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1.
J Med Life ; 12(3): 296-300, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31666834

RESUMO

During menstruation, endometrial hemostasis is achieved by platelet aggregation, fibrin deposition, and thrombus formation that interact with local endocrine and immunological factors which cause termination of menstrual bleeding. Interactions between steroidal sex hormones and platelet functions are not well understood. The aim of this study was to evaluate the effect of platelet function during the menstrual cycle and luteal phase in women of reproductive age. The cross-sectional study on women of reproductive age included 44 healthy women. Platelet function was assessed by PFA-100TM analyzer with collagen/epinephrine and collagen/ADP cartridges during the menstrual cycle and luteal phase. There were no significant differences in platelet function between menstruation and ovulatory phase. Platelet activity in Arab collagen/epinephrine cartridge increased during menstruation compared to non-Arab ethnic subjects and no significant differences in platelet function were found when using collagen/ADP cartridge. This study suggested modulation in platelet functions during menstruation and luteal phase in women of reproductive age. Further studies, including a large number of subjects, platelet genetic and progesterone factors change in platelet clotting associated to menstrual cycle should be conducted.


Assuntos
Plaquetas/fisiologia , Menstruação/fisiologia , Ovulação/fisiologia , Adulto , Colágeno/farmacologia , Estudos Transversais , Epinefrina/farmacologia , Feminino , Humanos , Pré-Menopausa/fisiologia
2.
Anaesthesia ; 74(11): 1389-1396, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31389614

RESUMO

We evaluated the effect of adrenaline on human skin microcirculation (nutritive and sub-papillary) and systemic cardiovascular variables after it was added to lidocaine in infraclavicular brachial plexus blocks. Twelve healthy, non-smoking male volunteers were included, each attending two study sessions 2 weeks apart, and they were studied using a crossover design. In both sessions, they received an ultrasound-guided infraclavicular brachial plexus block in the non-dominant arm with 0.4 ml.kg-1 lidocaine, 15 mg.ml-1 with or without adrenaline 5 µg.ml-1 . Microcirculation was assessed by laser Doppler fluxmetry (sub-papillary blood flow), capillary video microscopy (nutritive blood flow) and continuous temperature measurements. Heart rate and arterial pressure were recorded continuously and non-invasively. Median (IQR [range]) sub-papillary blood flow increased substantially 30 min after the brachial plexus block, from 8.5 (4.4-13.5 [2.9-28.2]) to 162.7 (111.0-197.8 [9.5-206.7]) arbitrary units with adrenaline (p = 0.017), and from 6.9 (5.3-28.5 [1.8-42.1] to 133.7 (16.5-216.7 [1.0-445.0] arbitrary units without adrenaline (p = 0.036). Nutritive blood flow (functional capillary density, capillaries.mm-2 , measured at the dorsal side of the hand) decreased in the blocked extremity when adrenaline was used as adjuvant, from median (IQR [range]) 45 (36-52 [26-59]) to 38 (29-41 [26-42]), p = 0.028, whereas no significant change occurred without adrenaline. Median finger skin temperature (°C) increased by 44% (data pooled) with no significant differences between the groups. No significant changes were found in the systemic cardiovascular variables with or without adrenaline. We conclude that lidocaine infraclavicular brachial plexus blocks caused an increase in skin sub-papillary blood flow. The addition of adrenaline produced stronger and longer lasting blocks, but decreased the nutritive blood flow.


Assuntos
Anestésicos Locais/farmacologia , Bloqueio do Plexo Braquial/métodos , Epinefrina/farmacologia , Hemodinâmica/efeitos dos fármacos , Lidocaína/farmacologia , Microcirculação/efeitos dos fármacos , Agonistas alfa-Adrenérgicos/farmacologia , Adulto , Estudos Cross-Over , Método Duplo-Cego , Quimioterapia Combinada , Hemodinâmica/fisiologia , Humanos , Masculino , Microcirculação/fisiologia , Pessoa de Meia-Idade , Estudos Prospectivos , Valores de Referência , Ultrassonografia de Intervenção/métodos , Adulto Jovem
3.
Hemoglobin ; 43(2): 88-94, 2019 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31290363

RESUMO

Vaso-occlusive crisis (VOC) occurs more frequently during stress in sickle cell disease patients. Epinephrine released during stress increases adhesion of sickled red blood cells (RBCs) to endothelium and to leukocytes, a process mediated through erythrocyte cyclic adenosine monophosphate (cAMP). Increased adhesion of sickled RBCs retards blood flow through the capillaries and promotes vaso-occlusion. Therefore, we examined the association of RBC-cAMP levels with frequency of acute pain episodes in sickle cell disease subjects. Using a case control study design, we measured RBC-cAMP levels, fetal hemoglobin (Hb F), α-thalassemia (α-thal) and other hematological parameters at baseline (sham treated) and after stimulation with epinephrine. The cases consisted of sickle cell disease subjects with three or more acute pain episodes in the last 12 months, and those without a single acute pain episode in the last 12 months were considered as controls. Significantly higher cAMP values were found in cases than the controls, in both sham treated (p < 0.001) and epinephrine treated RBCs (p < 0.001) by Wilcoxon Rank Sum test. However, significant association of cAMP values was observed both on univariate [odds ratio (OR): 4.8, 95% confidence interval (95% CI): 1.51-15.19, p < 0.008) and multivariate logistic regression analyses only in epinephrine treated (OR: 5.07, 95% CI: 1.53-16.82, p < 0.008) but not in sham-treated RBCs. In the covariates, Hb F consistently showed protective effects in univariate as well as in multivariate analyses. Frequent acute pain episodes are associated with higher cAMP levels than those with less frequent pain episodes, only after stimulation with epinephrine but not with baseline level.


