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1.
Zhejiang Da Xue Xue Bao Yi Xue Ban ; 50(1): 106-112, 2021 Feb 25.
Artigo em Inglês | MEDLINE | ID: mdl-34117854

RESUMO

:To investigate the effect of transient receptor potential melastatin 2 (TRPM2) inhibitor A10 on oxygen glucose deprivation/reperfusion (OGD/R) injury in SH-SY5Y cells.:Human neuroblastoma SH-SY5Y cells were subject to OGD/R injury,and then were divided into blank control group,model control group and A10 group randomly. The cell survival rate was detected by cell counting kit 8 (CCK-8); the level of cellular reactive oxygen species (ROS) was detected by reactive oxygen detection kit; the mitochondrial membrane potential was detected by tetramethylrhodamine (TMRM) method; the number of apoptotic cells was detected by TUNEL apoptosis assay kit; the protein expression level of cleaved caspase 3 was detected by Western blot.:Compared with 3,20,30,50, has lower cytotoxicity and better inhibition effect on channel activity. Compared with the model control group,ROS level was reduced,the mitochondrial membrane potential was improved,the number of apoptosis cells was reduced ,and the expression of cleaved caspase 3 was significantly reduced in the A10 group(all <0.05). : A10 can alleviate cell damage after OGD/R by inhibiting TRPM2 channel function,reducing extracellular calcium influx,reducing cell ROS levels,stabilizing mitochondrial membrane potential levels,and reducing apoptosis.


Assuntos
Glucose , Canais de Cátion TRPM , Apoptose , Benzenoacetamidas , Sobrevivência Celular , Humanos , Oxigênio/metabolismo , Piperidonas , Espécies Reativas de Oxigênio/metabolismo , Reperfusão
2.
Zhonghua Wei Zhong Bing Ji Jiu Yi Xue ; 33(5): 578-581, 2021 May.
Artigo em Chinês | MEDLINE | ID: mdl-34112296

RESUMO

OBJECTIVE: To explore the selection of strategies for early reperfusion therapy and its impact on prognosis in patients with acute ST segment elevation myocardial infarction (STEMI). METHODS: The treatment data and 3-year follow-up results of acute myocardial infarction (AMI) patients in 49 hospitals in Hebei Province from January to December 2016 were collected. Patients with STEMI who received either intravenous thrombolytic therapy (ITT) or primary percutaneous coronary intervention (PPCI) within 12 hours of onset were enrolled. Baseline data, the time from the first diagnosis to the start of reperfusion (FMC2N for ITT patients and FMC2B for PPCI patients), vascular recanalization rate, in-hospital mortality, 1-year mortality, and 3-year mortality were compared between ITT and PPCI groups. The efficacy and prognosis of ITT and PPCI at different starting time of reperfusion (FMC2N ≤ 30 minutes, FMC2N > 30 minutes, FMC2B ≤ 120 minutes, FMC2B > 120 minutes) were analyzed. RESULTS: A total of 1 371 STEMI patients treated with ITT or PPCI were selected, including 300 patients in the ITT group and 1 071 patients in the PPCI group. 1 055 patients were actually followed up (205 patients in the ITT group and 850 patients in the PPCI group), with a rate of 79.4%. There were no significant differences in age, gender, and previous history between the two groups. The time from the first diagnosis to the start of reperfusion in the ITT group was shorter than that in the PPCI group [minutes: 63 (38, 95) vs. 95 (60, 150), U = -9.286, P = 0.000], but was significantly longer than the guideline standard. Compared with the ITT group, the vascular recanalization rate in the PPCI group was higher [95.5% (1 023/1 071) vs. 88.3% (265/300), P < 0.01], and in-hospital mortality was lower [2.1% (22/1 071) vs. 6.7% (20/300), P < 0.01], but there were no significant differences in the 1-year mortality and 3-year mortality [5.3% (45/850) vs. 4.4% (9/205), 9.5% (81/850) vs. 9.3% (19/205), both P > 0.05]. Between ITT group and PPCI group with different reperfusion starting time, the FMC2N > 30 minutes group had the lowest vascular recanalization rate and the highest in-hospital mortality. Pairwise comparison showed that the vascular recanalization rate of the FMC2B ≤ 120 minutes group and the FMC2B > 120 minutes group were significantly higher than those of the FMC2N > 30 minutes group [95.5% (654/685), 95.6% (369/386) vs. 88.0% (220/250), both P < 0.008], the in-hospital mortality was significantly lower than that of the FMC2N > 30 minutes group [2.0% (14/685), 2.1% (8/386) vs. 7.6% (19/250), both P < 0.008]. There was no significant difference in 1-year mortality (χ2 = 2.507, P = 0.443) and 3-year mortality (χ2 = 2.204, P = 0.522) among the four groups. CONCLUSIONS: For STEMI patients within 12 hours of onset, reperfusion therapy should be performed as soon as possible. PPCI showed higher infarct related artery opening rate and lower in-hospital mortality compared with ITT, and had no effect on 1-year and 3-year mortality.


