title: Pre-existing endothelial cell activation predicts vasoplegia after mitral valve surgery.
abstract: OBJECTIVE
  Post-cardiac surgery vasoplegia is a common complication of cardiac surgery, characterized by profound loss of systemic vascular resistance. This results in severe hypotension, high cardiac output and metabolic acidosis reflecting inadequate tissue perfusion. The pathophysiological mechanisms underlying this syndrome remain unknown. We hypothesized that this vasoplegia reflects endothelial dysfunction, either as pre-existing condition or as a consequence of the surgical procedure.
  
  
  METHODS
  To examine these mechanisms, six established and distinct markers of endothelial cell activation were measured pre- and perioperatively in patients undergoing mitral valve surgery. Arterial (radial artery) and myocardial venous blood samples (coronary sinus) were collected simultaneously over the reperfused heart at various time points during the first hour after reperfusion. Additional samples were collected at baseline (brachial vein) and 1 day post-reperfusion (radial artery). Post-cardiac surgery vasoplegia was defined as a mean arterial blood pressure of <60 mmHg, with a cardiac index of ≥2.2 l/min/m(2) treated with continuous intravenous administration of norepinephrine.
  
  
  RESULTS
  No myocardial release of endothelial cell activation markers was observed upon reperfusion in patients with vasoplegia (n = 15; mean age 71 years, 73% male). In contrast, in patients without vasoplegia (n = 24; mean age 64 years, 54% male), reperfusion was characterized by a myocardial release of three endothelial cell activation markers. Myocardial von Willebrand Factor propeptide, osteoprotegerin and interleukin-8 were increased 107% (P < 0.001), 106% (P = 0.02) and 116% (P = 0.009), respectively, compared with arterial levels upon reperfusion. Similar systemic levels of all markers were found upon reperfusion in both groups, except for 120% increased soluble P-selectin (sP-selectin) levels in vasoplegia patients (P = 0.03). Remarkably, postoperative vasoplegia was identified with baseline von Willebrand Factor propeptide levels with a cut-off value of 11.9 nM as well as with baseline sP-selectin levels with a cut-off value of 64.4 ng/ml.
  
  
  CONCLUSIONS
  Pre-existing endothelial cell activation, reflected by higher baseline von Willebrand Factor propeptide and sP-selectin levels, is a predisposing factor for post-cardiac surgery vasoplegia. The pre-existing endothelial cell activation may have resulted in desensibilization of endothelium in patients who develop vasoplegic syndrome, resulting in no myocardial release of endothelial cell activation markers upon reperfusion.
authors.affiliation: Department of Cardiothoracic Surgery, Leiden University Medical Center, Leiden, Netherlands. k.a.kortekaas@lumc.nl
authors.forename: Kirsten A
authors.initials: KA
authors.lastname: Kortekaas
authors.forename: Jan H N
authors.initials: JH
authors.lastname: Lindeman
authors.forename: Marlies E J
authors.initials: ME
authors.lastname: Reinders
authors.forename: Meindert
authors.initials: M
authors.lastname: Palmen
authors.forename: Robert J M
authors.initials: RJ
authors.lastname: Klautz
authors.forename: Philip G
authors.initials: PG
authors.lastname: de Groot
authors.forename: Mark
authors.initials: M
authors.lastname: Roest
mesh_terms: D000368:Aged; D019540:Area Under Curve; D062186:Arterial Pressure; D015415:Biomarkers / Q000097:blood; D006348:Cardiac Surgical Procedures / Q000009:adverse effects*; D002316:Cardiotonic Agents / Q000008:administration & dosage; D016009:Chi-Square Distribution; D042783:Endothelial Cells / Q000378:metabolism*; D005260:Female; D006801:Humans; D007262:Infusions, Intravenous; D008297:Male; D008875:Middle Aged; D008943:Mitral Valve / Q000378:metabolism / Q000601:surgery*; D019007:P-Selectin / Q000097:blood; D011446:Prospective Studies; D011498:Protein Precursors / Q000097:blood; D012372:ROC Curve; D012307:Risk Factors; D013997:Time Factors; D016896:Treatment Outcome; D015854:Up-Regulation; D014662:Vasoconstrictor Agents / Q000008:administration & dosage; D056987:Vasoplegia / Q000097:blood / Q000188:drug therapy / Q000209:etiology* / Q000503:physiopathology; D014841:von Willebrand Factor
chemical_list: D015415:Biomarkers; D002316:Cardiotonic Agents; D019007:P-Selectin; D011498:Protein Precursors; C546937:SELP protein, human; D014662:Vasoconstrictor Agents; D014841:von Willebrand Factor; C067003:von Willebrand factor propolypeptide
keywords: Endothelial cell activation; Surgery; Vasoplegia