Assuntos
Dor Aguda/etiologia , Anemia Falciforme/patologia , AMP Cíclico/análise , Eritrócitos/química , Adulto , Anemia Falciforme/complicações , Estudos de Casos e Controles , Epinefrina/farmacologia , Feminino , Hemoglobina Fetal/farmacologia , Humanos , Índia , Masculino
4.
Anticancer Res ; 39(7): 3519-3529, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31262876

RESUMO

BACKGROUND/AIM: Although adrenergic agonists have been used in dental treatments and oral surgery for general anesthesia, their cytotoxicity against human oral malignant and non-malignant cell has not been well- understood. The present study was undertaken to investigate the cytotoxicity of five adrenergic agonists against human oral squamous cell carcinoma (OSCC), glioblastoma, promyelocytic leukemia, and normal oral mesenchymal cells (gingival fibroblast, pulp cell, periodontal ligament fibroblast) and normal epidermal keratinocytes. MATERIALS AND METHODS: Tumor-specificity (TS) was calculated by the ratio between the mean 50% cytotoxic concentration against normal cells to that of tumor cells. Internucleosomal DNA fragmentation was detected using agarose gel electrophoresis. Caspase-3 activity was measured by substrate cleavage. RESULTS: Both cytotoxicity and tumor-specificity of adrenergic agonists against OSCC cell lines was in the order of isoprenaline>dexmedetomidine> adrenaline>clonidine and phenylephrine. Isoprenaline and dexmedetomidine did not induce apoptosis markers, such as internucleosomal DNA fragmentation and caspase-3 activation, but induced a smear pattern of DNA fragmentation in OSCC cell lines. Their cytotoxicity was not reduced by pretreatment with autophagy inhibitors, or by adrenoceptors antagonists. Addition of superoxide dismutase and catalase significantly reduced the cytotoxicity of isoprenaline, but not that of dexmedetomidine. CONCLUSION: Isoprenaline and dexmedetomidine induce non-apoptotic cell death by different mechanisms.


Assuntos
Agonistas Adrenérgicos/farmacologia , Antineoplásicos/farmacologia , Carcinoma de Células Escamosas/tratamento farmacológico , Morte Celular/efeitos dos fármacos , Neoplasias Bucais/tratamento farmacológico , Catalase/farmacologia , Células Cultivadas , Criança , Clonidina/farmacologia , Fragmentação do DNA , Dexmedetomidina/farmacologia , Epinefrina/farmacologia , Humanos , Isoproterenol/farmacologia , Fenilefrina/farmacologia , Superóxido Dismutase/farmacologia
5.
Biomed Res Int ; 2019: 6539050, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31309111

RESUMO

Objective: To determine whether the administration of intra-arrest cyclosporine (CCY) and methylprednisolone (MP) preserves left ventricular ejection fraction (LVEF) and cardiac output (CO) after return of spontaneous circulation (ROSC). Methods: Eleven, 25-30kg female swine were randomized to receive 10mg/kg CCY + 40mg MP or placebo, anesthetized and given a transthoracic shock to induce ventricular fibrillation. After 8 minutes, standard CPR was started. After two additional minutes, the experimental agent was administered. Animals with ROSC were supported for up to 12h with norepinephrine as needed. Echocardiography was performed at baseline, and 1, 2, 6 and 12h post-ROSC. Analysis was performed using generalized estimating equations (GEE) after downsampling continuously sampled data to 5 minute epochs. Results: Eight animals (64%) achieved ROSC after a median of 7 [IQR 5-13] min of CPR, 2 [ IQR 1-3] doses of epinephrine and 2 [IQR 1-5] defibrillation shocks. Animals receiving CCY+MP had higher post ROSC MAP (GEE coefficient -10.2, P = <0.01), but reduced cardiac output (GEE coefficient 0.8, P = <0.01) compared to placebo. There was no difference in LVEF or vasopressor use between arms. Conclusions: Intra-arrest cyclosporine and methylprednisolone decreased post-arrest cardiac output and increased mean arterial pressure without affecting left ventricular ejection fraction.


Assuntos
Cardiomiopatias/tratamento farmacológico , Ciclosporina/farmacologia , Parada Cardíaca/tratamento farmacológico , Metilprednisolona/farmacologia , Animais , Débito Cardíaco/efeitos dos fármacos , Reanimação Cardiopulmonar/métodos , Ecocardiografia/métodos , Cardioversão Elétrica/métodos , Epinefrina/farmacologia , Feminino , Ventrículos do Coração/efeitos dos fármacos , Suínos , Vasoconstritores/farmacologia , Fibrilação Ventricular/tratamento farmacológico
6.
J Pharmacol Sci ; 140(2): 205-209, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31262461

RESUMO

The cardio-ankle vascular index (CAVI) has been established as a stiffness indicator from thoracic aorta to tibial arteries. To better understand physiological regulatory factors for the arterial stiffness, we assessed effects of angiotensin II and adrenaline on the CAVI in anesthetized rabbits. A hypertensive dose of angiotensin II (300 ng/kg, i.v.) increased the CAVI as well as the heart-ankle pulse wave velocity (haPWV). On the other hand, although a hypertensive dose of adrenaline (1000 ng/kg, i.v.) increased the haPWV, it did not affect the CAVI. These results suggest that angiotensin II may act as a regulatory factor for arterial stiffness.


