Effectiveness of remote ischemic preconditioning in patients undergoing transplant surgery: meta-analysis of randomized control studies.

Introduction: Remote ischemic preconditioning (RIPC) is a phenomenon in which the induction of shortened periods of ischemia prior to surgical procedures within a distant tissue preserves other tissues or organs of concern, such as the liver or kidney in transplant surgery, in the event of prolonged ischemic insults. The authors aim to evaluate the effectiveness of RIPC in patients undergoing transplant surgery, specifically kidney and liver transplants. Materials and methods: PubMed, Embase, and Scopus were searched until 19 December 2023 for trials evaluating RIPC in patients undergoing transplant surgery. A total of 9364 search articles were obtained, which yielded 10 eligible studies. Data analysis was done using RevMan 5.4 software. The risk of bias was done using Cochrane risk of bias tool. Results and discussion: For graft rejection, the study observed a relative risk of 0.99 (95% CI, 0.49-1.98, P=0.97) from 5 trials, indicating no significant effect of RIPC on graft survival in both kidney and liver transplants. The length of hospital stay also showed no significant decrease for those undergoing RIPC, with mean difference (MD) of -0.58 (95% CI, -1.38 to 0.23, P=0.16). GFR at 1-year post-kidney transplant did not significantly change in the RIPC group compared to controls, as evidenced by an MD of -0.13 (95% CI, -3.79 to 3.54, P=0.95). These results collectively suggest that RIPC may not be effective in reducing patient, or graft, outcomes.

Influence of Anesthetic Regimes on Extracellular Vesicles following Remote Ischemic Preconditioning in Coronary Artery Disease.

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.

Immediate Increase in the Root Mean Square of Successive Differences after Three Bouts of Remote Ischemic Preconditioning: A Randomized Controlled Trial.

(1) Background: Remote ischemic preconditioning (RIPC) is an intervention involving the application of brief episodes of ischemia and reperfusion to distant tissues to activate protective pathways in the heart. There is evidence suggesting the involvement of the autonomic nervous system (ANS) in RIPC-induced cardioprotection. This study aimed to investigate the immediate effects of RIPC on the ANS using a randomized controlled trial. (2) Methods: From March 2018 to November 2018, we conducted a single-blinded randomized controlled study involving 51 healthy volunteers (29 female, 24.9 [23.8, 26.4] years). Participants were placed in a supine position and heart rate variability was measured over 260 consecutive beats before they were randomized into either the intervention or the SHAM group. The intervention group underwent an RIPC protocol (3 cycles of 5 min of 200 mmHg ischemia followed by 5 min reperfusion) at the upper thigh. The SHAM group followed the same protocol but on the right upper arm, with just 40 mmHg of pressure inflation, resulting in no ischemic stimulus. Heart rate variability measures were reassessed afterward. (3) Results: The intervention group showed a significant increase in RMSSD, the possible marker of the parasympathetic nervous system (IG: 14.5 [5.4, 27.5] ms vs. CG: 7.0 [-4.3, 23.1 ms], p = 0.027), as well as a significant improvement in Alpha 1 levels compared to the control group (IG: -0.1 [-0.2, 0.1] vs. CG: 0.0 [-0.1, 0.2], p = 0.001). (4) Conclusions: Our results hint that RIPC increases the RMSSD and Alpha 1 parameters showing possible immediate parasympathetic modulations. RIPC could be favorable in promoting cardioprotective or/and cardiovascular effects by ameliorating ANS modulations.

Comparing the protective effects of local and remote ischemic preconditioning against ischemia-reperfusion injury in hepatectomy: a systematic review and network meta-analysis.

