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

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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; 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 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 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 TNFα was increased at 8 h in PLA compared to MP (243 ± 34 vs 90 ± 34 pg/ml, p ≪ 0.05). Myocardial TNFα was increased at 8 h 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.

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