Grant: Project Grant

Severe infection with systemic inflammation (ie sepsis) is a frequent cause of acute cardiovascular failure (CVF), for which no effective treatment exists. While loss of blood pressure contributes to sepsis-induced CVF, cardiac contractile dysfunction and cardiomyocyte injury also play important roles and are in fact believed to be important determinants of mortality. However, the underlying mechanisms remain unclear. In the present grant we focus on the notion that abnormalities at the level of mitochondria, the cellular powerhouses, are important sources of dysfunction/injury in the heart during sepsis, and thus potential targets for intervention. We will use a well establish model of sepsis in conjunction with several transgenic mouse models to pinpoint key mitochondrial abnormalities that precipitate cardiac failure and evaluate therapeutic interventions targeting these dysfunctions.