Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 898
Filtrar
1.
Shock ; 55(1): 121-127, 2021 01 01.
Artigo em Inglês | MEDLINE | ID: mdl-32433211

RESUMO

BACKGROUND: Our previous study demonstrated the types of platelet dysfunction varied at early stage (∼3 h) in trauma-induced coagulopathy (TIC) caused by different types of injuries. And arachidonic acid (AA)-dependent pathway inhibition in platelet seemed to be specific for TIC caused by multiple injury (MI). The aim of this research was to further study AA-dependent pathway inhibition in platelets in a rat model of TIC caused by MI and to explore its potential mechanisms. METHODS: Sprague-Dawley rat model of TIC caused by MI was established. We used thrombelastography with platelet mapping as a measure of platelet function to assess the inhibitory extent of AA-dependent activation pathway. Flow cytometry was used to determine the expression of activation-dependent granular protein P-selectin (CD62P). In addition, the plasma levels of 6-Keto-prostaglandin F1 alpha (6-Keto-PGF1α), Prostaglandin E2, and Thromboxane B2 were assessed by enzyme-linked immuno sorbent assay. RESULTS: The inhibition rate of AA-dependent pathway after injury was significantly higher than that of control. The maximum amplitude decreased in the MI group, compared with that of control. The percentage of CD62P expression in the MI group was remarkably lower than that of control after AA treatment. The plasma concentrations of 6-Keto-PGF1α and PGE2 increased in the MI group. CONCLUSION: Platelets inhibition was observed in TIC caused by MI at early stage after injury, which might be partially attributed to AA-dependent activation pathway dysfunction. The increase of plasma Prostacyclin and PGE2 levels may contribute to the inhibition process.


Assuntos
Ácido Araquidônico/metabolismo , Transtornos da Coagulação Sanguínea/sangue , Transtornos da Coagulação Sanguínea/etiologia , Traumatismo Múltiplo/sangue , Traumatismo Múltiplo/complicações , Ativação Plaquetária/fisiologia , 6-Cetoprostaglandina F1 alfa/sangue , Animais , Plaquetas , Dinoprostona/sangue , Modelos Animais de Doenças , Epoprostenol/sangue , Masculino , Selectina-P/sangue , Testes de Função Plaquetária , Ratos , Ratos Sprague-Dawley , Tromboelastografia , Tromboxano B2/sangue
2.
Med Sci Sports Exerc ; 52(10): 2107-2116, 2020 10.
Artigo em Inglês | MEDLINE | ID: mdl-32496738

RESUMO

PURPOSE: We examined whether 2 wk of one-leg immobilization would impair leg microvascular function and to what extent a subsequent period of intense aerobic cycle training could restore function. METHODS: Study participants were healthy young men (n = 12; 20-24 yr of age). Leg microvascular function was determined before the intervention, after the immobilization period, and after a 4-wk exercise training period. Microvascular function was assessed as the vasodilator response to intra-arterial infusion of acetylcholine and sodium nitroprusside and as the vasoconstrictor response to endogenous noradrenaline release induced by tyramine infusion. Vasodilator enzymes as well as prooxidant and antioxidant enzymes were assessed by protein analysis in skeletal muscle samples: endothelial nitric oxide synthase, NADPH oxidase (NOX p67 and NOX gp91), and superoxide dismutase 2 (SOD2). RESULTS: The acetylcholine-induced change in vascular conductance was reduced after the 2 wk of immobilization (P = 0.003), tended to increase (P = 0.061), and was back to baseline levels after the subsequent 4 wk of exercise training. Plasma prostacyclin levels in response to acetylcholine infusion were lower after immobilization than before (P = 0.041). The changes in vascular conductance with sodium nitroprusside and tyramine were similar during all conditions. Skeletal muscle protein levels of endothelial nitric oxide synthase in the experimental leg were unchanged with immobilization and subsequent training but increased 47% in the control leg with training (P = 0.002). NOX p67, NOX gp91, and SOD2 in the experimental leg remained unaltered with immobilization, and SOD2 was higher than preimmobilization after 4 wk of training (P < 0.001). CONCLUSIONS: The study shows that 2 wk of immobilization impairs leg microvascular endothelial function and prostacyclin formation but that 4 wk of intense aerobic exercise training restores the function. The underlying mechanism may reside in the prostacyclin system.


Assuntos
Endotélio Vascular/fisiologia , Imobilização/efeitos adversos , Perna (Membro)/irrigação sanguínea , Microcirculação/fisiologia , Músculo Liso Vascular/fisiologia , Condicionamento Físico Humano/fisiologia , 6-Cetoprostaglandina F1 alfa/sangue , Epoprostenol/sangue , Humanos , Masculino , Proteínas Musculares/metabolismo , Norepinefrina/sangue , Fluxo Sanguíneo Regional , Fatores de Tempo , Vasoconstrição/fisiologia , Vasodilatação/fisiologia , Adulto Jovem
3.
J Cardiovasc Pharmacol ; 76(1): 94-100, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-32398473

RESUMO

As part of a clinical trial, this study examined the pharmacokinetics (PK) of oral treprostinil (TRE) in children with pulmonary arterial hypertension. The trial consisted of the following 3 cohorts: transition from parenteral (cohort 1) or inhaled (cohort 2) TRE, or de novo addition (cohort 3). Oral TRE was dosed 3 times daily. PK samples were obtained before an oral TRE dose, and at 2, 4, 6, and 8 hours thereafter. The PK parameters were calculated using noncompartmental analysis. Thirty-two children (n = 10 in cohorts 1 and 2, n = 12 in cohort 3) were enrolled; the median age was 12 years (range 7-17 years), and the median weight was 42.2 kg (range 19.3-78 kg). The median oral TRE dose for all subjects was 3.8 mg (5.9, 3.5, and 4.0 mg for cohorts 1, 2, and 3, respectively). The TRE concentration versus time profile demonstrated a peak concentration at a median of 3.8 hours with wide variability. In cohort 1, oral dosing led to higher peak (5.9 ng/mL) and lower trough (1 ng/mL) concentrations than parenteral (peak 5.4 ng/mL and trough 4.2 ng/mL), but a lower mean concentration (3.61 vs. 4.46 ng/mL), likely due to variable metabolism and noncomparable dosing. Both the area under the curve and average concentration were linearly correlated with oral TRE dose and dose normalized to body weight, but not with weight or age alone. In pediatric patients, an increased oral TRE dose or dose frequency may be required to minimize PK variability and achieve greater correlation with parenteral dosing.


