This is a single-center, randomized, partially blinded study to determine whether 42-day old red blood cells (RBCs) deliver oxygen as effectively as 7-day old RBCs and also to determine whether transfusion with 28-day old RBCs is non-inferior to 7-day old RBCs with respect to oxygen delivery.

In this study, subjects will be randomized to be transfused with 2 units of autologous (one's own) RBCs that are either 7-, 28-, or 42-days old. Endpoints include changes in exercise duration and VO2 max (test of oxygen consumption/delivery) between groups.

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 corrected QT interval (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

End of study an average of 2 months