Ischemic preconditioning (IPC) has emerged as a promising intervention for enhancing health- and exercise-related outcomes. Initially recognized in the 1980s and 1990s for its cardioprotective effects in clinical and animal studies, IPC has since garnered attention for its potential ergogenic benefits. Despite growing interest, the underlying physiological mechanisms remain poorly understood, leading to research exploring cause-effect relationship and evaluating IPC efficacy across diverse exercise models, often yielding mixed results. This Leading Article aims to clarify proposed mechanisms by which IPC may enhance athletic performance and facilitate healing effects. Specifically, this Leading Article discusses both the immediate (short-term) and sustained (long-term) effects of IPC. Short-term effects primarily involve acute improvements in vascular function and exercise capacity, while long-term effects may include cumulative benefits such as enhanced recovery, mitigation of exercise-induced muscle damage and adaptative physiological responses. This article highlights the importance of optimizing experimental protocols by extending the time window between IPC application and testing, to maximize performance outcomes, particularly under conditions associated with muscle damage. Future research should prioritize exploring the long-term effects of IPC on performance and recovery to better understand its potential as a reliable ergogenic aid.

Remote ischemic conditioning (RIC) is a simple and low-cost intervention that is thought to increase collateral blood flow through the vasodilatory effects of nitric oxide (NO) produced by the endothelium and red blood cells (RBCs). The aim of this study was to investigate whether RBC form and function are associated with short- and long-term outcomes in patients with acute ischemic stroke, and whether RIC treatment modified this effect.

This is a predefined substudy to the RESIST (Remote Ischemic Conditioning in Patients with Acute Stroke Trial) randomized clinical trial conducted in Denmark. RIC was started in the ambulance and continued at the hospital for 7 days. RBC deformability and erythrocyte aggregation rate were assessed using ektacytometry, NO using flowcytometry, and nitrite content using ozone chemiluminescence. Logistic regression and mixed effect models were used. Out of 1500 prehospital randomized patients, and between July 28, 2020 and November 11, 2023, 486 patients had blood samples taken. Of these 249 (51%) had acute ischemic stroke and were included in this study. In the acute phase, higher levels of RBC deformability, aggregation, and RBC NO content were associated with worse clinical outcome if patients were treated with RIC compared with sham. Similar results were found at 24 hours, except for a potential effect on early neurological improvement in RIC-treated patients with an increased deformability level at 24 hours.

RIC may have time-dependent and biomarker-specific effects on stroke outcomes, and detrimental interactions between increasing biomarker levels and RIC were observed. This may explain previous failures to translate RIC into an effective neuroprotective therapy in the hyperacute phase.

Remote ischemic postconditioning (RIPostC), administered after the onset of local ischemia, has been shown to have beneficial effects on neurological, vascular, and motor functions in animal models. However, the precise mechanisms and interactions underlying these functional improvements remain unclear. Our study aimed to determine whether RIPostC exerts protective effects on the neurovascular units (NVU) and to investigate whether this protection is mediated by hypoxia-inducible factor-1α (HIF-1α). We used left middle cerebral artery occlusion and reperfusion (MCAO/r) to induce ischemic stroke in rats and applied RIPostC. YC-1 was used to inhibit the activity of HIF-1α. Following the 12-day RIPostC treatment, MRI scans showed a significant reduction in infarct volume in the affected area, accompanied by an increase in HIF-1α protein levels and its downstream angiogenic factors in the ischemic zone. Additionally, RIPostC promoted angiogenesis in the ischemic penumbra, which, in turn, reduced neuronal loss and astrocyte activation. Behavioral assessments further indicated that RIPostC treatment partially restored the motor function in MCAO/r rats. However, the therapeutic effects of RIPostC were counteracted by the addition of YC-1, suggesting that the protective effects of RIPostC against NVU are mediated through HIF-1α. Overall, our research demonstrates that RIPostC is an effective rehabilitative intervention for protecting NVU in MCAO/r rats through the HIF-1α-mediated pathway.

Remote ischemic conditioning (RIC) is a simple and low-cost intervention that is thought to increase collateral blood flow through the vasodilatory effects of nitric oxide (NO) produced by the endothelium and red blood cells (RBCs). This study aims to investigate whether RIC affects RBC deformability and levels of NO and nitrite in patients with ischemic stroke.

This is a predefined substudy to the RESIST (Remote Ischemic Conditioning in Patients With Acute Stroke Trial) randomized clinical trial conducted in Denmark. RIC was started in the ambulance and continued at the hospital for seven days. Blood samples were collected at different time points: prehospital in the ambulance, in-hospital upon arrival, 2 hours postadmission, and 24 hours postadmission. RBC deformability and erythrocyte aggregation rate were assessed using ektacytometry, NO using flowcytometry, and nitrite content using ozone chemiluminescence.

Of 1500 prehospital randomized patients, 486 patients were included in this study between July 28, 2020, and November 11, 2023, and had blood samples taken. Of these, 249 (51%) had AIS, and here RIC treatment was not associated with increased RBC maximal deformability (RIC, 0.549; sham, 0.548; P=0.31), RBC NO (RIC, 35 301 median fluorescence intensity; sham, 34979 median fluorescence intensity; P=0.89), or nitrite (RIC, 0.036 µmol/L; sham, 0.034 µmol/L; P=0.38), but RIC treatment was associated with a significantly reduced aggregation pressure and a slower erythrocyte aggregation rate (RIC, 323.76 millipascal; sham, 352.74 millipascal; P=0.0113).

Prehospital and in-hospital RIC significantly reduced erythrocyte aggregation rate in patients with acute ischemic stroke, while there was no change in RBC deformability, NO content, or whole blood nitrite levels.

URL: https://www.clinicaltrials.gov; Unique identifier: NCT03481777.

Cardiovascular disease is a leading cause of death, with ischemic heart disease being a significant contributor. While percutaneous coronary intervention (PCI) effectively reduces mortality in myocardial infarction patients, its efficacy for unstable angina (UA) patients is controversial. Complications associated with PCI further limit application in UA. RIC is hypothesized to be an effective co-intervention that reduces PCI-related complications and may potentially enhance the efficacy of the PCI procedure itself.

