Remote Ischemic Preconditioning Research Articles

Effect of distal ischemic preconditioning on cardiovascular events in adult patients with hip fracture one year after operation

To investigate the effect of remote ischemic preconditioning (RIPC) on major adverse cardiovascular events (MACE) in elderly patients with hip fracture 1 year after operation. Total of 314 elderly patients with hip fracture of gradeⅡand Ⅲ for American Society of Anesthesiologists (ASA) were treated by surgical operation from April 2015 to May 2020 including 116 males and 198 females, the age ranged from 60 to 76 years old. The subjects were divided into intervention group and control group according to whether received RIPC. Among them, 157 cases in intervention group included 56 males and 101 females with an average age of (68.12±7.13) years old and 157 cases in control group included 60 males and 97 females with an average age of (68.24±7.05) years old. Both groups were given routine anesthesia. The intervention group was treated with RIPC on the basis of routine anesthesia. The MACE events 1 year after operation in two groups were compared and analyzed. The OR values of RIPC for myocardial infarction, heart failure, stroke, nonfatal cardiac arrest, coronary revascularization, severe arrhythmia, peripheral artery thrombosis, readmission of cardiovascular disease, and all-cause death in patients with hip fracture one year after operation were 1.269, 1.304, 0.977, 1.089, 1.315, 1.335, 0.896, 0.774, 1.191, respectively, but there was no significant difference (P>0.05). RIPC did not significantly affect and change the occurrence of major cardiovascular adverse events within 1 year after hip fracture surgery. The long term impact of RIPC on clinical cardiovascular outcomes in non cardiac surgery needs to be confirmed in appropriate randomized clinical trials.

Does remote ischemic preconditioning affect the systemic inflammatory response by modulating presepsin levels?

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).

Potential effect of the non-neuronal cardiac cholinergic system on hepatic glucose and energy metabolism

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.

NGAL in the Development of Acute Kidney Injury in a Murine Model of Remote Ischaemic Preconditioning and Liver Ischaemia Reperfusion.

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.

Activation of PACAP+ vagal motoneurons following remote ischemic pre-conditioning

The Dorsal Motor Nucleus of the Vagus nerve (DMV) provides parasympathetic innervation of the intrinsic cardiac nervous system (ICN), and it has been shown that DMV activity is required for the cardioprotection induced by remote ischemic pre-conditioning (RIPC) against the pathological effects of myocardial infarction. However, the mechanism behind the DMV’s cardioprotective effects is not well understood. Previous literature has shown that the DMV and the other vagal motor nuclei, the nucleus ambiguus (NA), innervate distinct cells within the ICN. DMV neurons project to many other organs in addition to the heart. The cardioprotective neuropeptide Pituitary Adenylate Cyclase-Activating Polypeptide (PACAP) has been found to be expressed in the fibers innervating the ICN, where it is co-localized with the parasympathetic marker, ChAT. While we have found PACAP to be expressed in cardiac-projecting DMV neurons, it is unknown whether these neurons are preferentially activated in response to RIPC. To assess the activity of these neurons following RIPC, we performed immunofluorescence staining of brainstem tissue containing DMV neurons for both PACAP, and c-FOS, a neuronal activity-dependent marker. We hypothesized that PACAP+ DMV neurons would have increased activity following RIPC, and therefore increased c-FOS intensity and increased co-localization with PACAP compared to sham control. Our results suggest that PACAP+ neurons in the DMV show increased activity following RIPC compared to sham, as defined by increased c-FOS fluorescence intensity and co-localization with PACAP. These results suggest that PACAP+ neurons are activated during the cardioprotective response to remote ischemic pre-conditioning. Funding was provided by the R01 HL161696 grant through National Heart, Lung, and Blood institute and the National Institutes of Health Common Fund SPARC Program Grant OT2OD030534. This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

Neuromodulatory co-expression in cardiac vagal motor neurons of the Dorsal Motor Nucleus of the Vagus