Assuntos
Angiotensina II/farmacologia , Monitorização Fisiológica , Rigidez Vascular/efeitos dos fármacos , Vasoconstritores/farmacologia , Anestesia , Angiotensina II/fisiologia , Animais , Relação Dose-Resposta a Droga , Epinefrina/farmacologia , Masculino , Análise de Onda de Pulso , Coelhos
7.
Rev. cient. Esc. Univ. Cienc. Salud ; 6(1): 36-46, ene.-jun. 2019. tab
Artigo em Espanhol | LILACS | ID: biblio-1023753

RESUMO

Los anestésicos locales han cambiado de manera destacada la historia y la práctica de la medicina, la evolución en los métodos de desarrollo de anestésicos ha hecho posible el desarrollo de anestésicos convencionales para uso común en procedimientos médicos quirúrgicos locales, hablando en especial de dos anestésicos que se utilizan diariamente en los diferentes niveles de atención de salud mundial, la lidocaína y posteriormente la lidocaína con epinefrina. Es por el uso cotidiano de estos anestésicos que ahora es posible hacer procedimientos menores en los pacientes sin exponer a los mismos al dolor de los procedimientos propiamente dicho o la causa de dolor no procedimental. Se utiliza cada uno de acuerdo al efecto deseado que se requiera en el paciente, teniendo en cuenta las diversas precaucio-nes dada la potencial toxicidad que poseen, así como la técnica que se va a utilizar. En este artículo de revisión bibliográfica, se presentan las generalidades de ambos anestésicos, las indicaciones, precauciones, efectos adversos y comparación de toxici-dad entre ambos anestésicos. Esta revisión bibliográfica se realizó a partir de 36 artícu-los tomando como referencia los siguientes: literatura médica, artículos de revistas cien-tíficas y otras revisiones bibliográficas menores de 5 años de haber sido publica-dos o aquellos con relevancia histórica...(AU)


Assuntos
Humanos , Epinefrina/farmacologia , Anestésicos Locais , Lidocaína/farmacocinética , Revisão
8.
Medicine (Baltimore) ; 98(22): e15558, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-31145276

RESUMO

AIM: To measure changes in the sizes of Schlemm canal (SC) and trabecular meshwork (TM) in healthy individuals before and after topical application of 1% adrenaline at 15, 45, and 90 minutes using anterior segment optical coherence tomography (ASOCT). METHODS: Anterior chamber angle imaging of the nasal and temporal regions of the right eyes was performed with anterior segment optical coherence tomography (ASOCT) before and after topical application of 1% adrenaline at 15, 45, and 90 minutes. The diameter and area of SC, width and thickness of TM, anterior chamber depth (ACD) and pupil diameter (PD) were measured with ASOCT images. Intraocular pressure (IOP) was also recorded simultaneously. RESULTS: A total of 15 healthy individuals were enrolled and included 7 male subjects and 8 female subjects; Compared with the parameters before intervention, both the SC diameter and area in the 2 quadrants increased after the application of adrenaline at the 3 time points (P < .05). The TM width increased after medication (P < .05). IOP decreased significantly after application (P < .05). There were no statistically significant changes in TM thickness, ACD, and PD at any point of time (P > .05). CONCLUSION: Topical application of 1% adrenaline in eye led to decrease in IOP with the SC diameter and area as well as the TM width increased after medication. While the TM thickness, ACD, PD seemed to remain constant.


Assuntos
Epinefrina/farmacologia , Pressão Intraocular/efeitos dos fármacos , Esclera/efeitos dos fármacos , Malha Trabecular/efeitos dos fármacos , Administração Oftálmica , Adulto , Câmara Anterior/diagnóstico por imagem , Feminino , Voluntários Saudáveis , Humanos , Masculino , Tomografia de Coerência Óptica , Adulto Jovem
9.
PLoS One ; 14(5): e0216467, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31083675

RESUMO

Abnormal red blood cell (RBC) adhesion to endothelial αvß3 plays a crucial role in triggering vaso-occlusive episodes in sickle cell disease (SCD). It is known that epinephrine, a ß-adrenergic receptor (ß-AR) stimulator, increases the RBC surface density of active intercellular adhesion molecule-4 (ICAM-4) which binds to the endothelial αvß3. It has also been demonstrated that in human embryonic kidney 293 cells, mouse cardiomyocytes, and COS-7 cell lines, the ß-adrenergic and renin-angiotensin systems are interrelated and that there is a direct interaction and cross-regulation between ß-AR and angiotensin II type 1 receptor (AT1R). Selective blockade of AT1R reciprocally inhibits the downstream signaling of ß-ARs, similar to the inhibition observed in the presence of a ß-AR-blocker. However, it is not known if this mechanism is active in human RBCs. Here, we studied the effect of valsartan, an AT1R blocker, on the surface density of active ICAM-4 receptors in normal, sickle cell trait, and homozygous sickle RBCs. We applied single molecule force spectroscopy to detect active ICAM-4 receptors on the RBC plasma membrane with and without the presence of valsartan and epinephrine. We found that epinephrine significantly increased whereas valsartan decreased their surface density. Importantly, we found that pretreatment of RBCs with valsartan significantly impeded the activation of ICAM-4 receptors induced by epinephrine. The observed reduced expression of active ICAM-4 receptors on the RBC plasma membrane leads us to conjecture that valsartan may be used as a supporting remedy for the prevention and treatment of vaso-occlusive crisis in SCD.