This is a pragmatic, prospective, dual-center, double-blind, randomized controlled clinical trial assessing the effect of remote ischemic conditioning (RIC) during percutaneous coronary intervention (PCI) on injury in unstable angina patients aged ≥ 18 years undergoing coronary angiography. Participants will be randomized to receive either RIC or Sham RIC, in addition to standard pharmacotherapy. Primary outcome includes periprocedural myocardial injury measured by hs-cTnT levels, while secondary outcomes encompass major adverse cardiovascular events, coronary artery lesions Gensini Score, arrhythmia, angina incidence, SAQ scores, ECG changes, and cardiac function assessed by two-dimensional echocardiography. The trial aims to recruit 574 participants and is scheduled to be initiated on 15 January 2024. We will conduct the primary statistical analysis using the intention-to-treat principle. Results from the trial will be presented as comparative summary statistics following the Consolidated Standards of Reporting Trials (CONSORT) guidelines.

ChiCTR2400079855, 15 January 2024.

Mitochondrial reactive oxygen species (mROS) play a crucial physiological role in intracellular signalling. However, high levels of ROS can overwhelm antioxidant defences and lead to detrimental modifications in protein, lipid and DNA structure and function. Ischaemia-reperfusion injury is a multifaceted pathological state characterised by excessive production of mROS. There is a significant clinical need for therapies mitigating mitochondrial oxidative stress. To date, a variety of strategies have been investigated, ranging from enhancing antioxidant reserve capacity to metabolism reduction. While success has been achieved in non-clinical models, no intervention has yet successfully transitioned into routine clinical practice. In this article, we explore the different strategies investigated and discuss the possible reasons for the lack of translation.

Remote ischemic preconditioning (RIPC) is a therapy characterized by repeated bouts of limb ischemia and reperfusion. RIPC protects against ischemia-reperfusion injury (IRI), and preclinical studies suggest that this is mediated through the release of endogenous opioids. We aimed to interrogate the role of endogenous opioids in RIPC-signaling in humans, using an arm model of IRI. We hypothesized that RIPC would attenuate IRI-induced reductions in brachial artery flow-mediated dilation (FMD) and that this would be prevented by systemic opioid receptor blockade. Eleven healthy adults (8 M/3 F, age = 28 ± 8 yr) completed three experimental visits in which IRI was induced via 20-min upper arm ischemia and 20-min reperfusion achieved via upper arm cuff inflation to 250 mmHg. FMD was measured at rest and again following IRI. During the control condition, RIPC was not performed. During the RIPC condition, RIPC was performed on the contralateral arm via four cycles of 5-min cuff inflation (250 mmHg) with 5-min reperfusion. During the opioid receptor blockade condition (naloxone), RIPC was performed in the presence of systemic opioid receptor blockade via intranasal naloxone (4 mg), which was administered during the first 5-min cycle of RIPC. The change in FMD from baseline versus post-IRI was compared between visits via a two-way repeated measures ANOVA (factor 1: time, factor 2: condition) followed by Tukey post hoc tests. IRI reduced FMD during the control (pre = 6.1 ± 2.4%, post = 3.5 ± 2.8%, P < 0.001) and naloxone (pre = 6.6 ± 2.7%, post = 3.5 ± 1.9%, P < 0.001) conditions but not during the RIPC condition (pre = 5.9 ± 2.2%, post = 4.9 ± 2.8%, P = 0.14). These findings demonstrate that RIPC provides vascular protection from IRI in humans through an opioid-dependent mechanism.NEW & NOTEWORTHY Remote ischemic preconditioning (RIPC) is a cardioprotective therapy characterized by brief cycles of limb ischemia and reperfusion. We demonstrate that a single bout of arm RIPC provides protection from ischemia-reperfusion injury-induced reductions in vascular function in healthy adults. This protection was attenuated when RIPC was administered in the presence of systemic opioid-receptor blockade via intranasal naloxone. These findings suggest that endogenous opioids contribute to RIPC-induced protection of vascular function in humans.

The Canadian Cardiovascular Society recently put forth a new classification of acute reperfused myocardial infarction (MI) based on stages of myocardial injury. Backed by more than 5 decades of intense investigation in the field, the key message of this new classification is that not all MIs are the same and that the type and extent of myocardial injury should be considered in diagnosing and treating MI. We review the literature with the goal of highlighting the progressive advances that enabled the synthesis of the Canadian Cardiovascular Society classification into 4 distinct stages of tissue injury. We emphasize the major breakthroughs from insights gained from experimental, translational, and clinical studies to date. We also identify current gaps in knowledge and critical research directions that need to be pursued to improve patient care and reduce post-MI complications such as chronic heart failure and malignant arrhythmias, whose risk is linked to stage and extent of myocardial injury.

Limb ischemia-reperfusion injury caused by repeated tourniquet application usually leads to acute kidney injury, adversely affecting patient prognosis. This study aimed to investigate the renoprotective effect of remote ischemic preconditioning (RIPC) in patients undergoing extremity surgery with repeated tourniquet application.

64 patients were enrolled and randomly divided into an RIPC group and a control group, with 32 patients in each. Pretreatment was administered before surgery, and baseline characteristics were collected. Perioperative surgical characteristics, renal biomarkers, oxidative stress markers, inflammatory factors, and postoperative conditions were recorded.

2 participant were excluded from each group, leaving 30 patients per group. There were no significant differences between the two groups regarding baseline characteristics and perioperative surgical characteristics (p > 0.05). Compared to the control group, the RIPC group showed a significant decrease in BUN and SCr at 48 h postoperatively (p < 0.05). Levels of Cys-C, [TIMP-2] × [IGFBP-7], KIM-1, IL-18, and NGAL were significantly reduced at the first and second tourniquet releases and at 24 h postoperatively in the RIPC group (p < 0.05). From the first tourniquet release to 48 h postoperatively, MDA levels were significantly lower (p < 0.05) and SOD levels were significantly higher (p < 0.05) in the RIPC group compared to the control group. Postoperative conditions did not differ significantly between the groups.

RIPC effectively mitigated acute kidney injury caused by repeated tourniquet application, offering a robust method for perioperative renal protection in patients undergoing extremity surgery. Future studies should explore the underlying mechanisms and long-term clinical outcomes of RIPC in broader patient populations.

https://www.chictr.org.cn/showproj.html?proj=231266.

