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1.
Int J Mol Sci ; 22(13)2021 Jun 30.
Artigo em Inglês | MEDLINE | ID: mdl-34209006

RESUMO

Osteoarthritis (OA) is a common chronic disease with increasing prevalence in societies with more aging populations, therefore, it is causing more concern. S-Equol, a kind of isoflavones, was reported to be bioavailable and beneficial to humans in many aspects, such as improving menopausal symptoms, osteoporosis and prevention of cardiovascular disease. This study investigated the effects of S-Equol on OA progress in which rat primary chondrocytes were treated with sodium nitroprusside (SNP) to mimic OA progress with or without the co-addition of S-Equol for the evaluation of S-Equol's efficacy on OA. Results showed treatment of 0.8 mM SNP caused cell death, and increased oxidative stress (NO and H2O2), apoptosis, and proteoglycan loss. Furthermore, the expressions of MMPs of MMP-2, MMP-3, MMP-9, and MMP-13 and p53 were increased. The addition of 30 µM S-Equol could lessen those caused by SNP. Moreover, S-Equol activates the PI3K/Akt pathway, which is an upstream regulation of p53 and NO production and is associated with apoptosis and matrix degradation. As a pretreatment of phosphoinositide 3-kinases (PI3K) inhibitor, all S-Equol protective functions against SNP decrease or disappear. In conclusion, through PI3K/Akt activation, S-Equol can protect chondrocytes against SNP-induced matrix degradation and apoptosis, which are commonly found in OA, suggesting S-Equol is a potential for OA prevention.


Assuntos
Condrócitos/citologia , Equol/farmacologia , Nitroprussiato/efeitos adversos , Osteoartrite/metabolismo , Transdução de Sinais/efeitos dos fármacos , Animais , Sobrevivência Celular/efeitos dos fármacos , Células Cultivadas , Condrócitos/efeitos dos fármacos , Feminino , Regulação da Expressão Gênica , Humanos , Masculino , Modelos Biológicos , Osteoartrite/induzido quimicamente , Osteoartrite/tratamento farmacológico , Estresse Oxidativo/efeitos dos fármacos , Fosfatidilinositol 3-Quinases/metabolismo , Cultura Primária de Células , Proteínas Proto-Oncogênicas c-akt/metabolismo , Ratos
2.
J Cardiovasc Pharmacol ; 78(3): 403-406, 2021 09 01.
Artigo em Inglês | MEDLINE | ID: mdl-34173810

RESUMO

BACKGROUND: Sacubitril-valsartan is an angiotensin receptor-neprilysin inhibitor indicated for the treatment of patients with symptomatic heart failure with reduced ejection fraction (HFrEF). Little is known about outcomes of HFrEF patients transitioned from sodium nitroprusside (SNP) to sacubitril-valsartan during an admission for acute decompensated heart failure. We sought to describe characteristics of patients initiated on sacubitril-valsartan while receiving SNP and, in particular, those patients who did and did not experience hypotension requiring interruption or discontinuation of sacubitril-valsartan. METHODS: We performed a retrospective case series of adult patients (>18 years) with HFrEF (left ventricular ejection fraction ≤40%) admitted to the University of Michigan cardiac intensive care unit between July 2018 to September 2020 who received sacubitril-valsartan while on SNP. RESULTS: A total of 15 patients with acute decompensated heart failure were initiated on sacubitril-valsartan while on SNP. The mean age was 57 ± 15.9 years. Seven (46.7%) patients experienced hypotension. The patients in the cohort who experienced hypotension were numerically older (60 ± 17 vs. 55 ± 15.5), and the majority were white (86%). Patients with hypotension had a numerically lower left ventricular ejection fraction (13 ± 4.2 vs. 18 ± 8.2) and higher serum creatinine (1.4 ± 0.54 vs. 0.88 ± 0.25). Seven (100%) patients received a diuretic on the day of sacubitril-valsartan initiation in those who experienced hypotension compared with 2 (25%) in those who did not experience hypotension. CONCLUSIONS: In almost half of patients admitted to the cardiac intensive care unit with acutely decompensated HFrEF, significant hypotension was seen when initiating sacubitril-valsartan while on SNP. Future studies should evaluate appropriate patients for this transition and delineate appropriate titration parameters.


Assuntos
Aminobutiratos/efeitos adversos , Bloqueadores do Receptor Tipo 1 de Angiotensina II/efeitos adversos , Compostos de Bifenilo/efeitos adversos , Insuficiência Cardíaca/tratamento farmacológico , Hipotensão/induzido quimicamente , Nitroprussiato/efeitos adversos , Inibidores de Proteases/efeitos adversos , Valsartana/efeitos adversos , Vasodilatadores/efeitos adversos , Adulto , Idoso , Pressão Sanguínea/efeitos dos fármacos , Unidades de Cuidados Coronarianos , Diuréticos/efeitos adversos , Combinação de Medicamentos , Feminino , Insuficiência Cardíaca/diagnóstico , Insuficiência Cardíaca/fisiopatologia , Humanos , Hipotensão/diagnóstico , Hipotensão/fisiopatologia , Masculino , Pessoa de Meia-Idade , Neprilisina/antagonistas & inibidores , Estudos Retrospectivos , Fatores de Risco , Resultado do Tratamento
3.
Rev. bras. ter. intensiva ; 31(1): 15-20, jan.-mar. 2019. tab
Artigo em Português | LILACS | ID: biblio-1003626

RESUMO

RESUMO Objetivo: Descrever a incidência de eventos clínicos e não clínicos durante o transporte intra-hospitalar de pacientes críticos e analisar os fatores de risco associados. Métodos: Estudo de coorte, com coleta retrospectiva, no período de outubro de 2016 a outubro de 2017, tendo sido analisados todos os transportes intra-hospitalares para fins diagnósticos e terapêuticos em hospital de grande porte, que contava com seis unidades de terapia intensiva adulto, sendo avaliados os eventos adversos e os fatores de risco relacionados. Resultados: No período, foram realizados 1.559 transportes intra-hospitalares, em 1.348 pacientes, com média de idade de 66 ± 17 anos, tempo médio de transporte de 43 ± 34 minutos. Durante o transporte, 19,8% dos pacientes estavam em uso de drogas vasoativas; 13,7% em uso de sedativos e 10,6% estavam sob ventilação mecânica. Eventos clínicos ocorreram em 117 transportes (7,5%) e não clínicos em 125 transportes (8,0%). Falhas de comunicação foram prevalentes, no entanto, aplicando-se análise multivariada, uso de sedativos, noradrenalina e nitroprussiato, e o tempo de transporte maior que 36,5 minutos estiveram associados a eventos adversos clínicos. Uso de dobutamina e tempo de transporte superior a 36,5 minutos estiveram associados a eventos não clínicos. Ao final do transporte, 98,1% dos pacientes apresentaram condições clínicas inalteradas em relação ao seu estado basal. Conclusão: Transportes intra-hospitalares estão relacionados à alta incidência de eventos adversos; o tempo de transporte e a utilização de sedativos e drogas vasoativas estiveram relacionados a esses eventos.