Assuntos
Intervenção Coronária Percutânea , Infarto do Miocárdio com Supradesnível do Segmento ST , Hospitais , Humanos , Prognóstico , Reperfusão , Infarto do Miocárdio com Supradesnível do Segmento ST/cirurgia , Resultado do Tratamento
3.
J Stroke Cerebrovasc Dis ; 30(7): 105831, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-33940364

RESUMO

OBJECTIVES: Cardiocerebral infarction (CCI) is the rare occurrence of acute ischemic stroke (AIS) and acute myocardial infarction (AMI), either at the same time (simultaneous or synchronous) or one after the other (metachronous). The aim of this study is to describe the clinical profile, management and treatment outcomes of patients with CCI. MATERIALS AND METHODS: This is a 3-year cross-sectional study of patients with CCI describing their clinical presentation, management, and outcomes. The primary outcome measures were all-cause mortality and functional outcome measured with the modified Rankin Scale score (mRS) at discharge and at 30 days post-CCI. We also described the frequency of major and minor hemorrhagic events. RESULTS: Out of 1683 AIS patients and 1983 AMI patients admitted during our time period, 29 patients fulfilled the inclusion criteria (mean age 60 ±12, 79% males, median admission NIHSS 16 [range 1-26]). Of these, 20 (69%) had metachronous CCI while 9 (31%) had synchronous CCI. Most of the patients were given antithrombotics and only 14% were given reperfusion therapies. The all-cause mortality is 45% and 69% of which were cardiovascular deaths. Seventeen and 21% of CCI patients had a good functional outcome on discharge and at 30 days from CCI onset respectively. A total of 8 (28%) patients had hemorrhagic events. CONCLUSIONS: We present the largest single institutional series showing the prevalence rate of cardiocerebral infarction to be 0.79% (0.55% for metachronous, 0.25% for synchronous), with patients presenting as moderate-severe acute ischemic strokes and high-risk acute myocardial infarction. These patients have a high mortality rate with a significant proportion having cardiovascular deaths.


Assuntos
AVC Isquêmico/epidemiologia , Infarto do Miocárdio/epidemiologia , Adulto , Idoso , Estudos Transversais , Diabetes Mellitus/epidemiologia , Avaliação da Deficiência , Feminino , Fibrinolíticos/uso terapêutico , Estado Funcional , Humanos , Hipertensão/epidemiologia , AVC Isquêmico/diagnóstico , AVC Isquêmico/mortalidade , Masculino , Pessoa de Meia-Idade , Infarto do Miocárdio/diagnóstico , Infarto do Miocárdio/mortalidade , Infarto do Miocárdio/terapia , Prevalência , Recuperação de Função Fisiológica , Reperfusão , Estudos Retrospectivos , Medição de Risco , Fatores de Risco , Fumar/efeitos adversos , Fumar/epidemiologia , Resultado do Tratamento
4.
J Vis Exp ; (170)2021 04 18.
Artigo em Inglês | MEDLINE | ID: mdl-33938886

RESUMO

Blood flow recovery is a critical outcome measure after experimental hindlimb ischemia or ischemia-reperfusion. Laser Doppler perfusion imaging (LDPI) is a common, noninvasive, repeatable method for assessing blood flow recovery. The technique calculates overall blood flow in the sampled tissue from the Doppler shift in frequency caused when a laser hits moving red blood cells. Measurements are expressed in arbitrary perfusion units, so the contralateral non-intervened upon leg is usually used to help control measurements. Measurement depth is in the range of 0.3-1 mm; for hindlimb ischemia, this means that dermal perfusion is assessed. Dermal perfusion is dependent on several factors-most importantly skin temperature and anesthetic agent, which must be carefully controlled to result in reliable readings. Furthermore, hair and skin pigmentation can alter the ability of the laser to either reach or penetrate to the dermis. This article demonstrates the technique of LDPI in the mouse hindlimb.


