Myocardial adaptation to ischaemic tolerance can be evoked by preceding episodes of ischaemia and reperfusion, i.e. ischaemic preconditioning, performed in the heart itself or in other organs for acute or delayed protection. Analogous protection may be evoked by a range of pharmacological agents, such as activators of G-protein coupled membrane receptors, i.e. adenosine and volatile anaesthetics. In addition, agents inducing a low-graded inflammation such as reactive oxygen species, lipopolysaccharides, or changes in oxygen tension evoke a similar response. The latter stimuli involve signaling through nuclear factor kappa B (NFkB) and tumour necrosis factor alpha. NFkB is a key factor in innate and adaptive immunity, and regulates hundreds of genes including cell survival programs as well as proinflammatory programs. In delayed models of protection, the mechanism of NFkB-induced protection may be through transcription and translation of cardioprotective genes. However, NFkB appears to be important also for immediate protection, in models where the time frame is insufficient for transcription and translation of new mediators. Possibly the importance of NFkB-mediated signaling in this context is through reduction of apoptosis, and/or through an induced inhibition of its own activation by increase of the inhibitory IkBalpha and thus a reduction of inflammation during subsequent reperfusion.

NFkB may represent a novel therapeutic target of preconditioning signaling. However, many questions remain to be addressed before we fully understand the short-term and long-term effects and thus may have the clinical possibility to exploit it through pharmacological agents.