scholarly journals Remote Ischemic Conditioning in Ischemic Stroke and Myocardial Infarction: Similarities and Differences

2021 ◽  
Vol 12 ◽  
Author(s):  
Luigi F. Saccaro ◽  
Alberto Aimo ◽  
Michele Emdin ◽  
Fernando Pico
Keyword(s):  
Myocardial Infarction ◽  
Ischemic Stroke ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Myocardial Necrosis ◽  
Future Research ◽  
Safe Procedure ◽  
Remote Ischemic Conditioning ◽  
Ischemic Conditioning ◽  
Similarities And Differences

Acute myocardial infarction and ischemic stroke are leading causes of morbidity and mortality worldwide. Although reperfusion therapies have greatly improved the outcomes of patients with these conditions, many patients die or are severely disabled despite complete reperfusion. It is therefore important to identify interventions that can prevent progression to ischemic necrosis and limit ischemia-reperfusion injury. A possible strategy is ischemic conditioning, which consists of inducing ischemia – either in the ischemic organ or in another body site [i.e., remote ischemic conditioning (RIC), e.g., by inflating a cuff around the patient's arm or leg]. The effects of ischemic conditioning have been studied, alone or in combination with revascularization techniques. Based on the timing (before, during, or after ischemia), RIC is classified as pre-, per-/peri-, or post-conditioning, respectively. In this review, we first highlight some pathophysiological and clinical similarities and differences between cardiac and cerebral ischemia. We report evidence that RIC reduces circulating biomarkers of myocardial necrosis, infarct size, and edema, although this effect appears not to translate into a better prognosis. We then review cutting-edge applications of RIC for the treatment of ischemic stroke. We also highlight that, although RIC is a safe procedure that can easily be implemented in hospital and pre-hospital settings, its efficacy in patients with ischemic stroke remains to be proven. We then discuss possible methodological issues of previous studies. We finish by highlighting some perspectives for future research, aimed at increasing the efficacy of ischemic conditioning for improving tissue protection and clinical outcomes, and stratifying myocardial infarction and brain ischemia patients to enhance treatment feasibility.

Remote ischemic conditioning for acute moderate ischemic stroke (RICAMIS): Rationale and design

2019 ◽  
Vol 15 (4) ◽  
pp. 454-460
Author(s):  
Xiao-Qiu Li ◽  
Lin Tao ◽  
Zhong-He Zhou ◽  
Yu Cui ◽  
Hui-Sheng Chen ◽  
...  
Keyword(s):  
Ischemic Stroke ◽  
Clinical Studies ◽  
Ischemia Reperfusion Injury ◽  
Neuroprotective Effect ◽  
Ischemia Reperfusion ◽  
Control Group ◽  
Open Label ◽  
Remote Ischemic Conditioning ◽  
Ischemic Conditioning ◽  
Experimental Group

Rationale A large number of basic and clinical studies have proved that remote ischemic conditioning has neuroprotective effect. For example, remote ischemic conditioning showed a neuroprotective role in cerebral ischemia-reperfusion injury model. Recent clinical studies suggested that remote ischemic conditioning may improve neurological function and reduce the risk of recurrence in ischemic stroke patients. However, there is a lack of convincing evidence for the neuroprotective effect of remote ischemic conditioning on ischemic stroke, which deserves further study. Aim To explore the efficacy and safety of remote ischemic conditioning for acute moderate ischemic stroke. Sample size estimates A maximum of 1800 subjects are required to test the superiority hypothesis with 80% power according to a one-sided 0.025 level of significance, stratified by gender, age, time from onset to treatment, National Institutes of Health Stroke Scale (6–10 vs. 11–16), degree of responsible vessel stenosis, location of stenosis, and stroke etiology. Methods and design Remote Ischemic Conditioning for Acute Moderate Ischemic Stroke is a prospective, random, open label, blinded endpoint and multi-center study. The subjects are divided into experimental group and control group randomly. The experimental group was treated with remote ischemic conditioning twice daily with 200 mmHg pressure for 10–14 days besides guideline-based therapy. The control group was treated according to the guidelines. Study outcome The primary efficacy endpoint is favorable functional outcome, defined as modified Rankin Scale 0–1 at 90 days post-randomization.

scholarly journals Clinical translation of myocardial conditioning

2018 ◽  
Vol 314 (6) ◽  
pp. H1225-H1252 ◽  
Author(s):  
Hans Erik Bøtker ◽  
Thomas Ravn Lassen ◽  
Nichlas Riise Jespersen
Keyword(s):  
Myocardial Infarction ◽  
Heart Failure ◽  
Blood Flow ◽  
Reperfusion Injury ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Acute Ischemia ◽  
Remote Ischemic Conditioning ◽  
Ischemic Conditioning ◽  
Flow Restriction

