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 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.

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).

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.

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.

Routine treatment + interventions:Patients underwent a RIPC before surgery, and then normal medical procedures were performed with no additional intervention.

Four five-minute cycles of upper limb ischaemia and Four five-minute pauses using a blood pressure cuff inflated to 200 mmHg.

Myocardial perfusion was evaluated by Single Photon Emission Computed Tomography(SPECT): myocardial blood flow(MBF)

Myocardial perfusion was evaluated by Single Photon Emission Computed Tomography(SPECT): myocardial perfusion reserve(MPR)

Myocardial perfusion was evaluated by contrast echocardiography(CE): myocardial perfusion reserve(MPR)

Myocardial perfusion was evaluated by Single Photon Emission Computed Tomography(SPECT): myocardial blood flow(MBF)

Myocardial perfusion was evaluated by Single Photon Emission Computed Tomography(SPECT): myocardial perfusion reserve(MPR)

Myocardial perfusion was evaluated by contrast echocardiography(CE): and myocardial perfusion reserve(MPR)

Including the limited degree of physical activity, stable state of angina pectoris, angina attack frequency, treatment satisfaction, disease recognition and recognition of 5 dimensions.

left ventricular ejection fraction was evaluated by Single Photon Emission Computed Tomography(SPECT):

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;

One year after the end of the trial, other outside investigators could access the original data on reasonable requests

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.