Gp. Eising et al., EFFECTS OF INDUCED TOLERANCE TO BACTERIAL LIPOPOLYSACCHARIDE ON MYOCARDIAL INFARCT SIZE IN RATS, Cardiovascular Research, 31(1), 1996, pp. 73-81
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.