Pilot Study About the Harmful Effects of Blood Storage on Overweight People and the Role of iNO in This Setting

The objective of this study is to assess effects of the storage of PRBC on pulmonary vasoconstriction measured as increase in pulmonary artery pressure and endothelial function measured as a change in reactive hyperemia index in overweight people with existing endothelial dysfunction at baseline. The present study consists of three different parts, which will be scheduled in a randomized order on the same subject (crossover study). During one phase of the study, 14 healthy human volunteers will donate a unit of Packed Red Blood Cells (PRBC), which will be leukoreduced and stored in Additive Solutions-1 (AS-1), and then transfused back to the subjects after 3 days of storage at 4º C in the MGH Blood Bank (Fresh Blood arm). The second part of the study consists in the collection of another unit of PRBC from the same volunteers which will be transfused back to them after 40 days of storage (Old Blood arm). Finally in the third part, like in the second one, one unit of PRBC will be withdraw and stored for 40 days, but 80 ppm (parts per million by volume) Nitric Oxide in air will be administered together with the transfusion. There will be a 2 weeks interval after each PRBC transfusion. We hypothesize that old red blood cells stored under conventional conditions may trigger a complex, pro-inflammatory, pro-thrombotic and vasoconstriction response. We will compare the response to PRBC stored for 3 days with the response to PRBC stored for 40 days in the same healthy volunteers. We also want to test the hypothesis that inhaled nitric oxide may reverse these adverse effects. We will monitor/measure the following parameters: 1. Pulmonary vasoconstriction by trans-thoracic echocardiography 2. Endothelium-mediated changes in vascular (arterial) tone, measured as reactive hyperemia index.