Microparticle release in remote ischemic conditioning mechanism

2012 ◽  
Vol 303 (7) ◽  
pp. H871-H877 ◽  
Author(s):  
Julien Jeanneteau ◽  
Pierre Hibert ◽  
Maria Carmen Martinez ◽  
Simon Tual-Chalot ◽  
Sophie Tamareille ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Infarct Size ◽  
Annexin V ◽  
Limb Ischemia ◽  
Remote Ischemic Conditioning ◽  
Ischemic Conditioning ◽  
Healthy Humans ◽  
Biological Vector ◽  
Pressure Cuff ◽  
Circulating Microparticles

Remote ischemic conditioning (RCond) induced by short periods of ischemia and reperfusion of an organ or tissue before myocardial reperfusion is an attractive strategy of cardioprotection in the context of acute myocardial infarction. Nonetheless, its mechanism remains unknown. A humoral factor appears to be involved, although its identity is currently unknown. We hypothesized that the circulating microparticles (MPs) are the link between the remote tissue and the heart. MPs from rats and healthy humans undergoing RCond were characterized. In rats, RCond was induced by 10 min of limb ischemia. In humans, RCond was induced by three cycles of 5-min inflation and 5-min deflation of a blood-pressure cuff. In the second part of the study, rats underwent 40 min myocardial ischemia followed by 2 h reperfusion. Infarct size was measured and compared among three groups of rats: 1) myocardial infarction alone (MI) ( n = 6); 2) MI + RCond started 20 min after coronary ligation ( n = 6); and 3) MI + injection of RCond-derived rat MPs (MI + MPs) ( n = 5). MPs from endothelial cells (CD54+ and CD146+ for rats and humans, respectively) and procoagulant MPs (Annexin V+) markedly increased after RCond, both in rats and humans. RCond reduced infarct size (24.4 ± 5.9% in MI + RCond vs. 54.6 ± 4.7% in MI alone; P < 0.01). Infarct size did not decrease in MI + MPs compared with MI alone (50.2 ± 6.4% vs. 54.6 ± 4.7%, not significantly different). RCond increased endothelium-derived and procoagulant MPs in both rats and humans. However, MP release did not appear to be a biological vector of RCond in our model.

Effect of remote ischemic conditioning on infarct size in patients with anterior ST-elevation myocardial infarction

2016 ◽  
Vol 181 ◽  
pp. 66-73 ◽  
Author(s):  
Dinos Verouhis ◽  
Peder Sörensson ◽  
Andrey Gourine ◽  
Loghman Henareh ◽  
Jonas Persson ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Infarct Size ◽  
St Elevation Myocardial Infarction ◽  
Remote Ischemic Conditioning ◽  
Ischemic Conditioning ◽  
St Elevation

Abstract T P350: Phase I Clinical Feasibility &Safety Trial of Remote Ischemic Conditioning After Aneurysmal Subarachnoid Hemorrhage

Stroke ◽  
2014 ◽  
Vol 45 (suppl_1) ◽  
Author(s):  
Mark Connolly ◽  
Joshua Dusick ◽  
Paul Vespa ◽  
Nestor Gonzalez
Keyword(s):  
Subarachnoid Hemorrhage ◽  
Cerebral Infarction ◽  
Phase I ◽  
Aneurysmal Subarachnoid Hemorrhage ◽  
Limb Ischemia ◽  
Pain Scale ◽  
End Points ◽  
Remote Ischemic Conditioning ◽  
Ischemic Conditioning ◽  
Pressure Cuff

Objective: Remote ischemic conditioning (RIC) is a phenomenon by which brief periods of sublethal ischemia in one tissue confers protection from ischemia to distant tissues. The safety and feasibility of RIC must be assessed before testing it in efficacy trials. We report a phase I feasibility and safety trial of RIC in aneurysmal subarachnoid hemorrhage (aSAH) patients. Methods: Patients with aSAH received 2-4 RIC sessions on non-consecutive days. A complete session was defined as four rounds of 5 minutes of one sided lower limb ischemia with a thigh blood pressure cuff followed by 5 minutes of reperfusion (verified by pedal Doppler). Primary end-points were tolerance to the procedure and any complication attributable to RIC. Secondary end-points included cerebral infarction or hemorrhage. Results: Twenty-one patients (67% female, mean age 52, Fisher 3.5, H&H 3.3) were enrolled. Seventeen had evidence of vasospasm during hospitalization. Of 76 RIC sessions performed, 75 (98.7%) were completed and tolerated. One session was incomplete due to poor cooperation secondary to delirium. No patients developed DVTs or other local complications within 2 weeks of their final RIC session. No patients suffered cerebral infarction or hemorrhage throughout the duration of RIC sessions and through 72 hours after their last complete session. Three had infarction confirmed on MRI at 3 and 5 days following the final RIC session. In conscious patients, there was a small increase in the analog pain scale upon inflation of the cuff (deflated: 0.5 inflated: 1.2, p<0.0005), but none requested to stop the session. There was no significant change in other vitals. Conclusions: In aSAH patients, RIC was successfully applied and well tolerated with no procedure-related complications. No patient suffered ischemic stroke within 72 hours of RIC, consistent with our previous studies showing protective cerebral metabolic changes up to 48 hours after sessions. These results demonstrate that application of RIC is safe and feasible and suggest that RIC may be associated with transient tolerance to ischemia during the treatment period. The efficacy of RIC for neuroprotection should be investigated in larger controlled trials.

