Protective Effects of Long-term Remote Limb Ischemic Preconditioning For Carotid Artery Stenting
Protective Effects of Long-term Remote Limb Ischemic Preconditioning For Carotid Artery Stenting
Remote limb ischemic preconditioning (RIPC) has neuro-protective and anti-inflammatory
 effects on ischemia- reperfusion injury. As the extent of its effect is unknown, the
 investigators will use clinical outcome, serum biochemical markers and brain magnetic
 resonance imaging (MRI) to determine whether RIPC has neuro-protective and anti-inflammatory
 effects on patients undergoing carotid artery stenting.
BACKGROUND: Brain ischemia and injury contributed to perioperative morbidity and mortality in
 Carotid Artery Stenting. Remote ischemic preconditioning (RIPC), brief periods of ischemia
 followed by reperfusion, can provide systemic protection for prolonged ischemia. Our previous
 study found no significant protection to the patients who received once RIPC before Carotid
 Artery Stenting. In order to investigate whether long-term RIPC before Carotid Artery
 Stenting can protect these patients from the perioperative and long-term complications, a
 prospective randomized controlled trial will be performed in the current study.

 DESIGNING: About 189 patients who are eligible for carotid artery stenting will be randomly
 assigned in 1:1:1 ratio to RIPC group, sham RIPC group and conventional Carotid Artery
 Stenting group (control). Remote limb ischemic preconditioning (RIPC) is consisted of five
 5-min cycles of bilateral arm ischemia/reperfusion, it is induced by an automated
 cuff-inflator placed on bilateral arm and inflated to 200 mmHg for 5-min followed by
 deflating the cuff for 5-min, patients in the RIPC group will do it twice a day for at least
 two weeks before carotid artery stenting. Patients in the sham RIPC group receive sham RIPC
 treatment, which is consisted of five 5-min cycles of bilateral arm ischemia/reperfusion,
 induced by an automated cuff-inflator placed on bilateral arm and inflated to 60 mmHg for
 5-min followed by deflating the cuff for 5-min, they will do it twice a day for at least two
 weeks before carotid artery stenting. Patients in the control group receive conventional
 carotid artery stenting without RIPC or sham RIPC treatment. Cerebral injury is assessed by
 serum S-100B and Neuron specific enolase (NSE), systematic inflammation is assessed by serum
 high-sensitivity C-reactive protein (hs-CRP). Post-treatment infarctions, both symptomatic
 and asymptomatic, are detected by diffusion-weighted imaging (DWI) and clinical outcomes are
 determined by cerebrovascular events, cardiac events or death.
Inclusion Criteria:

 1. Symptomatic or asymptomatic carotid artery stenosis. In symptomatic patients the
 degree of stenosis should more than 60% (Based on NASCET Criteria), in asymptomatic
 patients the degree of stenosis should more than 70% (Based on NASCET Criteria);

 2. Tolerance to any of the study medications, including clopidogrel, aspirin and statins;

 3. Can cooperate with and complete brain MRI examination;

 4. Has a negative pregnancy test within 7 days before randomization and no childbearing
 potential;

 5. Vascular ultrasound excluded intravascular thrombosis and unstable plaques in blood
 vessels of the bilateral upper limbs;

 6. No hemorrhagic tendency;

 7. Stable vital sign, normal renal and hepatic functions;

 8. Informed consent.

 Exclusion Criteria:

 1. Evolving stroke;

 2. Prior major ipsilateral stroke, if likely to confound study endpoints;

 3. Severe dementia;

 4. Hemorrhagic conversion of an ischemic stroke within the past 60 days;

 5. Chronic atrial fibrillation;

 6. Myocardial infarction within previous 30 days;

 7. Inability to understand and cooperate with study procedures or provide informed
 consent;

 8. Participating in other device or drug trial that has not completed the required
 protocol follow-up period;

 9. Any conditions that hampers proper angiographic assessment or makes percutaneous
 arterial access unsafe;

 10. High risk candidates defined as the Carotid Revascularization Endarterectomy vs.
 Stenting Trial (CREST);

 11. Any vascular, extremity soft tissue or orthopedic injury that may contraindicate
 bilateral arm ischemic preconditioning (e.g. superficial wounds and fractures of the
 arm);

 12. Blood pressure cannot be controlled lower than 200 mmHg by medications;

 13. Peripheral blood vessel disease (especially subclavian arterial and upper limb artery
 stenosis or occlusion).