Remote Ischemic Preconditioning in Coronary Artery Bypass Grafting With Cold Crystalloid Cardioplegic Arrest

Study Overview
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Brief Summary
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Remote ischemic preconditioning (RIPC) with transient upper limb ischemia/reperfusion reduces myocardial injury in patients undergoing on-pump coronary artery bypass (CABG) surgery with cross-clamp fibrillation or blood cardioplegia for myocardial protection. The present study assesses protection of heart, brain and kidney by RIPC under crystalloid cardioplegic arrest. The study also addresses safety and clinical outcome.

Detailed Description
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Remote ischemic preconditioning (RIPC) protocol after induction of anesthesia and before skin incision consists of 3 cycles of 5 minutes left upper arm ischemia by inflation of a blood pressure cuff to 200 mmHg and 5 minutes of reperfusion. For myocardial molecular analyses, left ventricular biopsies are taken before induction of cardioplegic cardiac arrest and at 10 minutes after aortic unclamping during reperfusion of the myocardium.

Official Title
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Effect of Remote Ischemic Preconditioning in Patients Undergoing On-pump Coronary Artery Bypass Graft Surgery With Crystalloid Cardioplegic Arrest

Conditions
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Myocardial Injury

Intervention / Treatment
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* Procedure: RIPC
* Procedure: Control
* Drug: isoflurane+sufentanil anesthesia


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Consecutive patients >18 years of age Double- or triple-vessel coronary artery disease Elective isolated first-time CABG Combined valve surgery + CABG Written informed consent Exclusion Criteria: Renal failure (creatinine ≥ 200 µmol/L) Peripheral vascular disease affecting upper limbs Preoperative inotropic support Any kind of mechanical assist device Acute or recent (<4 weeks) acute coronary syndromes Any PCI (<6 weeks) Any reasons for preoperative cTnI elevation Emergency surgery Redo surgery

Ages Eligible for Study
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Minimum Age: 18 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
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: RIPC<br>Remote ischemic preconditioning (RIPC) protocol before coronary artery bypass surgery consists of 3 cycles of 5 minutes left upper arm ischemia by inflation of a blood pressure cuff to 200 mmHg and 5 minutes of reperfusion after induction of anesthesia before coronary artery bypass surgery. For myocardial molecular analyses, left ventricular biopsies are taken before induction of cardioplegic cardiac arrest and 5 and 10 Minutes after aortic unclamping during reperfusion of the myocardium. | Procedure: RIPC<br>* 3 cycles of 5 min left upper arm ischemia by inflation of a blood pressure cuff to 200 mmHg and 5 min reperfusion<br>* Other names: CABG: Coronary artery bypass grafting;Drug: isoflurane+sufentanil anesthesia<br>* Anaesthesia is maintained by inhaled isoflurane in concentrations 0.7-0.8 % end-tidal with additional sufentanil injected during surgery, as required. During extracorporal circulation patients receive isoflurane via a vaporizer incorporated in the extracorporeal gas supply in the same concentrations.<br>* Other names: Sufentanil, Sufenta, (R-30730);|
| Placebo Comparator: Control<br>Control group: Coronary artery bypass surgery without remote ischemic preconditioning protocol | Procedure: Control<br>* Coronary artery bypass surgery without remote ischemic preconditioning protocol<br>* Other names: Coronary artery bypass surgery;Drug: isoflurane+sufentanil anesthesia<br>* Anaesthesia is maintained by inhaled isoflurane in concentrations 0.7-0.8 % end-tidal with additional sufentanil injected during surgery, as required. During extracorporal circulation patients receive isoflurane via a vaporizer incorporated in the extracorporeal gas supply in the same concentrations.<br>* Other names: Sufentanil, Sufenta, (R-30730);|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Perioperative extent of myocardial injury as measured by cardiac troponin I serum release over 72 hours after CABG surgery and its area under the curve (AUC). |  | 72 hours postoperatively after CABG surgery | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| All-cause mortality |  | 30 days and 1 year and complete follow-up after CABG surgery | 
| Major adverse cardiac and cerebrovascular events (MACCE) |  | at 30 days and 1 year and complete follow-up after CABG surgery | 
| Myocardial infarction |  | 30 days and 1 year and complete follow-up after CABG surgery | 
| Renal function |  | 72 hours post CABG | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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remote ischemic preconditioning, coronary artery bypass grafting, myocardial injury