P2589Platelets serve as carriers of cardioprotective factors after remote ischemic conditioning in humans

2019 ◽  
Vol 40 (Supplement_1) ◽  
Author(s):  
H R Lieder ◽  
M Tsoumani ◽  
I Andreadou ◽  
G Heusch ◽  
P Kleinbongard
Keyword(s):  
Blood Pressure ◽  
Infarct Size ◽  
Healthy Volunteers ◽  
Blood Cells ◽  
Blood Pressure Cuff ◽  
Signal Transfer ◽  
Remote Ischemic Conditioning ◽  
Ischemic Conditioning ◽  
Pressure Cuff ◽  
Platelet Releasate

Abstract Background/Introduction Brief episodes of ischemia/reperfusion (I/R) in a tissue or organ remote from the heart reduce myocardial infarct size after sustained severe myocardial I/R in all species tested so far, including humans. Remote ischemic conditioning can be induced before (pre-), during (per-) or following (post-) myocardial ischemia. Signal transfer from the remote tissue/organ to the heart is both, neuronal and humoral. Humoral signal transfer has been evidenced by the transfer of cardioprotection via plasma or plasma derivatives from one individual to another individual's heart, even across species. Circulating blood cells have been considered as targets for cardioprotection, but so far not as carriers of cardioprotective signals. Purpose To investigate the role of platelets as potential carriers of cardioprotection by remote ischemic preconditioning (RIPC). Methods Peripheral venous blood samples were collected from healthy volunteers (5 male/5 female, mean age 26±5 years) before and 60 min after RIPC (3×5 min blood pressure cuff inflation at 200 mmHg on the left upper arm/5 min deflation) or placebo (PLA) protocol (blood pressure cuff uninflated). RIPC and PLA protocols, respectively, were performed in randomized sequence at an interval of one week. Blood (80 mL) was drawn into tubes containing sodium citrate, apyrase and prostaglandin E1. Blood cells were counted using a hematology analyzer. Blood was centrifuged (100 g, 15 min, at room temperature) to obtain platelet-rich plasma (PRP). PRP was washed twice with buffer (pH 6.5), and the pellet was re-suspended in suspension buffer (pH 7.35); the platelet amount was adjusted to 2.5x103 platelets/μL. The platelet suspension was supplemented with 1 mol/L CaCl2 and centrifuged (14,000 g) at 4°C for degranulation. The supernatant, i.e. the platelet releasate, was retrieved. Male Lewis rats were sacrificed, their hearts isolated and perfused at constant pressure. Diluted platelet releasate (1:10) was infused into the isolated perfused rat hearts for 8 min followed by 2 min washout before 30/120 min global I/R. Infarct size (percentage of ventricular mass) was demarcated with staining by triphenyltetrazolium chloride. Data are presented as mean±SD. Results The platelet count was increased after RIPC, but unchanged after PLA (RIPC: from 204±19x103 platelets/μL to 247±16x103 platelets/μL; PLA: from 230±16x103 cells/μL to 222±18x103 platelets/μL; PLA vs. RIPC p<0.01, RIPC before vs. after p<0.01, two-way ANOVA for repeated measures with Fisher's least significant differences post-hoc tests), whereas all other blood cell counts remained unchanged. Infarct size was less with infusion of platelet releasate after RIPC in comparison to platelet releasate before RIPC and to platelet releasate before and after PLA, respectively (see Figure). Conclusion In response to RIPC in healthy volunteers, platelets carry soluble cardioprotective factor(s). Their precise nature must still be identified.