Dorsal Motor Nucleus of the Vagus (DMV) activity is required for cardioprotection from physiological interventions such as remote ischemic pre-conditioning (RIPC). Herein, we discover the transcriptomic phenotypes of cardioprotective DMV neurons, by combining high throughput transcriptomics, 3D anatomical mapping, and neural tracing in 12 week old male and female Sprague Dawley rats. We find that DMV neurons appear to participate in neuromodulatory co-expression, including those that project to the heart. To distinguish potential mechanisms of cardioprotection, we highlight the functional significance of several transcripts in cardiac-projecting DMV neurons and we begin to validate these findings at the protein level. In our sc-RNAseq data we find that Snca (α-synuclein), the cardioprotective neuromodulator Adcyap1 (PACAP), and the neuropeptide Cartpt (CART) are enriched in cardiac-projecting DMV neurons. To contrast our molecular findings in cardioprotective DMV neurons, we have also collected single neuron HT-RTqPCR data from the other source of cardiac vagal motoneurons, the Nucleus Ambiguus (NA). Catecholaminergic transcripts, including Slc18a2 (VMAT2), Ddc, and Th, are enriched in cardiac-projecting DMV neurons relative to those of the NA. These findings implicate catecholaminergic processes, synuclein, and these secreted neuropeptides in cardioprotection. At the protein level, we found PACAP, CART, SNCA and TH enrichment, as well as co-localization of PACAP, TH, and ChAT, in cardiac-projecting DMV neurons. There is consistency between our findings from three spatial transcriptomics techniques and across sexes. Based on these results, we propose a 3D anatomical and molecular map of cardiac vagal motoneurons. This work fills a major gap in the understanding of the cellular mechanisms by which parasympathetic drive provides cardioprotection and provides a future translational path to emulating the positive vagal neuromodulatory effects on heart health. Funding was provided by the R01 HL161696 grant through National Heart, Lung, and Blood institute and the National Institutes of Health Common Fund SPARC Program Grant OT2OD030534. This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

Cardioprotective Effect of Remote Ischemic Preconditioning: From Bench to Bedside

Remote ischemic preconditioning (rIPC) refers to a cardioprotective phenomenon in which short episodes of ischemia, followed by reperfusion, in one organ or tissue might provide future protection against ischemia/reperfusion damage in other organs, namely the heart. The process involves the activation of humoral, neural, or systemic communication channels, which in turn induce various intracellular signals inside the heart. The primary objective of this review is to provide a concise overview of the potential processes implicated in rIPC cardioprotection, as well as to elucidate current clinical studies aimed at establishing the effectiveness of these techniques in safeguarding the heart from detrimental ischemia/reperfusion injury. In this context, many variables contribute to the attenuation of subcellular processes of rIPC in patients, including advanced age, presence of comorbidities, medication use, and variations in anaesthetic protocols. These factors may account for the observed variability in outcomes across different clinical studies. Additional research, meticulously planned, is needed in order to enhance our comprehension of the pathways and mechanisms associated with both early and late rIPC. A comprehensive understanding of the various routes is crucial in facilitating the translation of medical advancements to the benefit of patients. Keyword: Cardioprotection, Ischemic Preconditioning, Remote Ischemic Preconditioning.

Effect of remote ischemic preconditioning intervention on serum levels of microRNA-582–5p/HMGB1 in patients with acute cerebral infarction

ObjectiveAcute cerebral infarction (ACI) contributes to disability and death accross the globe. Remote ischemic preconditioning (RIPC) reduces cerebral infarct size and improves neurological function in ACI. We conducted this research to reveal the effects of RIPC intervention on serum levels of microRNA-582–5p (miR-582–5p)/high mobility group box-1 protein (HMGB1), inflammation, oxidative stress and neurological function in patients with ACI. MethodsIn this study, 158 patients with ACI were prospectively selected and randomized into the control (administered symptomatic medication alone) and the RIPC (underwent RIPC of the limbs based on medication) groups, with their clinical baseline data documented. Serum levels of miR-582–5p, and HMGB1 and inflammatory factors [tumor necrosis factor alpha (TNF-α)/interleukin-1beta (IL-1β)/IL-10] were assessed by RT-qPCR/ELISA, followed by comparisons of oxidative stress indices [glutathione-peroxidase (GSH-Px)/catalase (CAT)/superoxide dismutase (SOD)] using a fully automatic biochemical analyzer. Correlations between serum miR-582–5p with serum HMGB1, and between their levels with TNF-α/IL-1β/IL-10 were analyzed by Pearson analysis. The NIHSS score/Barthel Index scale were used to assess neurological function/daily living ability. Intervention safety for ACI patients was evaluated. ResultsRIPC intervention increased serum miR-582–5p levels and decreased serum HMGB1 levels in ACI patients. RIPC intervention significantly reduced inflammation (diminished TNF-α/IL-1β levels, increased IL-10 level) and oxidative stress (elevated GSH-Px/CAT/SOD levels) in ACI patients. Serum miR-582–5p was negatively correlated with TNF-α and IL-1β levels, while positively correlated with IL-10 level, while HMGB1 was positively correlated with TNF-α and IL-1β levels, while negatively correlated with IL-10 level. miR-582–5p was negatively correlated with HMGB1. RIPC intervention improved neurological function (reduced NIHSS, increased Barthel scores) in ACI patients to some extent. RIPC had certain effectiveness and safety in the treatment of ACI. ConclusionAfter RIPC intervention, serum miR-582–5p levels were increased, HMGB1 levels were decreased, and inflammation and oxidative stress were reduced in ACI patients, which mitigated neurological deficits, improved patients’ ability to perform life activities, and exerted neuroprotective effects to some extent.

