title: Timing of steroid treatment is important for cerebral protection during cardiopulmonary bypass and circulatory arrest: minimal protection of pump prime methylprednisolone.
abstract: OBJECTIVE
  The contact of cardiopulmonary bypass surface and patient's blood activates systemic inflammatory response which aggravates ischemia-reperfusion injury. This study evaluates the effects of cardiopulmonary bypass (CPB) and deep hypothermic circulatory arrest (DHCA) on cerebral protection using different steroid administration protocols.
  
  
  METHODS
  Eighteen (n=6/group) 4 week-old piglets were divided in three groups. Methylprednisolone (30 mg/kg) was administered intravenously 4 h prior to CPB in Group I, or added in pump prime in group II. Group III received no steroid. All animals were cooled to 15 degrees C followed by 100 min of DHCA, then rewarmed over 40 min and sacrificed 6 h after CPB. Post-operative weight gain, bioelectrical impedance, colloid oncotic pressure (COP) and interleukin-6 (IL-6) were evaluated. Determination of cerebral trypan blue and immunohistochemical assays of transforming growth factor (TGF)-beta1 and caspase-3 activities were performed.
  
  
  RESULTS
  Post-operative % weight gain (13.0+/-3.8 (I) versus 26.4+/-9.9 (II) versus 22.6+/-6.4 (III), P=0.02); % bioimpedance reduction (14.5+/-8.0 (I) versus 38.3+/-13.3 (II) versus 30.5+/-8.0 (III), P=0.003); mean COP (mmHg) (14.9+/-1.8 (I) versus 10.9+/-2.0 (II) versus 6.5+/-1.8 (III), P=0.0001) and systemic IL-6 levels (pg/ml) (208.2+/-353.0 (I) versus 1562.1+/-1111.4 (II) versus 1712.3+/-533.2 (III), P=0.01) were significantly different between the groups. Spectrophotometric analysis of cerebral trypan blue (ng/g dry weight) was significantly different between the groups (0.0053+/-0.0010 (I) versus 0.0096+/-0.0026 (II) versus 0.0090+/-0.0019 (III), P=0.004). TGF-beta1 scores were 3.3+/-0.8 (I) versus 1.5+/-0.8 (II) versus 1.5+/-0.5 (III), P<0.05, groups I versus II and I versus III. Remarkable perivascular caspase-3 activity was observed in groups II and III.
  
  
  CONCLUSIONS
  Different timing of steroid administration results in different inflammatory mediator response. Steroid in CPB prime is not significantly better than no steroid treatment, while systemic steroid pre-treatment significantly decreases systemic manifestation of inflammatory response and brain damage.
authors.affiliation: Division of Cardiovascular Surgery, The Montreal Children's Hospital, McGill University Health Center, Montreal, Quebec, Canada. dominique.shum-tim@muhc.mcgill.ca
authors.forename: Dominique
authors.initials: D
authors.lastname: Shum-Tim
authors.forename: Christo I
authors.initials: CI
authors.lastname: Tchervenkov
authors.forename: Eric
authors.initials: E
authors.lastname: Laliberté
authors.forename: Al-Maleek
authors.initials: AM
authors.lastname: Jamal
authors.forename: Toni
authors.initials: T
authors.lastname: Nimeh
authors.forename: Chwan-Yau
authors.initials: CY
authors.lastname: Luo
authors.forename: Bindu
authors.initials: B
authors.lastname: Bittira
authors.forename: Anie
authors.initials: A
authors.lastname: Philip
mesh_terms: D000818:Animals; D017209:Apoptosis; D015415:Biomarkers / Q000097:blood; D001921:Brain / Q000187:drug effects* / Q000473:pathology; D002315:Cardiopulmonary Bypass / Q000009:adverse effects*; D053148:Caspase 3; D020169:Caspases / Q000032:analysis; D004334:Drug Administration Schedule; D005938:Glucocorticoids / Q000008:administration & dosage*; D020925:Hypoxia-Ischemia, Brain / Q000097:blood / Q000517:prevention & control*; D015850:Interleukin-6 / Q000097:blood; D008775:Methylprednisolone / Q000008:administration & dosage*; D023421:Models, Animal; D011292:Premedication; D013552:Swine; D016212:Transforming Growth Factor beta / Q000032:analysis
chemical_list: D015415:Biomarkers; D005938:Glucocorticoids; D015850:Interleukin-6; D016212:Transforming Growth Factor beta; D053148:Caspase 3; D020169:Caspases; D008775:Methylprednisolone