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1.
Am J Physiol Lung Cell Mol Physiol ; 320(3): L331-L338, 2021 03 01.
Artigo em Inglês | MEDLINE | ID: mdl-33404365

RESUMO

Acute respiratory distress syndrome and subsequent respiratory failure remains the leading cause of death (>80%) in patients severely impacted by COVID-19. The lack of clinically effective therapies for COVID-19 calls for the consideration of novel adjunct therapeutic approaches. Though novel antiviral treatments and vaccination hold promise in control and prevention of early disease, it is noteworthy that in severe cases of COVID-19, addressing "run-away" inflammatory cascades are likely more relevant for improvement of clinical outcomes. Viral loads may decrease in severe, end-stage coronavirus cases, but a systemically damaging cytokine storm persists and mediates multiple organ injury. Remote ischemic conditioning (RIC) of the limbs has shown potential in recent years to protect the lungs and other organs against pathological conditions similar to that observed in COVID-19. We review the efficacy of RIC in protecting the lungs against acute injury and current points of consideration. The beneficial effects of RIC on lung injury along with other related cardiovascular complications are discussed, as are the limitations presented by sex and aging. This adjunct therapy is highly feasible, noninvasive, and proven to be safe in clinical conditions. If proven effective in clinical trials for acute respiratory distress syndrome and COVID-19, application in the clinical setting could be immediately implemented to improve outcomes.


Assuntos
/complicações , Precondicionamento Isquêmico/métodos , /isolamento & purificação , Humanos , /virologia
2.
ACS Chem Neurosci ; 11(22): 3732-3740, 2020 11 18.
Artigo em Inglês | MEDLINE | ID: mdl-33147964

RESUMO

This Article summarizes the likely benefits of central nervous system oxidative preconditioning in the reduction of COVID-19 based on its putative pathogenesis. The current COVID-19 outbreak caused a pandemic with millions of infected patients and death cases worldwide. The clinical features of severe acute respiratory syndrome coronavirus (SARS-CoV) was initially linked with respiratory disorders, but recent studies have reported alterations of neurological and cerebrovascular functions in COVID-19 patients. The main viral infection features are related to cell death, inflammation, and cytokine generation, which can be associated with the dysregulation of redox systems or oxidative stress. However, until now, there is no available and effective therapeutic approach. Thus, it is necessary to search for care and adequate protection against the disease, especially for susceptible and vulnerable groups. Preconditioning, a well-known antioxidative stress and anti-inflammatory approach, is protective against many neurological age-related disorders. COVID-19 severity and morbidity have been observed in elderly patients. The aim of the present study is to elucidate the possible protective role of oxidative preconditioning in aged patients at high risk of developing severe COVID-19 complications.


Assuntos
Betacoronavirus , Encéfalo/irrigação sanguínea , Infecções por Coronavirus/terapia , Precondicionamento Isquêmico/métodos , Estresse Oxidativo/fisiologia , Pneumonia Viral/terapia , Betacoronavirus/metabolismo , Encéfalo/metabolismo , Encéfalo/virologia , Infecções por Coronavirus/metabolismo , Humanos , Precondicionamento Isquêmico/tendências , Pandemias , Pneumonia Viral/metabolismo
3.
BMC Neurol ; 20(1): 266, 2020 Jul 02.
Artigo em Inglês | MEDLINE | ID: mdl-32615939

RESUMO

BACKGROUND: Remote ischemic conditioning during cerebral ischemia (remote ischemic perconditioning, RIPerC) refers to the application of several cycles of brief ischemia and reperfusion (I/R) commonly to a limb, and it represents a new paradigm in neuroprotection with multiple mechanisms of action in ischemic stroke (IS) patients during acute phase. Some clinical trials just finished, and a few others are still ongoing; gather the current knowledge and pull it down to influence the present and future studies was the goal of this paper. METHODS: A systematic review of published research papers and/or registered clinical trials since 2000 was performed. RESULTS: Nineteen studies were identified and only four studies were completed. All of them have demonstrated that RIPerC is safe, feasible and well tolerated in IS patients. However, a high heterogeneity of clinical trial characteristics was observed: five (26.3%) randomized clinical trials (RCTs) included only thrombolytic-treated patients, three (15.8%) RCTs only thrombectomy-treated patients, and five (26.3%) RCTs required radiological confirmation of IS. Temporal inclusion criteria vary from 4 h to 48 h. Most of the clinical trials used 4 cycles of RIPerC in the upper non-affected limb. Interestingly, only three (16.7%) RCTs applied RIPerC during the transportation in the ambulance. Neuroimaging outputs were the main endpoints when endovascular therapy was applied; functional outcome is also the main endpoint in large-medium size studies. CONCLUSIONS: This review summarizes the completed and ongoing clinical trials on RIPerC in IS patients, where RIPerC has been used alone or in combination with recanalization therapies. Ongoing clinical trials will provide new information on the best RIPerC intervention strategy and potentially improve the functional outcome of IS patients; definition of new RIPerC strategies would ideally aim at enhancing tissue preservation, promoting neurological recovery, and stratify patients to improve treatment feasibility.