Assuntos
Anti-Hipertensivos/administração & dosagem , Anti-Hipertensivos/farmacocinética , Pressão Arterial/efeitos dos fármacos , Epoprostenol/análogos & derivados , Hipertensão Arterial Pulmonar/tratamento farmacológico , Artéria Pulmonar/efeitos dos fármacos , Administração Oral , Adolescente , Fatores Etários , Anti-Hipertensivos/sangue , Criança , Esquema de Medicação , Epoprostenol/administração & dosagem , Epoprostenol/sangue , Epoprostenol/farmacocinética , Feminino , Humanos , Masculino , Modelos Biológicos , Hipertensão Arterial Pulmonar/sangue , Hipertensão Arterial Pulmonar/fisiopatologia , Artéria Pulmonar/fisiopatologia , Resultado do Tratamento , Estados Unidos
4.
Langenbecks Arch Surg ; 405(1): 81-90, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31820096

RESUMO

PURPOSE: MTS is elicited during open abdominal surgery and is characterized by facial flushing, hypotension, and tachycardia in response to the release of prostacyclin (PGI2) to plasma. MTS seems to affect postoperative morbidity, but data from larger cohorts are lacking. We aimed to determine the impact of severe mesenteric traction syndrome (MTS) on postoperative morbidity in patients undergoing open upper gastrointestinal surgery. METHODS: The study was a secondary analysis of data from three cohorts (n = 137). The patients were graded for severity of MTS intraoperatively, and hemodynamic variables and blood samples for plasma 6-keto-PGF1α, a stable metabolite of PGI2, were obtained at defined time points. Postoperative morbidity was evaluated by the comprehensive complication index (CCI) and the Dindo-Clavien classification (DC). RESULTS: Patients undergoing either esophagectomy (n = 70), gastrectomy (n = 22), liver- (n = 23), or pancreatic resection (n = 22) were included. Severe MTS was significantly associated with increased postoperative morbidity, i.e., CCI ≥ 26.2 (OR 3.06 [95% CI 1.1-6.6]; p = 0.03) and risk of severe complications, i.e., DC ≥3b (OR 3.1 [95% CI 1.2-8.2]; p = 0.023). Furthermore, patients with severe MTS had increased length of stay (OR 10.1 [95% CI 1.9-54.3]; p = 0.007) and were more likely to be admitted to the intensive care unit (OR = 7.3 [95% CI 1.3-41.9]; p = 0.027), but there was no difference in 1-year mortality. CONCLUSION: Occurrence of severe MTS during upper gastrointestinal surgery is associated with increased postoperative morbidity as indicated by an increased rate of severe complications, length of stay, and admission to the ICU. It remains to be determined whether inhibition of MTS enhances postoperative recovery.


Assuntos
Procedimentos Cirúrgicos do Sistema Digestório/efeitos adversos , Mesentério/cirurgia , Idoso , Dinamarca/epidemiologia , Procedimentos Cirúrgicos do Sistema Digestório/estatística & dados numéricos , Epoprostenol/sangue , Feminino , Rubor/sangue , Rubor/etiologia , Humanos , Hipotensão/sangue , Hipotensão/etiologia , Complicações Intraoperatórias/sangue , Complicações Intraoperatórias/epidemiologia , Complicações Intraoperatórias/etiologia , Masculino , Pessoa de Meia-Idade , Morbidade , Síndrome , Taquicardia/sangue , Taquicardia/etiologia
5.
J Cardiovasc Pharmacol ; 73(6): 383-393, 2019 06.
Artigo em Inglês | MEDLINE | ID: mdl-31162247

RESUMO

This study evaluated the pharmacokinetics of intravenous (IV) and subcutaneous (SC) treprostinil in pediatric patients with pulmonary vascular disease, and compared them with existing adult data from a similar cohort. Blood samples were collected from pediatric patients receiving steady-state IV or SC treprostinil and were assessed for plasma treprostinil concentration using liquid chromatography and tandem mass spectrometry. Forty participants, 15 receiving IV and 25 receiving SC treprostinil, were included in the analysis. Age ranged from 0.1 to 15.6 years. The median dose of treprostinil was 45.5 ng·kg·min with a range of 8-146 ng·kg·min. There was a linear relationship between treprostinil dose and plasma concentration with an R of 0.57. On average, there were higher blood concentrations per given dose of IV treprostinil compared with those per given dose of SC, but the difference was not significant. Compared with adult data, the slope of the pediatric data was similar, but the y-intercept was significantly lower. Additionally, the concentration per dose ratio was significantly higher in adults compared with children. Pediatric patients have significantly lower average blood concentrations of treprostinil per given dose compared with adults, and higher, but not significantly so, blood concentrations when treprostinil is administered IV as compared with SC administration.