Assuntos
Membro Posterior/diagnóstico por imagem , Animais , Hemodinâmica , Membro Posterior/irrigação sanguínea , Isquemia/diagnóstico por imagem , Isquemia/fisiopatologia , Fluxometria por Laser-Doppler , Lasers , Camundongos , Perfusão/métodos , Fluxo Sanguíneo Regional , Reperfusão
5.
Acta Cir Bras ; 36(3): e360306, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33978062

RESUMO

PURPOSE: To evaluate the preventive cardioprotective effects of resveratrol and grape products, such as grape juice and red wine, in animal model of cardiac ischemia and reperfusion. METHODS: Male Wistar rats orally pretreated for 21-days with resveratrol and grape products were anesthetized and placed on mechanical ventilation to surgically induce cardiac ischemia and reperfusion by obstruction (ischemia) followed by liberation (reperfusion) of blood circulation in left descending coronary artery. These rats were submitted to the electrocardiogram (ECG) analysis to evaluate the effects of pretreatment with resveratrol and grape products on the incidence of ventricular arrhythmias (VA), atrioventricular block (AVB) and lethality (LET) resulting from cardiac ischemia and reperfusion. RESULTS: It was observed that the incidence of AVB was significantly lower in rats pretreated with resveratrol (25%), grape juice (37.5%) or red wine (12.5%) than in rats treated with saline solution (80%) or ethanol (80%). Similarly, incidence of LET was also significantly lower in rats pretreated with resveratrol (25%), grape juice (25%) or red wine (0%) than in rats treated with saline solution (62.5%) or ethanol (75%). CONCLUSIONS: These results indicate that the cardioprotective response stimulated by resveratrol and grape products prevents the lethal cardiac arrhythmias in animal model of ischemia and reperfusion, supporting the idea that this treatment can be beneficial for prevention of severe cardiac arrhythmias in patients with ischemic heart disease.


Assuntos
Estilbenos , Vitis , Animais , Arritmias Cardíacas/etiologia , Arritmias Cardíacas/prevenção & controle , Humanos , Isquemia , Masculino , Ratos , Ratos Wistar , Reperfusão , Resveratrol/farmacologia , Estilbenos/farmacologia
6.
Clinics (Sao Paulo) ; 76: e2513, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33978073

RESUMO

OBJECTIVES: The current study compared the impact of pretreatment with melatonin and N-acetylcysteine (NAC) on the prevention of rat lung damage following intestinal ischemia-reperfusion (iIR). METHODS: Twenty-eight Wistar rats were subjected to intestinal ischemia induced by a 60 min occlusion of the superior mesenteric artery, followed by reperfusion for 120 min. Animals were divided into the following groups (n=7 per group): sham, only abdominal incision; SS+iIR, pretreated with saline solution and iIR; NAC+iIR, pretreated with NAC (20 mg/kg) and iIR; MEL+iIR, pretreated with melatonin (20 mg/kg) and iIR. Oxidative stress and inflammatory mediators were measured and histological analyses were performed in the lung tissues. RESULTS: Data showed a reduction in malondialdehyde (MDA), myeloperoxidase (MPO), and TNF-alpha in the animals pretreated with NAC or MEL when compared to those treated with SS+iIR (p<0.05). An increase in superoxide dismutase (SOD) levels in the NAC- and MEL-pretreated animals as compared to the SS+iIR group (34±8 U/g of tissue; p<0.05) was also observed. TNF-α levels were lower in the MEL+iIR group (91±5 pg/mL) than in the NAC+iIR group (101±6 pg/mL). Histological analysis demonstrated a higher lung lesion score in the SS+iIR group than in the pretreated groups. CONCLUSION: Both agents individually provided tissue protective effect against intestinal IR-induced lung injury, but melatonin was more effective in ameliorating the parameters analyzed in this study.


Assuntos
Lesão Pulmonar Aguda , Melatonina , Traumatismo por Reperfusão , Acetilcisteína/uso terapêutico , Lesão Pulmonar Aguda/etiologia , Lesão Pulmonar Aguda/prevenção & controle , Animais , Isquemia , Melatonina/uso terapêutico , Ratos , Ratos Wistar , Reperfusão , Traumatismo por Reperfusão/prevenção & controle
7.
Artigo em Russo | MEDLINE | ID: mdl-34037360

RESUMO

The narrative review discusses the data on efficacy and safety of reperfusion therapy (RT) and neuroprotective therapy in ischemic stroke. The influence of therapy on mortality, residual neurologic deficit and disability is analyzed. It was shown that RT (thrombolysis or mechanical thromboextraction) leads to significant decrease of residual neurologic deficit or disability. The influence of RT on mortality is controversial. There is some evidence that RT can increase early mortality due to hemorrhagic complications. Neuroprotective therapy is much less studied in stroke but is recognized as safe. Neuroprotective therapy (i.e. cerebrolysin) can diminish residual neurologic deficit and disability, while it has no influence on mortality.