Remote Ischemic Conditioning in Acute Myocardial Infarction and Shock States

2019 ◽  
Vol 25 (2) ◽  
pp. 103-109
Author(s):  
Robert A. Kloner ◽  
Jianru Shi ◽  
Wangde Dai ◽  
Juan Carreno ◽  
Lifu Zhao
Keyword(s):  
Myocardial Infarction ◽  
Experimental Studies ◽  
Large Clinical Trial ◽  
Early Reperfusion ◽  
Remote Ischemic Conditioning ◽  
Ischemic Conditioning ◽  
Pressure Cuff ◽  
Remote Organ ◽  
Risk Patients ◽  
Severe Ischemia

Remote ischemic conditioning is the phenomenon whereby brief, nonlethal episodes of ischemia in one organ (such as a limb) protect a remote organ from ischemic necrosis induced by a longer duration of severe ischemia followed by reperfusion. This phenomenon has been reproduced by dozens of experimental laboratories and was shown to reduce the size of myocardial infarction in many but not all clinical studies. In one recent large clinical trial, remote ischemic conditioning induced by repetitive blood pressure cuff inflations on the arm did not reduce infarct size or improve clinical outcomes. This negative result may have been related in part to the overall success of early reperfusion and current adjunctive therapies, such as antiplatelet therapy, antiremodeling therapies, and low-risk patients, that may make it difficult to show any advantage of newer adjunctive therapies on top of existing therapies. One relevant area in which current outcomes are not as positive as in the treatment of heart attack is the treatment of shock, where mortality rates remain high. Recent experimental studies show that remote ischemic conditioning may improve survival and organ function in shock states, especially hemorrhagic shock and septic shock. In this study, we review the preclinical studies that have explored the potential benefit of this therapy for shock states and describe an ongoing clinical study.

Remote Ischemic Conditioning

2017 ◽  
Vol 107 (4) ◽  
pp. 313-317 ◽  
Author(s):  
Jano A. Boghossian ◽  
Bellal Joseph ◽  
Marvin J. Slepian ◽  
David G. Armstrong
Keyword(s):  
Diabetic Foot ◽  
Limb Ischemia ◽  
Tissue Loss ◽  
Foot Ulcers ◽  
Diabetic Foot Ulcers ◽  
Blood Pressure Cuff ◽  
Remote Ischemic Conditioning ◽  
Ischemic Conditioning ◽  
Pressure Cuff ◽  
Organ Systems

Remote ischemic conditioning involves the use of a blood pressure cuff or similar device to induce brief (3–5 min) episodes of limb ischemia. This, in turn, seems to activate a group of distress signals that has shown the potential ability to improve healing of the heart muscle and other organ systems. Until recently, this has not been tested in people with diabetic foot ulcers. The purpose of this review was to provide background on remote ischemic conditioning and recent data to potentially support its use as an adjunct to healing diabetic foot ulcers and other types of tissue loss. We believe that this inexpensive therapy has the potential to be deployed and incorporated into a variety of other therapies to prime patients for healing and to reduce morbidity in patients with this common, complex, and costly complication.

scholarly journals Neuroprotection by remote ischemic conditioning in the setting of acute ischemic stroke: a preclinical two-centre study

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Maryna V. Basalay ◽  
Marlene Wiart ◽  
Fabien Chauveau ◽  
Chloe Dumot ◽  
Christelle Leon ◽  
...  
Keyword(s):  
Ischemic Stroke ◽  
Infarct Size ◽  
Acute Ischemic Stroke ◽  
Limb Ischemia ◽  
Male Rats ◽  
Area At Risk ◽  
Neuroprotective Effects ◽  
Remote Ischemic Conditioning ◽  
Ischemic Conditioning ◽  
Secondary Endpoints

Abstract Reperfusion is the only existing strategy for patients with acute ischemic stroke, however it causes further brain damage itself. A feasible therapy targeting reperfusion injury is remote ischemic conditioning (RIC). This was a two-centre, randomized, blinded international study, using translational imaging endpoints, aimed to examine the neuroprotective effects of RIC in ischemic stroke model. 80 male rats underwent 90-min middle cerebral artery occlusion. RIC consisted of 4 × 5 min cycles of left hind limb ischemia. The primary endpoint was infarct size measured on T2-weighted MRI at 24 h, expressed as percentage of the area-at-risk. Secondary endpoints were: hemispheric space-modifying edema, infarct growth between per-occlusion and 24 h MRI, neurofunctional outcome measured by neuroscores. 47 rats were included in the analysis after applying pre-defined inclusion criteria. RIC significantly reduced infarct size (median, interquartile range: 19% [8%; 32%] vs control: 40% [17%; 59%], p = 0.028). This effect was still significant after adjustment for apparent diffusion coefficient lesion size in multivariate analysis. RIC also improved neuroscores (6 [3; 8] vs control: 9 [7; 11], p = 0.032). Other secondary endpoints were not statistically different between groups. We conclude that RIC in the setting of acute ischemic stroke in rats is safe, reduces infarct size and improves functional recovery.

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