Myocardial dysfunction in septic shock: Basic mechanisms and emerging concepts

There is growing evidence that myocardial dysfunction in septic shock is induced by mediators of the systemic inflammatory response syndrome, in particular by cytokines such as tissue necrosis factor-α (TNF-α) and interleukin-1 (IL-1). TNF-α produces an immediate negative inotropic effect by alteration in intracellular calcium homeostasis. Longer term effects of TNF-α and IL-1 may involve increased expression of NO synthase and decreased responsiveness of β-adrenergic stimulation. Most recently, strategies have been formulated to try and inhibit or attenuate toxic effects of TNF-α and IL-1; this has included the use of anti-TNF-α antibodies, soluble receptors for TNF-α, and recombinant IL-1 receptor antagonists.