A Single Endotoxin Challenge Induces Delayed Myocardial Protection against Infarction

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 with cardiac ischemic protection. We therefore hypothesized that a 72-hr pretreatment with endotoxin (ETX) would reduce myocardial tissue necrosis in association with augmented catalase activity and stress protein expression. Rabbits were treated with normal saline or lipopolysaccharide (Salmonella typhimurium) at 10, 5, and 1 μg/kg doses. Three days after saline or ETX injection they were subjected to 45 min of coronary artery occlusion followed by 3 hr of reperfusion. Area of necrosis (tetrazolium staining) was normalized to anatomic risk zone size (Evans blue staining). Catalase activity was measured by a standard assay and HSP 72 was assessed by immunohistochemistry. During regional ischemia and reperfusion there were no differences in heart rate or mean arterial blood pressure between groups. ETX treated rabbits had the same risk zone size as controls. Infarct size was reduced in the ETX treated rabbits at the 10 and 5 μg/kg doses compared with control rabbits (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 μg/kg dose (38.0 ± 4.6%;P> 0.05 vs control). Catalase activity was not different between control and ETX (5 μg/kg) treated groups (997.8 ± 59.1 U/g vs 1099.6 ± 69.3 U/g myocardium;P> 0.05) but endotoxin induced expression of myocardial HSP 72. We conclude that a single challenge with endotoxin can induce delayed myocardial protection against infarctionin vivo.This delayed cardioprotective response involves enhanced stress protein expression without changes in myocellular catalase activity.