Cardioprotective effects of low dose bacterial lipopolysaccharide may not be directly associated with prostacyclin production

ABSTRACT

Sublethal dose of bacterial lipopolysaccharide (LPS) would induce protection against cardiac ischemic/ reperfusion (I/R) injury. This study examines the following areas 1) the temporal induction of the cardioprotection produced by LPS; and 2) the relations between a degree of protection and the myocardial prostacyclin (PGI2) production. Rats were administered LPS (2 mg/kg, i.v.), and hearts were removed 1, 4, 8, 14, 24, 48, 72, and 96 h later. Using Langendorff apparatus, haemodynamic differences during 25 min of global ischemia/30 min reperfusion were investigated. The concentration of PGI2 in aliquots of the coronary effluent was determined by radioimmunoassay as its stable hydrolysis product 6-keto-PGF1alpha and lactate dehydrogenase release were measured as an indicative of cellular injury. LPS-induced cardiac protection against I/R injury appeared 4 h after LPS treatment and remained until 96 h after treatment. PGI2 release increased 2-3 fold at the beginning of reperfusion compared to basal level except in hearts treated with LPS for 48 and 72 h. In hearts removed 48 and 72 h after LPS treatment, basal PGI2 Was increased. To determine the enzymatic step in relation to LPS-induced basal PGI2 production, we examined prostaglandin H synthase (PGHS) protein expression, a rate limiting enzyme of prostaglandin production, by using Western blot analysis. LPS increased PGHS protein expression in hearts at 24, 48, 72, 96 h after LPS treatment. Induction of PGHS expression appeared in both isotypes of PGHS, a constitutive PGHS-1 and an inducible PGHS-2. To identify the correlationship between PGI2 production and the cardioprotective effect against I/R injury, indomethacin was administered in vivo or in vitro. Indomethacin did not inhibit LPS-induced cardioprotection, which was not affected by the duration of LPS treatment. Taken together, our results suggest that PGI2 might not be the major endogenous mediator of LPS-induced cardioprotection.