Assuntos
Isquemia Encefálica/prevenção & controle , Precondicionamento Isquêmico/métodos , Acidente Vascular Cerebral/prevenção & controle , Humanos , Neuroproteção , Ensaios Clínicos Controlados Aleatórios como Assunto
4.
Acta Cir Bras ; 35(5): e202000503, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32578671

RESUMO

PURPOSE: To investigate the effect of hyperbaric oxygen therapy on colonic anastomosis healing with and without ischemia in rats. METHODS: Forty female rats underwent segmental resection of 1 cm of the left colon followed by end-to-end anastomosis. They were randomly assigned to four groups (n=10 each), a sham group; two groups were submitted to Hyperbaric Oxygen therapy (HBOT) with and without induced ischemia and the induced ischemia group without HBOT. The HBOT protocol evaluated was 100% O2 at 2.4 Atmosphere absolute pressure (ATA) for 60 minutes, two sessions before as a preconditioning protocol and three sessions after the operation. Clinical course and mortality were monitored during all experiment and on the day of euthanasia on the fourth day after laparotomy. Macroscopic appearance of the abdominal cavity were assessed and samples for breaking strength of the anastomosis and histopathological parameters were collected. RESULTS: There was no statistically significant difference in mortality or anastomosis leak between the four experimental groups. Anastomosis breaking strength was similar across groups. CONCLUSION: The HBOT protocol tested herein at 2.4 ATA did not affect histopathological and biomechanical parameters of colonic anastomotic healing, neither the clinical outcomes death and anastomosis leak on the fourth day after laparotomy.


Assuntos
Colo/irrigação sanguínea , Colo/cirurgia , Oxigenação Hiperbárica/métodos , Isquemia/patologia , Precondicionamento Isquêmico/métodos , Cicatrização , Anastomose Cirúrgica , Animais , Colo/patologia , Feminino , Isquemia/prevenção & controle , Período Pós-Operatório , Ratos Endogâmicos Lew , Reprodutibilidade dos Testes , Índice de Gravidade de Doença , Fatores de Tempo , Resultado do Tratamento
5.
Acta Cir Bras ; 35(4): e202000402, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32578722

RESUMO

PURPOSE: To investigate the effects of bradykinin on reperfusion injury in an experimental intestinal ischemia reperfusion model. METHODS: We used 32 Wistar-Albino rats. We composed 4 groups each containing 8 rats. Rats in sham group were sacrified at 100 minutes observation after laparotomy. Thirty minutes reperfusion was performed following 50 minutes ischaemia in control group after observing 20 minutes. Ischaemic preconditioning was performed in one group of the study. We performed the other study group pharmacologic preconditioning by infusional administration of 10 µg/kg/minute bradykinin intravenously. We sacrified all of the rats by taking blood samples to evaluate the lactate and lactate dehydrogenase (LDH) after resection of jejunum for detecting tissue myeloperoxidase (MPO) activity. RESULTS: Lactate and LDH levels were significantly higher in control and study groups than the sham group (P<0.001). There is no difference between the study groups statistically. (P>0.05). The results were the same for MPO levels. Although definitive cell damage was determinated in the control group by hystopatological evaluation, the damage in the study groups observed was lower in different levels. However, there was no significant difference between the study groups statistically (P>0.05). CONCLUSION: Either ischeamic preconditioning or pharmacologic preconditioning made by bradykinin reduced the ischemia reperfusion injury at jejunum.


Assuntos
Bradicinina/farmacologia , Modelos Animais de Doenças , Intestino Delgado/irrigação sanguínea , Precondicionamento Isquêmico/métodos , Traumatismo por Reperfusão/prevenção & controle , Vasodilatadores/farmacologia , Animais , Feminino , Laparotomia , Peroxidase/análise , Distribuição Aleatória , Ratos Wistar , Valores de Referência , Reprodutibilidade dos Testes , Fatores de Tempo , Resultado do Tratamento
6.
PLoS One ; 15(4): e0224720, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32348301

RESUMO

Small intestinal strangulation associated with ischaemia-reperfusion injury (IRI) is common in horses. In laboratory animals IRI can be ameliorated by ischaemic preconditioning (IPC) and pharmacological preconditioning (PPC) with dexmedetomidine. The aim of this study was to determine the effect of PPC with dexmedetomidine or IPC in an equine model of small intestinal ischaemia-reperfusion (IR). In a randomized controlled experimental trial, 15 horses were assigned to three groups: control (C), IPC, and PPC with dexmedetomidine (DEX). All horses were placed under general anaesthesia and 90% jejunal ischaemia was induced for 90 minutes, followed 30 minutes of reperfusion. In group IPC, three short bouts of ischaemia and reperfusion were implemented, and group DEX received a continuous rate infusion of dexmedetomidine prior to the main ischaemia. Jejunal biopsies were collected before ischaemia (P), and at the end of ischaemia (I) and reperfusion (R). Mucosal injury was assessed by the Chiu-Score, inflammatory cells were stained by cytosolic calprotectin. The degree of apoptosis and cell necrosis was assessed by cleaved-caspase-3 and TUNEL. Parametric data were analyzed by two-way ANOVA for repeated measurements followed by Dunnetts t-test. Non parametric data were compared between groups at the different time points by a Kruskal-Wallis-Test and a Wilcoxon-2-Sample-test. The mucosal injury score increased during I in all groups. After reperfusion, IRI further progressed in group C, but not in IPC and DEX. In all groups the number of cleaved caspase-3 and TUNEL positive cells increased from P to I. The number of TUNEL positive cells were lower in group DEX compared to group C after I and R. Infiltration with calprotectin positive cells was less pronounced in group DEX compared to group C, whereas in group IPC more calprotectin positive cells were seen. In conclusion, IPC and DEX exert protective effects in experimental small intestinal ischaemia in horses.


