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1.
Medicine (Baltimore) ; 98(34): e16929, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31441880

RESUMO

To examine the characteristics and short-term outcome of perioperative myocardial infarction (PMI), a single-center retrospective study was carried out. The electronic medical records of 278,939 patients aged 45 years or older who underwent non-cardiac surgery at Renji Hospital from January 2003 to December 2015 were screened based on diagnostic codes (ICD121, ICD121.0, ICD121.1, ICD121.2, ICD121.3, ICD121.4, or ICD121.9). The incidence and characteristics of PMI and mortality risk factors were analyzed after non-cardiac surgery. PMI was reported in 45 patients, with an incidence rate of 1.61 per 10,000 and a mortality rate of 75.6% (34/45). The PMI incidence rate increased significantly with age. The PMI incidence rate was the highest for vascular surgery (5.82 per 10,000 cases). PMI occurs mainly within 48 h of surgery, with most cases showing an onset in the general wards. Logistic analysis showed that the use of nitrates is the independent protective factor for the outcomes of patients with PMI. The incidence of PMI in non-cardiac surgery is approximately 2 of 10,000 in patients aged 45 years or older, and increased significantly with age. The use of nitrates might be helpful for their survival.


Assuntos
Infarto do Miocárdio/mortalidade , Período Perioperatório/mortalidade , Complicações Pós-Operatórias/mortalidade , Idoso , China , Feminino , Mortalidade Hospitalar , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Infarto do Miocárdio/prevenção & controle , Nitratos/uso terapêutico , Estudos Retrospectivos , Fatores de Risco , Fatores de Tempo
2.
Br J Anaesth ; 123(4): 439-449, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31383364

RESUMO

BACKGROUND: Nerve growth factor (NGF) has been implicated in hyperalgesia by sensitising nociceptors. A role for NGF in modulating myocardial injury through ischaemic nociceptive signalling is plausible. We examined whether inhibition of spinal NGF attenuates myocardial ischaemia-reperfusion injury and explored the underlying mechanisms. METHODS: In adult rats, lentivirus-mediated short-hairpin RNA targeted at reducing NGF gene expression (NGF-shRNA) or a transient receptor potential vanilloid 1 (TRPV1) antagonist (capsazepine) was injected intrathecally before myocardial ischaemia-reperfusion. Infarct size (expressed as the ratio of area at risk) and risk of arrhythmias were quantified. Whole-cell clamp patch electrophysiology was used to record capsaicin currents in primary dorsal root ganglion neurones. The co-expression of substance P (SP) and calcitonin gene-related peptide (CGRP), plus activation of TRPV1, protein kinase B (Akt) and extracellular signal-regulated kinase (ERK) were also quantified. RESULTS: NGF levels increased by 2.95 (0.34)-fold in dorsal root ganglion and 2.12 (0.27)-fold in spinal cord after myocardial ischaemia-reperfusion injury. Intrathecal injection of NGF-shRNA reduced infarct area at risk from 0.58 (0.02) to 0.37 (0.02) (P<0.01) and reduced arrhythmia score from 3.67 (0.33) to 1.67 (0.33) (P<0.01). Intrathecal capsazepine was similarly cardioprotective. NGF-shRNA suppressed expression of SP/CGRP and activation of Akt/ERK and TRPV1 in spinal cord. NGF increased capsaicin current amplitude from 144 (42) to 840 (132) pA (P<0.05), which was blocked by the TRPV1 antagonist 5'-iodoresiniferatoxin. Exogenous NGF enhanced capsaicin-induced Akt/ERK and TRPV1 activation in PC12 neuroendocrine tumour cells in culture. CONCLUSIONS: Spinal NGF contributes to myocardial ischaemia-reperfusion injury by mediating nociceptive signal transmission.


Assuntos
Terapia Genética/métodos , Lentivirus/genética , Traumatismo por Reperfusão Miocárdica/genética , Traumatismo por Reperfusão Miocárdica/prevenção & controle , Fator de Crescimento Neural/genética , RNA Interferente Pequeno/administração & dosagem , RNA Interferente Pequeno/uso terapêutico , Animais , Arritmias Cardíacas/prevenção & controle , Capsaicina/análogos & derivados , Capsaicina/farmacologia , Cardiotônicos/administração & dosagem , Cardiotônicos/uso terapêutico , Gânglios Espinais/efeitos dos fármacos , Gânglios Espinais/metabolismo , Injeções Espinhais , Sistema de Sinalização das MAP Quinases/efeitos dos fármacos , Infarto do Miocárdio/diagnóstico por imagem , Infarto do Miocárdio/prevenção & controle , Fator de Crescimento Neural/biossíntese , Células PC12 , Técnicas de Patch-Clamp , Ratos , Ratos Sprague-Dawley , Canais de Cátion TRPV/antagonistas & inibidores , Canais de Cátion TRPV/metabolismo
3.
Pharmacology ; 103(5-6): 291-302, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30820014

