Remote Ischemic Perconditioning Is Effective Alone and in Combination With Intravenous Tissue-Type Plasminogen Activator in Murine Model of Embolic Stroke

Hoda, Nasrul; Siddiqui, Shahneela; Herberg, Samuel; Periyasamy‐Thandavan, Sudharsan; Bhatia, Kanchan; Hafez, Sherif; Johnson, Maribeth H.; Hill, William; Ergul, Adviye; Fagan, Susan C.; Hess, David C.

doi:10.1161/strokeaha.112.660373

Cited by 126 publications

(156 citation statements)

References 32 publications

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“…Emerging clinical trials have corroborated the previous research, suggesting that remote preconditioning may indeed protect the heart [9][10][11]. In addition, recent findings in experimental animal models and clinical studies suggest that remote ischemic preconditioning may also be beneficial to the brain without exacerbating intracerebral hemorrhage [12][13][14][15][16][17][18][19].…”

Section: Introductionsupporting

confidence: 55%

Ischemic Conditioning Is Safe and Effective for Octo- and Nonagenarians in Stroke Prevention and Treatment

et al. 2015

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Symptomatic intracranial arterial stenosis (SIAS) is very common in octo-and nonagenarians, especially in the Chinese population, and is likely the most common cause of stroke recurrence worldwide. Clinical trials demonstrate that endovascular treatment, such as stenting, may not be suitable for octogenarians with systemic diseases. Hence, less invasive methods for the octogenarian patients are urgently needed. Our previous study (unique identifier: NCT01321749) showed that repetitive bilateral arm ischemic preconditioning (BAIPC) reduced the incidence of stroke recurrence by improving cerebral perfusion (confirmed by single photon emission computed tomography and transcranial Doppler sonography) in patients younger than 80 years of age; however, the safety and effectiveness of BAIPC on stroke prevention in octo-and nonagenarians with SIAS are still unclear. The objective of this study was to evaluate the safety and effectiveness of BAIPC in reducing stroke recurrence in octo-and nonagenarian patients with SIAS. Fifty-eight patients with SIAS were enrolled in this randomized controlled prospective study for 180 consecutive days. All patients enrolled in the study received standard medical management. Patients in the BAIPC group (n=30) underwent 5 cycles consisting of bilateral arm ischemia followed by reperfusion for 5 min each twice daily. Those in the control group (n=28) underwent sham-BAIPC twice daily. Blood pressure, heart rate, local skin status, plasma myoglobin, and plasma levels of thrombotic and inflammatory markers were documented in both groups before beginning the study and for the first 30 days. Finally, the incidences of stroke recurrence and magnetic resonance imaging during the 180 days of treatment were compared. Compared with the control, BAIPC had no adverse effects on blood pressure, heart rate, local skin integrity, or plasma myoglobin, and did not induce cerebral hemorrhage in the studied cohort. BAIPC reduced plasma high sensitive C-reactive protein, interleukin-6, plasminogen activator inhibitor-1, leukocyte count, and platelet aggregation rate and elevated plasma tissue plasminogen activator (all p<0.01). In 180 days, 2 infarctions and 7 transient ischemic attacks were observed in the BAIPC group compared with 8 infarctions and 11 transient ischemic attacks in the sham BAIPC group (p<0.05). BAIPC may safely inhibit stroke recurrence, protect against brain ischemia, and ameliorate plasma biomarkers of inflammation and coagulation in octo-and nonagenarians with SIAS. A multicenter trial is ongoing.Clinical Trial Registration: www.clinicaltrials.gov, unique identifier: NCT01570231.

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Section: Introductionsupporting

confidence: 55%

Ischemic Conditioning Is Safe and Effective for Octo- and Nonagenarians in Stroke Prevention and Treatment

et al. 2015

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“…5,6 In a recent study, rPerC was found to be effective alone and in combination with rtPA in a murine stroke model. 7 The protective effect seemingly involves the activation of multiple endogenous defense mechanisms. These include an upregulation of nitric oxide levels, improved cerebral blood flow in the ischemic penumbra, and downregulation of inflammation and glutamatergic excitotoxicity.…”

Section: Strokementioning

confidence: 99%

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

Hougaard

Hjort

Zeidler

et al. 2014

Stroke

247

324

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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.

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“…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 .…”

Section: ■ Discussionmentioning

confidence: 99%

“…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 .…”

Section: ■ Discussionmentioning

confidence: 99%

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Perconditioning combined with postconditioning on kidney ischemia and reperfusion

et al. 2017

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Purpose: To evaluate if combination of perconditioning and postconditioning provides improved renal protection compared to perconditioning alone in a model of renal reperfusion injury. Methods: Thirty rats were assigned into 6 groups: normality; sham; ischemia and reperfusion; postconditioning; perconditioning; perconditioning + postconditioning. Animals were subjected to right nephrectomy and left renal ischemia for 30 minutes. Postconditioning consisted of 3 cycles of 5 min renal perfusion followed by 5 min of renal ischemia after major ischemic period. Perconditioning consisted of 3 cycles of 5 min hindlimb ischemia followed by 5 min of hindlimb perfusion contemporaneously to renal major ischemic period. After 24 hours, kidney was harvested and blood collected to measure urea and creatinine. Results: Perconditioning obtained better values for creatinine and urea level than only postconditioning (p<0.01); performing both techniques contemporaneously had no increased results (p>0.05). Regarding tissue structure, perconditioning was the only technique to protect the glomerulus and tubules (p<0.05), while postconditioning protected only the glomerulus (p<0.05). Combination of both techniques shows no effect on glomerulus or tubules (p>0.05). Conclusions: Perconditioning had promising results on ischemia and reperfusion induced kidney injury, enhanced kidney function and protected glomerulus and tubules. There was no additive protection when postconditioning and perconditioning were combined.

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Remote Ischemic Perconditioning Is Effective Alone and in Combination With Intravenous Tissue-Type Plasminogen Activator in Murine Model of Embolic Stroke

Cited by 126 publications

References 32 publications

Ischemic Conditioning Is Safe and Effective for Octo- and Nonagenarians in Stroke Prevention and Treatment

Ischemic Conditioning Is Safe and Effective for Octo- and Nonagenarians in Stroke Prevention and Treatment

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

Perconditioning combined with postconditioning on kidney ischemia and reperfusion

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