Assuntos
Agonistas de Receptores Adrenérgicos alfa 2/uso terapêutico , Dexmedetomidina/uso terapêutico , Isquemia/terapia , Precondicionamento Isquêmico/métodos , Jejuno/irrigação sanguínea , Traumatismo por Reperfusão/terapia , Agonistas de Receptores Adrenérgicos alfa 2/administração & dosagem , Agonistas de Receptores Adrenérgicos alfa 2/farmacologia , Animais , Dexmedetomidina/administração & dosagem , Dexmedetomidina/farmacologia , Cavalos , Isquemia/tratamento farmacológico , Jejuno/efeitos dos fármacos , Jejuno/patologia , Distribuição Aleatória , Traumatismo por Reperfusão/tratamento farmacológico
7.
Acta Cir Bras ; 35(2): e202000203, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32348402

RESUMO

Purpose To evaluate the effect of remote ischemic conditioning associated to N-acetylcysteine (NAC) on testicular ischemia∕reperfusion (I∕R) injury in rats. Methods Twenty-five adult male Wistar rats were randomly distributed into five experimental groups (n=5), as follows: Sham, I∕R, Perconditioning (PER), NAC and PER+NAC. Two-hour ischemia was induced by rotating the left testis 720° to clockwise direction, followed by 4 hours of reperfusion. Perconditioning was performed by three I/R cycles of 10 min each on the left limb, 30 min before reperfusion. N-acetylcysteine (150 mg∕kg) was administered 30 min before reperfusion. Results Statistical differences were observed in MDA levels between I/R group with all groups (p<0.01), in addition there was statistical difference between PER and Sham, and PER+ NAC groups (p<0.05) in plasma. Conclusions The protective effect of perconditioning isolated in the reduction of lipid peroxidation related to oxidative stress was demonstrated. However, when Perconditioning was associated with NAC, there was no protective effect against testicular injury of ischemia and reperfusion.


Assuntos
Acetilcisteína/farmacologia , Depuradores de Radicais Livres/farmacologia , Precondicionamento Isquêmico/métodos , Estresse Oxidativo/efeitos dos fármacos , Traumatismo por Reperfusão , Testículo/irrigação sanguínea , Animais , Avaliação Pré-Clínica de Medicamentos , Masculino , Capacidade de Absorbância de Radicais de Oxigênio , Distribuição Aleatória , Ratos , Ratos Wistar , Testículo/efeitos dos fármacos
8.
J Am Soc Nephrol ; 31(4): 716-730, 2020 04.
Artigo em Inglês | MEDLINE | ID: mdl-32111728

RESUMO

BACKGROUND: Although AKI lacks effective therapeutic approaches, preventive strategies using preconditioning protocols, including caloric restriction and hypoxic preconditioning, have been shown to prevent injury in animal models. A better understanding of the molecular mechanisms that underlie the enhanced resistance to AKI conferred by such approaches is needed to facilitate clinical use. We hypothesized that these preconditioning strategies use similar pathways to augment cellular stress resistance. METHODS: To identify genes and pathways shared by caloric restriction and hypoxic preconditioning, we used RNA-sequencing transcriptome profiling to compare the transcriptional response with both modes of preconditioning in mice before and after renal ischemia-reperfusion injury. RESULTS: The gene expression signatures induced by both preconditioning strategies involve distinct common genes and pathways that overlap significantly with the transcriptional changes observed after ischemia-reperfusion injury. These changes primarily affect oxidation-reduction processes and have a major effect on mitochondrial processes. We found that 16 of the genes differentially regulated by both modes of preconditioning were strongly correlated with clinical outcome; most of these genes had not previously been directly linked to AKI. CONCLUSIONS: This comparative analysis of the gene expression signatures in preconditioning strategies shows overlapping patterns in caloric restriction and hypoxic preconditioning, pointing toward common molecular mechanisms. Our analysis identified a limited set of target genes not previously known to be associated with AKI; further study of their potential to provide the basis for novel preventive strategies is warranted. To allow for optimal interactive usability of the data by the kidney research community, we provide an online interface for user-defined interrogation of the gene expression datasets (http://shiny.cecad.uni-koeln.de:3838/IRaP/).


Assuntos
Lesão Renal Aguda/genética , Lesão Renal Aguda/prevenção & controle , Restrição Calórica , Hipóxia , Precondicionamento Isquêmico/métodos , RNA Mensageiro/metabolismo , Traumatismo por Reperfusão/genética , Traumatismo por Reperfusão/prevenção & controle , Animais , Perfilação da Expressão Gênica , Masculino , Camundongos , Camundongos Endogâmicos C57BL , RNA Mensageiro/genética
9.
Eur J Med Res ; 25(1): 10, 2020 Mar 19.
Artigo em Inglês | MEDLINE | ID: mdl-32192513

