Thromboxane A2 synthesis inhibitor OKY046 ameliorates vascular endothelial injury of pancreas graft during preservation by the two-layer UW solution/perfluorochemical method at 20°C

Matsumoto, Shinichi; Kuroda, Yoshikazu; Suzuki, Y; Ku, Yonson; Fujita, Hirofumi; Saitoh, Yoichi

doi:10.1016/s0041-1345(96)00595-7

Cited by 10 publications

(5 citation statements)

References 10 publications

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“…The donor characteristics of 18 processed retired breeders were not significantly different between the experimental groups with regard to the donor age, carcass, and pancreas weight (data not shown). The digestion parameters were almost similar in all experimental groups as reflected by the recirculation time of 23 (21–28), 26 (22–32), and 21 min (18–29) (NS) or the total dissociation time of 55 (48–64), 50 (48–53), and 47 min (35–56) (NS) as determined for pancreata either immediately processed or stored at 4°C or 20°C, respectively.…”

Section: Resultsmentioning

confidence: 86%

“…Another explanation for our conflicting results in terms of yield and posttransplant function of islets is the finding in dogs that pancreas oxygenation at 20°C has detrimental effects on the viability of endothelial cells resulting in failure of autotransplanted pancreata after 8 h of storage (28, 29). Because donor-derived intraislet endothelial cells seem to contribute significantly to islet revascularization in allogeneic and xenogeneic models, a temperature-induced deterioration of islet engraftment can not be excluded for pig-to-nude mouse transplantation (26, 31).…”

Section: Discussionmentioning

confidence: 95%

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Pig Pancreas Oxygenation at 20°C Increases Islet ATP Generation but Deteriorates Islet Function

et al. 2009

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Successful pancreas preservation during storage in oxygenated perfluorodecalin (PFD) is mainly related to oxidative ATP generation during storage. Increasing the storage temperature would accelerate this process essential for resuscitation of ischemically damaged pancreatic tissue. The present study aimed at comparing islet isolation outcome from adult pig pancreata preserved in oxygenated PFD by means of a one-layer method during storage on ice or at 20 degrees C. Resected pancreata were intraductally flushed with cold UW solution and promptly processed (n = 6) or stored for 3 h in continuously oxygenated PFD at 4 degrees C (n = 5) or 20 degrees C (n = 7). Prior to digestion-filtration pancreata were intraductally injected with UW supplemented with Serva collagenase NB8 and neutral protease. Islet quality assessment determined viability, glucose stimulation index, mitochondrial activity, intracellular ATP content, and transplant function in diabetic nude mice. Pancreata oxygenated for 3 h at 20 degrees C yielded islet numbers similar to organs oxygenated at 4 degrees C. Compared to a storage temperature of 20 degrees C, preservation at 4 degrees C reduced islet ATP content (p < 0.05) as well as islet viability (p < 0.05). Nevertheless, PFD storage at 20 degrees C decreased insulin response to glucose compared to unstored pancreata (p < 0.05). In contrast to unstored pancreata or cold-stored organs, transplantation of islets isolated after oxygenation at 20 degrees C was characterized by an early loss of transplant function in 50% of recipients (p < 0.05). The present study demonstrates that PFD storage at 20 degrees C enhances islet ATP synthesis within a short period of oxygenation but deteriorates islet function. We conclude that the present data reflect an equilibration between reduced depression of metabolic activity resulting in damage of islets and temperature-stimulated acceleration of ATP synthesis. Future studies are required to adjust the optimum storage temperature for pancreas oxygenation in different species.

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Section: Resultsmentioning

confidence: 86%

Section: Discussionmentioning

confidence: 95%

Pig Pancreas Oxygenation at 20°C Increases Islet ATP Generation but Deteriorates Islet Function

et al. 2009

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“…When those radicals overwhelm the scavenging mechanisms, chain reactions occur in cellular membranes, mostly by abstraction of hydrogen atoms from polyunsaturated fatty acids, thus resulting in widespread and self-sustaining lipid peroxidation primarily based on endothelial cell membrane [43]. It was also stressed that cycloxygenase metabolite, TXA 2 , plays a major role in reperfusion injury and the use of thromboxane synthetase inhibitors has been demonstrated to improve organ viability and cellular architecture in different organ systems [3,26,31,33,36]. Garvin et al [15] pointed out that after 48 h of hypothermic ischemia, treatment of the kidneys within 60 min of reperfusion with the thromboxane synthase inhibitor resulted in the reduction of TXB 2 synthesis.…”

