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Thioredoxin-1 (Trx1) has cardioprotective effects on ischemia/reperfusion (I/R) injury, although its role in ischemic postconditioning (PostC) in middle-aged mice is not understood. This study aimed to evaluate if combining two cardioprotective strategies, such as Trx1 overexpression and PostC, could exert a synergistic effect in reducing infarct size in middle-aged mice. Young or middle-aged wild-type mice (Wt), transgenic mice overexpressing Trx1, and dominant negative (DN-Trx1) mutant of Trx1 mice were used. Mice hearts were subjected to I/R or PostC protocol. Infarct size, hydrogen peroxide (H2O2) production, protein nitration, Trx1 activity, mitochondrial function, and Trx1, pAkt and pGSK3ß expression were measured. PostC could not reduce infarct size even in the presence of Trx1 overexpression in middle-aged mice. This finding was accompanied by a lack of Akt and GSK3ß phosphorylation, and Trx1 expression (in Wt group). Trx1 activity was diminished and H2O2 production and protein nitration were increased in middle-age. The respiratory control rate dropped after I/R in Wt-Young and PostC restored this value, but not in middle-aged groups. Our results showed that Trx1 plays a key role in the PostC protection mechanism in young but not middle-aged mice, even in the presence of Trx1 overexpression.

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BACKGROUND: Ischemic conditioning may help patients with ST-segment elevation myocardial infarction (STEMI) to limit ventricular remodeling. OBJECTIVES: To investigate the effect of remote ischemic postconditioning (RIPC) on left ventricular function during primary percutaneous coronary intervention (PPCI) in patients with STEMI. MATERIAL AND METHODS: Pre- and post-test intervention study with a total of 60 STEMI patients. Patients were divided in two groups: with and without RIPC. RESULTS: During the 6-month follow-up, a significant difference in left ventricular ejection fraction was observed in patients who underwent PPCI, which was higher in the group with RIPC in comparison with the group without RIPC: 1.0% (-1.0 to 4.3) vs. -1.0% (-4.0 to 1.3), p = 0.033. In addition, at 6-month measurement, left ventricular end-systolic volume in patients without RIPC was higher in comparison with their counterparts: 79.3 ± 30.5 mL vs. 64.4 ± 21.4 mL, p = 0.032. CONCLUSIONS: RIPC shows favorable effects on left ventricular function and, therefore, in the future, it could be a potential cardioprotective strategy against ischemia-reperfusion injury in STEMI patients.

ANTECEDENTES: En los pacientes con infarto agudo de miocardio con elevación del segmento ST (IAMCEST), el acondicionamiento isquémico puede ayudar a limitar la remodelación ventricular. OBJETIVOS: Investigar el efecto del posacondicionamiento isquémico remoto (PAIR) en la función del ventrículo izquierdo durante la intervención coronaria percutánea primaria (ICPP) en pacientes con IAMCEST. MATERIAL Y MÉTODOS: Estudio de intervención pre y posprueba con un total de 60 pacientes con IAMCEST. Los pacientes fueron divididos en dos grupos: con y sin PAIR. RESULTADOS: En el seguimiento de seis meses se observó una diferencia significativa en la fracción de eyección del ventrículo izquierdo en pacientes con ICPP, la cual fue mayor en el grupo con PAIR en comparación con el grupo sin PAIR: 1.0 (−1.0 a 4.3) versus −1.0 (−4.0 a ­1.3), p = 0.033. En la medición de seis meses, el volumen sistólico final del ventrículo izquierdo en los pacientes sin PAIR fue mayor en comparación con el grupo homólogo: 79.3 ± 30.5 mL versus 64.4 ± 21.4 mL, p = 0.032. CONCLUSIONES: PAIR muestra efectos favorables en la función ventricular izquierda y, por lo tanto, en el futuro podría ser una estrategia cardioprotectora potencial contra la lesión por isquemia-reperfusión en pacientes con IAMCEST.

