Rejuvenated RBC and VO2 Max in Healthy Subjects
Condition: Erythrocyte Transfusion
Intervention: Transfusion of rejuvenated and washed autolgous RBCs; Transfusion of washed autolgous RBCs
Intervention description: Rejuvenation refers to the process of adding a mix of solutes (Rejuvesol®, Citra Labs, Braintree, MA; consists of sodium pyruvate, inosine, adenine, mono- and dibasic sodium phosphate) to older, stored (i.e., 2-3 DPG-depleted) blood to immediately restore 2,3-DPG and ATP levels in the stored red blood cells15. Rejuvenation was originally developed to prolong the storage life of rare-phenotype RBC units. It is FDA-approved for use in RBC units stored in CPD, CPDA-1, and AS-1. The major contraindication for the use of Rejuvesol® is in RBC units stored for fewer than 6 days due to high baseline 2,3-DPG and ATP levels. Rejuvenated units must be washed prior to administration to remove residual Rejuvesol that is not approved for iv administration in such concentrations.; Autologous RBCs will be washed prior to transfusion to maintain blinding and equalize volume and Hct with the rejuvenated and washed intervention arm
Phase: Phase 4
Study type: Interventional
Primary purpose: Basic Science
Allocation: Randomized
Intervention model: Parallel Assignment
Intervention model description: Prospective randomized "healthy volunteer" study
Masking: Triple (Participant, Investigator, Outcomes Assessor)
Masking description: Addition of rejuvesol will be performed by the blood bank and only they will know of group assignment
Enrollment: 9.0
Sex: All
Minimum age: 18 Years
Maximum age: 40 Years
Healthy volunteers: Accepts Healthy Volunteers

Summary:

      To compare the physiologic benefits of rejuvenated RBCs (rejRBCs) to standards RBCs (PRBCs),
      we will emulate critical conditions by safely maximizing stress on the cardiovascular system,
      in an elective, feasible volunteer study. Maximal oxygen uptake (VO2max) will be measured in
      an anemic, post-donation, pre-transfusion state, and also after transfusing 14-day-old,
      autologous blood randomized to standard storage or standard storage with rejuvenation. We
      hypothesize that transfusion of standard PRBCs is less effective at increasing oxygen
      delivery (measured by VO2max) compared with transfusion of rejRBCs.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Healthy male or female

          -  Age 18-40 (the American College of Sports Medicine Guidelines for Exercise Testing
             defines this age group with no or no more than one coronary heart disease risk factor
             as low-risk for VO2 max testing)

          -  Habitual exerciser defined as ≥ 30 minutes of at least moderate or high intensity
             exercise ≥ 3 times per week. After consent, and at the subsequent screening visit, a
             VO2 max test will be performed, and subjects with a low value (< 35 mL/kg/min) will be
             excluded (screen failure). Based on our previous experience, we anticipate that up to
             25% of the subjects will fall into this category; therefore, 10 subjects will be
             screened to obtain 6-8 participants who go on to donate their blood.

          -  Calculated total blood volume of at least 4,500 mL using an established formula:

               1. Men: (0.006012 x H3) + (14.6 x W) + 604 = TBV

               2. Women: (0.005835 x H3) + (15 x W) + 183 = TBV [H= Height in inches; W=Weight in
                  pounds]

          -  Has access to transportation to visit the blood collection facility and to return to
             Duke for all study visits

          -  Weighs at least 130 pounds

        Exclusion Criteria:

          -  Any significant acute or chronic medical illness or problem, including, but not
             limited to, diabetes, hypertension, cardiac disease, asthma, COPD

          -  Current or recent (last 60 days) tobacco or nicotine use

          -  History of sickle cell trait or disease or any other acquired or hereditary
             hematological abnormality

          -  History of fainting or other significant adverse reaction during phlebotomy or
             donation of blood

          -  Known prolonged QTc (or evidence of such at screening) defined as QTc >470 ms

          -  Known or suspected illicit drug or alcohol abuse

          -  Known or suspected HIV, Hepatitis B, or Hepatitis C infection

          -  History of thrombophilia or anticoagulant therapy

          -  Pregnancy

          -  Obesity defined as BMI>30

          -  Recent history of blood donation:

               1. Single whole blood unit donation within the past 8 weeks

               2. Double RBC donation by apheresis within the past 16 weeks

               3. Plasma donation by apheresis within the past 4 weeks

          -  Inadequate red blood cell mass evidenced by total blood volume <4500 mL (above) or
             screening hemoglobin <13.3 g/dL

          -  Known hypersensitivity to lithium compounds.