Mechanisms of cardiac depression caused by lipoteichoic acids from Staphylococcus aureus in isolated rat hearts.
BACKGROUND
Lipoteichoic acid (LTA) represents a major virulence factor in gram-positive sepsis.


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 A2 (TXA2) 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.
Grandel
Ulrich
U
Department of Internal Medicine, Justus Liebig University, Giessen, Germany.
Hopf
Michael
M
Buerke
Michael
M
Hattar
Katja
K
Heep
Martina
M
Fink
Ludger
L
Bohle
Rainer M
RM
Morath
Siegfried
S
Hartung
Thomas
T
Pullamsetti
Soni
S
Schermuly
Ralph T
RT
Seeger
Werner
W
Grimminger
Friedrich
F
Sibelius
Ulf
U
D000818:Animals; D004195:Disease Models, Animal; D005786:Gene Expression Regulation; D006321:Heart / Q000382:microbiology*; D006333:Heart Failure / Q000139:chemically induced / Q000382:microbiology*; D066298:In Vitro Techniques; D008070:Lipopolysaccharides; D008297:Male; D012333:RNA, Messenger / Q000235:genetics; D051381:Rats; D017208:Rats, Wistar; D013211:Staphylococcus aureus / Q000502:physiology*; D013682:Teichoic Acids; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics
D008070:Lipopolysaccharides; D012333:RNA, Messenger; D013682:Teichoic Acids; D014409:Tumor Necrosis Factor-alpha; C009900:lipoteichoic acid