Long-term Remote Ischemic Preconditioning Improves Myocardial Perfusion and Prognosis of Patients After CABG (L-RIPC-CABG)

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

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.

Study Overview

• Status: Recruiting
• Conditions: Coronary Disease
• Intervention / Treatment: Other: remote ischemic preconditioning （RIPC）

Detailed Description

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).

• Study Type: Interventional
• Enrollment (Estimated): 210
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Quan Guo, MD; Phone Number: +8615670510031; Email: xinyiguoquan@163.com

Study Locations

• China
  • Henan
    • Zhengzhou, Henan, China
      • Recruiting
      • Fuwai Central China Cardiovascular Hospital
      • Contact: Quan Guo, MD; Email: xinyiguoquan@163.com
      • Principal Investigator: Muwei Life, MD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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;

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Experimental Group 1; 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）; Four five-minute cycles of upper limb ischaemia and Four five-minute pauses using a blood pressure cuff inflated to 200 mmHg.
Experimental: Experimental Group 2; 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）; Four five-minute cycles of upper limb ischaemia and Four five-minute pauses using a blood pressure cuff inflated to 200 mmHg.
No Intervention: Control group; routine treatment, no RIPC

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Henan Institute of Cardiovascular Epidemiology
• Investigators: Principal Investigator: Muwei Li, Ph.D, Fuwai central China cardiovascular hospotial; Principal Investigator: Zhaoyun Cheng, Ph.D, Fuwai central China cardiovascular hospotial

Publications and helpful links

General Publications

• Hausenloy DJ, Yellon DM. Remote ischaemic preconditioning: underlying mechanisms and clinical application. Cardiovasc Res. 2008 Aug 1;79(3):377-86. doi: 10.1093/cvr/cvn114. Epub 2008 May 2.
• Lau JK, Roy P, Javadzadegan A, Moshfegh A, Fearon WF, Ng M, Lowe H, Brieger D, Kritharides L, Yong AS. Remote Ischemic Preconditioning Acutely Improves Coronary Microcirculatory Function. J Am Heart Assoc. 2018 Oct 2;7(19):e009058. doi: 10.1161/JAHA.118.009058.
• Meybohm P, Bein B, Brosteanu O, Cremer J, Gruenewald M, Stoppe C, Coburn M, Schaelte G, Boning A, Niemann B, Roesner J, Kletzin F, Strouhal U, Reyher C, Laufenberg-Feldmann R, Ferner M, Brandes IF, Bauer M, Stehr SN, Kortgen A, Wittmann M, Baumgarten G, Meyer-Treschan T, Kienbaum P, Heringlake M, Schon J, Sander M, Treskatsch S, Smul T, Wolwender E, Schilling T, Fuernau G, Hasenclever D, Zacharowski K; RIPHeart Study Collaborators. A Multicenter Trial of Remote Ischemic Preconditioning for Heart Surgery. N Engl J Med. 2015 Oct 8;373(15):1397-407. doi: 10.1056/NEJMoa1413579. Epub 2015 Oct 5.
• Hausenloy DJ, Candilio L, Evans R, Ariti C, Jenkins DP, Kolvekar S, Knight R, Kunst G, Laing C, Nicholas J, Pepper J, Robertson S, Xenou M, Clayton T, Yellon DM; ERICCA Trial Investigators. Remote Ischemic Preconditioning and Outcomes of Cardiac Surgery. N Engl J Med. 2015 Oct 8;373(15):1408-17. doi: 10.1056/NEJMoa1413534. Epub 2015 Oct 5.

Study record dates

Study Major Dates

• Study Start (Actual): March 10, 2021
• Primary Completion (Estimated): December 1, 2025
• Study Completion (Estimated): December 1, 2026

Study Registration Dates

• First Submitted: February 4, 2021
• First Submitted That Met QC Criteria: February 28, 2021
• First Posted (Actual): March 3, 2021

Study Record Updates

• Last Update Posted (Estimated): September 18, 2025
• Last Update Submitted That Met QC Criteria: September 12, 2025
• Last Verified: September 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Vascular Diseases; Cardiovascular Diseases; Heart Diseases; Myocardial Ischemia; Coronary Disease
• Other Study ID Numbers: HenanICE202101

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: One year after the end of the trial, other outside investigators could access the original data on reasonable requests

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No