Protective strategies against ischemic injury of the liver Nazia Selzner, Hannes Rudiger, Rolf Graf, Pierre-Alain Clavien  Gastroenterology  Volume 125, Issue 3, Pages 917-936 (September 2003) DOI: 10.1016/S0016-5085(03)01048-5

Figure 1 Representative transmission electron micrographs of rat livers preserved in cold Euro-Collins solution for 16 hours of preservation (nonviable condition) and/or reperfused for 1 hour in the IPRL model. (A) Cold-preserved liver after 16 hours of cold ischemia. Note the typical cold preservation injury with rounding and detachment of endothelial cells and disruption of the sinusoidal wall. (B) Liver preserved for 16 hours and reperfused for 1 hour. An apoptotic endothelial cell is shown with typical shrinkage and chromatine condensation in the nucleus. Note the presence of intact mitochondria and numerous vacuoles (arrow). (C) In the same group are numerous activated Kupffer cells with phagolysosomes containing apoptotic bodies. s, sinusoid; ec, endothelial cell; k, Kupffer cell; l, lymphocyte; h, hepatocyte; r, red blood cell; a, apoptotic bodies. Reprinted with permission of Clavien et al.3 and Gao et al.10 Gastroenterology 2003 125, 917-936DOI: (10.1016/S0016-5085(03)01048-5)

Figure 2 Electron micrograph representing warm injury in the mouse liver. Endothelial cell swelling accompanied by hepatocyte necrosis (nh) is observed. Accumulation of polymorphonuclear leukocytes (pmn) and platelets (plts) are present in the sinusoids. r, red blood cell. Gastroenterology 2003 125, 917-936DOI: (10.1016/S0016-5085(03)01048-5)

Figure 3 Mechanisms of warm ischemic injury. Major pathways include TNF-α-mediated apoptosis, dysregulation of ion distribution, and the generation of reactive oxygen intermediates (roi). Intracellular sodium accumulation is caused by a combination of blocking sodium efflux driven by the Na+/K+ adenosine triphosphatase and activation of sodium influx by the Na+/H+ exchanger. In the cold, similar factors from the sinusoidal lumen cause injury on SECs. After reperfusion and rewarming, these cells rapidly undergo apoptosis. Gastroenterology 2003 125, 917-936DOI: (10.1016/S0016-5085(03)01048-5)

Figure 4 Continuous ischemia is used to prevent bleeding during liver resection. Three different surgical strategies are shown. Ischemic periods are drawn in black, and reperfusion is drawn in white. Gastroenterology 2003 125, 917-936DOI: (10.1016/S0016-5085(03)01048-5)

Figure 5 The necroapoptosis hypothesis proposed by Lemasters.88 Gastroenterology 2003 125, 917-936DOI: (10.1016/S0016-5085(03)01048-5)