Assuntos
Anti-Hipertensivos/administração & dosagem , Anti-Hipertensivos/farmacocinética , Epoprostenol/análogos & derivados , Hipertensão Arterial Pulmonar/tratamento farmacológico , Adolescente , Fatores Etários , Anti-Hipertensivos/sangue , Criança , Pré-Escolar , Cromatografia Líquida , Estudos Transversais , Monitoramento de Medicamentos , Epoprostenol/administração & dosagem , Epoprostenol/sangue , Epoprostenol/farmacocinética , Feminino , Humanos , Lactente , Infusões Intravenosas , Infusões Subcutâneas , Masculino , Hipertensão Arterial Pulmonar/diagnóstico , Hipertensão Arterial Pulmonar/fisiopatologia , Espectrometria de Massas em Tandem , Estados Unidos
6.
Molecules ; 24(13)2019 Jun 27.
Artigo em Inglês | MEDLINE | ID: mdl-31252591

RESUMO

Aspirin eugenol ester (AEE) is a novel compound that is formed from the esterification of aspirin (acetylsalicylic acid (ASA)) and eugenol. This study aimed to investigate the effects of AEE on blood stasis in rats and to characterize the underlying mechanisms using a plasma metabolomic study. The results indicate that AEE and ASA could modulate whole blood viscosity (WBV), plasma viscosity (PV), blood coagulation parameters, platelet count, platelet aggregation, lactate dehydrogenase (LDH), creatinine (CR) and the levels of thromboxane A2 (TXA2) and 6-keto prostaglandin F1α (6-keto-PGF1α). The metabolic profiles of the plasma samples from all groups were clearly separated in the score plots. Nineteen potential metabolites were selected and identified, and disordered levels of these metabolites could be regulated by AEE and ASA. Pathway analysis showed that the mechanism of action of AEE on blood stasis might be principally related to the metabolism of amino acid, fatty acid, energy and glycerophospholipid. The above results indicate that AEE protected the rats against blood stasis, and that this effect might have been caused by the anticoagulation activity of AEE and its abilities to maintain a balance between TXA2 and PGI2, reduce blood viscosity, inhibit platelet aggregation and normalize the plasma metabolic profile.


Assuntos
Aspirina/análogos & derivados , Sangue/efeitos dos fármacos , Eugenol/análogos & derivados , Doenças Hematológicas/tratamento farmacológico , Metabolômica/métodos , Animais , Aspirina/administração & dosagem , Aspirina/farmacologia , Análise Química do Sangue , Coagulação Sanguínea/efeitos dos fármacos , Viscosidade Sanguínea/efeitos dos fármacos , Cromatografia Líquida de Alta Pressão , Modelos Animais de Doenças , Epoprostenol/sangue , Eugenol/administração & dosagem , Eugenol/farmacologia , Feminino , Doenças Hematológicas/metabolismo , Agregação Plaquetária/efeitos dos fármacos , Ratos , Tromboxano A2/sangue
7.
J Clin Monit Comput ; 33(5): 903-910, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-30460600

RESUMO

The mesenteric traction syndrome (MTS) is associated with prostacyclin (PGI2) facilitated systemic vasodilatation during surgery and is identified by facial flushing. We hypothesized that severe facial flushing would be related to the highest concentrations of plasma PGI2 and accordingly to the highest levels of skin blood flow measured by laser speckle contrast imaging (LSCI). Patients scheduled for major upper abdominal surgery were consecutively included. Within the first hour of the procedure, facial flushing was scored according to a standardized scale, and skin blood flow (LSPU) was continuously measured on the forehead and the cheeks by LSCI. Arterial blood samples for 6-keto-PGF1α (stable metabolite of PGI2) and hemodynamic variables were obtained at defined time points. Overall, 66 patients were included. After 15 min of surgery, patients with severe flushing demonstrated the highest plasma 6-keto-PGF1α concentration and the most significant decrease in systemic vascular resistance. Accordingly, the skin blood flow on the forehead (238 [201-372] to 562 LSPU [433-729]) and the cheeks (341 [239-355] to 624 LSPU [468-917]) increased and were significantly higher than for patients with moderate or no flushing (both, P = 0.04). A cut-off value for skin blood flow could be defined for both the cheeks and the forehead for patients with severe flushing vs. no flushing (425/456 LSPU, sensitivity 75/76% and specificity 80/85%). MTS is linked to an increase in facial skin blood flow during upper gastrointestinal surgery. By applying LSCI, it is possible to quantitatively register facial blood flow, and thereby provide an objective tool for intraoperative verification of MTS.


Assuntos
Procedimentos Cirúrgicos do Sistema Digestório/efeitos adversos , Epoprostenol/sangue , Rubor , Neoplasias Gastrointestinais/cirurgia , Trato Gastrointestinal/cirurgia , 6-Cetoprostaglandina F1 alfa/metabolismo , Adolescente , Adulto , Idoso , Anestesia , Artérias/patologia , Face , Feminino , Neoplasias Gastrointestinais/complicações , Hemodinâmica , Humanos , Lasers , Fígado/cirurgia , Masculino , Pessoa de Meia-Idade , Monitorização Intraoperatória/métodos , Pâncreas/cirurgia , Complicações Pós-Operatórias , Pele/irrigação sanguínea , Estômago/cirurgia , Síndrome , Resistência Vascular , Vasodilatação , Adulto Jovem
8.
Biomed Chromatogr ; 33(2): e4403, 2019 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-30276833

RESUMO

Beraprost sodium is an oral prostacyclin analog that was first approved in 1992 (Japan) for the treatment of peripheral vascular disorders. It is administered orally as a tablet available in strength 20 µg. In this paper, we described a liquid chromatography tandem mass spectrometry method that was developed for the quantification of beraprost in human plasma with high sensitivity at picogram per milliliter concentration. The method had been validated in terms of selectivity, sensitivity, accuracy and precision, matrix effect, linearity, recovery and carry-over according to the Guideline on Bioanalytical Validation from the European Medicines Agency. The standard calibration curve for beraprost was 9.5-1419 pg/mL. This method has been applied successfully to a bioequivalence study with 60 µg of beraprost (three tablets) in 29 healthy volunteers. The results showed that the two formulations of beraprost are bioequivalent.


