Cardiopulmonary Bypass Induced Red Blood Cell Lysis

Study Overview
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Brief Summary
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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.

Detailed Description
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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.

Official Title
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Extra-Cellular Hemoglobin, Organ Injury in Extended Cardiopulmonary Bypass

Conditions
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Cardiopulmonary Bypass, Cardiac Surgery, Kidney Injury, Acute

Intervention / Treatment
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* Other: Blood and urine collection


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Cardiac Sugery Patients Requiring Cardiopulmonary >1hour<br>Patients admitted for a complex cardiac surgery, heart valve replacement and/or CABG surgery requiring CPB >1hour | Other: Blood and urine collection<br>* No intervention - Biological specimen collection<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Hemolysis | Change in Measure hemoglobin released into plasma (pfH), lactate dehydrogenase and iron | Change from baseline at hour 1 during procedure | 
| Hemolysis | Change in Measure hemoglobin released into plasma (pfH), lactate dehydrogenase and iron | Change from baseline at hour 2 during procedure | 
| Hemolysis | Change in Measure hemoglobin released into plasma (pfH), lactate dehydrogenase and iron | Change from baseline at hour 3 during procedure | 
| Hemolysis | Change in Measure hemoglobin released into plasma (pfH), lactate dehydrogenase and iron etc. Change from Baseline at Hour 1 during procedure | Change from baseline at hour 4 during procedure | 
| Hemolysis | Change in Measure hemoglobin released into plasma (pfH), lactate dehydrogenase and iron etc. Change from Baseline at Hour 1 during procedure | Change from baseline at hour 4 post procedure | 
| Hemolysis | Change in Measure hemoglobin released into plasma (pfH), lactate dehydrogenase and iron etc. Change from Baseline at Hour 1 during procedure | Change from baseline at hour 2 post procedure | 
| Hemolysis | Change in Measure hemoglobin released into plasma (pfH), lactate dehydrogenase and iron etc. Change from Baseline at Hour 1 during procedure | Change from baseline at hour 24 post procedure | 
| Hemolysis | Change in Measure hemoglobin released into plasma (pfH), lactate dehydrogenase and iron etc. Change from Baseline at Hour 1 during procedure | Change from baseline on day 2 post procedure | 
| Hemolysis | Change in Measure hemoglobin released into plasma (pfH), lactate dehydrogenase and iron etc. Change from Baseline at Hour 1 during procedure | Change from baseline on day 3 post procedure | 
| Hemolysis | Change in Measure hemoglobin released into plasma (pfH), lactate dehydrogenase and iron etc. Change from Baseline at Hour 1 during procedure | Change from baseline on day 4 post procedure | 
| Hemolysis | Change in Measure hemoglobin released into plasma (pfH), lactate dehydrogenase and iron etc. Change from Baseline at Hour 1 during procedure | Change from baseline on day 5 post procedure | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Kidney injury | Change in creatinine, KIM-1 and NGAL | Change from baseline at hour 1 during procedure | 
| Kidney injury | Change in creatinine, KIM-1 and NGAL | Change from baseline at hour 2 during procedure | 
| Kidney injury | Change in creatinine, KIM-1 and NGAL | Change from baseline at hour 3 during procedure | 
| Kidney injury | Change in creatinine, KIM-1 and NGAL | Change from baseline at hour 4 during procedure | 
| Kidney injury | Change in creatinine, KIM-1 and NGAL | Change from baseline at hour 2 post procedure | 
| Kidney injury | Change in creatinine, KIM-1 and NGAL | Change from baseline at hour 24 post procedure | 
| Kidney injury | Change in creatinine, KIM-1 and NGAL | Change from baseline at 2 days post procedure | 
| Kidney injury | Change in creatinine, KIM-1 and NGAL | Change from baseline at 3 days post procedure | 
| Kidney injury | Change in creatinine, KIM-1 and NGAL | Change from baseline at 4 days post procedure | 
| Kidney injury | Change in creatinine, KIM-1 and NGAL | Change from baseline at 5 days post procedure |