Background: Local ischemic preconditioning (LIPC) has been proven to be a protective strategy against hepatic ischemia-reperfusion injury (HIRI) during hepatectomy. Growing evidence suggests remote ischemic preconditioning (RIPC) has the potential to reduce liver injury in hepatectomy. Few studies have directly compared the protective effects of these two mechanical preconditioning strategies. Therefore, we performed a network meta-analysis to compare the efficacy of LIPC and RIPC for hepatic injury during liver resection. Methods: We searched Cochrane, PubMed, Embase, and China National Knowledge Infrastructure (CNKI) from the database inception to January 2023. We included studies directly comparing the effectiveness of LIPC and RIPC and those comparing LIPC or RIPC with no-preconditioning in liver resection. Postoperative liver function and surgical events were analyzed. Data were expressed as standardized mean differences (SMDs) or odds ratios (ORs) and analyzed using network meta-analysis with random effects model. Results: Following the screening of 268 citations, we identified 26 eligible randomized clinical trials (RCTs) involving 1,476 participants (LIPC arm: 789, RIPC arm: 859, no-preconditioning arm: 1,072). LIPC and RIPC were superior to no-preconditioning in reducing postoperative serum transaminase levels [aspartate aminotransferase (AST): SMD RIPC versus no-preconditioning: -2.05, 95% confidence interval (CI): -3.39, -0.71; SMD LIPC versus no-preconditioning: -1.10, 95% CI: -2.07, -0.12; alanine aminotransferase (ALT): SMD RIPC versus no-preconditioning: -2.24, 95% CI: -4.15, -0.32; SMD LIPC versus no-preconditioning: -1.32, 95% CI: -2.63, -0.01]. No significant difference was observed between RIPC and LIPC in postoperative liver function and surgical outcomes (AST: SMD RIPC versus LIPC: -0.95, 95% CI: -2.52, 0.62; ALT: SMD RIPC versus LIPC: -0.91, 95% CI: -3.11, 1.28). In addition, the subgroup analysis revealed the potential benefits of RIPC in improving liver function, especially in patients who diagnosed with cirrhosis or underwent major resection. Conclusions: RIPC and LIPC could serve as effective strategies in relieving HIRI during hepatectomy. No significant differences were observed between LIPC and RIPC, however, RIPC may be an easily applicable strategy to relieve liver injury in hepatectomy.

Remote ischaemic preconditioning for transcatheter aortic valve replacement: a protocol for a systematic review with meta-analysis and trial sequential analysis.

INTRODUCTION: 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. METHODS AND ANALYSIS: 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. ETHICS AND DISSEMINATION: Ethical approval was not required for this systematic review protocol. The results will be disseminated through peer-reviewed publications. PROSPERO REGISTRATION NUMBER: CRD42023462926.

Mycobacterial FtsEX-RipC interaction is required for normal growth and cell morphology in rifampicin and low ionic strength conditions.

Tuberculosis, a lung disease caused by Mycobacterium tuberculosis (Mtb), remains a major global health problem ranking as the second leading cause of death from a single infectious agent. One of the major factors contributing toward Mtb's success as a pathogen is its unique cell wall and its ability to counteract various arms of the host's immune response. A recent genome-scale study profiled a list of candidate genes that are predicted to be essential for Mtb survival of host-mediated responses. One candidate was FtsEX, a protein complex composed of an ATP-binding domain, FtsE, and a transmembrane domain, FtsX. FtsEX functions through interaction with a periplasmic hydrolase, RipC. Homologs of FtsEX exist in other bacteria and have been linked with playing a key role in regulating peptidoglycan hydrolysis during cell elongation and division. Here, we report on Mycobacterium smegmatis, FtsE, FtsX, and RipC and their protective roles in stressful conditions. We demonstrate that the individual genes of FtsEX complex and RipC are not essential for survival in normal growth conditions but conditionally essential in low-salt media and antibiotic-treated media. Growth defects in these conditions were characterized by short and bulgy cells as well as elongated filamentous cells. Our results suggest that FtsE, FtsX, and RipC are required for both normal cell elongation and division and ultimately for survival in stressful conditions. IMPORTANCE: Mycobacterial cell growth and division are coordinated with regulated peptidoglycan hydrolysis. Understanding cell wall gene complexes that govern normal cell division and elongation will aid in the development of tools to disarm the ability of mycobacteria to survive immune-like and antibiotic stresses. We combined genetic analyses and scanning electron microscopy to analyze morphological changes of mycobacterial FtsEX and RipC mutants in stressful conditions. We demonstrate that FtsE, FtsX, FtsEX, and RipC are conditionally required for the survival of Mycobacterium smegmatis during rifampicin treatment and in low-salt conditions. Growth defects in these conditions were characterized by short and bulgy cells as well as elongated filamentous cells. We also show that the FtsEX-RipC interaction is essential for the survival of M. smegmatis in rifampicin. Our results suggest that FtsE, FtsX, and RipC are required for normal cell wall regulation and ultimately for survival in stressful conditions.

Remote ischemic preconditioning protects against spinal cord ischemia-reperfusion injury in mice by activating NMDAR/AMPK/PGC-1α/SIRT3 signaling.

