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.
Studieoversikt
Detaljert beskrivelse
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.
Studietype
Registrering (Faktiske)
Fase
- Ikke aktuelt
Kontakter og plasseringer
Studiesteder
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Essen, Tyskland, 4130
- Herzzentrum Essen - Huttrop gGmbH, Einrichtung des Universitätsklinikums Essen
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Deltakelseskriterier
Kvalifikasjonskriterier
Alder som er kvalifisert for studier
Tar imot friske frivillige
Kjønn som er kvalifisert for studier
Beskrivelse
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
Studieplan
Hvordan er studiet utformet?
Designdetaljer
- Primært formål: Grunnvitenskap
- Tildeling: Randomisert
- Intervensjonsmodell: Parallell tildeling
- Masking: Trippel
Våpen og intervensjoner
Deltakergruppe / Arm |
Intervensjon / Behandling |
|---|---|
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Aktiv komparator: 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 |
3 sykluser på 5 min venstre overarmsiskemi ved oppblåsing av en blodtrykksmansjett til 200 mmHg og 5 min reperfusjon
Andre navn:
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Placebo komparator: 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 |
3 sykluser på 5 min venstre overarmsiskemi ved oppblåsing av en blodtrykksmansjett til 200 mmHg og 5 min reperfusjon
Andre navn:
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Hva måler studien?
Primære resultatmål
Resultatmål |
Tiltaksbeskrivelse |
Tidsramme |
|---|---|---|
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Myocardial protection
Tidsramme: 72 h, postoperatively
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Cumulative postoperative troponin T release
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72 h, postoperatively
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Sekundære resultatmål
Resultatmål |
Tiltaksbeskrivelse |
Tidsramme |
|---|---|---|
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All-cause mortality
Tidsramme: 30 days and 1 year after CABG surgery and after complete follow-up
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follow up done by studynurses
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30 days and 1 year after CABG surgery and after complete follow-up
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MACCE
Tidsramme: 30 days and 1 year after CABG surgery after complete follow-up
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Major adverse cardiac and cerebrovascular events
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30 days and 1 year after CABG surgery after complete follow-up
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renal function
Tidsramme: 72 h, postoperatively
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Creatinine and eGFR
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72 h, postoperatively
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Cardioprotective factors released into circulating blood
Tidsramme: before skin incision versus 1-72 h after RIPC
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Analysis of blood plasma
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before skin incision versus 1-72 h after RIPC
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Myocardial function in vitro
Tidsramme: after RIPC
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left ventricular pressure (lvp) and maximum left ventricular pressure (lvdp) in an isolated perfused rodent heart after blood plasma infusion
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after RIPC
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Samarbeidspartnere og etterforskere
Sponsor
Etterforskere
- Hovedetterforsker: Markus Kamler, MD, Herzzentrum Essen - Huttrop gGmbH, Einrichtung des Universitätsklinikums Essen, Essen, Germany
Studierekorddatoer
Studer hoveddatoer
Studiestart
Primær fullføring (Faktiske)
Studiet fullført (Faktiske)
Datoer for studieregistrering
Først innsendt
Først innsendt som oppfylte QC-kriteriene
Først lagt ut (Anslag)
Oppdateringer av studieposter
Sist oppdatering lagt ut (Faktiske)
Siste oppdatering sendt inn som oppfylte QC-kriteriene
Sist bekreftet
Mer informasjon
Begreper knyttet til denne studien
Andre studie-ID-numre
- RIPC-13-5507-BO
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