title: Prevention of TNFalpha-associated myocardial dysfunction resulting from cardiopulmonary bypass and cardioplegic arrest by glucocorticoid treatment.
abstract: OBJECTIVE
  Cardiac surgery on cardiopulmonary bypass (CPB) results in progressive myocardial dysfunction, despite unimpaired coronary blood flow, and is associated with increased myocardial tumor necrosis factor-alpha (TNFalpha) expression. We investigated whether anti-inflammatory treatment prevents increased TNFalpha expression and myocardial dysfunction after CPB.
  
  
  RESULTS
  Baseline systemic hemodynamics, myocardial contractile function, aortic and coronary blood flow were measured in anesthetized pigs. Then, placebo (PLA; saline; n=7) or methylprednisolone (MP; 30 mg/kg; n=6) was infused intravenously and CPB was instituted. Global ischemia was induced for 10 min by aortic cross-clamping, followed by 1 h of cardioplegic cardiac arrest. After declamping and reperfusion, CPB was terminated after a total of 3 h. Measurements were repeated at 15 min, 4 h, and 8 h following termination of CPB. Systemic TNFalpha-plasma concentrations and left ventricular TNFalpha expression were analyzed. With unchanged coronary blood flow in both groups, a progressive loss of myocardial contractile function to 38+/-2% of baseline (p<0.01) and cardiac index to 48+/-6% of baseline (p<0.01) at 8 h after CPB in PLA was attenuated in MP (myocardial function: 72+/-3%, p<0.01 vs PLA; cardiac index: 78+/-6%, p<0.05 vs PLA). Systemic TNFalpha was increased at 8 h in PLA compared to MP (243+/-34 vs 90+/-34 pg/ml, p<0.05). Myocardial TNFalpha was increased at 8 h after CPB compared to baseline and MP (p<0.05). Myocardial TNFalpha immunostaining was more pronounced in PLA than in MP (p<0.05), with TNFalpha-mRNA localization predominantly to cardiomyocytes.
  
  
  CONCLUSIONS
  Methylprednisolone attenuates both systemic and myocardial TNFalpha increases and progressive myocardial dysfunction induced by cardiac surgery, suggesting a key role for TNFalpha.
authors.affiliation: Department of Thoracic and Cardiovascular Surgery, University of Göttingen, Germany. oliver@liakopoulos.de
authors.forename: Oliver J
authors.initials: OJ
authors.lastname: Liakopoulos
authors.forename: Nils
authors.initials: N
authors.lastname: Teucher
authors.forename: Christian
authors.initials: C
authors.lastname: Mühlfeld
authors.forename: Peter
authors.initials: P
authors.lastname: Middel
authors.forename: Gerd
authors.initials: G
authors.lastname: Heusch
authors.forename: Friedrich A
authors.initials: FA
authors.lastname: Schoendube
authors.forename: Hilmar
authors.initials: H
authors.lastname: Dörge
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000627:therapeutic use; D009202:Cardiomyopathies / Q000209:etiology / Q000503:physiopathology / Q000517:prevention & control*; D002315:Cardiopulmonary Bypass / Q000009:adverse effects*; D003326:Coronary Circulation / Q000187:drug effects; D005786:Gene Expression Regulation / Q000187:drug effects; D005938:Glucocorticoids / Q000627:therapeutic use*; D006324:Heart Arrest, Induced / Q000009:adverse effects*; D006439:Hemodynamics / Q000187:drug effects; D017403:In Situ Hybridization; D015850:Interleukin-6 / Q000097:blood; D008775:Methylprednisolone / Q000627:therapeutic use; D009200:Myocardial Contraction / Q000187:drug effects; D009206:Myocardium / Q000378:metabolism / Q000473:pathology; D012333:RNA, Messenger / Q000235:genetics; D013552:Swine; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000502:physiology
chemical_list: D000893:Anti-Inflammatory Agents; D005938:Glucocorticoids; D015850:Interleukin-6; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha; D008775:Methylprednisolone