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Renal ischemia/reperfusion (I/R) injury is a common clinical challenge faced by clinicians in kidney transplantation. I/R is the leading cause of acute kidney injury, and it occurs when blood flow to the kidney is interrupted and subsequently restored. I/R impairs renal function in both short and long terms. Renal ischemic preconditioning refers to all maneuvers intended to prevent or attenuate ischemic damage. In this context, the present review focuses on the dual-specificity phosphatase 3 (DUSP3), also known as vaccinia H1-related phosphatase, an uncommon regulator of mitogen-activated protein kinase (MAPK) phosphorylation. DUSP3 has different biological functions: (1) it acts as a tumor modulator and (2) it is involved in the regulation of immune response, thrombosis, hemostasis, angiogenesis, and genomic stability. These functions occur either through MAPK-dependent or MAPK-independent mechanisms. DUSP3 genetic deletion dampens kidney damage and inflammation caused by I/R in mice, suggesting DUSP3 as a potential target for preventing renal I/R injury. Here, we discuss the putative role of DUSP3 in ischemic preconditioning and the potential mechanisms of such an attenuated inflammatory response via improved kidney perfusion and adequate innate immune response., Competing Interests: The authors declare no conflicts of interest., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Background: Ischemic preconditioning (IPC) has been suggested to improve exercise performance by 1-8%. Prior research concerning its impact on short-duration exercises, such as sprints, has been limited and yielded conflicting results. The aim of this study, which included a non-occlusion-based placebo control, was to determine whether IPC improves repeated sprint performance in a manner that accounted for psychophysiological effects., Methods: Twenty-two healthy males participated in this study, which employed a randomized crossover design. Following the 10-min baseline period, participants received intervention under four different conditions: 1) no-intervention control (CON); 2) non-occlusion-based placebo control (SHAM); 3) remote IPC (RIPC); and 4) local IPC (LIPC). Participants then performed a standardized repeated sprint cycling (5×10s maximal cycling sprint, separated by a 40-s rest in each set)., Results: Repeated sprint performance, as indexed by average power output, peak power output, and total work, the improvement was observed in the RIPC and LIPC during the initial phase (set 1-3) when compared with CON (P<0.05). SHAM condition also showed an increase in peak power output in the set 1 (CON 9.97±1.05 vs. SHAM 10.30±1.13 w/kg, P<0.05), which may represent a psychophysiological component in the IPC-induced improvement. Higher lactate concertation was found in the SHAM and LIPC groups, than in the CON group, 5 minutes after the exercise (CON 15.72±0.68 vs. SHAM 16.82±0.41 vs. LIPC 17.19±0.39 mmol/L, P<0.0001 for both, respectively)., Conclusions: In conclusion, LIPC enhanced repeated sprint cycling performance during the initial phase, beyond what could be accounted for entirely by a psychophysiological effect. The improvement associated with RIPC, however, did not surpass the effect of a placebo intervention.

Background and Purpose: Remote ischaemic preconditioning (rIPC) for cardioprotection is severely impaired in diabetes, and therapeutic options to restore it are lacking. The vascular endothelium plays a key role in rIPC. Given that the activity of endothelial nitric oxide synthase (eNOS) is inhibited by proline-rich tyrosine kinase 2 (Pyk2), we hypothesized that pharmacological Pyk2 inhibition could restore eNOS activity and thus restore remote cardioprotection in diabetes., Experimental Approach: New Zealand obese (NZO) mice that demonstrated key features of diabetes were studied. The consequence of Pyk2 inhibition on endothelial function, rIPC and infarct size after myocardial infarction were evaluated. The impact of plasma from mice and humans with or without diabetes was assessed in isolated buffer perfused murine hearts and aortic rings., Key Results: Plasma from nondiabetic mice and humans, both subjected to rIPC, caused remote tissue protection. Similar to diabetic humans, NZO mice demonstrated endothelial dysfunction. NZO mice had reduced circulating nitrite levels, elevated arterial blood pressure and a larger infarct size after ischaemia and reperfusion than BL6 mice. Pyk2 increased the phosphorylation of eNOS at its inhibitory site (Tyr656), limiting its activity in diabetes. The cardioprotective effects of rIPC were abolished in diabetic NZO mice. Pharmacological Pyk2 inhibition restored endothelial function and rescued cardioprotective effects of rIPC., Conclusion and Implications: Endothelial function and remote tissue protection are impaired in diabetes. Pyk2 is a novel target for treating endothelial dysfunction and restoring cardioprotection through rIPC in diabetes., (© 2024 The Author(s). British Journal of Pharmacology published by John Wiley & Sons Ltd on behalf of British Pharmacological Society.)

Ischemic tolerance is a robust internal defense mechanism of all living organisms. The effectiveness of this mechanism has been repeatedly demonstrated in experiments, but a comprehensive review of the clinical applicability of this phenomenon in practice has not yet been published. The results in clinical practice sound ambiguous and unconvincing in comparison with the results of experimental studies. Also, in many localities, the effect of ischemic tolerance was not clinically proven. For the reasons mentioned, the authors analyze the possible causes of the mentioned discrepancies and provide a comprehensive insight into the possible relevant clinical use of this phenomenon in practice for different groups of patients., (Copyright © 2024 Asian Surgical Association and Taiwan Society of Coloproctology. Published by Elsevier B.V. All rights reserved.)

Background: Large colon volvulus is a cause of colic in horses with high morbidity and mortality when not promptly treated. More treatment options are needed to improve the outcome of these cases by protecting against the damage caused by ischaemia and reperfusion injury., Objectives: To determine the effect of preconditioning with dexmedetomidine prior to induction of ischaemia-reperfusion (IR) injury in a large colon volvulus model in the horse., Study Design: Randomised blinded in vivo experiments., Methods: Horses received either a dexmedetomidine (DEX) or saline (CON) constant rate infusion (CRI) immediately following induction of anaesthesia. Venous, arterial, and transmural occlusion of a section of the large colon was performed for 3 h, after which the ligatures and clamps were removed to allow for reperfusion for 3 h. Biopsies of the large colon were taken at baseline, 1 and 3 h of ischaemia, and at 1 and 3 h of reperfusion., Results: The severity of crypt epithelial loss (DEX = 2.1 [0.8-2.8], CON = 3.1 [2.5-4], p = 0.03) and mucosal haemorrhage was decreased (DEX = 2.1 [1.3-3], CON = 3.5 [2.5-4], p = 0.03) in group DEX compared to group CON when graded on a scale of 0-4. Crypt length remained longer (DEX = 369.5 ± 91.7 μm, CON = 238.5 ± 72.6 μm, p = 0.02) and interstitium to crypt (I:C) ratio remained lower (DEX = 1.4 (1-1.7), CON = 2.6 [1.8-5.9], p = 0.03) in group DEX compared to group CON during reperfusion., Main Limitations: Clinical applicability of pharmacologic preconditioning is limited., Conclusion: Preconditioning with a dexmedetomidine CRI prior to IR injury demonstrated a protective effect histologically on the large colon in the horse. Further investigation into postconditioning with dexmedetomidine is warranted as a possible intervention in colic cases suspected of being large colon volvulus., (© 2024 The Author(s). Equine Veterinary Journal published by John Wiley & Sons Ltd on behalf of EVJ Ltd.)

Background: Ischemic necrosis in the distal portion of a flap is a challenging complication in plastic surgery. The authors hypothesized that a novel hybrid flap preconditioning (HFP) device combining foam-mediated external suction and nonsurgical delay can promote skin flap survival better than surgical delay., Method: Twenty-eight mice were divided into 4 groups: a control group, in which a 4 × 1.5-cm dorsal flap was made with no preconditioning; a surgical delay group, in which surgical delay occurred 7 days before flap elevation; a foam-mediated external suction (FMES) group, in which foam-mediated external suction at -100 mm Hg was used 5 hours a day for 6 days, and the flap was elevated on the seventh day; and a hybrid flap preconditioning (HFP) group, in which silicone strips were applied along the contour of the foam interface. The same negative-pressure protocol was used as in the FMES group. Seven days after flap elevation, macroscopic, histologic, and Western blot analyses were performed., Results: The flap survival rate was 46.25% (8.12%) in the control group, 68.72% (7.00%) in the surgical delay group, 57.03% (8.17%) in the FMES group, and 80.66% (3.27%) in the HFP group. Immunohistologic analysis of CD31 + cells in the distal end of viable tissue procured 7 days after flap elevation showed significantly higher angiogenesis in the surgical delay and HFP groups. Western blot results showed an increased expression of vascular endothelial growth factor in the surgical delay and HFP groups., Conclusions: The authors developed and fabricated a novel HFP device combining foam-mediated external suction and nonsurgical delay. The concept of HFP has proved to promote flap survival better than surgical delay., Clinical Relevance Statement: This study presented an innovative noninvasive method of flap preconditioning, which has been demonstrated to be superior to surgical delay in a murine model and holds promise for potential application in clinical settings., (Copyright © 2024 by the American Society of Plastic Surgeons.)