Assuntos
Cromatografia Líquida/métodos , Epoprostenol/análogos & derivados , Espectrometria de Massas em Tandem/métodos , Epoprostenol/sangue , Epoprostenol/química , Epoprostenol/farmacocinética , Humanos , Modelos Lineares , Inibidores da Agregação Plaquetária/sangue , Inibidores da Agregação Plaquetária/química , Inibidores da Agregação Plaquetária/farmacocinética , Reprodutibilidade dos Testes , Sensibilidade e Especificidade , Equivalência Terapêutica
10.
J Pharm Pract ; 32(5): 599-604, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-29558853

RESUMO

Treprostinil diolamine is the first oral dosage preparation of a prostacyclin analogue for use in treatment naive pulmonary arterial hypertension (PAH). This case series and review of the available literature describes the experience of patients with PAH receiving treprostinil by intravenous (IV), subcutaneous (SQ), or inhalation route who were transitioned to treprostinil diolamine. At our institution, 3 patients were transitioned to treprostinil diolamine who received treprostinil administered by each of the alternative routes: IV, SQ, and inhalation. All patients tolerated the transition without significant worsening of disease end points. In the literature, 5 additional reports representing 48 patients were transitioned to treprostinil diolamine from an alternate route of administration. A majority (92%) of patients were hospitalized during the cross-titration phase and tolerated the transition without changes in disease markers or significant adverse effect. Six (13%) patients required reinitiation of parenteral therapy due to clinical decline. The most common dosing frequency utilized for treprostinil diolamine was 3 times per day. In patients with stable PAH receiving parenteral or inhaled treprostinil, a transition to treprostinil diolamine was a safe approach in a highly select population meeting clinical end points. Additional studies are required to further describe this clinical strategy before accepted in clinical practice.


Assuntos
Anti-Hipertensivos/administração & dosagem , Anti-Hipertensivos/sangue , Epoprostenol/análogos & derivados , Hipertensão Pulmonar/sangue , Hipertensão Pulmonar/tratamento farmacológico , Administração por Inalação , Administração Oral , Adulto , Epoprostenol/administração & dosagem , Epoprostenol/sangue , Feminino , Humanos , Infusões Parenterais , Pessoa de Meia-Idade
11.
Braz J Cardiovasc Surg ; 33(4): 384-390, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30184036

RESUMO

OBJECTIVE: This study aimed to investigate the protective effects of baicalin on myocardial infarction in rats and explore the related mechanisms. METHODS: Fifty Sprague Dawley rats were randomly divided into the control, model, and low-, medium- and high-dose baicalin groups. The latter 3 groups were intraperitoneally injected with baicalin, with a dose of 12.5, 25 and 50 mg/kg, respectively. Then, the myocardial infarction model was established. The hemodynamic of rats was tested, the serum lactate dehydrogenase (LDH), creatine kinase-MB (CK-MB), prostacyclin (PGI2) and thromboxane A2 (TXA2) were determined, the myocardial superoxide dismutase (SOD) and malondialdehyde (MDA) levels were detected, and the myocardial B-cell lymphoma-2 (Bcl-2) and Bcl-2 associated X (Bax) protein expressions were determined. RESULTS: Compared with the model group, in the high-dose baicalin group the ST segment height and LVEDP were significantly decreased (P<0.05), the LVSP was significantly increased (P<0.05), the serum LDH, CK-MB and TXA2 levels were significantly decreased (P<0.05), the PGI2 level was significantly increased (P<0.05), the myocardial SOD level was significantly increased (P<0.05), and the myocardial MDA level was significantly decreased (P<0.05); the myocardial Bcl-2 protein level was significantly increased, and the Bax protein level was significantly decreased (P<0.05). CONCLUSION: Baicalin has protective effects on myocardial infarction in rats. The possible mechanisms may be related to its resistance to oxidative stress, and up-regulation of Bcl-2 protein expression and down-regulation of Bax protein expression in myocardial tissue.


Assuntos
Flavonoides/farmacologia , Infarto do Miocárdio/prevenção & controle , Substâncias Protetoras/farmacologia , Animais , Cromatografia Líquida de Alta Pressão , Creatina Quinase Forma MB/sangue , Ensaio de Imunoadsorção Enzimática , Epoprostenol/sangue , Genes bcl-2 , Hemodinâmica/efeitos dos fármacos , L-Lactato Desidrogenase/sangue , Malondialdeído/análise , Distribuição Aleatória , Ratos Sprague-Dawley , Valores de Referência , Reprodutibilidade dos Testes , Superóxido Dismutase/análise , Tromboxano A2/sangue , Resultado do Tratamento , Proteína X Associada a bcl-2/análise
12.
Acta Cir Bras ; 33(7): 577-587, 2018 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-30110059

RESUMO

PURPOSE: To investigate changes in the plasma concentrations of cardiac troponin I (CTnI), thromboxane A2 (TXA2), prostaglandin I2 (PGI2) and endothelin-1 (ET-1) in rabbits with massive pulmonary embolism (AMPE) and the impact of nitric oxide inhalation (NOI) on these indices. METHODS: A total of 30 Japanese rabbits were used to construct an MPE model and were divided into 3 groups equally (n=10), including an EXP group (undergoing modeling alone), an NOI group (receiving NOI 2 h post-modeling) and a CON group (receiving intravenous physiological saline). RESULTS: In the model group, plasma concentration of CTnI peaked at 16 h following modeling (0.46±0.10 µg/ml) and significantly decreased following NOI. Plasma levels of TXB2, PGI2 and ET-1 peaked at 12, 16 and 8 h following modeling, respectively, and significantly decreased at different time points (0, 2, 4, 8, 12, 16, 20 and 24 h) following NOI. A significant correlation was observed between the peak plasma CTnI concentration and peak TXB2, 6-keto prostaglandin F1α and ET-1 concentrations in the model and NOI groups. CONCLUSION: Increases in plasma TXA2, PGI2 and ET-1 levels causes myocardial damage in a rabbit model of AMPE; however, NOI effectively down regulates the plasma concentration of these molecules to produce a myocardial-protective effect.


