Mechanisms of cardiac depression caused by lipoteichoic acids from Staphylococcus aureus in isolated rat hearts

Article

关键词: NECROSIS-FACTOR-ALPHA;    NITRIC-OXIDE SYNTHASE;    FACTOR-KAPPA-B;    CORONARY VASOCONSTRICTION;    MYOCARDIAL DEPRESSION;    ESCHERICHIA-COLI;    CANINE MODEL;    ENDOTOXIN;    INDUCTION;    ACTIVATION;   

DOI  :  10.1161/CIRCULATIONAHA.104.503938

来源: SCIE

【 摘 要 】

Background - Lipoteichoic acid (LTA) represents a major virulence factor in gram-positive sepsis. Methods and Results - In the present study we perfused isolated rat hearts for 180 minutes with highly purified LTA from Staphylococcus aureus. A progressive decline of left ventricular contractile function paralleled by the expression of myocardial tumor necrosis factor-alpha(TNF-alpha) mRNA and protein as well as the release of TNF-alpha into the perfusate was observed in LTA-perfused hearts. Employment of an anti -TNF-alpha antibody completely prevented the loss in contractile function. When CD14, a prominent pathogen recognition receptor, was blocked by a specific antibody, induction of TNF-alpha mRNA and protein release as well as the associated cardiodepression was diminished in response to LTA. Synthesis of TNF-alpha protein was located to interstitial cells of LTA-challenged hearts as detected by immunohistochemistry. Besides progressive cardiodepression, coronary perfusion pressure (CPP) was moderately increased in LTA-perfused hearts. This was accompanied by the release of thromboxane A(2) ( TXA(2)) into the perfusate and the induction of cyclooxygenase ( Cox)- 2 mRNA and protein in the myocardium. Blocking of TXA2 by the nonspecific Cox inhibitor indomethacin, the thromboxane receptor antagonist daltroban, or the selective Cox-2 inhibitor NS-398 prevented the increase in CPP. Conclusions - LTA causes cardiac depression by activating myocardial TNF-alpha synthesis via CD14 and induces coronary vascular disturbances by activating Cox-2 - dependent TXA2 synthesis. These phenomena may contribute to cardiac depression in gram-positive sepsis.

【 授权许可】

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