Rt. Rowland et al., A SINGLE ENDOTOXIN CHALLENGE INDUCES DELAYED MYOCARDIAL PROTECTION AGAINST INFARCTION, The Journal of surgical research, 63(1), 1996, pp. 193-198
Sublethal endotoxemia attenuates cardiac functional injury from global
ischemia but it is unknown whether endotoxemia can protect myocardium
against infarction. Furthermore, increases in myocardial catalase and
heat shock protein (HSP) following endotoxemia have been associated w
ith cardiac ischemic protection. We therefore hypothesized that a 72-h
r pretreatment with endotoxin (ETX) would reduce myocardial tissue nec
rosis in association with augmented catalase activity and stress prote
in expression. Rabbits were treated with normal saline or lipopolysacc
haride (Salmonella typhimurium) at 10, 5, and 1 mu g/kg doses. Three d
ays after saline or ETX injection they were subjected to 45 min of cor
onary artery occlusion followed by 3 hr of reperfusion. Area of necros
is (tetrazolium staining) was normalized to anatomic risk zone size (E
vans blue staining). Catalase activity was measured by a standard assa
y and HSP 72 was assessed by immunohistochemistry. During regional isc
hemia and reperfusion there were no differences in heart rate or mean
arterial blood pressure between groups. ETX treated rabbits had the sa
me risk zone size as controls. Infarct size was reduced in the ETX tre
ated rabbits at the 10 and 5 mu g/kg doses compared with control rabbi
ts (17.5 +/- 1.5% and 22.2 +/- 3.1% vs 45.3 +/- 2.5%; P < 0.05) but no
protective effect was observed at the 1.0 mu g/kg dose (38.0 +/- 4.6%
; P > 0.05 vs control). Catalase activity was not different between co
ntrol and ETX (5 mu g/kg) treated groups (997.8 +/- 59.1 U/g vs 1099.6
+/- 69.3 U/g myocardium; P > 0.05) but endotoxin induced expression o
f myocardial HSP 72. We conclude that a single challenge with endotoxi
n can induce delayed myocardial protection against infarction in vivo.
This delayed cardioprotective response involves enhanced stress prote
in expression without changes in myocellular catalase activity. (C) 19
96 Academic Press, Inc.