BACKGROUND: To study the protective effects of delayed remote ischemic preconditioning (RIPC) against spinal cord ischemia-reperfusion injury (SCIRI) in mice and determine whether SIRT3 is involved in this protection and portrayed its upstream regulatory mechanisms. METHODS: In vivo, WT or SIRT3 global knockout (KO) mice were exposed to right upper and lower limbs RIPC or sham ischemia. After 24 h, the abdominal aorta was clamped for 20 min, then re-perfused for 3 days. The motor function of mice, number of Nissl bodies, apoptotic rate of neurons, and related indexes of oxidative stress in the spinal cord were measured to evaluate for neuroprotective effects. The expression and correlation of SIRT3 and NMDAR were detected by WB and immunofluorescence. In vitro, primary neurons were exacted and OGD/R was performed to simulate SCIRI in vivo. Neuronal damage was assessed by observing neuron morphology, detecting LDH release ratio, and flow cytometry to analyze the apoptosis. MnSOD and CAT enzyme activities, GSH and ROS level were also measured to assess neuronal antioxidant capacity. NMDAR-AMPK-PGC-1α signaling was detected by WB to portray upstream regulatory mechanisms of RIPC regulating SIRT3. RESULTS: Compared to the SCIRI mice without RIPC, mice with RIPC displayed improved motor function recovery, a reduced neuronal loss, and enhanced antioxidant capacity. To the contrary, the KO mice did not exhibit any effect of RIPC-induced neuroprotection. Similar results were observed in vitro. Further analyses with spinal cord tissues or primary neurons detected enhanced MnSOD and CAT activities, as well as increased GSH level but decreased MDA or ROS production in the RIPC + I/R mice or NMDA + OGD/R neurons. However, these changes were completely inhibited by the absence of SIRT3. Additionally, NMDAR-AMPK-PGC-1α signaling was activated to upregulate SIRT3 levels, which is essential for RIPC-mediated neuroprotection. CONCLUSIONS: RIPC enhances spinal cord ischemia tolerance in a SIRT3-dependent manner, and its induced elevated SIRT3 levels are mediated by the NMDAR-AMPK-PGC-1α signaling pathway. Combined therapy targeting SIRT3 is a promising direction for treating SCIRI.

Effect of remote ischemic preconditioning on postoperative gastrointestinal function in patients undergoing laparoscopic colorectal cancer resection.

PURPOSE: Patients undergoing laparoscopic colorectal cancer resection have a high incidence of postoperative gastrointestinal dysfunction (POGD). Remote ischemic preconditioning (RIPC) is an organ protection measure. The study investigated the effect of RIPC on postoperative gastrointestinal function. METHODS: In this single-center, prospective, double-blinded, randomized, parallel-controlled trial, 100 patients undergoing elective laparoscopic colorectal cancer resection were randomly assigned in a 1:1 ratio to receive RIPC or sham RIPC (control). Three cycles of 5-min ischemia/5-min reperfusion induced by a blood pressure cuff placed on the right upper arm served as RIPC stimulus. Patients were followed up continuously for 7 days after surgery. The I-FEED score was used to evaluate the patient's gastrointestinal function after the surgery. The primary outcome of the study was the I-FEED score on POD3. Secondary outcomes include the daily I-FEED scores, the highest I-FEED score, the incidence of POGD, the changes in I-FABP and the inflammatory markers (IL-6 and TNF-α), and the time to first postoperative flatus. RESULTS: A total of 100 patients were enrolled in the study, of which 13 patients were excluded. Finally, 87 patients were included in the analysis, 44 patients in the RIPC group and 43 patients in the sham-RIPC group. Patients assigned to the RIPC group had a lower I-FEED score on POD3 compared with the sham-RIPC group (mean difference 0.86; 95% CI: 0.06 to 1.65; P = 0.035). And patients in the RIPC group were also associated with a lower I-FEED score on POD4 vs the sham-RIPC group (mean difference 0.81; 95% CI: 0.03 to 1.60; P = 0.043). Compared with the sham-RIPC group, the incidence of POGD within 7 days after surgery was lower in the RIPC group (P = 0.040). At T1, T2, and T3 time points, inflammatory factors and I-FABP were considerably less in the RIPC group compared to the sham-RIPC group. The time to the first flatus and the first feces was similar in both groups. CONCLUSION: RIPC reduced I-FEED scores, decreased the incidence of postoperative gastrointestinal dysfunction, and lowered concentrations of I-FABP and inflammatory factors.