In patients with myocardial infarction, one of the complications that may occur after revascularization is myocardial ischemia-reperfusion injury (IRI), characterized by a depleted myocardial oxygen supply and absence of blood flow recovery after reperfusion, leading to expansion of myocardial infarction, poor healing of myocardial infarction and reversal of left ventricular remodeling, and an increase in the risk for major adverse cardiovascular events such as heart failure, arrhythmia, and cardiac cell death. As a risk factor for cardiovascular disease, diabetes mellitus increases myocardial susceptibility to myocardial IRI through various mechanisms, increases acute myocardial infarction and myocardial IRI incidence, decreases myocardial responsiveness to protective strategies and efficacy of myocardial IRI protective methods, and increases diabetes mellitus mortality through myocardial infarction. This Review summarizes the mechanisms, existing therapeutic strategies, and potential therapeutic targets of myocardial IRI in diabetic states, which has very compelling clinical significance.

Cardiopulmonary bypass (CPB) is a common technique in cardiac surgery but is associated with acute kidney injury (AKI), which carries considerable morbidity and mortality. In this review, we explore the range and definition of CPB-associated AKI and discuss the possible impact of different disease recognition methods on research outcomes. Furthermore, we introduce the specialized equipment and procedural intricacies associated with CPB surgeries. Based on recent research, we discuss the potential pathogenesis of AKI that may result from CPB, including compromised perfusion and oxygenation, inflammatory activation, oxidative stress, coagulopathy, hemolysis, and endothelial damage. Finally, we explore current interventions aimed at preventing and attenuating renal impairment related to CPB, and presenting these measures from three perspectives: (1) avoiding CPB to eliminate the fundamental impact on renal function; (2) optimizing CPB by adjusting equipment parameters, optimizing surgical procedures, or using improved materials to mitigate kidney damage; (3) employing pharmacological or interventional measures targeting pathogenic factors.

Hypoxia can drive tumor progression, suppress anti-tumor immunity, and reduce the effectiveness of radiotherapy and chemotherapy. This study aimed to assess the impact of remote ischemic conditioning (RIC) on tumor oxygenation (sO2) and the anti-tumor immune response.

Fourteen B16-Ova tumor-bearing C57BL/6N mice received six 5-minute RIC cycles, while another fourteen underwent anesthesia only. Pimonidazole was administered 1.5 hours before sacrifice. Blood flow, sO2, and hemoglobin levels were measured in the non-ischemic hind limb and tumor. Tumor hypoxia was assessed using pimonidazole and CA IX immunohistochemistry, and T cell infiltration by CD3 and FoxP3 staining. Serum levels of 23 cytokines were analyzed using a multiplex immunoassay.

Isoflurane anesthesia caused a slight intraindividual increase in blood flow (p = 0.07) and sO2 (p = 0.06) of the hind limb and a sole increase in tumor sO2 (p = 0.035), whereas RIC improved sO2 of the tumor in relation to the hind limb (p=0.03). The median of the tumor oxygen saturation reached 51.4% in the control group and 62.7% in the RIC group (p = 0.09), exhibiting a slight tendency towards better oxygenation in the RIC group. Pimonidazole (p=0.24) and CA IX hypoxia score (p=0.48) did not reveal statistically significant differences between the two groups. In RIC-treated tumors, the number of CD3 (p=0.006), but not FoxP3- positive cells (p = 0.84), in the tumor core was significantly higher compared to the control group. In the RIC group, the mean fluorescence intensity (MFI) of IL-17 was significantly higher (p=0.035), and TNF-α was trend-wise higher (p=0.063) compared to the control group.

Both isoflurane anesthesia and RIC have an impact on microcirculation. The application of RIC counteracted some of the effects of isoflurane, primarily in healthy tissue, and led to a significant improvement in relative tumor tissue oxygenation compared to the non-ischemic hind limb. RIC selectively enhanced immune infiltration within the tumor center, probably by previously activated tumor infiltrating T cells, while having no significant impact on T-regulatory cells. RIC appears to impact the cytokine profile, as indicated by elevated MFIs of TNF-α and IL-17.

Remote limb ischemic pre-conditioning (RIPreC) can invoke potent renal protection. The involvement of oxidative stress and inflammatory pathways in renal ischemia/reperfusion injury (I/RI) was also confirmed. This study was designed to investigate the RIPreC effects on IRI-induced kidney dysfunction in rats through NFĸB/TNF-α/TGF-ꞵ/apelin signaling pathway.

Renal I/RI was induced by occluding the kidney arteries for 45 min, then reperfusion for 24 h. Four similar cycles of left femoral artery ischemia (2 min)/reperfusion (3 min) before the onset of kidney ischemia were performed to create RIPreC. Animals were randomly divided into three groups: sham, I/R, and RIPreC + I/R. Following the reperfusion phase, urine and blood samples were taken, and the kidney was removed for functional, molecular, and histological examination.

When compared to sham rats, renal IRI resulted in decreased creatinine clearance and increased sodium fractional excretion, lower antioxidant enzyme activities, higher malondialdehyde content and higher nuclear factor-kappa B (NF-κB), tumor necrosis factor-alpha (TNF-α), transforming growth factor-betta (TGF-β), and Apelin expression levels, and histologically damaged kidney tissue. All of the alterations, as mentioned earlier, were alleviated using the RIPreC treatment.

Thus, RIPreC can protect against renal dysfunction after renal I/RI via modulation of the TNF-α/NF-κB/TGF-ꞵ/Apelin signaling pathway and strengthening the antioxidant defense system.

