Transfer of Cardioprotection During RIPC

Study Overview
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Brief Summary
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Remote ischemic preconditioning (RIPC) with transient upper limb ischemia/reperfusion provides peri-operative myocardial protection, is safe and improves prognosis in patients undergoing elective CABG surgery. The signal transfer from limb to heart is unknown. Thus, the aim of this study is to identify the pathways which transfer the cardioprotective signal from the ischemic/reperfused extremity to the heart in humans undergoing surgical coronary revascularization.

Detailed Description
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The investigators will obtain arterial blood samples before skin incision and 1-72 h after the remote ischemic preconditioning protocol and analyze them biochemically. The investigators focus on those ligands that have been previously implicated in conditioning protocols at any organ. In addition, the investigators will use a bioassay system, consisting of a Langendorff-perfused isolated heart with coronary occlusion/reperfusion and infarct size by TTC staining as endpoint, and then expose this bioassay system to arterial plasma obtained after the remote ischemic preconditioning stimulus or placebo. This approach will allow us to further characterize any potential transfer signal candidate with a pharmacological antagonist approach. The investigators will also obtain human atrial appendages after the remote ischemic preconditioning protocol or placebo and before patients were connected to the extracorporeal circulation. Contractile function of isolated trabeculae and vasomotor function of isolated arterial vessels will be analyzed in a bioassay system.

Official Title
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Transfer of Cardioprotection During Remote Ischemic Conditioning

Conditions
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CABG

Intervention / Treatment
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* Procedure: RIPC


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Consecutive patients > 18 years after written informed consent elective, isolated CABG surgery with and without valvuloplastic surgery two-stage cannulation, cardiopulmonary bypass antegrade Bretschneider cardioplegia mild hypothermia (32°C) preoperative standard medication (statins, betablocker, aspirin) standard anesthesia (see above) intraoperative standard protocol (full heparinization with ACT, aprotinin, protamin) postoperative standard protocol (500 mg aspirin after 2 h, low-dose heparin after 4 h) Exclusion Criteria: preoperative prior percutaneous coronary intervention (PCI) within 6 weeks any preoperative troponin T elevation renal insufficiency (creatinine >200 µmol/l) reoperation emergency surgery acute coronary syndrome (unstable angina, STEMI, NSTEMI) within 4 weeks dual anti-platelet therapy (clopidogrel+aspirin) intraoperative harvesting of a. radialis coronary thrombendarterectomy complications (bypass-low flow/ -occlusion) antithrombotic therapy (intraoperative clopidogrel + aspirin) retrograde cardioplegia

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: Basic Science
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Remote ischemic preconditioning<br>Remote ischemic preconditioning (RIPC) protocol before coronary artery bypass surgery (CABG): after induction of anesthesia and before surgery: 3 cycles of 5 minutes left upper arm ischemia by inflation of a blood pressure cuff to 200mmHg and 5 minutes of reperfusion Anesthesia is with isoflurane (0.7-0.8% end-tidal) +sufentanil | 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: RIPC: Remote ischemic preconditioning;|
| Placebo Comparator: Placebo<br>No Remote ischemic preconditioning (RIPC) protocol before coronary artery bypass surgery (CABG): after induction of anesthesia and before surgery: the cuff is left uninflated | 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: RIPC: Remote ischemic preconditioning;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Myocardial protection | Cumulative postoperative troponin T release | 72 h, postoperatively | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| All-cause mortality | follow up done by studynurses | 30 days and 1 year after CABG surgery and after complete follow-up | 
| MACCE | Major adverse cardiac and cerebrovascular events | 30 days and 1 year after CABG surgery after complete follow-up | 
| renal function | Creatinine and eGFR | 72 h, postoperatively | 
| Cardioprotective factors released into circulating blood | Analysis of blood plasma | before skin incision versus 1-72 h after RIPC | 
| Myocardial function in vitro | left ventricular pressure (lvp) and maximum left ventricular pressure (lvdp) in an isolated perfused rodent heart after blood plasma infusion | after RIPC |