Pathophysiological Appraisal of a Rat Model of Total Hepatic Ischemia with an Extracorporeal Portosystemic Shunt

Suzuki, Shohachi; Sakaguchi, Takanori; Mitsuoka, Hiroshi; Tsuchiya, Yasuo; Kojima, Yoshimitsu; Konno, Hiroyuki; Baba, Satoshi

doi:10.1006/jsre.1998.5419

Cited by 21 publications

(26 citation statements)

References 25 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…One model is the extracorporeal portosystemic shunt, 6 which uses a polyethylene tube with 1 mm inner diameter. Although this model reduced intestinal congestion following total hepatic ischemia and reperfusion in rats, 7 this technique is not feasible in mice due to their small size and vasculature. An alternative model is the subcutaneous ST method, 8 which requires that 3 weeks prior to hepatic ischemia, the mouse spleen is placed into a subcutaneous pouch in order to induce portosystemic collateral blood vessel synthesis.…”

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

View full text Add to dashboard Cite

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...

show abstract

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

View full text Add to dashboard Cite

show abstract

“…This lead to the impetus for various investigators to seek alternative methods to attenuate splanchnic venous stasis. Portacaval shunt, splenocaval shunt, extracorporeal PSS, and clamping of the celiac and superior mesenteric arteries are methods used for this purpose [3][4][5]9]. Suzuki et al [15] performed intracorporeal anastomosis between the splenic vein and inferior vena cava.…”

Section: Discussionmentioning

confidence: 99%

“…Two distinct modes of cell death, apoptosis and necrosis, are involved in the destruction of rat small intestinal epithelial cells following an ischemic insult [7,8]. Experimental models demonstrated that rats undergoing more than 30 min of portal vein occlusion showed necrosis in intestinal epithelial cells [1,3]. However, no data are available on the role of apoptotic damage in the rat small intestine during THI.…”

Section: Introductionmentioning

confidence: 98%

“…This maneuver reduces blood loss and operating time, but damage to the liver and other organs has been noted [1][2][3]. Prolonged clamping of the portal vein has been shown to induce different negative pathophysiological events, such as release of endotoxin, tumor necrosis factor (TNF), damage to the intestinal mucosa, and bacterial translocation [1,[3][4][5].…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Portosystemic Shunt Prevents Apoptosis in Rat Intestinal Mucosa Caused by Total Hepatic Ischemia

Bedirli

Şakrak²,

Soyuer³

et al. 2004

Eur Surg Res

View full text Add to dashboard Cite

Background: Prolonged splanchnic congestion due to total hepatic ischemia (THI) has been shown to induce damage to the intestinal mucosa. The present study was conducted to examine whether the protective effect of portosystemic shunt (PSS) can be seen on apoptosis of intestinal mucosa in a rat model of THI. Methods:Adult male Wistar rats were divided into the following 3 groups: control group; the THI group underwent THI for 30 min, and the PSS group was subjected to THI for 30 min with PSS. Rats were killed after 1, 2, and 6 h of reperfusion. For each time point, levels of serum liver enzymes, intestinal morphology, malondialdehyde (MDA) contents and DNA fragmentation in intestinal tissue were determined. In addition, the 7-day survival rate was measured. Results: The 7-day survival rate of THI group remained at 50%, whereas that of PSS group was significantly higher at 90% (p < 0.01). Serum AST and ALT levels of the THI and PSS groups rapidly increased after reperfusion, reaching peak values at 2 h. MDA levels after 1 and 2 h of reperfusion in the THI group were significantly increased as compared with the control group (p < 0.001). Increases in the percentage of fragmented DNA peaked 1 h after reperfusion in the THI group. PSS resulted in the reduction of DNA fragmentation and preserved the macroscopic and microscopic appearance of the intestinal mucosa. Conclusions: Splanchnic congestion due to portal occlusion increased apoptosis in the rat intestinal mucosa. PSS is very effective in counteracting the principal negative effects of total hepatic ischemia.

show abstract

“…Total hepatic ischemia has been shown to produce several pathological events, including splanchnic congestion, severe intestinal ischemia, mesenteric congestion, and systemic shock, thereby resulting in a high mortality rate (21,22,32,37). Furthermore, occlusion to all lobes of the liver causes venous congestion in the mesenteric bed and compromises the intestinal mucosa, resulting in bacterial translocation and onset of systemic inflammatory response syndrome (4,25).…”

Section: Technique Of Portal Triad Occlusionmentioning

confidence: 99%

Use of a hanging-weight system for liver ischemic preconditioning in mice

Hart

Much²,

Köhler³

et al. 2008

American Journal of Physiology-Gastrointestinal and Liver Physi

View full text Add to dashboard Cite

Hart ML, Much C, Kö hler D, Schittenhelm J, Gorzolla IC, Stahl GL, Eltzschig HK. Use of a hanging-weight system for liver ischemic preconditioning in mice. Am J Physiol Gastrointest Liver Physiol 294: G1431-G1440, 2008. First published April 24, 2008 doi:10.1152/ajpgi.00083.2008 represents a powerful experimental strategy to identify novel molecular targets to attenuate hepatic injury during ischemia. As a result, murine studies of hepatic IP have become an important field of research. However, murine IP is technically challenging, and experimental details can alter the results. Therefore, we systematically tested a novel model of hepatic IP by using a hanging-weight system for portal triad occlusion. This system has the benefit of applying intermittent hepatic ischemia and reperfusion without manipulation of a surgical clamp or suture, thus minimizing surgical trauma. Systematic evaluation of this model revealed a close correlation of hepatic ischemia time with liver damage as measured by alanine (ALT) and aspartate (AST) aminotransferase serum levels. Using different numbers of IP cycles and times intervals, we found optimal liver protection with four cycles of 3 min ischemia/3 min reperfusion as measured by ALT, AST, lactate dehydrogenase, and interleukin-6. Similarly, ischemiaassociated increases in hepatic infarct size, neutrophil infiltration, and histological injury were maximally attenuated with the above regimen. To demonstrate transcriptional consequences of liver IP, we isolated RNA from preconditioned liver and confirmed transcriptional modulation of known target genes (equilibrative nucleoside transporters, acute-phase complement genes). Taken together, these studies confirm highly reproducible liver injury and protection by IP when using the hanging-weight system for hepatic ischemia and intermittent reperfusion. Further studies of murine IP may consider this technique.

show abstract

Pathophysiological Appraisal of a Rat Model of Total Hepatic Ischemia with an Extracorporeal Portosystemic Shunt

Cited by 21 publications

References 25 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

Portosystemic Shunt Prevents Apoptosis in Rat Intestinal Mucosa Caused by Total Hepatic Ischemia

Use of a hanging-weight system for liver ischemic preconditioning in mice

Contact Info

Product

Resources

About