Background and Objectives: Postreperfusion syndrome (PRS) is a significant challenge in liver transplantation (LT), leading to severe circulatory and metabolic complications. Ischemic preconditioning (IPC), including remote IPC (RIPC), can mitigate ischemia-reperfusion injury, although its efficacy in LT remains unclear. This study evaluated the impact of paired RIPC, involving the application of RIPC to both the recipient and the living donor, on the incidence of PRS and the need for rescue epinephrine during living-donor LT (LDLT). Materials and Methods: This retrospective observational cohort analysis included 676 adult patients who had undergone elective LDLT between September 2012 and September 2022. After applying exclusion criteria and propensity score matching (PSM), 664 patients were categorized into the paired RIPC and non-RIPC groups. The primary outcomes were the occurrence of PRS and the need for rescue epinephrine during reperfusion. Results: The incidence of PRS and the need for rescue epinephrine were significantly lower in the paired RIPC group than in the non-RIPC group. Furthermore, the incidence of postoperative acute kidney injury was lower in the paired RIPC group. Multivariable logistic regression adjusted for propensity scores indicated that paired RIPC was significantly associated with a reduced occurrence of PRS (odds ratio: 0.672, 95% confidence interval: 0.479-0.953, p = 0.021). Conclusions: Paired RIPC, involving both the recipient and the living donor, effectively reduces the occurrence of PRS and the need for rescue epinephrine during LDLT. These findings suggest that paired RIPC protects against ischemia-reperfusion injury in LDLT. Future randomized controlled trials are needed to verify our results and to explore the underlying mechanisms of the protective effects of RIPC.

A single bout of aerobic exercise is known to induce a temporary reduction in post-exercise blood pressure termed post-exercise hypotension (PEH). Meanwhile, an ischemic preconditioning (IPC), a series of short ischemia-reperfusion intervention, has also shown antihypertensive effects showing a potential nonpharmacologic intervention for hypertension. While the acute BP reduction effects of aerobic exercise and IPC are individually well-investigated, it remains unclear if combining both interventions has an additive effect on PEH.

A total of twelve pre- or hypertensive men (six prehypertension, six stage 1 hypertension) underwent either 30 min of aerobic exercise at 50% VO2peak (CON) or IPC before exercise, in a counterbalanced order. IPC involved inflating cuffs on both thighs to 200 mmHg for 5 min, alternating between right and left thighs for three cycles, totaling 30 min. Brachial BP was measured during exercise and 1-h post-exercise recovery whereas muscle oxygen saturation (SmO2) from the rectus femoris was monitored using NIRs during exercise and recovery. Heart rate variability (HRV) and baroreflex sensitivity (BRS) together with a head-up tilt test (at 0 and 50°) were measured at the pre-test, post-test, and 24-h post-test. After the completion of each experiment, 24-h ambulatory blood pressure (ABP) was monitored to assess post-exercise hypotension within a 24-h window.

BP and heart rate responses during exercise and 1-h recovery did not differ between conditions while SmO2 was significantly elevated during exercise in IPC (p = 0.004). There was no difference in HRV and supine BRS. However, significantly reduced titled BRS after exercise was found in CON while IPC preserved BRS similar to pre-exercise value, extending to 24-h post period (p = 0.047). ABP monitoring revealed a significant reduction in systolic BP during sleep in IPC compared to CON (p = 0.046).

The present findings suggest that IPC with a single session of aerobic exercise results in a notable decrease in systolic ABP, particularly during sleep, compared to aerobic exercise alone. This supplementary antihypertensive effect was associated with a sustained BRS, persisting up to 24 h in contrast to the significant decrease observed in CON. Future studies are warranted to investigate long-term adaptations to IPC.

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.

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.

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.

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.

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.

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.

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.

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.

Coronary artery bypass grafting (CABG) is frequently used to treat severe coronary artery disease (CAD), but it can lead to increased oxidative stress and inflammation, worsening patient outcomes. Remote ischemic preconditioning (RIPC) has been suggested as a potential strategy to protect against these effects by modulating oxidative stress and inflammatory responses, though its impact on specific biomarkers requires further investigation. This study aims to assess the effects of remote ischemic preconditioning on inflammation markers and oxidative stress in patients with severe CAD undergoing coronary artery bypass grafting.

We conducted a case-control study involving 80 patients with severe coronary artery disease (CAD) scheduled for coronary artery bypass grafting (CABG). Fifty percent of these patients received ischemic preconditioning prior to surgery. Plasma levels of Lectin-like oxidized low-density lipoprotein receptor-1 (LOX-1) and Superoxide dismutase-1 (SOD-1) levels were measured in all individuals using the ELISA method at three important time points: before surgery (visit 1 or V1), immediately post-operatively (visit 2 or V2), and one week post-operatively (visit 3 or V3).

We enrolled 80 patients, of which 40 were assigned to the studied group receiving remote ischemic preconditioning (RIPC) and 40 to the control group. There were no statistically significant differences between the groups regarding baseline, clinical, or operative characteristics. RIPC treatment significantly reduced plasma levels of Lectin-like oxidized low-density lipoprotein (LDL) receptor-1 (LOX-1) (p < 0.05) as well as significantly increasing total values of Superoxide dismutase-1 (SOD-1) (p < 0.05, respectively). There were notable differences between the studied and control groups at V2 and V3. The studied group had higher SOD-1 levels (p < 0.05) and significantly lower LOX-1 levels at both time points (p < 0.05).

The significant changes in plasma levels of both LOX-1 and SOD-1 observed in this study strongly suggest that remote ischemic preconditioning (RIPC) plays an important role in reducing oxidative stress and enhancing the antioxidative status of patients. This is evidenced by the marked decrease in LOX-1 levels, alongside a corresponding increase in SOD-1 levels, indicating that RIPC may contribute to improved cardioprotection through these mechanisms.

Myocardial ischemia-reperfusion arrhythmia after cardiac surgery is common and seriously affects quality of life. Remote ischemic preconditioning can reduce the myocardial damage caused by severe ischemia. However, the underlying mechanism is not well understood. This study aimed to investigate the effects of exosomes derived from C2C12 mouse myoblasts after hypoxic preconditioning (HP) on ventricular conduction in hypothermic ischemia-reperfusion hearts. Myocardial ischemia-reperfusion model rats were established using the Langendorff cardiac perfusion system. Exosomes derived from normoxic (ExoA) and hypoxia-preconditioned (ExoB) C2C12 cells were injected into the jugular vein of the model rats. The time to heartbeat restoration, arrhythmia type and duration, and heart rate were recorded after myocardial ischemia-reperfusion. Conduction velocity on the surface of left ventricle was measured using a microelectrode array after 30 min of balanced perfusion, 15 min of reperfusion, and 30 min of reperfusion. Immunohistochemistry and western blotting were performed to determine the distribution and relative expression of connexin 43 (Cx43). ExoB contained more exosomes than ExoA, showing that HP stimulated the release of exosomes. The IR + ExoB group showed faster recovery of ventricular myocardial activity, a lower arrhythmia score, faster conduction velocity, and better electrical conductivity than the IR group. ExoB increased the expression of Cx43 and reduced its lateralization in the ventricular muscle. Our study showed that exosomes induced by hypoxic preconditioning can improve ventricular myocardial conduction and reperfusion arrhythmia in isolated hearts after hypothermic ischemia-reperfusion.