Remote Ischemic Pre-Conditioning (RIPC).

Ischemic pre-conditioning has been shown to protect hearts against ischemia/reperfusion (I/R)-induced cardiac injury. However, it is not feasible in clinic. Many researchers have tried to introduce brief I/R in skeletal muscle to mimic cardiac ischemic pre-conditioning, called remote ischemia pre-conditioning (RIPC). Studies from our group and other groups have shown that RIPC induces the release of cytokines from skeletal muscle (myokines) for tissue protection. Myokines play a central role in repair, inflammatory, and immune responses after injury. Thus, the detailed protocol for RIPC might be useful for researchers to study mechanisms underlying RIPC-mediated tissue protection and crosstalk. Here, we describe a detailed RIPC protocol and show MG53 secretion after RIPC into the blood.

Ischemic preconditioning upregulates Mitofusin2 and preserves muscle strength in tourniquet-induced ischemia/reperfusion.

Background: Tourniquet-induced ischemia and reperfusion (I/R) has been related to postoperative muscle atrophy through mechanisms involving protein synthesis/breakdown, cellular metabolism, mitochondrial dysfunction, and apoptosis. Ischemic preconditioning (IPC) could protect skeletal muscle against I/R injury. This study aims to determine the underlying mechanisms of IPC and its effect on muscle strength after total knee arthroplasty (TKA). Methods: Twenty-four TKA patients were randomized to receive either sham IPC or IPC (3 cycles of 5-min ischemia followed by 5-min reperfusion). Vastus medialis muscle biopsies were collected at 30 â€‹min after tourniquet (TQ) inflation and the onset of reperfusion. Western blot analysis was performed in muscle protein for 4-HNE, SOD2, TNF-ɑ, IL-6, p-Drp1ser616, Drp1, Mfn1, Mfn2, Opa1, PGC-1ɑ, ETC complex I-V, cytochrome c, cleaved caspase-3, and caspase-3. Clinical outcomes including isokinetic muscle strength and quality of life were evaluated pre- and postoperatively. Results: IPC significantly increased Mfn2 (2.0 â€‹± â€‹0.2 vs 1.2 â€‹± â€‹0.1, p â€‹= â€‹0.001) and Opa1 (2.9 â€‹± â€‹0.3 vs 1.9 â€‹± â€‹0.2, p â€‹= â€‹0.005) proteins expression at the onset of reperfusion, compared to the ischemic phase. There were no differences in 4-HNE, SOD2, TNF-ɑ, IL-6, p-Drp1ser616/Drp1, Mfn1, PGC-1ɑ, ETC complex I-V, cytochrome c, and cleaved caspase-3/caspase-3 expression between the ischemic and reperfusion periods, or between the groups. Clinically, postoperative peak torque for knee extension significantly reduced in the sham IPC group (-16.6 [-29.5, -3.6] N.m, p â€‹= â€‹0.020), while that in the IPC group was preserved (-4.7 [-25.3, 16.0] N.m, p â€‹= â€‹0.617). Conclusion: In TKA with TQ application, IPC preserved postoperative quadriceps strength and prevented TQ-induced I/R injury partly by enhancing mitochondrial fusion proteins in the skeletal muscle. The translational potential of this article: Mitochondrial fusion is a potential underlying mechanism of IPC in preventing skeletal muscle I/R injury. IPC applied before TQ-induced I/R preserved postoperative quadriceps muscle strength after TKA.

Effects of remote ischemic preconditioning (RIPC) and chronic remote ischemic preconditioning (cRIPC) on levels of plasma cytokines, cell surface characteristics of monocytes and in-vitro angiogenesis: a pilot study.