Rapid admission and acute interventional treatment combined with modern antithrombotic pharmacologic therapy have improved outcomes in patients with ST elevation myocardial infarction. The next major target to further advance outcomes needs to address ischemia-reperfusion injury, which may contribute significantly to the final infarct size and hence mortality and postinfarction heart failure. Mechanical conditioning strategies including local and remote ischemic pre-, per-, and postconditioning have demonstrated consistent cardioprotective capacities in experimental models of acute ischemia-reperfusion injury. Their translation to the clinical scenario has been challenging. At present, the most promising mechanical protection strategy of the heart seems to be remote ischemic conditioning, which increases myocardial salvage beyond acute reperfusion therapy. An additional aspect that has gained recent focus is the potential of extended conditioning strategies to improve physical rehabilitation not only after an acute ischemia-reperfusion event such as acute myocardial infarction and cardiac surgery but also in patients with heart failure. Experimental and preliminary clinical evidence suggests that remote ischemic conditioning may modify cardiac remodeling and additionally enhance skeletal muscle strength therapy to prevent muscle waste, known as an inherent component of a postoperative period and in heart failure. Blood flow restriction exercise and enhanced external counterpulsation may represent cardioprotective corollaries. Combined with exercise, remote ischemic conditioning or, alternatively, blood flow restriction exercise may be of aid in optimizing physical rehabilitation in populations that are not able to perform exercise practice at intensity levels required to promote optimal outcomes.

scholarly journals Neural Mechanisms of Cardioprotection

Physiology ◽  
2014 ◽  
Vol 29 (2) ◽  
pp. 133-140 ◽  
Author(s):  
Andrey Gourine ◽  
Alexander V. Gourine
Keyword(s):  
Myocardial Infarction ◽  
Reperfusion Injury ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Neural Mechanisms ◽  
Vagal Activity ◽  
Remote Ischemic Conditioning ◽  
Ischemic Conditioning ◽  
Reflex Pathways ◽  
Autonomic Reflex

This review highlights the importance of neural mechanisms capable of protecting the heart against lethal ischemia/reperfusion injury. Increased parasympathetic (vagal) activity limits myocardial infarction, and recent data suggest that activation of autonomic reflex pathways contributes to powerful innate mechanisms of cardioprotection underlying the remote ischemic conditioning phenomena.

scholarly journals Influence of long-term treatment with glyceryl trinitrate on remote ischemic conditioning

2018 ◽  
Vol 315 (1) ◽  
pp. H150-H158 ◽  
Author(s):  
Marie Hauerslev ◽  
Sivagowry Rasalingam Mørk ◽  
Kasper Pryds ◽  
Hussain Contractor ◽  
Jan Hansen ◽  
...  
Keyword(s):  
Endothelial Function ◽  
Glyceryl Trinitrate ◽  
Reperfusion Injury ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Rat Myocardium ◽  
Remote Ischemic Conditioning ◽  
Ischemic Conditioning ◽  
Human Endothelium

Remote ischemic conditioning (RIC) protects against sustained myocardial ischemia. Because of overlapping mechanisms, this protection may be altered by glyceryl trinitrate (GTN), which is commonly used in the treatment of patients with chronic ischemic heart disease. We investigated whether long-term GTN treatment modifies the protection by RIC in the rat myocardium and human endothelium. We studied infarct size (IS) in rat hearts subjected to global ischemia-reperfusion (I/R) in vitro and endothelial function in healthy volunteers subjected to I/R of the upper arm. In addition to allocated treatment, rats were coadministered with reactive oxygen species (ROS) or nitric oxide (NO) scavengers. Rats and humans were randomized to 1) control, 2) RIC, 3) GTN, and 4) GTN + RIC. In protocols 3 and 4, rats and humans underwent long-term GTN treatment for 7 consecutive days, applied subcutaneously or 2 h daily transdermally. In rats, RIC and long-term GTN treatment reduced mean IS (18 ± 12%, P = 0.007 and 15 ± 5%, P = 0.002) compared with control (35 ± 13%). RIC and long-term GTN treatment in combination did not reduce IS (29 ± 12%, P = 0.55 vs. control). ROS and NO scavengers both attenuated IS reduction by RIC and long-term GTN treatment. In humans, I/R reduced endothelial function ( P = 0.01 vs. baseline). Separately, RIC and long-term GTN prevented the reduction in endothelial function caused by I/R; given in combination, prevention was lost. RIC and long-term GTN treatment both protect against rat myocardial and human endothelial I/R injury through ROS and NO-dependent mechanisms. However, when given in combination, RIC and long-term GTN treatment fail to confer protection. NEW & NOTEWORTHY Remote ischemic conditioning (RIC) and long-term glyceryl trinitrate (GTN) treatment protect against ischemia-reperfusion injury in both human endothelium and rat myocardium. However, combined application of RIC and long-term GTN treatment abolishes the individual protective effects of RIC and GTN treatment on ischemia-reperfusion injury, suggesting an interaction of clinical importance.