This study aimed to investigate if remote ischemic preconditioning reduces the inflammatory process on patients undergoing coronary artery bypass grafting (CABG).

We conducted a case-control study involving 80 patients, half of whom underwent ischemic preconditioning for severe coronary artery disease (CAD) and subsequently underwent CABG. We assessed interleukin (IL)-1 and IL-6 levels using the enzyme-linked immunosorbent assay (ELISA) method, high-sensitivity troponin I (hsTnI) using chemiluminescent immunoassay (CLIA), and C-reactive protein (CRP) using the turbidimetric method at three key time points: before surgery (visit 1 or V1), immediately postoperatively (visit 2 or V2), and 1 week postoperatively (visit 3 or V3) in all subjects.

Ischemic preconditioned patients showed a significant decrease in proinflammatory markers (IL-1, IL-6) but not in CRP or hsTnI.

This study demonstrated that remote ischemic preconditioning significantly reduced the levels of specific proinflammatory markers (IL-1 and IL-6), which may suggest general systemic protection. However, it did not demonstrate cardioprotection per se, as evidenced by the absence of a statistically significant decrease in hsTnI level.

Ischemic heart disease (IHD) is a significant global health concern, resulting in high rates of mortality and disability among patients. Although coronary blood flow reperfusion is a key treatment for IHD, it often leads to acute myocardial ischemia-reperfusion injury (IRI). Current intervention strategies have limitations in providing adequate protection for the ischemic myocardium. DJ-1, originally known as a Parkinson's disease related protein, is a highly conserved cytoprotective protein. It is involved in enhancing mitochondrial function, scavenging reactive oxygen species (ROS), regulating autophagy, inhibiting apoptosis, modulating anaerobic metabolism, and exerting anti-inflammatory effects. DJ-1 is also required for protective strategies, such as ischemic preconditioning, ischemic postconditioning, remote ischemic preconditioning and pharmacological conditioning. Therefore, DJ-1 emerges as a potential target for the treatment of myocardial IRI. Our comprehensive review delves into its protective mechanisms in myocardial IRI and the structural foundations underlying its functions.

Ischemic Preconditioning (IPC) has emerged as a promising approach to mitigate the impact of hypoxia on physiological functions. However, the heterogeneity of occlusion pressures for inducing arterial occlusion has led to inconsistent hemodynamic outcomes across studies. This study aims to evaluate the peripheral hemodynamic responses to partial and total blood-flow occlusions on the left arm at rest, using absolute or individualized pressures, on two occasions. Thirty-five young males volunteered to participate in this study. IPC procedure (3 × 7-min) was performed on the left upper arm with cuff pressures at 50 mmHg (G1), 50 mmHg over the systolic blood pressure (SBP + 50 mmHg) (G2) or 250 mmHg (G3). NIRS-derived parameters were assessed for each occlusion and reperfusion phase in the brachioradialis. Results showed a significantly lower magnitude of deoxygenation (TSIAUC) for G1 compared to G2 (-1959.2 ± 1417.4 vs. -10908.1 ± 1607.5, P < 0.001) and G3 -1959.2 ± 1417.4 vs. -11079.3 ± 1828.1, P < 0.001), without differences between G2 and G3. However, G3 showed a significantly faster reoxygenation only for tissue saturation index (TSIslope) compared to G2 (1.3 ± 0.1 vs. 1.0 ± 0.2, P = 0.010), but without differences in the speed of recovery of deoxyhemoglobin [(HHb) slope], or in the magnitude of post-occlusive hyperemia (PORH). Besides TSI reoxygenation speed, G2 and G3 elicit comparable resting hemodynamic responses measured by NIRS. Thus, this study highlights the practicality and effectiveness of using relative occlusion pressures based on systolic blood pressure (SBP) rather than relying on excessively high absolute pressures.

The role of intravenous immunoglobulin in protecting the diabetic heart from ischemia/reperfusion (I/R) injury is unclear. Hearts isolated from adult diabetic and nondiabetic Wistar rats (n = 8 per group) were treated with intravenous immunoglobulin (IVIG) either 2 hours before euthanasia, before ischemia, or at reperfusion. Hemodynamic data were acquired using the Isoheart software version 1.524-S. Ischemia/reperfusion (I/R) injury was evaluated by 2,3,5-triphenyltetrazolium chloride staining and troponin T levels. The levels of apoptosis markers, caspases-3/8, antioxidant enzymes, superoxide dismutase and catalase, glucose transporters, GLUT-1 and GLUT-4, phosphorylated ERK1/2, and phosphorylated eNOS were estimated by Western blotting. Proinflammatory and anti-inflammatory cytokine levels were evaluated using enzyme-linked immunosorbent assays. Intravenous immunoglobulin administration abolished the effects of I/R injury in hearts subjected to hyperglycemia when infused at reperfusion, before ischemia, or at reperfusion in 4-week diabetic rat hearts and only at reperfusion in 6-week diabetic rat hearts. IVIG infusion resulted in a significant (P < 0.05) recovery of cardiac hemodynamics and decreased infarct size. IVIG also reduced the levels of troponin T, apoptotic enzymes, and proinflammatory cytokines. IVIG significantly (P < 0.05) increased the levels of anti-inflammatory cytokines, antioxidant enzymes, GLUT-4, and phosphorylated eNOS. Intravenous immunoglobulin protected the hearts from I/R injury if infused at reperfusion in the presence of hyperglycemia, in 4- and 6-week diabetic rat hearts, and when infused before ischemia in 4-week diabetic rat hearts. IVIG exerts its cardioprotective effects associated with the upregulated phosphorylated eNOS/GLUT-4 pathway.

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.

Noninvasive remote ischemic preconditioning (RIPC) is a practical, acceptable, and feasible conditioning technique reported to provide cardioprotection in myocardial ischemia-reperfusion injury (MIRI). It has been well-reported that quercetin possesses antioxidant and anti-inflammatory properties. This study investigates the modification of the cardioprotective response of RIPC by quercetin.

