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1.
Plast Reconstr Surg ; 144(4): 619e-629e, 2019 10.
Artigo em Inglês | MEDLINE | ID: mdl-31568298

RESUMO

BACKGROUND: The authors hypothesize that ischemic preconditioning of the recipient site with deferoxamine will increase fat graft survival by enhancing angiogenesis in a rat model. METHODS: Cell viability, tube formation, and mRNA expression were measured in human umbilical vein endothelial cells treated with deferoxamine. A total of 36 rats were then used for an in vivo study. A dose of 100 mg/kg of deferoxamine was injected subcutaneously into the rat scalp every other day for five treatments. On the day after the final injection, the scalp skin was harvested from half the animals to evaluate the effects of deferoxamine on the recipient site. In the remaining animals, inguinal fat tissue was transplanted to the scalp. Eight weeks after transplantation, the grafts were harvested to evaluate the effects of deferoxamine preconditioning on fat graft survival. RESULTS: In human umbilical vein endothelial cells, treatment with a deferoxamine concentration higher than 400 µM decreased cell viability compared with the control (p = 0.002). Treatment with 100 and 200 µM deferoxamine increased endothelial tube formation (p = 0.001) and mRNA levels of angiogenesis-related factors (p = 0.02). Rat scalps treated with deferoxamine exhibited increased capillary neoformation (p = 0.001) and vascular endothelial growth factor protein expression (p = 0.024) compared with controls. Fat graft volume retention, capillary density (p < 0.001), and adipocyte viability (p < 0.001) in the grafted fat increased when the recipient site was preconditioned with deferoxamine. CONCLUSION: This study demonstrated that recipient site preconditioning with deferoxamine increases fat graft survival by inducing vascular endothelial growth factor and neovascularization.


Assuntos
Tecido Adiposo/transplante , Desferroxamina/farmacologia , Sobrevivência de Enxerto/efeitos dos fármacos , Células Endoteliais da Veia Umbilical Humana/efeitos dos fármacos , Precondicionamento Isquêmico/métodos , Neovascularização Fisiológica/efeitos dos fármacos , Fatores de Crescimento do Endotélio Vascular/biossíntese , Fatores de Crescimento do Endotélio Vascular/efeitos dos fármacos , Animais , Humanos , Masculino , Modelos Animais , Distribuição Aleatória , Ratos , Ratos Sprague-Dawley , Fator A de Crescimento do Endotélio Vascular
2.
Acta Cir Bras ; 34(8): e201900805, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31618405

RESUMO

PURPOSE: To investigate the effect of sevoflurane preconditioning on ischemia/reperfusion (I/R)-induced pulmonary/hepatic injury. METHODS: Fifty-one Wistar rats were randomly grouped into sham, I/R, and sevoflurane groups. After reperfusion, the structural change of the lung was measured by Smith score, the wet and dry weights (W/D) were determined, malondialdehyde (MDA) myeloperoxidase (MPO) content was determined colorimetrically and by fluorescence, respectively, and matrix metalloprotein-9 (MMP-9) mRNA was quantified by RT-PCR. Biopsy and morphological analyses were performed on liver tissue, activities of aspartate aminotransferase (AST) and alanine aminotransferase (ALT) were determined, and tumor necrosis factor-alpha (TNF-α) level was determined. RESULTS: The sham group showed no changes in tissue structure. Structural lesions in the sevoflurane and I/R groups were mild and severe, respectively. Smith score, W/D, MDA, MPO, and MMP mRNA showed the same trend, and were increased in the I/R group and recovered in the sevoflurane group, compared with the sham group (both P<0.05). AST and ALT were significantly increased compared to the sham group (AST: 655±52.06 vs . 29±9.30 U/L; ALT: 693±75.56 vs . 37±6.71 U/L; P<0.05). In the sevoflurane group, AST and ALT levels were significantly decreased (464±47.71 and 516±78.84 U/L; P<0.001). TNF-α presented similar results. CONCLUSION: The protection of lung and liver by sevoflurane may be mediated by inhibited leukocyte recruitment and MMP-9 secretion.


Assuntos
Anestésicos Inalatórios/uso terapêutico , Precondicionamento Isquêmico/métodos , Fígado/irrigação sanguínea , Pulmão/irrigação sanguínea , Traumatismo por Reperfusão/prevenção & controle , Sevoflurano/uso terapêutico , Alanina Transaminase/sangue , Animais , Aspartato Aminotransferases/sangue , Modelos Animais de Doenças , Isquemia/prevenção & controle , Fígado/efeitos dos fármacos , Fígado/patologia , Pulmão/efeitos dos fármacos , Pulmão/patologia , Masculino , Malondialdeído/análise , Peroxidase/análise , Ratos , Ratos Wistar , Traumatismo por Reperfusão/tratamento farmacológico , Fator de Necrose Tumoral alfa/sangue
3.
Turk Neurosurg ; 29(6): 933-939, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31608967