Assuntos
Isquemia Encefálica , AVC Isquêmico , Fármacos Neuroprotetores , Acidente Vascular Cerebral , Isquemia Encefálica/tratamento farmacológico , Humanos , Neuroproteção , Fármacos Neuroprotetores/uso terapêutico , Reperfusão , Acidente Vascular Cerebral/tratamento farmacológico , Terapia Trombolítica , Resultado do Tratamento
8.
Biomed Res Int ; 2021: 6626604, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33997031

RESUMO

Objective: Currently, the standard treatment modality for patients with acute ischemic stroke (AIS) presenting with isolated M2 occlusions is not specific. We therefore assessed the difference in treatment outcomes for patients with isolated M2 occlusions. Methods: We retrospectively analyzed consecutive patients with AIS presenting with isolated M2 occlusions from October 1, 2018, to June 30, 2020. Patients were divided into 3 groups based on the treatments they received: no reperfusion therapy (NRT), intravenous thrombolysis treatment (IVT), and endovascular intervention (EVT), which comprised IVT in conjunction with EVT or EVT alone. The primary outcomes were improvements in modified Rankin Scale (mRS) scores at 90 days and National Institutes of Health Stroke Scale (NIHSS) scores at 24 hours after treatment compared with the baseline. The secondary efficacy outcome comprised a good outcome rate defined as a 90 - day mRS score ≤ 2, final infarct volume (FIV), 90-day mortality rate, and successful recanalization rate, which was defined as a modified thrombolysis in cerebral infarction score ≥ 2b. Safety outcomes included symptomatic intracerebral hemorrhage and procedure-related complications. Results: Seventy patients were enrolled and divided into 3 groups: the NRT group (n = 25), IVT group (n = 27), and EVT group (n = 18). Twenty-four-hour posttreatment NIHSS scores were substantially decreased by EVT compared with NRT (adjusted ß -4.01, 95% confidence interval [CI] -6.60 to -1.43; P = 0.003) or IVT (adjusted ß, -3.61 [95% CI, -6.45 to -0.77]; P = 0.013). Compared with the outcomes observed after NRT, patients who received EVT were more likely to achieve lower 90-day mRS scores (adjusted ß, -1.42 [95% CI, -2.66 to -0.63]; P = 0.007), higher good outcome rates (adjusted odds ratio, 8.73 [95% CI, 1.43-53.24]; P = 0.019), and smaller FIVs (adjusted ß, -29.66 [95% CI, -59.73 to 0.42]; P = 0.048). The recanalization rate of EVT was high (88.89%), and procedure-related complications were rare (5.56%). Conclusions: For acute, isolated M2 occlusions, EVT could dramatically and rapidly improve neurological deficits with high safety and effectiveness. These changes were observed at 24 hours after treatment and were maintained over the long term.


Assuntos
Infarto Cerebral , Procedimentos Endovasculares , AVC Isquêmico , Terapia Trombolítica , Idoso , Idoso de 80 Anos ou mais , Hemorragia Cerebral , Infarto Cerebral/mortalidade , Infarto Cerebral/fisiopatologia , Infarto Cerebral/terapia , Feminino , Humanos , AVC Isquêmico/mortalidade , AVC Isquêmico/fisiopatologia , AVC Isquêmico/terapia , Masculino , Reperfusão , Estudos Retrospectivos , Resultado do Tratamento
9.
F1000Res ; 10: 242, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34046164

RESUMO

Cerebral ischemic stroke is a leading cause of death and disability, but current pharmacological therapies are limited in their utility and effectiveness. In vitro and in vivo models of ischemic stroke have been developed which allow us to further elucidate the pathophysiological mechanisms of injury and investigate potential drug targets. In vitro models permit mechanistic investigation of the biochemical and molecular mechanisms of injury but are reductionist and do not mimic the complexity of clinical stroke. In vivo models of ischemic stroke directly replicate the reduction in blood flow and the resulting impact on nervous tissue. The most frequently used in vivo model of ischemic stroke is the intraluminal suture middle cerebral artery occlusion (iMCAO) model, which has been fundamental in revealing various aspects of stroke pathology. However, the iMCAO model produces lesion volumes with large standard deviations even though rigid surgical and data collection protocols are followed. There is a need to refine the MCAO model to reduce variability in the standard outcome measure of lesion volume. The typical approach to produce vessel occlusion is to induce an obstruction at the origin of the middle cerebral artery and reperfusion is reliant on the Circle of Willis (CoW). However, in rodents the CoW is anatomically highly variable which could account for variations in lesion volume. Thus, we developed a refined approach whereby reliance on the CoW for reperfusion was removed. This approach improved reperfusion to the ischemic hemisphere, reduced variability in lesion volume by 30%, and reduced group sizes required to determine an effective treatment response by almost 40%. This refinement involves a methodological adaptation of the original surgical approach which we have shared with the scientific community via publication of a visualised methods article and providing hands-on training to other experimental stroke researchers.