ABSTRACT Objective: To describe the incidence of clinical and non-clinical events during intrahospital transport of critically ill patients and to analyze the associated risk factors. Methods: Cohort study with retrospective data collected from October 2016 to October 2017. All cases of intrahospital transport for diagnostic and therapeutic purposes in a large hospital with six adult intensive care units were analyzed, and the adverse events and related risk factors were evaluated. Results: During the study period, 1,559 intrahospital transports were performed with 1,348 patients, with a mean age of 66 ± 17 years and a mean transport time of 43 ± 34 minutes. During transport, 19.8% of the patients were using vasoactive drugs; 13.7% were under sedation; and 10.6% were under mechanical ventilation. Clinical events occurred in 117 transports (7.5%), and non-clinical events occurred in 125 (8.0%) transports. Communication failures were prevalent; however, the multivariate analysis showed that the use of sedatives, noradrenaline and nitroprusside and a transport time greater than 36.5 minutes were associated with adverse clinical events. The use of dobutamine and a transport time greater than 36.5 minutes were associated with non-clinical events. At the end of transport, 98.1% of the patients presented unchanged clinical conditions compared with baseline. Conclusion: Intrahospital transport is related to a high incidence of adverse events, and transport time and the use of sedatives and vasoactive drugs were related to these events.


Assuntos
Humanos , Masculino , Feminino , Idoso , Idoso de 80 Anos ou mais , Transporte de Pacientes/métodos , Estado Terminal , Unidades de Terapia Intensiva , Respiração Artificial/efeitos adversos , Respiração Artificial/estatística & dados numéricos , Fatores de Tempo , Nitroprussiato/administração & dosagem , Nitroprussiato/efeitos adversos , Norepinefrina/administração & dosagem , Norepinefrina/efeitos adversos , Análise Multivariada , Estudos Retrospectivos , Fatores de Risco , Estudos de Coortes , Hospitais , Hipnóticos e Sedativos/administração & dosagem , Hipnóticos e Sedativos/efeitos adversos , Pessoa de Meia-Idade
4.
Eur J Pharmacol ; 828: 146-153, 2018 Jun 05.
Artigo em Inglês | MEDLINE | ID: mdl-29604245

RESUMO

The preventive and therapeutic effects of curcumin on degeneration of articular (joint) cartilage diseases have rarely been investigated. In the present study, the protective effects of curcumin against sodium nitroprusside (SNP)-induced chondrocyte apoptosis were evaluated and the underlying molecular mechanisms were elucidated. Curcumin was used to as a co-treatment with SNP in chondrocytes, and changes occurring in the cells were observed and evaluated. It was shown using a cell counting kit-8 (CCK-8) assay that curcumin protected the viability of chondrocytes against SNP damage. NO (nitric oxide) from SNP could be scavenged by curcumin. Flow cytometry and Hoechst 33342 staining showed that curcumin not only inhibited the cell apoptosis in a concentration-dependent pattern but also ameliorated the SNP-induced nuclear chromatin damage and reduction of the mitochondrial membrane potential in chondrocytes. In SNP-treated chondrocytes, curcumin downregulated the expression of Bax and cleaved caspase-3 but upregulated the expression of Bcl-2, as shown by western blot. Meanwhile, curcumin administration also protected extracellular matrix (ECM) synthesis and prevented its degradation. Taken together, these results support the hypothesis that curcumin exerts its protective effect on chondrocytes against SNP-induced apoptosis, at least partly, via blocking the mitochondrial-dependent apoptotic pathway and maintaining the metabolic balance of ECM. Thus, curcumin may be a potential candidate to be used as a unique biological agent for the prevent and treatment of osteoarthritis (OA).


Assuntos
Apoptose/efeitos dos fármacos , Condrócitos/citologia , Condrócitos/efeitos dos fármacos , Curcumina/farmacologia , Citoproteção/efeitos dos fármacos , Articulações/citologia , Nitroprussiato/efeitos adversos , Animais , Caspase 3/metabolismo , Proliferação de Células/efeitos dos fármacos , Condrócitos/metabolismo , Colágeno Tipo II/genética , Colágeno Tipo II/metabolismo , Masculino , Metaloproteinase 13 da Matriz/genética , Metaloproteinase 13 da Matriz/metabolismo , Potencial da Membrana Mitocondrial/efeitos dos fármacos , Óxido Nítrico/metabolismo , Proteólise/efeitos dos fármacos , Proteínas Proto-Oncogênicas c-bcl-2/metabolismo , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Coelhos , Proteína X Associada a bcl-2/metabolismo
5.
Int J Mol Med ; 41(5): 2485-2492, 2018 May.
Artigo em Inglês | MEDLINE | ID: mdl-29436588

RESUMO

Oxidative stress induced disc cell apoptosis plays an important role in intervertebral disc (IVD) degeneration. The present study aims to investigate effects of resveratrol (RV), a natural polyphenol compound, on sodium nitroprusside (SNP) induced nucleus pulposus (NP) cell apoptosis and related mechanism. Rat NP cells were pretreated with RV, N-acetyl cysteine (NAC) and carboxy-PTIO (PTIO) before SNP treatment. Cell Counting Kit-8 assay was carried out for cell viability evaluation. Annexin V/propidium iodide (PI), Hoechst 33258 and Actin­Tracker Green and Tubulin-Tracker Red staining were conducted to detect NP cell apoptosis and apoptotic structural changes. Mitochondrial membrane potential (ΔΨm) was analyzed with tetramethylrhodamine methyl ester staining. DCFH-DA and DAF-FM DA staining was used to determine intracellular reactive oxygen species (ROS) and nitric oxide (NO) levels. An ex vivo experiment was also carried out followed by TUNEL assay of sections of discs. SNP induced NP cell apoptosis, excessive production of intracellular ROS and NO, reduction of ΔΨm as well as disruption of cytoskeletal and morphological structure. Meanwhile, organ culture results showed that SNP induced NP cell apoptosis ex vivo. RV and NAC siginificantly inhibited SNP induced NP cell apoptosis, production of intracellular ROS, deline of ΔΨm as well as disruption of cytoskeletal and morphological structure, while RV did not suppress NO production. RV and NAC could also suppress SNP induced NP cell apoptosis ex vivo. However, PTIO did not prevent SNP induced NP cell apoptosis, though it scavenged NO significantly. In conclusion, RV protects against SNP induced NP cell apoptosis by scavenging ROS but not NO, suggesting a promising prospect of RV in IVD degeneration retardation.


