title: Hemolysis during cardiac surgery is associated with increased intravascular nitric oxide consumption and perioperative kidney and intestinal tissue damage.
abstract: BACKGROUND
  Acute kidney injury (AKI) and intestinal injury negatively impact patient outcome after cardiac surgery. Enhanced nitric oxide (NO) consumption due to intraoperative intravascular hemolysis, may play an important role in this setting. This study investigated the impact of hemolysis on plasma NO consumption, AKI, and intestinal tissue damage, after cardiac surgery.
  
  
  METHODS
  Hemolysis (by plasma extracellular (free) hemoglobin; fHb), plasma NO-consumption, plasma fHb-binding capacity by haptoglobin (Hp), renal tubular injury (using urinary N-Acetyl-β-D-glucosaminidase; NAG), intestinal mucosal injury (through plasma intestinal fatty acid binding protein; IFABP), and AKI were studied in patients undergoing off-pump cardiac surgery (OPCAB, N = 7), on-pump coronary artery bypass grafting (CABG, N = 30), or combined CABG and valve surgery (CABG+Valve, N = 30).
  
  
  RESULTS
  FHb plasma levels and NO-consumption significantly increased, while plasma Hp concentrations significantly decreased in CABG and CABG+Valve patients (p < 0.0001) during surgery. The extent of hemolysis and NO-consumption correlated significantly (r (2) = 0.75, p < 0.0001). Also, NAG and IFABP increased in both groups (p < 0.0001, and p < 0.001, respectively), and both were significantly associated with hemolysis (R s = 0.70, p < 0.0001, and R s = 0.26, p = 0.04, respectively) and NO-consumption (Rs = 0.55, p = 0.002, and R s = 0.41, p = 0.03, respectively), also after multivariable logistic regression analysis. OPCAB patients did not show increased fHb, NO-consumption, NAG, or IFABP levels. Patients suffering from AKI (N = 9, 13.4%) displayed significantly higher fHb and NAG levels already during surgery compared to non-AKI patients.
  
  
  CONCLUSIONS
  Hemolysis appears to be an important contributor to postoperative kidney injury and intestinal mucosal damage, potentially by limiting NO-bioavailability. This observation offers a novel diagnostic and therapeutic target to improve patient outcome after cardiothoracic surgery.
authors.affiliation: Department of Surgery, Maastricht University Medical Center Maastricht, Netherlands ; NUTRIM School for Nutrition, Toxicology & Metabolism, Maastricht University Medical Center Maastricht, Netherlands.
authors.forename: Iris C
authors.initials: IC
authors.lastname: Vermeulen Windsant
authors.affiliation: Central Diagnostic Laboratory, Maastricht University Medical Center Maastricht, Netherlands.
authors.forename: Norbert C J
authors.initials: NC
authors.lastname: de Wit
authors.affiliation: Department of Pharmacology, Ribeirao Preto Medical School, University of Sao Paolo Ribeirao Preto, Brazil.
authors.forename: Jonas T C
authors.initials: JT
authors.lastname: Sertorio
authors.affiliation: Department of Surgery, Maastricht University Medical Center Maastricht, Netherlands ; NUTRIM School for Nutrition, Toxicology & Metabolism, Maastricht University Medical Center Maastricht, Netherlands.
authors.forename: Annemarie A
authors.initials: AA
authors.lastname: van Bijnen
authors.affiliation: Department of Extracorporeal Circulation, Maastricht University Medical Center Maastricht, Netherlands.
authors.forename: Yuri M
authors.initials: YM
authors.lastname: Ganushchak
authors.affiliation: Department of Anesthesiology, Maastricht University Medical Center Maastricht, Netherlands.
authors.forename: John H
authors.initials: JH
authors.lastname: Heijmans
authors.affiliation: Department of Pharmacology, Ribeirao Preto Medical School, University of Sao Paolo Ribeirao Preto, Brazil.
authors.forename: Jose E
authors.initials: JE
authors.lastname: Tanus-Santos
authors.affiliation: Department of Surgery, Maastricht University Medical Center Maastricht, Netherlands ; Cardiovascular Research Institute Maastricht, Maastricht University Medical Center Maastricht, Netherlands ; Department of Vascular Surgery, European Vascular Center Aachen-Maastricht, University Hospital Aachen Aachen, Germany.
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Jacobs
authors.affiliation: Cardiovascular Research Institute Maastricht, Maastricht University Medical Center Maastricht, Netherlands ; Department of Cardiothoracic Surgery, Maastricht University Medical Center Maastricht, Netherlands.
authors.forename: Jos G
authors.initials: JG
authors.lastname: Maessen
authors.affiliation: Department of Surgery, Maastricht University Medical Center Maastricht, Netherlands ; Central Diagnostic Laboratory, Maastricht University Medical Center Maastricht, Netherlands.
authors.forename: Wim A
authors.initials: WA
authors.lastname: Buurman
keywords: acute kidney injury; cardiopulmonary bypass; hemolysis; intestinal fatty acid binding protein; nitric oxide