title: Prophylactic treatment with alkaline phosphatase in cardiac surgery induces endogenous alkaline phosphatase release.
abstract: BACKGROUND
  Laboratory and clinical data have implicated endotoxin as an important factor in the inflammatory response to cardiopulmonary bypass. We assessed the effects of the administration of bovine intestinal alkaline phosphatase (bIAP), an endotoxin detoxifier, on alkaline phosphatase levels in patients undergoing coronary artery bypass grafting.
  
  
  METHODS
  A total of 63 patients undergoing coronary artery bypass grafting were enrolled and prospectively randomized. Bovine intestinal alkaline phosphatase (n=32) or placebo (n=31) was administered as an intravenous bolus followed by continuous infusion for 36 hours. The primary endpoint was to evaluate alkaline phosphatase levels in both groups and to find out if administration of bIAP to patients undergoing CABG would lead to endogenous alkaline phosphatase release.
  
  
  RESULTS
  No significant adverse effects were identified in either group. In all the 32 patients of the bIAP-treated group, we found an initial rise of plasma alkaline phosphatase levels due to bolus administration (464.27±176.17 IU/L). A significant increase of plasma alkaline phosphatase at 4-6 hours postoperatively was observed (354.97±95.00 IU/L) as well. Using LHA inhibition, it was shown that this second peak was caused by the generation of tissue non specific alkaline phosphatase (TNSALP-type alkaline phosphatase).
  
  
  CONCLUSIONS
  Intravenous bolus administration plus 8 hours continuous infusion of alkaline phosphatase in patients undergoing coronary artery bypass grafting with cardiopulmonary bypass results in endogenous alkaline phosphatase release. This endogenous alkaline phosphatase may play a role in the immune defense system.
authors.affiliation: Department of Cardiothoracic Surgery, MUMC, Maastricht, The Netherlands.
authors.forename: Suzanne
authors.initials: S
authors.lastname: Kats
authors.forename: Ruud
authors.initials: R
authors.lastname: Brands
authors.forename: Mohamed A Soliman
authors.initials: MA
authors.lastname: Hamad
authors.forename: Willem
authors.initials: W
authors.lastname: Seinen
authors.forename: Volkher
authors.initials: V
authors.lastname: Scharnhorst
authors.forename: Raymond W
authors.initials: RW
authors.lastname: Wulkan
authors.forename: Jacques P
authors.initials: JP
authors.lastname: Schönberger
authors.forename: Wim van
authors.initials: Wv
authors.lastname: Oeveren
mesh_terms: D000368:Aged; D000469:Alkaline Phosphatase / Q000008:administration & dosage* / Q000097:blood; D002315:Cardiopulmonary Bypass / Q000009:adverse effects; D001026:Coronary Artery Bypass / Q000009:adverse effects; D004311:Double-Blind Method; D004334:Drug Administration Schedule; D005260:Female; D006801:Humans; D007113:Immunity, Innate; D007249:Inflammation / Q000209:etiology / Q000276:immunology / Q000517:prevention & control; D007262:Infusions, Intravenous; D007422:Intestines / Q000201:enzymology*; D008297:Male; D008875:Middle Aged; D009426:Netherlands; D011292:Premedication; D011446:Prospective Studies; D013997:Time Factors; D016896:Treatment Outcome; D015854:Up-Regulation
chemical_list: C548267:ALPL protein, human; D000469:Alkaline Phosphatase