Purpose: This study aimed to investigate the effect of remote ischemic preconditioning (RIPC) on the healing of small intestinal anastomoses, evaluated by tensile strength and histologic wound healing on postoperative day 5., Methods: A total of 22 female pigs were randomized 1:1 into either an intervention or control group. The intervention group received 5 cycles of 3-minute ischemia followed by 3-minute reperfusion on the right forelimb. Two end-to-end anastomoses, a distal and a proximal, were created in the small intestine 30 and 60 min after RIPC, respectively. On postoperative day 5, the anastomoses were harvested and underwent a maximal anastomotic tensile strength (MATS) test (MATS 1-3) followed by histologic analyses., Results: MATS 1, when a tear became visible in the serosa, was significantly increased in the proximal anastomoses of the RIPC group compared with the control group (4.91 N vs 3.83 N; P = .005). No other significant differences were found when comparing these 2 groups., Conclusion: Our study showed no convincing results of RIPC on intestinal anastomotic healing to recommend its use in a general clinical setting. Further animal studies on RIPC's effect after relative or absolute intestinal ischemia may be recommended., Competing Interests: Declaration of competing interest The authors declare no competing interests., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Ischaemic preconditioning (IPC), brief periods of ischaemia immediately followed by reperfusion applied to a vascular bed, has emerged as a method to improve exercise performance. There is, however, a lack of research exploring repeated episodes of IPC on anaerobic performance. The aim of this study was to determine if a 2-week repeated IPC intervention could enhance anaerobic performance in male academy football players. Eight male academy football players completed two, 2-week intervention trials: six IPC episodes (4 × 5 min at 220 mmHg per episode), and six SHAM episodes (4 × 5 min at 20 mmHg per episode). Prior to and following each intervention trial, the participants completed assessments of anaerobic performance (Running Anaerobic Sprint Test [RAST]), and superficial femoral artery endothelial function (flow-mediated dilation [FMD]). IPC significantly enhanced peak and mean power output by 12% ( p  = 0.026) and 11% ( p  = 0.019) and significantly improved superficial femoral artery FMD ( p  = 0.049). The increase in endothelial function suggests that this may be a mechanism contributing to this enhancement of anaerobic performance. The present study supports the use of repeated IPC prior to matches and training sessions to enhance anaerobic performance.

Background: Ischemia-reperfusion injury (IRI) inevitably occurs during kidney transplantation and extended ischemia is associated with delayed graft function and poor outcomes. Remote ischemic preconditioning (RIPC) is a simple, noninvasive procedure aimed at reducing IRI and improving graft function. Experimental studies have implicated the kynurenine pathway as a protective mechanism behind RIPC., Methods: First, paired biopsies from 11 living kidney donors were analyzed to characterize the acute transcriptomic response to IRI. Second, 16 living kidney donors were subjected to either RIPC (n = 9) or no pretreatment (n = 7) to evaluate the impact of RIPC on the transcriptomic response to IRI. Finally, the effect of RIPC on plasma metabolites was analyzed in 49 healthy subjects., Results: There was a robust immediate response to IRI in the renal transcriptomes of living-donor kidney transplantation, including activation of the mitogen-activated protein kinase (MAPK) and epidermal growth factor receptor (EGFR) pathways. Preconditioning with RIPC did not significantly alter the transcriptomic response to IRI or the concentration of plasma metabolites., Conclusions: The present data validate living-donor kidney transplantation as a suitable model for mechanistic studies of IRI in human kidneys. The failure of RIPC to alter transcriptomic responses or metabolites in the kynurenine pathway raises the question of the robustness of the standard procedure used to induce RIPC, and might explain the mixed results in clinical trials evaluating RIPC as a method to attenuate IRI., Competing Interests: J.S.R. reports funding from GSK and Sanofi and fees from Travere Therapeutics and Astex. This does not alter our adherence to PLOS ONE policies on sharing data and materials. There are no patents, products in development, or marketed products associated with this research to declare., (Copyright: © 2024 Nordström et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Anastomotic leaks and stenoses remain critical complications in esophagectomy and are related to conduit perfusion. Surgical gastric preconditioning has been described but requires additional surgery and creates scar tissue, potentially hindering future operation. We sought to evaluate the feasibility and safety of percutaneous gastric preconditioning by angioembolization to improve perfusion of gastric conduits before esophagectomy in a high-risk patient cohort. Patients pending an esophagectomy for cancer and deemed to be high risk for anastomotic complications underwent preconditioning by image-guided angioembolization. Preconditioning was performed on an outpatient basis by means of superselective embolization of the left gastric and short gastric arteries. Intraoperative conduit perfusion evaluation with indocyanine green and postoperative surgical outcomes was reviewed. Seventeen patients underwent gastric preconditioning, with no complications observed. Thirteen of the 17 patients ultimately underwent esophagectomy; the remaining four patients were not candidates for an operation. Patients proceeded to surgery a median of 23 days (interquartile range, 21-27 days) after preconditioning. The intraoperative indocyanine green perfusion of all conduits was appropriate, with no tip demarcation and with a median time to dye uptake of 20s (interquartile range, 15-20s). There were no anastomotic stenoses or leaks noted within the series. Gastric conduit preconditioning by percutaneous angioembolization of the left gastric and short gastric arteries can be performed safely and without operative delay in high-risk patients. Further evaluation of preconditioning for conduit optimization is warranted to limit the critical complications of anastomotic leak and stenosis in esophagectomy., (© The Author(s) 2024. Published by Oxford University Press on behalf of International Society for Diseases of the Esophagus. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background: Remote ischemic preconditioning (RIPC) has 2 time windows for organ protection: acute and delayed. Previous studies have mainly focused on the organoprotective effects of acute RIPC. We aimed to determine whether delayed RIPC can reduce the occurrence of acute kidney injury (AKI) and postoperative complications in patients undergoing cardiac surgery., Methods: This prospective, single-center, double-blind, randomized controlled trial involved 509 patients at high risk for AKI who were scheduled for elective cardiac surgery requiring cardiopulmonary bypass. Patients were randomized to receive RIPC (4 cycles of 5-minute inflation and 5-minute deflation on 1 upper arm with a blood pressure cuff) 24 hours before surgery or a sham condition (control group) that was induced by 4 cycles of 5-minute inflation to a pressure of 20 mm Hg followed by 5-minute cuff deflation. The primary end point was the incidence of AKI within the prior 7 days after cardiac surgery. The secondary end points included renal replacement therapy during hospitalization, change in urinary biomarkers of AKI and markers of myocardial injury, duration of intensive care unit stay and mechanical ventilation, and occurrence of nonfatal myocardial infarction, stroke, and all-cause mortality by day 90., Results: A total of 509 patients (mean age, 65.2±8.2 years; 348 men [68.4%]) were randomly assigned to the RIPC group (n=254) or control group (n=255). AKI was significantly reduced in the RIPC group compared with the control group (69/254 [27.2%] versus 90/255 [35.3%]; odds ratio, 0.68 [95% CI, 0.47-1.00]; P =0.048). There were no significant between-group differences in the secondary end points of perioperative myocardial injury (assessed by the concentrations of cardiac troponin T, creatine kinase myocardial isoenzyme, and NT-proBNP [N-terminal pro-brain natriuretic peptide]), duration of stay in the intensive care unit and hospital, and occurrence of nonfatal myocardial infarction, stroke, and all-cause mortality by day 90., Conclusions: Among high-risk patients undergoing cardiac surgery, delayed RIPC significantly reduced the occurrence of AKI., Registration: URL: https://www.chictr.org.cn; Unique identifier: ChiCTR2000035568., Competing Interests: None.

In recent years, ischemic preconditioning (IPC) has garnered significant attention in sports research. While IPC has demonstrated positive effects in high-intensity sports such as judo and swimming, its potential benefits for enhancing the performance of Taekwondo athletes have not been extensively studied. This study aimed to investigate the effects of IPC on taekwondo performance and to observe the metabolic characteristics associated with enhancing sports performance via LC‒MS/MS-based plasma metabolomics. Seventeen participants underwent the repeated frequency speed of kick test (FSKT) after IPC, along with pre- and post-exercise plasma metabolite analysis. Differential abundance metabolite analysis, enriched pathway analysis, and weighted gene coexpression network analysis (WGNCA) were employed to delve into metabolic characteristics. The findings highlighted a significant enhancement in FSKT performance in the experimental group. Metabolomic analysis revealed 109 differentially abundant metabolites, including Dl-lactate, hypoxanthine, acetylcarnitine, and acetylsalicylic acid. Enriched pathway analysis revealed pathways such as pentose and glucuronic acid interconversion, ascorbic acid and aldonic acid metabolism, the pentose phosphate pathway (PPP), and the Warburg effect. In conclusion, IPC can significantly increase the specific athletic abilities of Taekwondo athletes, with enhancements linked to anaerobic metabolism, PPP utilization, the Warburg effect for energy production, redox system stability, reduced muscle fatigue, and pain alleviation., (© 2024. The Author(s).)

Objective: This study aimed to evaluate the efficacy of six non-invasive remote ischemic preconditioning (RIPC) interventions during the nursing care of patients with heart failure (HF) prior to cardiac catheterization., Methods: A comprehensive search of nine Chinese and English online databases was conducted from the date of their inception to June 2023 to identify randomized controlled trials (RCTs) investigating RIPC in patients with HF prior to cardiac catheterization. Two independent investigators screened the articles, extracted data, and assessed their quality. The risk of bias was evaluated using the Cochrane risk-of-bias tool, and a network meta-analysis was conducted using R software., Results: Four trials involving 511 patients with a low risk of bias were included in the analysis. Six non-invasive RIPC interventions were identified, all demonstrating effectiveness in reducing the incidence of contrast-induced acute kidney injury (CI-AKI). Among these, Intervention F (applying up to 50 mmHg above the resting systolic pressure for 5 min to the dominant leg or upper limb, repeated three times with an 18-minute interval) was deemed optimal, although the timing of the procedure was not specified. Intervention D (applying up to 200 mmHg pressure to the upper limb for 5 min, repeated four times with 5-minute intervals, within 45 min prior to cardiac catheterization, ) was considered suboptimal., Conclusion: Although Intervention D was recommended as the preferred option, none of the four trials examined its impact on the cardiac function of patients with HF. Large-scale, multi-center RCTs are required, with outcome indicators including cardiac function and the occurrence of CI-AKI, to better understand the therapeutic effects of RIPC on HF and reduce the incidence of CI-AKI. This will provide a more robust foundation for clinical practice., (© 2024. The Author(s).)

