Long-term Remote Ischemic Preconditioning Improves Myocardial Perfusion and Prognosis of Patients After CABG

Study Overview
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Brief Summary
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Remote Ischemic preconditioning (RIPC) has been reported to improve myocardial microcirculation, promote collateral circulation recruitment, and improve myocardial perfusion in patients.Two large randomized controlled trials demonstrated a perioperative cardioprotective effect of RIPC (reduced troponin levels), but did not find that a single preoperative RIPC improved long-term outcomes of coronary artery bypass grafting(CABG).The effect of a single RIPC before CABG may be too short. This study aims to investigate whether long-term RIPC improved myocardial perfusion in patients 3 months and 6 months after CABG surgery , and to detect changes in blood vascular endothelial growth factor, Nitrc Oxide, adenosine，and Endothelin-1, and to observe MACCE event rates at 12 months.

Detailed Description
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A total of 210 patients were randomly divided into three groups according to the inclusion and exclusion criteria, with 70 patients in each group. Experimental Group 1: The patient underwent one RIPC (Four five-minute cycles of upper limb ischaemia and Four five-minute pauses using a blood pressure cuff air vehicle to 200 mmHg) 1 hours before surgery, then normal surgery, and RIPC was performed on the second day after surgery and every day after surgery, which lasted for 1 year. Experiment Group 2: Patients underwent once RIPC 1 hours before surgery, and then normal medical procedures were performed with no additional intervention. Control group: Patients did not receive any additional intervention. All patients were evaluated in three ways. First: 7days and 3 months after surgery , the quantitative examination of myocardial blood flow was conducted to observe the improvement of myocardial blood perfusion. Second: The changes in the concentrations of vascular colorectal growth factor, Nitrc Oxide, adenosine, and endothelin-1. Third, patients were evaluated for 6 months and 12months MACCE incidence (cardiovascular death, Nonfatal myocardial infarction, unplanned revascularization, and stroke).

Official Title
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Long-term Remote Ischemic Preconditioning Improves Myocardial Perfusion and Prognosis of Patients After Coronary Artery Bypass Grafting

Conditions
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Coronary Disease

Intervention / Treatment
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* Other: remote ischemic preconditioning （RIPC）


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Three coronary artery lesions, CABG surgery was planned Exclusion Criteria: The patients could not tolerate ripc; peripheral vascular disease affecting upper limbs Acute myocardial infarction complicated with cardiogenic shock，in recent 30 days, Emergency cases Severe structural heart disease and severe arrhythmia ； The uncontrolled systolic blood pressure and diastolic blood pressure of severe hypertension were 180 mmHg and 120 mmHg respectively; Severe liver, renal and pulmonary disease Mental disorder can't cooperate; Inability to give informed consent； Patients on glibenclamide or nicorandil, as these medications may interfere with RIC pregnant;

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 80 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Experimental Group 1:The patient underwent one RIPC (Four five-minute cycles of upper limb ischaemia and Four five-minute pauses using a blood pressure cuff air vehicle to 200 mmHg) 4 hours before surgery, then normal surgery, and RIPC was performed on the second day after surgery and every day after surgery, which lasted for 1 year. Experiment Group 2: Patients underwent once RIPC 4 hours before surgery, and then normal medical procedures were performed with no additional intervention. Control group: Patients did not receive any additional intervention.
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Experimental Group 1<br>Routine treatment + interventions:The patient underwent one RIPC (Four five-minute cycles of upper limb ischaemia and Four five-minute pauses using a blood pressure cuff air vehicle to 200 mmHg) before surgery, then normal surgery, and RIPC was performed on the second day and Once RIPC/day after CABG for one year. | Other: remote ischemic preconditioning （RIPC）<br>* Four five-minute cycles of upper limb ischaemia and Four five-minute pauses using a blood pressure cuff inflated to 200 mmHg.<br>|
| Experimental: Experimental Group 2<br>Routine treatment + interventions:Patients underwent a RIPC before surgery, and then normal medical procedures were performed with no additional intervention. | Other: remote ischemic preconditioning （RIPC）<br>* Four five-minute cycles of upper limb ischaemia and Four five-minute pauses using a blood pressure cuff inflated to 200 mmHg.<br>|
| No Intervention: Control group<br>routine treatment, no RIPC | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change of MBF by SPECT | Myocardial perfusion was evaluated by Single Photon Emission Computed Tomography(SPECT): myocardial blood flow(MBF) | 3 months | 
| Change of MPR by SPECT | Myocardial perfusion was evaluated by Single Photon Emission Computed Tomography(SPECT): myocardial perfusion reserve(MPR) | 3 months | 
| Change of MBF by CE | Myocardial perfusion was evaluated by contrast echocardiography(CE): myocardial blood flow(MBF) | 3 months | 
| Change of MPR by CE | Myocardial perfusion was evaluated by contrast echocardiography(CE): myocardial perfusion reserve(MPR) | 3 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| MBF by SPECT | Myocardial perfusion was evaluated by Single Photon Emission Computed Tomography(SPECT): myocardial blood flow(MBF) | 1 weeks | 
| MPR by SPECT | Myocardial perfusion was evaluated by Single Photon Emission Computed Tomography(SPECT): myocardial perfusion reserve(MPR) | 1 weeks | 
| MBF by CE | Myocardial perfusion was evaluated by contrast echocardiography(CE): myocardial blood flow(MBF) | 1 weeks | 
| MPR by CE | Myocardial perfusion was evaluated by contrast echocardiography(CE): and myocardial perfusion reserve(MPR) | 1 weeks | 
| Rate of major adverse cardiovascular and cerebrovascular events | Cardiovascular death, non-fatal acute myocardial infarction, revascularization, stroke | 12 months | 
| Rate of major adverse cardiovascular and cerebrovascular events | Cardiovascular death, non-fatal acute myocardial infarction, revascularization, stroke | 6 months | 
| Concentration of VEGF | Blood vascular colorectal growth factor | -1days，1 weeks，3months post surgery | 
| Concentration of NO | Blood Nitrc Oxide | -1days，1 weeks，3months post surgery | 
| Concentration of BK | Blood bradykinin | -1days，1 weeks，3months post surgery | 
| Concentration of ET-1 | Blood endothelin-1 | -1days，1 weeks，3months post surgery | 
| Concentration of adenosine | Blood adenosine | -1days，1 weeks，3months post surgery | 
| Concentration of troponin | Blood troponin | Before surgery and after surgery | 
| 6 minute Walk Test | 6 minute Walk Test | 1 weeks, 3/6/9 and 12 months post surgery | 
| Seattle angina questionnaire score | Including the limited degree of physical activity, stable state of angina pectoris, angina attack frequency, treatment satisfaction, disease recognition and recognition of 5 dimensions. | 1 weeks, 3/6/9 and 12 months post surgery | 
| Change of LVEF by SPECT | left ventricular ejection fraction was evaluated by Single Photon Emission Computed Tomography(SPECT): | 1 weeks, 3 months,6 months |