Transfusion Related Complication
Conditions
Keywords
S-Nitrosylation, Tissue Oxygenation, Anemia-induced tissue hypoxia, Red blood cell Transfusion
Brief summary
The Purpose of the study is to test the hypothesis that administration of an S-nitrosylating (SNO) agent can improve tissue oxygenation during transfusion of packed red blood cells (RBCs).
Detailed description
Transfusion is the most common therapeutic intervention employed to maintain and/or improve tissue and end-organ oxygen delivery. Despite the conceptual simplicity of this treatment recent studies indicate that RBC infusion often produces little clinical benefit and may actually harm the recipient by exacerbating rather than correcting anemia-induced tissue hypoxia. The main driver/regulator of tissue oxygenation is blood flow not blood oxygen content. In turn flow into the microvasculature is controlled by small molecules called S-nitrosothiols (SNOs), the most important of which is S-nitrosylated hemoglobin (SNO-Hb). The investigators determined that storage of human blood leads to rapid losses in SNO-Hb that are precisely paralleled by losses in the ability of stored RBCs to dilate blood vessels and thereby deliver oxygen. The investigators have now recently completed an autologous human blood transfusion that confirms the pre-clinical findings in that administration of 1 unit of packed RBCs to young healthy subjects did not improve tissue oxygenation and reduced circulating SNO-Hb levels. This novel mechanism for the loss of physiological activity in banked blood and, more importantly, a putative intervention for its correction, raise the possibility that restoration of NO bioactivity could correct the deficit in oxygen delivery. As such, The Investigators plan to repeat our transfusion study with the addition of administering an S-nitrosylating agent during RBC infusion.
Interventions
DRUGSNO
S-nitrosylating agent (SNO) Inhalation
DRUGNormal Saline
Normal Saline transfusion
DRUGRed Blood Cell
Blood transfusion (RBCs)
Sponsors
Case Western Reserve University
National Heart, Lung, and Blood Institute (NHLBI)
James Reynolds
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
This is an open-label phase I trial. Healthy young adult volunteers that would considered eligible by American Red Cross standards to donate blood will be screened by qualified practitioners for eligibility to participate in the above mentioned study. We anticipate an accrual number of 35, with subjects randomized to receive their blood (n=30) or saline (n=5) while breathing an SNO agent.
Eligibility
Sex/Gender
ALL
Age
18 Years to 35 Years
Healthy volunteers
Yes
Inclusion criteria
Eligibility Criteria Recruiting and studying of healthy human subjects with no pre-existing pathologic conditions from the local population. As a result the inclusion criteria is deliberately broad. Inclusion Criteria 1. Hemoglobin \> 12 g/dl 2. Healthy, non-pregnant adults with no pre-existing blood disorders or disease states that impact oxygen delivery. 2a. Active blood and platelet donors will be sought as study participants since these individuals are familiar with the routines for blood withdrawal and re-infusion.
Exclusion criteria
The
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Peripheral Tissue Oxygenation | Monitoring is continuous once the probes are placed on the skin. It will start approximately 30 minutes prior to blood transfsuion and continue overnight and then stopped next morning when subject is discharged. Total time is up to 24 hours. | Measurement of small vessel blood flow and oxygenation status with near infrared spectroscopy (NIRS). NIRS can record the amount of oxygenated and de-oxygenated hemoglobin (the main protein in red blood cells) using different light frequencies shined through probes attached to the skin. The tissue oxygenation measurement is expressed as a percentage based on the ratio of oxygenated to de-oxygenated hemoglobin. It is continually-measured to see if it is changing in response to transfusion or administration of the study drug. |
| Oxygen Utilization | Blood samples are obtained every 3 to 6 hours before during and after blood transfsuion until subject is discharged Total time is up to 24 hour | Determined by measuring arterial and venous blood oxygen levels - Blood Gas (BG) A BG is a test that measures the the levels of oxygen (O2) in the blood obtained from an artery or vein. The test is used to check the function of the patient's lungs and how well they are able to move oxygen around the body. The amount of oxygen is expressed as percent of the overall amount of hemoglobin. The difference in the amount of oxygen in arterial and venous blood is calculated as the measure of oxygen utilization and if it is changing in response to transfusion or administration of the study drug. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Kidney Function Test | Blood samples are obtained every 3 to 6 hours before during and after blood transfsuion until subject is discharged Total time is up to 24 hour | Blood samples will be assayed for markers of kidney function: creatinine - milligram per deciliter albumin - grams per deciliter blood urea nitrogen - milligram per deciliter This 3 blood markers are incorporated into a formula to calculate glomerular filtration rate or GFR. This is a measure of how well your kidneys are filtering your blood and if it is changing in response to transfusion or administration of the study drug. |
| Liver Function Test | Blood samples are obtained every 3 to 6 hours before during and after blood transfsuion until subject is discharged Total time is up to 24 hour | Blood samples will be assayed for markers of liver function: alanine transaminase or ALT - units per liter aspartate aminotransferase or AST - units per liter The individual values are determined then the AST/ALT ratio is calculated to provide further information on liver status and if it is changing in response to transfusion or administration of the study drug. |
| Assessment of Immune Status | Blood samples are obtained every 3 to 6 hours before during and after blood transfsuion until subject is discharged Total time is up to 24 hour | The number of white blood cells is counted in each blood sample. White blood cells (also called leukocytes) are an important measure of how the immune system is working and if it is changing in response to transfusion or administration of the study drug. leukocytes - reported as cell counts |
Countries
United States
Contacts
Primary ContactJames D Reynolds, PhD
Backup ContactSindhuja Senigarapu, MD
Outcome results
None listed