Assuntos
Broncodilatadores/farmacologia , Endotelina-1/sangue , Epoprostenol/sangue , Óxido Nítrico/farmacologia , Embolia Pulmonar/sangue , Embolia Pulmonar/tratamento farmacológico , Tromboxano A2/sangue , Troponina I/sangue , Doença Aguda , Administração por Inalação , Animais , Regulação para Baixo , Ensaio de Imunoadsorção Enzimática , Feminino , Masculino , Embolia Pulmonar/patologia , Coelhos , Distribuição Aleatória , Valores de Referência , Reprodutibilidade dos Testes , Fatores de Tempo , Resultado do Tratamento
13.
Rev. bras. cir. cardiovasc ; 33(4): 384-390, July-Aug. 2018. tab, graf
Artigo em Inglês | LILACS | ID: biblio-958430

RESUMO

Abstract Objective: This study aimed to investigate the protective effects of baicalin on myocardial infarction in rats and explore the related mechanisms. Methods: Fifty Sprague Dawley rats were randomly divided into the control, model, and low-, medium- and high-dose baicalin groups. The latter 3 groups were intraperitoneally injected with baicalin, with a dose of 12.5, 25 and 50 mg/kg, respectively. Then, the myocardial infarction model was established. The hemodynamic of rats was tested, the serum lactate dehydrogenase (LDH), creatine kinase-MB (CK-MB), prostacyclin (PGI2) and thromboxane A2 (TXA2) were determined, the myocardial superoxide dismutase (SOD) and malondialdehyde (MDA) levels were detected, and the myocardial B-cell lymphoma-2 (Bcl-2) and Bcl-2 associated X (Bax) protein expressions were determined. Results: Compared with the model group, in the high-dose baicalin group the ST segment height and LVEDP were significantly decreased (P<0.05), the LVSP was significantly increased (P<0.05), the serum LDH, CK-MB and TXA2 levels were significantly decreased (P<0.05), the PGI2 level was significantly increased (P<0.05), the myocardial SOD level was significantly increased (P<0.05), and the myocardial MDA level was significantly decreased (P<0.05); the myocardial Bcl-2 protein level was significantly increased, and the Bax protein level was significantly decreased (P<0.05). Conclusion: Baicalin has protective effects on myocardial infarction in rats. The possible mechanisms may be related to its resistance to oxidative stress, and up-regulation of Bcl-2 protein expression and down-regulation of Bax protein expression in myocardial tissue.


Assuntos
Animais , Flavonoides/farmacologia , Substâncias Protetoras/farmacologia , Infarto do Miocárdio/prevenção & controle , Valores de Referência , Superóxido Dismutase/análise , Tromboxano A2/sangue , Ensaio de Imunoadsorção Enzimática , Distribuição Aleatória , Reprodutibilidade dos Testes , Cromatografia Líquida de Alta Pressão , Epoprostenol/sangue , Resultado do Tratamento , Ratos Sprague-Dawley , Genes bcl-2 , Creatina Quinase Forma MB/sangue , Proteína X Associada a bcl-2/análise , Hemodinâmica/efeitos dos fármacos , L-Lactato Desidrogenase/sangue , Malondialdeído/análise
14.
Acta cir. bras ; 33(7): 577-587, July 2018. tab, graf
Artigo em Inglês | LILACS | ID: biblio-949362

RESUMO

Abstract Purpose: To investigate changes in the plasma concentrations of cardiac troponin I (CTnI), thromboxane A2 (TXA2), prostaglandin I2 (PGI2) and endothelin-1 (ET-1) in rabbits with massive pulmonary embolism (AMPE) and the impact of nitric oxide inhalation (NOI) on these indices. Methods: A total of 30 Japanese rabbits were used to construct an MPE model and were divided into 3 groups equally (n=10), including an EXP group (undergoing modeling alone), an NOI group (receiving NOI 2 h post-modeling) and a CON group (receiving intravenous physiological saline). Results: In the model group, plasma concentration of CTnI peaked at 16 h following modeling (0.46±0.10 µg/ml) and significantly decreased following NOI. Plasma levels of TXB2, PGI2 and ET-1 peaked at 12, 16 and 8 h following modeling, respectively, and significantly decreased at different time points (0, 2, 4, 8, 12, 16, 20 and 24 h) following NOI. A significant correlation was observed between the peak plasma CTnI concentration and peak TXB2, 6-keto prostaglandin F1α and ET-1 concentrations in the model and NOI groups. Conclusion: Increases in plasma TXA2, PGI2 and ET-1 levels causes myocardial damage in a rabbit model of AMPE; however, NOI effectively down regulates the plasma concentration of these molecules to produce a myocardial-protective effect.


