Remote Ischemic Postconditioning Increases HIF-1α Plasma Levels and Improves Cardiac Markers After Cardiac Surgery

NCT04284592 | Completed DMC

• 1 other identifier: PI07/0836
• Study Type: interventional
• Target: 70
• Locations: 0 countries
• Sites: N/A

Brief Summary

Background. Cardiopulmonary bypass in on-pump cardiac surgery (OPCS) can have harmful effects by ischemia-reperfusion. No data about the effects of remote ischemic postconditioning (RIP) in hypoxia-inducible factor-1 alpha (HIF-1α) plasma level after OPCS. The aim of this study is evaluate the effects of RIP on postoperative HIF-1α plasma levels, cardiac markers and arterial oxygenation of patients after OPCS. Methods. Randomised controlled study in 70 patients undergoing OPCS: 35 patients receive RIP (RIP group) and 35 patients not (control group). Patients receive RIP on upper limb: 5 min of ischemia followed by 5 min of reperfusion (3 cycles) immediately after leaving on-pump. The primary outcome was to know the HIF-1α plasma levels after surgery in both groups: before starting surgery (T0) and after CPB period at 2 h (T1), 8 h (T2), 24 h (T3), 36 h (T4), 48 h (T5). Secondary outcomes included to measure the cardiac markers levels (Troponin T, CK-MB, CPK), arterial oxygenation (PaO2/FiO2) and others.

Conditions

Ischemia-reperfusion Injury

Keywords

on-pump cardiac surgery; HIF-1α; Remote ischemic postconditioning; postoperative cardiac markers; cardiopulmonary bypass

Outcome Measures

Primary Outcomes (6)

• Study of time course of HIF-1α plasma levels (absorbance units) after on-pump cardiac surgery

  Hipoxia induced factor 1 alpha (HIF-1α) is a transcriptional factor. Arterial blood samples were collected from the radial artery to evaluate the changes in HIF-1α plasma levels induced in patients undergoing on-pump cardiac surgery. Because we think that ischemic post-conditioning (RIP) can increase plasma HIF-1α plasma levels.

  Before starting surgery, is the basal time (Time 0)

• Study of time course of HIF-1α plasma levels (absorbance units) after on-pump cardiac surgery

  Hipoxia induced factor 1 alpha (HIF-1α) is a transcriptional factor. Arterial blood samples were collected from the radial artery to evaluate the changes in HIF-1α plasma levels induced in patients undergoing on-pump cardiac surgery. Because we think that ischemic post-conditioning (RIP) can increase plasma HIF-1α plasma levels.

  2 hours after cardiopulmonary bypass period (Time 1)

• Study of time course of HIF-1α plasma levels (absorbance units) after on-pump cardiac surgery

  Hipoxia induced factor 1 alpha (HIF-1α) is a transcriptional factor. Arterial blood samples were collected from the radial artery to evaluate the changes in HIF-1α plasma levels induced in patients undergoing on-pump cardiac surgery. Because we think that ischemic post-conditioning (RIP) can increase plasma HIF-1α plasma levels.

  8 hours after cardiopulmonary bypass period (Time 2)

• Study of time course of HIF-1α plasma levels (absorbance units) after cardiac surgery

  Hipoxia induced factor 1 alpha (HIF-1α) is a transcriptional factor. Arterial blood samples were collected from the radial artery to evaluate the changes in HIF-1α plasma levels induced in patients undergoing on-pump cardiac surgery. Because we think that ischemic post-conditioning (RIP) can increase plasma HIF-1α plasma levels.

  24 hours after cardiopulmonary bypass period (Time 3)

• Study of time course of HIF-1α plasma levels (absorbance units) after on-pump cardiac surgery

  Hipoxia induced factor 1 alpha (HIF-1α) is a transcriptional factor. Arterial blood samples were collected from the radial artery to evaluate the changes in HIF-1α plasma levels induced in patients undergoing on-pump cardiac surgery. Because we think that ischemic post-conditioning (RIP) can increase plasma HIF-1α plasma levels.

  36 hours after cardiopulmonary bypass period (Time 4)

• Study of time course of HIF-1α plasma levels (absorbance units) after on-pump cardiac surgery

  Hipoxia induced factor 1 alpha (HIF-1α) is a transcriptional factor. Arterial blood samples were collected from the radial artery to evaluate the changes in HIF-1α plasma levels induced in patients undergoing on-pump cardiac surgery. Because we think that ischemic post-conditioning (RIP) can increase plasma HIF-1α plasma levels.

  48 hours after cardiopulmonary bypass period (Time 5).

Secondary Outcomes (4)

• Study of time course of cardiac marker, Troponin T plasma levels (ng/l)

  In summary, not repetitive (6 time points): after anesthetic induction, before starting surgery (Time 0) and after cardiopulmonary bypass period, at 2 hrs (Time 1), 8 hrs (Time 2), 24 hrs (Time 3), 36 hrs (T4), 48 hrs (Time 5).

• Study of time course of cardiac marker, creatine phospho-kinase (CPK) plasma levels (U/l)

  In summary, not repetitive (6 time points): after anesthetic induction, before starting surgery (Time 0) and after cardiopulmonary bypass period, at 2 hrs (Time 1), 8 hrs (Time 2), 24 hrs (Time 3), 36 hrs (T4), 48 hrs (Time 5).

• Study of time course of cardiac marker, creatine kinase-MB (CK-MB) plasma levels (ng/ml)

  In summary, not repetitive (6 time points): after anesthetic induction, before starting surgery (Time 0) and after cardiopulmonary bypass period, at 2 hrs (Time 1), 8 hrs (Time 2), 24 hrs (Time 3), 36 hrs (T4), 48 hrs (Time 5).