RESUMO

BACKGROUND/AIMS: Rhapontigenin (RPG) is a stilben derivative and is known to bear several effects such as antiallergic, anticoagulative, hypoglycemic, antiangiogenic, and purgative. The investigation was conducted to evaluate the cardioprotective efficacy of RPG in rats having acute myocardial infarction (MI) induced by isoproterenol (ISO). METHODS: Animals were divided into 6 groups: group I (control group), group II (ISO-treated), group III (1.0 mg/kg/day RPG and ISO-treated), group IV (2.5 mg/kg/day RPG and ISO-treated), group V (5.0 mg/kg/day RPG and ISO-treated), and group VI (treated with RPG 5.0 mg/kg/day). Various cardiac stress markers, including infarct size and heart/body weight index, were investigated in animals with ISO-induced MI, such as inducible nitric oxide synthase (iNOS), creatinine kinase (CK), lactate dehydrogenase (LD), cardiac troponin-T (CTT), superoxide dismutase (SOD), and malondialdehyde. INOS, p38, caspase-3, and connexin 43 expressions were analyzed in animals. Inflammatory mediators, tissue necrosis factor-α (TNF-α) and interleukin-6 (IL-6), were detected in serum of experimental animals. RESULTS: Group I animals indicated normal levels of biochemical parameters, whereas group II animals indicated high levels of these parameters and successful induction of MI. Pretreatment of animal groups III, IV, and V with RPG revealed amelioration of infarct size, heart/body weight index, CK, LD, CTT in rats, whereas group VI animals were treated only with RPG (5.0 mg/kg/day) and not with ISO. Levels of TNF-α, IL-6, MD, SOD, p38, and iNOS expressions were significantly downregulated by RPG administration (5.0 mg/kg/day). CONCLUSION: RPG ameliorates MI caused by ISO in rats and provides cardioprotective effect, via anti-inflammatory, antioxidant, and antiapoptotic effect.


Assuntos
Cardiotônicos/farmacologia , Infarto do Miocárdio/prevenção & controle , Estresse Oxidativo/efeitos dos fármacos , Estilbenos/farmacologia , Animais , Anti-Inflamatórios/administração & dosagem , Anti-Inflamatórios/farmacologia , Antioxidantes/administração & dosagem , Antioxidantes/farmacologia , Apoptose/efeitos dos fármacos , Cardiotônicos/administração & dosagem , Modelos Animais de Doenças , Relação Dose-Resposta a Droga , Isoproterenol/toxicidade , Masculino , Ratos , Ratos Sprague-Dawley , Estilbenos/administração & dosagem
5.
Biomed Res Int ; 2019: 4870350, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30834266

RESUMO

Object: The purpose of this study was to fully assess the role of statins in the primary prevention of coronary heart disease (CHD). Methods: We searched six databases (PubMed, the Cochrane Library, Web of Science, China National Knowledge Infrastructure, Wanfang Database, and Chinese Scientific Journal Database) to identify relevant randomized controlled trials (RCTs) from inception to 31 October 2017. Two review authors independently assessed the methodological quality and analysed the data using Rev Man 5.3 software. Risk ratios and 95% confidence intervals (95% CI) were pooled using fixed/random-effects models. Funnel plots and Begg's test were conducted to assess publication bias. The quality of the evidence was evaluated using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach. Results: Sixteen RCTs with 69159 participants were included in this review. Statins can effectively decrease the occurrence of angina (RR=0.70, 95% CI: 0.58~0.85, I2 =0%), nonfatal myocardial infarction (MI) (RR=0.60, 95% CI: 0.51~0.69, I2 =14%), fatal MI (RR=0.49, 95% CI: 0.24~0.98, I2 =0%), any MI (RR=0.53, 95% CI: 0.42~0.67, I2 =0%), any coronary heart events (RR=0.73, 95% CI: 0.68~0.78, I2=0%), coronary revascularization (RR=0.66, 95% CI: 0.55~0.78, I2 = 0%), and any cardiovascular events (RR=0.77, 95% CI: 0.72~82, I2 = 0%). However, based on the current evidence, there were no significant differences in CHD deaths (RR=0.82, 95% CI: 0.66~1.02, I2=0%) and all-cause mortality (RR=0.88, 95% CI: 0.76 ~1.01, I2 =58%) between the two groups. Additionally, statins were more likely to result in diabetes (RR=1.21, 95% CI: 1.05~1.39, I2 =0%). There was no evidence of publication biases, and the quality of the evidence was considered moderate. Conclusion: Statins seemed to be beneficial for the primary prevention of CHDs but have no effect on CHD death and all-cause mortality.