Remote ischemic preconditioning (RIPC) protects the heart against myocardial ischemia/reperfusion (I/R) injury and recent work also suggested chronic remote ischemic conditioning (cRIPC) for cardiovascular protection. Based on current knowledge that systemic immunomodulatory effects of RIPC and the anti-inflammatory capacity of monocytes might be involved in cardiovascular protection, the aim of our study was to evaluate whether RIPC/cRIPC blood plasma is able to induce in-vitro angiogenesis, identify responsible factors and evaluate the effects of RIPC/cRIPC on cell surface characteristics of circulating monocytes. Eleven healthy volunteers were subjected to RIPC/cRIPC using a blood pressure cuff inflated to > 200 mmHg for 3 × 5 min on the upper arm. Plasma and peripheral blood monocytes were isolated before RIPC (Control), after 1 × RIPC (RIPC) and at the end of 1 week of daily RIPC (cRIPC) treatment. Plasma concentrations of potentially pro-angiogenic humoral factors (CXCL5, Growth hormone, IGFBP3, IL-1α, IL-6, Angiopoietin 2, VEGF, PECAM-1, sTie-2, IL-8, MCSF) were measured using custom made multiplex ELISA systems. Tube formation assays for evaluation of in-vitro angiogenesis were performed with donor plasma, monocyte conditioned culture media as well as IL-1α, CXCL5 and Growth hormone. The presence of CD14, CD16, Tie-2 and CCR2 was analyzed on monocytes by flow cytometry. Employing in-vitro tube formation assays, several parameters of angiogenesis were significantly increased by cRIPC plasma (number of nodes, P < 0.05; number of master junctions, P < 0.05; number of segments, P < 0.05) but were not influenced by culture medium from RIPC/cRIPC treated monocytes. While RIPC/cRIPC treatment did not lead to significant changes of the median plasma concentrations of any of the selected potentially pro-angiogenic humoral factors, in-depth analysis of the individual subjects revealed differences in plasma levels of IL-1α, CXCL5 and Growth hormone after RIPC/cRIPC treatment in some of the volunteers. Nevertheless, the positive effects of RIPC/cRIPC plasma on in-vitro angiogenesis could not be mimicked by the addition of the respective humoral factors alone or in combination. While monocyte conditioned culture media did not affect in-vitro tube formation, flow cytometry analyses of circulating monocytes revealed a significant increase in the number of Tie-2 positive and a decrease of CCR2 positive monocytes after RIPC/cRIPC (Tie-2: cRIPC, P < 0.05; CCR2: RIPC P < 0.01). Cardiovascular protection may be mediated by RIPC and cRIPC via a regulation of plasma cytokines as well as changes in cell surface characteristics of monocytes (e.g. Tie-2). Our results suggest that a combination of humoral and cellular factors could be responsible for the RIPC/cRIPC mediated effects and that interindividual variations seem to play a considerable part in the RIPC/cRIPC associated mechanisms.

Pharmacologic Inhibition of Pain Response to Incomplete Vascular Occlusion Blunts Cardiovascular Preconditioning Response.

Complete vascular occlusion to distant tissue prior to an ischemic cardiac event can provide significant cardioprotection via remote ischemic preconditioning (RIPC). Despite understanding its mechanistic basis, its translation to clinical practice has been unsuccessful, likely secondary to the inherent impossibility of predicting (and therefore preconditioning) an ischemic event, as well as the discomfort that is associated with traditional, fully occlusive RIPC stimuli. Our laboratory has previously shown that non-occlusive banding (NOB) via wrapping of a leather band (similar to a traditional Jewish ritual) can elicit an RIPC response in healthy human subjects. This study sought to further the pain-mediated aspect of this observation in a mouse model of NOB with healthy mice that were exposed to treatment with and without lidocaine to inhibit pain sensation prior to ischemia/reperfusion injury. We demonstrated that NOB downregulates key inflammatory markers resulting in a preconditioning response that is partially mediated via pain sensation.

Agony of choice: How anesthetics affect the composition and function of extracellular vesicles.

The choice of the anesthetic regime is suggested to affect clinical outcomes following major surgery. Propofol was shown to exert beneficial effects on different cancer outcomes, while volatile anesthetics may be favorable in cardiac surgery. Recently, extracellular vesicles (EVs) were discovered as essential signal mediators in physiological and pathophysiological processes including carcinogenesis and metastasis. Furthermore, depending on their cell source, EVs fulfill therapeutic functions. In addition to extracorporally produced EVs, appropriate systemic intervention such as remote ischemic preconditioning (RIPC) is considered to promote endogenous release of therapeutically active EVs to mediate cardioprotective effects. EVs are assembled in cell-type specific manners and the composition of EVs is not only affected by the disease, but also by the applied anesthetic of anesthetized patients. Here, we compare known impacts of anesthetic agents on outcomes in cancer surgery and cardioprotection and link these effects to the composition and therapeutic potential of EVs.

Microarray analysis reveals a potential role of lncRNA expression in remote ischemic preconditioning in myocardial ischemia-reperfusion injury.