Assuntos
Moléculas de Adesão Celular/metabolismo , Epinefrina/farmacologia , Membrana Eritrocítica/metabolismo , Eritrócitos Anormais/metabolismo , Traço Falciforme/metabolismo , Valsartana/farmacologia , Adolescente , Adulto , Animais , Células COS , Membrana Eritrocítica/ultraestrutura , Eritrócitos Anormais/ultraestrutura , Feminino , Células HEK293 , Humanos , Masculino , Camundongos , Microscopia de Força Atômica , Receptor Tipo 1 de Angiotensina/metabolismo , Traço Falciforme/patologia
10.
Anesth Analg ; 128(6): 1336-1343, 2019 06.
Artigo em Inglês | MEDLINE | ID: mdl-31094809

RESUMO

BACKGROUND: The objective of the experiment was to assess the antinociceptive effect of dibucaine, bupivacaine, and epinephrine. To assess the mechanism of action of the interaction between dibucaine and epinephrine, phentolamine, a nonselective α-adrenergic antagonist, was added to the mixture. METHODS: We assessed sensory blockade with these drugs by injecting 0.6 mL of drug-in-saline in the dorsal thoracolumbar area of rats; pinprick of the "wheal" formed by the injectate was the area targeted for stimulation to elicit a cutaneous trunci muscle reflex. The sensory block of dibucaine was compared with that of bupivacaine or epinephrine. Drug-drug interactions were analyzed by isobologram. Phentolamine was added to investigate the antinociceptive effect of dibucaine coinjected with epinephrine. RESULTS: We demonstrated that dibucaine, epinephrine, and bupivacaine produced dose-dependent skin antinociception. On the median effective dose (ED50) basis, the potency was higher for epinephrine (mean, 0.011 [95% confidence interval {CI}, 0.007-0.015] µmol) than for dibucaine (mean, 0.493 [95% CI, 0.435-0.560] µmol) (P < .01), while there were no significant differences between dibucaine and bupivacaine (mean, 0.450 [95% CI, 0.400-0.505] µmol). On the equipotent basis (75% effective dose, median effective dose, and 25% effective dose), sensory block duration provoked by epinephrine was greater (P < .01) than that provoked by dibucaine or bupivacaine. Coadministration of dibucaine with epinephrine produced a synergistic nociceptive block, whereas phentolamine blocked that synergistic block. CONCLUSIONS: The preclinical data indicated that there is no statistically significant difference between the potency and duration of dibucaine and bupivacaine in this model. Epinephrine synergistically enhances the effects of dibucaine, while phentolamine partially blocked those effects. α-Adrenergic receptors play an important role in controlling synergistic analgesic effect of dibucaine combined with epinephrine.


Assuntos
Antagonistas Adrenérgicos alfa/farmacologia , Analgésicos/farmacologia , Bupivacaína/farmacologia , Dibucaína/farmacologia , Epinefrina/farmacologia , Fentolamina/farmacologia , Pele/efeitos dos fármacos , Analgesia , Anestésicos Locais/farmacologia , Animais , Área Sob a Curva , Relação Dose-Resposta a Droga , Interações de Medicamentos , Sinergismo Farmacológico , Injeções Subcutâneas , Masculino , Dor/tratamento farmacológico , Ratos , Ratos Sprague-Dawley
11.
PLoS One ; 14(4): e0214733, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30998713

RESUMO

The study aims to clarify the mechanism in patients with neurally mediated syncope (NMS), focusing on the adenylate cyclase (AC) activity level in lymphocytes. This study included 40 subjects: 22 healthy volunteers and 18 NMS patients. We investigated the changes in AC activity that occur during of syncope at rest and during the head-up tilt (HUT) test. We obtained 8 mL of blood at rest time and four times during the HUT test. Then, we measured the AC activity and the test reagent was added to the lymphocytes (10,000) and reacted for 30 min at room temperature. We were able to determine the standard value of AC activity when adrenaline (AD) and isoproterenol (IP) were added to lymphocytes. The results of our study showed one of the causes of NMS has a difference in AC activity level and classification of the patients into two different types of NMS was possible: either the vasodepressor type (VT) or mixed type (MT). At rest time, VT patients showed significantly higher AC activity (AD; 100 µM: p = 0.005, IP; 50 µM: p = 0.02) and MT patients showed significantly lower AC activity (AD; 10 µM: p = 0.02, IP; 50 µM: p = 0.004) than the average AC activity in healthy volunteers. Moreover, VT patients had significantly higher AC activity than healthy volunteers at the four points of the HUT test. MT patients had significantly lower AC activity (AD: p = 0.04 and IP: p = 0.04) than healthy volunteers at the rest time of HUT. Our study showed a significant difference in AC activities between NMS patients and healthy volunteers at rest. Therefore, a detailed NMS diagnosis can be made by examining AC activity levels in blood taken at rest time.