Assuntos
Antioxidantes/farmacologia , Apoptose/efeitos dos fármacos , Doadores de Óxido Nítrico/efeitos adversos , Nitroprussiato/efeitos adversos , Núcleo Pulposo/efeitos dos fármacos , Espécies Reativas de Oxigênio/metabolismo , Estilbenos/farmacologia , Animais , Células Cultivadas , Núcleo Pulposo/citologia , Ratos Sprague-Dawley , Resveratrol
6.
Cardiovasc Revasc Med ; 19(2): 168-174, 2018 03.
Artigo em Inglês | MEDLINE | ID: mdl-28888873

RESUMO

BACKGROUND: FFR is useful in defining the physiological significance of intermediate coronary stenosis and requires induction of maximal hyperemia and measurement of pressure proximal and distal to the stenosis. Hyperemia normally is induced by either IV or IC adenosine, a medication associated with short-term side effects. IV regadenoson and IC nitroprusside have been suggested as viable alternatives. This meta-analysis aims to identify all studies comparing use of intravenous (IV) regadenoson or intracoronary (IC) nitroprusside with IV adenosine to determine differences related to the agent utilized for assessment of fractional flow reserve (FFR). METHODS: We searched PubMed, EMBASE, Web of Science, SCOPUS, ClinicalTrials.gov and the Cochrane Library databases for studies comparing IV regadenoson or IC nitroprusside to IV adenosine for FFR assessment. The main outcome was difference in mean FFR measurement. The main secondary outcomes were composite side-effect profile and reclassification of lesions. RESULTS: Seven studies were included in the analysis, with a total of 375 patients. Compared to IV adenosine, there was no difference in the mean FFR derived from IV regadenoson (p=1.0) or IC nitroprusside (p=0.48). IV regadenoson was associated with 53% lower risk of pooled side effects compared to IV adenosine (p=0.05). IC nitroprusside was associated with 97% lower risk of pooled side effects compared to IV adenosine (p<0.001). CONCLUSIONS: IV regadenoson and IC nitroprusside produce similar pressure-derived FFR measurements compared to IV adenosine and have a favorable side effect profile. Both can be considered as alternative agents to IV adenosine for FFR measurement. Further clinical validation is warranted.


Assuntos
Cateterismo Cardíaco , Doença da Artéria Coronariana/diagnóstico , Estenose Coronária/diagnóstico , Vasos Coronários/fisiopatologia , Reserva Fracionada de Fluxo Miocárdico , Nitroprussiato/administração & dosagem , Purinas/administração & dosagem , Pirazóis/administração & dosagem , Vasodilatadores/administração & dosagem , Administração Intravenosa , Adulto , Idoso , Doença da Artéria Coronariana/fisiopatologia , Estenose Coronária/fisiopatologia , Feminino , Humanos , Hiperemia/fisiopatologia , Masculino , Pessoa de Meia-Idade , Nitroprussiato/efeitos adversos , Valor Preditivo dos Testes , Purinas/efeitos adversos , Pirazóis/efeitos adversos , Reprodutibilidade dos Testes , Índice de Gravidade de Doença , Vasodilatadores/efeitos adversos
7.
Chin J Physiol ; 60(1): 1-10, 2017 Feb 28.
Artigo em Inglês | MEDLINE | ID: mdl-28052641

RESUMO

Sodium nitroprusside (SNP) is an antihypertensive drug with proven dose-dependent toxic effects attributed mainly to the production of cyanide but also excesive nitric oxide (NO) and derived reactive species. The present study evaluated whether melatonin administration would have time-dependent protective effect against SNP−induced toxicity. Male Swiss mice were used in this study. Control mice were treated with 0.9% NaCl; the second group was injected with 10 mg melatonin (MEL)/kg body weight (b.w.); the third group was given SNP at the dose of 3,6 mg/kg b.w.; the fourth group received both MEL and SNP at the same doses. In homogenates of brain, liver and kidneys, activities of superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GSH-Px) were estimated after 3, 6 and 24 h of drugs administration. The concentration of reduced glutathione (GSH) was also evaluated in the blood, brain, liver and kidneys of mice at the same time intervals. In animals receiving MEL, the highest levels of GSH were observed in all the organs as compared to the control after 3, 6 h. Meanwhile, SNP decreased GSH concentration in the blood, brain, liver and kidneys in all time intervals. Administration of MEL in combination with SNP increased the GSH levels in all organs, as compared to the administration of SNP alone; this effect was observed after 3, 6 and 24 h. The activity of SOD, CAT and GSH-Px in the MEL-treated group increased after 3 h in all the organs, while in liver and kidney the increase was also observed after 6 h. Conversely, the SNP intoxication caused a decrease of the activity of enzymes in the tested organs in all intervals, while administration of MEL + SNP resulted in increased activities of SOD, CAT and GSH-Px in all the organs after 3 h and 6 h. The investigation carried out in the present study provide new data to add to the study of antioxidant properties of MEL and SNP-induced oxidative stress with regard to time-dependent properties in different types of tissues.