• Study of time course of arterial oxygenation marker (PO2/FiO2), after on-pump cardiac surgery

  In summary, not repetitive (6 time points): after anesthetic induction, before starting surgery (Time 0) and after cardiopulmonary bypass period, at 2 hrs (Time 1), 8 hrs (Time 2), 24 hrs (Time 3), 36 hrs (T4), 48 hrs (Time 5).

Study Arms (2)

Control group

NO INTERVENTION

Patients do not receive remote ischemic post-conditioning (RIP) after cardiopulmonary bypass

RIP group

EXPERIMENTAL

Patients receive remote ischemic post-conditioning (RIP) after cardiopulmonary bypass

Procedure: Remote ischemic post-conditioning (RIP)

Interventions

Remote ischemic post-conditioning (RIP) PROCEDURE

The limb RIP was applied after leaving of cardiopulmonary bypass and consisted of 3 cycles: 5 min of ischemia by a cuff-inflator on an arm and inflated to 200 mmHg, followed by 5 min deflated. The control group had during the same time a deflated cuff.

RIP group

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• elective cardiac surgery (coronary arteries and/or valve replacement)
• ASA physical status III or less

You may not qualify if:

• pregnancy
• previous cardiac surgery
• myocardial infarction (\< 6 weeks)
• renal failure
• severe chronic pulmonary disease.

Sponsors & Collaborators

• José García de la Asunción: lead

Related Publications (8)

• Przyklenk K, Bauer B, Ovize M, Kloner RA, Whittaker P. Regional ischemic 'preconditioning' protects remote virgin myocardium from subsequent sustained coronary occlusion. Circulation. 1993 Mar;87(3):893-9. doi: 10.1161/01.cir.87.3.893.

  PMID: 7680290 BACKGROUND

• Heusch G, Botker HE, Przyklenk K, Redington A, Yellon D. Remote ischemic conditioning. J Am Coll Cardiol. 2015 Jan 20;65(2):177-95. doi: 10.1016/j.jacc.2014.10.031.

  PMID: 25593060 BACKGROUND

• Hausenloy DJ, Candilio L, Evans R, Ariti C, Jenkins DP, Kolvekar S, Knight R, Kunst G, Laing C, Nicholas J, Pepper J, Robertson S, Xenou M, Clayton T, Yellon DM; ERICCA Trial Investigators. Remote Ischemic Preconditioning and Outcomes of Cardiac Surgery. N Engl J Med. 2015 Oct 8;373(15):1408-17. doi: 10.1056/NEJMoa1413534. Epub 2015 Oct 5.

  PMID: 26436207 BACKGROUND

• Hausenloy DJ, Yellon DM. Ischaemic conditioning and reperfusion injury. Nat Rev Cardiol. 2016 Apr;13(4):193-209. doi: 10.1038/nrcardio.2016.5. Epub 2016 Feb 4.

  PMID: 26843289 BACKGROUND

• Wang GL, Jiang BH, Rue EA, Semenza GL. Hypoxia-inducible factor 1 is a basic-helix-loop-helix-PAS heterodimer regulated by cellular O2 tension. Proc Natl Acad Sci U S A. 1995 Jun 6;92(12):5510-4. doi: 10.1073/pnas.92.12.5510.

  PMID: 7539918 BACKGROUND

• Garcia-de-la-Asuncion J, Pastor E, Perez-Griera J, Belda FJ, Moreno T, Garcia-del-Olmo E, Marti F. Oxidative stress injury after on-pump cardiac surgery: effects of aortic cross clamp time and type of surgery. Redox Rep. 2013;18(5):193-9. doi: 10.1179/1351000213Y.0000000060.

  PMID: 24020718 BACKGROUND

• Kalakech H, Tamareille S, Pons S, Godin-Ribuot D, Carmeliet P, Furber A, Martin V, Berdeaux A, Ghaleh B, Prunier F. Role of hypoxia inducible factor-1alpha in remote limb ischemic preconditioning. J Mol Cell Cardiol. 2013 Dec;65:98-104. doi: 10.1016/j.yjmcc.2013.10.001. Epub 2013 Oct 17.

  PMID: 24140799 BACKGROUND

• Cai Z, Luo W, Zhan H, Semenza GL. Hypoxia-inducible factor 1 is required for remote ischemic preconditioning of the heart. Proc Natl Acad Sci U S A. 2013 Oct 22;110(43):17462-7. doi: 10.1073/pnas.1317158110. Epub 2013 Oct 7.

  PMID: 24101519 BACKGROUND

MeSH Terms

Conditions

Reperfusion Injury

Condition Hierarchy (Ancestors)

Vascular Diseases; Cardiovascular Diseases; Postoperative Complications; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Officials

• José García de la Asunción, MD, PhD

  Instituto de Investigacion Sanitaria INCLIVA

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, CARE PROVIDER
• Purpose: BASIC SCIENCE
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Principal investigator and clinical chief

Model Details: 35 patients receive RIP on upper limb: 5 min of ischemia followed by 5 min of reperfusion (3 cycles) immediately after leaving on-pump. The primary outcome was to know the time course of HIF-1α plasma levels after surgery in both groups and compare the two groups at specific time points: before starting surgery (T0) and after CPB period at 2 h (T1), 8 h (T2), 24 h (T3), 36 h (T4), 48 h (T5). Secondary outcomes included to measure the cardiac markers levels (Troponin T, CK-MB, CPK), arterial oxygenation (PaO2:FiO2) and others.

Study Record Dates

• First Submitted: February 21, 2020
• First Posted: February 26, 2020
• Study Start: October 1, 2012
• Primary Completion: June 1, 2015
• Study Completion: October 1, 2017
• Last Updated: February 26, 2020

Record last verified: 2020-02

Data Sharing

• IPD Sharing: Will not share