Assuntos
Animais , Masculino , Feminino , Coelhos , Embolia Pulmonar/tratamento farmacológico , Embolia Pulmonar/sangue , Tromboxano A2/sangue , Broncodilatadores/farmacologia , Epoprostenol/sangue , Endotelina-1/sangue , Troponina I/sangue , Óxido Nítrico/farmacologia , Embolia Pulmonar/patologia , Valores de Referência , Fatores de Tempo , Administração por Inalação , Ensaio de Imunoadsorção Enzimática , Distribuição Aleatória , Regulação para Baixo , Doença Aguda , Reprodutibilidade dos Testes , Resultado do Tratamento
15.
Am J Physiol Heart Circ Physiol ; 315(4): H855-H870, 2018 10 01.
Artigo em Inglês | MEDLINE | ID: mdl-29932769

RESUMO

It has long been known that chronic metabolic disease is associated with a parallel increase in the risk for developing peripheral vascular disease. Although more clinically relevant, our understanding about reversing established vasculopathy is limited compared with our understanding of the mechanisms and development of impaired vascular structure/function under these conditions. Using the 13-wk-old obese Zucker rat (OZR) model of metabolic syndrome, where microvascular dysfunction is sufficiently established to contribute to impaired skeletal muscle function, we imposed a 7-wk intervention of chronic atorvastatin treatment, chronic treadmill exercise, or both. By 20 wk of age, untreated OZRs manifested a diverse vasculopathy that was a central contributor to poor muscle performance, perfusion, and impaired O2 exchange. Atorvastatin or exercise, with the combination being most effective, improved skeletal muscle vascular metabolite profiles (i.e., nitric oxide, PGI2, and thromboxane A2 bioavailability), reactivity, and perfusion distribution at both individual bifurcations and within the entire microvascular network versus responses in untreated OZRs. However, improvements to microvascular structure (i.e., wall mechanics and microvascular density) were less robust. The combination of the above improvements to vascular function with interventions resulted in an improved muscle performance and O2 transport and exchange versus untreated OZRs, especially at moderate metabolic rates (3-Hz twitch contraction). These results suggest that specific interventions can improve specific indexes of function from established vasculopathy, but either this process was incomplete after 7-wk duration or measures of vascular structure are either resistant to reversal or require better-targeted interventions. NEW & NOTEWORTHY We used atorvastatin and/or chronic exercise to reverse established microvasculopathy in skeletal muscle of rats with metabolic syndrome. With established vasculopathy, atorvastatin and exercise had moderate abilities to reverse dysfunction, and the combined application of both was more effective at restoring function. However, increased vascular wall stiffness and reduced microvessel density were more resistant to reversal. Listen to this article's corresponding podcast at https://ajpheart.podbean.com/e/reversal-of-microvascular-dysfunction/ .


Assuntos
Atorvastatina/farmacologia , Inibidores de Hidroximetilglutaril-CoA Redutases/farmacologia , Síndrome Metabólica/terapia , Microcirculação/efeitos dos fármacos , Microvasos/efeitos dos fármacos , Músculo Esquelético/irrigação sanguínea , Doenças Vasculares Periféricas/terapia , Condicionamento Físico Animal/métodos , Esforço Físico , Animais , Biomarcadores/sangue , Modelos Animais de Doenças , Epoprostenol/sangue , Hemodinâmica/efeitos dos fármacos , Masculino , Síndrome Metabólica/sangue , Síndrome Metabólica/patologia , Síndrome Metabólica/fisiopatologia , Microvasos/patologia , Microvasos/fisiopatologia , Modelos Cardiovasculares , Músculo Esquelético/metabolismo , Óxido Nítrico/metabolismo , Consumo de Oxigênio/efeitos dos fármacos , Doenças Vasculares Periféricas/sangue , Doenças Vasculares Periféricas/patologia , Doenças Vasculares Periféricas/fisiopatologia , Ratos Zucker , Fluxo Sanguíneo Regional , Corrida , Tromboxano A2/sangue , Fatores de Tempo
16.
Zhongguo Zhong Yao Za Zhi ; 43(1): 147-153, 2018 Jan.
Artigo em Chinês | MEDLINE | ID: mdl-29552825

RESUMO

This study aimed to investigate the antihypertensive effect and possible mechanism of Dendrobium officinale flos on hypertensive rats induced by high glucose and high fat compound alcohol. The hypertensive models were successfully made by high-glucose and high-fat diet, with gradient drinking for 4 weeks, and then divided into model control group, valsartan (5.7 mg·kg⁻¹) positive control group and D. officinale flos groups (3,1 g·kg⁻¹). After 6 weeks of treatment, the blood pressure of rats was measured regularly. After the last administration, endothelin-1 (ET-1), thromboxane B2 (TXB2), prostacyclin (PGI2) and nitric oxide (NO) were tested. Endothelial nitric oxide synthase (eNOS) expression and lesion status in thoracic aorta were detected. The vascular endothelium dependent dilation of the thoracic aorta was detected by the isolated vascular loop tension test. The results showed that D. officinale flos could significantly reduce systolic blood pressure and mean arterial pressure in hypertensive rats, inhibit the thickening of thoracic aorta and the loss of endothelial cells, reduce plasma content of ET-1 and TXB2, and increase the content of PGI2 and NO. After long-term administration, vascular endothelium dependent dilation of the thoracic aorta was significantly increased, and could be blocked by the eNOS inhibitor (L-NAME) and increase the expression of eNOS. Therefore, D. officinale flos has an obvious antihypertensive effect on high glucose and high fat compound alcohol-induced hypertensive rats. Its mechanism may be correlated with the improvement of vascular diastolic function by protecting vascular endothelial cells, and finally resist hypertension.


