1. Characterizing the Inflammatory Response to Cardiopulmonary Bypass in Children 
Deborah J. Kozik, DO, James S. Tweddell, MD 
The Annals of Thoracic Surgery 
Volume 81, Issue 6, Pages S2347-S2354 (June 2006)
DOI: /j.athoracsur
Copyright © 2006 The Society of Thoracic Surgeons Terms and Conditions

2. Fig 1
An overview of the inflammatory response to cardiopulmonary bypass. Cardiopulmonary bypass exposes the body to extreme, nonphysiologic conditions that initiates a global inflammatory response. Blood–artificial surface interaction results in activation of several amplifying protein cascade systems including those of the coagulation, fibrinolytic, kallikrein, and complement systems. Additional ischemia–reperfusion injury occurs as a result of the altered flow states and hypothermia. White blood cells, platelets, and endothelial cells are activated, leading to production of additional inflammatory mediators capable of further activation of humoral and cellular elements resulting in amplifying positive feedback loops. Ultimately capillary integrity is altered and multisystem organ dysfunction occurs. (IL = interleukin; TNF = tumor necrosis factor.)
The Annals of Thoracic Surgery  , S2347-S2354DOI: ( /j.athoracsur )
Copyright © 2006 The Society of Thoracic Surgeons Terms and Conditions

3. Fig 2
Contact of the blood with foreign surfaces results in production of kallikrein. Kallikrein enters into a positive feedback loop with factor XII, activating both the coagulation cascade and the fibrinolytic system. Kallikrein results in production of bradykinin. In addition kallikrein activates the renin–angiotensin system and complement cascades. (HMW = high-molecular-weight.) (Reprinted from Murkin JM. Cardiopulmonary bypass and the inflammatory response: a role for serine protease inhibitors? J Cardiothoracic Vasc Anesth 1997:11(Suppl 2):19–23, by permission of Elsevier Science, Inc.)
The Annals of Thoracic Surgery  , S2347-S2354DOI: ( /j.athoracsur )
Copyright © 2006 The Society of Thoracic Surgeons Terms and Conditions

4. Fig 3
Function of transcription factor nuclear factor kappa B (NF-κB). In the inactive state NF-κB is found in the cytoplasm of endothelial cells. With stimulation by a variety of agents, including proinflammatory cytokines and other mediators of inflammation, the inhibitory IκB subunit is phosphorylated and separates from the heterodimer. Nuclear factor kappa B then translocates to the nucleus, where it upregulates transcription of inflammatory genes including proinflammatory cytokines, adhesion molecules, and inducible nitric oxide synthase. These protein products are themselves activators of NF-κB, and this action results in a positive feedback loop. (Reprinted from [2] by permission of Cambridge University Press.)
The Annals of Thoracic Surgery  , S2347-S2354DOI: ( /j.athoracsur )
Copyright © 2006 The Society of Thoracic Surgeons Terms and Conditions