Assuntos
Doença das Coronárias/tratamento farmacológico , Bases de Dados Factuais , Inibidores de Hidroximetilglutaril-CoA Redutases/uso terapêutico , Prevenção Primária , Angina Pectoris/tratamento farmacológico , Angina Pectoris/mortalidade , Angina Pectoris/patologia , Angina Pectoris/prevenção & controle , Causas de Morte , China/epidemiologia , Doença das Coronárias/mortalidade , Doença das Coronárias/patologia , Doença das Coronárias/prevenção & controle , Feminino , Humanos , Inibidores de Hidroximetilglutaril-CoA Redutases/efeitos adversos , Masculino , Infarto do Miocárdio/tratamento farmacológico , Infarto do Miocárdio/mortalidade , Infarto do Miocárdio/patologia , Infarto do Miocárdio/prevenção & controle , Acidente Vascular Cerebral/tratamento farmacológico , Acidente Vascular Cerebral/mortalidade , Acidente Vascular Cerebral/patologia , Acidente Vascular Cerebral/prevenção & controle
6.
J Pharmacol Sci ; 139(3): 193-200, 2019 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-30827890

RESUMO

Ischemia/reperfusion (I/R)-induced oxidative stress is a serious clinical problem in the reperfusion therapy for ischemic diseases. Tumstatin is an endogenous bioactive peptide cleaved from type IV collagen α3 chain. We previously reported that T3 peptide, an active subfragment of tumstatin, exerts cytoprotective effects on H2O2-induced apoptosis through the inhibition of intracellular reactive oxygen species (ROS) production in H9c2 cardiomyoblasts. In this study, we investigated whether T3 peptide has cardioprotective effects against I/R injury by using in vitro and ex vivo experimental models. H9c2 cardiomyoblasts were stimulated with oxygen and glucose deprivation (OGD) for 12 h followed by reoxygenation for 1-8 h (OGD/R; in vitro model). The cells were treated with T3 peptide (30-1000 ng/ml) during OGD. Ten minutes after the pre-perfusion of T3 peptide (300 ng/ml), Langendorff perfused rat hearts were exposed to ischemia for 30 min followed by reperfusion for 1 h (ex vivo model). T3 peptide inhibited OGD/R-induced apoptosis through the inhibition of mitochondrial ROS production and dysfunction in H9c2 cardiomyoblasts. T3 peptide also prevented I/R-induced cardiac dysfunction, arrhythmia and myocardial infarction in the perfused rat heart. In conclusion, we for the first time demonstrated that T3 peptide exerts cardioprotective effects against I/R injury.


Assuntos
Apoptose/efeitos dos fármacos , Autoantígenos/administração & dosagem , Cardiotônicos/administração & dosagem , Colágeno Tipo IV/administração & dosagem , Traumatismo por Reperfusão Miocárdica/tratamento farmacológico , Animais , Arritmias Cardíacas/etiologia , Arritmias Cardíacas/prevenção & controle , Autoantígenos/química , Autoantígenos/farmacologia , Cardiotônicos/farmacologia , Linhagem Celular , Colágeno Tipo IV/química , Colágeno Tipo IV/farmacologia , Modelos Animais de Doenças , Relação Dose-Resposta a Droga , Masculino , Infarto do Miocárdio/etiologia , Infarto do Miocárdio/prevenção & controle , Traumatismo por Reperfusão Miocárdica/complicações , Peptídeos/administração & dosagem , Peptídeos/farmacologia , Ratos , Ratos Wistar , Espécies Reativas de Oxigênio/metabolismo
7.
Trials ; 20(1): 185, 2019 Mar 28.
Artigo em Inglês | MEDLINE | ID: mdl-30922358

RESUMO

BACKGROUND: Group-randomized trials of communities often rely on the convenience of pre-existing administrative divisions, such as school district boundaries or census entities, to divide the study area into intervention and control sites. However, these boundaries may include substantial heterogeneity between regions, introducing unmeasured confounding variables. This challenge can be addressed by the creation of exchangeable intervention and control territories that are equally weighted by pertinent socio-demographic characteristics. The present study used territory design software as a novel approach to partitioning study areas for The Minnesota Heart Health Program's "Ask about Aspirin" Initiative. METHODS: Twenty-four territories were created to be similar in terms of age, sex, and educational attainment, as factors known to modify aspirin use. To promote ease of intervention administration, the shape and spread of the territories were controlled. Means of the variables used in balancing the territories were assessed as well as other factors that were not used in the balancing process. RESULTS: The analysis demonstrated that demographic characteristics did not differ significantly between the intervention and control territories created by the territory design software. CONCLUSIONS: The creation of exchangeable territories diminishes geographically based impact on outcomes following community interventions in group-randomized trials. The method used to identify comparable geographical units may be applied to a wide range of population-based health intervention trials. TRIAL REGISTRATION: National Institutes of Health (Clinical Trials.gov), Identifier: NCT02607917 . Registered on 16 November 2015.