Assuntos
Anti-Hipertensivos/farmacologia , Dendrobium/química , Medicamentos de Ervas Chinesas/farmacologia , Endotélio Vascular/efeitos dos fármacos , Hipertensão/tratamento farmacológico , Animais , Pressão Sanguínea , Dieta Hiperlipídica , Endotelina-1/sangue , Epoprostenol/sangue , Glucose , Hipertensão/induzido quimicamente , Óxido Nítrico/sangue , Óxido Nítrico Sintase Tipo III/metabolismo , Ratos , Proteínas com Domínio T/sangue , Vasodilatação
17.
Circ Res ; 122(12): 1689-1702, 2018 06 08.
Artigo em Inglês | MEDLINE | ID: mdl-29545367

RESUMO

RATIONALE: Pulmonary arterial hypertension (PH) is a life-threatening condition associated with immune dysregulation and abnormal regulatory T cell (Treg) activity, but it is currently unknown whether and how abnormal Treg function differentially affects males and females. OBJECTIVE: To evaluate whether and how Treg deficiency differentially affects male and female rats in experimental PH. METHODS AND RESULTS: Male and female athymic rnu/rnu rats, lacking Tregs, were treated with the VEGFR2 (vascular endothelial growth factor receptor 2) inhibitor SU5416 or chronic hypoxia and evaluated for PH; some animals underwent Treg immune reconstitution before SU5416 administration. Plasma PGI2 (prostacyclin) levels were measured. Lung and right ventricles were assessed for the expression of the vasoprotective proteins COX-2 (cyclooxygenase 2), PTGIS (prostacyclin synthase), PDL-1 (programmed death ligand 1), and HO-1 (heme oxygenase 1). Inhibitors of these pathways were administered to athymic rats undergoing Treg immune reconstitution. Finally, human cardiac microvascular endothelial cells cocultured with Tregs were evaluated for COX-2, PDL-1, HO-1, and ER (estrogen receptor) expression, and culture supernatants were assayed for PGI2 and IL (interleukin)-10. SU5416-treatment and chronic hypoxia produced more severe PH in female than male athymic rats. Females were distinguished by greater pulmonary inflammation, augmented right ventricular fibrosis, lower plasma PGI2 levels, decreased lung COX-2, PTGIS, HO-1, and PDL-1 expression and reduced right ventricular PDL-1 levels. In both sexes, Treg immune reconstitution protected against PH development and raised levels of plasma PGI2 and cardiopulmonary COX-2, PTGIS, PDL-1, and HO-1. Inhibiting COX-2, HO-1, and PD-1 (programmed death 1)/PDL-1 pathways abrogated Treg protection. In vitro, human Tregs directly upregulated endothelial COX-2, PDL-1, HO-1, ERs and increased supernatant levels of PGI2 and IL-10. CONCLUSIONS: In 2 animal models of PH based on Treg deficiency, females developed more severe PH than males. The data suggest that females are especially reliant on the normal Treg function to counteract the effects of pulmonary vascular injury leading to PH.


Assuntos
Hipertensão Pulmonar/prevenção & controle , Fatores Sexuais , Linfócitos T Reguladores/fisiologia , Inibidores da Angiogênese/farmacologia , Animais , Antígeno B7-H1/análise , Antígeno B7-H1/antagonistas & inibidores , Antígeno B7-H1/metabolismo , Doença Crônica , Ciclo-Oxigenase 2/análise , Ciclo-Oxigenase 2/metabolismo , Sistema Enzimático do Citocromo P-450/análise , Sistema Enzimático do Citocromo P-450/metabolismo , Epoprostenol/antagonistas & inibidores , Epoprostenol/sangue , Epoprostenol/metabolismo , Feminino , Heme Oxigenase (Desciclizante)/análise , Heme Oxigenase (Desciclizante)/antagonistas & inibidores , Heme Oxigenase (Desciclizante)/metabolismo , Hipertensão Pulmonar/sangue , Hipertensão Pulmonar/induzido quimicamente , Hipertensão Pulmonar/etiologia , Hipóxia/complicações , Indóis/farmacologia , Oxirredutases Intramoleculares/análise , Oxirredutases Intramoleculares/antagonistas & inibidores , Oxirredutases Intramoleculares/metabolismo , Pulmão/metabolismo , Masculino , Prostaglandinas I/biossíntese , Pirróis/farmacologia , Ratos , Ratos Nus , Receptores de Estrogênio/análise , Receptores de Estrogênio/antagonistas & inibidores , Receptores de Estrogênio/metabolismo , Linfócitos T Reguladores/imunologia , Receptor 2 de Fatores de Crescimento do Endotélio Vascular/antagonistas & inibidores
18.
Med Hypotheses ; 108: 81-85, 2017 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-29055406

RESUMO

Preeclampsia is a serious complication of pregnancy characterized by the development of vasospasm, hypertension and often associated with proteinuria after the 20th week of gestation. Because termination of pregnancy results in the most efficacious resolution of preeclampsia, it is a leading cause of premature delivery worldwide. In pregnancy, 14,15-epoxyeicosatrienoic acids (EETs) have been shown to facilitate uterine blood flow during preeclampsia, in which the classic vasodilator agents such as nitric oxide and prostacyclin are reduced. EETs are converted to dihydroxyeicosatrienoic acids (DHETs) by the activity of soluble epoxide hydrolase (sEH). We tested the hypothesis that sEH activity is increased in preeclampsia by measuring urinary 14,15-DHET in healthy and preeclamptic pregnant women. Urine samples were collected and incubated with or without ß-glucuronidase to enable the measurement of both the glucuronidated and free forms of 14,15-DHET, which were quantified using a 14,15-DHET ELISA. Levels of total (free+glucuronidated) 14,15-DHET, which is a measurement of EET-dependent sEH activity, were higher in urine samples obtained from preeclamptic women compared to healthy pregnant women. Considering the fact that free+glucuronidated 14,15-DHET levels are increased in urine of preeclamptic women, we hypothesize that sEH expression or activity is augmented in these patients, reducing EET and increasing blood pressure. Moreover we suggest that novel anti-hypertensive agents that target sEH might be developed as therapeutics to control high blood pressure in women with preeclampsia.