Assuntos
Anti-Hipertensivos/efeitos adversos , Antioxidantes/uso terapêutico , Melatonina/uso terapêutico , Nitroprussiato/efeitos adversos , Estresse Oxidativo/efeitos dos fármacos , Animais , Antioxidantes/metabolismo , Catalase/metabolismo , Avaliação Pré-Clínica de Medicamentos , Glutationa/metabolismo , Glutationa Peroxidase/metabolismo , Masculino , Camundongos , Superóxido Dismutase/metabolismo
8.
Eur J Pharmacol ; 789: 109-118, 2016 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-27445236

RESUMO

Berberine chloride (BBR) is an isoquinoline derivative alkaloid isolated from medicinal herbs, including Coptis chinensis and Berberis aristate. This compound plays significant roles in the treatment of osteoarthritis (OA). The purpose of this study was to investigate the effects of BBR on the proliferation of sodium nitroprusside (SNP)-stimulated chondrocytes in vitro, the articular cartilage in a rat OA model, as well as to discuss the molecular mechanisms underlying these effects. In vitro, we demonstrated that BBR led to cell proliferation, increased the cell population in S-phase and decreased that in G0/G1-phase; moreover, the F-actin remodeling in SNP-stimulated chondrocytes were prevented. In addition, BBR markedly up-regulated ß-catenin, c-Myc, and cyclin D1 expression of genes and proteins, and down-regulated glycogen synthase kinase-3ß (GSK-3ß) and matrix metalloproteinase-7 (MMP-7) expression. Notably, inhibition of the Wnt/ß-catenin pathway by XAV939 partially blocked these effects. The in vivo results suggested that BBR promoted ß-catenin protein level and enhanced proliferating cell nuclear antigen (PCNA) expression in osteoarthritic rat cartilage. In conclusion, these findings indicate that BBR promotes SNP-stimulated chondrocyte proliferation by promoting G1/S phase transition and synthesis of PCNA in cartilage through activation of Wnt/ß-catenin signaling pathway.


Assuntos
Berberina/farmacologia , Cartilagem Articular/patologia , Condrócitos/citologia , Condrócitos/efeitos dos fármacos , Nitroprussiato/efeitos adversos , Osteoartrite/patologia , Via de Sinalização Wnt/efeitos dos fármacos , Animais , Ciclo Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Condrócitos/metabolismo , Condrócitos/patologia , Ciclina D1/genética , Citoesqueleto/efeitos dos fármacos , Citoesqueleto/metabolismo , Proteínas de Ligação a DNA/genética , Regulação Enzimológica da Expressão Gênica/efeitos dos fármacos , Glicogênio Sintase Quinase 3 beta/genética , Fator 1 de Ligação ao Facilitador Linfoide/metabolismo , Antígeno Nuclear de Célula em Proliferação/metabolismo , Proteínas Proto-Oncogênicas c-myc/genética , Ratos , Ratos Sprague-Dawley , Fator de Transcrição 4 , Fatores de Transcrição/genética
9.
Cardiovasc Revasc Med ; 17(7): 441-443, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-27432209

RESUMO

INTRODUCTION: The aim of this study was to investigate the efficacy and safety of intracoronary (IC) sodium nitroprusside infusion in comparison to IC adenosine for fractional flow reserve (FFR) measurement in moderately diseased coronary artery lesions for functional assessment. METHODS: During a nine month period, a consecutive of 98 patients with suspected or known coronary artery disease with moderate stenosis found during angiography (40% to 70% stenosis), were enrolled in this study. Hyperemia was induced by bolus doses of IC adenosine followed by sodium nitroprusside for FFR measurement. RESULTS: Both IC adenosine and IC sodium nitroprusside induced similar and significant reduction in FFR. There was no statistically difference in FFR values between adenosine vs sodium nitroprusside infusions (mean FFR 84.3±6.3 vs 85.7±6.2, p=0.1) respectively. Furthermore, comparing different FFR cut-off points between the groups (FFR<0.75, 0.75-0.8 and >0.8) showed no significant differences (p value=0.7). CONCLUSION: An IC bolus of sodium nitroprusside (0.6µg/kg) infusion induces a similar degree of hyperemia to IC bolus of 100-300µg of adenosine. Therefore, IC sodium nitroprusside could be considered as an alternative drug to adenosine for FFR measurement with lower side effect profile.


Assuntos
Adenosina/administração & dosagem , Cateterismo Cardíaco , Estenose Coronária/diagnóstico , Reserva Fracionada de Fluxo Miocárdico , Nitroprussiato/administração & dosagem , Vasodilatadores/administração & dosagem , Adenosina/efeitos adversos , Idoso , Cateterismo Cardíaco/efeitos adversos , Angiografia Coronária , Estenose Coronária/fisiopatologia , Vasos Coronários , Feminino , Humanos , Hiperemia/fisiopatologia , Infusões Intra-Arteriais , Masculino , Pessoa de Meia-Idade , Nitroprussiato/efeitos adversos , Valor Preditivo dos Testes , Prognóstico , Índice de Gravidade de Doença , Vasodilatadores/efeitos adversos
10.
Nutr Neurosci ; 19(1): 1-10, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-26241203

RESUMO

OBJECTIVES: Aging represents a major risk factor for neurodegenerative diseases such as Alzheimer's disease. Mitochondria are significantly involved in both the aging process and neurodegeneration. One strategy to protect the brain and to prevent neurodegeneration is a healthy lifestyle including a diet rich in antioxidants and polyphenols. Rice bran extract (RBE) contains various antioxidants including natural vitamin E forms (tocopherols and tocotrienols) and gamma-oryzanol. In this work, we examined the effects of a stabilized RBE on mitochondrial function in 18-month-old Naval Medical Research Institute mice (340 mg/kg body weight/day), which received the extract for 3 weeks via oral gavage. METHODS: Mitochondrial parameters were measured using high-resolution respirometry (Oroboros Oxygraph-2k), Western blot analysis, and photometric methods in dissociated brain cells, isolated mitochondria, and brain homogenate. Vitamin E concentrations in blood plasma and brain tissue were measured using HPLC with fluorescence detection. RESULTS: Aging leads to decreased mitochondrial function (decreased mitochondrial respiration and ATP production) and decreased protein expression of peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC1alpha). RBE administration increased alpha-tocopherol concentrations in the brain and compensated for age-related mitochondrial dysfunction by increasing mitochondrial respiration, membrane potential, PGC1alpha protein expression, and citrate synthase activity. Furthermore, resistance of brain cells to sodium nitroprusside-induced nitrosative stress was improved. DISCUSSION: According to these results, RBE is a promising candidate nutraceutical for the prevention of age-related neurodegenerative diseases.