Aims: There is a lack of therapies able to prevent anthracycline cardiotoxicity (AC). Remote ischaemic conditioning (RIC) has shown beneficial effects in preclinical models of AC., Methods: REmote iSchemic condItioning in Lymphoma PatIents REceiving ANthraCyclinEs (RESILIENCE) is a multinational, prospective, phase II, double-blind, sham-controlled, randomized clinical trial that evaluates the efficacy and safety of RIC in lymphoma patients receiving anthracyclines. Patients scheduled to undergo ≥5 chemotherapy cycles including anthracyclines and with ≥1 AC-associated risk factors will be randomized to weekly RIC or sham throughout the chemotherapy period. Patients will undergo three multiparametric cardiac magnetic resonance (CMR) studies, at baseline, after the third cycle (intermediate CMR), and 2 months after the end of chemotherapy. Thereafter, patients will be followed up for clinical events over an anticipated median of ≥24 months. The primary endpoint is the absolute change from baseline in CMR-based left ventricular ejection fraction (LVEF). The main secondary outcome is the incidence of AC events, defined as (1) a drop in CMR-based LVEF of ≥10 absolute points, or (2) a drop in CMR-based LVEF of ≥5 and <10 absolute points to a value <50%. Intermediate CMR will test the ability of T2 mapping to predict AC versus classical markers (left ventricular strain and cardiac injury biomarkers). A novel CMR sequence allowing ultrafast cine acquisition will be validated in this vulnerable population., Conclusions: The RESILIENCE trial will test RIC (a novel non-invasive intervention to prevent AC) in a cohort of high-risk patients. The trial will also test candidate markers for their capacity to predict AC and will validate a novel CMR sequence reducing acquisition time in a vulnerable population., (© 2024 The Author(s). European Journal of Heart Failure published by John Wiley & Sons Ltd on behalf of European Society of Cardiology.)

Remote ischemic preconditioning (RIPC) exerts a protective role on myocardial ischemia/reperfusion (I/R) injury by the release of various humoral factors. Lactate is a common metabolite in ischemic tissues. Nevertheless, little is known about the role lactate plays in myocardial I/R injury and its underlying mechanism. This investigation revealed that RIPC elevated the level of lactate in blood and myocardium. Furthermore, AZD3965, a selective monocarboxylate transporter 1 inhibitor, and 2-deoxy-d-glucose, a glycolysis inhibitor, mitigated the effects of RIPC-induced elevated lactate in the myocardium and prevented RIPC against myocardial I/R injury. In an in vitro hypoxia/reoxygenation model, lactate markedly mitigated hypoxia/reoxygenation-induced cell damage in H9c2 cells. Further studies suggested that lactate contributed to RIPC, rescuing I/R-induced autophagy deficiency by promoting transcription factor EB (TFEB) translocation to the nucleus through activating the AMP-activated protein kinase (AMPK)-mammalian target of rapamycin (mTOR) pathway without influencing the phosphatidylinositol 3-kinase-Akt pathway, thus reducing cardiomyocyte damage. Interestingly, lactate up-regulated the mRNA and protein expression of connexin 43 (CX43) by facilitating the binding of TFEB to CX43 promoter in the myocardium. Functionally, silencing of TFEB attenuated the protective effect of lactate on cell damage, which was reversed by overexpression of CX43. Further mechanistic studies suggested that lactate facilitated CX43-regulated autophagy via the AMPK-mTOR-TFEB signaling pathway. Collectively, this research demonstrates that RIPC protects against myocardial I/R injury through lactate-mediated myocardial autophagy via the AMPK-mTOR-TFEB-CX43 axis., Competing Interests: Disclosure Statement None declared., (Copyright © 2024 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.)

Study Design: Experimental animal study., Objectives: To investigate the protective effect of remote limb ischemia preconditioning (RLPreC) on traumatic spinal cord injury (SCI) and explore the underlying biological mechanisms using RNA sequencing., Setting: China Rehabilitation Science Institute; Beijing; China., Methods: spinal cord injury was induced in mice using a force of 0.7 N. RLPreC treatment was administered. Motor function, pain behavior, and gene expression were assessed., Results: RLPreC treatment significantly improved motor function and reduced pain-like behavior in SCI mice. RNA-Seq analysis identified 5247 differentially expressed genes (DEGs). GO analysis revealed enrichment of immune response, inflammatory signaling, and synaptic transmission pathways among these DEGs. KEGG analysis indicated suppression of inflammation and promotion of synapse-related pathways., Conclusions: RLPreC is a promising therapeutic strategy for improving motor function and alleviating pain after traumatic SCI. RNA-Seq analysis provides insights into potential therapeutic targets and warrants further investigation., (© 2024. The Author(s), under exclusive licence to International Spinal Cord Society.)

Purpose: To examine whether isoflurane preconditioning (IsoP) has a protective effect against renal ischemia/reperfusion injury (I/RI) in diabetic conditions and to further clarify the underlying mechanisms., Methods: Control and streptozotocin-induced diabetic rats were randomly assigned to five groups, as follows: normal sham, normal I/R, diabetic sham, diabetic I/R, and diabetic I/R + isoflurane. Renal I/RI was induced by clamping renal pedicle for 45 min followed by reperfusion for 24 h. IsoP was achieved by exposing the rats to 2% isoflurane for 30 min before vascular occlusion. Kidneys and blood were collected after reperfusion for further analysis. Renal histology, blood urea nitrogen, serum creatinine, oxidative stress, inflammatory cytokines, and renal cell apoptosis were assessed. Furthermore, the expression of brahma related gene 1 (Brg1), nuclear factor-erythroid 2-related factor 2 (Nrf2), heme oxygenase-1 (HO-1), and nuclear factor-κB (NF-κB) were determined., Results: Compared with control, diabetic rats undergoing I/R presented more severe renal injury, oxidative stress, inflammatory reaction, and apoptosis with the impairment of Brg1/Nrf2/HO-1 signaling. All these alterations were significantly attenuated by pretreatment with isoflurane., Conclusions: These findings suggest that isoflurane could alleviate renal I/RI in diabetes, possibly through improving Brg1/Nrf2/HO-1 signaling.

We conducted a post hoc analysis of Remote Ischemic Conditioning for Acute Moderate Ischemic Stroke (RICAMIS) to investigate whether red blood cell (RBC) indices are associated with efficacy of remote ischemic conditioning (RIC), and whether the association is affected by age. In this post hoc analysis, patients with RBC indices at admission were enrolled. RBC indices including RBC count, hematocrit (HCT), mean corpuscular volume (MCV), hemoglobin (HB), mean corpuscular hemoglobin (MCH), and mean corpuscular hemoglobin concentration (MCHC) were analyzed. According to the median of these RBC indices, eligible patients were divided into high and low groups, which were further subdivided into RIC and control subgroups. Primary endpoint was excellent functional outcome defined as a modified Rankin Scale score of 0-1 at 90 days, which was used to evaluate RIC efficacy. RIC efficacy as well as effect of age on RIC efficacy were analyzed across the high and low groups of different RBC indices, and the interaction effects of RBC indices on RIC efficacy were evaluated. A total of 1640 patients were enrolled in the final analysis. In overall patients, no significant interaction effects of RIC intervention by all RBC indices were found, although there was a trend in interaction effect of RIC intervention by MCH (p = 0.116). However, we found an effect of age on the association of MCH with RIC efficacy. In patients over 60 years old, MCH significantly affected RIC efficacy (p = 0.006) and RIC significantly produced a higher proportion of primary outcome in high MCH (72.6% vs. 59.1%, P < 0.001) vs. low MCH group (61.2% vs. 62%, P = 0.829), which was not identified in patients under 60 years old. Furthermore, RIC efficacy decreased with increasing age in patients with low MCH with significant interaction effect (p = 0.012), while RIC efficacy increased with increasing age in patients with high MCH although no significant interaction (p = 0.126). No significant interaction effects of RIC intervention by RBC count, HCT, MCV, HB, and MCHC were found regardless of age. This secondary analysis of RICAMIS suggested that RIC exhibited more obvious benefit in AIS patients over 60 years old with high MCH compared with those with low MCH group, but RBC count, HCT, MCV, HB, and MCHC were not associated with the efficacy of RIC treatment regardless of age., (© 2024. The Author(s).)

Wu et al. (2021) investigated the neuroprotective effects of hypoxia preconditioning (HPC) in a rat model of traumatic brain injury (TBI). The study demonstrated that HPC enhances brain resilience to TBI by upregulating glucose transporters GLUT1 and GLUT3 through the HIF-1α signaling pathway. Comprehensive molecular and histological analyses confirmed increased expression of these transporters, correlating with reduced neuronal apoptosis and cerebral edema. The robust methodology, including rigorous statistical validation and time-course assessments, underscores HPC's potential therapeutic role in mitigating neuronal loss and improving glucose transport post-injury. However, the study could be strengthened by incorporating additional preconditioning controls, comparative analyses with other neuroprotective strategies, and exploring downstream metabolic effects in greater detail. Furthermore, expanding the research to include diverse animal models and examining sex-dependent responses would enhance the generalizability and translational relevance of the findings. Future studies should also integrate metabolic flux analysis and advanced imaging techniques to further elucidate HPC's mechanisms of action., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

