Cardiac remodeling and genic changes induced by LPS: RNAi for terapeuctic use in heart dysfunction

Abstract

In 2003 Brazilian Health System spend about R$ 17,34 billions in Intensive Care Medicine, it represents 30 to 35% of total health budget. Sepsis is the main cause of costs in public and private health system. Severe sepsis and septic shock present mortality rate of 40 a 60%. In the last two decades the numbers of sepsis mortality has not been changed, in spite development of new antibiotics and new procedures for intensive care.Septic heart function has been studied in many works, however, for a long time was thought that heart was one of last organs damage by sepsis. In a recent study from our group (in press in Critical Care Medicine ) we showed a correlation among troponin, stroke work index and poly(ADP ribose) polimerase activation, a signal of severe oxidative stress and futile energy expenditure leading to cell death. Also we observe an inflammatory infiltration and collagen deposition. Next we realize preliminary studies in rats, and we found cardiac dysfunction in the very initial endotoxemic process. In conclusion, during a septic shock there is na intense vasodilatation, so any other factor that add some reduction in oxygen delivery to tissues will imply in a vicious cicle with organ damage. In this scenario heart dysfunction can intensify a mortality rate. The main stein of this study is to characterize the pathophysiologic mechanisms of heart dysfunction for an appropriate therapeutic intervention. (AU)