Assuntos
Adenilil Ciclases/análise , Síncope Vasovagal/diagnóstico , Adenilil Ciclases/metabolismo , Adulto , Idoso , Pressão Sanguínea , Estudos de Casos e Controles , Ativação Enzimática/efeitos dos fármacos , Epinefrina/farmacologia , Feminino , Humanos , Isoproterenol/farmacologia , Japão , Linfócitos/citologia , Linfócitos/metabolismo , Pessoa de Meia-Idade , Estações do Ano , Teste da Mesa Inclinada , Adulto Jovem
12.
Microb Pathog ; 131: 270-276, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-30981718

RESUMO

Stress hormones have been recently suggested to influence the pathogenicity of bacteria significantly. Stress has been identified as part of the factors causing an outbreak of infections in the aquaculture industry. The most studied neuroendocrine hormonal family from a microbial endocrinology perspective is the catecholamine comprising of norepinephrine, epinephrine, and dopamine. It is of importance that catecholamine affects the growth and virulence of bacteria. The influence of stress on bacterial infections is attributed to the ability of catecholamines to suppress the immune system as the mode of action for increased bacterial growth. Catecholamines have increased the growth of bacteria, virulence-associated factors, adhesions, and biofilm formation and consequently influence the outcome of infections by these bacteria in many hosts. The siderophores and the ferric iron transport system plays a vital role in the mechanism by which catecholamines stimulates growth and exposure of genes to stress hormones enhances the expression of genes involved in bacterial virulence. In recent years, it has been discovered that intestinal microflora takes part in bidirectional communication between the gut and brain. The rapidly growing field of microbiome research, understanding the communities of bacteria living within our bodies and the genes they contain is yielding new perspectives. This review reveals catecholamines effects on the growth and virulence of bacteria and the latest trends in microbial endocrinology.


Assuntos
Bactérias/efeitos dos fármacos , Bactérias/crescimento & desenvolvimento , Infecções Bacterianas , Catecolaminas/farmacologia , Aquicultura , Bactérias/genética , Bactérias/patogenicidade , Infecções Bacterianas/microbiologia , Biofilmes/efeitos dos fármacos , Biofilmes/crescimento & desenvolvimento , Catecolaminas/química , Dopamina/farmacologia , Endocrinologia , Epinefrina/farmacologia , Microbioma Gastrointestinal/efeitos dos fármacos , Regulação Bacteriana da Expressão Gênica/efeitos dos fármacos , Humanos , Sistema Imunitário , Norepinefrina/farmacologia , Percepção de Quorum/efeitos dos fármacos , Virulência/efeitos dos fármacos , Virulência/genética , Fatores de Virulência/genética
13.
Crit Care ; 23(1): 101, 2019 Mar 27.
Artigo em Inglês | MEDLINE | ID: mdl-30917838

RESUMO

BACKGROUND: The benefits of early epinephrine administration in pediatric with nontraumatic out-of-hospital cardiac arrest (OHCA) have been reported; however, the effects in pediatric cases of traumatic OHCA are unclear. Since the volume-related pharmacokinetics of early epinephrine may differ obviously with and without hemorrhagic shock (HS), beneficial or harmful effects of nonselective epinephrine stimulation (alpha and beta agonists) may also be enhanced with early administration. In this study, we aimed to analyze the therapeutic effect of early epinephrine administration in pediatric cases of HS and non-HS traumatic OHCA. METHODS: This was a multicenter retrospective study (2003-2014). Children (aged ≤ 19 years) who experienced traumatic OHCA and were administered epinephrine for resuscitation were included. Children were classified into the HS (blood loss > 30% of total body fluid) and non-HS groups. The demographics, outcomes, postresuscitation hemodynamics (the first hour) after the sustained return of spontaneous circulation (ROSC), and survival durations were analyzed and correlated with the time to epinephrine administration (early < 15, middle 15-30, late > 30 min) in the HS and non-HS groups. Cox regression analysis was used to adjust for risk factors of mortality. RESULTS: A total of 509 children were included. Most of them (n = 348, 68.4%) had HS OHCA. Early epinephrine administration was implemented in 131 (25.7%) children. In both the HS and non-HS groups, early epinephrine administration was associated with achieving sustained ROSC (both p < 0.05) but was not related to survival or good neurological outcomes (without adjusting for confounding factors). However, early epinephrine administration in the HS group increased cardiac output but induced metabolic acidosis and decreased urine output during the initial postresuscitation period (all p < 0.05). After adjusting for confounding factors, early epinephrine administration was a risk factor of mortality in the HS group (HR 4.52, 95% CI 2.73-15.91). CONCLUSION: Early epinephrine was significantly associated with achieving sustained ROSC in pediatric cases of HS and non-HS traumatic OHCA. For children with HS, early epinephrine administration was associated with both beneficial (increased cardiac output) and harmful effects (decreased urine output and metabolic acidosis) during the postresuscitation period. More importantly, early epinephrine was a risk factor associated with mortality in the HS group.


