Intraoperative ventilation strategy during cardiopulmonary bypass attenuates the release of matrix metalloproteinases and improves oxygenation.

Abstract

BACKGROUND:

Patients undergoing open heart surgery with cardiopulmonary bypass (CPB) often develop a systemic immune reaction, characterized by an increase of proinflammatory and anti-inflammatory mediators. We previously demonstrated that continued mechanical ventilation during CPB reduces this response. We hypothesized that this strategy may also impact on matrix metalloproteinase (MMP) release.

MATERIAL AND METHODS:

Thirty consecutive patients undergoing coronary artery bypass grafting with CPB were randomized into a ventilated (VG) (n = 15) and a standard non-ventilated group (NVG) (n = 15). Blood was collected at the beginning, at the end of surgery, and on the five consecutive days. MMPs, tissue inhibitor of matrix metalloproteinase 1 (TIMP-1), and lipocalin 2 (LCN2) were measured by enzyme-linked immunosorbent assay. Parameters of transpulmonary oxygen transport were assessed at different time points.

RESULTS:

MMP-8, MMP-9, and LCN2 were significantly lower at the end of surgery in VG compared with those in NVG patients (MMP-8 [ng/mL]: 7.1 [3.5] versus 12.5 [7.7], P = 0.02; MMP-9 [ng/mL]: 108 [42] versus 171 [98], P = 0.029; LCN2 [ng/mL]: 109 [42] versus 171 [98], P = 0.03). TIMP-1 concentrations were lower on postoperative day one, (TIMP-1 [ng/mL]: 174 [55] versus 273 [104], P = 0.003), whereas MMP-3 levels were lower on postoperative days four and five (MMP-3 [ng/mL]: 44 [17] versus 67 [35], P = 0.026). The arterial partial pressure of oxygen/fraction of inspired oxygen ratio was significantly higher in VG patients throughout the postoperative observation period, which did not affect the length of postoperative ventilatory support.

CONCLUSIONS:

Continued mechanical ventilation during CPB reduces serum levels of MMPs, their inhibitor TIMP-1 and LCN2, which preserves MMP-9 activity. The present study suggests that continued mechanical ventilation improves postoperative oxygenation and could potentially prevent aggravation of lung injury after CPB.

• Authors: Lucian Beer, Joanna Maria Warszawska, Peter Schenk, Tamás Debreceni, Martin Dworschak, Georg A Roth, Tamás Szerafin, Hendrik Jan Ankersmit
• Journal: The Journal of surgical research (J Surg Res) Vol. 195 Issue 1 Pg. 294-302 (May 01 2015) ISSN: 1095-8673 [Electronic] United States
• PMID: 25577145 (Publication Type: Journal Article, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2015 Elsevier Inc. All rights reserved.

Chemical References

• Acute-Phase Proteins
• LCN2 protein, human
• Lipocalin-2
• Lipocalins
• Proto-Oncogene Proteins
• TIMP1 protein, human
• Tissue Inhibitor of Metalloproteinase-1
• Matrix Metalloproteinases
• Oxygen

Topics

• Acute-Phase Proteins
• Aged
• Aged, 80 and over
• Cardiopulmonary Bypass
• Female
• Humans
• Lipocalin-2
• Lipocalins (blood)
• Male
• Matrix Metalloproteinases (blood)
• Middle Aged
• Oxygen (blood)
• Proto-Oncogene Proteins (blood)
• Respiration, Artificial
• Tissue Inhibitor of Metalloproteinase-1 (blood)