Differential sensitivity to LPS-induced myocardial dysfunction in the isolated brown Norway and Dahl S rat hearts: roles of mitochondrial function, NF-κB activation, and TNF-α production. Shock 2012 Mar;37(3):325-32
Date
11/18/2011Pubmed ID
22089203Pubmed Central ID
PMC3288738DOI
10.1097/SHK.0b013e31823f146fScopus ID
2-s2.0-84857540652 (requires institutional sign-in at Scopus site) 17 CitationsAbstract
Recently, we reported that Brown Norway (BN) rats were more resistant to lipopolysaccharide (LPS)-induced myocardial dysfunction than Dahl S (SS) rats. This differential sensitivity was exemplified by reduced production of proinflammatory cytokines and diminished nuclear factor-κB pathway activation. To further clarify the mechanisms of different susceptibility of these two strains to endotoxin, this study was designed to examine the alterations of cardiac and mitochondrial bioenergetics, proinflammatory cytokines, and signaling pathways after hearts were isolated and exposed to LPS ex vivo. Isolated BN and SS hearts were perfused with LPS (4 μg/mL) for 30 min in the Langendorff preparation. Lipopolysaccharide depressed cardiac function as evident by reduced left ventricular developed pressure and decreased peak rate of contraction and relaxation in SS hearts but not in BN hearts. These findings are consistent with our previous in-vivo data. Under complex I substrates, a higher oxygen consumption and hydrogen peroxide (H2O2) production were observed in mitochondria from SS hearts than those from BN hearts. Lipopolysaccharide significantly increased H2O2 levels in both SS and BN heart mitochondria; however, the increase in oxygen consumption and H2O2 production in BN heart mitochondria was much lower than that in SS heart mitochondria. In addition, LPS significantly decreased complex I activity in SS hearts but not in BN hearts. Furthermore, LPS induced higher levels of tumor necrosis factor-α and increased phosphorylation of IκκB and p65 more in SS hearts than in BN hearts. Our results clearly demonstrate that less mitochondrial dysfunction combined with a reduced production of tumor necrosis factor-α and diminished activation of nuclear factor-κB are involved in the mechanisms by which isolated BN hearts were more resistant to LPS-induced myocardial dysfunction.
Author List
An J, Du J, Wei N, Guan T, Camara AK, Shi YAuthor
Amadou K. Camara PhD Professor in the Anesthesiology department at Medical College of WisconsinMESH terms used to index this publication - Major topics in bold
AnimalsElectron Transport Complex I
Electron Transport Complex II
Heart
Heart Failure
Hydrogen Peroxide
In Vitro Techniques
Interleukin-1beta
Interleukin-6
Lipopolysaccharides
Male
Mitochondria, Heart
Mitogen-Activated Protein Kinases
Myocardial Contraction
Myocardium
NF-kappa B
Oxygen Consumption
Perfusion
Rats
Rats, Inbred BN
Rats, Inbred Dahl
Tumor Necrosis Factor-alpha