Assuntos
Antioxidantes/farmacologia , Encéfalo/efeitos dos fármacos , Mitocôndrias/efeitos dos fármacos , Oryza/química , Extratos Vegetais/farmacologia , Envelhecimento/efeitos dos fármacos , Doença de Alzheimer/prevenção & controle , Animais , Citrato (si)-Sintase/genética , Citrato (si)-Sintase/metabolismo , Suplementos Nutricionais , Modelos Animais de Doenças , Feminino , Camundongos , Mitocôndrias/metabolismo , Nitroprussiato/efeitos adversos , Estresse Oxidativo/efeitos dos fármacos , Coativador 1-alfa do Receptor gama Ativado por Proliferador de Peroxissomo , Fenilpropionatos/farmacologia , Fatores de Transcrição/genética , Fatores de Transcrição/metabolismo , Vitamina E/farmacologia
12.
Trials ; 15: 371, 2014 Sep 25.
Artigo em Inglês | MEDLINE | ID: mdl-25252600

RESUMO

BACKGROUND: Microvascular obstruction (MVO) secondary to ischaemic-reperfusion injury is an important but underappreciated determinant of short- and longer-term outcome following percutaneous coronary intervention (PCI) treatment of ST-elevation myocardial infarction (STEMI). Several small studies have demonstrated a reduction in the degree of MVO utilising a variety of vasoactive agents, with adenosine and sodium nitroprusside (SNP) being most evaluated. However, the evidence base remains weak as the trials have had variable endpoints, differing drug doses and delivery. As such, the results regarding benefit are conflicting. METHODS: The REperfusion Facilitated by LOcal adjunctive therapy in STEMI (REFLO-STEMI) trial is a multicentre, prospective, randomised, controlled, open label, study with blinded endpoint analysis: Patients presenting within 6 h of onset of STEMI and undergoing planned primary PCI (P-PCI) with TIMI 0/1 flow in the infarct-related artery (IRA) and no significant bystander coronary artery disease on angiography, are randomised into one of three groups: PCI with adjunctive pharmacotherapy (intracoronary adenosine or SNP) or control (standard PCI). All receive Bivalirudin anticoagulation and thrombus aspiration. The primary outcome is infarct size (IS) (determined as a percentage of total left ventricular mass) measured by cardiac magnetic resonance imaging (CMRI) undertaken at 48 to 72 h post P-PCI. Secondary outcome measures include MVO (hypoenhancement within infarct core) on CMRI, angiographic markers of microvascular perfusion and MACE during 1-month follow-up. The study aims to recruit 240 patients (powered at 80% to detect a 5% absolute reduction in IS). DISCUSSION: The REFLO-STEMI study has been designed to address the weaknesses of previous trials, which have collectively failed to demonstrate whether adjunctive pharmacotherapy with adenosine and/or SNP can reduce measures of myocardial injury (infarct size and MVO) and improve clinical outcome, despite good basic evidence that they have the potential to attenuate this process. The REFLO-STEMI study will be the most scientifically robust trial to date evaluating whether adjunctive therapy (intracoronary adenosine or SNP following thrombus aspiration) reduces CMRI measured IS and MVO in patients undergoing P-PCI within 6 h of onset of STEMI. TRIAL REGISTRATION: Trial registered 20th November 2012: ClinicalTrials.gov Identifier NCT01747174.


Assuntos
Adenosina/administração & dosagem , Circulação Coronária/efeitos dos fármacos , Vasos Coronários/efeitos dos fármacos , Microcirculação/efeitos dos fármacos , Infarto do Miocárdio/terapia , Nitroprussiato/administração & dosagem , Fenômeno de não Refluxo/prevenção & controle , Intervenção Coronária Percutânea , Traumatismo por Reperfusão/prevenção & controle , Projetos de Pesquisa , Vasodilatadores/administração & dosagem , Adenosina/efeitos adversos , Protocolos Clínicos , Angiografia Coronária , Vasos Coronários/fisiopatologia , Humanos , Imageamento por Ressonância Magnética , Infarto do Miocárdio/diagnóstico , Infarto do Miocárdio/fisiopatologia , Imagem de Perfusão do Miocárdio , Nitroprussiato/efeitos adversos , Fenômeno de não Refluxo/diagnóstico , Fenômeno de não Refluxo/etiologia , Fenômeno de não Refluxo/fisiopatologia , Intervenção Coronária Percutânea/efeitos adversos , Estudos Prospectivos , Traumatismo por Reperfusão/diagnóstico , Traumatismo por Reperfusão/etiologia , Traumatismo por Reperfusão/fisiopatologia , Fatores de Tempo , Resultado do Tratamento , Reino Unido , Vasodilatadores/efeitos adversos
13.
J Invasive Cardiol ; 26(3): 119-22, 2014 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-24610505

RESUMO

The purpose of this study was to compare the efficacy and safety of intracoronary (IC) sodium nitroprusside (SNP) and IC adenosine (AD) for fractional flow reserve (FFR) measurement. We compared the FFR response and side effect profiles of IC AD and IC SNP in 40 patients with a combined total of 53 moderate coronary stenoses. Boluses of AD at doses of 40 µg (A1) and 60 µg (A2), and SNP at doses of 0.3 µg/kg (S1), 0.6 µg/kg (S2), and 0.9 µg/kg (S3) were used to achieve coronary hyperemia. The mean FFR value decreased significantly by 7.96% (A1), 10.51% (A2), 8.74% (S1), 10.58% (S2), and 10.73% (S3) compared with the baseline distal coronary pressure/aortic pressure. IC SNP delayed the mean time to peak value of FFR by 87.5%, 79.0%, and 88.6% in S1, S2, and S3, respectively, compared with A2 (P<.001). The mean duration of the plateau phase was longer in S1 (50.47 ± 14.25 s), S2 (51.33 ± 16.41 s) and S3 (57.60 ± 18.07 s) compared with A2 (27.93 ± 11.90 s; P<.01). IC AD caused shortness of breath in 11 patients (27.5%), flushing in 4 patients (10%), headache in 8 patients (20%), and transient second-degree atrioventricular block (AVB) in 6 patients (15%). IC SNP may be used as a hyperemic agent in FFR measurements. It may be preferable to IC AD as a routine clinical stimulus and has the additional advantage of showing a longer plateau phase.


