Protection of the Heart With Remote Ischemic Preconditioning During Heart Surgery: A Pilot Study
Condition: Remote Ischemic Preconditioning; Myocardial Protection
MeSH terms: Ischemia
Study type: Interventional

Summary: 
      The purpose of this study is to compare a treatment called remote ischemic preconditioning
      (rIP) to no treatment. rIP is a simple treatment that is believed to help patients recover
      better after heart surgery. This treatment involves applying a large blood pressure cuff to
      one leg. The blood pressure cuffs will be inflated for 5 minutes and then deflated for 5
      minutes. This will be done 4 times in a row.
    

Detailed description: 
      Purpose:

        1. Determine, in a pilot study, if surrogate markers of rIP can be detected in patients
           presenting for cardiac surgery. Specifically measure the effect of rIP on the expression
           profile of HSP-70, iNOS, PKC-E, p38 MAPK, PI3K, and sarcolemmal KATP

        2. Determine if rIP influences the expression of genes known to influence substrate
           preference and thereby myocardial metabolism in patients undergoing heart surgery.
           Specifically the expression of HIF-1a, PPAR-a and AMPK

      Hypothesis:

      We hypothesize that rIP provides myocardial protection in patients presenting for heart
      surgery and that this protection is defined by a distinct gene expression profile with
      regards to genes involved in rIP and myocardial metabolism.

      Study Design:

      This proposal is for a randomized blinded pilot study on the use of rIP in patients requiring
      heart surgery.

      Study Population:

      The study will include 100 male and female patients undergoing elective heart surgery with
      cardiopulmonary bypass (CPB).

      Randomization:

      Patients will be randomized 1:1 to receive either rIP or no treatment.

      Blinding Procedures:

      The patient will be blinded as well as those performing the experimental analysis.

      Interventions:

      Remote Ischemic Preconditioning

      rIP will be induced immediately following induction of anesthesia. Four 5 minute cycles of
      lower unilateral limb ischemia and reperfusion induced tourniquet inflation to 300 mmHg will
      constitute the preconditioning stimulus.

      Blood sample collection/analysis

        1. Two cardiac biopsies (50 - 200 mg) will be collected pre-bypass and post- bypass and
           will be analyzed for gene and protein expression.

        2. Blood samples (4 mL) will be drawn immediately before induction of anesthesia, and at
           the same times as cardiac tissue samples are harvested and analyzed for gene/protein
           expression as well as at 1, 24, 48 and 72 hours post surgery. Troponin I and NT-ProBNP
           will be measured at baseline, 1, 24, 48 and 72 hours after surgery and 3 mL of blood
           will be collected for these tests. A total of 43 mL of blood will be collected per
           patient.

        3. rIP induced changes in leukocyte gene expression will be measured at the aforementioned
           time points.

      Other

      ECG assessment on post-operative day 1, 2, and 3.

      National Institute of Health stroke scale assessment will be conducted at screening and post
      operatively prior to hospital discharge.

      Each patient will receive a telephone follow-up call at 30 days post operatively to collect
      adverse events and mortality data.

      Experimental Methods:

        1. qRT-PCR will be used to measure gene expression.

        2. Immunoblotting will be used to measure protein expression
    

Intervention name(s): Blood Pressure Cuff
Intervention type(s): Device
Intervention description(s): The blood pressure cuff will be inflated for 5 minutes and then deflated for 5 minutes. This will be done 4 times in a row.
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Double (Participant, Outcomes Assessor)
Primary purpose: Prevention