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The effects of leukocyte reduction on matrix metalloproteinase release in cardiopulmonary bypass
Jessica R Garner1, Robert E Stroud, Laura Finklea
1Division of Cardiothoracic Surgery, Cardiovascular Perfusion Program, Medical University of South Carolina, Charleston, South Carolina 29425, USA.
Abstract:
Matrix metalloproteinases (MMPs) are a family of enzymes responsible for degrading the extracellular matrix, a process that likely contributes to the development of altered vascular permeability. Past studies in patients undergoing cardiopulmonary bypass (CPB) have documented increased levels of MMPs with CPB. The purpose of this study was to evaluate the effect of leukocyte reduction on MMP release during CPB. Patients (n = 17) undergoing elective coronary revascularization requiring CPB were randomly assigned to either a leukocyte-reducing filter (LRF) group (n = 9) or the standard CPB circuit with no LRF (n = 8). White blood cell (WBC) counts, MMP-2, and MMP-9 levels were serially measured at baseline and up to 12 hours post CPB. MMP levels were measured by enzyme-linked immunoassay. ProMMP-2 levels increased in both the non-LRF and LRF groups but to a higher degree in the LRF group. ProMMP-9 levels increased by 40% in the non-LRF group. In contrast, proMMP-9 decreased by 30% in the LRF group. The addition of leukocyte-reducing filters in the CPB circuit attenuated the release of MMP-9 but increased release of MMP-2 post-CPB. Because MMPs can degrade the extracellular matrix, leading to increased vascular permeability, attenuation of MMPs may have decreased the local tissue injury known to occur as a result of these enzymes. However, future prospective studies to test this hypothesis directly are warranted.
Insights
Leukocyte reduction during cardiopulmonary bypass (CPB) attenuated matrix metalloproteinase-9 (MMP-9) release but increased MMP-2 release. This suggests leukocyte reduction may impact vascular permeability and tissue injury during CPB.
Area of Science:
- Cardiovascular Surgery
- Biochemistry
- Immunology
Background:
- Matrix metalloproteinases (MMPs) degrade extracellular matrix, influencing vascular permeability.
- Elevated MMP levels are observed in patients during cardiopulmonary bypass (CPB).
Purpose of the Study:
- To investigate the impact of leukocyte reduction on MMP-2 and MMP-9 release during CPB.
Main Methods:
- Seventeen patients undergoing coronary revascularization with CPB were randomized into leukocyte-reducing filter (LRF) and standard CPB groups.
- White blood cell (WBC) counts, MMP-2, and MMP-9 levels were measured serially up to 12 hours post-CPB.
Main Results:
- ProMMP-2 levels increased in both groups, with a higher increase in the LRF group.
- ProMMP-9 levels increased by 40% in the non-LRF group but decreased by 30% in the LRF group.
- Leukocyte reduction attenuated MMP-9 release while increasing MMP-2 release post-CPB.
Conclusions:
- Leukocyte reduction during CPB differentially affects MMP-2 and MMP-9 release.
- Attenuating MMP release via leukocyte reduction may mitigate local tissue injury, warranting further investigation.