Assuntos
Isquemia Encefálica , Acidente Vascular Cerebral , Animais , Modelos Animais de Doenças , Infarto da Artéria Cerebral Média , Reperfusão
10.
Clin Med (Lond) ; 21(3): 215-221, 2021 05.
Artigo em Inglês | MEDLINE | ID: mdl-33947658

RESUMO

This article aims to provide a comprehensive overview of key advances on various aspects of hyper-acute management of acute ischaemic stroke. These include neuroimaging, acute stroke unit care, management of blood pressure, reperfusion therapy including intravenous thrombolysis, mechanical thrombectomy and decompressive hemicraniectomy for malignant stroke syndrome. The challenge ahead is to ensure these evidence-based treatments are now being delivered and implemented to maximise the benefits across the population.


Assuntos
Isquemia Encefálica , AVC Isquêmico , Acidente Vascular Cerebral , Isquemia Encefálica/terapia , Humanos , Reperfusão , Acidente Vascular Cerebral/terapia , Trombectomia , Terapia Trombolítica
11.
J Stroke Cerebrovasc Dis ; 30(7): 105796, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-33887664

RESUMO

INTRODUCTION: Novel machine learning (ML) methods are being investigated across medicine for their predictive capabilities while boasting increased adaptability and generalizability. In our study, we compare logistic regression with machine learning for feature importance analysis and prediction in first-pass reperfusion. METHODS: We retrospectively identified cases of ischemic stroke treated with mechanical thrombectomy (MT) at our institution from 2012-2018. Significant variables used in predictive modeling were demographic characteristics, medical history, admission NIHSS, and stroke characteristics. Outcome was binarized TICI on first pass (0-2a vs 2b-3). Shapley feature importance plots were used to identify variables that strongly affected outcomes. RESULTS: Accuracy for the Random Forest and SVM models were 67.1% compared to 65.8% for the logistic regression model. Brier score was lower for the Random Forest model (0.329 vs 0.342) indicating better predictive capability. Other supervised learning models performed worse than the logistic regression model, with accuracy of 56.2% for Naïve Bayes and 61.6% for XGBoost. Shapley plots for the Random Forest model showed use of aspiration, hyperlipidemia, hypertension, use of stent retriever, and time between symptom onset and catheterization as the top five predictors of first pass reperfusion. CONCLUSION: Use of machine learning models, such as Random Forest, for the study of MT outcomes, is more accurate than logistic regression for our dataset, and identifies new factors that contribute to achieving first pass reperfusion. The benefits of machine learning, such as improved predictive capabilities, integration of new data, and generalizability, establish ML as the preferred model for studying outcomes in stroke.


Assuntos
AVC Isquêmico/terapia , Aprendizado de Máquina , Reperfusão , Trombectomia , Circulação Cerebrovascular , Feminino , Humanos , AVC Isquêmico/diagnóstico , AVC Isquêmico/fisiopatologia , Masculino , Reperfusão/efeitos adversos , Estudos Retrospectivos , Medição de Risco , Fatores de Risco , Trombectomia/efeitos adversos , Resultado do Tratamento
12.
In Vivo ; 35(3): 1537-1543, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33910832

RESUMO

BACKGROUND/AIM: Neuropathic pain and neuropathy is commonly seen after ischemia-reperfusion injuries. Our aim was to evaluate the effect of lutein on ischemia-reperfusion (I/R)-induced vasculitic neuropathic pain and neuropathy in rats. MATERIALS AND METHODS: An hour before anesthesia, 6 Albino Wistar male rats with I/R were orally administered with 1 mg/kg lutein (LIR group). Two groups of 6 such rats who underwent surgery were provided with 0.5 ml distilled water (as solvent) either via oral administration (SIR group) or by gavage (sham group or SG). One hour following the administration, the later femoral arteries of the LIR and SIR rats were closed using a sterile silk thread and ischemia was induced in the sciatic nerve for 4 h, followed by reperfusion for 24 h. The femoral artery of the SG group was not closed with suture. Next, 1 mg/kg lutein was re-administered only to the LIR group for 1 h, followed by measurement of the paw pain thresholds by the Basile Algesimeter. The levels of malondialdehyde (MDA), total glutathione (tGSH), nuclear factor-kB (NF-κB), and tumor necrosis factor-alpha (TNF-α) in the sciatic nerve tissues were measured, and the tissues were histopathologically examined. RESULTS: We found that the MDA, NF-κB, and TNF-α levels were higher and the tGSH level was lower in the SIR group relative to those in the LIR group, and the differences were statistically significant. Significant histopathological damage was noted in the SIR group, whereas the LIR group demonstrated protection from oxidative damage. CONCLUSION: Lutein is potentially useful in the treatment of I/R-related neuropathy and neuropathic pain.


