Remote Ischemic Perconditioning as an Adjunct Therapy to Thrombolysis in Patients With Acute Ischemic Stroke

Abstract

Background and Purpose— Remote ischemic preconditioning is neuroprotective in models of acute cerebral ischemia. We tested the effect of prehospital rPerC as an adjunct to treatment with intravenous alteplase in patients with acute ischemic stroke. Methods— Open-label blinded outcome proof-of-concept study of prehospital, paramedic-administered rPerC at a 1:1 ratio in consecutive patients with suspected acute stroke. After neurological examination and MRI, patients with verified stroke receiving alteplase treatment were included and received MRI at 24 hours and 1 month and clinical re-examination after 3 months. The primary end point was penumbral salvage, defined as the volume of the perfusion–diffusion mismatch not progressing to infarction after 1 month. Results— Four hundred forty-three patients were randomized after provisional consent, 247 received rPerC and 196 received standard treatment. Patients with a nonstroke diagnosis (n=105) were excluded from further examinations. The remaining patients had transient ischemic attack (n=58), acute ischemic stroke (n=240), or hemorrhagic stroke (n=37). Transient ischemic attack was more frequent ( P =0.006), and National Institutes of Health Stroke Scale score on admission was lower ( P =0.016) in the intervention group compared with controls. Penumbral salvage, final infarct size at 1 month, infarct growth between baseline and 1 month, and clinical outcome after 3 months did not differ among groups. After adjustment for baseline perfusion and diffusion lesion severity, voxelwise analysis showed that rPerC reduced tissue risk of infarction ( P =0.0003). Conclusions— Although the overall results were neutral, a tissue survival analysis suggests that prehospital rPerC may have immediate neuroprotective effects. Future clinical trials should take such immediate effects, and their duration, into account. Clinical Trial Registration— URL: http://www.clinicaltrials.gov . Unique identifier: NCT00975962.

Perconditioning combined with postconditioning on kidney ischemia and reperfusion

“…Perconditioning is the newest technique described to mitigate IR injury in many tissues 15,18,20 . Our study is the first evaluate of the potential protective effect of PER alone or combined with POS on kidney IR-induced injury, that only be test before in myocardium 15,20 , brain 17,26 , and liver 18 .…”

“…Based on fact that perconditioning is performed in a distant tissue, is a non-invasive procedure and do not increase the surgical time, thus does not require direct access to the artery and could be easily applied during the surgery or endovascular surgery [15][16][17][18][19] ; this ischemic conditioning must be test in human IR syndromes 20,31 . However, new studies aim to understanding the mechanism are need 32 .…”

“…This technique led to a pronounced protection to the myocardium against the deleterious effects of the ischemia and reperfusion. Since then, this technique has been demonstrated to protect brain, liver, myocardium and kidney from the IR syndrome in various animal models and in clinical settings [16][17][18][19][20][21] .…”

Ischemic Preconditioning: The Long-Awaited Savior of Neuroprotection. Has It Arrived?

“…Transient ischemic attack was more frequent, and National Institutes of Health Stroke Scale score on admission was lower in the rIPC group compared with controls. The risk of tissue infarction as assessed by diffusion-perfusion magnetic resonance imaging was also reduced in the rIPC group [5]. Another proof-of-concept study by Meng et al [6] evaluated the protective effects of rIPC in 88 Chinese patients younger than 80 years of age with symptomatic intracranial atherosclerosis.…”

“…The studies of Meng et al and others [5][6][7] indicate that rIPC holds promise as a simple and easy neuroprotective strategy for a large number of stroke patients. It is suited for 1) primary and secondary stroke prevention in multiple settings, including symptomatic and asymptomatic intra-and perhaps extracranial arterial occlusive lesions; 2) as an adjunctive strategy with or without reperfusion therapy for acute ischemic stroke; and 3) as a prophylactic strategy against delayed ischemic injury in subarachnoid hemorrhage.…”