Cardiopulmonary Bypass Induced Red Blood Cell Lysis
Study Details
Study Description
Brief Summary
Studying the dynamics of red blood cell lysis, pfH, protective proteins and organ injury, limits will be set for safe levels of pfH following the use of CPB. These results will be compared to existing laboratory-based methods for determining red blood cell damage to predict CPB assist device safety. Further, results from the studies described in this proposal will help develop therapeutic strategies to benefit patients by early detection of pfH and clearance protein levels that occur during CPB.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Detailed Description
Cost estimates for brain, lung, cardiac, and kidney complications following complex cardiac surgeries that require a medical assist device to by-pass the heart and lungs (cardiopulmonary bypass, CPB) is estimated to cost $80 million per individual states in the US over a ten-year period. These extra costs represent a significant burden on the healthcare system but could be reduced by understanding how medical assist devices lead to organ injury associated with complex cardiac surgeries. The primary goals of this research are to (1) understand how hemoglobin released into plasma (pfH) from damaged red blood cells that passage through CPB contributes to organ injury. (2) Determine the amount of pfH necessary to cause organ injury. (3) Determine the concentration changes in protective proteins (called haptoglobin, hemopexin and transferrin) that remove pfH and its degradation products from the circulation. (4) Design a computer-based model that will determine the levels of pfH and protective proteins to predict the potential for organ injury. By studying the dynamics of red blood cell lysis, pfH, protective proteins and organ injury limits will be set for safe levels of pfH following the use of CPB. These results will be compared to existing laboratory-based methods for determining red blood cell damage to predict CPB assist device safety. Further, results from the studies described in this proposal will help develop therapeutic strategies to benefit patients by early detection of pfH and clearance protein levels that occur during CPB. The primary goals of this research are to (1) understand how hemoglobin released into plasma (pfH) from damaged red blood cells that passage through CPB contributes to organ injury. (2) Determine the amount of pfH necessary to cause organ injury. (3) Determine the concentration changes in protective proteins (called haptoglobin, hemopexin and transferrin) that remove pfH and its degradation products from the circulation. (4) Design a computer-based model that will determine the levels of pfH and protective proteins to predict the potential for organ injury. By studying the dynamics of red blood cell lysis, pfH, protective proteins and organ injury limits will be set for safe levels of pfH following the use of CPB. These results will be compared to existing laboratory-based methods for determining red blood cell damage to predict CPB assist device safety. Further, results from the studies described in this proposal will help develop therapeutic strategies to benefit patients by early detection of pfH and clearance protein levels that occur during CPB.
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Cardiac Sugery Patients Requiring Cardiopulmonary >1hour Patients admitted for a complex cardiac surgery, heart valve replacement and/or CABG surgery requiring CPB >1hour |
Other: Blood and urine collection
No intervention - Biological specimen collection
|
Outcome Measures
Primary Outcome Measures
- Hemolysis [Change from baseline at hour 1 during procedure]
Change in Measure hemoglobin released into plasma (pfH), lactate dehydrogenase and iron
- Hemolysis [Change from baseline at hour 2 during procedure]
Change in Measure hemoglobin released into plasma (pfH), lactate dehydrogenase and iron
- Hemolysis [Change from baseline at hour 3 during procedure]
Change in Measure hemoglobin released into plasma (pfH), lactate dehydrogenase and iron
- Hemolysis [Change from baseline at hour 4 during procedure]
Change in Measure hemoglobin released into plasma (pfH), lactate dehydrogenase and iron etc. Change from Baseline at Hour 1 during procedure
- Hemolysis [Change from baseline at hour 4 post procedure]
Change in Measure hemoglobin released into plasma (pfH), lactate dehydrogenase and iron etc. Change from Baseline at Hour 1 during procedure
- Hemolysis [Change from baseline at hour 2 post procedure]
Change in Measure hemoglobin released into plasma (pfH), lactate dehydrogenase and iron etc. Change from Baseline at Hour 1 during procedure
- Hemolysis [Change from baseline at hour 24 post procedure]
Change in Measure hemoglobin released into plasma (pfH), lactate dehydrogenase and iron etc. Change from Baseline at Hour 1 during procedure
- Hemolysis [Change from baseline on day 2 post procedure]
Change in Measure hemoglobin released into plasma (pfH), lactate dehydrogenase and iron etc. Change from Baseline at Hour 1 during procedure
- Hemolysis [Change from baseline on day 3 post procedure]