Assuntos
Aspirina/uso terapêutico , Fármacos Cardiovasculares/uso terapêutico , Serviços de Saúde Comunitária/métodos , Sistemas de Informação Geográfica , Infarto do Miocárdio/prevenção & controle , Seleção de Pacientes , Prevenção Primária/métodos , Acidente Vascular Cerebral/prevenção & controle , Idoso , Aspirina/efeitos adversos , Fármacos Cardiovasculares/efeitos adversos , Estudos Cross-Over , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Minnesota/epidemiologia , Estudos Multicêntricos como Assunto , Infarto do Miocárdio/diagnóstico , Infarto do Miocárdio/epidemiologia , Ensaios Clínicos Controlados Aleatórios como Assunto , Fatores Socioeconômicos , Software , Acidente Vascular Cerebral/diagnóstico , Acidente Vascular Cerebral/epidemiologia
8.
J Am Acad Orthop Surg ; 27(7): 256-263, 2019 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-30897607

RESUMO

INTRODUCTION: Large cohort studies evaluating cardiac complications in patients undergoing spine surgery are lacking. The purpose of this study was to determine the incidence, timing, risk factors, and effect of cardiac complications in spine surgery by using a national database, the American College of Surgeons National Surgical Quality Improvement Program. METHODS: Patients who underwent spine surgery in the 2005 to 2012 National Surgical Quality Improvement Program database were identified. The primary outcome was an occurrence of cardiac arrest or myocardial infarction during the operation or the 30-day postoperative period. Risk factors for development of cardiac complications were identified using multivariate regression. The postoperative length of stay, 30-day readmission, and mortality were compared between patients who did and did not experience a cardiac complication. RESULTS: A total of 30,339 patients who underwent spine surgery were identified. The incidence of cardiac complications was 0.34% (95% confidence interval [CI], 0.27% to 0.40%). Of the cases in which a cardiac complication developed, 30% were diagnosed after discharge. Risk factors for the development of cardiac complications were greater age (most notably ≥80 years, relative risk [RR] = 5.53; 95% CI = 2.28 to 13.43; P < 0.001), insulin-dependent diabetes (RR = 2.58; 95% CI = 1.51 to 4.41; P = 0.002), preoperative anemia (RR = 2.46; 95% CI = 1.62 to 3.76; P < 0.001), and history of cardiac disorders and treatments (RR = 1.88; 95% CI = 1.16 to 3.07; P = 0.011). Development of a cardiac complication before discharge was associated with a greater length of stay (7.9 versus 2.6 days; P < 0.001), and a cardiac complication after discharge was associated with increased 30-day readmission (RR = 12.32; 95% CI = 8.17 to 18.59; P < 0.001). Development of a cardiac complication any time during the operation or 30-day postoperative period was associated with increased mortality (RR = 113.83; 95% CI = 58.72 to 220.68; P < 0.001). DISCUSSION: Perioperative cardiac complications were diagnosed in approximately 1 in 300 patients undergoing spine surgery. High-risk patients should be medically optimized and closely monitored through the perioperative period. LEVEL OF EVIDENCE: Level III.


Assuntos
Parada Cardíaca/epidemiologia , Complicações Intraoperatórias/epidemiologia , Infarto do Miocárdio/epidemiologia , Procedimentos Ortopédicos , Complicações Pós-Operatórias/epidemiologia , Coluna Vertebral/cirurgia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Bases de Dados Factuais , Feminino , Parada Cardíaca/mortalidade , Parada Cardíaca/prevenção & controle , Humanos , Incidência , Complicações Intraoperatórias/mortalidade , Complicações Intraoperatórias/prevenção & controle , Tempo de Internação , Masculino , Pessoa de Meia-Idade , Monitorização Fisiológica , Análise Multivariada , Infarto do Miocárdio/mortalidade , Infarto do Miocárdio/prevenção & controle , Procedimentos Ortopédicos/mortalidade , Procedimentos Ortopédicos/estatística & dados numéricos , Readmissão do Paciente , Período Perioperatório , Complicações Pós-Operatórias/mortalidade , Complicações Pós-Operatórias/prevenção & controle , Fatores de Risco , Fatores de Tempo , Adulto Jovem
9.
J Biosci ; 44(1)2019 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-30837370

RESUMO

Among the last consequences of metabolic syndrome are cardiovascular complications such as infarcts. The hypoxic heart switches its lipid-based metabolism to carbohydrates, and a glucose-insulin-potassium (GIK) solution can be the metabolic support to protect the organ. Due to the physiology and cardiac risks associated with the metabolic syndrome, we studied the effect of GIK solution during hypoxia in a metabolic syndrome model by observing the participation of glucose transporters (GLUTs). The metabolic syndrome characteristics were established by giving a 30% sucrose drinking solution to Wistar rats for 24 weeks. The GIK solution's effect on myocyte glucose uptake during hypoxia and oxygenation was observed using a colorimetric method, and Western blot technique visualized the GLUT participation. Oxygenated control myocytes consumed 1.7 +/- 0.2 µg of glucose per gram of fresh tissue per hour using the GLUT1, and during hypoxia, they incorporated 41.1% more glucose by GLUT1 and GLUT4. The GIK solution improved glucose uptake in oxygenation by 70.5% through GLUT1. In hypoxia, the uptake was 21% more than the hypoxic control group and by both GLUTs too. Oxygenated metabolic syndrome myocytes uptake was similar to control cells but achieved by both carriers in oxygenation and hypoxia. Also, the GIK solution had a better response in both oxygenation (113%) and hypoxia (71%). Despite the metabolic energy disorders of this syndrome, the GIK solution protects cardiomyocytes, in conditions of hypoxia, through the modulation of both GLUTs. So, this solution can be considered a useful resource during a heart attack in cases of metabolic syndrome.


