Pilot Study About the Harmful Effects of Blood Storage on Overweight People and the Role of iNO in This Setting
Condition: Blood Transfusion; Endothelial Physiopathology; Nitric Oxide; Pulmonary Hypertension
MeSH terms: Hypertension, Pulmonary; Hypertension; Overweight
Study type: Interventional
Phase: Phase 2

Summary: 
      The purpose of this study is to determine whether storage time affects how human body
      responds to autologous blood transfusion. An autologous blood transfusion is when a person
      donates blood and then receives that same blood back in the transfusion. We also want to find
      out if in this situation inhaled nitric oxide can help to prevent the potential reduction of
      vasodilation capacity. Vasodilation capacity is the ability of the blood vessel to widen when
      needed.
    

Detailed description: 
      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.
    

Intervention name(s): Red blood Cells auto-transfusion; Red blood Cells auto-transfusion; Inhaled Nitric Oxide (iNO) administration
Intervention type(s): Procedure; Procedure; Drug
Intervention description(s): Withdrawal from 14 overweight volunteers of one unit of red blood cells and auto-transfusion after 3 days storage time. The same 14 subjects will be included in every arm of the study.; Withdrawal from the same 14 overweight volunteers of one unit of red blood cells and auto-transfusion after 40 days storage time.; Subjects will breath iNO (80ppm) for 10 minutes before, during and for one hour after the autologous old-blood transfusion.
Intervention MeSH terms: Nitric Oxide
Allocation: Randomized
Intervention model: Crossover Assignment
Masking: Single (Outcomes Assessor)
Primary purpose: Basic Science
Keywords: Blood Transfusion, Autologous; Blood Preservation/adverse effects; Blood Transfusion/adverse effects; Endothelium, Vascular/physiopathology; Hemoglobins; Nitric Oxide; Pulmonary Hypertension