Prevention of TNF alpha-associated myocardial dysfunction resulting from cardiopulmonary bypass and cardioplegic arrest by glucocorticoid treatment

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 (TNF alpha) expression. We investigated whether anti-inflammatory treatment prevents increased TNF alpha expression and myocardial dysfunction after CPB. Methods and 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 TNF alpha-plasma concentrations and left ventricular TNF alpha expression were analyzed. With unchanged coronary blood flow in both groups, a progressive toss 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 TNFa was increased at 8 h in PLA compared to MP (243 +/- 34 vs 90 +/- 34 pg/ml, p < 0.05). Myocardial TNF alpha was increased at 8 h after CPB compared to baseline and MP (p < 0.05). Myocardial TNF alpha immunostaining was more pronounced in PLA than in MP (p < 0.05), with TNF alpha-mRNA localization predominantly to cardiomyocytes. Conclusions: Methylprednisolone attenuates both systemic and myocardial TNF alpha increases and progressive myocardial dysfunction induced by cardiac surgery, suggesting a key rote for TNF alpha. (c) 2006 Elsevier B.V. All rights reserved.