Postischemic liver damage in rats: Effect of some therapeutic interventions on survival rate.

Yamauchi, Hidemi; Baca, Ibo; Mittmann, U.; Geisen, H. P.; Salzer, M.

doi:10.1620/tjem.138.63

Cited by 16 publications

(16 citation statements)

References 15 publications

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“…This physiological derangement enables immediate breaching of pathogenic vectors (eg bacteria) across the intestinal barrier with the subsequent risk of higher mortality. 4 As shown in Figure 3, 80% of naive mice that underwent 30 min of total hepatic ischemia without any method of portosystemic shunting died within 24 h as a result of this procedure.…”

Section: Discussionmentioning

confidence: 97%

“…3 In contrast, THI in rodents has been shown to produce several pathologic events, including splanchnic congestion, severe intestinal ischemia, mesenteric congestion and systemic shock. 4 Consequently, these animals poorly tolerate even short periods of total hepatic ischemia. For example, 30 min of ischemia induces an immediate and delayed intestinal barrier failure, which results in significant increases in bacterial translocation and endotoxemia.…”

mentioning

confidence: 99%

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Splenic transposition is superior to caudal shunt as a model of murine total hepatic ischemia

Matsumoto

Efron

Tsujimoto

et al. 2005

Laboratory Investigation

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Murine total hepatic ischemia (THI) followed by reperfusion without shunting of the portal vein induces significant lethality in rodents due to intestinal congestion. Two methods have been promulgated to study THI and reperfusion in mice without intestinal congestion: subcutaneous splenic transposition which creates a portosystemic shunt via epigastric vessels, and a caudal shunt with 30% hepatectomy, which creates a portosystemic shunt via the small remnant of remaining caudal lobe. We compared outcome, inflammatory response and hepatic injury due to THI and reperfusion in these two models. Female C57BL/6 mice underwent ST, caudal shunt or no surgery prior to having 30 min of total hepatic ischemia followed by 60 min of reperfusion. Survival, surgical complications, serum AST/ALT and IL-6 were determined. Apoptotic and necrotic hepatocytes were identified by morphological criteria. Complication rates for the ST and caudal shunt procedures were 6.7 and 20%, respectively. Subsequent mortality rates following THI and 60 min reperfusion were 5.9 and 50% in mice with ST and caudal shunt, respectively. Both groups had elevated serum AST/ALT concentrations. However, in mice undergoing caudal shunt, AST/ALT levels were also significantly increased even without THI. The number of apoptotic hepatocytes after THI and reperfusion in mice following caudal shunt was significantly higher compared with those of ST (Po0.001). Both ST and caudal shunt can be used in models of THI and reperfusion to prevent significant lethality due to intestinal congestion. However, ST is a simple, safe and suitable model, whereas caudal shunt requires manipulation of the liver, and is associated with significant hepatic injury and morbidity. Keywords: intestinal congestion; mouse; portal hypertension; splenic transposition; total hepatic ischemia and reperfusion Total hepatic ischemia (THI) and reperfusion injury are inevitable consequences of various surgical maneuvers that occur during hepatobiliary surgery, liver transplantation and hepatic trauma surgery. 1 Models of hepatic warm ischemia in rodents have been instrumental in elucidating mechanisms of injury during liver transplantation and hepatic ischemic/reperfusion injury.In humans and primates, occlusion of the hepatoduodenal ligament (containing the portal vein, hepatic artery and the common bile duct) is well tolerated because of a more efficient portosystemic collateral network through which splanchnic blood can return to the heart (Pringle maneuver 2 ). Interruption of blood flow to the normothermic liver is safe for at least 60 min even without a venous bypass to decompress the vasculature proximal to the occlusion. 3 In contrast, THI in rodents has been shown to produce several pathologic events, including splanchnic congestion, severe intestinal ischemia, mesenteric congestion and systemic shock. 4 Consequently, these animals poorly tolerate even short periods of total hepatic ischemia. For example, 30 min of ischemia induces an immediate and delayed intestinal barrier failure, w...

