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

Phase 2

Completed

Conditions: Blood Transfusion
Nitric Oxide
Endothelial Physiopathology
Pulmonary Hypertension

Interventions: Procedure: Red blood Cells auto-transfusion
Drug: Inhaled Nitric Oxide (iNO) administration

Registration Number: NCT01529502

Lead Sponsor: Massachusetts General Hospital

Brief 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.

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 14

Inclusion Criteria

Have a photo ID
Age>18 years old (required to provide informed consent)
Age <60 years old
Mild impairment of endothelial function, assessed by post ischemic vasodilation (L_RHI,<0.7) (38)
Body mass index (BMI) >27 kg/m^2 and <40 kg/m^2
Fasting during the days of transfusion.
Avoiding intake of high nitrate food (i.e. green leafy vegetables: lettuce, spinach) on the day prior to the study
Feel well on the day of blood donation
KG within normal limits
Normotensive (systolic blood pressure <140 mmHg and diastolic <90 mmHg)
Normal physical exam and blood test results as indicated by:
1. WBC 4.5-11.0 n x103/μL
2. HGB 12.0-17.5 gm/dl
3. PLT 150-400 n x103/μL
4. Plasma Sodium 135-145 mmol/L
5. Plasma Potassium 3.4-4.8 mmol/L
6. Plasma Chloride 98-108 mmol/L
7. Plasma Carbon Dioxide 23.0-31.9 mmol/L
8. Plasma Urea Nitrogen 8-25 mg/dl
9. Plasma Creatinine 0.60-1.50 mg/dl
10. Plasma Glucose 70-110 mg/dl
11. Transaminase-SGPT 10-55 U/L
12. Transaminase-SGOT 10-40 U/L
13. Total Bilirubin < 2 mg/dl
14. Fasting plasma glucose < 110 mg/dl
15. Methemoglobin < 3%

Exclusion Criteria

Psychiatric disturbances such as anxiety, depression, schizophrenia requiring pharmacological treatment or hospitalization in the last year
Systemic disease with or without any functional limitation
Pregnancy determined by urine pregnancy test, detecting presence of human chorionic gonadotropin (hCG), or less than six weeks postpartum
Active smoking. Volunteers may be enrolled if they quit smoking for more than 1 year.
Excess alcohol use: more than ½ L/day of wine consumption or equivalent
Any current use of a medication other than: over-the-counter oral medications, herbal remedies, nutritional supplements, and oral contraceptives.
Antibiotic use within 48 hours of blood donation
Use of NSAIDS, corticosteroids, aspirin during the past 7 days
Dental work within 24 hours prior to the donation
Received or donated blood in the last 4 months
Have had any forms of cancer with the exceptions of basal cell skin cancer or treatment for in situ uterine cervical cancer
Currently enrolled in another research study

Study & Design

Study Type: INTERVENTIONAL

Study Design: CROSSOVER

Arm && Interventions

Group	Intervention	Description
Fresh blood	Red blood Cells auto-transfusion	-
Old blood	Red blood Cells auto-transfusion	-
Old blood + inhaled Nitric Oxide	Red blood Cells auto-transfusion	-
Old blood + inhaled Nitric Oxide	Inhaled Nitric Oxide (iNO) administration	-

Primary Outcome Measures

Name	Time	Method
Systolic Pulmonary Artery Pressure	Post-transfusion	Pulmonary vasoconstriction was measured by estimation of Systolic Pulmonary Artery Pressure in millimeter of mercury (mmHg) by trans-thoracic echocardiography

Secondary Outcome Measures

Name	Time	Method
Endothelial Function: Reactive Hyperemia Index	Post-transfusion	Reactive Hyperemia Index (RHI) measures Endothelial function and is assessed by digital pulse amplitude tonometry and it is a sensitive indicator of endothelial function. RHI is a calculated as a ratio between tested versus contralateral finger dilatation, thus there is no unit measure.