Assuntos
Adenosina , Estenose Coronária/diagnóstico por imagem , Estenose Coronária/fisiopatologia , Vasos Coronários/diagnóstico por imagem , Vasos Coronários/fisiopatologia , Reserva Fracionada de Fluxo Miocárdico/fisiologia , Nitroprussiato , Adenosina/administração & dosagem , Adenosina/efeitos adversos , Adulto , Idoso , Angiografia Coronária/métodos , Estenose Coronária/diagnóstico , Dispneia/induzido quimicamente , Dispneia/epidemiologia , Rubor/induzido quimicamente , Rubor/epidemiologia , Cefaleia/induzido quimicamente , Cefaleia/epidemiologia , Hemodinâmica/fisiologia , Humanos , Hiperemia/fisiopatologia , Incidência , Injeções Intra-Arteriais , Pessoa de Meia-Idade , Nitroprussiato/administração & dosagem , Nitroprussiato/efeitos adversos , Índice de Gravidade de Doença
14.
Food Funct ; 5(5): 984-9, 2014 May.
Artigo em Inglês | MEDLINE | ID: mdl-24637610

RESUMO

Curcumin, a polyphenolic compound has several pharmacological activities, such as anticancer, anti-inflammatory and antioxidant effects. However, curcumin shows poor oral bioavailability. The purpose of this study was to investigate the protective effects of highly bioavailable curcumin, Theracurmin(®), and curcumin, against sodium nitroprusside (SNP)-induced oxidative damage in mice brain. Intrastriatal microinjection of Theracurmin(®) or curcumin with SNP significantly protected against SNP-induced brain damage and motor dysfunction. Oral administration of Theracurmin(®) (1 and 3 g kg(-1), containing 100 and 300 mg kg(-1) curcumin, respectively) significantly protected against SNP-induced brain damage and motor dysfunction. However, oral administration of 300 mg kg(-1) curcumin did not protect against motor dysfunction induced by SNP. These results suggest that curcumin and Theracurmin(®) have protective effects against SNP-induced oxidative damage. Moreover, oral administration of Theracurmin(®), had more potency in protecting against brain damage, suggesting a higher bioavailability of Theracurmin(®) following oral administration.


Assuntos
Encéfalo/efeitos dos fármacos , Curcumina/farmacocinética , Doenças Neurodegenerativas/tratamento farmacológico , Fármacos Neuroprotetores/farmacocinética , Estresse Oxidativo/efeitos dos fármacos , Animais , Disponibilidade Biológica , Encéfalo/metabolismo , Curcumina/administração & dosagem , Humanos , Masculino , Camundongos , Camundongos Endogâmicos ICR , Doenças Neurodegenerativas/metabolismo , Fármacos Neuroprotetores/administração & dosagem , Nitroprussiato/administração & dosagem , Nitroprussiato/efeitos adversos
15.
J Surg Res ; 182(1): e15-24, 2013 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-23088919

RESUMO

OBJECTIVE: The present study investigated the effect of controlled hypotension (CH) levels regulated by nitroprusside on hippocampal CA1 neurons. MATERIALS AND METHODS: All experimental rabbits were randomly divided into five groups to perform CH for recording their vital signs and survived for a certain time. The arterial blood was collected to measure the serum levels of interleukin 6 and tumor necrosis factor α and then the brain tissues were perfused and sectioned to carry out hematoxylin-eosin staining, TdT-mediated dUTP nick end labeling fluorescence, c-fos immunohistochemistry, and ultrastructural observation of hippocampal neuronal mitochondria. All data were analyzed with SPSS13.0 software, and P < 0.05 was indicated as statistically significant. RESULTS: Heart rate, mean arterial pressure, and the dosage of sodium nitroprusside were not statistically significant between groups, but at T2, heart rate levels in groups II-IV were lower than those in groups I and V. Simultaneously, interleukin 6 was remarkably overexpressed in group II than in other groups at T2, whereas tumor necrosis factor α was higher in groups I-III than in groups IV and V. At the light and electronic microscopic levels, the CA1 regional neurons of group IV were more seriously damaged and deranged compared with other groups so was the expression of c-fos. However, fluorescence from TdT-mediated dUTP nick end labeling assay was more intensive in groups II-IV than that in other groups. Results further showed that Flameng scores of mitochondria were the highest in group IV, but they were not statistically significant among the other groups. CONCLUSIONS: The different levels of CH remarkably affected the functional activities of hippocampal CA1 neurons; with the decrease of mean arterial pressure, neuronal apoptosis, and c-fos expression was gradually increased and reached the peak in 45% of basic values of blood pressure.


Assuntos
Anti-Hipertensivos/farmacologia , Pressão Sanguínea/efeitos dos fármacos , Região CA1 Hipocampal/patologia , Hipotensão/fisiopatologia , Neurônios/patologia , Nitroprussiato/farmacologia , Animais , Anti-Hipertensivos/efeitos adversos , Apoptose/efeitos dos fármacos , Pressão Sanguínea/fisiologia , Região CA1 Hipocampal/metabolismo , Região CA1 Hipocampal/fisiopatologia , Modelos Animais de Doenças , Frequência Cardíaca/efeitos dos fármacos , Frequência Cardíaca/fisiologia , Hipotensão/sangue , Hipotensão/induzido quimicamente , Interleucina-6/sangue , Masculino , Mitocôndrias/ultraestrutura , Neurônios/metabolismo , Neurônios/fisiologia , Nitroprussiato/efeitos adversos , Proteínas Proto-Oncogênicas c-fos/metabolismo , Coelhos , Fator de Necrose Tumoral alfa/sangue
16.
Asian Pac J Allergy Immunol ; 30(3): 243-5, 2012 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-23156856

RESUMO

Sodium nitroprusside (SNP) is one of the most widely used parenteral antihypertensive agents in severe hypertension management. Toxic epidermal necrolysis (TEN) is a rare, mostly drug-induced, severe muco-cutoneous reaction with various complications and high mortality. A fifteen years old girl who is on hemodialysis for chronic renal insufficiency and was hospitalized for emergency management of hypertension, developed a diffuse maculopapular rash within minutes after SNP infusion. In 72 hours, approximately 40% of the body surface was involved with skin detachment indicating epidermal necrolysis and a skin biopsy confirmed the diagnosis of TEN. To the best of our knowledge there is no report of an association of SNP and TEN in the English literature and the clinical data exemplifying consequent IgE and non-IgE mediated hypersensitivity reactions are scanty. With this report we wanted to present a rare complication of SNP infusion indicating another rare occurrence of sequential IgE and non-IgE mediated hypersensitivity reactions.