Assuntos
Epinefrina/farmacologia , Parada Cardíaca Extra-Hospitalar/tratamento farmacológico , Fatores de Tempo , Adolescente , Criança , Pré-Escolar , Epinefrina/administração & dosagem , Epinefrina/uso terapêutico , Feminino , Humanos , Lactente , Masculino , Parada Cardíaca Extra-Hospitalar/etiologia , Fatores de Proteção , Estudos Retrospectivos , Fatores de Risco , Análise de Sobrevida , Taiwan , Ferimentos e Lesões/complicações , Ferimentos e Lesões/tratamento farmacológico
14.
Thromb Res ; 176: 95-100, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30798105

RESUMO

This study evaluated by thrombelastography® (TEG) and Multiplate® analyses the role of the spleen and the liver for adrenaline-induced enhanced hemostatic competence. Eight splenectomized subjects and eight matched healthy control subjects were exposed to one-hour infusion of adrenaline (6 µg/kg/h). Administration of adrenaline to the healthy subjects reduced time to TEG-detected initial fibrin formation (by 22%) and increased rate of clot development (by 10%), maximal amplitude (by 8%), platelet count (by 30%), and Multiplate evaluated Ristocetin-induced platelet aggregation (by 21%) (all p ≤ 0.05), but infusion of adrenaline did not result in significant arterial to liver vein differences for plasma markers of coagulation. In the splenectomized subjects, adrenaline reduced the TEG-determined time to initial fibrin formation (by 17%; p = 0.005) whereas rate of clot development and maximum amplitude were unaffected. Also, 6 patients undergoing liver transplantation were exposed to infusion of adrenaline (4.8 µg/kg/h) during the anhepatic phase of the operation and that increased TEG-determined rate of clot formation (by 10%; p < 0.05), maximal amplitude (by 9%; p = 0.002) and tended to reduce time to initial fibrin formation (p = 0.1). In conclusion, adrenaline enhances hemostasis as evaluated by TEG in both healthy subjects and in anhepatic patients during liver transplantation and Ristocetin-induced aggregation in control subjects. In contrast, infusion of adrenaline reduces only time to initial fibrin formation in splenectomized subjects. These findings suggest that mobilization of platelets from the spleen dominates the adrenaline-induced enhanced hemostatic competence.


Assuntos
Epinefrina/farmacologia , Hemostasia/efeitos dos fármacos , Hemostáticos/farmacologia , Adulto , Coagulação Sanguínea/efeitos dos fármacos , Epinefrina/administração & dosagem , Feminino , Hemostáticos/administração & dosagem , Humanos , Fígado/efeitos dos fármacos , Fígado/fisiologia , Transplante de Fígado , Masculino , Baço/efeitos dos fármacos , Baço/fisiologia , Esplenectomia , Tromboelastografia
15.
Crit Care Med ; 47(4): e349-e357, 2019 04.
Artigo em Inglês | MEDLINE | ID: mdl-30747772

RESUMO

OBJECTIVES: Epinephrine is routinely administered to sudden cardiac arrest patients during resuscitation, but the neurologic effects on patients treated with epinephrine are not well understood. This study aims to assess the cerebral oxygenation and metabolism during ventricular fibrillation cardiac arrest, cardiopulmonary resuscitation, and epinephrine administration. DESIGN: To investigate the effects of equal dosages of IV epinephrine administrated following sudden cardiac arrest as a continuous infusion or successive boluses during cardiopulmonary resuscitation, we monitored cerebral oxygenation and metabolism using hyperspectral near-infrared spectroscopy. SETTINGS: A randomized laboratory animal study. SUBJECTS: Nine healthy pigs. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Our study showed that although continuous epinephrine administration had no significant impact on overall cerebral hemodynamics, epinephrine boluses transiently improved cerebral oxygenation (oxygenated hemoglobin) and metabolism (cytochrome c oxidase) by 15% ± 6.7% and 49% ± 18%, respectively (p < 0.05) compared with the baseline (untreated) ventricular fibrillation. Our results suggest that the effects of epinephrine diminish with successive boluses as the impact of the third bolus on brain oxygen metabolism was 24.6% ± 3.8% less than that of the first two boluses. CONCLUSIONS: Epinephrine administration by bolus resulted in transient improvements in cerebral oxygenation and metabolism, whereas continuous epinephrine infusion did not, compared with placebo. Future studies are needed to evaluate and optimize the use of epinephrine in cardiac arrest resuscitation, particularly the dose, timing, and mode of administration.