RESUMO

PURPOSE: Contrast-induced acute kidney injury (CI-AKI) resulting from administration of iodinated contrast media (CM) is the third leading cause of hospital-acquired acute kidney injury and is associated with substantial morbidity and mortality. Deteriorated renal microcirculation plays an important role in CI-AKI. Limb ischemic preconditioning (LIPC), where brief and non-injurious ischemia/reperfusion is applied to a limb prior to the administration of the contrast agent, is emerging as a promising strategy for CI-AKI prevention. However, it is not known whether the renal protection of LIPC against CI-AKI is mediated by regulation of renal microcirculation and the molecular mechanisms remain largely unknown. METHODS: In this study, we examined the renal cortical and medullary blood flow in a stable CI-AKI model using 5/6-nephrectomized (NE) rat. The LIPC and sham procedures were performed prior to the injection of CM. Furthermore, we analyzed renal medulla hypoxia using in vivo labeling of hypoxyprobe. Pharmacological inhibitions and western blotting were used to determine the underlying molecular mechanisms. RESULTS: In this study, we found LIPC significantly ameliorated CM-induced reduction of medullary blood flow and attenuated CM-induced hypoxia. PI3K inhibitor (wortmannin) treatment blocked the regulation of medullary blood flow and the attenuation of hypoxia of LIPC. Phosphorylation of Akt/eNOS was significantly decreased via wortmannin treatment compared with LIPC. Nitric oxide synthase-inhibitor [Nω-nitro-L-arginine methyl ester (L-NAME)] treatment abolished the above effects and decreased phosphorylation of eNOS, but not Akt. CONCLUSIONS: Collectively, the results demonstrate that LIPC ameliorates CM-induced renal vasocontraction and is mediated by activation of PI3K/Akt/eNOS signaling pathway.


Assuntos
Lesão Renal Aguda/metabolismo , Extremidades/irrigação sanguínea , Rim/metabolismo , Microcirculação/fisiologia , Proteínas Proto-Oncogênicas c-akt/metabolismo , Animais , Apoptose/efeitos dos fármacos , Extremidades/fisiopatologia , Precondicionamento Isquêmico/métodos , Rim/fisiopatologia , Fosfatidilinositol 3-Quinases/metabolismo , Ratos Sprague-Dawley , Traumatismo por Reperfusão/metabolismo , Transdução de Sinais/fisiologia
10.
Int J Surg ; 77: 77-82, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-32198097

RESUMO

INTRODUCTION: Anastomotic leaks remain a major complication following oesophagectomy, accounting for high morbidity and mortality. Recently, gastric ischaemic conditioning (GIC) has been proposed to improve anastomotic integrity through neovascularisation of the gastric conduit. This systematic review and meta-analysis aim to determine the impact of GIC on postoperative outcomes following oesophagectomy. METHODS: A systematic literature search was performed to identify studies reporting GIC for any indication of oesophageal resection up to April 25, 2019. The primary outcome was anastomotic leak. Secondary outcomes were conduit necrosis, anastomotic strictures, overall and major complications or in-hospital mortality. Meta-analyses were conducted using random-effects modelling. RESULTS: Nineteen studies reported on GIC, of which 13 were comparative studies. GIC was performed through ligation in 13 studies and embolisation in six studies. GIC did not appear to reduce anastomotic leakages (OR 0.80, CI95: 0.51-1.24, p = 0.3), anastomotic strictures (OR 0.75, CI95: 0.35-1.60, p = 0.5), overall complications (OR 1.02, CI95: 0.48-2.16, p = 0.9), major complications (OR 1.06, CI95: 0.53-2.11, p = 0.9), or in-hospital mortality (OR 0.70, CI95: 0.32-1.53, p = 0.4). However, GIC was associated with reduced rates of conduit necrosis (OR 0.30, CI95: 0.11-0.77, p = 0.013). CONCLUSION: GIC does not appear to reduce overall rates of anastomotic leakage after oesophagectomy but seems to reduce severity of leakages. More in depth studies are recommended.


Assuntos
Neoplasias Esofágicas/cirurgia , Esofagectomia/efeitos adversos , Precondicionamento Isquêmico/métodos , Fístula Anastomótica/prevenção & controle , Neoplasias Esofágicas/mortalidade , Esofagectomia/mortalidade , Mortalidade Hospitalar , Humanos
11.
Oxid Med Cell Longev ; 2020: 7098505, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32047578

RESUMO

Background and Aims: Perioperative kidney injury affects 12.7% of patients undergoing lower limb revascularisation surgery. Remote ischaemic preconditioning (RIPC) is a potentially protective procedure against organ damage and consists of short nonlethal episodes of ischaemia. The main objective of this substudy was to evaluate the effect of RIPC on kidney function, inflammation, and oxidative stress in patients undergoing open surgical lower limb revascularisation. Materials and Methods. This is a subgroup analysis of a randomised, sham-controlled, double-blinded, single-centre study. A RIPC or a sham procedure was performed noninvasively along with preparation for anaesthesia in patients undergoing open surgical lower limb revascularisation. The RIPC protocol consisted of 4 cycles of 5 minutes of ischaemia, with 5 minutes of reperfusion between every episode. Blood was collected for analysis preoperatively, 2, 8, and 24 hours after surgery, and urine was collected preoperatively and 24 hours after surgery. Results: Data of 56 patients were included in the analysis. Serum creatinine, cystatin C, and beta-2 microglobulin increased, and eGFR decreased across all time points significantly more in the sham group than in the RIPC group (p = 0.021, p = 0.021, p = 0.021, p = 0.021, p = 0.021. Conclusions: Our finding of reduced release of kidney injury biomarkers may indicate the renoprotective effect of RIPC in patients undergoing open surgical lower limb revascularisation. The trial is registered with ClinicalTrials.gov NCT02689414.