Assuntos
Neuralgia , Traumatismo por Reperfusão , Animais , Isquemia , Luteína/farmacologia , Masculino , Malondialdeído , Neuralgia/tratamento farmacológico , Neuralgia/etiologia , Ratos , Ratos Wistar , Reperfusão , Traumatismo por Reperfusão/complicações , Traumatismo por Reperfusão/tratamento farmacológico , Fator de Necrose Tumoral alfa
13.
Adv Clin Exp Med ; 30(4): 413-420, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-33908199

RESUMO

BACKGROUND: Myocardial ischemia-reperfusion (I/R) injury is still thought to be an unsolved puzzle that may lead to reperfusion arrhythmias and sudden cardiac death. Inflammation plays a key role in myocardial I/R. Studies have indicated that purinoceptor 2Y12 (P2Y12) antagonists have anti-inflammatory properties that are cardioprotective. OBJECTIVES: In this study, we explored whether inhibition of P2Y12 in macrophages could reduce cardiac inflammation and attenuate reperfusion arrhythmias after myocardial I/R. MATERIAL AND METHODS: Rats were randomly divided into 4 groups: group A (control + vehicle); group B (control + P2Y12 shRNA lentiviral vector); group C (myocardial I/R + vehicle); and group D (myocardial I/R + P2Y12 shRNA lentiviral vector). Infarct size, reperfusion arrhythmias, and P2Y12 and platelet endothelial cell adhesion molecule-1 (CD31) protein expression were measured. RESULTS: The incidence of reperfusion ventricular tachycardia and fibrillation (VT/VF) was 90% in the I/R group, while it was reduced to 50% by P2Y12 shRNA treatment. Ionized calcium binding adapter molecule 1 and P2Y12 immunoreactivity in the myocardial I/R + P2Y12 shRNA group was lower compared to the myocardial I/R group. P2Y12 shRNA treatment increased α-smooth muscle actin (α-SMA) and CD31 protein expression, as evidence by western blot and immunohistochemistry analyses (0.31 ±0.01 compared to 0.26 ±0.008, group D compared to group C, p < 0.05). CONCLUSIONS: Inhibition of P2Y12 in macrophages improved reperfusion arrhythmias in our rat I/R model, suggesting that blocking P2Y12 could decrease the inflammatory response after cardiac perfusion.


Assuntos
Traumatismo por Reperfusão Miocárdica , Animais , Arritmias Cardíacas/prevenção & controle , Macrófagos , Traumatismo por Reperfusão Miocárdica/prevenção & controle , Ratos , Ratos Wistar , Receptores Purinérgicos , Receptores Purinérgicos P2Y12 , Reperfusão
15.
Clinics (Sao Paulo) ; 76: e2683, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33909827

RESUMO

OBJECTIVES: Ischemia and reperfusion (I/R) in the intestine could lead to severe endothelial injury, compromising intestinal motility. Reportedly, estradiol can control local and systemic inflammation induced by I/R injury. Thus, we investigated the effects of estradiol treatment on local repercussions in an intestinal I/R model. METHODS: Rats were subjected to ischemia via the occlusion of the superior mesenteric artery (45 min) followed by reperfusion (2h). Thirty minutes after ischemia induction (E30), 17ß-estradiol (E2) was administered as a single dose (280 µg/kg, intravenous). Sham-operated animals were used as controls. RESULTS: I/R injury decreased intestinal motility and increased intestinal permeability, accompanied by reduced mesenteric endothelial nitric oxide synthase (eNOS) and endothelin (ET) protein expression. Additionally, the levels of serum injury markers and inflammatory mediators were elevated. Estradiol treatment improved intestinal motility, reduced intestinal permeability, and increased eNOS and ET expression. Levels of injury markers and inflammatory mediators were also reduced following estradiol treatment. CONCLUSION: Collectively, our findings indicate that estradiol treatment can modulate the deleterious intestinal effects of I/R injury. Thus, estradiol mediates the improvement in gut barrier functions and prevents intestinal dysfunction, which may reduce the systemic inflammatory response.


