Carolina Rinse Solution—a New Strategy to Increase Survival Time After Orthotopic Liver Transplantation in the Rat

Gao, Wenshi; Takei, Yoshiyuki; Marzi, Ingo; Lindert, Kelly; Caldwell‐Kenkel, Jane C.; Currin, Robert T.; Tanaka, Yukio; Lemasters, John J.; Thurman, Ronald G.

doi:10.1097/00007890-199109000-00005

Cited by 108 publications

(57 citation statements)

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“…Therefore, the success of some treatments, aimed at improving survival after ORLT and extended cold ischemia in cold UW solution, may result from their action on the endotoxin-Kupffer cell relationship activated by prolonged warm intestinal ischemia, and not from the protection of livers from the cold ischemia/ reperfusion itself. 13,35,46,47 In conclusion, at odds with the current theories, preservation of rat livers in cold UW solution for 24 hours is not a severe condition leading to primary liver nonfunction, irrespective of the marked SEC alteration. Thus, longer preservation times should be used when studying the physiopathological mechanisms leading to primary liver nonfunction of the rat liver and certain therapeutic strategies aimed at improving SEC and hepatocyte viability under these conditions.…”

Section: Discussionmentioning

confidence: 72%

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Decreased survival in rat liver transplantation with extended cold preservation: Role of portal vein clamping time

Urata¹,

Nguyen²,

Brault³

et al. 1998

Hepatology

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Primary liver graft dysfunction is currently related to cold ischemia-reperfusion injury, although a wide survival range has been reported using 24-hour preservation in cold University of Wisconsin (UW) solution. We hypothesized that the portal vein clamping time (PVCT) played a more important role than cold preservation injury in the postoperative outcome. Rat liver transplantation was performed using different clamping times after 24-hour cold ischemia in the UW solution. Survival rates, plasma tumor necrosis factor (TNF), and nitrate/nitrite levels were examined. Subsequently, the effect of clamping time was evaluated on hepatocyte and sinusoidal endothelial cell (SEC) function using isolated perfused livers. Survival rate was directly related to clamping time length. Marked increases in TNF and nitrate/nitrite levels were found after surgery, particularly after long clamping times. In perfusion studies, the SEC function was already markedly altered after preservation alone and was not further modified by transplantation. By contrast, the hepatocyte function was moderately altered after transplantation, irrespective of clamping times, even when rats operated with long clamping times were in terminal conditions. In rats, 24-hour preservation in cold UW solution is not a severely compromising condition leading to primary liver nonfunction. Long PVCTs are associated with an endotoxemia-like syndrome more related to a warm intestinal ischemia than to cold ischemia injury of the liver. (HEPATOLOGY 1998;28:366-373.)The underlying mechanism of cold ischemia-reperfusion injury of the liver culminating in primary liver nonfunction is still poorly understood. It is currently hypothesized that Kupffer cell activation plays a causal role in cold ischemiareperfusion injury of the liver, precipitating sinusoidal endothelial cell (SEC) death, and leading to microcirculatory disturbances. [1][2][3][4][5][6][7] This hypothesis is based on experimental findings using mainly the orthotopic rat liver transplantation (ORLT) model, first described by Lee et al. 8 and subsequently modified by Kamada and Calne. 9 However, recent experimental reports have shown that, after ORLT following extended cold ischemia, the mortality of animals could not be related to the severity of SEC dysfunction. 10 Moreover, Imamura et al. 11 and Reinders et al. 12 have reported that the presence or absence of Kupffer cells did not modify the effect of 24-hour cold ischemia/ reperfusion using the isolated perfused rat liver model and/or the ORLT model.Indeed, the ORLT model has been widely used for studying cold ischemia-reperfusion injury of the liver, particularly the effects of various solutions and of different biochemical strategies aimed at protecting the transplanted liver. A large number of these studies used cold University of Wisconsin (UW) solution as the preservation solution and 24 hours as the preservation time, conditions considered severely compromising for the grafted rat liver. However, under these preservation conditions, reported su...

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Section: Discussionmentioning

confidence: 72%

“…After 20 minutes of equilibration, plasma samples were obtained at several time points (20,25,30,35, and 40 minutes). 14 C-TC plasma levels were determined in duplicate using a beta counter (Beckman, Montreal, Quebec, Canada).…”

Section: Assessment Of Tc Eliminationmentioning

confidence: 99%

Decreased survival in rat liver transplantation with extended cold preservation: Role of portal vein clamping time