This study investigated the antioxidant and neuroprotective effects of nicotinamide combined with ischemic preconditioning against cerebral ischemia reperfusion (CIR) injury. Thirty-five Wistar albino male rats were randomly divided into five groups: sham, preconditioned ischemia/reperfusion (IP+IR), ischemia/reperfusion (IR), preconditioned ischemia/reperfusion + nicotinamide (IP+IR+N), and ischemia/reperfusion + nicotinamide (IR+N). CIR was achieved with bilateral common carotid artery occlusion. IP+IR and IP+IR+N groups 30 min before ischemia; Three cycles of 10 sec ischemia/30 sec reperfusion followed by 20 min IR were applied. The IP+IR+N and IR+N groups received 500 mg/kg nicotinamide intraperitoneally. After 24 h of reperfusion, a neurological evaluation was performed and vertıcal pole test. Biochemically, malondialdehyde (MDA), glutathione (GSH) levels and catalase (CAT) activity were measured in blood and brain tissue samples. Rates of red neurons, sateliosis and spongiosis were determined histopathologically in the prefrontal cortex areas. After CIR, MDA levels increased significantly in serum and brain tissue in the IR group compared to the sham group, while GSH and CAT activity decreased in the brain tissue (p < 0.05). MDA levels in the tissues were found significantly decreased in the IR+N group compared to the IR group (p < 0.05). Administration of nicotinamide together with IP significantly decreased MDA levels in brain tissue and increased GSH and CAT activity (p < 0.05). Compared to the IR group, the morphological and neurological damage in the prefrontal cortex areas decreased in the IP+IR, IP+IR+N, and IR+N groups (p < 0.05). In addition, red neuron, sateliosis and spongiosis rates increased significantly in the IR group compared to the Sham, IP+IR+N, IR+N groups (p < 0.001 for all). In neurological evaluation, while the neurological score increased and the time on the vertical pole decreased significantly in the IR group, preconditioning, and nicotinamide groups reversed (p < 0.05). The study's results show that nicotinamide administration with ischemic preconditioning alleviates cerebral ischemia/reperfusion injury., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Objective: This study designed experiments to explore the effects of ischemic preconditioning (IPC) intervention with different cycling periods on the upper limb strength performance of college male bodybuilding athletes. Methods: Ten bodybuilding athletes were recruited for a randomized, double-blind, crossover experimental study. All subjects first underwent pre-tests with two sets of exhaustive bench presses at 60% of their one-repetition maximum (1RM) to assess upper limb strength performance. They then experienced three different IPC intervention modes (T1: 1 × 5 min, T2: 2 × 5 min, T3: 3 × 5 min), as well as a non-IPC intervention mode (CON), followed by a retest of the bench press. An Enode pro device was used to record the barbell's velocity during the bench press movement (peak velocity (PV), mean velocity (MV)); power (peak power (PP), mean power (MP)); and time under tension (TUT) to evaluate upper limb strength performance. Results: PV values: T1 showed significant increases compared to pre-tests in the first ( p = 0.02) and second ( p = 0.024) tests, and were significantly greater than the CON ( p = 0.032); T2 showed a significant increase in PV in the first test ( p = 0.035), with no significant differences in other groups. MV values: T1 showed a significant increase in MV in the first test compared to the pre-test ( p = 0.045), with no significant differences in other groups. PP values: T1 showed a highly significant increase in PP in the first test compared to the pre-test ( p = 0.001), and was significantly higher than the CON ( p = 0.025). MP values: T1 showed highly significant increases in MP in both the first ( p = 0.004) and second ( p = 0.003) tests compared to the pre-test; T2 showed a highly significant increase in MP in the first test ( p = 0.039) and a significant increase in the second test ( p = 0.039). T1's MP values were significantly higher than the CON in both tests; T2's MP values were significantly higher than the CON in the first ( p = 0.005) and second ( p = 0.024) tests. TUT values: T1 showed highly significant increases in TUT in the first ( p < 0.001) and second ( p = 0.002) tests compared to the pre-test, and were significantly higher than the CON. Conclusions: (1) Single-cycle and double-cycle IPC interventions both significantly enhance upper limb strength performance, significantly improving the speed and power in exhaustive bench press tests, with the single-cycle IPC intervention being more effective than the double-cycle IPC intervention. (2) The triple-cycle IPC intervention does not improve the upper limb strength performance of bodybuilding athletes in exhaustive bench presses.

The inflammation and coagulopathy during coronavirus disease (COVID-19) impairs the efficiency of the current stroke treatments. Remote ischaemic conditioning (RIC) has shown potential in recent years to protect the brain and other organs against pathological conditions. This study aimed to evaluate the efficiency of RIC in brain infarct size using TTC staining and lung injury reduction by H&E staining during the hyper-inflammatory response in rats. The inflammation and coagulopathy were assessed by sedimentation rate, haematocrit, systemic oxidative stress and clotting time. Moreover, we observed changes in the cytokine profile. The results of the first part of the experiment showed that the inflammation and lung injury are fully developed after 24 h of intratracheal LPS administration. At this time, we induced focal brain ischaemia and examined the effect of RIC pre- and post-treatment. Our results showed that RIPre-C reduced the infarct size by about 23%, while RIPost-C by about 30%. The lung injury was also reduced following both treatments. Moreover, RIC modulated systemic inflammation. The level of chemokines CINC-1, LIX and RANTES decreased after 24 h of post-ischaemic reperfusion in treated animals compared to non-treated. The RIC-mediated decrease of inflammation was reflected in improved sedimentation rate and hematocrit, as well as reduced systemic oxidative stress. The results of this work showed neuroprotective and lung protective effects of RIC with a decrease in inflammation response. On the basis of our results, we assume that immunomodulation through the chemokines CINC-1, LIX, and RANTES play a role in RIC-mediated protection., (© 2024. The Author(s).)

Background: Ischemic preconditioning-induced serum exosomes (IPC-exo) protected rat heart against myocardial ischemia/reperfusion injury. However, whether IPC-exo regulate replacement fibrosis after myocardial infarction (MI) and the underlying mechanisms remain unclear. MicroRNAs (miRs) are important cargos of exosomes and play an essential role in cardioprotection. We aim to investigate whether IPC-exo regulate post-MI replacement fibrosis by transferring cardioprotective miRs and its action mechanism., Methods: Exosomes obtained from serum of adult rats in control (Con-exo) and IPC groups were identified and analyzed, subsequently intracardially injected into MI rats following ligation. Their miRs profiles were identified using high-throughput miR sequencing to identify target miRs for bioinformatics analysis. Luciferase reporter assays confirmed target genes of selected miRs. IPC-exo transfected with selected miRs antagomir or NC were intracardially administered to MI rats post-ligation. Cardiac function and degree of replacement fibrosis were detected 4 weeks post-MI., Results: IPC-exo exerted cardioprotective effects against excessive replacement fibrosis. MiR sequencing and RT-qPCR identified miR-133a-3p as most significantly different between IPC-exo and Con-exo. MiR-133a-3p directly targeted latent transforming growth factor beta binding protein 1 (LTBP1) and protein phosphatase 2, catalytic subunit, alpha isozyme (PPP2CA). KEGG analysis showed that transforming growth factor-β (TGF-β) was one of the most enriched signaling pathways with miR-133a-3p. Comparing to injection of IPC-exo transfected with miR-133a-3p antagomir NC, injecting IPC-exo transfected with miR-133a-3p antagomir abolished protective effects of IPC-exo on declining excessive replacement fibrosis and cardiac function enhancement, while increasing the messenger RNA and protein expression of LTBP1, PPP2CA, and TGF-β1in MI rats., Conclusion: IPC-exo inhibit excessive replacement fibrosis and improve cardiac function post-MI by transferring miR-133a-3p, the mechanism is associated with directly targeting LTBP1 and PPP2CA, and indirectly regulating TGF-β pathway in rats. Our finding provides potential therapeutic effect of IPC-induced exosomal miR-133a-3p for cardiac repair., Competing Interests: The authors report no conflicts of interest in this work., (© 2024 Yang et al.)

Aims: Ischemic stroke is a major cause of disability and mortality worldwide. Transcranial direct current stimulation (tDCS) and isoflurane (ISO) preconditioning exhibit neuroprotective properties. However, it remains unclear whether tDCS enhances the protective effect of ISO preconditioning on ischemic stroke, and the underlying mechanisms are yet to be clarified., Method: A model of middle cerebral artery occlusion (MCAO), a rat ischemia-reperfusion (I/R) injury model, and an in vitro oxygen-glucose deprivation/re-oxygenation (O/R) model of ischemic injury were developed. ISO preconditioning and tDCS were administered daily for 7 days before MCAO modeling. Triphenyltetrazolium chloride staining, modified neurological severity score, and hanging-wire test were conducted to assess infarct volume and neurological outcomes. Untargeted metabolomic experiments, adeno-associated virus, lentiviral vectors, and small interfering RNA techniques were used to explore the underlying mechanisms., Results: tDCS/DCS enhanced the protective effects of ISO pretreatment on I/R injury-induced brain damage. This was evidenced by reduced infarct volume and improved neurological outcomes in rats with MCAO, as well as decreased cortical neuronal death after O/R injury. Untargeted metabolomic experiments identified oxidative phosphorylation (OXPHOS) as a critical pathological process for ISO-mediated neuroprotection from I/R injury. The combination of tDCS/DCS with ISO preconditioning significantly inhibited I/R injury-induced OXPHOS. Mechanistically, Akirin2, a small nuclear protein that regulates cell proliferation and differentiation, was found to decrease in the cortex of rats with MCAO and in cortical primary neurons subjected to O/R injury. Akirin2 functions upstream of phosphatase and tensin homolog deleted on chromosome 10 (PTEN). tDCS/DCS was able to further upregulate Akirin2 levels and activate the Akirin2/PTEN signaling pathway in vivo and in vitro, compared with ISO pretreatment alone, thereby contributing to the improvement of cerebral I/R injury., Conclusion: tDCS treatment enhances the neuroprotective effects of ISO preconditioning on ischemic stroke by inhibiting oxidative stress and activating Akirin2-PTEN signaling pathway, highlighting potential of combination therapy in ischemic stroke., (© 2024 The Author(s). CNS Neuroscience & Therapeutics published by John Wiley & Sons Ltd.)

