterone acetate (DOCA)-salt hypertension; however, the duration of these effects was altered, suggestive of hypertension-induced impairment of the baroreflex. Similarly, increased GCaMP6s fluorescence observed after administration of phenylephrine was delayed in mice subjected to DOCA-salt or chronic delivery of angiotensin II. Collectively, these results reveal the structure and function of NGAT1aR and suggest that such neurons may be exploited to discern and relieve hypertension.


Assuntos
Acetato de Desoxicorticosterona , Hipertensão , Camundongos , Masculino , Feminino , Animais , Acetato de Desoxicorticosterona/farmacologia , Núcleo Solitário/fisiologia , Células Receptoras Sensoriais , Pressão Sanguínea/fisiologia , Fenilefrina/farmacologia , Canais Iônicos
17.
Int J Mol Sci ; 25(2)2024 Jan 10.
Artigo em Inglês | MEDLINE | ID: mdl-38255931

RESUMO

We studied whether the function of presynaptic inhibitory cannabinoid CB1 receptors on the sympathetic nerve fibres innervating resistance vessels is increased in spontaneously hypertensive rats (SHR) like in deoxycorticosterone (DOCA)-salt hypertension. An increase in diastolic blood pressure (DBP) was induced by electrical stimulation of the preganglionic sympathetic neurons or by phenylephrine injection in pithed SHR and normotensive Wistar-Kyoto rats (WKY). The electrically (but not the phenylephrine) induced increase in DBP was inhibited by the cannabinoid receptor agonist CP55940, similarly in both groups, and by the endocannabinoid reuptake inhibitor AM404 in SHR only. The effect of CP55940 was abolished/reduced by the CB1 receptor antagonist AM251 (in both groups) and in WKY by endocannabinoid degradation blockade, i.e., the monoacylglycerol lipase (MAGL) inhibitor MJN110 and the dual fatty acid amide hydrolase (FAAH)/MAGL inhibitor JZL195 but not the FAAH inhibitor URB597. MJN110 and JZL195 tended to enhance the effect of CP55940 in SHR. In conclusion, the function of presynaptic inhibitory CB1 receptors depends on the hypertension model. Although no differences occurred between SHR and WKY under basal experimental conditions, the CB1 receptor function was better preserved in SHR when the endocannabinoid tone was increased by the inhibition of MAGL or the endocannabinoid transporter.


Assuntos
Canabinoides , Carbamatos , Cicloexanóis , Hipertensão , Piperazinas , Succinimidas , Ratos , Animais , Ratos Endogâmicos WKY , Endocanabinoides/farmacologia , Ratos Endogâmicos SHR , Fenilefrina
18.
Mikrochim Acta ; 191(2): 96, 2024 01 15.
Artigo em Inglês | MEDLINE | ID: mdl-38225436

RESUMO

The combination of multi-walled carbon nanotubes (MWCNT) and carbon black (CB) is presented to produce a high-performance electrically conductive recycled additive manufacturing filament. The filament and subsequent additively manufactured electrodes were characterised by TGA, XPS, Raman, and SEM and showed excellent low-temperature flexibility. The MWCNT/CB filament exhibited an improved electrochemical performance compared to an identical in-house produced bespoke filament using only CB. A heterogeneous electrochemical rate constant, [Formula: see text] of 1.71 (± 0.19) × 10-3 cm s-1 was obtained, showing an almost six times improvement over the commonly used commercial conductive CB/PLA. The filament was successfully tested for the simultaneous determination of acetaminophen and phenylephrine, producing linear ranges of 5-60 and 5-200 µM, sensitivities of 0.05 µA µM-1 and 0.14 µA µM-1, and limits of detection of 0.04 µM and 0.38 µM, respectively. A print-at-home device is presented where a removable lid comprised of rPLA can be placed onto a drinking vessel and the working, counter, and reference components made from our bespoke MWCNT/CB filament. The print-at-home device was successfully used to determine both compounds within real pharmaceutical products, with recoveries between 87 and 120% over a range of three real samples. This work paves the way for fabricating new highly conductive filaments using a combination of carbon materials with different morphologies and physicochemical properties and their application to produce additively manufactured electrodes with greatly improved electrochemical performance.


Assuntos
Acetaminofen , Nanotubos de Carbono , Acetaminofen/análise , Nanotubos de Carbono/química , Fuligem , Fenilefrina , Técnicas Eletroquímicas
19.
Sci Rep ; 14(1): 2566, 2024 01 31.
Artigo em Inglês | MEDLINE | ID: mdl-38297133

RESUMO

A posterior approach is recommended for the correction of mild to moderate upper eyelid ptosis in adults. The aim of this study is to propose a new algorithm that helps to predict outcomes in the transconjunctival correction of moderate to severe blepharoptosis. This study included adult patients with moderate to severe upper eyelid ptosis treated between 2019 and 2021. Patients meeting inclusion criteria underwent ptosis correction through a posterior approach using an algorithm: 4 mm Mueller's muscle transconjunctival resection to correct 1 mm ptosis (depending on a test with 10% phenylephrine: 3-12 mm) ± tarsal plate resection: 1 mm for every 1 mm of residual ptosis after phenylephrine test, but leaving a minimum of 4 mm upper tarsus intact. Outcomes were ovserved within at least 6-months. Outcomes were assessed based on pre- and postoperative MRD1 changes, inter-eyelid height symmetry, cosmetic effect, and complications. Outcomes of 118 procedures in 81 patients (average age 69, range: 47-87) were analyzed. MRD1 changes were statistically significant, from 0.2 ± 1.6 mm before to 4.1 ± 1 mm after surgery. The function of the levator palpebrae superioris muscle was 10.2 ± 3.4 (range 5-17) mm. Upper eyelid lifted by an average of 1.8 ± 0.7 (range 0-3) mm after the instillation of 10% phenylephrine eyedrops. An average of 8.5 ± 0.8 (range 8-10) mm of conjunctiva and Mueller's muscle and 2.2 ± 0.9 (range 1-5) mm of the tarsal plate were resected during the procedure. Inter-eyelid height symmetry within 1 mm was achieved in 95% of outcomes. The algorithm introduced in this study appears to be useful to achieve repeatable satisfactory outcomes in the transconjunctival correction of moderate to severe upper eyelid ptosis in adults with at least "fair" levator function.


Assuntos
Blefaroplastia , Blefaroptose , Adulto , Humanos , Idoso , Blefaroptose/cirurgia , Blefaroplastia/métodos , Estudos Retrospectivos , Pálpebras/cirurgia , Fenilefrina , Algoritmos
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