Assuntos
Anti-Hipertensivos/efeitos adversos , Nitroprussiato/efeitos adversos , Síndrome de Stevens-Johnson/etiologia , Adolescente , Feminino , Humanos
17.
Arq. bras. cardiol ; 99(3): 848-856, set. 2012. ilus, graf, tab
Artigo em Português | LILACS | ID: lil-649264

RESUMO

FUNDAMENTO: A hipertensão pulmonar é associada ao pior prognóstico no pós-transplante cardíaco. O teste de reatividade pulmonar com Nitroprussiato de Sódio (NPS) está associado a elevados índices de hipotensão arterial sistêmica, disfunção ventricular do enxerto transplantado e elevadas taxas de desqualificação para o transplante. OBJETIVO: Neste estudo, objetivou-se comparar os efeitos do Sildenafil (SIL) e NPS sobre variáveis hemodinâmicas, neuro-hormonais e ecocardiográficas durante teste de reatividade pulmonar. MÉTODOS: Os pacientes foram submetidos, simultaneamente, ao cateterismo cardíaco direito, ao ecocardiograma e à dosagem de BNP e gasometria venosa, antes e após administração de NPS (1 - 2 µg/Kg/min) ou SIL (100 mg, dose única). RESULTADOS: Ambos reduziram a hipertensão pulmonar, porém o nitrato promoveu hipotensão sistêmica significativa (Pressão Arterial Média - PAM: 85,2 vs. 69,8 mmHg, p < 0,001). Ambos reduziram as dimensões cardíacas e melhoraram a função cardíaca esquerda (NPS: 23,5 vs. 24,8 %, p = 0,02; SIL: 23,8 vs. 26 %, p < 0,001) e direita (SIL: 6,57 ± 2,08 vs. 8,11 ± 1,81 cm/s, p = 0,002; NPS: 6,64 ± 1,51 vs. 7,72 ± 1,44 cm/s, p = 0,003), medidas pela fração de ejeção ventricular esquerda e Doppler tecidual, respectivamente. O SIL, ao contrário do NPS, apresentou melhora no índice de saturação venosa de oxigênio, medido pela gasometria venosa. CONCLUSÃO: Sildenafil e NPS são vasodilatadores que reduzem, de forma significativa, a hipertensão pulmonar e a geometria cardíaca, além de melhorar a função biventricular. O NPS, ao contrário do SIL, esteve associado a hipotensão arterial sistêmica e piora da saturação venosa de oxigênio.


BACKGROUND: Pulmonary hypertension is associated with a worse prognosis after cardiac transplantation. The pulmonary hypertension reversibility test with sodium nitroprusside (SNP) is associated with a high rate of systemic arterial hypotension, ventricular dysfunction of the transplanted graft and high rates of disqualification from transplantation. OBJECTIVE: This study was aimed at comparing the effects of sildenafil (SIL) and SNP on hemodynamic, neurohormonal and echocardiographic variables during the pulmonary reversibility test. METHODS: The patients underwent simultaneously right cardiac catheterization, echocardiography, BNP measurement, and venous blood gas analysis before and after receiving either SNP (1 - 2 µg/kg/min) or SIL (100 mg, single dose). RESULTS: Both drugs reduced pulmonary hypertension, but SNP caused a significant systemic hypotension (mean blood pressure - MBP: 85.2 vs. 69.8 mm Hg; p < 0.001). Both drugs reduced cardiac dimensions and improved left cardiac function (SNP: 23.5 vs. 24.8%, p = 0.02; SIL: 23.8 vs. 26%, p < 0.001) and right cardiac function (SIL: 6.57 ± 2.08 vs. 8.11 ± 1.81 cm/s, p = 0.002; SNP: 6.64 ± 1.51 vs. 7.72 ± 1.44 cm/s, p = 0.003), measured through left ventricular ejection fraction and tissue Doppler, respectively. Sildenafil, contrary to SNP, improved venous oxygen saturation, measured on venous blood gas analysis. CONCLUSION: Sildenafil and SNP are vasodilators that significantly reduce pulmonary hypertension and cardiac geometry, in addition to improving biventricular function. Sodium nitroprusside, contrary to SIL, was associated with systemic arterial hypotension and worsening of venous oxygen saturation.


Assuntos
Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Hemodinâmica/efeitos dos fármacos , Hipertensão Pulmonar/tratamento farmacológico , Hipotensão/induzido quimicamente , Nitroprussiato/uso terapêutico , Piperazinas/uso terapêutico , Sulfonas/uso terapêutico , Vasodilatadores/uso terapêutico , Pressão Sanguínea/efeitos dos fármacos , Pressão Sanguínea/efeitos da radiação , Hemodinâmica/fisiologia , Hipertensão Pulmonar/fisiopatologia , Hipotensão/tratamento farmacológico , Nitroprussiato/efeitos adversos , Cuidados Pré-Operatórios , Purinas/uso terapêutico , Resistência Vascular/efeitos dos fármacos , Resistência Vascular/fisiologia , Vasodilatadores/efeitos adversos , Função Ventricular/efeitos dos fármacos
18.
Heart Surg Forum ; 15(2): E92-6, 2012 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-22543344

RESUMO

Postoperative bleeding is common in patients undergoing cardiac surgery with cardiopulmonary bypass. Most cases of severe postoperative bleeding not due to incomplete surgical hemostasis are related to acquired transient platelet dysfunction mediated by platelet activation during contact with the synthetic surfaces of the cardiopulmonary bypass equipment. Antihypertensive agents nitroglycerin and sodium nitroprusside have been shown to have platelet inhibitory properties, yet the clinical consequence in terms of postoperative bleeding has been little studied. Knowing that cardiopulmonary bypass causes platelet dysfunction, it is prudent for physicians to be aware of the additional platelet inhibition caused by these commonly used antihypertensive agents.