Aims: Incidence of acute mountain sickness (AMS) ranges from 40%-90%, with high-altitude cerebral edema (HACE) representing a life-threatening end stage of severe AMS. However, practical and convenient preventive strategies for HACE are lacking. Remote ischemic preconditioning (RIPC) has demonstrated preventive effects on ischemia- or hypoxia-induced cardiovascular and cerebrovascular diseases. This study aimed to investigate the potential molecular mechanism of HACE and the application of RIPC in preventing HACE onset., Methods: A hypobaric hypoxia chamber was used to simulate a high-altitude environment of 7000 meters. Metabolomics and metabolic flux analysis were employed to assay metabolite levels. Transcriptomics and quantitative real-time PCR (q-PCR) were used to investigate gene expression levels. Immunofluorescence staining was performed on neurons to label cellular proteins. The fluorescent probes Mito-Dendra2, iATPSnFR1.0, and CMTMRos were used to observe mitochondria, ATP, and membrane potential in cultured neurons, respectively. TUNEL staining was performed to detect and quantify apoptotic cell death. Hematoxylin and eosin (H&E) staining was utilized to analyze pathological changes, such as tissue swelling in cerebral cortex samples. The Rotarod test was performed to assess motor coordination and balance in rats. Oxygen-glucose deprivation (OGD) of cultured cells was employed as an in vitro model to simulate the hypoxia and hypoglycemia induced by RIPC in animal experiments., Results: We revealed a causative perturbation of glucose metabolism in the brain preceding cerebral edema. Ischemic preconditioning treatment significantly reprograms glucose metabolism, ameliorating cell apoptosis and hypoxia-induced energy deprivation. Notably, ischemic preconditioning improves mitochondrial membrane potential and ATP production through enhanced glucose-coupled mitochondrial metabolism. In vivo studies confirm that RIPC alleviates cerebral edema, reduces cell apoptosis induced by high-altitude hypoxia, and improves motor dysfunction resulting from cerebral edema., Conclusions: Our study elucidates the metabolic basis of HACE pathogenesis. This study provides a new strategy for preventing HACE that RIPC reduces brain edema through reprogramming metabolism, highlighting the potential of targeting metabolic reprogramming for neuroprotective interventions in neurological diseases caused by ischemia or hypoxia., (© 2024 The Author(s). CNS Neuroscience & Therapeutics published by John Wiley & Sons Ltd.)

Background: Moyamoya disease (MMD) is a significant cause of childhood stroke and transient ischemic attacks (TIAs). This study aimed to assess the safety and efficacy of remote ischemic conditioning (RIC) in children with MMD., Methods: In a single-center pilot study, 46 MMD patients aged 4 to 14 years, with no history of reconstructive surgery, were randomly assigned to receive either RIC or sham RIC treatment twice daily for a year. The primary outcome measured was the cumulative incidence of major adverse cerebrovascular events (MACEs). Secondary outcomes included ischemic stroke, recurrent TIA, hemorrhagic stroke, revascularization rates, and clinical improvement assessed using the patient global impression of change (PGIC) scale during follow-up. RIC-related adverse events were also recorded, and cerebral hemodynamics were evaluated using transcranial Doppler., Results: All 46 patients completed the final follow-up (23 each in the RIC and sham RIC groups). No severe adverse events associated with RIC were observed. Kaplan-Meier analysis indicated a significant reduction in MACEs frequency after RIC treatment [log-rank test (Mantel-Cox), P = 0.021]. At 3-year follow-up, two (4.35%) patients had an ischemic stroke, four (8.70%) experienced TIAs, and two (4.35%) underwent revascularization as the qualifying MACEs. The clinical improvement rate in the RIC group was higher than the sham RIC group on the PGIC scale (65.2% vs. 26.1%, P < 0.01). No statistical difference in cerebral hemodynamics post-treatment was observed., Conclusions: RIC is a safe and effective adjunct therapy for asymptomatic children with MMD. This was largely due to the reduced incidence of ischemic cerebrovascular events., (© 2024. The Author(s).)

Ischemic preconditioning (IPC) appears to improve exercise performance although there is uncertainty about the intensity dependence of this effect. The present study sought to clarify effects of IPC on physiological responses at and below peak oxygen uptake, including the gas exchange threshold (GET). Ten male and female participants completed five cycling ramp tests (10 W/min) to failure, with the final two tests preceded by either IPC (4 × 5 min 220 mmHg bilateral leg occlusions) or SHAM (20 mmHg), in a randomised crossover design. The rates of O 2 uptake ( V ˙ O 2 ), carbon dioxide output ( V ˙ CO 2 ), and expired ventilation ( V ˙ E ) were measured at rest and throughout exercise. Exercise data were fitted using several functions to identify GET, two ventilatory thresholds and peak V ˙ O 2 . IPC increased V ˙ O 2 at GET by ~ 9% (IPC: 1.89 ± 0.51 L/min, SHAM: 1.73 ± 0.56 L/min; p = 0.055) and power output at GET by ~ 11% (IPC: 133 ± 36 W, SHAM: 120 ± 39 W; p = 0.022). In addition, peak power output increased by 2.4% following IPC (IPC: 217 ± 50 W, SHAM: 212 ± 51 W; p = 0.052), but there was no significant effect of IPC on peak V ˙ O 2 (IPC: 2.87 ± 0.68 L/min, SHAM: 2.84 ± 0.73 L/min; p = 0.60) or the ventilatory thresholds. The present results suggest that IPC improves GET and peak power output but not peak V ˙ O 2 during a maximal graded test., (© 2024. The Author(s).)

Acute kidney injury (AKI) is the most common complication of cardiac surgery. Cardiac surgery-associated AKI (CSA-AKI) is caused by systemic and renal hemodynamic impairment and parenchymal injury. Prophylaxis of CSA-AKI remains an unmet priority, for which preventive strategies based on drug therapies, hydration procedures, and remote ischemic preconditioning (RIPC) have been tested in pre-clinical and clinical studies, with variable success. Contradicting reports and scarce or insufficiently pondered information have blurred conclusions. Therefore, with an aim to contribute to consolidating the available information, we carried out a wide scope, pan-comparative meta-analysis including the accessible information about the most relevant nephroprotective approaches assayed. After a thorough examination of 1892 documents retrieved from PubMed and Web of Science, 150 studies were used for the meta-analysis. Individual odds ratios of efficacy at reducing AKI incidence, need for dialysis, and plasma creatinine elevation were obtained for each alleged protectant. Also, the combined class effect of drug families and protective strategies was also meta-analyzed. Our results show that no drug family or procedure affords substantial protection against CSA-AKI. Only, a mild but significant reduction in the incidence of CSA-AKI by preemptive treatment with dopaminergic and adrenergic drugs, vasodilators, and the RIPC technique. The integrated analysis suggests that single-drug approaches are unlikely to cope with the variety of individual pathophysiological scenarios potentially underlying CSA-AKI. Accordingly, a theragnostic approach involving the etiopathological diagnosis of kidney frailty is necessary to guide research towards the development of pharmacological combinations concomitantly and effectively addressing the key mechanisms of CSA-AKI., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Masson SAS.. All rights reserved.)

Remote ischemic preconditioning (RIPC) reduces ischemia-reperfusion injury in aortocoronary bypass surgery, potentially via extracellular vesicles (EVs) and their micro-RNA content. Clinical data implicate that propofol might inhibit the cardioprotective RIPC effect. This prospective, randomized study investigated the influence of different anesthetic regimes on RIPC efficacy and EV micro-RNA signatures. We also assessed the impact of propofol on cell protection after hypoxic conditioning and EV-mediated RIPC in vitro. H9c2 rat cardiomyoblasts were subjected to hypoxia, with or without propofol, and subsequent simulated ischemia-reperfusion injury. Apoptosis was measured by flow cytometry. Blood samples of 64 patients receiving anesthetic maintenance with propofol or isoflurane, along with RIPC or sham procedures, were analyzed, and EVs were enriched using a polymer-based method. Propofol administration corresponded with increased Troponin T levels (4669 ± 435.6 pg/mL), suggesting an inhibition of the cardioprotective RIPC effect. RIPC leads to a notable rise in miR-21 concentrations in the group receiving propofol anesthesia (fold change 7.22 ± 6.6). In vitro experiments showed that apoptosis reduction was compromised with propofol and only occurred in an EV-enriched preconditioning medium, not in an EV-depleted medium. Our study could clinically and experimentally confirm propofol inhibition of RIPC protection. Increased miR-21 expression could provide evidence for a possible inhibitory mechanism.

Purpose: The purpose of this study was to investigate the effects of acute ischemic preconditioning (IPC) on tennis skill and physical exercise performance, as well as to explore whether 7-day repeated IPC (RIPC) accelerated fatigue recovery after a simulated tennis match., Methods: Twenty-nine male tennis-specific current students were randomly allocated into 1 of 2 groups: SHAM (n = 14, 3 × 5 min at 20 mm Hg) and IPC (n = 15, 3 × 5 min at 220 mm Hg). Participants in both groups engaged in acute IPC and RIPC interventions. After the first acute IPC intervention, assessments were conducted to evaluate tennis-specific skills and overall physical exercise capacity. Following completion of chronic RIPC interventions, all participants competed in a simulated tennis match specifically designed to induce fatigue. To evaluate recovery from this induced fatigue, physical exercise capacity tests were conducted at 24 and 48 hours postmatch, allowing for an assessment of the participants' recovery capabilities over time., Results: After the first acute intervention, notable differences were observed between the IPC and SHAM groups in their performance on the repeated-sprint ability test. Specifically, the total times recorded were significantly shorter in the IPC group compared with the SHAM group (IPC: 109.05 [2.70] vs SHAM: 114.57 [7.45] s, P = .012), and this trend was also reflected in their best times (IPC: 4.20 [0.18] s vs SHAM: 4.39 [0.30] s, P = .042), indicating an immediate benefit of the IPC intervention on sprint performance. After a 7-day RIPC intervention, significant changes were noted in the SHAM group's performance metrics postmatch. There was an increase (P < .001) in fatigue index from 22% (8%) to 30% (9%) during repeated-sprint ability test and a decrease in serve speed from 120.2 (17.5) to 106.7 (13.0) km/h (P = .002) and knee peek torque from 196.0 (49.0) to 162.7 (39) N (extension, 60°/s, P < .001) in the SHAM group 24 hours postmatch, relative to the IPC group. Moreover, compared with the SHAM group, the IPC group showed a lower rate of perceived exertion during the match (P < .001) and a decrease in visual analog scale score (P = .026) 24 hours postmatch, suggesting enhanced recovery and reduced perception of pain relative to the SHAM group., Conclusion: IPC could serve as a strategy to generate an ergogenic effect and recovery during training and competition.

