title: 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.
  
  
  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.affiliation: Department of Thoracic Surgery, Medical University Vienna, Vienna, Austria; Christian Doppler Laboratory for Cardiac and Thoracic Diagnosis and Regeneration, Vienna, Austria.
authors.forename: Lucian
authors.initials: L
authors.lastname: Beer
authors.affiliation: Department of Anesthesia, General Intensive Care and Pain Management, Medical University of Vienna, Vienna, Austria.
authors.forename: Joanna Maria
authors.initials: JM
authors.lastname: Warszawska
authors.affiliation: Department of Pulmonology, Landesklinikum Thermenregion Hochegg, Grimmenstein, Austria.
authors.forename: Peter
authors.initials: P
authors.lastname: Schenk
authors.affiliation: Department of Cardiac Surgery, Institute of Cardiology, Medical- and Health Science Centre of University of Debrecen, Debrecen, Hungary.
authors.forename: Tamás
authors.initials: T
authors.lastname: Debreceni
authors.affiliation: Department of Anesthesia, General Intensive Care and Pain Management, Medical University of Vienna, Vienna, Austria.
authors.forename: Martin
authors.initials: M
authors.lastname: Dworschak
authors.affiliation: Department of Anesthesia, General Intensive Care and Pain Management, Medical University of Vienna, Vienna, Austria.
authors.forename: Georg A
authors.initials: GA
authors.lastname: Roth
authors.affiliation: Department of Cardiac Surgery, Institute of Cardiology, Medical- and Health Science Centre of University of Debrecen, Debrecen, Hungary.
authors.forename: Tamás
authors.initials: T
authors.lastname: Szerafin
authors.affiliation: Department of Thoracic Surgery, Medical University Vienna, Vienna, Austria; Christian Doppler Laboratory for Cardiac and Thoracic Diagnosis and Regeneration, Vienna, Austria. Electronic address: hendrik.ankersmit@meduniwien.ac.at.
authors.forename: Hendrik Jan
authors.initials: HJ
authors.lastname: Ankersmit
mesh_terms: D000209:Acute-Phase Proteins; D000368:Aged; D000369:Aged, 80 and over; D002315:Cardiopulmonary Bypass; D005260:Female; D006801:Humans; D000071068:Lipocalin-2; D054834:Lipocalins / Q000097:blood*; D008297:Male; D020782:Matrix Metalloproteinases / Q000097:blood*; D008875:Middle Aged; D010100:Oxygen / Q000097:blood; D011518:Proto-Oncogene Proteins / Q000097:blood*; D012121:Respiration, Artificial; D019715:Tissue Inhibitor of Metalloproteinase-1 / Q000097:blood*
chemical_list: D000209:Acute-Phase Proteins; C489506:LCN2 protein, human; D000071068:Lipocalin-2; D054834:Lipocalins; D011518:Proto-Oncogene Proteins; C560822:TIMP1 protein, human; D019715:Tissue Inhibitor of Metalloproteinase-1; D020782:Matrix Metalloproteinases; D010100:Oxygen
keywords: Cardiopulmonary bypass; Lipocalin 2; Matrix metalloproteinases; Mechanical ventilation; Systemic lung injury