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Resumen Antecedentes: En los pacientes con infarto agudo de miocardio con elevación del segmento ST (IAMCEST), el acondicionamiento isquémico puede ayudar a limitar la remodelación ventricular. Objetivos: Investigar el efecto del posacondicionamiento isquémico remoto (PAIR) en la función del ventrículo izquierdo durante la intervención coronaria percutánea primaria (ICPP) en pacientes con IAMCEST. Material y métodos: Estudio de intervención pre y posprueba con un total de 60 pacientes con IAMCEST. Los pacientes fueron divididos en dos grupos: con y sin PAIR. Resultados: En el seguimiento de seis meses se observó una diferencia significativa en la fracción de eyección del ventrículo izquierdo en pacientes con ICPP, la cual fue mayor en el grupo con PAIR en comparación con el grupo sin PAIR: 1.0 (−1.0 a 4.3) versus −1.0 (−4.0 a –1.3), p = 0.033. En la medición de seis meses, el volumen sistólico final del ventrículo izquierdo en los pacientes sin PAIR fue mayor en comparación con el grupo homólogo: 79.3 ± 30.5 mL versus 64.4 ± 21.4 mL, p = 0.032. Conclusiones: PAIR muestra efectos favorables en la función ventricular izquierda y, por lo tanto, en el futuro podría ser una estrategia cardioprotectora potencial contra la lesión por isquemia-reperfusión en pacientes con IAMCEST.

Abstract Background: Ischemic conditioning may help patients with ST-segment elevation myocardial infarction (STEMI) to limit ventricular remodeling. Objectives: To investigate the effect of remote ischemic postconditioning (RIPC) on left ventricular function during primary percutaneous coronary intervention (PPCI) in patients with STEMI. Material and methods: Pre- and post-test intervention study with a total of 60 STEMI patients. Patients were divided in two groups: with and without RIPC. Results: At 6-month follow-up evaluation, a significant difference in left ventricular ejection fraction was observed in patients who underwent PPCI, which was higher in the group with RIPC in comparison with the group without RIPC: 1.0 (−1.0 to 4.3) vs. −1.0 (−4.0 to –1.3), p = 0.033. In addition, at 6-month measurement, left ventricular end-systolic volume in patients without RIPC: was higher in comparison with their counterparts: 79.3 ± 30.5 mL versus 64.4 ± 21.4 mL, p = 0.032. Conclusions: RIPC shows favorable effects on left ventricular function and, therefore, in the future, it could be a potential cardioprotective strategy against ischemia-reperfusion injury in STEMI patients.

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Caveolae-associated signaling toward mitochondria contributes to the cardioprotective mechanisms against ischemia-reperfusion (I/R) injury induced by ischemic postconditioning. In this work, we evaluated the role that the actin-cytoskeleton network exerts on caveolae-mitochondria communication during postconditioning. Isolated rat hearts subjected to I/R and to postconditioning were treated with latrunculin A, a cytoskeleton disruptor. Cardiac function was compared between these hearts and those exposed only to I/R and to the cardioprotective maneuver. Caveolae and mitochondria structures were determined by electron microscopy and maintenance of the actin-cytoskeleton was evaluated by phalloidin staining. Caveolin-3 and other putative caveolae-conforming proteins were detected by immunoblot analysis. Co-expression of caveolin-3 and actin was evaluated both in lipid raft fractions and in heart tissue from the different groups. Mitochondrial function was assessed by respirometry and correlated with cholesterol levels. Treatment with latrunculin A abolishes the cardioprotective postconditioning effect, inducing morphological and structural changes in cardiac tissue, reducing F-actin staining and diminishing caveolae formation. Latrunculin A administration to post-conditioned hearts decreases the interaction between caveolae-forming proteins, the co-localization of caveolin with actin and inhibits oxygen consumption rates in both subsarcolemmal and interfibrillar mitochondria. We conclude that actin-cytoskeleton drives caveolae signaling to mitochondria during postconditioning, supporting their functional integrity and contributing to cardiac adaption against reperfusion injury.