Perioperative acute kidney injury (AKI), which is mainly mediated by renal ischemia‒reperfusion (I/R) injury, is commonly observed in clinical practice. However, effective measures for preventing and treating this perioperative complication are still lacking in the clinic. Thus, we designed this study to examine whether remote liver ischemic preconditioning (RLIPC) has a protective effect on damage caused by renal I/R injury. In a rodent model, 30 mice were divided into five groups to assess the effects of RLIPC and ERK1/2 inhibition on AKI. The groups included the sham-operated (sham), kidney ischemia and reperfusion (CON), remote liver ischemic preconditioning (RLIPC), CON with the ERK1/2 inhibitor U0126 (CON+U0126), and RLIPC with U0126 (RLIPC+U0126). RLIPC consisted of 4 liver ischemia cycles before renal ischemia. Renal function and injury were assessed through biochemical assays, histology, cell apoptosis and protein phosphorylation analysis. RLIPC significantly mitigated renal dysfunction, tissue damage, inflammation, and apoptosis caused by I/R, which was associated with ERK1/2 phosphorylation. Furthermore, ERK1/2 inhibition with U0126 negated the protective effects of RLIPC and exacerbated renal injury. To summarize, we demonstrated that RLIPC has a strong renoprotective effect on kidneys post I/R injury and that this effect may be mediated by phosphorylation of ERK1/2., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Wang et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Anastomotic stricture is a typical complication of esophageal atresia surgery. Remote ischemic conditioning (RIC) has demonstrated multiorgan benefits, however, its efficacy in the esophagus remains unclear. This study aimed to investigate whether applying RIC after esophageal resection and anastomosis in rats could attenuate esophageal stricture and improve inflammation. Sixty-five male Sprague-Dawley rats were categorized into the following groups: controls with no surgery, resection and anastomosis only, resection and anastomosis with RIC once, and resection and anastomosis with RIC twice. RIC included three cycles of hind-limb ischemia followed by reperfusion. Inflammatory markers associated with the interleukin 6/Janus kinase/ signal transducer and activator of transcription 3 (IL-6/JAK/STAT3) and tumor necrosis factor-alpha/nuclear factor-κB (TNF-α/NF-kB) signaling pathways were evaluated with RNA and protein works. The RIC groups showed significantly lower stricture rates, lower inflammatory markers levels than the resection and anastomosis-only group. The RIC groups had significantly lower IL-6 and TNFa levels than the resection and anastomosis-only group, confirming the inhibitory role of remote ischemic conditioning in the IL-6/JAK/STAT3 and TNF-α/NF-kB signaling pathways. RIC after esophageal resection and anastomosis can reduce the inflammatory response, improving strictures at the esophageal anastomosis site, to be a novel noninvasive intervention for reducing esophageal anastomotic strictures., (© 2024. The Author(s).)

Ischemic preconditioning (IPC) can enhance maximal strength likely due to neural priming. Cruz et al. (Cruz R, Tramontin AF, Oliveira AS, Caputo F, Denadai BS, Greco CC. Scand J Med Sci Sports 34: e14591, 2024) examined the neurophysiological mechanisms responsible for the ergogenic effect. Although key neurophysiological measures remained largely unchanged, voluntary activation and maximal strength were greater following IPC than sham-IPC. Although the mechanistic evidence remains inconclusive, the greater maximal strength provides further evidence of the ergogenic benefit of IPC. Researchers should continue examining the broader functional implications of IPC.

Background: Remote ischemic conditioning (RIC) is considered a promising non-pharmacological therapeutic strategy to mitigate ischemic injury. Although the precise mechanisms of RIC's protective effects remain elusive, existing data suggest that exosomes contribute significantly to these processes through cell-to-cell communication OBJECTIVE: This review aims to elucidate the role of exosomes in RIC-mediated multi-organ protection., Methods: We systematically searched multiple databases through October 2023 for preclinical studies evaluating the effect of exosomes in ischemic models using RIC procedures. Key outcomes, such as improved organ function and reduced infarct size, were recorded. Articles were selected and data were extracted by independent pairs of reviewers., Findings: A total of 16 relevant studies were identified in this review, showing that circulating exosomes derived from the plasma of RIC-treated animals exhibited protective effects akin to those of the RIC procedure itself. Exosome concentrations were measured in eight studies, six of which reported significant increases in the RIC group. Additional findings indicated that RIC might primarily modulate the expression of miRNAs and bioactive molecules delivered by exosomes, rather than directly altering circulating exosome levels. Notably, the expression of 11 distinct exosomal miRNAs was altered after RIC intervention, potentially involving multiple pathways., Conclusion: Exosomes appear to play a pivotal role in the protective effects induced by RIC. Clarifying their function in RIC under different pathological situations represents a grand challenge for future research., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. Declaration of competing interest The authors have no relevant financial or non-financial interests to disclose., (Copyright © 2024 The Authors. Published by Elsevier Masson SAS.. All rights reserved.)

Brief, repeated cycles of limb ischemia and reperfusion [ischemic preconditioning (IPC)] can protect against vascular insult. Few papers have considered the effect of IPC on resting vascular function, and no single study has simultaneously considered the local (trained arm) and remote (untrained arm) effects of a single session of IPC and following repeated sessions. We determined macrovascular [allometrically scaled flow-mediated dilation (FMD)] and microvascular [cutaneous vascular conductance (CVC)] function in healthy adults before, immediately post, 20 min post, and 24 h post a single session of IPC (4 × 5 min of single arm ischemia). These outcomes also were remeasured 24 h after six IPC sessions, performed over 2 wk. FMD and CVC increased in both arms 20 min post [FMD mean difference (MD) 1.1%, P < 0.001; CVC MD 0.08 arbitrary units (AU), P = 0.004] but not 24 h post (FMD MD -0.2%, P = 0.459; CVC MD -0.02 AU, P = 0.526] a single session of IPC, with no differences between trained and untrained arms. Although FMD did not increase 24 h after one IPC session, it was elevated in both arms 24 h after the sixth session (MD 1.2%, P = 0.009). CVC was not altered in either arm 24 h after the last IPC session. These data indicate that the local and remote effects of IPC on vascular health may be equivalent and that the benefits to FMD may be greater with sustained training compared with a single IPC exposure.

Background: Ischemic-reperfusion injury resulting from kidney transplantation declines the post-transplant graft function. Remote ischemic conditioning (RIC) is known to be able to reduce the criticality of ischemic reperfusion injury. This study aimed to meta-analyze whether the application of remote ischemic conditioning to kidney transplantation patients improves clinical outcomes., Methods: Researchers included randomized controlled studies of the application of RIC to either kidney donors or recipients. Articles were retrieved from PubMed, Embase, Web of Science, and Cochrane Library. The risk of bias was evaluated using RoB 2.0. The primary outcome was mortality after transplantation. Secondary outcomes were the incidence of delayed graft function, graft rejection, and post-transplant laboratory results. All outcomes were integrated by RevMan 5.4.1., Results: Out of 90 papers, 10 articles (8 studies, 1977 patients) were suitable for inclusion criteria. Mortality collected at all time points did not show a significant difference between the groups. Three-month mortality (RR, 3.11; 95% CI, 0.13-75.51, P = 0.49) tended to increase in the RIC group, but 12-month (RR, 0.70; 95% CI, 0.14-3.45, P = 0.67) or final-reported mortality (RR, 0.49; 95% CI, 0.23-1.06, P = 0.07) was higher in the sham group than the RIC group. There was no significant difference between the RIC and sham group in delayed graft function (RR, 0.64; 95% CI, 0.30-1.35, P = 0.24), graft rejection (RR, 1.13; 95% CI, 0.73-1.73, P = 0.59), and the rate of time required for a 50% reduction in baseline serum creatinine concentration of less than 24 h (RR, 0.98; 95% CI, 0.61-1.56, P = 0.93)., Conclusions: It could not be concluded that the application of RIC is beneficial to kidney transplantation patients. However, it is noteworthy that long-term mortality tended to decrease in the RIC group. Since there were many limitations due to the small number of included articles, researchers hope that large-scale randomized controlled trials will be included in the future., Systematic Review Registration: PROSPERO CRD42022336565., (© 2024. The Author(s).)