Assuntos
Transportador de Glucose Tipo 1/genética , Transportador de Glucose Tipo 4/genética , Síndrome Metabólica/prevenção & controle , Infarto do Miocárdio/prevenção & controle , Animais , Hipóxia Celular/efeitos dos fármacos , Modelos Animais de Doenças , Metabolismo Energético/efeitos dos fármacos , Regulação da Expressão Gênica/efeitos dos fármacos , Glucose/administração & dosagem , Glucose/metabolismo , Humanos , Insulina/administração & dosagem , Síndrome Metabólica/complicações , Síndrome Metabólica/genética , Síndrome Metabólica/metabolismo , Infarto do Miocárdio/etiologia , Infarto do Miocárdio/genética , Infarto do Miocárdio/metabolismo , Miócitos Cardíacos/efeitos dos fármacos , Miócitos Cardíacos/metabolismo , Miócitos Cardíacos/patologia , Potássio/administração & dosagem , Ratos
10.
Life Sci ; 222: 140-147, 2019 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-30849417

RESUMO

AIM: To investigate the cardioprotective effects of prolonged and moderate exercise training on cellular and molecular events early after myocardial infarction. MATERIALS AND METHODS: Male Wistar rats were divided in sedentary or exercised group; both groups underwent to a myocardial infarction. All the molecular and immunohistochemical analyses on hearts of sedentary and exercised rats were performed 48 h after surgical procedure. SIRT1 and SIRT3 expression were measured and two of the pathways activated by sirtuins, p53-induced apoptosis and Forkhead boxO (FOXO)3a-induced oxidative stress, were investigated. All the experiments were performed also in presence of the SIRT inhibitor, EX527. KEY FINDINGS: Fourty-eight hours post myocardial infarction, exercise training induced the activation of SIRT1 and SIRT3 pathway reducing cardiomyocytes apoptosis and oxidative damage. Molecular data were confirmed by immunohistochemical evaluations. These effects are more evident in border infarcted zone than in the remote myocardium. SIGNIFICANCE: Exercise training is a non-pharmacological prevention strategy in cardiovascular diseases and the sirtuins family seems to be as novel and attractive target in cardioprotection.


Assuntos
Infarto do Miocárdio/metabolismo , Infarto do Miocárdio/prevenção & controle , Condicionamento Físico Animal/fisiologia , Transdução de Sinais/fisiologia , Sirtuína 1/metabolismo , Sirtuínas/metabolismo , Animais , Carbazóis/farmacologia , Masculino , Estresse Oxidativo/fisiologia , Condicionamento Físico Animal/tendências , Distribuição Aleatória , Ratos , Ratos Wistar , Comportamento Sedentário , Transdução de Sinais/efeitos dos fármacos , Sirtuína 1/antagonistas & inibidores , Fatores de Tempo
11.
Molecules ; 24(6)2019 Mar 20.
Artigo em Inglês | MEDLINE | ID: mdl-30897711

RESUMO

Oxidative stress plays an important role in the pathogenesis of myocardial infarction (MI). Schisandra chinensis bee pollen extract (SCBPE) possesses powerful antioxidant capacity. This study aimed to further explore the antioxidative and cardioprotective effects of SCBPE on acute MI induced by isoprenaline (ISO) in rats. The rats were intragastrically administrated with SCBPE (600, 1200, or 1800 mg/kg/day) and Compound Danshen dropping pills (270 mg/kg/day) for 30 days, then subcutaneously injected with ISO (65 mg/kg/day) on the 29th and 30th day. Compared with the model group, pretreatment with middle and high doses of SCBPE significantly reduced serum aspartate transaminase, lactate dehydrogenase, and creatine kinase activities and increased myocardial superoxide dismutase, glutathione peroxidase, and catalase activities. The histopathologic aspects showed that pathological heart change was found in the model group and reduced to varying degrees in the SCBPE groups. Moreover, the protein expression of nuclear factor-erythroid 2-related factor 2 (Nrf-2), heme oxygenase-1 (HO-1), and Bcl2 in the heart increased in the SCBPE groups, while that of Bax decreased compared to the model group. Besides this, uridine was isolated from S. chinensis bee pollen for the first time. This study could provide a scientific basis for using Schisandra chinensis bee pollen as a functional food for the prevention of MI.