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ABSTRACT Objective: To explore the effect of ischemic postconditioning on myocardial ischemia-reperfusion-induced acute lung injury (ALI). Methods: Forty adult male C57BL/6 mice were randomly divided into sham operation group (SO group), myocardial ischemia-reperfusion group (IR group), ischemic preconditioning group (IPRE group) and ischemic postconditioning group (IPOST group) (10 mice in each group). Anterior descending coronary artery was blocked for 60 min and then reperfused for 15 min to induce myocardial IR. For the IPRE group, 3 consecutive cycles of 5 min of occlusion and 5 minutes of reperfusion of the coronary arteries were performed before ischemia. For the IPOST group, 3 consecutive cycles of 5 min reperfusion and 5 minutes of occlusion of the coronary arteries were performed before reperfusion. Pathological changes of lung tissue, lung wet-to-dry (W/D) weight ratio, inflammatory factors, oxidative stress indicators, apoptosis of lung cells and endoplasmic reticulum stress (ERS) protein were used to evaluate lung injury. Results: After myocardial IR, lung injury worsened significantly, manifested by alveolar congestion, hemorrhage, structural destruction of alveolar septal thickening, and interstitial neutrophil infiltration. In addition, lung W/D ratio was increased, plasma inflammatory factors, including interleukin (IL)-6, tumor necrosis factor (TNF)-α, and IL-17A, were increased, malondialdehyde (MDA) activity of lung tissue was increased, and superoxide dismutase (SOD) activity was decreased after myocardial IR. It was accompanied by the increased protein expression levels of ERS-related protein glucose regulatory protein 78 (GRP78), CCAAT/enhancer-binding protein (C/EBP) homologous protein (CHOP), and caspase-12, and the increased apoptotic indices of lung tissues. Conclusion: IPOST can effectively improve myocardial IR-induced ALI by inhibiting ERS-induced apoptosis of alveolar epithelial cells.

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OBJECTIVE: To explore the effect of ischemic postconditioning on myocardial ischemia-reperfusion-induced acute lung injury (ALI). METHODS: Forty adult male C57BL/6 mice were randomly divided into sham operation group (SO group), myocardial ischemia-reperfusion group (IR group), ischemic preconditioning group (IPRE group) and ischemic postconditioning group (IPOST group) (10 mice in each group). Anterior descending coronary artery was blocked for 60 min and then reperfused for 15 min to induce myocardial IR. For the IPRE group, 3 consecutive cycles of 5 min of occlusion and 5 minutes of reperfusion of the coronary arteries were performed before ischemia. For the IPOST group, 3 consecutive cycles of 5 min reperfusion and 5 minutes of occlusion of the coronary arteries were performed before reperfusion. Pathological changes of lung tissue, lung wet-to-dry (W/D) weight ratio, inflammatory factors, oxidative stress indicators, apoptosis of lung cells and endoplasmic reticulum stress (ERS) protein were used to evaluate lung injury. RESULTS: After myocardial IR, lung injury worsened significantly, manifested by alveolar congestion, hemorrhage, structural destruction of alveolar septal thickening, and interstitial neutrophil infiltration. In addition, lung W/D ratio was increased, plasma inflammatory factors, including interleukin (IL)-6, tumor necrosis factor (TNF)-α, and IL-17A, were increased, malondialdehyde (MDA) activity of lung tissue was increased, and superoxide dismutase (SOD) activity was decreased after myocardial IR. It was accompanied by the increased protein expression levels of ERS-related protein glucose regulatory protein 78 (GRP78), CCAAT/enhancer-binding protein (C/EBP) homologous protein (CHOP), and caspase-12, and the increased apoptotic indices of lung tissues. CONCLUSION: IPOST can effectively improve myocardial IR-induced ALI by inhibiting ERS-induced apoptosis of alveolar epithelial cells.

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Purpose: Acute mesenteric ischemia (AMI) is a condition in pediatric surgery that ranges from intestine necrosis to death. Ischemic postconditioning (IPoC) methods were developed to reduce the damage caused by revascularization. This study aimed to evaluate the efficacy of these methods in an experimental weaning rat model. Methods: Thirty-two 21-day-old Wistar rats were allocated into four groups according to the surgical procedure performed: control, ischemia-reperfusion injury (IRI), local (LIPoC) and remote IPoC (RIPoC). At euthanasia, fragments of the intestine, liver, lungs, and kidneys were submitted to histological, histomorphometric, and molecular analyses. Results: In the duodenum, intestines, and kidneys histological alterations promoted by IRI were reversed by remote postconditioning method. In the distal ileum, the histomorphometric alterations could be reversed by the postconditioning methods with more evident effects promoted by the remote method. The molecular analysis found that the levels of expression of Bax (proapoptotic) and Bcl-XL (antiapoptotic) genes in the intestine were increased by IRI. These alterations were equally reversed by the postconditioning methods, with more evident effects of the remote method. Conclusions: IPoC methods positively reduced the damage caused by IRI in weaning rats.

