• Oliver J Liakopoulos, Nils Teucher, Christian Mühlfeld, Peter Middel, Gerd Heusch, Friedrich A Schoendube, and Hilmar Dörge.
• Department of Thoracic and Cardiovascular Surgery, University of Göttingen, Germany. oliver@liakopoulos.de
• Eur J Cardiothorac Surg. 2006 Aug 1; 30 (2): 263-70.

ObjectiveCardiac 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.Methods And ResultsBaseline 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.ConclusionsMethylprednisolone attenuates both systemic and myocardial TNFalpha increases and progressive myocardial dysfunction induced by cardiac surgery, suggesting a key role for TNFalpha.

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