Assuntos
Lesão Renal Aguda/metabolismo , Biomarcadores/metabolismo , Precondicionamento Isquêmico/métodos , Rim/patologia , Lesão Renal Aguda/patologia , Idoso , Creatinina/sangue , Cistatina C/sangue , Método Duplo-Cego , Feminino , Taxa de Filtração Glomerular , Humanos , Extremidade Inferior/cirurgia , Masculino , Pessoa de Meia-Idade , Procedimentos Cirúrgicos Vasculares
12.
PLoS One ; 15(2): e0228948, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32059016

RESUMO

Remote ischemic preconditioning (RIPC) can evoke cardioprotection following ischemia/reperfusion and this may depend on the anesthetic used. We tested whether 1) extracellular vesicles (EVs) isolated from humans undergoing RIPC protect cardiomyoblasts against hypoxia-induced apoptosis and 2) this effect is altered by cardiomyoblast exposure to isoflurane or propofol. EVs were isolated before and 60 min after RIPC or Sham from ten patients undergoing coronary artery bypass graft surgery with isoflurane anesthesia and quantified by Nanoparticle Tracking Analysis. Following EV-treatment for 6 hours under exposure of isoflurane or propofol, rat H9c2 cardiomyoblasts were cultured for 18 hours in normoxic or hypoxic atmospheres. Apoptosis was detected by flow cytometry. Serum nanoparticle concentrations in patients had increased sixty minutes after RIPC compared to Sham (2.5x1011±4.9x1010 nanoparticles/ml; Sham: 1.2x1011±2.0x1010; p = 0.04). Hypoxia increased apoptosis of H9c2 cells (hypoxia: 8.4%±0.6; normoxia: 2.5%±0.1; p<0.0001). RIPC-EVs decreased H9c2 cell apoptosis compared to control (apoptotic ratio: 0.83; p = 0.0429) while Sham-EVs showed no protection (apoptotic ratio: 0.97). Prior isoflurane exposure in vitro even increased protection (RIPC-EVs/control, apoptotic ratio: 0.79; p = 0.0035; Sham-EVs/control, apoptotic ratio:1.04) while propofol (50µM) abrogated protection by RIPC-EVs (RIPC-EVs/control, Apoptotic ratio: 1.01; Sham-EVs/control, apoptotic ratio: 0.94; p = 0.602). Thus, EVs isolated from patients undergoing RIPC under isoflurane anesthesia protect H9c2 cardiomyoblasts against hypoxia-evoked apoptosis and this effect is abrogated by propofol. This supports a role of human RIPC-generated EVs in cardioprotection and underlines propofol as a possible confounder in RIPC-signaling mediated by EVs.


Assuntos
Vesículas Extracelulares/fisiologia , Isquemia/metabolismo , Miócitos Cardíacos/fisiologia , Idoso , Anestesia/métodos , Animais , Apoptose/fisiologia , Ponte de Artéria Coronária/métodos , Vesículas Extracelulares/metabolismo , Feminino , Humanos , Hipóxia/metabolismo , Precondicionamento Isquêmico/métodos , Isoflurano/farmacologia , Masculino , Pessoa de Meia-Idade , Miócitos Cardíacos/metabolismo , Propofol/farmacologia , Ratos
13.
PLoS One ; 15(2): e0227263, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32017777

RESUMO

Remote limb ischemic conditioning (RLIC) is a clinically feasible method in which brief, sub-lethal bouts of ischemia protects remote organs or tissues from subsequent ischemic injury. A single session of RLIC can improve exercise performance and increase muscle activation. The purpose of this study, therefore, was to assess the effects of a brief, two-week protocol of repeated RLIC combined with strength training on strength gain and neural adaptation in healthy young adults. Participants age 18-40 years were randomized to receive either RLIC plus strength training (n = 15) or sham conditioning plus strength training (n = 15). Participants received RLIC or sham conditioning over 8 visits using a blood pressure cuff on the dominant arm with 5 cycles of 5 minutes each alternating inflation and deflation. Visits 3-8 paired conditioning with wrist extensors strength training on the non-dominant (non-conditioned) arm using standard guidelines. Changes in one repetition maximum (1 RM) and electromyography (EMG) amplitude were compared between groups. Both groups were trained at a similar workload. While both groups gained strength over time (P = 0.001), the RLIC group had greater strength gains (9.38 ± 1.01 lbs) than the sham group (6.3 ± 1.08 lbs, P = 0.035). There was not a significant group x time interaction in EMG amplitude (P = 0.231). The RLIC group had larger percent changes in 1 RM (43.8% vs. 26.1%, P = 0.003) and EMG amplitudes (31.0% vs. 8.6%, P = 0.023) compared to sham conditioning. RLIC holds promise for enhancing muscle strength in healthy young and older adults, as well as clinical populations that could benefit from strength training.