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Liver ischemia-reperfusion (IR) injury is associated with poor outcome after liver transplantation and liver resections. Hexafluoroisopropanol (HFIP) is a tri-fluorinated metabolites of volatile anesthetics and has modulatory effects on inflammation that have been observed mainly in cell culture experiments. In this survey, we investigated the effects of HFIP in a rat model of normothermic hepatic ischemia-reperfusion injury. Twenty-four male Wistar rats were randomized into three groups: (1) control in which animals were submitted to 30 min of partial liver ischemia with resection of non-ischemic liver lobes immediate after reperfusion, (2) pre-ischemia (PI) group in which animals received intravenous HFIP (67 mg/kg) 5 min before liver ischemia, and (3) pre-reperfusion (PR) group in which animals received intravenous HFIP (67 mg/kg) 5 min before reperfusion. Four hours after reperfusion, all animals were euthanized for sample collection. Aspartate and alanine transaminases, glucose, and high mobility group box-1 (HMGB-1) protein concentrations showed a significant decreased, and malondialdehyde was increased in the PR group compared with control and PI groups. Interleukin 6 (IL-6) was increased in the PI group compared with control and PR groups. IL-10 and -12 were increased in the PR and PI groups, respectively, when compared with the control group. Glucose decreased in the PR when compared with the control group. Post-conditioning with HFIP led to a decrease in hepatocellular injury and was associated with a downregulation of HMGB-1. The HFIP resulted in a better control of inflammatory response to ischemia-reperfusion even without causing a reduction in oxidative stress.

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Since damage induced by ischemia-reperfusion (I/R) involves alterations in Ca2+ homeostasis and is reduced by ischemic postconditioning (IP) and that CoCl2 can trigger changes resembling the response to a hypoxic event in normoxia and its blockade on Ca2+ current in heart muscle, our aim was to evaluate CoCl2 as an IP therapeutic tool. Mechanic and energetic parameters of isolated and arterially perfused male Wistar rat heart ventricles were simultaneously analyzed in a model of I/R in which 0.23 mmol/L CoCl2 was introduced upon reperfusion and kept or withdrawn after 20 min or introduced after 20 min of reperfusion. The presence of CoCl2 did not affect diastolic pressure but increased post-ischemic contractile recovery, which peaked at 20 min and decreased at the end of reperfusion. This decrease was prevented when CoCl2 was removed at 20 min of reperfusion. Total heat release increased throughout reperfusion, while economy increased between 15 and 25 min. No effect was observed when CoCl2 was introduced at 20 min of reperfusion. In addition, both the area under the contracture curve evoked by 10 mmol/L caffeine-36 mmol/L Na+ and the contracture tension relaxation rate were higher with CoCl2.Furthermore, CoCl2 decreased the number of arrhythmias during reperfusion and the ventricular damaged area. The presence of CoCl2 in reperfusion induces cardioprotection consistent with the improvement in cellular calcium handling. The use of CoCl2 constitutes a potential cardioprotective tool of clinical relevance.

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Abstract Ischemic postconditioning (IPTC) brings cardioprotection endogenously, Atrial natriuretic peptide (ANP) produces the same effect. It happens due to down expression of endothelial nitric oxide synthase (eNOS). Thus, experimental protocol associating IPTC has been formulated to find the role of ANP in the cardioprotection of heart in OVX rats. For this experiment, heart was isolated from OVX rat and held tightly on Langendorff's apparatus in a manner that ischemia of 30 min and reperfusion of 120 min were also given. Simultaneously, IPTC with four cycles of 5 min ischemia and 5 min reperfusion of each was applied. Parameters like size of myocardial infarct, levels of lactate dehydrogenase (LDH) and release of creatine kinase- MB (CK-MB) in coronary effluent were noted after each stage of experiment for ensuring the extent of myocardial injury. Some significant changes were also seen in the histopathology of cardiovascular tissues. The cardio-protection has been made by four cycles of IPTC. It was confirmed by decline in the size of myocardial infarct. It diminishes the release of LDH and CK-MB in heart of OVX rat. Thus, IPTC induces cardio-protection in the isolated heart from OVX rat. Perfusion of ANP associating with IPTC favors the cardioprotection which is further confirmed by rise in the NO release and heart rate. The level of myocardial damage changes using IPTC, IPTC+OVX, IPTC+OVX+ANP, IPTC+ OVX+ANP+L-NAME and other groups were observed significantly and were found to be less than those in I/R control group. Thus, it is recommended that ANP involving IPTC restores attenuated cardio-protection in OVX rat heart. Therefore, Post-conditioning is useful in various clinical aspects.