Adult Wistar rats were randomized into 12 groups of six animals each. MIRI was induced by subjecting the isolated hearts of Wistar rats to global ischemia for 30 min, succeeded by reperfusion of 120 min after mounting on the Langendorff PowerLab apparatus. Hind limb RIPC was applied in four alternate cycles of ischemia and reperfusion of 5 min each by tying the pressure cuff before isolation of hearts.

MIRI was reflected by significantly increased infarct size, LDH-1, and CK-MB, TNF-α, TBARS, and decreased GSH, catalase, and hemodynamic index, and modulated Nrf2. Pretreatment of quercetin (25 and 50 mg/kg; i.p.) significantly attenuated the MIRI-induced cardiac damage and potentiated the cardioprotective response of RIPC at the low dose. Pretreatment of ketamine (10 mg/kg; i.p.), an mTOR-dependent autophagy inhibitor, significantly abolished the cardioprotective effects of quercetin and RIPC.

The findings highlight the modification of the cardioprotective effect of RIPC by quercetin and that quercetin protects the heart against MIRI through multiple mechanisms, including mTOR-dependent activation of autophagy and Nrf-2 activation.

Background: Remote ischemic preconditioning (RIPC) is reported to have early-phase and delayed-phase organ-protective effects. Previous studies have focused on the organ protection of a single RIPC protocol, and the clinical outcomes remain uncertain. Whether the modified RIPC (mRIPC) protocol performed repeatedly provides cardiopulmonary protection is still uncertain. Methods: In this single-center, randomized, controlled trial, 86 patients undergoing elective mitral valve replacement (MVR) surgery were randomized 1:1 to receive either mRIPC or no ischemic preconditioning (control). Three cycles of 5 min ischemia and 5 min reperfusion induced by a blood pressure cuff served as the RIPC stimulus. mRIPC was induced at the following three time points: 24 h, 12 h, and 1 h before surgery. Blood samples were withdrawn at 10 min after intubation (T0), at 1 h after aortic declamping (T1), and at 6 h (T2), 12 h (T3), and 24 h (T4) after surgery to measure the serum concentrations of myocardial enzymes and other biomarkers, including cardiac troponin I (cTnI), which was the primary endpoint of this study. Creatine kinase isoenzyme (CK-MB), lactate dehydrogenase (LDH), inotropic score (IS), and inflammatory mediators were also measured. Blood gas analysis was conducted to calculate the PaO2/FiO2 ratio and A-aDO2, and the incidence of acute lung injury (ALI) was also recorded. Results: mRIPC significantly decreased the serum concentrations of cTnI, CK-MB, and LDH at T2, T3, and T4 (p < 0.01), and the IS decreased compared with that in the control group (12.0 ± 1.0 vs. 14.2 ± 1.1, p < 0.01). In addition, the incidence of ALI in the mRIPC group was decreased (32.6% vs. 51.2%, p = 0.039), and the PaO2/FiO2 was higher at T4 (p < 0.05). Compared with those in the control group, the levels of interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) were decreased at T1, T2, T3, and T4 (p < 0.05) in the mRIPC group, and the level of IL-10 increased at the same time. Conclusions: mRIPC decreased the incidence of myocardial and lung injury in MVR surgery, providing new evidence for the clinical application of RIPC in valve surgery. Trial Registration: ClinicalTrials.gov (NCT01406678).

Neuronal death resulting from ischemic stroke is the primary cause of adult mortality and disability, and effective neuroprotective agents for poststroke intervention are still lacking. Remote ischemic postconditioning (RIPostC) has demonstrated significant protective effects against ischemia in various organs; however, the specific mechanisms are not fully understood. This study investigated the potential neuroprotective mechanisms of RIPostC in the context of ischemic stroke. Using a rat model of middle cerebral artery occlusion, we found that RIPostC mitigated neurological damage, improved movement in the open-field test, and protected against neuronal apoptosis. In terms of energy metabolism, RIPostC enhanced ATP levels, suppressed lactate content, and increased the production of ketone bodies (KBs). In the ferroptosis assay, RIPostC protected against lipoperoxidation, reversed the reduction of glutathione peroxidase 4 (GPX4), and mitigated the excessive expression of long-chain acyl-CoA synthetase family member 4 (ACSL4). In oxygen-glucose deprivation/reoxygenation-treated HT22 cells, KBs maintained GPX4 levels, suppressed ACSL4 expression, and preserved the mitochondrial cristae number. However, the effect of KBs on the expression of GPX4, ACSL4, and the number of mitochondrial cristae was blocked by erastin. Moreover, both RIPostC and KBs reduced total iron and ferrous ion content by repressing iron transporters both in vitro and in vivo. In conclusion, KBs-induced mitigation of ferroptosis could represent a new therapeutic mechanism for RIPostC in treating stroke.

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 (µHbO2), 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.

We investigated the effect of Remote Ischemic Preconditioning (RIPC) on the inflammatory response during CPB by means of serum presepsin levels at preoperative and postoperative 1st and 24th h.

In this prospective, randomized, cross-sectional study we included 81 patients undergoing coronary artery bypass graft surgery with cardiopulmonary bypass (CPB). Patients were randomized and RIPC was applied to 40 patients in the study group before anesthesia. The remaining 41 patients were determined as the control group. The relationships between RIPC and factors such as presepsin, C-reactive protein (CRP), and leukocyte levels were investigated.

There was no significant difference between the groups in postoperative leukocyte and CRP values (p = 0.52, p = 0.13, respectively). When the preoperative and postoperative first hour presepsin values of the patients were compared, no significant difference was found in the control group (p = 0.17), but a significant difference was found in the study group (p < 0.05). When the presepsin values were compared between the groups, a significant difference was found only in the postoperative first hour value (p < 0.05).

It was observed that RIPC application caused to increase the presepsin levels in the postoperative first hour significantly in the study group (p < 0.05).

