TITLE

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

AUTHOR(S)
Liakopoulos, Oliver J.; Teucher, Nils; Mühlfeld, Christian; Middel, Peter; Heusch, Gerd; Schoendube, Friedrich A.; Dörge, Hilmar
PUB. DATE
August 2006
SOURCE
European Journal of Cardio-Thoracic Surgery;Aug2006, Vol. 30 Issue 2, p263
SOURCE TYPE
Academic Journal
DOC. TYPE
Article
ABSTRACT
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-α (TNFα) expression. We investigated whether anti-inflammatory treatment prevents increased TNFα 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; 30mg/kg; n =6) was infused intravenously and CPB was instituted. Global ischemia was induced for 10min by aortic cross-clamping, followed by 1h of cardioplegic cardiac arrest. After declamping and reperfusion, CPB was terminated after a total of 3h. Measurements were repeated at 15min, 4h, and 8h following termination of CPB. Systemic TNFα-plasma concentrations and left ventricular TNFα 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 8h 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 TNFα was increased at 8h in PLA compared to MP (243±34 vs 90±34pg/ml, p <0.05). Myocardial TNFα was increased at 8h after CPB compared to baseline and MP (p <0.05). Myocardial TNFα immunostaining was more pronounced in PLA than in MP (p <0.05), with TNFα-mRNA localization predominantly to cardiomyocytes. Conclusions: Methylprednisolone attenuates both systemic and myocardial TNFα increases and progressive myocardial dysfunction induced by cardiac surgery, suggesting a key role for TNFα.
ACCESSION #
21665222

 

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