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Mitochondria are the central target of ischemic preconditioning and postconditioning cardioprotective strategies, which consist of either the application of brief intermittent ischemia/reperfusion (I/R) cycles or the administration of pharmacological agents. Such strategies reduce cardiac I/R injury by activating protective signaling pathways that prevent the exacerbated production of reactive oxygen/nitrogen species, inhibit opening of mitochondrial permeability transition pore and reduce apoptosis, maintaining normal mitochondrial function. Cardioprotection also involves the activation of mitochondrial quality control (MQC) processes, which replace defective mitochondria or eliminate mitochondrial debris, preserving the structure and function of the network of these organelles, and consequently ensuring homeostasis and survival of cardiomyocytes. Such processes include mitochondrial biogenesis, fission, fusion, mitophagy and mitochondrial-controlled cell death. This review updates recent advances in MQC mechanisms that are activated in the protection conferred by different cardiac conditioning interventions. Furthermore, the role of extracellular vesicles in mitochondrial protection and turnover of these organelles will be discussed. It is concluded that modulation of MQC mechanisms and recognition of mitochondrial targets could provide a potential and selective therapeutic approach for I/R-induced mitochondrial dysfunction.

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Since the discovery of ischemic pre- and post-conditioning, more than 30 years ago, the knowledge about the mechanisms and signaling pathways involved in these processes has significantly increased. In clinical practice, on the other hand, such advancement has yet to be seen. This article provides an overview of ischemic pre-, post-, remote, and pharmacological conditioning related to the heart. In addition, we reviewed the cardioprotective signaling pathways and therapeutic agents involved in the above-mentioned processes, aiming to provide a comprehensive evaluation of the advancements in the field. The advancements made over the last decades cannot be ignored and with the exponential growth in techniques and applications. The future of pre- and post-conditioning is promising.

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ABSTRACT Purpose: The aim of this study is to compare the hepatic protective effect of both remote and local postconditioning (POS). Methods: Twenty-eight Wistar rats were assigned into four groups: sham group(SHAM), ischemia-reperfusion group (IR), local ischemic POS group (lPOS) and remote ischemic POS group (rPOS). Animals were subjected to liver ischemia for 30 min. Local ischemic POS group consisted of four cycles of 5 min liver ischemia, followed by 5 min reperfusion (40 min). Remote ischemic POS group consisted of four cycles of 5 min hind limb ischemia, followed by 5 min hind limb perfusion after the main liver ischemia period. After 190 minutes median and left liver lobes were harvested for biochemical and histopathology analysis. Results: All the conditioning techniques were able to increase the level of bothglutathione reductase and peroxidase, showing higher values in the rPOS group when compared to the lPOS. Also, thiobarbituric acid reactive substances were higher in all intervention groups when compared to SHAM, but rPOS had the lower rates of increase, showing the best result. The histopathology analysis showed that all groups had worst injury levels than SHAM, but rPOS had lower degrees of damage when compared to the lPOS, although it was not statistically significant. Conclusion: Remote postconditioning is a promising technique to reduce liver ischemia-reperfusion injury, once it increased antioxidants substances and reduced the damage.