Systolic blood pressure variability (SBPV) is associated with outcome in acute ischemic stroke. Remote ischemic conditioning (RIC) has been demonstrated to be effective in stroke and may affect blood pressure. Relationship between SBPV and RIC treatment after stroke warrants investigation. A total of 1707 patients from per-protocol analysis set of RICAMIS study were included. The SBPV was calculated based on blood pressure measured at admission, Day 7, and Day 12. (I) To investigate the effect of SBPV on efficacy of RIC in stroke, patients were divided into High and Low categories in each SBPV parameter. Primary outcome was excellent functional outcome at 90 days. Compared with Control, efficacy of RIC in each category and interaction between categories were investigated. (II) To investigate the effect of RIC treatment on SBPV, SBPV parameters were compared between RIC and Control groups. Compared with Control, a higher likelihood of primary outcome in RIC was found in high category (max-min: adjusted risk difference [RD] = 7.2, 95% CI 1.2-13.1, P = 0.02; standard deviation: adjusted RD = 11.5, 95% CI 1.6-21.4, P = 0.02; coefficient of variation: adjusted RD = 11.2, 95% CI 1.4-21.0, P = 0.03). Significant interaction of RIC on outcomes were found between High and Low standard deviations (adjusted P < 0.05). No significant difference in SBPV parameters were found between treatment groups. This is the first report that Chinese patients with acute moderate ischemic stroke and presenting with higher SBPV, who were non-cardioemoblic stroke and not candidates for intravenous thrombolysis or endovascular therapy, would benefit more from RIC with respect to functional outcomes at 90 days, but 2-week RIC treatment has no effect on SBPV during hospital., (© 2024. The Author(s).)

Background: Surgical stress may lead to postsurgical hypercoagulability, endothelial dysfunction and systemic inflammation, which can impact on patient recovery. Remote ischaemic preconditioning is a procedure that activates the body's endogenous defences against ischaemia and reperfusion injury. Studies have suggested that remote ischaemic preconditioning has antithrombotic, antioxidative and anti-inflammatory effects. The hypothesis was that remote ischaemic preconditioning reduces surgery-induced systemic stress response., Method: During a 24-month period (2019-2021), adult patients undergoing subacute laparoscopic cholecystectomy due to acute cholecystitis were randomized to remote ischaemic preconditioning or control. Remote ischaemic preconditioning was performed less than 4 h before surgery on the upper arm. It consisted of four cycles of 5 min ischaemia and 5 min reperfusion. The gene expression of 750 genes involved in inflammatory processes, oxidative stress and endothelial function was investigated preoperatively and 2-4 h after surgery in both groups. In addition, changes in 20 inflammation- and vascular trauma-associated proteins were assessed preoperatively, 2-4 h after surgery and 24 h after surgery., Results: A total of 60 patients were randomized. There were no statistically significant differences in gene expression 2-4 h after surgery between the groups (P > 0.05). Remote ischaemic preconditioning did not affect concentrations of circulating proteins up to 24 h after surgery (P > 0.05)., Conclusion: The study did not demonstrate any effect of remote ischaemic preconditioning on expression levels of the chosen genes or in circulating immunological cytokines and vascular trauma-associated proteins up to 24 h after subacute laparoscopic cholecystectomy in patients with acute cholecystitis., (© Crown copyright 2024.)

Background: Remote ischemic conditioning (RIC) has shown great advantages in protecting organs from ischemia-reperfusion loss and applied research on RIC continues to increase. We performed a systematic review and meta-analysis to comprehensively investigate the value of RIC for different organ transplantation., Methods: We searched PubMed, EMBASE, and the Cochrane Library from inception to November 1, 2023, for randomized controlled trials investigating whether RIC has an advantage in organ transplantation (including heart, lung, liver, and kidney) compared with controls. The primary outcomes varied according to the transplanted organ, including liver transplantation (graft loss, early allograft dysfunction, acute kidney injury, days in hospital, and mortality); kidney transplantation (delayed graft function, acute rejection (AR), graft loss, 50% decrease in serum creatinine, glomerular filtration rate, days in hospital, and mortality); heart and lung transplantation (AR, mortality). Two investigators independently selected suitable trials, assessed trial quality, and extracted the data., Results: A total of 11 randomized controlled trials were included in this study, including six kidney transplants, three liver transplants, and one heart and lung transplant each, with 561 RIC cases and 564 controls, and a total of 1125 patients. The results showed that RIC did not reduce mortality in transplant patients compared with controls (liver transplant: RR0.9, 95% confidence interval [0.31-2.66]; kidney transplant: RR 0.76, 95% confidence interval [0.17-3.33]), graft failure rate (liver transplantation: RR 0.3, 95% confidence interval [0.07, 1.19]; kidney transplantation: RR 0.89, 95% confidence interval [0.35, 2.27]), length of hospital stay (liver transplantation: standard mean difference [SMD] 0.14, 95% confidence interval [-0.15, 0.42]; kidney transplantation: SMD -0.1, 95% confidence interval [-0.3, 0.11]). In addition, RIC did not improve early liver function after liver transplantation (RR 0.97, 95% confidence interval [0.55,1.7]), acute kidney injury after liver transplantation (RR 1.17 95% confidence interval [0.9, 1.54]), delayed functional recovery after renal transplantation (RR 0.84, 95% confidence interval [0.62, 1.15]), AR rate (RR 1.04, 95% confidence interval [0.72, 1.49]), 50% serum creatinine decline rate (RR 1.1, 95% confidence interval [0.88, 1.37]), glomerular filtration rate 3 months after surgery (SMD 0.13, 95% confidence interval [-0.05, 0.31]) and postoperative 12 months glomerular filtration rate (SMD 0.13, 95% confidence interval [-0.06, 0.31])., Conclusion: Remote ischemic modulation does not improve clinical outcomes in patients undergoing organ transplantation (heart, lung, liver, and kidney)., Competing Interests: Declaration of competing interest The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

Introduction: Despite the appearance of off-pump coronary artery bypass grafting (CABG), ischemia-reperfusion injury (IRI) in the perioperative period still arouses concerns of clinicians. Remote ischemic conditioning (RIC) is the process of repeated ischemia and reperfusion in the peripheral vessels, which is proven to reduce IRI in vital organs. However, the effect of RIC in patients undergoing off-pump CABG is still unclear., Methods: This IMPROVE trial is a national, multicenter, randomized, controlled, open-label, blinded-endpoint clinical trial designed to assess whether RIC intervention can improve short-term prognosis of patients undergoing off-pump CABG. It plans to enroll 648 patients who will be randomly assigned into a RIC group or control group. Patients in the RIC group will receive four cycles of 5 min of pressurization (about 200 mmHg) and 5 min of rest in the 3 days before and 7 days after the surgery., Planned Outcomes: The primary outcome is the occurrence of major adverse cardiovascular and cerebrovascular events (MACCE) within the 3-month follow-up. MACCE is defined as all-cause death, myocardial infarction, stroke, and coronary revascularization surgery., Clinical Trial Registration: NCT06141525 (ClinicalTrials.gov)., (© 2024. The Author(s), under exclusive licence to Springer Healthcare Ltd., part of Springer Nature.)

Objective: We performed a post hoc exploratory analysis of Remote Ischemic Conditioning for Acute Moderate Ischemic Stroke (RICAMIS) to determine whether hypertension history and baseline systolic blood pressure (SBP) affect the efficacy of remote ischemic conditioning (RIC)., Methods: Based on the full analysis set of RICAMIS, patients were divided into hypertension versus non-hypertension group, or <140 mmHg versus ≥140 mmHg group. Each group was further subdivided into RIC and control subgroups. The primary outcome was modified Rankin Scale (mRS) 0-1 at 90 days. Efficacy of RIC was compared among patients with hypertension versus nonhypertension history and SBP of <140 mmHg versus ≥140 mmHg. Furthermore, the interaction effect of treatment with hypertension and SBP was assessed., Results: Compared with control group, RIC produced a significantly higher proportion of patients with excellent functional outcome in the nonhypertension group (RIC vs. control: 65.7% vs. 57.0%, OR 1.45, 95% CI 1.06-1.98; p = 0.02), but no significant difference was observed in the hypertension group (RIC vs. control: 69.1% vs. 65.2%, p = 0.17). Similar results were observed in SBP ≥140 mmHg group (RIC vs. control: 68.0% vs. 61.2%, p = 0.009) and SBP <140 mmHg group (RIC vs. control: 65.6% vs. 64.7%, p = 0.77). No interaction effect of RIC on primary outcome was identified., Interpretation: Hypertension and baseline SBP did not affect the neuroprotective effect of RIC, but they were associated with higher probability of excellent functional outcome in patients with acute moderate ischemic stroke who received RIC treatment., (© 2024 The Authors. Annals of Clinical and Translational Neurology published by Wiley Periodicals LLC on behalf of American Neurological Association.)

Background: Benign anastomotic stricture is a recognized complication following esophagectomy. Laparoscopic gastric ischemic preconditioning (LGIP) prior to esophagectomy has been associated with decreased anastomotic leak rates; however, its effect on stricture and the need for subsequent endoscopic intervention is not well studied., Methods: This was a case-control study at an academic medical center using consecutive patients undergoing oncologic esophagectomies (July 2012-July 2022). Our institution initiated an LGIP protocol on 1 January 2021. The primary outcome was the occurrence of stricture within 1 year of esophagectomy, while secondary outcomes were stricture severity and frequency of interventions within the 6 months following stricture. Bivariable comparisons were performed using Chi-square, Fisher's exact, or Mann-Whitney U tests. Multivariable regression controlling for confounders was performed to generate risk-adjust odds ratios and to identify the independent effect of LGIP., Results: Of 253 esophagectomies, 42 (16.6%) underwent LGIP prior to esophagectomy. There were 45 (17.7%) anastomotic strictures requiring endoscopic intervention, including three patients who underwent LGIP and 42 who did not. Median time to stricture was 144 days. Those who underwent LGIP were significantly less likely to develop anastomotic stricture (7.1% vs. 19.9%; p = 0.048). After controlling for confounders, this difference was no longer significant (odds ratio 0.46, 95% confidence interval 0.14-1.82; p = 0.29). Of those who developed stricture, there was a trend toward less severe strictures and decreased need for endoscopic dilation in the LGIP group (all p < 0.20)., Conclusion: LGIP may reduce the rate and severity of symptomatic anastomotic stricture following esophagectomy. A multi-institutional trial evaluating the effect of LGIP on stricture and other anastomotic complications is warranted., (© 2024. Society of Surgical Oncology.)

