Endotoxin induces a second window of protection in the rat heart as determined by using p-nitro-blue tetrazolium staining, cardiac troponin T release, and histology

Pretreatment of rats with small doses of lipopolysaccharide (LPS), eg, for 24 hours, attenuates the cardiac dysfunction caused by subsequent period of myocardial ischemia. This phenomenon of enhanced tolerance to an ischemic insult has been termed "second window of protection." Although the cardiopr otective effects of LPS were first reported in 1989, it is still unclear wh ether the observed attenuation by LPS of the ischemia-induced cardiac dysfu nction is indeed secondary to the protection of cardiac myocytes against is chemic cell injury and death. This study was designed to investigate the ef fects of "preconditioning" with LPS on cell injury caused by regional myoca rdial ischemia and reperfusion in the anesthetized rat. Thirty-five Wistar rats were subjected to 25 minutes occlusion of the left anterior descending coronary artery followed by 2 hours of reperfusion. Hemodynamic parameters were continuously recorded, and at the end of the experiments, infarct siz e (using p-nitro-blue tetrazolium staining), cardiac troponin T release, an d histological markers of cell injury and death were determined. In rats pr etreated with a bolus of saline (vehicle for LPS) 2 or 24 hours before left anterior descending coronary artery occlusion and reperfusion, the infarct size was 59+/-4% (2 hours saline-control, n=6) and 61+/-3% (24 hours salin e-control, n=6), respectively. Pretreatment of animals with a bolus of LPS (1 mg/kg IP) 24 hours before the onset of myocardial ischemia and reperfusi on reduced both infarct size (to 18+/-7%; P<0.05, n=6) as well as histologi cal signs of cell injury. Pretreatment (24 hours, as above) of rats with LP S also reduced the release of cardiac troponin T from 58+/-13 ng/mL (saline -control) to 16+/-9 ng/mL. In contrast, pretreatment of rats with LPS (2 ho urs, as above) did not affect infarct size (56+/-8%, n=6), cardiac troponin T release, or the histological parameters of cell injury. These data provi de the first conclusive evidence that pretreatment of rats with a bolus of LPS 24 hours before intervention reduces the cell injury and death caused b y a subsequent period of myocardial ischemia and reperfusion.