The challenge to avoid or reduce cardiopulmonary bypass-related injuries in cardiovascular surgery remains a major issue. Remote ischemic preconditioning (RIPC) remains a promising strategy whose clinical applications appear to be significantly more realistic and extensive as compared with other conservative or surgical strategies. However, considering its underlying mechanism(s) are still unclear, novel ideas and methods must be explored to enhance its potential in clinical applications. Long noncoding RNAs (LncRNAs) are a kind of RNAs that have been implicated in the occurrence and development of cardiovascular diseases. The differently expressed LncRNAs and their biological effects during RIPC have not been explored previously. In this study, mouse and human LncRNA microarrays were used to investigate the expression signatures of LncRNAs and mRNAs in the myocardial tissue after RIPC. Therafter, homology comparisons were used to screen homologous genes from differentially expressed LncRNAs. Competing endogenous RNA (ceRNA) mechanism analysis were employed to find the matching relationship among homologous LncRNA, mRNA and microRNA. 554 differentially expressed mouse LncRNAs (281 up-regulated/273 down-regulated) and 1392 differentially expresssed human LncRNAs (635 up-regulated/757 down-regulated) were selected for further analysis. Quantitative real-time polymerase chain reaction (qRT-PCR) was used to quantify these LncRNAs, homology comparison and ceRNA mechanism analysis provided a pair of homologous LncRNAs (ENST00000574727 & ENSMUST00000123752) for further research investigation. Overall, in this study, a number of differentially expressed LncRNAs were identified which may play an important role the regulation of both inflammation and cell proliferation. The findings may thus unveil the mystery of RIPC and discover a novel protective mechanism for the mitigation of cardiovascular ischemia-reperfusion disease.

Case Report of a Remote Ischemic Preconditioning Intervention during Aerobic Exercise in a 44-year-old Amateur Triathlete Male with a History of Acute Myocardial Infarction.

Over the years, exercise has become increasingly important in patients with acute myocardial infarction (AMI). However, AMI patients need to be closely monitored since they maintain cardiovascular disease risks, such as ventricular repolarization abnormalities in electrocardiograms during exercise and rest. A recent study showed the need to focus on the different potential mechanisms and the applicability of remote ischemic preconditioning (RIPC) for cardiac patients engaged in exercise rehabilitation. This is the first case report that explores the effectiveness of an RIPC intervention in a 44-year-old amateur triathlete male with a history of AMI during a moderate (75% of gas exchange threshold) and high (115% of gas exchange threshold) intensity steady-state cycling aerobic exercise. Prior to aerobic exercise, the participant was allocated to either RIPC intervention or CTL (control) with four cycles of five minutes of ischemia followed by five minutes of reperfusion. ECG was continuously recorded during the protocol. These findings showed that RIPC improved participant's oxygen uptake response and shortened his ventricular repolarization during steady-state aerobic exercises. By measuring the physiological and electrophysical parameters, this case report adds new evidence for the benefits of RIPC. This study also demonstrates the safety of the intervention for cardiac patients in addition to showing that the intervention is not dangerous or harmful. This provides a new approach to cardiac rehabilitation programs. Future studies with cardiac patients are needed to provide a safe, standardized exercise intervention in cardiac rehabilitation.

Preconditioning strategies to prevent acute kidney injury.

Acute kidney injury is a common clinical disorder resulting in significantly increased morbidity and mortality. However, despite extensive research, strategies for prevention or treatment are still lacking in routine clinical practice. Already decades ago, several preconditioning strategies (e. g. ischemic/hypoxic preconditioning and calorie restriction) have been published and their extraordinary effectiveness - especially in rodents - has raised the hope for powerful clinical tools to prevent acute kidney injury. However, the underlying mechanisms are still not completely understood and translation to the clinics has not been successful yet. In this review, the most attractive strategies and the current mechanistic concepts are introduced and discussed. Furthermore, we present clinical trials evaluating the feasibility of preconditioning in the clinical setting.

Neuro-autonomic changes induced by remote ischemic preconditioning (RIPC) in healthy young adults: Implications for stress.