Assuntos
Estradiol , Traumatismo por Reperfusão , Animais , Estradiol/farmacologia , Estrogênios , Intestinos , Isquemia , Masculino , Permeabilidade , Ratos , Reperfusão , Traumatismo por Reperfusão/tratamento farmacológico , Traumatismo por Reperfusão/prevenção & controle
16.
Acta Cir Bras ; 36(3): e360305, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33909821

RESUMO

PURPOSE: To evaluate the effect of creatine supplementation in the diet of rats subjected to ischemia and reperfusion of hind limbs. METHODS: Eighteen male Wistar rats were randomized to receive dietary creatine supplementation (G1) or no supplementation (G2), before being subjected to 4 h of ischemia followed by 4 h of reperfusion. In addition, 10 rats (G3) underwent the same surgical procedure, without ischemia, but with supplementation. After reperfusion, kidney and musculature were evaluated for histological damage and serum levels of alanine aminotransferase, urea and creatinine were obtained. RESULTS: The urea dosage showed significant differences between the groups (averages G1 = 155.1; G2 = 211.27; G3 = 160.42). Histological analysis found significant differences between G1 and G2 (but not between G1 and G3) in renal myoglobin cylinders and vacuolar degeneration variables and in hypereosinophilia and karyopyknosis variables in muscle fibers. There were no significant differences in the other variables studied. CONCLUSIONS: Creatine supplementation was related to fewer histological lesions, as well as lower levels of plasma urea, which may suggest a protective effect against lesions caused by ischemia and reperfusion of posterior paws muscles in Wistar rats.


Assuntos
Creatina , Traumatismo por Reperfusão , Animais , Dieta , Suplementos Nutricionais , Isquemia , Rim , Masculino , Músculo Esquelético , Ratos , Ratos Wistar , Reperfusão , Traumatismo por Reperfusão/prevenção & controle
17.
J Int Med Res ; 49(3): 300060521997618, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-33730893

RESUMO

Electrical storm is a life-threatening emergency condition defined as three or more episodes of ventricular tachycardia or ventricular fibrillation (VF) within 24 hours requiring anti-tachycardia therapy, electrical cardioversion, or defibrillation. However, studies of the incidence of electrical storm after chronic total occlusion-percutaneous coronary intervention (CTO-PCI) are limited,7 and post-procedural VF after revascularization of CTO has not been described. The purpose of this article was to present a case of post-operative VF electrical storm after revascularization of CTO of the left anterior descending (LAD) artery to determine whether the electrical storm was caused by reperfusion arrhythmia or compromise of either branch vessels or the collateral circulation during intervention.


Assuntos
Oclusão Coronária , Intervenção Coronária Percutânea , Arritmias Cardíacas , Doença Crônica , Oclusão Coronária/diagnóstico por imagem , Oclusão Coronária/cirurgia , Humanos , Reperfusão , Resultado do Tratamento , Fibrilação Ventricular/etiologia , Fibrilação Ventricular/terapia
18.
Anal Chem ; 93(14): 5782-5788, 2021 04 13.
Artigo em Inglês | MEDLINE | ID: mdl-33783186

RESUMO

Hepatic ischemia-reperfusion (IR) injury is a severe pathophysiological event during liver surgery or transplantation and could lead to liver failure or even death. The energy supply of mitochondria plays an essential role in preventing IR injury. Mitochondrial DNA (mtDNA) is involved in maintaining the balance of energy by participating in an oxidative phosphorylation process. However, the exact relationship between IR and mtDNA remains unclear by reason of the lack of an accurate real-time analysis method. Herein, we fabricated a mitochondria-targeting fluorescent probe (mtDNA-BP) to explore mtDNA stability and supervise the changes in mtDNA in IR liver. By virtue of pyridinium electropositivity and suitable size, mtDNA-BP could accumulate in mitochondria and insert into the mtDNA groove, which made mtDNA-BP fluoresce strongly. This is attributed to the reduction of the intramolecular rotation energy loss that is restricted by DNA. By in situ fluorescence imaging, we observed in real time that mtDNA damage was aggravated by deteriorating IR injury, so the ROS-mtDNA-mediated IR damage signal pathway was speculated. Furthermore, on the basis of mtDNA-BP real-time response capability for mtDNA, we established a drug-screening method for inhibiting IR injury and found superior therapeutic performance of two potential drugs: pioglitazone and salidroside. This work contributes to our understanding of mtDNA-related disease and provides a new drug analysis method.


