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.

Study Overview

• Status: Completed
• Conditions: CABG
• Intervention / Treatment: Procedure: RIPC

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 Type: Interventional
• Enrollment (Actual): 392
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Germany
  • Essen, Germany, 4130
    • Herzzentrum Essen - Huttrop gGmbH, Einrichtung des Universitätsklinikums Essen

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Remote ischemic preconditioning; 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; 3 cycles of 5 min left upper arm ischemia by inflation of a blood pressure cuff to 200 mmHg and 5 min reperfusion; Other Names: RIPC: Remote ischemic preconditioning
Placebo Comparator: Placebo; 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; 3 cycles of 5 min left upper arm ischemia by inflation of a blood pressure cuff to 200 mmHg and 5 min reperfusion; Other Names: RIPC: Remote ischemic preconditioning

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: University Hospital, Essen
• Investigators: Principal Investigator: Markus Kamler, MD, Herzzentrum Essen - Huttrop gGmbH, Einrichtung des Universitätsklinikums Essen, Essen, Germany

Study record dates

Study Major Dates

• Study Start: September 1, 2013
• Primary Completion (Actual): April 20, 2020
• Study Completion (Actual): April 20, 2020

Study Registration Dates

• First Submitted: September 27, 2013
• First Submitted That Met QC Criteria: October 7, 2013
• First Posted (Estimate): October 8, 2013

Study Record Updates

• Last Update Posted (Actual): October 18, 2021
• Last Update Submitted That Met QC Criteria: October 8, 2021
• Last Verified: October 1, 2021

More Information

Terms related to this study

• Other Study ID Numbers: RIPC-13-5507-BO