Transfer of Cardioprotection During RIPC

Not Applicable

Completed

• Conditions: CABG
• Interventions: Procedure: RIPC

• Registration Number: NCT01956708
• Lead Sponsor: University Hospital, Essen

Brief Summary

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

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.

Study Timeline

• Study Start: 2013-09
• Study First Submitted: 2013-09-27
• Study First Submitted QC: 2013-10-07
• Study First Posted: 2013-10-08
• Primary Completion: 2020-04-20
• Study Completion: 2020-04-20
• Status Verified: 2021-10
• Last Update Submitted: 2021-10-08
• Last Update Posted: 2021-10-18

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 392

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Placebo	RIPC	No Remote ischemic preconditioning (RIPC) protocol before coronary artery bypass surgery (CABG): after induction of anesthesia and before surgery: the cuff is left uninflated
Remote ischemic preconditioning	RIPC	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

Primary Outcome Measures

Name	Time	Method
Myocardial protection	72 h, postoperatively	Cumulative postoperative troponin T release

Secondary Outcome Measures

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

Trial Locations

Locations (1)

Herzzentrum Essen - Huttrop gGmbH, Einrichtung des Universitätsklinikums Essen; 🇩🇪 Essen, Germany