Assuntos
Hepatopatias , Traumatismo por Reperfusão , DNA Mitocondrial/genética , Humanos , Isquemia , Mitocôndrias , Reperfusão , Traumatismo por Reperfusão/genética
19.
J Biomed Nanotechnol ; 17(1): 64-77, 2021 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-33653497

RESUMO

Apigenin as a natural flavonoid product has been proved previously to play a renoprotective effect during ischemia/reperfusion injury (IRI), but the particular mechanisms involving the positive effects of apigenin remain totally unclear. The study investigated apigenin's roles and underlying biological mechanisms in IR-induced acute kidney injury (AKI). Thirty-six mice received a right nephrectomy and clamping of the left renal artery for 30 minutes, and then perfusion for 24 h. Apigenin was loaded onto a biodegradable polymer carrier (nanoparticle) to enhance its bioavailability. Mice were subjected to intraperitoneally injection with apigenin (5, 10 or 20 mg/kg) for 24 h before surgery. For in vitro experiments, mouse renal tubular epithelial cells (mRTECs) and miR-140-5p mimic/inhibitor transfected mRTECs were subjected to hypoxia/reoxygenation in the presence or absence of apigenin. In vitro, we uncovered that hypoxia/reoxygenation stimulation caused inflammatory injury in mRTECs. Apigenin reduced the hypoxia/reoxygenation-induced cell inflammatory injury and NF- B p65 nuclear translocation from cytoplasm and activation. Moreover, apigenin reduced hypoxia/reoxygenationtriggered miR-140-5p down-regulation. What's more, the luciferase reporter system revealed that miR-140-5p negatively regulates CXCL12, which is its direct target of action. CXCL12 exhibited an inhibitory effect on the apigenin-induced inactivation of NF- B signaling pathway. Furthermore, we observed that apigenin pretreatment attenuated the IR-triggered up-regulation of serum creatinine and blood urea nitrogen, elevation of pro-inflammatory cytokines secretion and tubular cell apoptosis, enhancement of CXCL12 and decline of miR-140-5p in vivo. Our studies show that apigenin protects against IR-triggered renal cell inflammatory injury in vivo and in vitro by miR-140-5p up-regulation and CXCL12 downregulation via quenching the NF- B pathway activation. Apigenin may be an encouraging therapeutic agent for patients with IR-associated kidney injury.


Assuntos
MicroRNAs , Nanopartículas , Traumatismo por Reperfusão , Animais , Apigenina/farmacologia , Apoptose , Quimiocina CXCL12 , Humanos , Isquemia , Rim , Camundongos , MicroRNAs/genética , NF-kappa B/metabolismo , Reperfusão , Traumatismo por Reperfusão/tratamento farmacológico , Transdução de Sinais
20.
Andrologia ; 53(4): e14000, 2021 May.
Artigo em Inglês | MEDLINE | ID: mdl-33550644

RESUMO

This study was performed to evaluate the effect of liraglutide on experimental testicular ischaemia reperfusion in rats in terms of biochemistry, histopathology and immunohistochemistry. A total of 28 male Wistar-Albino rats were divided randomly into 4 groups: control (7), sham (7), ischaemia-reperfusion (7) and ischaemia-reperfusion + liraglutide (7). Biochemically, Nitric Oxide, Malondialdehyde, Superoxide dismutase, Glutathione peroxidase and Catalase levels were measured in the testis. Apoptosis protease activating factor-1 and inducible nitric oxide synthase activity were evaluated immunohistochemically as well. Statistical analyses were made via the Kruskal-Wallis and Mann-Whitney U tests. In the reperfusion group, CAT and SOD values were increased (p > .05), NO and MDA values were decreased (p < .05) after administration of liraglutide. In addition, GPx values were significantly increased in ischaemia reperfusion + liraglutide administered group compared to reperfusion group (p < .05). Apaf-1 and iNOS activity were significantly decreased with the addition of liraglutide treatment to the ischaemia-reperfusion group (p < .05). First of all, we would like to say that liraglutide treatment is moderately preventive against I/R injury in testicular torsion. The anti-inflammatory, antioxidant and antiapoptotic properties of liraglutide are create a moderately protective effect as we show in this study.


Assuntos
Traumatismo por Reperfusão , Torção do Cordão Espermático , Animais , Humanos , Isquemia , Liraglutida/metabolismo , Liraglutida/farmacologia , Liraglutida/uso terapêutico , Masculino , Malondialdeído/metabolismo , Estresse Oxidativo , Ratos , Ratos Wistar , Reperfusão , Traumatismo por Reperfusão/metabolismo , Traumatismo por Reperfusão/prevenção & controle , Torção do Cordão Espermático/metabolismo , Superóxido Dismutase/metabolismo , Testículo/metabolismo
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