Assuntos
Extremidades/irrigação sanguínea , Precondicionamento Isquêmico/métodos , Força Muscular/fisiologia , Músculo Esquelético/irrigação sanguínea , Treinamento de Resistência/métodos , Adolescente , Adulto , Feminino , Voluntários Saudáveis , Humanos , Masculino , Adulto Jovem
14.
J Plast Reconstr Aesthet Surg ; 73(5): 975-982, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-31899115

RESUMO

BACKGROUND: Management of avulsion injuries remains a challenge due to necrosis. The aim of the present study is to create an experimental model reproducing an avulsion injury and investigate the effects of hyperoxygenated solution (HOS), a method of oxygen delivery that has been widely used in the therapy of ischaemia-hypoxia diseases, on avulsion injury flap survival in rats. METHODS: Forty male rats were divided into four groups (n = 10 each). Dorsal random pattern flaps measuring 3 × 9 cm, including the panniculus carnosus, were elevated and run over by the skin avulsion model machine, and the flaps were then sutured into their original places. The sham+HOS and avulsion+HOS groups received intravenous HOS (20 ml/kg) each day for 7 days after the operation. The sham+saline and avulsion+saline groups received intravenous saline solution (20 ml/kg) each day for 7 days after the operation. Percutaneous O2 pressure (TcpO2) measurement, serial examinations of skin flap blood perfusion, skin flap survival evaluation and histopathology were performed to assess the efficacy of HOS on avulsion injury. RESULTS: Compared to the avulsion+saline groups, TcpO2 was significantly higher in the avulsion+HOS groups at 15, 30 and 60 min after infusion (P < 0.05). The blood perfusion of flaps in the avulsion+HOS group was higher than in the avulsion+saline group (P < 0.05). The survival rate was higher in the avulsion+HOS group than in the avulsion+saline group (P < 0.05), and the histopathology assays supported the data. CONCLUSION: We succeeded in developing an avulsion injury model and demonstrated that HOS could improve the survival of the avulsion injury flaps in rats by effectively increasing the local oxygen content and blood perfusion and ameliorating inflammatory damage.


Assuntos
Sobrevivência de Enxerto , Precondicionamento Isquêmico/métodos , Oxigênio/uso terapêutico , Traumatismo por Reperfusão/prevenção & controle , Lesões dos Tecidos Moles/cirurgia , Retalhos Cirúrgicos/irrigação sanguínea , Animais , Modelos Animais de Doenças , Masculino , Necrose , Ratos , Ratos Sprague-Dawley , Soluções , Técnicas de Sutura
15.
Int J Mol Med ; 45(4): 1141-1149, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-31985019

RESUMO

The kidneys are prone to developing ischemia reperfusion injury (IRI) following certain renal surgeries and cardiovascular surgeries requiring cardiac arrest. Sevoflurane and ischemic preconditioning reportedly alleviate IRI, which is mediated via microRNAs. The present study compared anesthetic preconditioning (APC) and ischemic preconditioning (IPC) on microRNAs, which promote cell­survival pathways in rats in a randomized controlled study. After undergoing right nephrectomy under general anesthesia, male Wistar rats (336±24 g) and were divided into four groups (IRI, APC, IPC and sham; n=7 each). The IRI group underwent 45 min clamping of the left renal vasculature, followed by 4 h of reperfusion. APC involved exposure to one minimum alveolar concentration sevoflurane for 15 min. IPC included three cycles of two­min clamping and five­min reperfusion. Blood and renal biopsy samples were assessed postoperatively to measure serum creatinine and to analyze renal microRNA (miR) expression using reverse transcription­quantitative polymerase chain reaction (RT­qPCR) testing and their target pathways with Ingenuity Pathway Analysis™. The present study found that serum creatinine values in APC (0.71±0.08 mg/dl) and IPC (0.73±0.1 mg/dl) groups were lower than in the IRI group (0.96±0.13 mg/dl; P<0.05), indicating amelioration of IRI by APC and IPC. RT­qPCR followed by pathway analysis indicated that APC and IPC affect 'protein kinase B (Akt)'. APC promoted miR­17­3p and suppressed miR­27a. IPC promoted miR­19a. All the miRs were predicted to regulate phosphorylated Akt, which promotes cell­protection. Western blot analysis showed that expression of phosphorylated Akt increased and phosphatase and tensin homologue deleted from chromosome 10 (PTEN) decreased following APC and IPC. The present study concluded that APC and IPC affect different miRs, although they are estimated to similarly promote the PTEN/phosphoinositide 3­kinase/Akt signaling pathway, resulting in reno­protection.


Assuntos
Precondicionamento Isquêmico/métodos , MicroRNAs/metabolismo , Traumatismo por Reperfusão/prevenção & controle , Sevoflurano/uso terapêutico , Animais , Western Blotting , Creatinina/sangue , Hemodinâmica/efeitos dos fármacos , Masculino , Ratos , Ratos Wistar
16.
Clin Hemorheol Microcirc ; 75(2): 151-162, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-31985456