Assuntos
Epinefrina/administração & dosagem , Parada Cardíaca/tratamento farmacológico , Oxigênio/sangue , Animais , Reanimação Cardiopulmonar , Circulação Cerebrovascular , Epinefrina/farmacologia , Parada Cardíaca/sangue , Oxigênio/metabolismo , Espectrofotometria Infravermelho , Suínos
16.
Gen Comp Endocrinol ; 279: 109-113, 2019 08 01.
Artigo em Inglês | MEDLINE | ID: mdl-30654022

RESUMO

Interleukin-6 (IL-6) is a pleiotropic cytokine secreted by immune tissues such as monocytes/macrophages and have pro-inflammatory/anti-inflammatory and neuroendocrine actions. In this study, we report the modulatory effects of stress hormones, the cortisol agonist dexamethasone and catecholamines on lipopolysaccharide (LPS) - induced stimulation of head kidney IL-6 in the catfish Heteropneustes fossilis. In the in vivo study, the intraperitoneal administration of LPS stimulated, and dexamethasone time-dependently inhibited IL-6 level. In the in vitro study, the incubation of macrophage cultures with LPS stimulated IL-6 level significantly in all incubation times. Dexamethasone did not alter the basal IL-6 level but inhibited time-dependently the LPS-induced stimulation. Likewise, catecholamines did not alter the basal level of IL-6. Both epinephrine and norepinephrine inhibited the LPS-induced stimulation of IL-6. Dopamine, on the other hand, was ineffective. The results indicate that IL-6 is a useful marker of head kidney macrophage activity for studying endocrine-immune interactions in the catfish.


Assuntos
Catecolaminas/farmacologia , Peixes-Gato/metabolismo , Rim Cefálico/metabolismo , Interleucina-6/biossíntese , Lipopolissacarídeos/farmacologia , Estresse Fisiológico , Animais , Dexametasona/farmacologia , Epinefrina/farmacologia , Rim Cefálico/efeitos dos fármacos , Hidrocortisona/farmacologia , Norepinefrina/farmacologia
17.
Int J Lab Hematol ; 41(1): 102-108, 2019 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-30328683

RESUMO

INTRODUCTION: While it is suggested that platelet hyperreactivity plays a role in the arterial thrombi, its link with venous thromboembolism (VTE) is not well defined. Aggregometry using low concentrations of agonists is proposed as a reliable method to detect hyperreactivity. The aim of this study was to examine whether platelet hyperreactivity affects the development of VTE after total knee arthroplasty (TKA). METHODS: Total 150 elderly patients without VTE history were enrolled. Mechanical prophylaxis was used for VTE after TKA. We performed platelet aggregation using Chrono-log (Chrono-log Corporation, USA) in the presence of low concentrations of ADP (1.0 µmol/L) and epinephrine (0.4, 1.0 µmol/L), and measured maximal aggregation (%). RESULTS: At 0.4 µmol/L epinephrine, 69.3%, 15.3%, and 15.3% displayed low (<40%), moderate (40-60%), and high (>60%) levels of aggregation, respectively. The proportion of high level of aggregation was 36.7%, 30.7% at 1.0 µmol/L of epinephrine and ADP, respectively. The incidence of VTE was higher in the moderate/high aggregation group (10/46, 21.7%) than in the low aggregation group (1/104, 1.0%) at 0.4 µmol/L epinephrine (P < 0.0001). In predicting postoperative VTE, sensitivity and specificity of ≥40% aggregation at 0.4 µmol/L epinephrine were 90.9% and 74.1%. Higher mean platelet volume and lower volume of blood loss were seen in the high aggregation group than in the low aggregation group. CONCLUSION: Aggregation response to 0.4 µmol/L epinephrine is an optimal assay to classify platelet activity. Platelet hyperreactivity may increase the risk of postoperative VTE in an elderly population, and can be an indication of pharmacologic prophylaxis.


Assuntos
Artroplastia do Joelho/efeitos adversos , Ativação Plaquetária/efeitos dos fármacos , Pré-Medicação/efeitos adversos , Tromboembolia Venosa/etiologia , Idoso , Epinefrina/farmacologia , Feminino , Humanos , Masculino , Volume Plaquetário Médio , Pessoa de Meia-Idade
18.
Ann Hematol ; 98(3): 581-588, 2019 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-30446804

RESUMO

The thrombopoietin receptor agonist romiplostim is used for the long-term treatment of chronic immune thrombocytopenia (ITP). ITP patients have an increased thrombotic risk, which could be exacerbated if romiplostim increased platelet hyperreactivity or caused spontaneous platelet aggregation. To investigate this possibility, this study examined platelet function in romiplostim-treated ITP patients and healthy subjects. Light transmission platelet aggregometry utilizing arachidonic acid, collagen, epinephrine, ristocetin, ADP, and saline (to assess spontaneous aggregation) was performed for each subject. In addition, the ADP AC50 (ADP concentration that induced half-maximal aggregation) was determined for each patient as a sensitive measurement of altered platelet reactivity. Fifteen ITP patients and 7 healthy subjects entered the study. All ITP patients had active disease and were receiving weekly romiplostim as the sole ITP-directed therapy. Platelet aggregation in response to the strong agonists arachidonic acid, collagen, and ristocetin was not significantly different between ITP patients and healthy subjects (P = 0.2442, P = 0.0548, and P = 0.0879, respectively). Platelet aggregation in response to weak agonists was significantly reduced in ITP patients compared with that in healthy subjects: median (range) aggregation to ADP, 45% (15-84%) versus 89% (70-95%) (P = 0.0010), and epinephrine, 21% (1.6-90%) versus 88% (79-94%) (P = 0.0085). The median AC50 of ADP was threefold higher in ITP patients versus that in healthy subjects (6.3 µM vs 2.1 µM) (P = 0.0049). Significant spontaneous aggregation was not observed in any patient. Platelets from romiplostim-treated ITP patients do not show evidence for spontaneous aggregation or hyperreactivity, but instead have a modestly reduced aggregation response to ADP and epinephrine.


