Clinical and Genomic Responses to Open Heart Surgery
Condition: Ischemia-reperfusion (IR) Injury
MeSH terms: Ischemia
Study type: Interventional
Phase: Phase 3

Summary: 
      This study will be the first large scale randomized study of remote ischemic preconditioning
      (RIPC) ever performed and will define the role of this novel therapy as a clinical tool. This
      study will also be the first to define preoperative gene expression profiles associated with
      poor postoperative outcomes in a control (SHAM) population of children undergoing cardiac
      surgery. Finally, the role of RIPC in modifying these gene expression profiles will be
      examined. Therefore, mechanistic insight into the proven ability of RIPC to improve markers
      of tissue injury, and the expected improvement in clinically relevant endpoints, will be
      examined.
    

Detailed description: 
      Remote ischemic preconditioning (RIPC) is a powerful, innate mechanism of protection against
      ischemia-reperfusion (IR) injury. During the course of previous investigations, it was shown
      in animal models that transient limb ischemia (our stimulus for generating remote ischemic
      preconditioning) leads to induction of a portfolio of myocardial genomic responses concerned
      with stress-response and repair mechanisms, reduces myocardial infarction after prolonged
      coronary occlusion, protects against cardiopulmonary bypass-induced neural, pulmonary and
      myocardial damage, and when administered to the recipient, reduces IR injury in the
      transplanted heart.

      In humans, it has been have shown that RIPC downregulates genes responsible for
      pro-inflammatory pathways concerned with TNFα-signaling, apoptosis and exocytosis in
      circulating leukocytes, reduces ischemia-induced endothelial dysfunction, and decreases
      markers of myocardial and lung injury in a pilot study of children undergoing open heart
      surgery. However, the latter study was not powered to demonstrate differences in anatomic and
      age-related subgroups, or clinically relevant 'hard' end-points such as ventilation time,
      intensive care, and length of hospital stay.

      Thus, we are now proposing a large-scale clinical study examining genetic predictors of
      clinically relevant postoperative outcomes, and how they are modified by remote
      preconditioning.
    

Intervention name(s): Remote ischemic preconditioning (RIPC); SHAM
Intervention type(s): Procedure; Procedure
Intervention description(s): The RIPC stimulus will be delivered in the OR prep room after the induction of anesthesia (while the anesthesiologist and staff are inserting vascular cannulae and preparing the patient for surgery). Whenever possible, the left lower limb will be selected for delivery of the stimulus. An appropriate sized cuff will be selected and connected to a hand aneroid sphygmomanometer. A second cuff and hand aneroid sphygmomanometer will be placed beside the one connected to the study subject. The cuff on the limb will be inflated and deflated to provide a total of four cycles of limb ischemia and reperfusion.; For this group, the procedure will be identical for that described for the RIPC stimulus, with the exception that the blood pressure cuff placed on the subject will not be inflated, but the second cuff, that has been placed beside, will be inflated.
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Triple (Participant, Investigator, Outcomes Assessor)
Keywords: children; cardiac surgery; remote ischemic preconditioning; SHAM; ischemia-reperfusion