The mechanisms underlying the protective effects of remote ischemic preconditioning (RIPC) are not presently clear. Recent studies in experimental models suggest the involvement of the autonomic nervous system (ANS) in cardioprotection. The aim of this study was to investigate the changes in ANS in healthy young volunteers divided into RIPC (n = 22) or SHAM (n = 18) groups. RIPC was induced by 1 cycle of 4 min inflation/5 min deflation followed by 2 cycles of 5 min inflation/5 min deflation of a cuff placed on the upper left limb. The study included analysis of heart rate (HR), blood pressure (BP), heart rate variability (HRV), measurements of microcirculation and porphyrin fluorescence in the limb before and after the RIPC. RIPC caused reactive hyperemia in the limb and reduced blood porphyrin level. A mental load (serial sevens test) and mild motor stress (hyperventilation) were performed on all subjects before and after RIPC or corresponding rest in the SHAM group. Reduction of HR occurred during the experiments in both RIPC and SHAM groups reflecting RIPC-independent adaptation of the subjects to the experimental procedure. However, in contrast to the SHAM group, RIPC altered several of the spectral indices of HRV during the serial sevens test and hyperventilation. This was expressed predominantly as an increase in power of the very low-frequency band of the spectrum, increased values of detrended fluctuation analysis and weakening of correlation between the HRV parameters and HR. In conclusion, RIPC induces changes in the activity of ANS that are linked to stress resistance.

The effect of remote ischemic pre-conditioning on pulmonary vascular pressure and gas exchange in healthy humans during hypoxia.

This study investigated whether rIPC alters the typical changes in pulmonary arterial pressure, pulmonary gas exchange associated with exercise in hypoxia. METHODS: 16 healthy adults were randomized to either rIPC treatment (n = 8) or control (n = 8). Afterward, subjects performed supine ergometry at constant load (30 W, 40˜50 rpm) for 25 min during hypoxia (12.5% O2). Following a 90˜120 min rest, either rIPC or sham treatment was performed, which was then followed by post-assessment exercise. Throughout exercise, pulmonary arterial systolic pressure (PASP) and mean pulmonary arterial pressure (mPAP) were measured via echocardiography, while pulmonary gas exchange was being assessed. RESULTS: The rICP group demonstrated improved PASP and mPAP (p < 0.05), whereas the control group did not. Additionally, breathing efficiency (VE/VCO2) and end-tidal CO2 (PETCO2) were improved in rIPC group (p < 0.05), but not in controls. CONCLUSION: These data suggest that rIPC contributes to reduced pulmonary arterial pressure, and improved pulmonary gas exchange during hypoxic exercise. However, follow-up studies are needed to apply these findings to patient care settings.

Effect of Remote Ischemic Preconditioning on Intestinal Ischemia-Reperfusion Injury in Adults Undergoing On-Pump CABG Surgery: A Randomized Controlled Pilot Trial.

OBJECTIVE: Cardiopulmonary bypass (CPB) surgery commonly threatens the heart and remote organs with ischemia-reperfusion injury. Transient episodes of ischemia to nonvital tissue, known as remote ischemic preconditioning (RIPC), is thought to help local and remote vital organs to withstand subsequent ischemic insults. DESIGN: Prospective, randomized, double-blinded control trial. SETTING: Tertiary referral academic teaching hospital. PARTICIPANTS: Thirty patients undergoing elective CPB surgery INTERVENTION: RIPC was achieved via three 5-minute cycles of upper limb ischemia using a blood pressure cuff or control (sham cuff). MEASUREMENTS AND MAIN RESULTS: Primary outcome was the occurrence of intestinal injury, as measured by an increase in intestinal fatty acid binding protein (I-FABP). Secondary outcomes included incidence of gastrointestinal complications and duration of intensive care unit (ICU) stay. RIPC did not affect serum IFABP levels at the end of surgery and on the first postoperative day (p = 0.697 and p = 0.461, respectively). For all patients, mean I-FABP levels significantly increased at the end of surgery and decreased to under baseline levels on the first postoperative day (from a mean [± standard deviation] baseline value of 764 ± 492 pg/mL to 2,002 ± 974 pg/mL and decreased to 568 ± 319 pg/mL, p < 0.001). All patients remained clinically absent of gastrointestinal complications until hospital discharge. Duration of ICU stay was not correlated with I-FABP levels at the end of surgery. Neither duration of CPB nor duration of aortic clamping significantly correlated with postoperative I-FABP levels. CONCLUSIONS: These findings suggest that RIPC does not affect intestinal injury in patients undergoing CPB surgery. In patients undergoing cardiac surgery, intestinal injury appears to be moderate and transient without any clinical relevant complication.