Rheo-Erythrocrine Dysfunction as a Biomarker for RIC Treatment in Acute Ischemic Stroke
Condition: Stroke, Acute; Ischemic Stroke; Cerebrovascular Disorders; Central Nervous System Diseases
MeSH terms: Stroke; Ischemic Stroke; Cerebral Infarction; Nervous System Diseases; Central Nervous System Diseases; Cerebrovascular Disorders; Ischemia
Study type: Interventional

Summary: 
      This study aims to investigate whether Remote Ischemic Conditioning (RIC) improves
      rheo-erythrocrine dysfunction in acute ischemic stroke
    

Detailed description: 
      Stroke is a leading cause of death and disability worldwide. Of all strokes, 85% are ischemic
      strokes caused by a thrombus or an embolus. The additional 15% are caused by hemorrhage.
      Currently the only approved treatments for ischemic strokes are thrombolysis given within 4.5
      hours and thrombectomy performed within 6 hours of symptom onset - in some cases up to 24
      hours. The majority of stroke patients are not however eligible for acute reperfusion
      therapy, mainly due to time constrains and late presentation. Novel neuroprotective
      strategies available for all stroke patients are thus urgently needed.

      Remote Ischemic Conditioning (RIC) is a simple intervention in which transient ischemia is
      induced in an extremity by repetitive inflation-deflation of a blood pressure cuff. It
      remains uncertain exactly how the protective effect of RIC is transmitted and communicated
      between the extremity and the brain. Both humoral, immunological and neuronal pathways seem
      to be involved. Treatment with RIC and has proven to be a safe, feasible and low-cost
      treatment in clinical settings.

      Biomarkers of the RIC treatment is a new area of stroke research and are important to
      establish in order to assess and predict responders of the conditioning treatment.
      Rheo-erythrocrine dysfunction of the Red Blood Cell (RBC) is a novel biomarker in both
      ischemic strokes in general and on the effect of RIC. Red Blood Cells with a diameter of 6-8
      μm must be highly deformable in order to deliver oxygen to brain tissue by travelling through
      micro vessels with a diameter of just 2-3 μm. RBC's can carry nitric oxide as
      NO2-/s-nitrosylated proteins. These proteins improve RBC deformability and induce hypoxic
      vasodilation thereby improving passage through the microvasculature. RBC's also express
      Erythrocyte Nitric Oxide Synthase 3, which regulate the rheo-erythrocrine function.
      Erythrocyte Nitric Oxide Synthase 3 is activated by shear stress and provide an extra source
      of NO for hypoxic vasodilation. Preliminary data have shown that experimental stroke on mice
      seems to cause a rheo-erythrocrine dysfunction of the RBC's leading to a loss of
      deformability. The RBC's become rigid, which can lead to occlusion of micro vessels in the
      brain and further ischemic damage. Loss of deformability can be measured as a reduced
      Elongation Index (EI) by ektacytometry and may be attenuated by RIC.
    

Intervention name(s): Remote Ischemic Conditioning; Sham Remote Ischemic Conditioning
Intervention type(s): Device; Device
Intervention description(s): RIC is commonly achieved by inflation of a blood pressure cuff to induce 5-minute cycles of limb ischemia alternating with 5 minutes of reperfusion; Sham Comparator (Sham-RIC)
Allocation: Randomized
Intervention model: Parallel Assignment
Intervention model description: Pilot, Single-center, Randomized, Patient-assessor blinded, Sham-controlled Trial
Masking: Double (Participant, Outcomes Assessor)
Primary purpose: Treatment
Keywords: Remote Ischemic Conditioning; Neuroprotection