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

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. 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. 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. 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

IntroductionTranscatheter 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...

Stroke prevention strategies for cardiac surgery: a systematic review and meta-analysis of randomized controlled trials.

Stroke is a much-feared complication of cardiac surgery, but existing literature on preventive strategies is fragmented. Hence, a systematic review and meta-analysis of stroke prevention strategies for cardiac surgery was conducted. An electronic literature search was conducted to retrieve randomized controlled trials (RCTs) investigating perioperative interventions for cardiac surgery, with stroke as an outcome. Random-effects meta-analyses were conducted to generate risk ratios (RRs), 95% confidence intervals (95% CI), and forest plots. Descriptive analysis and synthesis of literature was conducted for interventions not amenable to meta-analysis, focusing on risks of stroke, myocardial infarction and study-defined major adverse cardiovascular events (MACE). Fifty-six RCTs (61 894 patients) were retrieved. Many included trials were underpowered to detect differences in stroke risk. Among pharmacological therapies, only preoperative amiodarone was shown to reduce stroke risk in one trial. Concomitant left atrial appendage closure (LAAC) significantly reduced stroke risk (RR = 0.55, 95% CI = 0.36-0.84, P = 0.006) in patients with preoperative atrial fibrillation, and there was no difference in on-pump versus off-pump coronary artery bypass grafting (CABG) (RR = 0.94, 95% CI = 0.64-1.37, P = 0.735). Much controversy exists in literature on the timing of carotid endarterectomy relative to CABG in patients with severe carotid stenosis. The use of preoperative remote ischemic preconditioning was not found to reduce rates of stroke or MACE. This review presents a comprehensive synthesis of existing interventions for stroke prevention in cardiac surgery, and identifies gaps in research which may benefit from future, large-scale RCTs. LAAC should be considered to reduce stroke incidence in patients with preoperative atrial fibrillation.

Protective Effect of Dexmedetomidine Combined with Remote Ischemic Preconditioning on Hepatic Ischemia-reperfusion Injury: A Report on 16 Cases

Protective Effect of Dexmedetomidine Combined with Remote Ischemic Preconditioning on Hepatic Ischemia-reperfusion Injury: A Report on 16 Cases

Bilateral remote ischemic conditioning in children: A two-center, double-blind, randomized controlled trial in young children undergoing cardiac surgery

