Transfer of Cardioprotection During RIPC

Transfer of Cardioprotection During Remote Ischemic Conditioning

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.

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.

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