The vagus nerve belongs to the parasympathetic nervous system, which is involved in the regulation of organs throughout the body. Since the discovery of the non-neuronal cardiac cholinergic system (NNCCS), several studies have provided evidence for the positive role of acetylcholine (ACh) released from cardiomyocytes against cardiovascular diseases, such as sympathetic hyperreactivity-induced cardiac remodeling and dysfunction as well as myocardial infarction. Non-neuronal ACh released from cardiomyocytes is believed to regulate key physiological functions of the heart, such as attenuating heart rate, offsetting hypertrophic signals, maintaining action potential propagation, and modulating cardiac energy metabolism through the muscarinic ACh receptor in an auto/paracrine manner. Moreover, the NNCCS may also affect peripheral remote organs (e.g., liver) through the vagus nerve. Remote ischemic preconditioning (RIPC) and NNCCS activate the central nervous system and afferent vagus nerve. RIPC affects hepatic glucose and energy metabolism through the central nervous system and vagus nerve. In this review, we discuss the mechanisms and potential factors responsible for NNCCS in glucose and energy metabolism in the liver.

Acute kidney injury (AKI) is common following liver transplantation and is associated with liver ischeamia reperfusion (IR) injury. The purpose of this study was to use a mouse model of liver IR injury and AKI to study the role of Neutrophil Gelatinase Associated Lipocalin (NGAL), a biomarker of AKI, in liver IR injury and AKI. We demonstrate an adapted, reproducible model of liver IR injury and AKI in which remote ischemic preconditioning (RIPC) by repeated episodes of hindleg ischemia prior to liver IR reduced the severity of the IR injury. In this model, serum NGAL at 2 h post reperfusion correlated with AKI development early following IR injury. This early rise in serum NGAL was associated with hepatic but not renal upregulation of NGAL mRNA, suggesting NGAL production in the liver but not the kidney in the early phase post liver IR injury.

Remote ischemic conditioning (RIC) has the potential to benefit graft function following kidney transplantation by reducing ischemia-reperfusion injury; however, the current clinical evidence is inconclusive. This meta-analysis with trial sequential analysis (TSA) aimed to determine whether RIC improves graft function after kidney transplantation.

A comprehensive search was conducted on PubMed, Cochrane Library, and EMBASE databases until June 20, 2023, to identify all randomized controlled trials that examined the impact of RIC on graft function after kidney transplantation. The primary outcome was the incidence of delayed graft function (DGF) post-kidney transplantation. The secondary outcomes included the incidence of acute rejection, graft loss, 3- and 12-month estimated glomerular filtration rates (eGFR), and the length of hospital stay. Subgroup analyses were conducted based on RIC procedures (preconditioning, perconditioning, or postconditioning), implementation sites (upper or lower extremity), and graft source (living or deceased donor).

Our meta-analysis included eight trials involving 1038 patients. Compared with the control, RIC did not significantly reduce the incidence of DGF (8.8% vs. 15.3%; risk ratio = 0.76, 95% confidence interval [CI], 0.48-1.21, P = 0.25, I2 = 16%), and TSA results showed that the required information size was not reached. However, the RIC group had a significantly increased eGFR at 3 months after transplantation (mean difference = 2.74 ml/min/1.73 m2, 95% CI: 1.44-4.05 ml/min/1.73 m2, P < 0.0001, I2 = 0%), with a sufficient evidence suggested by TSA. The secondary outcomes were comparable between the other secondary outcomes. The treatment effect of RIC did not differ between the subgroup analyses.

In this meta-analysis with trial sequential analysis, RIC did not lead to a significant reduction in the incidence of DGF after kidney transplantation. Nonetheless, RIC demonstrated a positive correlation with 3-month eGFR. Given the limited number of patients included in this study, well-designed clinical trials with large sample sizes are required to validate the renoprotective benefits of RIC.

This systematic review and meta-analysis was registered at the International Prospective Register of Systematic Reviews (Number CRD42023464447).

Remote ischemic conditioning (RIC) is a therapeutic strategy to protect a vital organ like the brain from ischemic injury through brief and repeat cycles of ischemia and reperfusion in remote body parts such as arm or leg. RIC has been applied in different aspects of the stroke field and has shown promise. This narrative review will provide an overview of how to implement RIC in stroke patients, summarize the clinical evidence of RIC on stroke recovery, and discuss unresolved questions and future study directions.

Transcatheter aortic valve replacement (TAVR) has become an important treatment in patients with aortic valve disease with the continuous advancement of technology and the improvement of outcomes. However, TAVR-related complications still increase patient morbidity and mortality. Remote ischaemic preconditioning (RIPC) is a simple procedure that provides perioperative protection for many vital organs. However, the efficiency of RIPC on TAVR remains unclear based on inconsistent conclusions from different clinical studies. Therefore, we will perform a protocol for a systematic review and meta-analysis to identify the efficiency of RIPC on TAVR.

English databases (PubMed, Web of Science, Ovid Medline, Embase and Cochrane Library), Chinese electronic databases (Wanfang Database, VIP Database and China National Knowledge Infrastructure) and trial registry databases will be searched from inception to December 2023 to identify randomised controlled trials of RIPC on TAVR. We will calculate mean differences or standardised mean differences with 95% CIs for continuous data, and the risk ratio (RR) with 95% CIs for dichotomous data by Review Manager version 5.4. Fixed-effects model or random-effects model will be used according to the degree of statistical heterogeneity assessed by the I-square test. We will evaluate the risk of bias using the Cochrane risk-of-bias tool 2 and assess the evidence quality of each outcome by the Grading of Recommendations Assessment, Development and Evaluation. The robustness of outcomes will be evaluated by trial sequential analysis. In addition, we will evaluate the publication bias of outcomes by Funnel plots and Egger's regression test.

Ethical approval was not required for this systematic review protocol. The results will be disseminated through peer-reviewed publications.

CRD42023462926.

Myocardial ischemia-reperfusion injury (MIRI) remains a challenge in the context of reperfusion procedures for myocardial infarction (MI). While early revascularization stands as the gold standard for mitigating myocardial injury, recent insights have illuminated the paradoxical role of reperfusion, giving rise to the phenomenon known as ischemia-reperfusion injury. This comprehensive review delves into the intricate pathophysiological pathways involved in MIRI, placing a particular focus on the pivotal role of endothelium. Beyond elucidating the molecular intricacies, we explore the diverse clinical manifestations associated with MIRI, underscoring its potential to contribute substantially to the final infarct size, up to 50%. We further navigate through current preventive approaches and highlight promising emerging strategies designed to counteract the devastating effects of the phenomenon. By synthesizing current knowledge and offering a perspective on evolving preventive interventions, this review serves as a valuable resource for clinicians and researchers engaged in the dynamic field of MIRI.

