Effect of RIC on 2,3-BPG in Erythrocyte (RIC-BPG)

Study Overview
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Brief Summary
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Under hypoxia or high-altitude hypoxia ,it has been found that 2,3-bisphosphoglycerate(2,3-BPG) in erythrocyte increased and facilitated oxygen release to tissues.Remote Ischemic Conditioning(RIC) can also cause hypoxic conditions in local limbs.Thus,we hypothesize that whether RIC could also increase 2,3-BPG in erythrocyte.

Detailed Description
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RIC is induced by short-term insulting blood-flow of nonvital distant organs intermittently and has been proved to be effective in ischemic stroke and myocardial infarction(MI).The possible mechanisms of RIC protection is complicated.RIC leads to local ischemia and hypoxia and has been demonstrated to play a role in vital organs through hypoxia inducible factors(HIF) against stroke and MI.Besides HIF, hypoxia or high-altitude hypoxia could also change glycolytic process in erythrocyte through adenosine or sphingosine-1-phosphate(S1P).Accompanying with alternating glucolysis, 2,3-diphosphoglycerate(2,3-BPG) in erythrocyte increases and it also facilitating oxygen release to tissues.Thus,we hypothesize that whether RIC could also increase 2,3-BPG in erythrocyte.There are 8 arms in this trial: All arms are RIC treatment. The level of 2,3-BPG in erythrocyte will be assessed by ELISA before and after the treatment.

Official Title
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The Effect of Remote Ischemic Conditioning on 2,3-bisphosphoglycerate in Erythrocyte

Conditions
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2,3-Bisphosphoglycerate

Intervention / Treatment
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* Device: remote ischemic conditioning


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age:18-65 years old Healthy adults Exclusion Criteria: Individuals with various chronic diseases. Individuals with various acute diseases. Individuals who take any medicines Individuals who have taken health supplements for more than 2 weeks. individuals with BMI<18.5 or BMI≥24

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Basic Science
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Unilateral upper limb 60mmHg RIC<br>RIC is a physical strategy performed by an electric autocontrol device with cuffs placed on unilateral upper limb and inflated to 60 mmHg for 5-min followed by deflation for 5-min, the procedures is performed repeatedly for 5 times. | Device: remote ischemic conditioning<br>* RIC is induced by short-term insulting blood-flow of nonvital distant organs intermittently.<br>|
| Experimental: Bilateral upper limb 60mmHg RIC<br>RIC is a physical strategy performed by an electric autocontrol device with cuffs placed on bilateral upper limb and inflated to 60 mmHg for 5-min followed by deflation for 5-min, the procedures is performed repeatedly for 5 times. | Device: remote ischemic conditioning<br>* RIC is induced by short-term insulting blood-flow of nonvital distant organs intermittently.<br>|
| Experimental: Unilateral upper limb 200mmHg RIC<br>RIC is a physical strategy performed by an electric autocontrol device with cuffs placed on unilateral upper limb and inflated to 200 mmHg for 5-min followed by deflation for 5-min, the procedures is performed repeatedly for 5 times. | Device: remote ischemic conditioning<br>* RIC is induced by short-term insulting blood-flow of nonvital distant organs intermittently.<br>|
| Experimental: Bilateral upper limb 200mmHg RIC<br>RIC is a physical strategy performed by an electric autocontrol device with cuffs placed on bilateral upper limb and inflated to 200 mmHg for 5-min followed by deflation for 5-min, the procedures is performed repeatedly for 5 times. | Device: remote ischemic conditioning<br>* RIC is induced by short-term insulting blood-flow of nonvital distant organs intermittently.<br>|
| Experimental: Unilateral lower limb 60mmHg RIC<br>RIC is a physical strategy performed by an electric autocontrol device with cuffs placed on unilateral lower limb and inflated to 60 mmHg for 5-min followed by deflation for 5-min, the procedures is performed repeatedly for 5 times. | Device: remote ischemic conditioning<br>* RIC is induced by short-term insulting blood-flow of nonvital distant organs intermittently.<br>|
| Experimental: Bilateral lower limb 60mmHg RIC<br>RIC is a physical strategy performed by an electric autocontrol device with cuffs placed on bilateral lower limb and inflated to 60 mmHg for 5-min followed by deflation for 5-min, the procedures is performed repeatedly for 5 times. | Device: remote ischemic conditioning<br>* RIC is induced by short-term insulting blood-flow of nonvital distant organs intermittently.<br>|
| Experimental: Unilateral lower limb 200mmHg RIC<br>RIC is a physical strategy performed by an electric autocontrol device with cuffs placed on unilateral lower limb and inflated to 200 mmHg for 5-min followed by deflation for 5-min, the procedures is performed repeatedly for 5 times. | Device: remote ischemic conditioning<br>* RIC is induced by short-term insulting blood-flow of nonvital distant organs intermittently.<br>|
| Experimental: Bilateral lower limb 200mmHg RIC<br>RIC is a physical strategy performed by an electric autocontrol device with cuffs placed on bilateral lower limb and inflated to 200 mmHg for 5-min followed by deflation for 5-min, the procedures is performed repeatedly for 5 times. | Device: remote ischemic conditioning<br>* RIC is induced by short-term insulting blood-flow of nonvital distant organs intermittently.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Changes of 2,3-BPG levels in erythrocyte | Whole blood for testing effect of RIC on 2,3-BPG in Erythrocyte | through study completion, an average of 24 hours | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Changes of prothrombin time(PT) | Whole blood for testing effect of RIC on PT | through study completion, an average of 24 hours | 
| Changes of activated partial thromboplastin time(APPT) | Whole blood for testing effect of RIC on APPT | through study completion, an average of 24 hours | 
| Changes of activated partial thrombin time(TT) | Whole blood for testing effect of RIC on TT | through study completion, an average of 24 hours | 
| Changes of Fibrinogen(FIB) | Whole blood for testing effect of RIC on FIB | through study completion, an average of 24 hours | 
| Changes of D-dimer | Whole blood for testing effect of RIC on D-dimer | through study completion, an average of 24 hours | 
| Changes of hypoxia inducible factor-1(HIF-1) | Whole blood for testing effect of RIC on HIF-1 | through study completion, an average of 24 hours | 
| Changes of lower limbs venous blood flow | Vascular ultrasound for detecting venous blood flow in lower limbs | through study completion, an average of 24 hours | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Remote ischemic conditioning, 2,3-Bisphosphoglycerate, Erythrocyte, Oxygen, healthy subjects