Lipoteichoic acid induces delayed protection in the rat heart - A comparison with endotoxin

Classic ischemic preconditioning transiently (30 to 120 minutes) protects t he myocardium against subsequent lethal ischemia/reperfusion injury. After dissipation of this acute protection, a second window of protection (SWOP) appears 12 to 24 hours later; this SWOP lasts up to 3 days. Several trigger s induce a SWOP, including brief repetitive cycles of coronary artery occlu sion, rapid ventricular Facing, stimulation of adenosine A, receptors, and administration of wall fragments of Gram-negative bacteria, such as lipopol ysaccharide (LPS), The aim of this study was to investigate whether lipotei choic acid (LTA), a cell wall fragment of Gram-positive bacteria, can induc e a SWOP in a rat model of left anterior descending coronary artery (LAD) o cclusion (25 minutes) and reperfusion (2 hours). Thus, 166 male Wistar rats were pretreated (2 to 24 hours) with saline, LTA (1 mg/kg IF), or LPS (1 m g/kg IF) and subjected to LAD occlusion/reperfusion. Pretreatment with LTA or LPS for 16 hours led to a substantial, approximate to 65%, reduction in infarct size and a reduction in the release of cardiac troponin T into the plasma. The dose of LTA used had no toxic effect ton any of the parameters studied), whereas the same dose of LPS caused a time-dependent activation o f the coagulation system and liver injury. By use of RNase protection assay s, it was determined that LPS caused a time-dependent induction of turner n ecrosis factsr-alpha, interleukin-1 beta, and manganese superoxide dismutas e mRNA content in the heart, whereas LTA failed to induce manganese superox ide dismutase, LPS also caused an upregulation of the expression of interce llular adhesion molecule-1 and P-selectin, whereas LTA downregulated these molecules and attenuated the accumulation of polymorphonuclear granulocytes caused by myocardial ischemia/reperfusion. This study demonstrates for the first time that pretreatment with LTA at 8 to 24 hours before myocardial i schemia significantly reduces (1) infarct size, (2) cardiac tropanin T, and (3) the histological signs of tissue injury in rats subjected to LAD occlu sion and reperfusion. The mechanism(s) underlying the observed cardioprotec tive effects of LTA warrants further investigation but is likely to be rela ted to its ability to inhibit the interactions between the coronary vascula r endothelium and polymorphonuclear granulocytes. Therefore, LTA represents a novel and promising agent capable of enhancing myocardial tolerance to i schemia/reperfusion injury.