Assuntos
Isoproterenol/toxicidade , Infarto do Miocárdio/prevenção & controle , Pólen/química , Schisandra/química , Animais , Antioxidantes/metabolismo , Glutationa Peroxidase/metabolismo , Masculino , Malondialdeído/imunologia , Malondialdeído/metabolismo , Infarto do Miocárdio/induzido quimicamente , Infarto do Miocárdio/metabolismo , Fator 2 Relacionado a NF-E2/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Ratos , Ratos Sprague-Dawley , Superóxido Dismutase/metabolismo
12.
Mol Genet Genomic Med ; 7(4): e00579, 2019 04.
Artigo em Inglês | MEDLINE | ID: mdl-30811871

RESUMO

BACKGROUND: Myocardial infarction is one of the most common life threatening diseases that may lead to renal disorders via oxidative stress and inflammation. Betaine is a safe and well-tolerated compound exhibiting beneficial antioxidant and anti-inflammatory properties. Previous studies have demonstrated protective effects of betaine against myocardial infarction and renal injury. This study aimed to investigate the protective effect of betaine on tissue structure and renal function after isoprenaline-induced myocardial infarction in rats. METHODS: Fifty Wistar strain male albino rats, weighing 200 ± 10, were selected for the study. The animals were housed individually under standard environmental conditions (Light-dark cycle, temperature and constant humidity) for 1 week. After acclimatization, they were randomly divided into five groups. G1, G2, and G3 groups received betaine at doses of 50, 150, and 250 mg/kg body weight/day via gavage for a period of 60 days. After 60 days, isoprenaline is injected subcutaneously (200 mg/kg body weight). In the isoprenaline group (G4), the rats were injected with isoprenaline (200 mg/kg body weight) and the control group (G5) received a standard diet (Without isoprenaline). Then, isoproterenol solution was used for induction of myocardial infarction. At the end, the expression of nitric oxide synthase (iNOS) protein was detected using immunohistochemical analysis and kidney tissues were assessed via histopathological analysis. In addition, serum level of TNF-α and creatinine level were measured via ELISA test and colorimetric methods, respectively. RESULTS: The results of our study indicate that isoproterenol-induced renal histopathological injury without changing creatinine level. Betaine has protective effects against renal injuries induced by isoprenaline and the expression of nitric oxide synthase (nNOS) protein showed no significant difference in all groups. Further, betaine reduced TNF-α level significantly. CONCLUSION: According to our results, betaine has protective effects on isoprenaline-induced renal failure via a decrease in TNF-α level and nitric oxide synthase.


Assuntos
Betaína/uso terapêutico , Cardiotônicos/uso terapêutico , Infarto do Miocárdio/tratamento farmacológico , Insuficiência Renal/tratamento farmacológico , Animais , Betaína/farmacologia , Cardiotônicos/farmacologia , Isoproterenol/toxicidade , Rim/efeitos dos fármacos , Rim/metabolismo , Masculino , Infarto do Miocárdio/etiologia , Infarto do Miocárdio/prevenção & controle , Miócitos Cardíacos/efeitos dos fármacos , Miócitos Cardíacos/metabolismo , Óxido Nítrico Sintase Tipo II/metabolismo , Ratos , Ratos Wistar , Insuficiência Renal/etiologia , Insuficiência Renal/prevenção & controle , Fator de Necrose Tumoral alfa/metabolismo
14.
Vnitr Lek ; 64(12): 1148-1152, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30704249

RESUMO

Bilirubin is the major catabolic product of heme degradation. It has long been regarded as an unimportant waste product. However, within the last twenty-five years, it has been demonstrated to play a very important role in maintaining the bodys redox equilibrium. Disturbances of this equilibrium - increased oxidative stress - are currently considered one of the major risk factors for the development of non-communicable diseases. Although the exact mechanism is not known, a number of human studies have proved a reduced incidence of a number of (especially cardiovascular but also cancer) diseases in individuals with mildly elevated bilirubin concentrations. Key words: bilirubin - cardiovascular disease - morbidity - mortality.


Assuntos
Bilirrubina , Infarto do Miocárdio , Bilirrubina/fisiologia , Humanos , Infarto do Miocárdio/prevenção & controle , Estresse Oxidativo , Resíduos
16.
Int J Mol Sci ; 20(2)2019 Jan 11.
Artigo em Inglês | MEDLINE | ID: mdl-30641885