RESUMO

AIM: To evaluate the effect of different remote ischemic preconditioning (RIPC) methods in spinal cord ischemia-reperfusion (IR) injury. MATERIAL AND METHODS: A total of 36 rats were distributed to the 6 groups: sham surgery, control (only spinal cord IR), unilateral (hind limb RIPC before spinal cord IR), bilateral (hind limbs RIPC before spinal cord IR), ipsilateral (hind and fore limbs RIPC to the right before spinal cord IR), contralateral (right hind limb and left fore limb as RIPC before spinal cord IR). Thirty minutes after RIPC, the spinal cord was subjected to ischemia for 60 minutes. Seventy two hours after IR, all rats were evaluated by neurological function, histological and biochemical examinations. RESULTS: The mean Motor Deficit Index (MDI) scores in the ipsilateral, contralateral, and bilateral groups were lower than that of the unilateral group (p < 0.05). The mean malondialdehyde (MDA) in ipsilateral group was lower than were control group (p < 0.05). The mean total antioxidant capacity (TAC) and the mean number of normal motor neurons in the experimental groups were significantly higher than increased control group (p < 0.05). The mean plasma levels of catalase in the contralateral, ipsilateral, and bilateral groups were significantly increased compared to control group (p < 0.05). The mean scores of white matter damage in contralateral, bilateral, and unilateral groups were lower than control group (p < 0.05). CONCLUSION: The results of this study show that contralateral, ipsilateral, and bilateral limb RIPC may reduce the complications of spinal cord ischemic injury.


Assuntos
Precondicionamento Isquêmico/métodos , Neuroproteção , Traumatismo por Reperfusão/terapia , Isquemia do Cordão Espinal/terapia , Animais , Extremidades/irrigação sanguínea , Masculino , Neuroproteção/fisiologia , Ratos , Ratos Sprague-Dawley , Traumatismo por Reperfusão/patologia , Isquemia do Cordão Espinal/patologia
4.
Acta Cir Bras ; 34(7): e201900707, 2019 Sep 16.
Artigo em Inglês | MEDLINE | ID: mdl-31531528

RESUMO

PURPOSE: To evaluate the effects of splenic ischemic preconditioning (sIPC) on oxidative stress induced by hepatic ischemia-reperfusion in rats. METHODS: Fifteen male Wistar rats were equally divided into 3 groups: SHAM, IRI and sIPC. Animals from IRI group were subjected to 45 minutes of partial liver ischemia (70%). In the sIPC group, splenic artery was clamped in 2 cycles of 5 min of ischemia and 5 min of reperfusion (20 min total) prior to hepatic ischemia. SHAM group underwent the same surgical procedures as in the remaining groups, but no liver ischemia or sIPC were induced. After 1h, hepatic and splenic tissue samples were harvested for TBARS, CAT, GPx and GSH-Rd measurement. RESULTS: sIPC treatment significantly decreased both hepatic and splenic levels of TBARS when compared to IRI group (p<0.01). Furthermore, the hepatic and splenic activities of CAT, GPx and GSH- Rd were significantly higher in sIPC group than in IRI group. CONCLUSION: sIPC was able to attenuate hepatic and splenic IRI-induced oxidative stress.


Assuntos
Precondicionamento Isquêmico/métodos , Hepatopatias/prevenção & controle , Fígado/irrigação sanguínea , Estresse Oxidativo/fisiologia , Traumatismo por Reperfusão/prevenção & controle , Animais , Modelos Animais de Doenças , Fígado/fisiologia , Hepatopatias/fisiopatologia , Masculino , Distribuição Aleatória , Ratos , Ratos Wistar , Traumatismo por Reperfusão/fisiopatologia
5.
Br J Anaesth ; 123(5): 584-591, 2019 11.
Artigo em Inglês | MEDLINE | ID: mdl-31521337

RESUMO

BACKGROUND: The REnal Protection Against Ischaemia-Reperfusion in transplantation (REPAIR) RCT examined whether remote ischaemic preconditioning (RIPC) improved renal function after living-donor kidney transplantation. The primary endpoint, glomerular filtration rate (GFR), quantified by iohexol at 12 months, suggested that RIPC may confer longer-term benefit. Here, we present yearly follow-up data of estimated GFR for up to 5 yr after transplantation. METHODS: In this double-blind, factorial RCT, we enrolled 406 adult live donor kidney transplant donor-recipient pairs in 15 European transplant centres. RIPC was performed before induction of anaesthesia. RIPC consisted of four 5 min inflations of a BP cuff on the upper arm to 40 mm Hg above systolic BP separated by 5 min periods of cuff deflation. For sham RIPC, cuff inflation to 40 mm Hg was undertaken. Pairs were randomised to sham RIPC, early RIPC only (immediately pre-surgery), late RIPC only (24 h pre-surgery), or dual RIPC (early and late RIPC). The pre-specified secondary outcome of estimated GFR (eGFR) was calculated from serum creatinine measurements, using the Chronic Kidney Disease Epidemiology Collaboration equation. Predefined safety outcomes were mortality and graft loss. RESULTS: There was a sustained improvement in eGFR after early RIPC, compared with control from 3 months to 5 yr (adjusted mean difference: 4.71 ml min-1 (1.73 m)-2 [95% confidence interval, CI: 1.54-7.89]; P=0.004). Mortality and graft loss were similar between groups (RIPC: 20/205 [9.8%] vs control 24/201 [11.9%]; hazard ratio: 0.79 [95% CI: 0.43-1.43]). CONCLUSIONS: RIPC safely improves long-term kidney function after living-donor renal transplantation when administered before induction of anaesthesia. CLINICAL TRIAL REGISTRATION: ISRCTN30083294.


