title: Bradykinin and histamine generation with generalized enhancement of microvascular permeability in neonates, infants, and children undergoing cardiopulmonary bypass surgery.
abstract: OBJECTIVE
  To investigate whether generation and liberation of bradykinin and histamine contribute to generalized edema formation in pediatric cardiopulmonary bypass surgery.
  
  
  METHODS
  Prospective observational study.
  
  
  METHODS
  Pediatric heart surgery of a university hospital.
  
  
  METHODS
  Forty-one neonates, infants, and children undergoing cardiopulmonary bypass to correct congenital cardiac anomalies.
  
  
  METHODS
  Plasma concentrations of bradykinin and histamine were determined before, during, and after cardiopulmonary bypass. Fluid balance was evaluated by control of fluid intake and output.
  
  
  RESULTS
  The susceptibility to generalized edema formation increased significantly (r = -.457; p <.005) with decreasing age. Approximately three times higher plasma concentrations of bradykinin (p <.001) were found at the onset of anesthesia and during the total observation period in patients with a fluid retention of >6% of body weight compared with patients with a lower retention rate. Plasma bradykinin reached significantly (p <.01) higher peak concentrations of 237.9 +/- 58.6 fmol/mL during cardiopulmonary bypass and of 227.5 +/- 90.7 fmol/mL during the early postoperative period in patients with severe edema formation in contrast to only 86.6 +/- 10.9 and 65.5 +/- 26.8 fmol/mL in patients with minor fluid retention. A tendency (p =.06) to slightly increasing histamine concentrations from 2.07 +/- 0.13 nmol/L at baseline to 3.32 +/- 1.41 nmol/L during 90 mins of cardiopulmonary bypass was only observed in patients with high fluid retention.
  
  
  CONCLUSIONS
  Bradykinin seems to be essentially involved in the enhancement of microvascular permeability in pediatric cardiopulmonary bypass surgery, although a dominant causal role cannot be claimed by this study. Histamine, however, doesn't appear to play a major role and may only contribute as a cofactor. To what extent an increased expression of bradykinin-1 and bradykinin-2 receptors or a reduced potential of bradykinin-degrading enzymes is involved is the object of a further clinical study.
authors.affiliation: Department of Internal Medicine/Cardiology, Justus-Liebig-University of Giessen, Germany. heinz.neuhof@innere.med.uni-giessen.de
authors.forename: Christiane
authors.initials: C
authors.lastname: Neuhof
authors.forename: Olaf
authors.initials: O
authors.lastname: Walter
authors.forename: Friedhelm
authors.initials: F
authors.lastname: Dapper
authors.forename: Jürgen
authors.initials: J
authors.lastname: Bauer
authors.forename: Bernfried
authors.initials: B
authors.lastname: Zickmann
authors.forename: Edwin
authors.initials: E
authors.lastname: Fink
authors.forename: Harald
authors.initials: H
authors.lastname: Tillmanns
authors.forename: Heinz
authors.initials: H
authors.lastname: Neuhof
mesh_terms: D000328:Adult; D000367:Age Factors; D001920:Bradykinin / Q000097:blood / Q000502:physiology*; D002199:Capillary Permeability; D002315:Cardiopulmonary Bypass; D002648:Child; D002675:Child, Preschool; D003627:Data Interpretation, Statistical; D004487:Edema / Q000209:etiology* / Q000503:physiopathology; D006330:Heart Defects, Congenital / Q000601:surgery*; D006439:Hemodynamics; D006632:Histamine / Q000097:blood / Q000502:physiology*; D006801:Humans; D007231:Infant, Newborn; D008833:Microcirculation; D011183:Postoperative Complications / Q000209:etiology; D011184:Postoperative Period; D011446:Prospective Studies; D013997:Time Factors
chemical_list: D006632:Histamine; D001920:Bradykinin