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ABSTRACT Purpose To investigate the effect of ischemic postconditioning (IPostC) on skeletal muscle and its optimal protocol. Methods This article is about an animal study of rat model of crush syndrome. Sixty rats were randomized into nine different IPostC intervention groups and a control group. The anesthetized rats were subjected to unilateral hindlimb 3-kg compression with a compression device for 6 h, followed by nine different IPostC intervention protocols. Results Serum levels of creatine kinase (CK) at 3 h post-crush became 2.3-3.9 times among all 10 groups after crush. At 72 h post-crush, serum CK level was reduced to 0.28-0.53 time in all intervention groups. The creatinine (CREA) level in the control group was elevated to 3.11 times at 3 h post-crush and reduced to1.77 time at 72 h post-crush. The potassium (K+) level in the control group was elevated to 1.65 and 1.41 time at 3 and 72 h post-crush, respectively. Conclusions Our IPostC intervention protocols can effectively protect rats from crush-induced elevation of serum CK, CREA, and K+ levels. The timing of IPostC intervention should be as early as possible, to ensure the protective effect.

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ABSTRACT Purpose To clarify the best protocol for performing remote ischemic conditioning and to minimize the consequences of ischemia and reperfusion syndrome in brain, the present study aimed to evaluate different time protocols and the relation of the organs and the antioxidant effects of this technique. Methods The rat's left femoral artery was clamped with a microvascular clamp in times that ranged from 1 to 5 minutes, according to the corresponding group. After the cycles of remote ischemic conditioning and a reperfusion of 20 minutes, the brain and the left gastrocnemius were collected. The samples were used to measure glutathione peroxidase, glutathione reductase and catalase levels. Results In the gastrocnemius, the 4-minute protocol increased the catalase concentration compared to the 1-minute protocol, but the latter increased both glutathione peroxidase and glutathione reductase compared to the former. On the other hand, the brain demonstrated higher catalase and glutathione peroxidase in 5-minute group, and the 3-minute group reached higher values of glutathione reductase. Conclusions Remote ischemic conditioning increases brain antioxidant capacity in a time-dependent way, while muscle presents higher protection on 1-minute cycles and tends to decrease its defence with longer cycles of intermittent occlusions of the femoral artery.

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Purpose: The aim of this study is to compare the hepatic protective effect of both remote and local postconditioning (POS). Methods: Twenty-eight Wistar rats were assigned into four groups: sham group(SHAM), ischemia-reperfusion group (IR), local ischemic POS group (lPOS) and remote ischemic POS group (rPOS). Animals were subjected to liver ischemia for 30 min. Local ischemic POS group consisted of four cycles of 5 min liver ischemia, followed by 5 min reperfusion (40 min). Remote ischemic POS group consisted of four cycles of 5 min hind limb ischemia, followed by 5 min hind limb perfusion after the main liver ischemia period. After 190 minutes median and left liver lobes were harvested for biochemical and histopathology analysis. Results: All the conditioning techniques were able to increase the level of bothglutathione reductase and peroxidase, showing higher values in the rPOS group when compared to the lPOS. Also, thiobarbituric acid reactive substances were higher in all intervention groups when compared to SHAM, but rPOS had the lower rates of increase, showing the best result. The histopathology analysis showed that all groups had worst injury levels than SHAM, but rPOS had lower degrees of damage when compared to the lPOS, although it was not statistically significant. Conclusion: Remote postconditioning is a promising technique to reduce liver ischemia-reperfusion injury, once it increased antioxidants substances and reduced the damage.(AU)

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It has been demonstrated that brief cycles of ischemia followed by reperfusion (IR) applied before exercise can improve performance and, IR intervention, applied immediately after exercise (post-exercise ischemic conditioning-PEIC) exerts a potential ergogenic effect to accelerate recovery. Thus, the purpose of this systematic review with meta-analysis was to identify the effects of PEIC on exercise performance, recovery and the responses of associated physiological parameters, such as creatine kinase, perceived recovery and muscle soreness, over 24 h after its application. From 3281 studies, six involving 106 subjects fulfilled the inclusion criteria. Compared to sham (cuff administration with low pressure) and control interventions (no cuff administration), PEIC led to faster performance recovery (p = 0.004; ES = -0.49) and lower increase in creatine kinase (p < 0.001; effect size (ES) = -0.74) and muscle soreness (p < 0.001; ES = -0.88) over 24 h. The effectiveness of this intervention is more pronounced in subjects with low/moderate fitness level and at least a total time of 10 min of ischemia (e.g., two cycles of 5 min) is necessary to promote positive effects.

