Preconditioning and cardiac surgery Jarle Vaage, MD, PhD, Guro Valen, MD, PhD  The Annals of Thoracic Surgery  Volume 75, Issue 2, Pages S709-S714 (February 2003) DOI: 10.1016/S0003-4975(02)04696-9

Fig 1 A schematic presentation of the events leading to preconditioning protection. Ischemic preconditioning will elicit release of trigger substances, which may be adenosine, bradykinin, prostacyclin, nitric oxide, or reactive oxygen species (ROS). These may act through G-protein coupled membrane receptors or directly cause activation of protein kinases where protein kinase C, mitogen activated kinases, as well as tyrosine kinases have been indicated to be involved. Phosphorylated protein kinases may lead to the opening of mitochondrial KATP channels, which may be end effectors of organ protection. In models of delayed preconditioning it is likely that transcription factors such as nuclear factor kappa B (NFkB) are involved in the signaling. NFkB may translocate to the nucleus causing transcription of possible cardioprotective agents such as inducible nitric oxyde synthase, inducible cyclooxygenase (COX-2), or manganese superoxide dismutase (MnSOD). Furthermore, NFkB activation during preconditioning will increase IkB alpha, thus reducing NFkB activation during sustained ischemia and thus reducing inflammation. A third possible involvement of NFkB is reduction of apoptosis during reperfusion through increasing the antiapoptotic factors inhibitor of apoptosis 1 (IAP-1) or Bcl2. Heat shock proteins have their own regulation but do influence NFkB activation. The Annals of Thoracic Surgery 2003 75, S709-S714DOI: (10.1016/S0003-4975(02)04696-9)