RESUMO

The effects of remote ischemic preconditioning (RIPC) in cardiac surgery have been inconsistent. We investigated whether anesthesia or beta-blockers interfere with RIPC cardioprotection. Fifty patients undergoing cardiac surgery were randomized to receive limb RIPC (four cycles of 5-min of upper arm cuff inflation/deflation) in the awake state (no-anesthesia; n = 17), or under sevoflurane (n = 17) or propofol (n = 16) anesthesia. In a separate crossover study, 11 healthy volunteers received either carvedilol or no medication prior to RIPC. Plasma dialysates were obtained and perfused through an isolated male Sprague⁻Dawley rat heart subjected to 30-min ischemia/60-min reperfusion, following which myocardial infarct (MI) size was determined. In the cardiac surgery study, pre-RIPC MI sizes were similar among the groups (39.7 ± 4.5% no-anesthesia, 38.9 ± 5.3% sevoflurane, and 38.6 ± 3.6% propofol). However, post-RIPC MI size was reduced in the no-anesthesia group (27.5 ± 8.0%; p < 0.001), but not in the anesthesia groups (35.7 ± 6.9% sevoflurane and 35.8 ± 5.8% propofol). In the healthy volunteer study, there was a reduction in MI size with RIPC in the no-carvedilol group (41.7 ± 4.3% to 30.6 ± 8.5%; p < 0.0001), but not in the carvedilol group (41.0 ± 4.0% to 39.6 ± 5.6%; p = 0.452). We found that the cardioprotective effects of limb RIPC were abolished under propofol or sevoflurane anesthesia and in the presence of carvedilol therapy.


Assuntos
Carvedilol/efeitos adversos , Extremidades/irrigação sanguínea , Precondicionamento Isquêmico/métodos , Infarto do Miocárdio/prevenção & controle , Propofol/efeitos adversos , Sevoflurano/efeitos adversos , Adulto , Idoso , Animais , Procedimentos Cirúrgicos Cardíacos , Carvedilol/administração & dosagem , Estudos de Casos e Controles , Estudos Cross-Over , Modelos Animais de Doenças , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Propofol/administração & dosagem , Distribuição Aleatória , Ratos , Ratos Sprague-Dawley , Sevoflurano/administração & dosagem
17.
Cardiovasc Drugs Ther ; 33(1): 13-23, 2019 02.
Artigo em Inglês | MEDLINE | ID: mdl-30637549

RESUMO

PURPOSE: Necroptosis is an important form of cell death following myocardial ischemia/reperfusion (I/R) and phosphoglycerate mutase 5 (PGAM5) functions as the convergent point for multiple necrosis pathways. This study aims to investigate whether inhibition of PGAM5 could reduce I/R-induced myocardial necroptosis and the underlying mechanisms. METHODS: The SD rat hearts (or H9c2 cells) were subjected to 1-h ischemia (or 10-h hypoxia) plus 3-h reperfusion (or 4-h reoxygenation) to establish the I/R (or H/R) injury model. The myocardial injury was assessed by the methods of biochemistry, H&E (hematoxylin and eosin), and PI/DAPI (propidium iodide/4',6-diamidino-2-phenylindole) staining, respectively. Drug interventions or gene knockdown was used to verify the role of PGAM5 in I/R (or H/R)-induced myocardial necroptosis and possible mechanisms. RESULTS: The I/R-treated heart showed the injuries (increase in infarct size and creatine kinase release), upregulation of PGAM5, dynamin-related protein 1 (Drp1), p-Drp1-S616, and necroptosis-relevant proteins (RIPK1/RIPK3, receptor-interacting protein kinase 1/3; MLKL, mixed lineage kinase domain-like); these phenomena were attenuated by inhibition of PGAM5 or RIPK1. In H9c2 cells, H/R treatment elevated the levels of PGAM5, RIPK1, RIPK3, MLKL, Drp1, and p-Drp1-S616 and induced mitochondrial dysfunctions (elevation in mitochondrial membrane potential and ROS level) and cellular necrosis (increase in LDH release and the ratio of PI+/DAPI+ cells); these effects were blocked by inhibition or knockdown of PGAM5. CONCLUSIONS: Inhibition of PGAM5 can reduce necroptosis in I/R-treated rat hearts through suppression of Drp1; there is a positive feedback between RIPK1 and PGAM5, and PGAM5 might serve as a novel therapeutic target for prevention of myocardial I/R injury.


Assuntos
DNA (Citosina-5-)-Metiltransferase 1/metabolismo , Inibidores Enzimáticos/farmacologia , Glicolatos/farmacologia , Proteínas Mitocondriais/antagonistas & inibidores , Infarto do Miocárdio/prevenção & controle , Traumatismo por Reperfusão Miocárdica/prevenção & controle , Miócitos Cardíacos/efeitos dos fármacos , Fosfoglicerato Mutase/antagonistas & inibidores , Fosfoproteínas Fosfatases/antagonistas & inibidores , Animais , Morte Celular/efeitos dos fármacos , Linhagem Celular , Modelos Animais de Doenças , Regulação para Baixo , Masculino , Proteínas Mitocondriais/genética , Proteínas Mitocondriais/metabolismo , Infarto do Miocárdio/enzimologia , Infarto do Miocárdio/patologia , Traumatismo por Reperfusão Miocárdica/enzimologia , Traumatismo por Reperfusão Miocárdica/patologia , Miócitos Cardíacos/enzimologia , Miócitos Cardíacos/patologia , Fosfoglicerato Mutase/genética , Fosfoglicerato Mutase/metabolismo , Fosfoproteínas Fosfatases/genética , Fosfoproteínas Fosfatases/metabolismo , Proteínas Serina-Treonina Quinases/metabolismo , Ratos Sprague-Dawley , Transdução de Sinais/efeitos dos fármacos
18.
Nat Commun ; 10(1): 187, 2019 01 14.
Artigo em Inglês | MEDLINE | ID: mdl-30643122