Assuntos
Precondicionamento Isquêmico/métodos , Transplante de Rim , Traumatismo por Reperfusão/prevenção & controle , Adolescente , Adulto , Idoso , Aloenxertos , Método Duplo-Cego , Europa (Continente) , Feminino , Seguimentos , Taxa de Filtração Glomerular/fisiologia , Humanos , Rim/fisiologia , Rim/cirurgia , Doadores Vivos , Masculino , Pessoa de Meia-Idade , Tempo , Resultado do Tratamento , Adulto Jovem
6.
Eur J Appl Physiol ; 119(10): 2363-2373, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31473805

RESUMO

PURPOSE: Unaccustomed exercise can result in delayed onset muscle soreness (DOMS), particularly as a result of the eccentric phase of the muscle contraction. Resistance training combined with venous blood flow restriction (vBFR) may attenuate DOMS, but the available information in this regard is conflicting. Therefore, the purpose of this study was to examine the effects of low-load eccentric vBFR (Ecc-vBFR) and concentric vBFR (Con-vBFR) resistance training on indices of DOMS. METHODS: Twenty-five previously untrained women completed seven days of either Ecc-vBFR (n = 12) or Con-vBFR (n = 13) forearm flexion resistance training at a velocity of 120° s-1 on an isokinetic dynamometer. The Ecc-vBFR group used a training load that corresponded to 30% of eccentric peak torque and the Con-vBFR group used a training load that corresponded to 30% of concentric peak torque. RESULTS: There were no differences between Ecc-vBFR and Con-vBFR at any of the seven training sessions on any of the indices of DOMS. There were no decreases in the maximal voluntary isometric contraction torque which increased at days 6 and 7. Similarly, there were no changes in perceived muscle soreness, pain pressure threshold, elbow joint angle, or edema (as assessed by echo intensity via ultrasound) across the seven training sessions. CONCLUSIONS: The Ecc-vBFR and Con-vBFR low-load training protocols were not associated with DOMS and there were no differences between protocols when performed using the same relative training intensity. These findings suggested that both unaccustomed eccentric and concentric low-load training did not result in DOMS when combined with vBFR.


Assuntos
Precondicionamento Isquêmico/métodos , Músculo Esquelético/fisiologia , Mialgia/prevenção & controle , Treinamento de Resistência/métodos , Feminino , Humanos , Precondicionamento Isquêmico/efeitos adversos , Contração Muscular , Músculo Esquelético/irrigação sanguínea , Mialgia/etiologia , Tempo de Reação , Treinamento de Resistência/efeitos adversos , Adulto Jovem
7.
Eur J Appl Physiol ; 119(10): 2177-2183, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31385030

RESUMO

PURPOSE: Traditional resistance exercise decreases vagal tone up to 30 min after an acute bout of resistance exercise, which may increase the risk of cardiovascular events. However, the effects of resistance exercise with blood flow restriction (BFR) on autonomic modulation are unclear. To evaluate autonomic modulation after resistance exercise with and without BFR in resistance-trained men. METHODS: Eleven young men volunteered for the study. Autonomic modulation was assessed at rest, 15 (Rec 1), and 25 (Rec 2) minutes after low-load bench press with BFR (LL-BFR), traditional high-load bench press (HL), and a control (CON). Autonomic modulation assessments were expressed as natural logarithm (Ln), and included total power (LnTP), low-frequency power (LnLF), high-frequency power (LnHF), sympathovagal balance (LnLF/LnHF ratio), root mean square of the successive differences (LnRMSSD), and the proportion of intervals differing by > 50 ms from the preceding intervals (LnPNN50). A repeated measures ANOVA was used to evaluate conditions (LL-BFR, HL and CON) across time (Rest, Rec1, and Rec2) on autonomic modulation. RESULTS: There were significant condition by time interactions for LnTP, LnHF, and LnRMSSD such that they were reduced during recovery after LL-BFR and HL compared to Rest and CON. There were no interactions in the LnLF, LnLF/LnHF ratio, and LnPNN50. CONCLUSIONS: These data suggest that LL-BFR and HL significantly alter autonomic modulation up to 30 min after exercise with significant reduction after HL compared to LL-BFR when exercise volume is equated.


Assuntos
Sistema Nervoso Autônomo/fisiologia , Precondicionamento Isquêmico/métodos , Treinamento de Resistência/métodos , Adulto , Pressão Sanguínea , Frequência Cardíaca , Humanos , Masculino , Fluxo Sanguíneo Regional
8.
BMC Neurol ; 19(1): 206, 2019 Aug 23.
Artigo em Inglês | MEDLINE | ID: mdl-31443692

RESUMO

BACKGROUND: Subcortical ischemic vascular dementia (SIVD) is very common among the older people, but has no approved treatment. Preclinical trials show that remote ischemic conditioning (RIC) reduces recurrence of ischemic stroke. We hypothesize that RIC may also be an effective therapy for patients with SIVD. METHODS: Thirty-seven consecutive SIVD cases were enrolled in this randomized control study. Eighteen RIC patients underwent five brief cycles of conditioning (bilateral upper limb compression at 200 mmHg) followed by reperfusion twice daily over 6 consecutive months. Nineteen control patients underwent the same process, but at a pressure of 60 mmHg which caused no restriction on the blood flow of the upper limb. The primary outcome measures were changes in neuropsychological assessments. The secondary outcomes included the changes in high-sensitive C-reactive protein (hs-CRP) concentration, white matter lesion volume (WMLV), diffusion tension imaging (DTI) metrics of white matter. All data were collected at baseline and follow-up. RESULTS: A significant treatment difference favoring RIC at 6 months was observed on performance of Hopkins Verbal Learning Test-Revised (HVLT-R), Controlled Oral Word Association Test (COWAT), Trail Making Test A and B (TMT-A & TMT-B), and Judgment of Line Orientation (JLO) (p < 0.05). The control group did not show much improvement after the treatment, and only with a slight change in HVLT-R and TMT-R (p < 0.05). Covariance analysis of efficacy between the two groups suggested that RIC patients performed better on JLO than control patients at the 6-month follow-up (RIC 23.10 vs. control 18.56; p = 0.013). Although DTI metrics were comparable, Hs-CRP levels and WMLV in RIC patients showed a declining trend. CONCLUSIONS: Over the 6-month treatment period, we found that RIC was safe and effective for improving cognitive function in SIVD patients. TRIAL REGISTRATION: Clinical Trial Registration ( http://www.clinicaltrials.gov ), Unique identifier: NCT03022149; Retrospectively registered; Date of registration: January 16, 2017.