ObjectiveThe study objective was to determine whether adequately delivered bilateral remote ischemic preconditioning is cardioprotective in young children undergoing surgery for 2 common congenital heart defects with or without cyanosis. MethodsWe performed a prospective, double-blind, randomized controlled trial at 2 centers in the United Kingdom. Children aged 3 to 36 months undergoing tetralogy of Fallot repair or ventricular septal defect closure were randomized 1:1 to receive bilateral preconditioning or sham intervention. Participants were followed up until hospital discharge or 30 days. The primary outcome was area under the curve for high-sensitivity troponin-T in the first 24 hours after surgery, analyzed by intention-to-treat. Right atrial biopsies were obtained in selected participants. ResultsBetween October 2016 and December 2020, 120 eligible children were randomized to receive bilateral preconditioning (n = 60) or sham intervention (n = 60). The primary outcome, area under the curve for high-sensitivity troponin-T, was higher in the preconditioning group (mean: 70.0 ± 50.9 μg/L/h, n = 56) than in controls (mean: 55.6 ± 30.1 μg/L/h, n = 58) (mean difference, 13.2 μg/L/h; 95% CI, 0.5-25.8; P = .04). Subgroup analyses did not show a differential treatment effect by oxygen saturations (pinteraction = .25), but there was evidence of a differential effect by underlying defect (pinteraction = .04). Secondary outcomes and myocardial metabolism, quantified in atrial biopsies, were not different between randomized groups. ConclusionsBilateral remote ischemic preconditioning does not attenuate myocardial injury in children undergoing surgical repair for congenital heart defects, and there was evidence of potential harm in unstented tetralogy of Fallot. The routine use of remote ischemic preconditioning cannot be recommended for myocardial protection during pediatric cardiac surgery.

The effect of short-term remote ischemic preconditioning on endothelial function of patients with chronic kidney disease: A randomized pilot study.

Patients with chronic kidney disease (CKD) are more susceptible to endothelial dysfunction and cardiovascular disease (CV). Remote ischemic preconditioning (rIPC) has been proven efficient in improving endothelial function and lowering the risk of CV. However, the safety and effect of rIPC on endothelial function in patients with CKD have not been effectively assessed. 45 patients with CKD (average estimated glomerular filtration rate: 48.4 mL/min/1.73 m2 ) were randomly allocated to either 7-day daily upper-arm rIPC (4 × 5 min 200 mmHg, interspaced by 5-min reperfusion) or control (4 × 5 min 60 mmHg, interspaced by 5-min reperfusion). Vascular endothelial function was assessed by natural log-transformed reactive hyperemia index (LnRHI) before and after a 7-day intervention. Arterial elasticity was assessed by augmentation index (AI). The results showed that LnRHI could be improved by rIPC treatment (Pre = 0.57 ± 0.04 vs. Post = 0.67 ± 0.04, p = .001) with no changes relative to control (Pre = 0.68 ± 0.06 vs. Post = 0.64 ± 0.05, p = .470). Compared with the control group, the improvement of LnRHI was greater after rIPC treatment (rIPC vs. Control: 0.10 ± 0.03 vs. -0.04 ± 0.06, between-group mean difference, -0.15 [95% CI, -0.27 to -0.02], p = .027), while there was no significant difference in the change of AI@75 bpm (p = .312) between the two groups. RIPC is safe and well tolerated in patients with CKD. This pilot study suggests that rIPC seems to have the potential therapeutic effect to improve endothelial function. Of note, further larger trials are still warranted to confirm the efficacy of rIPC in improving endothelial function in CKD patients.

First Characterization of Tissue Oxygen Saturation Recovery Patterns in Pediatric Cardiac Surgery Patients Undergoing Remote Ischemic Preconditioning and the Association With Clinical Outcomes

This study aimed to delineate the recovery patterns of regional oxygen saturation (SrO2) in pediatric cardiac surgery patients subjected to remote ischemic preconditioning (RIPC), utilizing near-infrared spectroscopy (NIRS) for quantification. It also sought to establish the correlation between these perfusion patterns and postoperative clinical outcomes. A prospective longitudinal observational study. The study was conducted at Fundación Valle Del Lili, a high-complexity service provider institution in Fundación Valle Del Lili. Pediatric patients (younger than 18 years of age) scheduled for elective cardiac surgery requiring cardiopulmonary bypass between August 2022 and July 2023. RIPC was performed after anesthetic induction, involving cycles of ischemia and reperfusion on a lower limb. Monitoring included SrO2 using NIRS. The study identified 4 distinct patterns of SrO2 during RIPC. Findings demonstrated a significant association between the negative SrO2 pattern and increased postoperative adverse events, including extended hospital stays and higher mortality, while a positive pattern was associated with better outcomes. Specific patterns of SrO2 response to RIPC may serve as important indicators for risk stratification in congenital heart surgery. This study illustrated the potential of NIRS in detecting hypoxic states and predicting postoperative outcomes, emphasizing the need for standardized clinical interpretation of RIPC patterns.

The New Orientation of Postoperative Analgesia: Remote Ischemic Preconditioning.

