Pathophysiology of cardiovascular dysfunction in sepsis

Abstract

### Key points Sepsis is a common condition with a high mortality, which can also lead to severe sepsis and shock. This review will look at the physiological disruption of the cardiovascular system and the reflexes which occur during sepsis. The host response to sepsis is controlled by inflammatory mediators, which transmit, amplify, and maintain the generation of the host response. A specific myocardial-depressant factor has been suggested for some time, but the concept of a single agent underestimates the complexity of the immune system in sepsis.1 ### Toll-like receptors These are intermediate signalling molecules, which respond to the inflammatory stimulus and lead to the release of tumour necrosis factor α (TNF-α). These receptors impair myocyte function in vitro . ### Cytokines The major pro-inflammatory mediators in sepsis are TNF-α, interleukin (IL) 1β, IL-6, and IL-8. They are secreted from macrophages and monocytes and are responsible for amplification of the septic cascade and have been demonstrated to cause fever, hypotension, and myocardial suppression. ### Nitric oxide Nitric oxide (NO) is secreted from the endothelium and is central to cardiovascular control in health. During sepsis, NO production is increased after activation of the endothelium by pro-inflammatory mediators, resulting in up-regulation of the enzyme inducible NO synthetase (iNOS). This inducible (pathological) NO is responsible for vasodilatation. It is also responsible for dysfunction of enzyme messenger systems associated with normal intracellular calcium homeostasis and the maintenance of reflexes. ### Oxidative stress Oxidative stress is a term …