Assuntos
Encéfalo/irrigação sanguínea , Cognição , Demência Vascular , Precondicionamento Isquêmico/métodos , Idoso , Idoso de 80 Anos ou mais , Encéfalo/patologia , Encéfalo/fisiopatologia , Demência Vascular/patologia , Demência Vascular/fisiopatologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Extremidade Superior/fisiopatologia
9.
Int Urol Nephrol ; 51(11): 2083-2089, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31407138

RESUMO

PURPOSE: To determine the role of remote perconditioning (RPeC) on renal function and histology in an animal model of unilateral renal ischemia and reperfusion (IR) injury. METHODS: Rats were subjected to 60 min unilateral renal ischemia. RPeC protocol was the application of four cycles of 5 min IR of left femoral artery during renal ischemia. Assessments of histological changes and renal function were made 24 h, 1 week, or 3 weeks later. 99mTc-DMSA scan was performed using a small-animals SPECT system. RESULTS: 24-h reperfusion decreased the 99mTc-DMSA uptake in the left kidney compared to the intact kidney of control animals. RPeC group has higher uptake compared to the IR group. After 1 week and 3 weeks, uptakes were gradually increased in both groups and no differences were observed. Severe morphological changes in the ischemic kidneys of both groups were observed after 24 h which attenuated after 1 week and 3 weeks. Moreover, no differences in creatinine and BUN levels between IR-treated and intact animals were observed. CONCLUSION: These data suggest that RPeC exerts a partially transient improvement in the renal function in the first day after reperfusion. However, long-term follow-up study showed no beneficial effects of RPeC. Moreover, noninvasive 99mTc-DMSA scan revealed a suitable tool in the follow-up evaluation of recovery process in the unilateral renal IR injury models.


Assuntos
Precondicionamento Isquêmico , Rim/irrigação sanguínea , Traumatismo por Reperfusão/prevenção & controle , Animais , Modelos Animais de Doenças , Precondicionamento Isquêmico/métodos , Estudos Longitudinais , Masculino , Cintilografia , Ratos , Ratos Wistar , Traumatismo por Reperfusão/diagnóstico por imagem
10.
Eur J Appl Physiol ; 119(10): 2255-2263, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31420736

RESUMO

AIM: Exercise training with blood flow restriction (BFR) increases muscle size and strength. However, there is limited investigation into the effects of BFR on cardiovascular health, particularly central hemodynamic load. PURPOSE: To determine the effects of BFR exercise on central hemodynamic load (heart rate-HR, central pressures, arterial wave reflection, and aortic stiffness). METHODS: Fifteen males (age = 25 ± 2 years; BMI = 27 ± 2 kg/m2, handgrip max voluntary contraction-MVC = 50 ± 2 kg) underwent 5-min bouts (counter-balanced, 10 min rest between) of rhythmic unilateral handgrip (1 s squeeze, 2 s relax) performed with a moderate-load (60% MVC) with and without BFR (i.e., 71 ± 5% arterial inflow flow reduction, assessed via Doppler ultrasound), and also with a low-load (40% MVC) with BFR. Outcomes included HR, central mean arterial pressure (cMAP), arterial wave reflection (augmentation index, AIx; wave reflection magnitude, RM%), aortic arterial stiffness (pulse wave velocity, aPWV), and peripheral (vastus lateralis) microcirculatory response (tissue saturation index, TSI%). RESULTS: HR increased above baseline and time control for all handgrip bouts, but was similar between the moderate load with and without BFR conditions (moderate-load with BFR = + 9 ± 2; moderate-load without BFR = + 8 ± 2 bpm, p < 0.001). A similar finding was noted for central pressure (e.g., moderate load with BFR, cMAP = + 14 ± 1 mmHg, p < 0.001). No change occurred for RM% or AIx (p > 0.05) for any testing stage. TSI% increased during the moderate-load conditions (p = 0.01), and aPWV increased above baseline following moderate-load handgrip with BFR only (p = 0.012). CONCLUSIONS: Combined with BFR, moderate load handgrip training with BFR does not significantly augment central hemodynamic load during handgrip exercise in young healthy men.


