VO2 Max: In Vivo Model for Functional Red Cell Testing. Can RECESS be Explained?

The US Food and Drug Administration (FDA) regulations permit additive-containing RBCs to be
stored for up to 42 days prior to transfusion. However, RBCs progressively develop
abnormalities during storage. The efficacy of older stored blood, i.e., effective oxygen
delivery, has not been established in rigorous controlled studies. Due to pragmatic reasons,
a large clinical trial that randomizes patients to "old" blood may not be feasible.

Every subject will have 2 phlebotomy visits at Stony Brook University Hospital. Subjects
randomized to the 7- and 42-day old groups will have 2 units of blood removed at Week 0 and
another 2 units removed at Week 5. However, the remaining 28-day group will have 2 units of
blood removed at Week 2 and only 1 unit of blood removed at Week 5. During week 6, each
subjects will have 3 study visits: 1) On Monday, a VO2 max test; 2) On Wednesday, a
transfusion with 2 units of autologous RBCs (each over 1 hour), followed by a VO2 max test 2
hours later; 3) On Friday, a VO2 max test will be done in order to calculate a delta VO2 max
(Friday minus Monday results).

Inclusion Criteria:

- 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 <10%
of the subjects will fall into this category

- Calculated total blood volume (TBV) ≥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
Stony Brook for all study visits.

Exclusion Criteria:

- Any significant acute or chronic medical illness or problem, including, but not
limited to, diabetes, hypertension, cardiac disease, asthma, chronic obstructive lung
disease

- 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) on electrocardiogram defined as
>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: a) Single whole blood unit donation within the past
8 weeks; b) Double RBC donation by apheresis within the past 16 weeks; or c) Plasma
donation by apheresis within the past 4 weeks

- Inadequate RBC mass based on TBV <4500 ml (above) or screening Hb <14 g/dL