Myocardial gene reprogramming associated with a cardiac cross-resistant state induced by LPS preconditioning

Lipopolysaccharide (LPS) preconditioning induces cardiacresistance to subsequent LPS or ischemia. This study tested thehypothesis that resistance to LPS and resistance to ischemiaare two manifestations of cardiac cross-resistance which may involvereprogramming of cardiac gene expression. Rats were preconditioned witha single dose of LPS (0.5 mg/kg ip). Cardiac resistance to LPS wasexamined with a subsequent LPS challenge. Cardiac resistance toischemia was determined by subjecting hearts toischemia-reperfusion. Total RNA was extracted from myocardiumfor Northern analysis of mRNAs encoding protooncoproteins, antioxidantenzymes, and contractile protein isoforms. Rats preconditioned with LPS1-7 days earlier acquired cardiac resistance to endotoxemicdepression. This resistance temporally correlated with resistance toischemia. Pretreatment with cycloheximide (0.5 mg/kg ip)abolished resistance to both LPS and ischemia. LPSpreconditioning induced the expression of c-jun andc-fos mRNAs. LPS also transientlyincreased mRNAs encoding catalase and Mn-containing superoxidedismutase. The expression of both - and -myosin heavy chain mRNAswas upregulated, whereas the expression of cardiac -actin mRNA wassuppressed. We conclude that 1)LPS induces sustained cardiac resistance to both LPS and ischemia, 2) resistance toischemia and resistance to LPS seem to be two mechanisticallyindistinct components of cardiac cross-resistance, and3) the cardiac cross-resistance isassociated with reprogramming of myocardial gene expression.