Assuntos
Força da Mão , Frequência Cardíaca , Precondicionamento Isquêmico/métodos , Condicionamento Físico Humano/métodos , Rigidez Vascular , Adulto , Humanos , Masculino , Músculo Esquelético/irrigação sanguínea , Músculo Esquelético/fisiologia , Consumo de Oxigênio , Distribuição Aleatória
11.
Eur J Appl Physiol ; 119(10): 2123-2149, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31451953

RESUMO

Ischemic preconditioning (IPC) has been suggested as a potential ergogenic aid to improve exercise performance, although controversial findings exist. The controversies may be explained by several factors, including the mode of exercise, the ratio between the magnitude of improvement, or the error of measurement and physiological meaning. However, a relevant aspect has been lacking in the literature: the interpretation of the findings considering statistical tests and adequate effect size (ES) according to the fitness level of individuals. Thus, we performed a systematic review with meta-analysis to update the effects of IPC on exercise performance and physiological responses, using traditional statistics (P values), ES, and smallest worth change (SWC) approach contextualizing the IPC application to applied Sports and Exercise performance. Forty-five studies met the inclusion criteria. Overall, the results show that IPC has a minimal or nonsignificant effect on performance considering the fitness level of the individuals, using statistical approaches (i.e., tests with P value, ES, and SWC). Therefore, IPC procedures should be revised and refined in future studies to evaluate if IPC promotes positive effects on performance in a real-world scenario with more consistent interpretation.


Assuntos
Precondicionamento Isquêmico/métodos , Condicionamento Físico Humano/métodos , Tolerância ao Exercício , Humanos , Precondicionamento Isquêmico/efeitos adversos , Consumo de Oxigênio , Condicionamento Físico Humano/efeitos adversos , Aptidão Física
12.
Eur J Appl Physiol ; 119(10): 2313-2325, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31468172

RESUMO

PURPOSES: This study quantified performance, physiological, and perceptual responses during resistance exercise to task failure with blood flow restriction (BFR), in systemic hypoxia, and with these stimuli combined. METHODS: Fourteen young men were tested for 1-repetition maximum (1RM) in the barbell biceps curl and lying triceps extension exercises. On separate visits, subjects performed exercise trials (4 sets to failure at 70% 1RM with 90 s between sets) in six separate randomized conditions, i.e., in normoxia or hypoxia (fraction of inspired oxygen = 20.9% and 12.9%, respectively) combined with three different levels of BFR (0%, 45%, or 60% of resting arterial occlusion pressure). Muscle activation and oxygenation were monitored via surface electromyography and near-infrared spectroscopy, respectively. Arterial oxygen saturation, heart rate, and perceptual responses were assessed following each set. RESULTS: Compared to set 1, the number of repetitions before failure decreased in sets 2, 3, and 4 for both exercises (all P < 0.001), independently of the condition (P > 0.065). Arterial oxygen saturation was lower with systemic hypoxia (P < 0.001), but not BFR, while heart rate did not differ between conditions (P > 0.341). Muscle oxygenation and activation during exercise trials remained unaffected by the different conditions (all P ≥ 0.206). A significant main effect of time, but not condition, was observed for overall perceived discomfort, difficulty breathing, and limb discomfort (all P < 0.001). CONCLUSION: Local and systemic hypoxic stimuli, or a combination of both, did not modify the fatigue-induced change in performance, trends of muscle activation or oxygenation, nor exercise-related sensations during a multi-set resistance exercise to task failure.


Assuntos
Precondicionamento Isquêmico/métodos , Músculo Esquelético/fisiologia , Treinamento de Resistência/métodos , Tolerância ao Exercício , Frequência Cardíaca , Humanos , Hipóxia/fisiopatologia , Precondicionamento Isquêmico/efeitos adversos , Masculino , Músculo Esquelético/irrigação sanguínea , Consumo de Oxigênio , Treinamento de Resistência/efeitos adversos , Respiração , Adulto Jovem
13.
Mol Med Rep ; 20(2): 1837-1845, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31257533

RESUMO

Hypoxic preconditioning (HPC) is neuroprotective against ischaemic brain injury; however, the roles of potential anti­apoptotic signals in this process have not been assessed. To elucidate the molecular mechanisms involved in HPC­induced neuroprotection, the effects of HPC on the cyclic adenosine monophosphate (cAMP)/protein kinase A (PKA)/cAMP response element­binding protein (CREB) signalling pathway and apoptosis in Sprague­Dawley pups (postnatal day 7) treated with propofol were investigated. Western blot and histological analyses demonstrated that HPC exerts multiple effects on the hippocampus, including the upregulation of cAMP and phosphorylation of CREB. These effects were partially blocked by intracerebroventricular injection of the protein kinase antagonist H89 (5 µmol/5 µl). Notably, the level of cleaved caspase­3 was significantly downregulated by treatment with the cAMP agonist Sp­cAMP (20 nmol/5 µl). The results indicate that propofol increased the level of cleaved caspase­3 and Bax by suppressing the activity of cAMP­dependent proteins and Bcl­2; thus, HPC prevents propofol from triggering apoptosis via the cAMP/PKA/CREB signalling pathway.