Postoperative analgesia is currently a significant topic in anesthesiology. Currently, the predominant approach for achieving multimodal analgesia involves the utilization of pharmacotherapy and regional anesthesia procedures. The primary objectives of this approach are to mitigate postoperative pain, enhance patient satisfaction, and diminish overall opioid usage. Nevertheless, there is a scarcity of research on the use of remote ischemia preconditioning aimed at mitigating postoperative pain. Transient stoppage of blood flow to an organ has been found to elicit remote ischemia preconditioning (RIPC), which serves as a potent intrinsic mechanism for protecting numerous organs. In addition to its established role in protecting against reperfusion injury, RIPC has recently been identified as having potential benefits in the context of postoperative analgesia. In addition to traditional perioperative analgesia, RIPC provides perioperative analgesia and organ protection.

Association between Ranolazine, Ischemic Preconditioning, and Cardioprotection in Patients Undergoing Scheduled Percutaneous Coronary Intervention.

Background and Objectives: Remote ischemic preconditioning (RIPC) has demonstrated efficacy in protecting against myocardial ischemia-reperfusion injury when applied before percutaneous coronary revascularization. Ranolazine, an anti-ischemic drug, has been utilized to minimize ischemic events in chronic angina patients. However, there is a lack of trials exploring the combined effects of ranolazine pretreatment and RIPC in patients undergoing percutaneous coronary interventions (PCIs). Materials and Methods: The present study is a prospective study which enrolled 150 patients scheduled for nonemergent percutaneous coronary revascularization. Three groups were formed: a control group undergoing only PCIs, an RIPC group with RIPC applied to either upper limb before the PCI (preconditioning group), and a group with RIPC before the PCI along with prior ranolazine treatment for stable angina (ranolazine group). Statistical analyses, including ANOVAs and Kruskal-Wallis tests, were conducted, with the Bonferroni correction for type I errors. A repeated-measures ANOVA assessed the changes in serum enzyme levels (SGOT, LDH, CRP, CPK, CK-MB, troponin I) over the follow-up. Statistical significance was set at p < 0.05. Results: The ranolazine group showed (A) significantly lower troponin I level increases compared to the control group for up to 24 h, (B) significantly lower CPK levels after 4, 10, and 24 h compared to the preconditioning group (p = 0.020, p = 0.020, and p = 0.019, respectively) and significantly lower CPK levels compared to the control group after 10 h (p = 0.050), and (C) significantly lower CK-MB levels after 10 h compared to the control group (p = 0.050). Conclusions: This study suggests that combining RIPC before scheduled coronary procedures with ranolazine pretreatment may be linked to reduced ischemia induction, as evidenced by lower myocardial enzyme levels.

Inhibition of NOX2 or NLRP3 inflammasome prevents cardiac remote ischemic preconditioning.

Introduction: Short episodes of ischemia-reperfusion (IR) in the heart (classical ischemic preconditioning, IPC) or in a limb (remote ischemic preconditioning, RIPC) before a prolonged ischemic episode, reduce the size of the infarct. It is unknown whether IPC and RIPC share common mechanisms of protection. Animals KO for NOX2, a superoxide-producing enzyme, or KO for NLRP3, a protein component of inflammasome, are not protected by IPC. The aim of this study was to investigate if NOX2 or NLRP3 inflammasome are involved in the protection induced by RIPC. Methods: We preconditioned rats using 4 × 5min periods of IR in the limb with or without a NOX2 inhibitor (apocynin) or an NLRP3 inhibitor (Bay117082). In isolated hearts, we measured the infarct size after 30min of ischemia and 60min of reperfusion. In hearts from preconditioned rats we measured the activity of NOX2; the mRNA of Nrf2, gamma-glutamylcysteine ligase, glutathione dehydrogenase, thioredoxin reductase and sulfiredoxin by RT-qPCR; the content of glutathione; the activation of the NLRP3 inflammasome and the content of IL-1β and IL-10 in cardiac tissue. In exosomes isolated from plasma, we quantified NOX2 activity. Results: The infarct size after IR decreased from 40% in controls to 9% of the heart volume after RIPC. This protective effect was lost in the presence of both inhibitors. RIPC increased NOX2 activity in the heart and exosomes, as indicated by the increased association of p47phox to the membrane and by the increased oxidation rate of NADPH. RIPC also increased the mRNA of Nrf2 and antioxidant enzymes. Also, RIPC increased the content of glutathione and the GSH/GSSG ratio. The inflammasome proteins NLRP3, procaspase-1, and caspase-1 were all increased in the hearts of RIPC rats. At the end of RIPC protocol, IL-1β increased in plasma but decreased in cardiac tissue. At the same time, IL-10 did not change in cardiac tissue but increased by 70% during the next 50min of perfusion. Conclusion: RIPC activates NOX2 which upregulates the heart's antioxidant defenses and activates the NLRP3 inflammasome which stimulates a cardiac anti-inflammatory response. These changes may underlie the decrease in the infarct size induced by RIPC.

