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

Abstract

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.

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

“…More study is needed. Although the overall findings of Meng et al [7] and others are consistent with data from animal models and are promising, the translation into a possible clinical benefit remains to be shown in large phase III trials. In addition, the optimal timing, frequency, and duration of rIPC need to be better defined.…”

“…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.…”

“…In this issue, Meng et al [7] expand on their earlier study by investigating the safety and potential effectiveness of rIPC in 59 octo-and nonagenarian patients with symptomatic intracranial atherosclerosis. They conclude that rIPC safely ameliorates plasma biomarkers of inflammation and reduces stroke recurrence in these patients.…”

Repeated ischaemic preconditioning: a novel therapeutic intervention and potential underlying mechanisms

“…Improvement in event-free survival in the group that received repeated RIPC was recently reinforced by another study from the same group. In that study, significant protection against stroke recurrence was observed after 180 days of twice daily RIPC in symptomatic intracranial arterial stenosis patients (Meng et al 2015). Another recent study examined the impact of repeated RIPC on diabetic wound healing in patients with diabetes mellitus type 1 or type 2 (Shaked et al 2015).…”

Hypoxic conditioning and the central nervous system: A new therapeutic opportunity for brain and spinal cord injuries?

“…The efficiency of remote ischemic conditioning (consisting in brief ischemic episodes induced in the lower or upper limb by cyclic cuff inflation and deflation) in the prevention of stroke recurrence in patients with symptomatic intracranial arterial stenosis has been tested with supportive results. 51,52 Postconditioning might be a useful paradigm in a rehabilitative perspective but remains to be evaluated in humans. Results of remote ischemic postconditioning in patients at an acute phase of ischemic stroke, alone or as an adjunct therapy to conventional fibrinolysis, are encouraging.…”