Assuntos
Epóxido Hidrolases/sangue , Pré-Eclâmpsia/sangue , Ácido 8,11,14-Eicosatrienoico/análogos & derivados , Ácido 8,11,14-Eicosatrienoico/sangue , Ácido 8,11,14-Eicosatrienoico/urina , Adulto , Anti-Hipertensivos/farmacologia , Pressão Sanguínea , Epoprostenol/sangue , Feminino , Glucuronidase/sangue , Humanos , Hipertensão/tratamento farmacológico , Idade Materna , Óxido Nítrico/sangue , Gravidez , Complicações na Gravidez/sangue , Vasoconstrição , Vasodilatadores/farmacologia , Adulto Jovem
19.
PLoS One ; 12(9): e0184345, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28880908

RESUMO

BACKGROUND: Pregnancy increases the risk of morbidity and mortality in sickle cell disease. We previously showed pregnant women with sickle cell disease to have a relatively low plasma renin concentration in late pregnancy, associated with a lack of the expected plasma volume expansion. We hypothesized this to be due to increased systemic vascular resistance through an imbalance between the vasodilator prostacyclin and vasoconstrictor thromboxane, associated with decreased glomerular filtration rate (GFR). OBJECTIVE: To compare estimated prostacyclin, thromboxane and GFR in non-pregnant and pregnant women with hemoglobin SS (HbSS) and AA (HbAA). STUDY DESIGN: Four groups of 20 normotensive, nulliparous women were studied in Lagos, Nigeria: pregnant HbSS or HbAA women at 36-40 weeks gestation; non-pregnant HbSS and HbAA controls. We measured stable metabolites of prostacyclin and thromboxane A2 by enzyme-linked immunosorbent assay; GFR using the Cockcroft-Gault equation. Data analysis was by independent (Student's) t-test or Mann-Whitney U test for comparisons between any two groups of continuous variables, univariate ANOVA for multiple groups and Pearson's correlation coefficient for degree of association between variables. RESULTS: HbSS women had lower serum 6-keto-PGF1α concentrations than HbAA, whether pregnant or non-pregnant (P<0.001; P<0.004 respectively). Conversely, pregnant HbSS women had higher serum TxB2 (P<0.001); non-pregnant HbSS women had non-significantly higher TxB2 concentrations. The 6-keto-PGF1α:TxB2 ratio was markedly increased (pro-vasodilatory) in HbAA pregnancy (P<0.001) but reduced in HbSS pregnancy (P = 0.037). GFRs (mL/min) were higher in non-pregnant HbSS than HbAA (P<0.008) but only marginally raised in HbSS women in late pregnancy (P = 0.019) while markedly raised in HbAA pregnancy (P<0.001). CONCLUSION: The lower ratio of prostacyclin-thromboxane metabolites in HbSS pregnancy may indicate endothelial damage and an increased tendency to vasoconstriction and clotting. If confirmed by subsequent longitudinal studies, interventions to increase prostacyclin and reduce thromboxane, such as low dose aspirin, may be potentially useful in their management.


Assuntos
Anemia Falciforme/sangue , Epoprostenol/sangue , Tromboxanos/sangue , 6-Cetoprostaglandina F1 alfa/sangue , Adulto , Pressão Sanguínea/fisiologia , Creatinina/sangue , Estudos Transversais , Eicosanoides/sangue , Feminino , Genótipo , Taxa de Filtração Glomerular/fisiologia , Humanos , Estudos Longitudinais , Gravidez , Resultado da Gravidez , Tromboxano A2/sangue , Tromboxano B2/sangue , Adulto Jovem
20.
Dis Markers ; 2017: 9506527, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28630527

RESUMO

PURPOSE: The study was designed to evaluate the disease outcome based on multiple biomarkers related to cerebral ischemia. METHODS: Rats were randomly divided into sham, permanent middle cerebral artery occlusion, and edaravone-treated groups. Cerebral ischemia was induced by permanent middle cerebral artery occlusion surgery in rats. To form a simplified crosstalk network, the related multiple biomarkers were chosen as S100ß, HIF-1α, IL-1ß, PGI2, TXA2, and GSH-Px. The levels or activities of these biomarkers in plasma were detected before and after ischemia. Concurrently, neurological deficit scores and cerebral infarct volumes were assessed. Based on a mathematic model, network balance maps and three integral disruption parameters (k, φ, and u) of the simplified crosstalk network were achieved. RESULTS: The levels or activities of the related biomarkers and neurological deficit scores were significantly impacted by cerebral ischemia. The balance maps intuitively displayed the network disruption, and the integral disruption parameters quantitatively depicted the disruption state of the simplified network after cerebral ischemia. The integral disruption parameter u values correlated significantly with neurological deficit scores and infarct volumes. CONCLUSION: Our results indicate that the approach based on crosstalk network may provide a new promising way to integrally evaluate the outcome of cerebral ischemia.


Assuntos
Isquemia Encefálica/sangue , Modelos Teóricos , Animais , Biomarcadores/sangue , Isquemia Encefálica/patologia , Epoprostenol/sangue , Glutationa Peroxidase/sangue , Subunidade alfa do Fator 1 Induzível por Hipóxia/sangue , Interleucina-1beta/sangue , Masculino , Ratos , Ratos Sprague-Dawley , Subunidade beta da Proteína Ligante de Cálcio S100/sangue , Tromboxano A2/sangue
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA
...