Urata¹,

Nguyen²,

Brault³

et al. 1998

Hepatology

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“…Kupffer cell activation, which results in the release of eicosanoids, reactive oxygen intermediates (ROIs), and cytokines, 4 is implicated as a mediator of reperfusion injury in many, [5][6][7][8][9][10][11][12] but not all, 13 studies. Pretreatment with methyl palmitate inhibits Kupffer cell activation and improves transplant survival threefold.…”

confidence: 99%

“…6 Rinsing stored allografts with Carolina rinse solution reduces Kupffer cell activation and also improves graft survival. 5 Similarly, fasting of donor animals before liver explantation depresses Kupffer cell activation and improves graft survival. 9 Studies using gadolinium chloride (GdCl 3 ), a selective Kupffer cell toxicant, 14 further support a role for Kupffer cells in the induction of reperfusion injury.…”

confidence: 99%

Activation of nuclear factor-κB during orthotopic liver transplantation in rats is protective and does not require kupffer cells

et al. 1999

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“…Although studies enalapril may contribute considerably to the postreperfusion on modified flush solutions and pretreatment of recipients hemodynamic instability of recipients. In fact, mean arterial with oxygen free radical scavengers or calcium channel block-pressure in the enalapril group was significantly reduced ers have already proven to have favorable effects on early compared with untreated controls; however, prolonged perigraft function, [13][14][15][16] none of these has been introduced into ods of severe shock were never observed. Enalapril may have routine clinical practice.…”

Section: ) Inmentioning

confidence: 99%

Angiotensin-converting enzyme inhibition by enalapril: A novel approach to reduce ischemia/reperfusion damage after experimental liver transplantation

et al. 1997

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emia/reperfusion injury in clinical liver transplantaAngiotensin-converting enzyme (ACE) inhibitors tion. (HEPATOLOGY 1997; 25:648-651.) have proven to be effective in the reduction of ischemia/reperfusion damage after myocardial ischemia. Whether this favorable effect can be related to other models of ischemia and reperfusion has not After more than 20 years of clinical experience, liver transyet been investigated. Therefore, we studied in a plantation is an established treatment modality for end-stage model of syngeneic liver transplantation in the rat liver disease, acute liver failure, and selected hepatic maligthe effect of recipient enalapril treatment on post-nancies. 1,2 The timing of transplantation and selection of suitischemic liver injury. Untreated animals served as able donors and recipients are crucial cornerstones for a sucthe control group. Treatment with enalapril was cessful outcome of the costly procedure. In up to 22% of cases, started 5 minutes before reperfusion by intravenous primary graft dysfunction after transplantation is observed, infusion of enalapril at a dosage of 5 mg/kg/h. By initiating a cascade of severe postoperative complications means of in vivo microscopy, the sinusoidal perfusion with considerable impact on morbidity and mortality. 3 Pathorate and leukocyte adherence in sinusoids and post-physiologically, graft dysfunction is based on preexisting dosinusoidal venules were analyzed during 45 to 60 min-nor liver damage and insults from cold/warm ischemia and utes of reperfusion. Liver function was monitored by reperfusion. measuring bile output over a period of 60 minutes.In recent years, many attempts have been made to improve Analysis of coagulation factors (prothrombin time, organ preservation, e.g., to prolong the tolerable ischemic factor V, fibrinogen) and liver enzymes (alanine time, and to better protect the graft from both anoxic and transaminase [ALT], aspartate transaminase [AST]) oxygen free radical-mediated damage. Therapeutic strateserved for the evaluation of organ dysfunction and gies in recipients were aimed particularly at the reduction of damage secondary to ischemia/reperfusion injury. reperfusion injury mediated by oxygen free radicals, which The sinusoidal perfusion rate was significantly im-are generated with reoxygenation of the liver. Results in ani- first time that ACE inhibition in the liver recipient g body weight; recipients: 190-250 g) underwent orthotopic liver by enalapril attenuates hepatic ischemia/reperfusion transplantation according to the cuff technique described by Kamada damage after experimental liver transplantation. Our and Calne. 8 In contrast to Kamada's original technique, grafts were results may offer a novel approach to reduce isch-rearterialized and simultaneously reperfused by the portal and arterial route as described by Post et al. 9 Livers were preserved by retrograde aortal flush with University of Wisconsin solution and stored at 4ЊC for 24 hours. Before reperfusion, the grafts were flushed with 10 mL of Ringer's lactat...

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Carolina Rinse Solution—a New Strategy to Increase Survival Time After Orthotopic Liver Transplantation in the Rat

Cited by 108 publications

References 0 publications

Decreased survival in rat liver transplantation with extended cold preservation: Role of portal vein clamping time

Decreased survival in rat liver transplantation with extended cold preservation: Role of portal vein clamping time

Activation of nuclear factor-κB during orthotopic liver transplantation in rats is protective and does not require kupffer cells

Angiotensin-converting enzyme inhibition by enalapril: A novel approach to reduce ischemia/reperfusion damage after experimental liver transplantation

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