scholarly journals The application of remote ischemic conditioning in cardiac surgery

F1000Research ◽  
2017 ◽  
Vol 6 ◽  
pp. 928 ◽  
Author(s):  
Zeljko J. Bosnjak ◽  
Zhi-Dong Ge
Keyword(s):  
Cardiac Surgery ◽  
Reperfusion Injury ◽  
Ischemia Reperfusion Injury ◽  
Clinical Success ◽  
Ischemia Reperfusion ◽  
Preclinical Research ◽  
Remote Ischemic Conditioning ◽  
Ischemic Conditioning ◽  
Remote Conditioning ◽  
Multicenter Clinical Trials

Perioperative myocardial ischemia and infarction are the leading causes of morbidity and mortality following anesthesia and surgery. The discovery of endogenous cardioprotective mechanisms has led to testing of new methods to protect the human heart. These approaches have included ischemic pre-conditioning, per-conditioning, post-conditioning, and remote conditioning of the myocardium. Pre-conditioning and per-conditioning include brief and repetitive periods of sub-lethal ischemia before and during prolonged ischemia, respectively; and post-conditioning is applied at the onset of reperfusion. Remote ischemic conditioning involves transient, repetitive, non-lethal ischemia and reperfusion in one organ or tissue (remote from the heart) that renders myocardium more resistant to lethal ischemia/reperfusion injury. In healthy, young hearts, many conditioning maneuvers can significantly increase the resistance of the heart against ischemia/reperfusion injury. The large multicenter clinical trials with ischemic remote conditioning have not been proven successful in cardiac surgery thus far. The lack of clinical success is due to underlying risk factors that interfere with remote ischemic conditioning and the use of cardioprotective agents that have activated the endogenous cardioprotective mechanisms prior to remote ischemic conditioning. Future preclinical research using remote ischemic conditioning will need to be conducted using comorbid models.

Abstract 15436: Remote Ischemic Conditioning Modulates Myocardial Perfusion and Coronary Vascular Resistance in Ischemic and Non-ischemic Myocardial Territories in Humans

Circulation ◽  
2015 ◽  
Vol 132 (suppl_3) ◽  
Author(s):  
Kasper Pryds ◽  
Roni Ranghøj Nielsen ◽  
Michael Rahbek Schmidt ◽  
Camilla Molich Hoff ◽  
Lars Tolbod Poulsen ◽  
...  
Keyword(s):  
Myocardial Perfusion ◽  
Vascular Resistance ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Stable Coronary Artery Disease ◽  
Coronary Vascular Resistance ◽  
Remote Ischemic Conditioning ◽  
Ischemic Conditioning ◽  
Flow Reserve ◽  
Before And After

Purpose: Remote ischemic conditioning (RIC) confers protection against myocardial ischemia-reperfusion injury through cellular protective pathways but may also involve modulation of the myocardial perfusion (MP). We investigated whether RIC modulates MP and coronary vascular resistance (CVR) in ischemic and non-ischemic myocardial territories in humans. Methods: In a prospective, single blinded study, we studied 49 patients with suspected stable coronary artery disease. MP was quantified by 82 Rb-PET before and after RIC, and CVR was calculated as mean arterial pressure divided by MP. RIC was conducted as 4 cycles of 5 min upper arm ischemia followed by 5 min of reperfusion. A subsequent adenosine 82 Rb-PET stress scanning identified non-ischemic, reversibly and irreversibly ischemic myocardial segments by summed difference scores, and quantified coronary flow reserve (CFR). Results: Stress 82 Rb-PET data were available for 47 patients and identified 682 non-ischemic, 38 reversibly ischemic, and 37 irreversibly ischemic myocardial segments. Mean CFR was decreased in reversibly ischemic myocardial segments. Global MP and CVR were not affected by RIC (p=0.64 and p=0.53). RIC decreased MP and increased CVR in reversibly ischemic myocardial segments but not in non-ischemic or irreversibly ischemic myocardial segments (Table). Overall, CFR correlated with a change in MP and CVR by RIC (r 2 =0.08, p<0.001 and r 2 =0.10, p<0.001), and allowed identification of a cut-off of CFR<2.3 for a decrease in MP by RIC. Conclusion: RIC modulated MP and CVR dependent on the ischemic status of the myocardium and the vasodilatative capacity of the microcirculation. These findings support the assumption that gentle perfusion may be involved in the cardioprotective mechanisms underlying RIC.