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Section: Discussionmentioning

confidence: 97%

mentioning

confidence: 99%

Splenic transposition is superior to caudal shunt as a model of murine total hepatic ischemia

Matsumoto

Efron

Tsujimoto

et al. 2005

Laboratory Investigation

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“…In order to minimize these factors in ischemia/reperfusion injury (IRI) animal studies, technically demanding and unphysiological portocaval shunt models have been developed [9,10] . Another way to reduce the pooling of intestinal blood is to induce partial ischemia, a model often used in rats [8,[12][13][14] . Since many of the metabolic events in IRI are difficult to detect systemically, tissue biopsies are needed to detect and characterize cellular injury.…”

Section: Introductionmentioning

confidence: 99%

Segmental Ischemia of the Liver – Microdialysis in a Novel Porcine Model

et al. 2009

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Background: Segmental liver ischemia is often used in rodents to study ischemia and reperfusion injuries (IRI). There are no reports of protocols using segmental ischemia in porcine models. Microdialysis (MD) provides the opportunity to study local effects of IRI in vivo. Methods: Eight pigs received an MD catheter placed in liver segments IV and V, respectively. All circulation to segment IV was stopped for 80 min, and reperfusion was followed for 240 min. Results: During ischemia the levels of lactate, glycerol and glucose increased 3-fold (p < 0.001), 40-fold (p < 0.001) and 4-fold (p < 0.01), respectively, in the ischemic segment compared to the perfused segment, whereas the levels of pyruvate fell to a tenth of the preischemic level (p < 0.001). All values returned to baseline after reperfusion. Serum levels of aspartate aminotransferase increased (p < 0.05). Polymorphonuclear cells increased in both segments, although the density was significantly higher in segment IV. Conclusion: Clamping of one liver segment in pigs is a simple, stable and reproducible model to study IRI with minimal systemic effects. MD revealed no signs of anaerobic metabolism in the perfused segment but still there was an increase in the number of polymorphonuclear neutrophils in this segment, although it was lower than that in the ischemic segment.

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“…To avoid splanchnic congestion, many experimental researchers have recently used a model of a partial selective hepatic ischemia of the left lateral and median lobes followed by a resection of the nonischemic right lobe [30,31] . It is clear that the Pringle maneuver induces severer splanchnic congestion and shock in rats than in humans [32] . In addition, IR of the intestine is known to induce remote microcirculatory dysfunction in the liver, probably due to the translation of inflammatory mediators and blood cells [33,34] .…”

Section: Discussionmentioning

confidence: 99%

Modification of the Hepatic Mitochondrial Proteome in Response to Ischemic Preconditioning following Ischemia-Reperfusion Injury of the Rat Liver

et al. 2007

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Background/Aim: Ischemic preconditioning (IPC) may reduce hepatic ischemia-reperfusion (IR) injury, but efficacy of IPC on mitochondrial proteome is not demonstrated. We investigated how IPC modifies the mitochondrial proteome after IR injury. Methods: Rats were subjected to 25 min of portal triad crossclamping (IR group, n = 8). In the IPC group (n = 8), 10 min of temporal portal triad clamping was performed before 25 min of portal clamping. Samples were obtained after 24 h. The mitochondrial inner-membrane potential was measured by the uptake of a lipophilic cationic carbocyanine probe and mitochondrial proteome was also investigated using 2-dimensional differential in-gel electrophoresis and liquid chromatography-tandem mass spectrometry. Results: Mitochondrial inner-membrane potential and glutathione were lower and serum transaminase was higher in the IPC group than in the IR group. The mitochondrial precursor of aldehyde dehydrogenase 2 and α-methylacyl-CoA-racemase were upregulated in the IPC group in comparison to the IR group. In contrast, protein disulfide-isomerase A3 precursor, 60S acid ribosomal protein P0, carbonic anhydrase 3 and superoxide dismutase were significantly more downregulated in the IPC group than in the IR group. Conclusions: A hepatoprotective effect by IPC was not shown; however, IPC caused significant up- or downregulation of several mitochondrial proteins.

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Postischemic liver damage in rats: Effect of some therapeutic interventions on survival rate.

Cited by 16 publications

References 15 publications

Splenic transposition is superior to caudal shunt as a model of murine total hepatic ischemia

Splenic transposition is superior to caudal shunt as a model of murine total hepatic ischemia

Segmental Ischemia of the Liver – Microdialysis in a Novel Porcine Model

Modification of the Hepatic Mitochondrial Proteome in Response to Ischemic Preconditioning following Ischemia-Reperfusion Injury of the Rat Liver

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