RESUMO

BACKGROUND: Ischemic preconditioning (IPC) is defined as raising tolerance to subsequent ischemic stress by exposing tissues to sub-lethal ischemia. Although many candidates have been suggested, recent studies have clearly demonstrated that adenosine-mediated ADORA2B receptor (ADORA2BR) activation is the main mechanism involved in IPC. While the tissue-protective role of this mechanism has been demonstrated in different ischemia/reperfusion (I/R) models, its role in flap surgery-derived I/R damage has not to date been investigated. OBJECTIVE: To investigate the role of adenosine and ADORA2BR activation in IPC-mediated tissue protection in an epigastric flap model. METHODS: Animals were divided into five main groups, all of which were then divided into two subgroups depending on whether or not they were exposed to IPC before the I/R procedure, which consisted of 6 hours of ischemia and 6 days of reperfusion. No drugs were administered in Group 1 (the control group). Animals in Group 2 were pretreated with CD73-inhibitor before IPC application or the ischemic period. Animals in Group 3 were pretreated with adenosine. Animals in Group 4 were pretreated with an ADORA2BR antagonist, and those in Group 5 with an ADORA2BR agonist. After 6 days of reperfusion, tissue survival was evaluated via histological and macroscopic analysis. RESULTS: IPC application significantly enhanced CD73 expressions and adenosine concentrations (p < 0.01). Flap survivals were increased by IPC in Group 1 (p < 0.05). However, CD73 inhibition blocked this increase (Group 2). In Group 3, adenosine improved flap survival even in the absence of IPC (p < 0.01). While an ADORA2BR antagonist attenuated the tissue-protective effect of IPC (p < 0.01), the ADORA2BR agonist improved flap survival by mimicking IPC in groups 4 and 5. CONCLUSION: These results provide pharmacological evidence for a contribution of CD73 enzyme-dependent adenosine generation and signaling through ADORA2BR to IPC-mediated tissue protection. They also suggest for the first time that ADORA2BR agonists may be used as a potential preventive therapy against I/R injury in flap surgeries.


Assuntos
Adenosina/metabolismo , Precondicionamento Isquêmico/métodos , Receptor A2B de Adenosina/metabolismo , Traumatismo por Reperfusão/patologia , Retalhos Cirúrgicos/patologia , Sobrevivência de Tecidos/efeitos dos fármacos , Animais , Feminino , Humanos , Ratos , Ratos Wistar
17.
Exp Neurol ; 325: 113142, 2020 03.
Artigo em Inglês | MEDLINE | ID: mdl-31812555

RESUMO

BACKGROUND AND PURPOSE: A major gap in the field of ischemic preconditioning (IPC) is whether or not long-lasting neuroprotection can be achieved. Moreover, the specific mechanisms underlying IPC and how they can be translated into the clinic remain uncertain. To fill these gaps, we tested the hypothesis that IPC exerts long-lasting structural and functional neuroprotection against ischemic stroke through the master gatekeeper of antioxidant defenses, nuclear factor erythroid 2-related factor 2 (Nrf2). We also tested whether the brain could be pharmaceutically preconditioned with a potent and blood-brain barrier-permeable Nrf2 activator, 2-cyano-3,12-dioxo-oleana-1,9(11)-dien-28-trifluoethyl amide (CDDO-TFEA). METHODS: IPC was induced by transient middle cerebral artery occlusion (MCAO) for 12 min, and ischemic stroke was generated by MCAO for 60 min in wild-type (WT) or Nrf2 knockout (KO) mice. Sensorimotor function, learning/memory skills, and brain tissue loss were measured up to 35 days after stroke. Primary rodent cortical neurons from wildtype (WT) and Nrf2 KO mice were subjected to lethal oxygen-glucose deprivation (OGD) or a brief OGD episode as a preconditioning (PC) stimulus before OGD. Cell viability/death, lipid electrophile generation, and Nrf2 activation were measured. CDDO-TFEA or its vehicle was administered in vivo for three consecutive days before MCAO. Tissue loss and neurological tests were performed 35 days after stroke. RESULTS: IPC significantly reduced sensorimotor deficits, post-stroke cognitive impairments, and brain tissue loss, 35 days after MCAO in WT mice. These enduring protective effects of IPC were inhibited in Nrf2 KO mice. In neuronal cultures, PC also endowed primary neurons with ischemic tolerance against OGD-induced cell death, an effect that was abolished by loss of Nrf2 expression in KO neurons. PC induced the generation of low levels of lipid electrophiles and led to activation of the Nrf2 pathway. The mechanism underlying IPC may be translatable, as exogenous administration of the Nrf2 activator CDDO-TFEA significantly reduced neurological dysfunction and ischemic brain damage after MCAO. CONCLUSIONS: IPC provides long-lasting neuroprotection against ischemic brain injury and post-stroke cognitive dysfunction. Nrf2 activation plays a key role in this beneficial outcome and is a promising therapeutic target for the attenuation of ischemic brain injury.


Assuntos
Encéfalo/irrigação sanguínea , Infarto da Artéria Cerebral Média/metabolismo , Infarto da Artéria Cerebral Média/patologia , Precondicionamento Isquêmico , Fator 2 Relacionado a NF-E2/metabolismo , Animais , Encéfalo/efeitos dos fármacos , Encéfalo/metabolismo , Precondicionamento Isquêmico/métodos , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Neurônios/efeitos dos fármacos , Neurônios/metabolismo , Fármacos Neuroprotetores/farmacologia , Ácido Oleanólico/análogos & derivados , Ácido Oleanólico/farmacologia , Recuperação de Função Fisiológica/efeitos dos fármacos
18.
Surg Today ; 50(11): 1323-1331, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31612330

RESUMO

Staged esophagectomy was developed in the mid-twentieth century in an attempt to reduce high rates of postoperative morbidity and mortality. Nowadays, the operation has almost been abandoned due to its significant disadvantages, especially the need for multiple surgeries, inability of patients to feed between operations, and morbidity of esophageal stoma. However, staged esophagectomy is still occasionally useful for very high-risk patients and in particular cases, for example multiple cancers of the aerodigestive tract and emergent esophagectomy. Staged esophagectomy is based on the division of surgical stress into two operations, which gives the patient time to recover before final restoration. Gastric tube ischemic preparation may be a more important mechanism in staged esophagectomy. This approach may survive and expand with the application of ischemic gastric pre-conditioning through embolization or laparoscopic ligation of the gastric arteries, which is a less explored and promising technique.