Ischemic Conditioning as a Hemostatic Intervention in Surgery and Cardiac Procedures: A Systematic Review

2017 ◽  
Vol 43 (07) ◽  
pp. 716-731 ◽  
Author(s):  
Andreas Krag ◽  
Anne-Mette Hvas
Keyword(s):  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Platelet Activity ◽  
Remote Ischemic Conditioning ◽  
Laboratory Parameters ◽  
Arterial Thromboembolism ◽  
Ischemic Conditioning ◽  
Tissue Ischemia ◽  
Cardiac Procedures ◽  
Meta Analyses

AbstractIschemic conditioning induced by nonlethal cycles of tissue ischemia and reperfusion attenuates ischemia–reperfusion injury. The objective of this study is to systematically review the effects of local and remote ischemic conditioning on laboratory parameters of hemostasis and the clinical outcomes of thromboembolism or bleeding in patients undergoing surgery or cardiac procedures. PubMed and Embase were searched for relevant human trials published in English between January 1, 1986, and September 7, 2016, and additional studies were identified from reference lists. Data on laboratory parameters of hemostasis, thromboembolism, and bleeding were extracted for qualitative synthesis. In total, 69 studies were included; of these, 53 were randomized controlled trials (RCTs) and 11 were meta-analyses. Local and remote ischemic conditioning reduced platelet activation in patients undergoing cardiac procedures. Local ischemic conditioning did not reduce the thromboembolic risk in patients undergoing surgery or cardiac procedures. Remote ischemic conditioning reduced the incidence of arterial thromboembolism after surgery or cardiac procedures in 3 out of 28 RCTs and 4 out of 5 meta-analyses. Local and remote ischemic conditioning did not increase operative bleeding. In conclusion, ischemic conditioning reduced platelet activity without increasing the risk of bleeding in patients undergoing surgery or cardiac procedures. Limited evidence supports the proposal that ischemic conditioning reduces the incidence of arterial thromboembolism in patients undergoing surgery or cardiac procedures.

scholarly journals Remote ischemic conditioning enhances heart and brain antioxidant defense

2020 ◽  
Vol 19 ◽  
Author(s):  
Felipe Lobato da Silva Costa ◽  
Renan Kleber Costa Teixeira ◽  
Vitor Nagai Yamaki ◽  
André Lopes Valente ◽  
Sandro Percário ◽  
...  
Keyword(s):  
Antioxidant Capacity ◽  
Wistar Rats ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Antioxidant Defenses ◽  
Early Reperfusion ◽  
Remote Ischemic Conditioning ◽  
Ischemic Conditioning ◽  
Protection Mechanisms ◽  
Male Wistar Rats

Abstract Background Ischemia-reperfusion injury contributes to morbidity after revascularization procedures. Along with early reperfusion, tissue conditioning by alternating intervals of brief ischemia-reperfusion episodes is considered the best approach to limit tissue damage. Remote ischemic conditioning is conducted remotely, in tissues other than those under ischemia. Despite this, remote ischemic conditioning protection mechanisms are poorly understood, which can lead to misapplication. Objectives To assess whether remote ischemic conditioning works in the heart and brain through enhancement of cells’ antioxidant defenses and whether the response is sustained or temporary. Methods Twenty-one male Wistar rats were assigned to three groups (n = 7): SHAM: same procedure as the other groups, but no remote ischemic conditioning was carried out. RIC 10: heart and brain were harvested 10 minutes after the remote ischemic conditioning protocol. RIC 60: heart and brain were harvested 60 minutes after the remote ischemic conditioning protocol. The remote ischemic conditioning protocol consisted of 3 cycles of 5 min left hindlimb ischemia followed by 5 min left hindlimb perfusion, lasting 30 min in total. Heart and brain samples were used to measure the tissue antioxidant capacity. Results Remote ischemic conditioning increased heart and brain antioxidant capacity after 10 minutes (0.746 ± 0.160/0.801 ± 0.227 mM/L) when compared to SHAM (0.523 ± 0.078/0.404 ± 0.124 mM/L). No enhancement of heart or brain antioxidant capacity was detected 60 minutes after remote ischemic conditioning (0.551 ± 0.073/0.455 ± 0.107 mM/L). Conclusions Remote ischemic conditioning temporarily enhances heart and brain antioxidant defenses in male Wistar rats.

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