Remote Ischemic Postconditioning Increases HIF-1α Plasma Levels and Improves Cardiac Markers After Cardiac Surgery
Condition: Ischemia-reperfusion Injury
MeSH terms: Reperfusion Injury; Ischemia
Study type: Interventional

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.
    

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.
    

Intervention name(s): Remote ischemic post-conditioning (RIP)
Intervention type(s): Procedure
Intervention description(s): 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.
Allocation: Randomized
Intervention model: Parallel Assignment
Intervention model description: 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.
Masking: Double (Participant, Care Provider)
Primary purpose: Basic Science
Keywords: on-pump cardiac surgery; HIF-1α; Remote ischemic postconditioning; postoperative cardiac markers; cardiopulmonary bypass