Assuntos
Neoplasias Esofágicas/cirurgia , Esofagectomia/métodos , Esôfago/cirurgia , Precondicionamento Isquêmico/métodos , Artéria Gástrica/cirurgia , Humanos , Laparoscopia/métodos , Ligadura/métodos , Cuidados Pré-Operatórios/métodos
19.
Glia ; 68(1): 76-94, 2020 01.
Artigo em Inglês | MEDLINE | ID: mdl-31420975

RESUMO

Ischemic preconditioning (IPC) is an experimental phenomenon in which a subthreshold ischemic insult applied to the brain reduces damage caused by a subsequent more severe ischemic episode. Identifying key molecular and cellular mediators of IPC will provide critical information needed to develop novel therapies for stroke. Here we report that the transcriptomic response of acutely isolated preconditioned cortical microglia is dominated by marked upregulation of genes involved in cell cycle activation and cellular proliferation. Notably, this transcriptional response occurs in the absence of cortical infarction. We employed ex vivo flow cytometry, immunofluorescent microscopy, and quantitative stereology methods on brain tissue to evaluate microglia proliferation following IPC. Using cellular colocalization of microglial (Iba1) and proliferation (Ki67 and BrdU) markers, we observed a localized increase in the number of microglia and proliferating microglia within the preconditioned hemicortex at 72, but not 24, hours post-IPC. Our quantification demonstrated that the IPC-induced increase in total microglia was due entirely to proliferation. Furthermore, microglia in the preconditioned hemisphere had altered morphology and increased soma volumes, indicative of an activated phenotype. Using transgenic mouse models with either fractalkine receptor (CX3CR1)-haploinsufficiency or systemic type I interferon signaling loss, we determined that microglial proliferation after IPC is dependent on fractalkine signaling but independent of type I interferon signaling. These findings suggest there are multiple distinct targetable signaling pathways in microglia, including CX3CR1-dependent proliferation that may be involved in IPC-mediated protection.


Assuntos
Ciclo Celular/fisiologia , Córtex Cerebral/metabolismo , Infarto da Artéria Cerebral Média/metabolismo , Precondicionamento Isquêmico/métodos , Microglia/metabolismo , Transcriptoma/fisiologia , Animais , Proliferação de Células/fisiologia , Córtex Cerebral/patologia , Infarto da Artéria Cerebral Média/patologia , Infarto da Artéria Cerebral Média/prevenção & controle , Masculino , Camundongos , Camundongos Endogâmicos C57BL
20.
Ann Vasc Surg ; 62: 452-462, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31394251

RESUMO

BACKGROUND: Whether remote ischemic preconditioning (RIPC), through several cycles of ischemia-reperfusion, can generate endogenous protective substances to protect patients undergoing elective major vascular surgery remains unclear. The results derived from many randomized controlled trials (RCTs) have been discrepant. METHODS: PubMed (1966 to May 2018) and EMBASE (1966 to May 2018) databases were searched to identify all published RCTs that assessed the effect of RIPC in patients undergoing elective major vascular surgery. Then, we performed a systematic review and meta-analysis to merge the outcomes of RIPC procedures from each RCT, which included all-cause mortality, myocardial infarction (MI), acute kidney injury (AKI), and/or new-onset arrhythmia. RESULTS: A total of 909 patients were enrolled from 10 eligible studies that were conducted from 2007 through 2016. A fixed effect model was utilized in this study to pool each effect size. Pooled analyses of all RCTs showed that RIPC did not reduce the incidence of all-cause mortality (pooled risk ratio [RR] 1.36, 95% confidence interval [CI] 0.63-2.92, P = 0.56), MI (pooled RR 0.77, 95% CI 0.48-1.22, P = 0.38), AKI (pooled RR 0.93, 95% CI 0.68-1.27, P = 0.10), or new-onset arrhythmia (pooled RR 1.47, 95% CI 0.83-2.60, P = 0.52) compared with the control treatment. The publication bias detected by Begg's test was low. CONCLUSIONS: There is no prominent evidence to support the hypothesis that RIPC can provide perioperative protection to patients undergoing elective major vascular surgery. Therefore, the routine use of RIPC to reduce the incidence of perioperative complications of these operations may not be recommended.


Assuntos
Precondicionamento Isquêmico/métodos , Oclusão Terapêutica , Procedimentos Cirúrgicos Vasculares , Lesão Renal Aguda/etiologia , Lesão Renal Aguda/mortalidade , Lesão Renal Aguda/prevenção & controle , Idoso , Arritmias Cardíacas/etiologia , Arritmias Cardíacas/mortalidade , Arritmias Cardíacas/prevenção & controle , Procedimentos Cirúrgicos Eletivos , Feminino , Humanos , Precondicionamento Isquêmico/efeitos adversos , Masculino , Pessoa de Meia-Idade , Infarto do Miocárdio/etiologia , Infarto do Miocárdio/mortalidade , Infarto do Miocárdio/prevenção & controle , Ensaios Clínicos Controlados Aleatórios como Assunto , Fluxo Sanguíneo Regional , Fatores de Risco , Oclusão Terapêutica/efeitos adversos , Fatores de Tempo , Resultado do Tratamento , Procedimentos Cirúrgicos Vasculares/efeitos adversos , Procedimentos Cirúrgicos Vasculares/mortalidade
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