RESUMO

Pharmacologic activation of stress-responsive signaling pathways provides a promising approach for ameliorating imbalances in proteostasis associated with diverse diseases. However, this approach has not been employed in vivo. Here we show, using a mouse model of myocardial ischemia/reperfusion, that selective pharmacologic activation of the ATF6 arm of the unfolded protein response (UPR) during reperfusion, a typical clinical intervention point after myocardial infarction, transcriptionally reprograms proteostasis, ameliorates damage and preserves heart function. These effects were lost upon cardiac myocyte-specific Atf6 deletion in the heart, demonstrating the critical role played by ATF6 in mediating pharmacologically activated proteostasis-based protection of the heart. Pharmacological activation of ATF6 is also protective in renal and cerebral ischemia/reperfusion models, demonstrating its widespread utility. Thus, pharmacologic activation of ATF6 represents a proteostasis-based therapeutic strategy for ameliorating ischemia/reperfusion damage, underscoring its unique translational potential for treating a wide range of pathologies caused by imbalanced proteostasis.


Assuntos
Fator 6 Ativador da Transcrição/metabolismo , Infarto Cerebral/prevenção & controle , Nefropatias/prevenção & controle , Infarto do Miocárdio/prevenção & controle , Substâncias Protetoras/farmacologia , Traumatismo por Reperfusão/tratamento farmacológico , Fator 6 Ativador da Transcrição/genética , Animais , Animais Recém-Nascidos , Células Cultivadas , Infarto Cerebral/etiologia , Infarto Cerebral/patologia , Modelos Animais de Doenças , Retículo Endoplasmático/metabolismo , Feminino , Ventrículos do Coração/patologia , Humanos , Rim/irrigação sanguínea , Rim/patologia , Nefropatias/etiologia , Nefropatias/patologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Infarto do Miocárdio/etiologia , Infarto do Miocárdio/patologia , Miócitos Cardíacos , Cultura Primária de Células , Substâncias Protetoras/uso terapêutico , Proteostase/efeitos dos fármacos , Ratos , Traumatismo por Reperfusão/etiologia , Resultado do Tratamento , Resposta a Proteínas não Dobradas/efeitos dos fármacos
19.
Nutrients ; 11(1)2019 Jan 06.
Artigo em Inglês | MEDLINE | ID: mdl-30621358

RESUMO

Type 2 diabetic women have a high risk of mortality via myocardial infarction even with anti-diabetic treatments. Resveratrol (RSV) is a natural polyphenol, well-known for its antioxidant property, which has also shown interesting positive effects on mitochondrial function. Therefore, we aim to investigate the potential protective effect of 1 mg/kg/day of RSV on high energy compounds, during myocardial ischemia-reperfusion in type 2 diabetic female Goto-Kakizaki (GK) rats. For this purpose, we used 31P magnetic resonance spectroscopy in isolated perfused heart experiments, with a simultaneous measurement of myocardial function and coronary flow. RSV enhanced adenosine triphosphate (ATP) and phosphocreatine (PCr) contents in type 2 diabetic hearts during reperfusion, in combination with better functional recovery. Complementary biochemical analyses showed that RSV increased creatine, total adenine nucleotide heart contents and citrate synthase activity, which could be involved in better mitochondrial functioning. Moreover, improved coronary flow during reperfusion by RSV was associated with increased eNOS, SIRT1, and P-Akt protein expression in GK rat hearts. In conclusion, RSV induced cardioprotection against ischemia-reperfusion injury in type 2 diabetic female rats via increased high energy compound contents and expression of protein involved in NO pathway. Thus, RSV presents high potential to protect the heart of type 2 diabetic women from myocardial infarction.


Assuntos
Diabetes Mellitus Tipo 2/complicações , Metabolismo Energético/efeitos dos fármacos , Traumatismo por Reperfusão Miocárdica/prevenção & controle , Óxido Nítrico Sintase Tipo III/genética , Resveratrol/administração & dosagem , Sirtuína 1/genética , Trifosfato de Adenosina/análise , Animais , Cardiotônicos , Cardiomiopatias Diabéticas/prevenção & controle , Feminino , Expressão Gênica/efeitos dos fármacos , Espectroscopia de Ressonância Magnética , Infarto do Miocárdio/prevenção & controle , Traumatismo por Reperfusão Miocárdica/genética , Miocárdio/química , Óxido Nítrico/metabolismo , Fosfocreatina/análise , Ratos , Ratos Wistar
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