Assuntos
Lesões Encefálicas/terapia , Precondicionamento Isquêmico/métodos , Neurônios/metabolismo , Neuroproteção/genética , Animais , Animais Recém-Nascidos , Apoptose/genética , Lesões Encefálicas/genética , Lesões Encefálicas/patologia , Lesões Encefálicas/prevenção & controle , AMP Cíclico , Proteína de Ligação ao Elemento de Resposta ao AMP Cíclico/genética , Proteínas Quinases Dependentes de AMP Cíclico/genética , Hipocampo/metabolismo , Hipocampo/patologia , Humanos , Neurônios/patologia , Fosforilação/genética , Propofol/toxicidade , Ratos , Transdução de Sinais/genética , Lobo Temporal/metabolismo , Lobo Temporal/patologia
14.
Chem Biol Interact ; 310: 108738, 2019 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-31283913

RESUMO

Ischemic stroke and reperfusion injury are a common and serve medical situation in the elderly population. H2S is a gas neuromodulator which also possesses anti-oxidant and anti-inflammatory properties, and is found to play neuroprotective effect in neurodegenerative diseases. This study investigated the effect of endogenous and exogenous H2S in a mouse model of ischemic stroke. 129P2-Cbstm1Unc/J mice with heterozygous mutants in H2S generating enzyme cystathionine ß-synthase were used to study the effect of endogenous H2S. H2S donor NaHS was used as exogenous H2S. Animals were pretreated with H2S and then subjected to middle cerebral artery occlusion surgery. Behavioral outcome was evaluated by novel object recognition test. Inflammatory cytokines were measured using ELISA. Western blot was used to detect the activation of NF-κB. Aged 129P2-Cbstm1Unc/J mice showed exaggerated inflammation and more severe cognitive impairment after ischemia, while exogenous H2S treatment inhibited inflammation and attenuated behavioral impairment. The anti-inflammatory effect of H2S was mediated by inhibiting NF-κB. Our findings suggest that both endogenous and exogenous H2S are involved in the neuroprotection against ischemia/reperfusion-induced cerebral injury.


Assuntos
Sulfeto de Hidrogênio/uso terapêutico , Precondicionamento Isquêmico/métodos , Fármacos Neuroprotetores/farmacologia , Traumatismo por Reperfusão/tratamento farmacológico , Animais , Comportamento Animal/efeitos dos fármacos , Disfunção Cognitiva/tratamento farmacológico , Citocinas/metabolismo , Sulfeto de Hidrogênio/farmacologia , Infarto da Artéria Cerebral Média/complicações , Inflamação/tratamento farmacológico , Camundongos , NF-kappa B/metabolismo , Traumatismo por Reperfusão/prevenção & controle
15.
Graefes Arch Clin Exp Ophthalmol ; 257(10): 2095-2101, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31273510

RESUMO

PURPOSE: Remote ischemic conditioning (RIC) implies that transient ischemia in one organ can affect blood flow and protect from ischemia in another remote organ such as the retina. The purpose of the present study was to investigate the effect of RIC on the diameter of retinal arterioles in patients with diabetic retinopathy and whether this effect differs among peripheral and macular vessels. METHODS: In twenty type 1 diabetes patients aged 20-31 years, the Dynamic Vessel Analyzer (DVA) was used to measure diameters of peripheral and macular arterioles during rest, isometric exercise, and flicker stimulation. Measurements were obtained before, immediately after, and 1 h after RIC, and were compared to responses obtained from normal persons. RESULTS: The reduced baseline diameter (p < 0.009) and contraction of peripheral retinal arterioles during isometric exercise (p = 0.025) observed immediately after RIC in normal persons were absent in the studied diabetic patients. CONCLUSIONS: RIC affects the diameter of peripheral but not macular arterioles in normal persons, but the response is abolished in diabetic patients. TRIAL REGISTRATION: NCT03906383.


Assuntos
Diabetes Mellitus Tipo 1/complicações , Retinopatia Diabética/diagnóstico , Isquemia/diagnóstico , Fluxo Sanguíneo Regional/fisiologia , Artéria Retiniana/diagnóstico por imagem , Tomografia de Coerência Óptica/métodos , Vasodilatação/fisiologia , Adulto , Arteríolas/patologia , Arteríolas/fisiopatologia , Retinopatia Diabética/complicações , Retinopatia Diabética/fisiopatologia , Feminino , Humanos , Isquemia/etiologia , Isquemia/fisiopatologia , Precondicionamento Isquêmico/métodos , Masculino , Artéria Retiniana/fisiopatologia , Adulto Jovem
16.
J Surg Res ; 244: 241-250, 2019 12.
Artigo em Inglês | MEDLINE | ID: mdl-31301480

RESUMO

BACKGROUND: Ischemic preconditioning (IPC) can provide a defense against ischemia-reperfusion (IR)-induced acute inflammation and barrier dysfunction in many organs. Because nitric oxide (NO) has been implicated as a trigger or mediator in the IPC mechanism and because neuronal NO synthase (nNOS) is a dominant isoform of NOS in the gastrointestinal tract, our aim was to investigate the role of nNOS in IPC-induced protection after mesenteric IR. MATERIALS AND METHODS: Intestinal IR was induced in sodium pentobarbital-anesthetized dogs by clamping the superior mesenteric artery for 60 min followed by 2 h of reperfusion (IR group; n = 7). In further groups, IPC was used (three cycles of 5-min ischemia/5-min reperfusion periods) before IR in the presence or absence of selective inhibition of nNOS with 7-nitroindazole (5 mg/kg, intravenously, in a bolus 15 min before IPC, n = 6 each). Changes in mesenteric vascular resistance, intramucosal pH (pHi), and small bowel motility were monitored. Plasma nitrite/nitrate levels, intestinal NO synthase activity, leukocyte accumulation, mast cell degranulation, and histologic injury were also determined. RESULTS: Ischemia significantly decreased mesenteric vascular resistance and pHi, whereas IR induced a temporary bowel hypermotility and acute inflammatory reaction. IPC facilitated pHi recovery, attenuated motility dysfunction, elevated NOS-dependent NO production, and reduced leukocyte accumulation, mast cell degranulation, and mucosal injury. Pretreatment with 7-nitroindazole halted the IPC-induced increase in NO availability, pHi recovery, and the anti-inflammatory and morphologic effects. CONCLUSIONS: Our data demonstrate that NO generated by intestinal nNOS plays a pivotal role in IPC-linked tissue protection by inhibiting an IR-related acute inflammatory response.


