Anti-Inflammatory Effects of Alkaline Phosphatase in Coronary Artery Bypass Surgery with Cardiopulmonary Bypass

Suzanne      Kats; Ruud      Brands; Willem      Seinen; Wilco      de Jager; Margreet   W.A.   Bekker; Mohamed   A.   Soliman Hamad; M.   Erwin   S.H. Tan; Jacques   P.A.M.   Schonberger

Abstract

Laboratory and clinical data have implicated endotoxin as an important factor in the inflammatory response to cardiopulmonary bypass. Alkaline phosphatase prevents endotoxin-induced systemic inflammation in animals and humans. We assessed the effects of the administration of bovine intestinal alkaline phosphatase on surgical complications in patients undergoing coronary artery bypass grafting. In a double blind, randomized, placebo-controlled study, a total of 63 patients undergoing coronary artery bypass grafting were enrolled. Bovine intestinal alkaline phosphatase or placebo was administered as an intravenous bolus followed by continuous infusion for 36 hours. The primary endpoint was reduction of post-surgical inflammation. No significant safety concerns were identified. The overall inflammatory response to coronary artery bypass grafting with cardiopulmonary bypass was low in both placebo and bovine intestinal alkaline phosphatase patient group. Five patients in the placebo group displayed a significant TNFα response followed by an increase in plasma levels of IL-6 and IL-8. Such a TNFα response was not observed in the bovine intestinal alkaline phosphatase group, suggesting anti-inflammatory activity of bovine intestinal alkaline phosphatase. Other variables related to systemic inflammation showed no statistically significant differences. Bovine intestinal alkaline phosphatase can be administered safely in an attempt to reduce the inflammatory response in coronary artery bypass grafting patients with a low to intermediate EuroSCORE. The anti-inflammatory effects might be more pronounced in patients developing more fulminant postoperative inflammatory responses. This will be investigated in a further trial with inclusion of patients undergoing complicated cardiac surgery, demanding extended cardiopulmonary bypass and aortic cross clamp time. In this review article some recent patents related to the field are also discussed.

Keywords: Cardiopulmonary bypass, inflammatory response, endotoxin, alkaline phosphatase, coronary artery bypass grafting

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