Ignite Creation Date:
2024-05-06 @ 2:20 PM
Last Modification Date:
2024-10-26 @ 1:29 PM
Study NCT ID:
NCT04284592
Status:
COMPLETED
Last Update Posted:
2020-02-26
First Post:
2020-02-21
Brief Title:
Remote Ischemic Postconditioning Increases HIF-1α Plasma Levels and Improves Cardiac Markers After Cardiac Surgery
Sponsor:
José García de la Asunción
Organization:
INCLIVA
Study Overview
Official Title:
Remote Ischemic Postconditioning Increases HIF-1α Plasma Levels and Improves Cardiac Markers After Cardiac Surgery a Randomised Controlled Study
Status:
COMPLETED
Status Verified Date:
2020-02
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
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 PaO2FiO2 and others
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 PaO2FiO2 and others
Detailed Description:
Cardiac surgery with cardiopulmonary bypass CPB is associated with ischemia-reperfusion I-R injury Acute myocardial injury after cardiac surgery is associated with increased mortality and morbidity In 1993 reported that brief circumflex artery occlusion reduces myocardial infarct size induced by a definitive occlusion of the left anterior descending artery a phenomenon which has been named remote ischemic preconditioning RIPC This approach confers resistance to subsequent ischemic episodes in remote organs possibly by transferring protective mediators through humoral neuronal and systemic mechanisms however the mechanisms involved are not yet fully known A recent study has found that cardioprotection induced by RIPC the mitochondria appear to be an important subcellular effector organelle It has been reported that RIPC could be a potential protective approach for perioperative complications Therefore the effects on myocardial injury and clinical outcome in patients undergoing on-pump cardiac surgery OPCS are inconclusive In the present study we conducted a randomized clinical trial on patients undergoing OPCS by application of remote ischemic postconditioning RIP an alternative to remote ischemic preconditioning RIP can be applied in different clinical situations medical or surgical when reperfusion is initiated and associated to acidosis nitric oxide formation mitochondrial permeability transition pore inhibition and reactive oxygen species generation In the present study we have opted for remote postconditioning because we speculate a possible losses of plasmatic effectors during CPB procedures using polyvinylchloride PVC tubing Since when blood is exposed to the PVC surface the plasma proteins may be adsorbed Also to minimize the bleeding or hemodilution effects on the potential protective plasmatic effectors levels during CPB
Tissue exposure to low O2 concentration starts a hypoxic response of the hypoxia-inducible factor 1 HIF-1 a transcription factor heterodimer consisting of an O2 regulated HIF-1α subunit and a constitutively expressed HIF-1β subunit that binds to the consensus sequence 5-RCGTG-3 which is present near HIF-1-regulated genes HIF-1α protein stability is upregulated in response to hypoxia HIF-1α protein stability is negatively regulated by O2-dependent prolyl hydroxylation and is degraded under normoxia by prolyl hydroxylase HIF-1α plays a critical role in the mammalian cells activating genes associate with angiogenesis ischemia energy metabolism and cell cycle
The aim of this study carried out in patients undergoing OPCS was the determination of the time course of HIF-1α plasma levels in response to RIP and the possible correlation between aortic cross-clamping time and HIF-1α plasma levels in both groups HIF-1α role in remote ischemic conditioning pre or post is very little known Therefore we tested the hypothesis that RIP induces cardiac protection after OPCS and that this is associated to an increase of HIF-1α plasma levels
Tissue exposure to low O2 concentration starts a hypoxic response of the hypoxia-inducible factor 1 HIF-1 a transcription factor heterodimer consisting of an O2 regulated HIF-1α subunit and a constitutively expressed HIF-1β subunit that binds to the consensus sequence 5-RCGTG-3 which is present near HIF-1-regulated genes HIF-1α protein stability is upregulated in response to hypoxia HIF-1α protein stability is negatively regulated by O2-dependent prolyl hydroxylation and is degraded under normoxia by prolyl hydroxylase HIF-1α plays a critical role in the mammalian cells activating genes associate with angiogenesis ischemia energy metabolism and cell cycle
The aim of this study carried out in patients undergoing OPCS was the determination of the time course of HIF-1α plasma levels in response to RIP and the possible correlation between aortic cross-clamping time and HIF-1α plasma levels in both groups HIF-1α role in remote ischemic conditioning pre or post is very little known Therefore we tested the hypothesis that RIP induces cardiac protection after OPCS and that this is associated to an increase of HIF-1α plasma levels
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
False
Is a FDA Regulated Device?:
False
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None