Beneficial Effects of Pentoxifylline Pretreatment in Non-Heart-Beating Donors in Rats

Astarcioglu, Huseyin; Karademir, Sedat; Ünek, Tarkan; Özer, Ender; S, Menekay; Coker, Allison; Astarcıoğlu, İbrahim

doi:10.1097/00007890-200001150-00017

Cited by 22 publications

(7 citation statements)

References 15 publications

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“…PTX has well established hemorheologic effects on red blood cells, leucocytes, and platelets, resulting in increased deformability and lower blood viscosity, possibly because of increased concentrations of cellular adenosine triphosphate, stabilizing the cellular membrane (28). Also, PTX improved the survival from 0% to 60% in a non-heart-beating rat liver transplantation model with 60 min warm ischemia plus 9 h cold ischemia (29). It is tempting to correlate these findings with a number of clinical observations showing increased portal pressure and possibly flow in smallfor-size OLT, with a beneficial effects of a variety of strategies decreasing portal pressure such as porto-systemic shunt (30).…”

Section: Discussionmentioning

confidence: 99%

“…Small-for-size liver transplantation was performed in wild-type mice and three treatment groups with appropriate controls. For the PTX group, PTX (100 mg͞kg) was dissolved in saline and injected s.c. into the donor and recipient animal 1 h before the operation, and then twice a day in the recipient for 5 days postoperatively (10,15,29). For the GdCl 3 group, GdCl 3 (10 mg͞kg) was injected i.p.…”

Section: Methodsmentioning

confidence: 99%

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Kupffer cell-dependent TNF-α signaling mediates injury in the arterialized small-for-size liver transplantation in the mouse

Tian¹,

Jochum

Georgiev³

et al. 2006

Proc. Natl. Acad. Sci. U.S.A.

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Implantation of small liver grafts causes liver injury and defective regeneration leading to graft failure. We investigated whether Kupffer cell-dependent TNF-␣ signaling contributes to this poor outcome. Partial 30% liver transplantation was performed in C57BL͞6 wild-type mice (control group), and in three groups with down-regulation of the TNF-␣ pathway: (i) TNF receptor 1 knockout [TNFR-1(؊͞؊)] mice, and mice pretreated with (ii) gadolinium chloride or (iii) pentoxifylline (PTX). Fifty-percent partial liver transplantation, a model associated with full recovery, and transplantation in IL-6 knockout [IL-6(؊͞؊)] mice were performed in some experiments. Graft injury, regeneration, portal flow, liver microcirculation, leukocyte adhesion, and animal survival were assessed. Animal survival rates were 14% in the control group vs. 43% in the gadolinium chloride group, 57% for the TNFR-1(؊͞؊) group, and 86% in the PTX group (P < 0.001). Markers of liver injury were reduced in all treated groups when compared with controls. Each treated group disclosed better portal flow and sinusoid perfusion, decreased leukocyte adherence, particularly in the PTX group. Liver regeneration occurred only in the treated groups. IL-6 and IL-10 levels were dramatically up-regulated (50؋) in the PTX group, and at lower levels in other experimental groups. The protective effect of PTX was lost in IL-6(؊͞؊) mice and protection was restored by a single dose of r-IL-6. In conclusion, interruption of TNF-␣ signaling or depletion of Kupffer cells improves survival after 30% liver transplantation, reduces liver injury, and enhances regeneration. The superior effects of PTX are mediated by IL-6.

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Section: Discussionmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Kupffer cell-dependent TNF-α signaling mediates injury in the arterialized small-for-size liver transplantation in the mouse

Tian¹,

Jochum

Georgiev³

et al. 2006

Proc. Natl. Acad. Sci. U.S.A.

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“…101 For NHBD, machine perfusion with the addition of pentoxifylline or arginine to perfusion solutions may also improve the quality of these grafts by reversing ischemic damage. 102,103 Hypernatremia was shown by the UCLA group to be one of five variables with prognostic value in predicting graft survival after transplantation. 28 The mechanism for the deleterious effect of elevated donor sodium on graft function is thought to be a result of cell swelling and exacerbation of reperfusion-mediated injury.…”

Section: Experimental Strategies For the Manipulation Of Marginal Donorsmentioning

confidence: 99%

The utility of marginal donors in liver transplantation

Busuttil¹

2003

Liver Transplantation

628

508

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The shortage of organs has led centers to expand their criteria for the acceptance of marginal donors. The combination of multiple marginal factors seems to be additive on graft injury. In this review, the utility of various marginal donors in patients requiring liver transplantation will be described, including older donors, steatotic livers, non-heart-beating donors, donors with viral hepatitis, and donors with malignancies. The pathophysiology of the marginal donor will be discussed, along with strategies for minimizing the ischemia reperfusion injury experienced by these organs. Finally, new strategies for improving the function of the marginal/expanded donor liver will be reviewed. (Liver Transpl 2003;9:651-663.)

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“…ATP, TNA (Total adenine nucleotides) and EC in all groups were decreased dramatically after warm ischemia injury [16,17] . ATP in WIT 10, 15, 20, 30, 60 min groups was decreased to 58.7%, 34.7%, 30.1%, 20.5%, 15.3%, and 9.3% of that in WIT 0 min group, respectively.…”

Section: Measurement Of Energy Metabolismmentioning

confidence: 99%

Safe time to warm ischemia and posttransplant survival of liver graft from non-heart-beating donors

He¹

2004

WJG

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AIM:To explore the dynamical changes of histology, histochemistry, energy metabolism, liver microcirculation, liver function and posttransplant survival of liver graft in rats under different warm ischemia times (WIT) and predict the maximum limitation of liver graft to warm ischemia. METHODS:According to WIT, the rats were randomized into 7 groups, with WIT of 0, 10, 15, 20, 30, 45, 60 min, respectively. The recovery changes of above-mentioned indices were observed or measured after liver transplantation. The graft survival and postoperative complications in each subgroup were analyzed. RESULTS:Liver graft injury was reversible and gradually resumed normal structure and function after reperfusion when WIT was less than 30 min. In terms of graft survival, there was no significant difference between subgroups within 30 min WIT. When WIT was prolonged to 45 min, the recipients' long-term survival was severely insulted, and both function and histological structure of liver graft developed irreversible damage when WIT was prolonged to 60 min. CONCLUSION:The present study indicates that rat liver graft can be safely subjected to warm ischemia within 30 min. The levels of ATP, energy charge, activities of glycogen, enzyme-histochemistry of liver graft and its recovery potency after reperfusion may serve as the important criteria to evaluate the quality of liver graft.

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Beneficial Effects of Pentoxifylline Pretreatment in Non-Heart-Beating Donors in Rats

Abstract: Donor and recipient PTX pretreatment significantly improves the viability of the liver grafts procured from NHBDs.

Cited by 22 publications

References 15 publications

Kupffer cell-dependent TNF-α signaling mediates injury in the arterialized small-for-size liver transplantation in the mouse

Kupffer cell-dependent TNF-α signaling mediates injury in the arterialized small-for-size liver transplantation in the mouse

The utility of marginal donors in liver transplantation

Safe time to warm ischemia and posttransplant survival of liver graft from non-heart-beating donors

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