EFFECTS OF INDUCED TOLERANCE TO BACTERIAL LIPOPOLYSACCHARIDE ON MYOCARDIAL INFARCT SIZE IN RATS

Objectives: Induced tolerance to bacterial lipopolysaccharide (LPS) by pretreatment with sublethal doses of LPS has been shown to reduce the inflammatory response of monocytes, circulating PMNs and PMN adhesion to endothelial cells in response to subsequent stimuli, and also to i ncrease cellular and organ tolerance to stress by other mechanisms. Th erefore, we undertook to determine whether or not LPS desensitization is associated with reduced myocardial infarct size at 3 days after rep erfusion following coronary occlusion. Methods: Rats were randomized t o either daily intraperitoneal LPS injections to provide LPS tolerance , or to equal volumes of saline (controls). In both groups at day 7 no ntransmural infarction was produced by a 45 min coronary occlusion fol lowed by 3 days of reperfusion during which LPS injections were contin ued. Histologic infarct size was assessed as percent of the left ventr icle and as a percent of the risk zone (determined by fluorescent micr ospheres). Results: Myocardial infarct size as percent of the left ven tricle and of the risk zone were significantly reduced in the LPS-tole rant group (n = 14) compared to control rats (n = 12), the latter bein g reduced by 37% (33.6 +/- 18.4 vs. 54.1 +/- 8.6% of the risk zone, P < 0.002). The percentages of activated circulating PMN after LPS desen sitization and saline pretreatment were not different prior to coronar y occlusion (at 7 days), but 3 days after coronary occlusion and reper fusion the percent of activated PMNs in the treated group was markedly reduced compared to controls (2.9 +/- 1.6 vs. 11.4 +/- 7.2%, respecti vely, P < 0.02). Conclusions: LPS desensitization in rats for 1 week p rior to coronary occlusion inhibited activation of circulating PMNs 3 days after reperfusion following 45 min of coronary occlusion. LPS als o is well-known to induce heat stress proteins and may affect other pr otective mechanisms. These actions are associated with a significant r eduction in myocardial infarct size in LPS-tolerant animals compared t o untreated controls.