Change in Measure hemoglobin released into plasma (pfH), lactate dehydrogenase and iron etc. Change from Baseline at Hour 1 during procedure
- Hemolysis [Change from baseline on day 4 post procedure]
Change in Measure hemoglobin released into plasma (pfH), lactate dehydrogenase and iron etc. Change from Baseline at Hour 1 during procedure
- Hemolysis [Change from baseline on day 5 post procedure]
Change in Measure hemoglobin released into plasma (pfH), lactate dehydrogenase and iron etc. Change from Baseline at Hour 1 during procedure
Secondary Outcome Measures
- Kidney injury [Change from baseline at hour 1 during procedure]
Change in creatinine, KIM-1 and NGAL
- Kidney injury [Change from baseline at hour 2 during procedure]
Change in creatinine, KIM-1 and NGAL
- Kidney injury [Change from baseline at hour 3 during procedure]
Change in creatinine, KIM-1 and NGAL
- Kidney injury [Change from baseline at hour 4 during procedure]
Change in creatinine, KIM-1 and NGAL
- Kidney injury [Change from baseline at hour 2 post procedure]
Change in creatinine, KIM-1 and NGAL
- Kidney injury [Change from baseline at hour 24 post procedure]
Change in creatinine, KIM-1 and NGAL
- Kidney injury [Change from baseline at 2 days post procedure]
Change in creatinine, KIM-1 and NGAL
- Kidney injury [Change from baseline at 3 days post procedure]
Change in creatinine, KIM-1 and NGAL
- Kidney injury [Change from baseline at 4 days post procedure]
Change in creatinine, KIM-1 and NGAL
- Kidney injury [Change from baseline at 5 days post procedure]
Change in creatinine, KIM-1 and NGAL
Other Outcome Measures
- Blood cell function [Change from baseline at hour 1 during procedure]
CBC and red blood cell deformability
- Blood cell function [Change from baseline at hour 2 during procedure]
CBC and red blood cell deformability
- Blood cell function [Change from baseline at hour 3 during procedure]
CBC and red blood cell deformability
- Blood cell function [Change from baseline at hour 4 during procedure]
CBC and red blood cell deformability
- Blood cell function [Change from baseline at hour 2 post procedure]
CBC and red blood cell deformability
- Blood cell function [Change from baseline at hour 24 post procedure]
CBC and red blood cell deformability
- Blood cell function [Change from baseline at day 2 post procedure]
CBC and red blood cell deformability
- Blood cell function [Change from baseline at day 3 post procedure]
CBC and red blood cell deformability
- Blood cell function [Change from baseline at day 4 post procedure]
CBC and red blood cell deformability
- Blood cell function [Change from baseline at day 5 post procedure]
CBC and red blood cell deformability
- Outcome Hemoglobin Clearance [Change from baseline at hour 1 during procedure]
Change in hemoglobin clearance measured by plasma haptoglobin and transferrin concentrations
- Outcome Hemoglobin Clearance [Change from baseline at hour 2 during procedure]
Change in hemoglobin clearance measured by plasma haptoglobin and transferrin concentrations
- Outcome Hemoglobin Clearance [Change from baseline at hour 3 during procedure]
Change in hemoglobin clearance measured by plasma haptoglobin and transferrin concentrations
- Outcome Hemoglobin Clearance [Change from baseline at hour 4 during procedure]
Change in hemoglobin clearance measured by plasma haptoglobin and transferrin concentrations
- Outcome Hemoglobin Clearance [Change from baseline at hour 2 post procedure]
Change in hemoglobin clearance measured by plasma haptoglobin and transferrin concentrations
- Outcome Hemoglobin Clearance [Change from baseline at hour 24 post procedure]
Change in hemoglobin clearance measured by plasma haptoglobin and transferrin concentrations
- Outcome Hemoglobin Clearance [Change from baseline at day 2 post procedure]
Change in hemoglobin clearance measured by plasma haptoglobin and transferrin concentrations
- Outcome Hemoglobin Clearance [Change from baseline at day 3 post procedure]
Change in hemoglobin clearance measured by plasma haptoglobin and transferrin concentrations
- Outcome Hemoglobin Clearance [Change from baseline at day 4 post procedure]
Change in hemoglobin clearance measured by plasma haptoglobin and transferrin concentrations
- Outcome Hemoglobin Clearance [Change from baseline at day 5 post procedure]
Change in hemoglobin clearance measured by plasma haptoglobin and transferrin concentrations
Eligibility Criteria
Criteria
Inclusion Criteria:
-
Admitted to UMMC for cardiac procedure
-
Age: >/=18 y.o TO 75 y.o.
-
Undergoing CPB >1hr for the following surgeries (a) complex cardiac surgery (b) heart valve replacement surgery OR (c) CABG surgery.
Exclusion Criteria:
-
Pregnant
-
Non English speaking
-
Unable to consent or have Legally Authorized Representative (LAR) assent to study
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Center for Blood Oxygen Transport and Hemostasis | Baltimore | Maryland | United States | 21201 |
Sponsors and Collaborators
- University of Maryland, Baltimore
- National Institutes of Health (NIH)
Investigators
- Principal Investigator: Paul Buehler, PhD, University of Maryland
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- HP-00094849