Assuntos
Transtornos Plaquetários/induzido quimicamente , Púrpura Trombocitopênica Idiopática/tratamento farmacológico , Receptores Fc/uso terapêutico , Proteínas Recombinantes de Fusão/uso terapêutico , Trombopoetina/uso terapêutico , Difosfato de Adenosina/farmacologia , Adulto , Idoso , Ácido Araquidônico/farmacologia , Colágeno/farmacologia , Epinefrina/farmacologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Agregação Plaquetária/efeitos dos fármacos , Púrpura Trombocitopênica Idiopática/sangue , Receptores de Trombopoetina/agonistas , Proteínas Recombinantes de Fusão/efeitos adversos , Proteínas Recombinantes de Fusão/farmacologia , Ristocetina/farmacologia , Trombofilia/induzido quimicamente , Trombopoetina/efeitos adversos , Trombopoetina/farmacologia , Adulto Jovem
19.
J Exp Zool A Ecol Integr Physiol ; 331(1): 27-37, 2019 01.
Artigo em Inglês | MEDLINE | ID: mdl-30288937

RESUMO

Catecholamines protect the fish heart during hypoxia. However, the humoral adrenergic stress response may only be invoked in extremis. We investigated the hypothesis that endogenous (e.g., neuronal) myocardial catecholamines may also impact cardiac performance during hypoxia in a hypoxia-tolerant tropical fish, the red-bellied piranha (Pygocentrus nattereri). First, we measured endogenous tissue catecholamines and in vitro catecholamine release from piranha myocardium using ultraperformance liquid chromatography. Ventricle homogenates contained detectable levels of both adrenaline (7.27 ng/g) and noradrenaline (14.48 ng/g), but only noradrenaline was released from ventricular tissue incubated in Ringer's solution. Noradrenaline released in this assay was not affected by hypoxia but was promoted by the catecholamine releasing agent tyramine. Our second series of experiments explored cardiac contractile performance in vitro using tyramine, exogenous noradrenaline or adrenaline, and propranolol (a ß-adrenoceptor antagonist). In ventricular strip preparations, ß-adrenergic blockade with propranolol had no effects on twitch force or contraction kinetics in either normoxia or hypoxia, confirming that spontaneous endogenous catecholamine release did not impact cardiac performance. However, in the absence of propranolol, tyramine mimicked the positive inotropic effect of noradrenaline (10 µM) during hypoxia, although adrenaline was capable of generating larger effects. Our results suggest that, although it is not spontaneously released, inducible endogenous noradrenaline release may have a significant ß-adrenoceptor-dependent impact on hypoxic performance in the fish heart.


Assuntos
Caraciformes/fisiologia , Epinefrina/farmacologia , Norepinefrina/farmacologia , Antagonistas Adrenérgicos beta/farmacologia , Animais , Catecolaminas/farmacologia , Epinefrina/metabolismo , Feminino , Masculino , Contração Miocárdica , Miocárdio , Norepinefrina/metabolismo , Oxigênio , Propranolol/farmacologia , Simpatomiméticos/farmacologia , Tiramina/farmacologia
20.
Psychoneuroendocrinology ; 99: 191-195, 2019 01.
Artigo em Inglês | MEDLINE | ID: mdl-30253326

RESUMO

Signaling through ß-adrenergic receptors drives cancer progression and ß-blockers are being evaluated as a novel therapeutic strategy to prevent metastasis. Orthotopic mouse models of breast cancer show that ß-adrenergic signaling induced by chronic stress accelerates metastasis, and that ß2-adrenergic receptors on tumor cells are critical for this. Endogenous catecholamines are released during chronic stress: norepinephrine from the adrenal medulla and sympathetic nerves, and epinephrine from the adrenal medulla. ß2-adrenergic receptors are much more sensitive to epinephrine than to norepinephrine. To determine if epinephrine is necessary in the effects of stress on cancer progression, we used a denervation strategy to eliminate circulating epinephrine, and quantified the effect on metastasis. Using both human xenograft and immune-intact murine models of breast cancer, we show that circulating epinephrine is dispensable for the effects of chronic stress on cancer progression. Measured levels of circulating norepinephrine were sufficiently low that they were unlikely to influence ß2-adrenergic signaling, suggesting a possible role for norepinephrine release from sympathetic nerve terminals.


Assuntos
Epinefrina/fisiologia , Metástase Neoplásica/fisiopatologia , Estresse Psicológico/metabolismo , Medula Suprarrenal/fisiopatologia , Antagonistas Adrenérgicos beta/farmacologia , Animais , Neoplasias da Mama/fisiopatologia , Modelos Animais de Doenças , Epinefrina/sangue , Epinefrina/farmacologia , Feminino , Camundongos , Camundongos Endogâmicos BALB C , Neoplasias/metabolismo , Neoplasias/fisiopatologia , Norepinefrina/fisiologia , Receptores Adrenérgicos beta , Transdução de Sinais/efeitos dos fármacos , Circulação Esplâncnica , Nervos Esplâncnicos/metabolismo , Sistema Nervoso Simpático
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