Assuntos
Nitroglicerina/efeitos adversos , Nitroprussiato/efeitos adversos , Hemorragia Pós-Operatória/induzido quimicamente , Hemorragia Pós-Operatória/prevenção & controle , Pré-Medicação/efeitos adversos , Anti-Hipertensivos/efeitos adversos , Feminino , Humanos , Hipertensão/prevenção & controle , Masculino , Nitroprussiato/uso terapêutico , Resultado do Tratamento , Vasodilatadores/efeitos adversos
19.
JACC Cardiovasc Interv ; 5(4): 402-8, 2012 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-22516396

RESUMO

OBJECTIVES: This study sought to compare increasing doses of intracoronary (i.c.) adenosine or i.c. sodium nitroprusside versus intravenous (i.v.) adenosine for fractional flow reserve (FFR) assessment. BACKGROUND: Maximal hyperemia is the critical prerequisite for FFR assessment. Despite i.v. adenosine currently representing the recommended approach, i.c. administration of adenosine or other coronary vasodilators constitutes a valuable alternative in everyday practice. However, it is surprisingly unclear which i.c. strategy allows the achievement of FFR values comparable to i.v. adenosine. METHODS: Fifty intermediate coronary stenoses (n = 45) undergoing FFR measurement were prospectively and consecutively enrolled. Hyperemia was sequentially induced by incremental boli of i.c. adenosine (ADN) (60 µg ADN60, 300 µg ADN300, 600 µg ADN600), by i.c. sodium nitroprusside (NTP) (0.6 µg/kg bolus) and by i.v. adenosine infusion (IVADN) (140 µg/kg/min). FFR values, symptoms, and development of atrioventricular block were recorded. RESULTS: Incremental doses of i.c. adenosine and NTP were well tolerated and associated with fewer symptoms than IVADN. Intracoronary adenosine doses (0.881 ± 0.067, 0.871 ± 0.068, and 0.868 ± 0.070 with ADN60, ADN300, and ADN600, respectively) and NTP (0.892 ± 0.072) induced a significant decrease of FFR compared with baseline levels (p < 0.001). Notably, ADN600 only was associated with FFR values similar to IVADN (0.867 ± 0.072, p = 0.28). Among the 10 patients with FFR values ≤0.80 with IVADN, 5 were correctly identified also by ADN60, 6 by ADN300, 7 by ADN600, and 6 by NTP. CONCLUSIONS: Intracoronary adenosine, at doses higher than currently suggested, allows obtaining FFR values similar to i.v. adenosine. Intravenous adenosine, which remains the gold standard, might thus be reserved for those lesions with equivocal FFR values after high (up to 600 µg) i.c. adenosine doses.


Assuntos
Adenosina , Estenose Coronária/diagnóstico , Reserva Fracionada de Fluxo Miocárdico/efeitos dos fármacos , Hiperemia/fisiopatologia , Imagem de Perfusão do Miocárdio/métodos , Nitroprussiato , Vasodilatadores , Adenosina/administração & dosagem , Adenosina/efeitos adversos , Idoso , Algoritmos , Bloqueio Atrioventricular/induzido quimicamente , Cateterismo Cardíaco , Angiografia Coronária , Estenose Coronária/diagnóstico por imagem , Estenose Coronária/fisiopatologia , Relação Dose-Resposta a Droga , Feminino , Humanos , Infusões Intra-Arteriais , Infusões Intravenosas , Injeções Intra-Arteriais , Masculino , Pessoa de Meia-Idade , Nitroprussiato/administração & dosagem , Nitroprussiato/efeitos adversos , Valor Preditivo dos Testes , Estudos Prospectivos , Cidade de Roma , Índice de Gravidade de Doença , Vasodilatadores/administração & dosagem , Vasodilatadores/efeitos adversos
20.
Anesth Analg ; 114(5): 956-61, 2012 May.
Artigo em Inglês | MEDLINE | ID: mdl-22392971

RESUMO

BACKGROUND: Cyanide (CN) toxicity is a serious clinical problem and can occur with sodium nitroprusside (SNP) administration, accidental smoke inhalation, industrial mishaps, and bio-terrorism. In this study, we induced severe CN toxicity independently with SNP or sodium cyanide (NaCN) in a juvenile pig model to demonstrate reversal of severe CN toxicity with a new antidote, sulfanegen sodium, a prodrug of 3-mercaptopyruvate. METHODS: SNP study: A pilot study in 11 anesthetized, mechanically ventilated juvenile pigs allowed us to determine the dose of SNP to induce CN toxicity. Blood CN, serum lactates, and blood gases were monitored. CN toxicity was defined as the occurrence of severe lactic acidosis accompanied by significant elevation in blood CN levels. Based on this pilot study, 8 anesthetized pigs received a high-dose i.v. infusion of SNP (100 mg/h) for 2 hours to induce CN toxicity. They were then randomized to receive either sulfanegen sodium or placebo. Four pigs received 3 doses of sulfanegen sodium (2.5 g i.v.) every hour after induction of severe CN toxicity, and 4 pigs received placebo. NaCN study: A pilot study was conducted in 4 spontaneously ventilating pigs sedated with propofol plus ketamine to demonstrate hemodynamic and metabolic stability for several hours. After this, 6 pigs were similarly sedated and given NaCN in bolus aliquots to produce CN toxicity ultimately resulting in death. Hemodynamics and metabolic variables were followed to define peak CN toxicity. In another group of 6 pigs, severe CN toxicity was induced by this method, and at peak toxicity, the animals were given sulfanegen sodium (2.5 g i.v.) followed by a repeat dose 60 minutes later in surviving animals. RESULTS: SNP study: The pilot study demonstrated the occurrence of a significant increase in blood CN levels (P < 0.05) accompanied by severe lactic acidemia (P < 0.05) in all pigs receiving a high dose of SNP. Administration of the sulfanegen antidote resulted in progressive significant reduction in blood lactate and CN levels with 100% survival (P < 0.05), whereas the placebo-treated pigs deteriorated and did not survive (P < 0.05). NaCN study: NaCN injection resulted in CN toxicity accompanied by severe lactic acidosis and mortality in all the pigs. Sulfanegen sodium reversed this toxicity and prevented mortality in all the pigs treated with this antidote. CONCLUSIONS: CN toxicity can be successfully induced in a juvenile pig model with SNP or NaCN. The prodrug, sulfanegen sodium, is effective in reversing CN toxicity induced by SNP or NaCN.


Assuntos
Cianetos/antagonistas & inibidores , Cianetos/toxicidade , Cisteína/análogos & derivados , Compostos Heterocíclicos com 1 Anel/farmacologia , Pró-Fármacos/farmacologia , Animais , Gasometria , Pressão Sanguínea/efeitos dos fármacos , Pressão Venosa Central/efeitos dos fármacos , Cianetos/sangue , Cisteína/farmacologia , Frequência Cardíaca/efeitos dos fármacos , Concentração de Íons de Hidrogênio , Ácido Láctico/sangue , Nitroprussiato/efeitos adversos , Projetos Piloto , Artéria Pulmonar/efeitos dos fármacos , Suínos , Vasodilatadores/efeitos adversos
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