Randomized controlled trial of remote ischemic preconditioning in children having cardiac surgery

BackgroundChildren undergoing cardiac surgery are at risk for acute kidney injury (AKI) and cardiac dysfunction. Opportunity exists in protecting end organ function with remote ischemic preconditioning. We hypothesize this intervention lessens kidney and myocardial injury.MethodsWe conducted a randomized, double blind, placebo controlled trial of remote ischemic preconditioning in children undergoing cardiac surgery. Pre-specified end points are change in creatinine, estimated glomerular filtration rate, development of AKI, B-type natriuretic peptide and troponin I at 6, 12, 24, 48, 72 h post separation from bypass.ResultsThere were 45 in the treatment and 39 patients in the control group, median age of 3.5 and 3.8 years, respectively. There were no differences between groups in creatinine, cystatin C, eGFR at each time point. There was a trend for a larger rate of decrease, especially for cystatin C (p = 0.042) in the treatment group but the magnitude was small. AKI was observed in 21 (54%) of control and 16 (36%) of treatment group (p = 0.094). Adjusting for baseline creatinine, the odds ratio for AKI in treatment versus control was 0.31 (p = 0.037); adjusting for clinical characteristics, the odds ratio was 0.34 (p = 0.056). There were no differences in natriuretic peptide or troponin levels between groups. All secondary end points of clinical outcomes were not different.ConclusionsThere is suggestion of RIPC delivering some kidney protection in an at-risk pediatric population. Larger, higher risk population studies will be required to determine its efficacy.Trial registration and date: Clinicaltrials.gov NCT01260259; 2021.

Remote ischemic preconditioning and cognitive dysfunction following coronary artery bypass grafting: A systematic review and meta-analysis of randomized controlled trials.

Postoperative cognitive dysfunction (POCD) is a common neurological issue following cardiopulmonary bypass (CPB)-assisted heart surgery. Remote ischemic preconditioning (RIPC) increases the tolerance of vital organs to ischemia/reperfusion injury, leading to reduced brain injury biomarkers and improved cognitive control. However, the exact mechanisms underlying RIPC's neuroprotective effects remain unclear. This systematic review aimed to explore the hypothesis that RIPC lowers neurocognitive dysfunction in patients undergoing CPB surgery. All relevant studies were searched in PubMed, ScienceDirect, EBSCOhost, Google Scholar, Semantic Scholar, Scopus, and Cochrane Library database. Assessment of study quality was carried out by two independent reviewers individually using the Cochrane Risk of Bias (RoB-2) tool. Meta-analysis was performed using a fixed-effect model due to low heterogeneity among studies, except for those with substantial heterogeneity. A total of five studies with 1,843 participants were included in the meta-analysis. RIPC was not associated with reduced incidence of postoperative cognitive dysfunction (five RCTs, odds ratio [OR:] 0.79, 95% confidence interval [CI]: 0.56-1.11) nor its improvement (three RCTs, OR: 0.80, 95% CI: 0.50-1.27). In addition, the analysis of the effect of RIPC on specific cognitive function tests found that pooled SMD for RAVLT 1-3 and RAVLT LT were -0.07 (95% CI: -0.25,012) and -0.04 (95% CI: -0.25-0.12), respectively, and for VFT semantic and phonetic were -0.15 (95% CI: -0.33-0.04) and 0.11 (95% CI: -0.40-0.62), respectively. The effect of RIPC on cognitive performance in CABG patients remained insignificant. Results from previous studies were unable to justify the use of RIPC as a neuroprotective agent in CABG patients.