Cardiomyopathies (CMs) are highly heterogeneous progressive heart diseases characterised by structural and functional abnormalities of the heart, whose intricate pathogenesis has resulted in a lack of effective treatment options. Mitsugumin 53 (MG53), also known as Tripartite motif protein 72 (TRIM72), is a tripartite motif family protein from the immuno-proteomic library expressed primarily in the heart and skeletal muscle. Recent studies have identified MG53 as a potential cardioprotective protein that may play a crucial role in CMs. Therefore, the objective of this review is to comprehensively examine the underlying mechanisms mediated by MG53 responsible for myocardial protection, elucidate the potential role of MG53 in various CMs as well as its dominant status in the diagnosis and prognosis of human myocardial injury, and evaluate the potential therapeutic value of recombinant human MG53 (rhMG53) in CMs. It is expected to yield novel perspectives regarding the clinical diagnosis and therapeutic treatment of CMs.

Stroke is a leading cause of global morbidity and mortality, indicating the necessity and urgency of effective prevention and treatment. Remote ischemic conditioning (RIC) is a convenient, simple, non-intrusive, and effective method that can be easily added to the treatment regime of stroke patients. Animal experiments and clinical trials have proved the neuroprotective effects of RIC on brain injury including (examples of neuroprotective effects). This neuroprotection is achieved by raising brain tolerance to ischemia, increasing local cerebral blood perfusion, promoting collateral circulations, neural regeneration, and reducing the incidence of hematomas in brain tissue. This current paper will summarize the studies within the last 2 years for the comprehensive understanding of the use of RIC in the treatment of stroke.

This paper summarizes the clinical research progress of RIC on stroke (ischemic stroke and hemorrhagic stroke (HS)). This paper is a systematic review of research published on registered clinical trials using RIC in stroke from inception through November 2022. Four major databases (PUBMED, WEB OF SCIENCE, EMBASE, and ClinicalTrials.gov) were searched.

Forty-eight studies were identified meeting our criteria. Of these studies, 14 were in patients with acute ischemic stroke with onset times ranging from 6 h to 14 days, seven were in patients with intravenous thrombolysis or endovascular thrombectomy, 10 were in patients with intracranial atherosclerotic stenosis, six on patients with vascular cognitive impairment, three on patients with moyamoya disease, and eight on patients with HS. Of the 48 studies, 42 were completed and six are ongoing.

RIC is safe, feasible, and effective in the treatment of stroke. Large-scale research is still required to explore the optimal treatment options and mechanisms of RIC in the future to develop a breakthrough in stroke prevention and treatment.

Acute myocardial infarction (AMI) is the leading cause of cardiovascular death and remains the most common cause of heart failure. Reopening of the occluded artery, i.e., reperfusion, is the only way to save the myocardium. However, the expected benefits of reducing infarct size are disappointing due to the reperfusion paradox, which also induces specific cell death. These ischemia-reperfusion (I/R) lesions can account for up to 50% of final infarct size, a major determinant for both mortality and the risk of heart failure (morbidity). In this review, we provide a detailed description of the cell death and inflammation mechanisms as features of I/R injury and cardioprotective strategies such as ischemic postconditioning as well as their underlying mechanisms. Due to their biological properties, the use of mesenchymal stromal/stem cells (MSCs) has been considered a potential therapeutic approach in AMI. Despite promising results and evidence of safety in preclinical studies using MSCs, the effects reported in clinical trials are not conclusive and even inconsistent. These discrepancies were attributed to many parameters such as donor age, in vitro culture, and storage time as well as injection time window after AMI, which alter MSC therapeutic properties. In the context of AMI, future directions will be to generate MSCs with enhanced properties to limit cell death in myocardial tissue and thereby reduce infarct size and improve the healing phase to increase postinfarct myocardial performance.

Animal experiments have confirmed that remote ischemic preconditioning (RIPC) can reduce hepatic ischemia-reperfusion injuries (HIRIs), significantly improving early tissue perfusion and oxygenation of the residual liver after resections, accelerating surgical prognoses, and improving survival rates. However, there is still controversy over the role of RIPC in relieving HIRI in clinical studies, which warrants clarification. This study aimed to evaluate the beneficial effects and applicability of RIPC in hepatectomy and to provide evidence-based information for clinical decision-making.

Randomized controlled trials (RCTs) evaluating the efficacy and safety of RIPC interventions were collected, comparing RIPC to no preconditioning in patients undergoing hepatectomies. This search spanned from database inception to January 2024. Data were extracted independently by two researchers according to the PRISMA guidelines. The primary outcomes assessed were postoperative alanine transaminase (ALT), aspartate transaminase (AST), total bilirubin (TBIL), and albumin (ALB) levels. The secondary outcomes assessed included duration of surgery and Pringle, length of postoperative hospital stay, intraoperative blood loss and transfusion, indocyanine green (ICG) clearance, hepatocyte apoptosis index, postoperative complications, and others.

Ten RCTs were included in this meta-analysis, with a total of 865 patients (428 in the RIPC group and 437 in the control group). ALT levels in the RIPC group were lower than those in the control group on postoperative day (POD) 1 (WMD = - 59.24, 95% CI: - 115.04 to - 3.45; P = 0.04) and POD 3 (WMD = - 27.47, 95% CI: - 52.26 to - 2.68; P = 0.03). However, heterogeneities were significant (I2 = 89% and I2 = 78%), and ALT levels on POD 3 were unstable based on a sensitivity analysis. AST levels on POD 1 in the RIPC group were lower than those in the control group (WMD = - 50.03, 95% CI: - 94.35 to - 5.71; P = 0.03), but heterogeneity was also significant (I2 = 81%). A subgroup analysis showed no significant differences in ALT and AST levels on POD 1 between groups, regardless of whether the Pringle maneuver or propofol was used for anesthesia (induction only or induction and maintenance, P > 0.05). The remaining outcome indicators were not statistically significant or could not be analyzed due to lack of sufficient data.

RIPC has some short-term liver protective effects on HIRIs during hepatectomies. However, there is still insufficient evidence to encourage its routine use to improve clinical outcomes.

The protocol of this study was registered with PROSPERO (CRD42022333383).