Cerebral ischemic preconditioning (CIP) has been shown to improve brain ischemic tolerance against subsequent lethal ischemia. Reactive astrocytes play important roles in cerebral ischemia-reperfusion. Recent studies have shown that reactive astrocytes can be polarized into neurotoxic A1 phenotype (C3d) and neuroprotective A2 phenotype (S100A10). However, their role in CIP remains unclear. Here, we focused on the role of N-myc downstream-regulated gene 2 (NDRG2) in regulating the transformation of A1/A2 astrocytes and promoting to brain ischemic tolerance induced by CIP. A Sprague Dawley rat model of middle cerebral artery occlusion/reperfusion (MCAO/R) was used. Rats were divided into the following six groups: (1) sham group; (2) CIP group: left middle cerebral artery was blocked for 10 min; (3) MCAO/R group: left middle cerebral artery was blocked for 90 min; (4) CIP + MCAO/R group: CIP was performed 72 h before MCAO/R; (5) AAV-NDRG2 + CIP + MCAO/R group: adeno-associated virus (AAV) carrying NDRG2 was administered 14 days before CIP + MCAO/R; (6) AAV-Ctrl + CIP + MCAO/R group: empty control group. The rats were subjected to neurological evaluation 24 h after the above treatments, and then were sacrificed for 2, 3, 5-triphenyltetraolium chloride staining, thionin staining, immunofluorescence and western blot analysis. In CIP + MCAO/R group, the neurological deficit scores decreased, infarct volume reduced, and neuronal density increased compared with MCAO/R group. Notably, CIP significantly increased S100A10 expression and the number of S100A10 + /GFAP + cells, and also increased NDRG2 expression. MCAO/R significantly decreased S100A10 expression and the number of S100A10 + /GFAP + cells yet increased C3d expression and the number of C3d + /GFAP + cells and NDRG2 expression, and these trends were reversed by CIP + MCAO/R. Furthermore, over-expression of NDRG2 before CIP + MCAO/R, the C3d expression and the number of C3d + /GFAP + cells increased, while S100A10 expression and the number of S100A10 + /GFAP + cells decreased. Meanwhile, over-expression of NDRG2 blocked the CIP-induced brain ischemic tolerance. Taken together, these results suggest that CIP exerts neuroprotective effects against ischemic injury by suppressing A1 astrocyte polarization and promoting A2 astrocyte polarization via inhibiting NDRG2 expression., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Introduction: Cerebral ischemia reperfusion injury (CIRI) often leads to deleterious complications after stroke patients receive reperfusion therapy. Exercise preconditioning (EP) has been reported to facilitate brain function recovery. We aim to explore the specific mechanism of EP in CIRI., Methods: Sprague-Dawley rats were randomized into Sham, middle cerebral artery occlusion (MCAO), and EP groups (n = 11). The rats in the EP group received adaptive training for 3 days (10 m/min, 20 min/day, with a 0° incline) and formal training for 3 weeks (6 days/week, 25 m/min, 30 min/day, with a 0° incline). Then, rats underwent MCAO surgery to establish CIRI models. After 48 h, neurological deficits and cerebral infarction of the rats were measured. Neuronal death and apoptosis in the cerebral cortices were detected. Furthermore, RNA sequencing was conducted to investigate the specific mechanism of EP on CIRI, and qPCR and Western blotting were further applied to confirm RNA sequencing results., Results: EP improved neurological deficit scores and reduced cerebral infarction in MCAO rats. Additionally, pre-ischemic exercise also alleviated neuronal death and apoptosis of the cerebral cortices in MCAO rats. Importantly, 17 differentially expressed genes (DEGs) were identified through RNA sequencing, and these DEGs were mainly enriched in the HIF-1 pathway, cellular senescence, proteoglycans in cancer, and so on. qPCR and Western blotting further confirmed that EP could suppress TIMP1, SOCS3, ANGPTL4, CDO1, and SERPINE1 expressions in MCAO rats., Conclusion: EP can improve CIRI in vivo, the mechanism may relate to TIMP1 expression and HIF-1 pathway, which provided novel targets for CIRI treatment., (© 2024 The Author(s). Brain and Behavior published by Wiley Periodicals LLC.)

The maintenance of intestinal integrity and barrier function under conditions of restricted oxygen availability is crucial to avoid bacterial translocation and local inflammation. Both lead to secondary diseases after hemorrhagic shock and might increase morbidity and mortality after surviving the initial event. Monitoring of the intestinal integrity especially in the early course of critical illness remains challenging. Since microcirculation and mitochondrial respiration are main components of the terminal stretch of tissue oxygenation, the evaluation of microcirculatory and mitochondrial variables could identify tissues at risk during hypoxic challenges, indicate an increase of intestinal injury, and improve our understanding of regional pathophysiology during acute hemorrhage. Furthermore, improving intestinal microcirculation or mitochondrial respiration, e.g. by remote ischemic preconditioning (RIPC) that was reported to exert a sufficient tissue protection in various tissues and was linked to mediators with vasoactive properties could maintain intestinal integrity. In this study, postcapillary oxygen saturation (µHbO 2 ), microvascular flow index (MFI) and plasmatic D-lactate concentration revealed to be early markers of intestinal injury in a rodent model of experimental hemorrhagic shock. Mitochondrial function was not impaired in this experimental model of acute hemorrhage. Remote ischemic preconditioning (RIPC) failed to improve intestinal microcirculation and intestinal damage during hemorrhagic shock., (© 2024. The Author(s).)

We investigated the effect of ischemic preconditioning (IPC) with and without caffeine supplementation on mean power output (MPO) during a 4-min cycling time-trial (TT). In a double-blinded, randomized, crossover-design, 11 trained men performed a TT on 4 days separated by ∼1 week. One hour before TT, participants ingested either caffeine (3 mg kg bw -1 ) or placebo pills, after which femoral blood-flow was either restricted with occlusion cuffs inflated to ∼180 mmHg (IPC), or sham-restricted (0-10 mmHg; Sham) during 3 × 2-min low-intensity cycling (10% of incremental peak power output). Then, participants performed a standardized warm-up followed by the TT. Plasma lactate and K + concentrations and ratings of perceived exertion (RPE) were measured throughout trials. TT MPO was 382 ± 17 W in Placebo + Sham and not different from Placebo + IPC (-1 W; 95% CI: -9 to 7; p = 0.848; d: 0.06), whereas MPO was higher with Caffeine + Sham (+6W; 95% CI: -2 to 14; p = 0.115; d: 0.49) and Caffeine + IPC (+8 W; 95% CI: 2-13; p = 0.019; d: 0.79) versus Placebo + Sham. MPO differences were attributed to caffeine (caffeine main-effect: +7 W; 95% CI: 2-13; p = 0.015; d: 0.54. IPC main-effect: 0 W; 95% CI: -6 to 7; p = 0.891; d: 0.03; caffeine × IPC interaction-effect: p = 0.580; d: 0.17). TT RPE and plasma variables were not different between treatments. In conlcusion, IPC with co-ingestion of placebo does not improve short-term high-intensity performance in trained men versus a double-placebo control (Placebo + Sham) and does not additively enhance performance with caffeine. These data do not support IPC as a useful strategy for athletes prior to competition but confirms caffeine's performance-enhancing effect., (© 2024 The Authors. European Journal of Sport Science published by Wiley‐VCH GmbH on behalf of European College of Sport Science.)

Objective: Acute cerebral infarction (ACI) contributes to disability and death accross the globe. Remote ischemic preconditioning (RIPC) reduces cerebral infarct size and improves neurological function in ACI. We conducted this research to reveal the effects of RIPC intervention on serum levels of microRNA-582-5p (miR-582-5p)/high mobility group box-1 protein (HMGB1), inflammation, oxidative stress and neurological function in patients with ACI., Methods: In this study, 158 patients with ACI were prospectively selected and randomized into the control (administered symptomatic medication alone) and the RIPC (underwent RIPC of the limbs based on medication) groups, with their clinical baseline data documented. Serum levels of miR-582-5p, and HMGB1 and inflammatory factors [tumor necrosis factor alpha (TNF-α)/interleukin-1beta (IL-1β)/IL-10] were assessed by RT-qPCR/ELISA, followed by comparisons of oxidative stress indices [glutathione-peroxidase (GSH-Px)/catalase (CAT)/superoxide dismutase (SOD)] using a fully automatic biochemical analyzer. Correlations between serum miR-582-5p with serum HMGB1, and between their levels with TNF-α/IL-1β/IL-10 were analyzed by Pearson analysis. The NIHSS score/Barthel Index scale were used to assess neurological function/daily living ability. Intervention safety for ACI patients was evaluated., Results: RIPC intervention increased serum miR-582-5p levels and decreased serum HMGB1 levels in ACI patients. RIPC intervention significantly reduced inflammation (diminished TNF-α/IL-1β levels, increased IL-10 level) and oxidative stress (elevated GSH-Px/CAT/SOD levels) in ACI patients. Serum miR-582-5p was negatively correlated with TNF-α and IL-1β levels, while positively correlated with IL-10 level, while HMGB1 was positively correlated with TNF-α and IL-1β levels, while negatively correlated with IL-10 level. miR-582-5p was negatively correlated with HMGB1. RIPC intervention improved neurological function (reduced NIHSS, increased Barthel scores) in ACI patients to some extent. RIPC had certain effectiveness and safety in the treatment of ACI., Conclusion: After RIPC intervention, serum miR-582-5p levels were increased, HMGB1 levels were decreased, and inflammation and oxidative stress were reduced in ACI patients, which mitigated neurological deficits, improved patients' ability to perform life activities, and exerted neuroprotective effects to some extent., Competing Interests: Declaration of Competing Interest The authors have no conflicts of interest to declare., (Copyright © 2024 Elsevier B.V. All rights reserved.)