Assuntos
Mucosa Intestinal/imunologia , Precondicionamento Isquêmico/métodos , Óxido Nítrico Sintase Tipo I/metabolismo , Óxido Nítrico/imunologia , Traumatismo por Reperfusão/prevenção & controle , Animais , Degranulação Celular/imunologia , Modelos Animais de Doenças , Cães , Feminino , Humanos , Mucosa Intestinal/irrigação sanguínea , Mucosa Intestinal/metabolismo , Masculino , Mastócitos/imunologia , Artéria Mesentérica Superior/cirurgia , Óxido Nítrico/metabolismo , Traumatismo por Reperfusão/etiologia
17.
Int Immunopharmacol ; 74: 105711, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31302450

RESUMO

Old livers are more damaged by hepatic ischemia and reperfusion (IR) injury than young livers. The aim of this study was to investigate the effects of ischemic and rapamycin preconditioning on IR injury in old livers. Young (8-week-old) and aged (60-week-old) mice were subjected to IR or a sham control procedure. The aged mice were randomly divided into six groups: IR (CON), IR with ischemic preconditioning (IPC), IR with rapamycin preconditioning (RAPA), IR with combined ischemic and rapamycin preconditioning (IPC + RAPA), IR with 3-methyladenine (3-MA), IR with combined ischemic and rapamycin preconditioning with 3-MA pretreatment (IPC + RAPA+3-MA). Liver injury was evaluated 6 h after reperfusion. Hepatocellular autophagy induction was also analyzed by western blotting. The results revealed that aged mice had aggravated liver IR injury as compared to young mice. In aged mice following IR, IPC + RAPA but not IPC or RAPA alleviated liver injury, as evidenced by lower levels of serum ALT, improved preservation of liver architecture with lower Suzuki scores, and decreased caspase-3 activity compared with CON. In addition, western blot analysis revealed increased LC3B II but decreased p62 protein expression levels in the IPC + RAPA group, indicating that autophagic flux was restored by combined ischemic and rapamycin preconditioning. Furthermore, autophagy inhibition by the inhibitor 3-MA abrogated the protective role in the IPC + RAPA group, while no significant effects were observed in the CON group. In conclusions, our results demonstrated that combined ischemic and rapamycin preconditioning protected old livers against IR injury, which was likely attributed to restored autophagy activation.


Assuntos
Imunossupressores/uso terapêutico , Precondicionamento Isquêmico/métodos , Fígado/patologia , Traumatismo por Reperfusão/terapia , Sirolimo/uso terapêutico , Envelhecimento , Animais , Autofagia/efeitos dos fármacos , Caspase 3/metabolismo , Células Cultivadas , Terapia Combinada , Modelos Animais de Doenças , Humanos , Fígado/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Proteínas Associadas aos Microtúbulos/metabolismo
18.
Rev Cardiovasc Med ; 20(2): 59-71, 2019 Jun 30.
Artigo em Inglês | MEDLINE | ID: mdl-31344998

RESUMO

Remote ischemic conditioning of the heart (including pre-, per-, and post-conditioning) is a phenomenon where short episodes of non-lethal ischemia in the distant vessels within the heart or distant organs from the heart protects the myocardium against sustained ischemia/reperfusion injury. Several pathways have been proposed to be involved in the mechanisms of Remote ischemic conditioning. While triggers of Remote ischemic conditioning act in preconditioned areas, its mediators transduce protective signals via humoral or neuronal pathways to the heart. Remote ischemic conditioning is mediated via receptor and nonreceptor signaling through secondary mediators, which transfer the signal within the cardiomyocyte and activate cardioprotective pathways that lead to higher resistance of the heart to ischemia/reperfusion. Apparently, identification of endogenous signal molecules involved in the mechanisms of Remote ischemic conditioning have therapeutic implications in the management of patients suffering from myocardial ischemia through the development of diverse beneficial effects. Recently, different non-coding RNAs such as microRNAs or long non-coding RNAs have been identified as emerging factors that trigger protective mechanisms in the heart. These non-coding RNAs are transferred to the heart via extracellular vesicles that exert remote cardioprotection. This review is intended to summarize the existing knowledge about the potential role of extracellular vesicles as humoral transmitters of Remote ischemic conditioning and emphasize the involvement of non-coding RNAs in the mechanism of cardioprotection by Remote ischemic conditioning.