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Purpose To investigate whether heat shock protein 90 (HSP90) is involved in complement regulation in ischemic postconditioning (IPC). Methods The left coronary artery of rats underwent 30 min of occlusion, followed by 120 min of reperfusion and treatment with IPC via 3 cycles of 30s reperfusion and 30s occlusion. The rats were injected intraperitoneally with 1 mg/kg HSP90 inhibitor geldanamycin (GA) after anesthesia. Eighty rats were randomly divided into four groups: sham, ischemia-reperfusion (I/R), IPC and IPC + GA. Myocardial infarct size, apoptosis index and the expression of HSP90, C3, C5a, tumor necrosis factor (TNF)-alpha, interleukin (IL)-1β and c-Jun N-terminal kinase (JNK) were assessed. Results Compared with the I/R injury, the IPC treatment significantly reduced infarct size, release of troponin T, creatine kinase-MB, and lactate dehydrogenase, and cardiomyocyte apoptosis. These beneficial effects were accompanied by a decrease in TNF-α, IL-1β, C3, C5a and JNK expression levels. However, all these effects were abrogated by administration of the HSP90 inhibitor GA. Conclusion HSP90 exerts a profound effect on IPC cardioprotection, and may be linked to the inhibition of the complement system and JNK, ultimately attenuating I/R-induced myocardial injury and apoptosis.(AU)

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Purpose Patients with diabetes are vulnerable to myocardial I/R (ischaemia/reperfusion) injury, but are not responsive to IPO (ischaemic post-conditioning). We hypothesized that decreased cardiac Adiponectin (APN) is responsible for the loss of diabetic heart sensitivity to IPO cardioprotecton. Methods Diabetic rats were subjected to I/R injury (30 min of LAD occlusion followed by 120 min of reperfusion). Myocardial infarct area was determined by TTC staining. Cardiac function was monitored by a microcatheter. ANP, 15-F2t-isoprostane, nitrotyrosine and MDA were measured by assay kits. Levels of p-Akt, total-Akt and GAPDH were determined by Western Blot. Results Diabetic rats subjected to myocardial IR exhibited severe myocardial infarction and oxidative stress injury, lower APN in the plasma and cardiac p-Akt expression ( P <0.05). IPO significantly attenuated myocardial injury and up-regulated plasma APN content and cardiac p-Akt expression in non-diabetic rats but not in diabetic rats. Linear correlation analysis showed that the expression of adiponectin was positively correlated with p-Akt and negatively correlated with myocardial infarction area ( P <0.01). Conclusion Protective effect of IPO was tightly correlated with the expression of adiponectin, exacerbation of I/R injury and ineffectiveness of IPO was partially due to the decline of adiponectin and inactivation of Akt in diabetes mellitus.(AU)

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Abstract Purpose To investigate whether heat shock protein 90 (HSP90) is involved in complement regulation in ischemic postconditioning (IPC). Methods The left coronary artery of rats underwent 30 min of occlusion, followed by 120 min of reperfusion and treatment with IPC via 3 cycles of 30s reperfusion and 30s occlusion. The rats were injected intraperitoneally with 1 mg/kg HSP90 inhibitor geldanamycin (GA) after anesthesia. Eighty rats were randomly divided into four groups: sham, ischemia-reperfusion (I/R), IPC and IPC + GA. Myocardial infarct size, apoptosis index and the expression of HSP90, C3, C5a, tumor necrosis factor (TNF)-alpha, interleukin (IL)-1β and c-Jun N-terminal kinase (JNK) were assessed. Results Compared with the I/R injury, the IPC treatment significantly reduced infarct size, release of troponin T, creatine kinase-MB, and lactate dehydrogenase, and cardiomyocyte apoptosis. These beneficial effects were accompanied by a decrease in TNF-α, IL-1β, C3, C5a and JNK expression levels. However, all these effects were abrogated by administration of the HSP90 inhibitor GA. Conclusion HSP90 exerts a profound effect on IPC cardioprotection, and may be linked to the inhibition of the complement system and JNK, ultimately attenuating I/R-induced myocardial injury and apoptosis.

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