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

Official title

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

Overview

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

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).

Interventions

• 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.

Primary outcome measures

• Change of MBF by SPECT [Time frame: 3 months]
• Change of MPR by SPECT [Time frame: 3 months]
• Change of MBF by CE [Time frame: 3 months]
• Change of MPR by CE [Time frame: 3 months]

Secondary outcome measures (12)

• MBF by SPECT [Time frame: 1 weeks]
• MPR by SPECT [Time frame: 1 weeks]
• MBF by CE [Time frame: 1 weeks]
• MPR by CE [Time frame: 1 weeks]
• Rate of major adverse cardiovascular and cerebrovascular events [Time frame: 12 months]
• Rate of major adverse cardiovascular and cerebrovascular events [Time frame: 6 months]
• Concentration of VEGF [Time frame: -1days，1 weeks，3months post surgery]
• Concentration of NO [Time frame: -1days，1 weeks，3months post surgery]
• Concentration of BK [Time frame: -1days，1 weeks，3months post surgery]
• Concentration of ET-1 [Time frame: -1days，1 weeks，3months post surgery]
• Concentration of adenosine [Time frame: -1days，1 weeks，3months post surgery]
• Concentration of troponin [Time frame: Before surgery and after surgery]

Eligibility criteria

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;

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Open label

Primary purpose

Treatment

Study locations

China · 1 center

• Fuwai central China cardiovascular Hospital — Zhengzhou

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. PMID 18456674
• 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. PMID 30371329
• 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, Zacharows PMID 26436208
• 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. PMID 26436207

Identifiers

NCT: NCT04779008 · HenanICE202101

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