Assuntos
Vesículas Extracelulares/metabolismo , Pós-Condicionamento Isquêmico/métodos , Precondicionamento Isquêmico/métodos , Traumatismo por Reperfusão Miocárdica/prevenção & controle , Miocárdio/metabolismo , RNA não Traduzido/metabolismo , Animais , Vesículas Extracelulares/genética , Vesículas Extracelulares/patologia , Regulação da Expressão Gênica , Humanos , Traumatismo por Reperfusão Miocárdica/genética , Traumatismo por Reperfusão Miocárdica/metabolismo , Traumatismo por Reperfusão Miocárdica/patologia , Miocárdio/patologia , RNA não Traduzido/genética , Transdução de Sinais
19.
Turk J Med Sci ; 49(4): 1249-1255, 2019 08 08.
Artigo em Inglês | MEDLINE | ID: mdl-31342735

RESUMO

Background/aim: Since the nature of ischemia/reperfusion (IR)-induced tissue damage is multifactorial and complex, in the current study, the effects of multiple treatment strategies via concomitant administration of erythropoietin (EPO) and N-acetylcysteine (NAC) with an ischemic preconditioning (IPC) regimen on renal IR injury were examined. Materials and methods: Thirty male Wistar rats were subjected to bilateral occlusion of the renal pedicles for 50 min followed by reperfusion. EPO (1000 IU/kg) was administered for 3 days, as well as IPC before the IR and NAC (150 mg/kg) administration for 4 days after IR. The animals were randomly allocated into 6 groups (n = 5): sham, IR, EPO+IR, IPC+IR, NAC+IR, and EPO+IPC+NAC+IR. Kidney tissues and blood samples were obtained for oxidative stress, proinflammatory cytokines, and renal functional evaluations. Results: IR caused significant inflammatory response, oxidative stress, and reduced renal function. Treatment with EPO, IPC, and NAC or a combination of two of them attenuated renal dysfunction and reduced the oxidative stress and inflammatory markers. Rats treated with the combination of EPO, IPC, and NAC showed a higher degree of protection compared to the other groups. Conclusion: These results showed that concomitant administration of EPO and IPC along with posttreatment NAC may have additive beneficial effects on kidney IR injury during IR-induced acute renal failure.


Assuntos
Acetilcisteína/farmacologia , Eritropoetina/farmacologia , Precondicionamento Isquêmico/métodos , Rim , Traumatismo por Reperfusão , Animais , Nitrogênio da Ureia Sanguínea , Creatinina/sangue , Citocinas/sangue , Modelos Animais de Doenças , Rim/efeitos dos fármacos , Rim/lesões , Rim/fisiopatologia , Nefropatias/metabolismo , Nefropatias/fisiopatologia , Masculino , Estresse Oxidativo/efeitos dos fármacos , Ratos , Ratos Wistar , Traumatismo por Reperfusão/metabolismo , Traumatismo por Reperfusão/fisiopatologia
20.
Plast Reconstr Surg ; 144(1): 124-133, 2019 07.
Artigo em Inglês | MEDLINE | ID: mdl-31246814

RESUMO

BACKGROUND: Free jejunal flaps are among the most commonly used flaps for esophageal reconstruction. However, ischemia-reperfusion injury caused by warm ischemia seen during transfer limits their use. Iloprost, a prostacyclin analogue, has been shown to reduce ischemia-reperfusion injury in various organs. The authors investigated tissue damage in jejunal flaps with iloprost and ischemic preconditioning and compared the effectiveness of these two modalities. METHODS: Thirty-four Sprague-Dawley rats were randomized into five groups: sham, ischemia-reperfusion (control), ischemic preconditioning, iloprost, and ischemic preconditioning plus iloprost. All flaps, except those in the sham group, underwent ischemia for 60 minutes and reperfusion for 2 hours. Flap perfusion was assessed by laser Doppler perfusion monitoring. Histologic sections were scored using the Chiu scoring system. Superoxide dismutase and myeloperoxidase levels were measured spectrophotometrically. RESULTS: Animals that were administered iloprost and/or underwent ischemic preconditioning had better postischemic recovery of mesenteric perfusion (ischemic preconditioning, 78 percent; iloprost, 83 percent; ischemic preconditioning plus iloprost, 90 percent; versus ischemia-reperfusion, 50 percent; p < 0.05). All intervention groups showed improved histology of jejunal flaps following ischemia-reperfusion injury (ischemic preconditioning, 3; iloprost, 2.3; ischemic preconditioning plus iloprost, 3.2; versus ischemia-reperfusion, 4.7; p < 0.01, p < 0.001, and p < 0.05, respectively). Superoxide dismutase levels were higher in ischemic preconditioning, iloprost plus ischemic preconditioning, and iloprost groups (ischemic preconditioning, 2.7 ± 0.2; ischemic preconditioning plus iloprost, 2.5 ± 0.3; versus ischemia-reperfusion, 1.2 ± 0.1; p < 0.01; iloprost, 2.4 ± 1.1; versus ischemia-reperfusion, 1.2 ± 0.1; p < 0.05). Myeloperoxidase, a marker for neutrophil infiltration, was lower in the iloprost group (iloprost, 222 ± 5; versus ischemia-reperfusion, 291 ± 25; p < 0.05). CONCLUSIONS: This study showed that both iloprost and ischemic preconditioning reduced reperfusion injury in jejunal flaps. Based on histologic results, iloprost may be a novel treatment alternative to ischemic preconditioning.


Assuntos
Retalhos de Tecido Biológico , Iloprosta/farmacologia , Precondicionamento Isquêmico/métodos , Jejuno/transplante , Inibidores da Agregação de Plaquetas/farmacologia , Traumatismo por Reperfusão/prevenção & controle , Animais , Antioxidantes/metabolismo , Biomarcadores/metabolismo , Modelos Animais de Doenças , Esôfago/cirurgia , Fluxometria por Laser-Doppler/métodos , Masculino , Infiltração de Neutrófilos/efeitos dos fármacos , Peroxidase/metabolismo , Distribuição Aleatória , Ratos Sprague-Dawley , Superóxido Dismutase/metabolismo
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