Review

Authors: Derek J Hausenloy, Derek M Yellon

The 30-year anniversary of the discovery of 'ischaemic preconditioning' is in 2016. This endogenous phenomenon can paradoxically protect the heart from acute myocardial infarction by subjecting it to one or more brief cycles of ischaemia and reperfusion. Apart from complete reperfusion, this method is the most powerful intervention known for reducing infarct size. The concept of ischaemic preconditioning has evolved into 'ischaemic conditioning', a term that encompasses a number of related endogenous cardioprotective strategies, applied either directly to the heart (ischaemic preconditioning or postconditioning) or from afar, for example a limb (remote ischaemic preconditioning, perconditioning, or postconditioning). Investigations of signalling pathways underlying ischaemic conditioning have identified a number of therapeutic targets for pharmacological manipulation. Over the past 3 decades, a number of ischaemic and pharmacological cardioprotection strategies, discovered in experimental studies, have been examined in the clinical setting of acute myocardial infarction and CABG surgery. The results from many of the studies have been disappointing, and no effective cardioprotective therapy is currently used in clinical practice. Several large, multicentre, randomized, controlled clinical trials on cardioprotection have highlighted the challenges of translating ischaemic conditioning and pharmacological cardioprotection strategies into patient benefit. However, a number of cardioprotective therapies have shown promising results in reducing infarct size and improving clinical outcomes in patients with ischaemic heart disease.

Topics: Animals; Cardiovascular Agents; Humans; Ischemic Postconditioning; Ischemic Preconditioning; Ischemic Preconditioning, Myocardial; Myocardial Infarction; Myocardial Reperfusion Injury; Treatment Outcome

PubMed: 26843289
DOI: 10.1038/nrcardio.2016.5

Authors: Luigi Vetrugno, Tiziana Bove

Topics: Hepatectomy; Humans; Ischemic Preconditioning; Liver; Reperfusion Injury

PubMed: 32013338
DOI: 10.23736/S0375-9393.20.14344-X

Authors: E Dale Abel

Topics: Ischemic Preconditioning, Myocardial; TOR Serine-Threonine Kinases

PubMed: 34219792
DOI: 10.1161/circresaha.121.318874

Authors: Yeong-Renn Chen

Topics: Humans; Ischemic Preconditioning; Reperfusion Injury

PubMed: 29579594
DOI: 10.1016/j.ijcard.2018.02.019

Authors: Quintin J Quinones, Jerrold H Levy

Topics: Antifibrinolytic Agents; Ischemic Preconditioning; Tranexamic Acid

PubMed: 29346202
DOI: 10.1213/ANE.0000000000002690

Meta-Analysis

Authors: Chun Tian, Aihua Wang, He Huang...

BACKGROUND

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.

METHODS

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.

RESULTS

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 (I = 89% and I = 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 (I = 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.

CONCLUSION

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.

TRIAL REGISTRATION

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

Topics: Animals; Humans; Hepatectomy; Ischemic Preconditioning; Liver; Reperfusion Injury; Postoperative Complications; Alanine Transaminase

PubMed: 38532332
DOI: 10.1186/s12871-024-02506-9

Review

Authors: Jia Liu, Yakun Gu, Mengyuan Guo...

As the organ with the highest demand for oxygen, the brain has a poor tolerance to ischemia and hypoxia. Despite severe ischemia/hypoxia induces the occurrence and development of various central nervous system (CNS) diseases, sublethal insult may induce strong protection against subsequent fatal injuries by improving tolerance. Searching for potential measures to improve brain ischemic/hypoxic is of great significance for treatment of ischemia/hypoxia related CNS diseases. Ischemic/hypoxic preconditioning (I/HPC) refers to the approach to give the body a short period of mild ischemic/hypoxic stimulus which can significantly improve the body's tolerance to subsequent more severe ischemia/hypoxia event. It has been extensively studied and been considered as an effective therapeutic strategy in CNS diseases. Its protective mechanisms involved multiple processes, such as activation of hypoxia signaling pathways, anti-inflammation, antioxidant stress, and autophagy induction, etc. As a strategy to induce endogenous neuroprotection, I/HPC has attracted extensive attention and become one of the research frontiers and hotspots in the field of neurotherapy. In this review, we discuss the basic and clinical research progress of I/HPC on CNS diseases, and summarize its mechanisms. Furthermore, we highlight the limitations and challenges of their translation from basic research to clinical application.

Topics: Animals; Autophagy; Brain; Humans; Hypoxia-Ischemia, Brain; Ischemic Preconditioning; Nervous System Diseases; Neuroprotection; Treatment Outcome

PubMed: 34237192
DOI: 10.1111/cns.13642

Authors: Victor A Ferraris

Topics: Autophagy; Hibernation; Ischemic Preconditioning, Myocardial; Mitochondria; Myocardium; Stem Cells

PubMed: 32029210
DOI: 10.1016/j.jtcvs.2020.01.002

Authors: Maral Ouzounian, Thomas F Lindsay, Thomas L Forbes...

Topics: Animals; Female; Hindlimb; Ischemic Preconditioning; Spinal Cord; Spinal Cord Ischemia

PubMed: 26707723
DOI: 10.1016/j.jtcvs.2015.11.036

Authors: Alexander Zarbock, John A Kellum

OBJECTIVE

Acute kidney injury is a common complication in critically ill patients and is associated with increased morbidity and mortality. Sepsis, major surgery, and nephrotoxic drugs are the most common causes of acute kidney injury. There is currently no effective strategy available to prevent or treat acute kidney injury. Therefore, novel treatment regimens are required to decrease acute kidney injury prevalence and to improve clinical outcomes. Remote ischemic preconditioning, triggered by brief episodes of ischemia and reperfusion applied in distant tissues or organs before the injury of the target organ, attempts to invoke adaptive responses that protect against acute kidney injury. We sought to evaluate the clinical evidence for remote ischemic preconditioning as a potential strategy to protect the kidney and to review the underlying mechanisms in light of recent studies.

DATA SOURCES

We searched PubMed for studies reporting the effect of remote ischemic preconditioning on kidney function in surgical patients (search terms: "remote ischemic preconditioning," "kidney function," and "surgery"). We also reviewed bibliographies of relevant articles to identify additional citations.

STUDY SELECTION

Published studies, consisting of randomized controlled trials, are reviewed.

DATA EXTRACTION

The authors used consensus to summarize the evidence behind the use of remote ischemic preconditioning.

DATA SYNTHESIS

In addition, the authors suggest patient populations and clinical scenarios in which remote ischemic preconditioning might be best applied.

CONCLUSIONS

Several experimental and clinical studies have shown tissue-protective effects of remote ischemic preconditioning in various target organs, including the kidneys. Remote ischemic preconditioning may offer a novel, noninvasive, and inexpensive treatment strategy for decreasing acute kidney injury prevalence in high-risk patients. Although many new studies have further advanced our knowledge in this area, the appropriate intensity of remote ischemic preconditioning, its mechanisms of action, and the role of biomarkers for patient selection and monitoring are still unknown.

Topics: Acute Kidney Injury; Animals; Biomarkers; Critical Illness; Humans; Ischemia; Ischemic Preconditioning; Randomized Controlled Trials as Topic; Reperfusion Injury

PubMed: 26496454
DOI: 10.1097/CCM.0000000000001381