Lipoteichoic acid induces delayed myocardial protection in isolated rat hearts: a comparison with endotoxin.
OBJECTIVE
Preconditioning with bacterial wall fragments lipopolysaccharide (LPS) or lipoteichoic acid (LTA) reduce myocardial infarct size after ischaemia and reperfusion (I/R) in rats. Preconditioning with LTA reduces neutrophil accumulation during reperfusion and thereby ameliorates one of myocardial reperfusion injury's most important mechanisms. In this study, we use an ex vivo model of regional myocardial I/R to investigate LTA versus LPS induced preconditioning in a system devoid of leukocytes.


METHODS
Rats were subjected to LTA or LPS with or without dexamethasone pre-treatment. Twenty-four hours after LTA or LPS challenge, hearts were removed and retrogradely perfused in a Langendorff set-up. Hearts underwent 20 min of regional ischaemia followed by 2 h of reperfusion. Ischaemic preconditioning (IPC) was performed as a positive control. Myocardial infarct size was determined as the primary end-point.


RESULTS
LTA and LPS preconditioning both lead to a marked reduction in infarct size similar to IPC, however, no significant differences were found between LTA and LPS. The reduction in infarct size was abrogated by dexamethasone pre-treatment.


CONCLUSIONS
We conclude that preconditioning with LTA and likewise with LPS confers myocardial protection in an ex vivo setting devoid of leukocytes. Dexamethasone inhibits preconditioning, suggesting that the underlying mechanism is dependent upon induction of a systemic inflammatory response to a LTA or LPS stimulus.
Schober
Patrick
P
Department of Anaesthesiology, VU University Medical Center, PO Box 7057, 1007 MB Amsterdam, The Netherlands.
Oprea
Guenther
G
Mersmann
Jan
J
Nebert
Antje
A
Zacharowski
Kai
K
Zacharowski
Paula A
PA
D000818:Animals; D000893:Anti-Inflammatory Agents / Q000627:therapeutic use; D003907:Dexamethasone / Q000627:therapeutic use; D004195:Disease Models, Animal; D004731:Endotoxins / Q000627:therapeutic use*; D019157:Ischemic Preconditioning, Myocardial / Q000379:methods*; D008070:Lipopolysaccharides / Q000627:therapeutic use*; D008297:Male; D009203:Myocardial Infarction / Q000473:pathology* / Q000517:prevention & control*; D009504:Neutrophils; D051381:Rats; D017208:Rats, Wistar; D018746:Systemic Inflammatory Response Syndrome / Q000517:prevention & control; D013682:Teichoic Acids / Q000627:therapeutic use*
D000893:Anti-Inflammatory Agents; D004731:Endotoxins; D008070:Lipopolysaccharides; D013682:Teichoic Acids; C009900:lipoteichoic acid; C044101:endotoxin, Escherichia coli; D003907:Dexamethasone