Section: Discussionmentioning

confidence: 99%

The effects of thromboxane synthase inhibition on reperfusion injury and endothelin-1,2 levels in allograft kidney transplantation in rats

et al. 1998

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Thromboxane A2 is a proaggregative vasoconstrictor that is synthesized and released in reperfusion injury. We aimed to investigate the effects of thromboxane synthase inhibitor, UK 38485, on endothelin-1,2 (ET) response of the renal endothelium and lipid peroxidation and protein oxidation in the early period of kidney transplantation. Four groups (n=8 in group IV and n=10 in the others) [corrected] of Sprague-Dawley rats were designed as Group I (sham nephrectomy), Group II (autotransplantation), Group III (allotransplantation) and Group IV (allotransplantation group in which the allografts were perfused with UK 38485. All subjects underwent right nephrectomy after transplantation. The grafts were flushed with 4 ml of ice-cold Ringer's lactate and in Group IV 10 microg of UK 38485 was added into the solution for each kidney. In allotransplantation groups, the kidneys were harvested from allogeneic white Wistar albino rats. The kidney grafts were allowed 120 min of reperfusion after 40 min of cold ischemic period. ET-1,2 plasma concentrations in the renal vein blood and diene conjugates (DC), hydroxyalkanals (HAA), hydroxyalkenals (HAE) and malondialdehyde (MDA) levels as the products of lipid peroxidation, protein carbonyls and protein sulfhydryls as the indicators of protein oxidation were analyzed in kidney tissue. Plasma ET-1,2 concentrations increased significantly in Group II and Group III (P<0.01) when compared to Group I but decreased in Group IV in comparison with Group III (P<0.05). DC, HAA, HAE and MDA levels increased in Groups II and III (P<0.001). Significant protein oxidation occurred only in Group III (P<0.01). Perfusion of the allografts with UK 38485 prevented lipid peroxidation and protein oxidation in Group IV. Histopathological changes were mild in the last group. We concluded that, in kidney transplantation, local administration of UK 38485 has cytopreservative effects on the allografts and this effect can be related to ET-1,2 concentrations.

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“…This ATP is used to drive a sodium-potassium pump to maintain cell integrity; and thus, TLM prevents pancreas swelling more effectively than UW solution (22,56). Furthermore, TLM improves the viability of vascular endothelium and microcirculation (13,25,28). After pancreas transplantation and reperfusion, the level of pancreatic tissue ATP remains high and heat shock proteins are strongly expressed (6).…”

Section: Mechanisms Of the Tlmmentioning

confidence: 99%

Pancreas Preservation by the Two-Layer Method: Does it Have a Beneficial Effect Compared with Simple Preservation in University of Wisconsin Solution?

Noguchi¹,

Levy²,

Kobayashi

et al. 2009

Cell Transplant

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A large number of reports have shown that the two-layer method (TLM), which employs oxygenated perfluorochemical (PFC) and University of Wisconsin (UW) solution, is superior to simple cold storage in UW in islet transplantation. However, two recent large-scale studies showed no beneficial effect of TLM compared with UW storage in human islet transplantation. We reevaluated the effect of TLM by following three groups: group 1: UW simple storage; group 2: TLM performed by multiorgan procurement teams (not specialists of islet isolation); and group 3: TLM performed by specialists of islet isolation (Noguchi and Matsumoto). There were no significant differences between groups 1 and 2, whereas islet yields were significantly higher in group 3 compared with either group 1 or 2. Our data suggest that exact, complete performance of TLM could improve the outcome of islet isolation and transplantation. In this review, we describe the mechanisms of the TLM, the procedure of preoxygenated TLM, and the several possibilities for the reasons of the discrepancy.

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Thromboxane A2 synthesis inhibitor OKY046 ameliorates vascular endothelial injury of pancreas graft during preservation by the two-layer UW solution/perfluorochemical method at 20°C

Cited by 10 publications

References 10 publications

Pig Pancreas Oxygenation at 20°C Increases Islet ATP Generation but Deteriorates Islet Function

Pig Pancreas Oxygenation at 20°C Increases Islet ATP Generation but Deteriorates Islet Function

The effects of thromboxane synthase inhibition on reperfusion injury and endothelin-1,2 levels in allograft kidney transplantation in rats

Pancreas Preservation by the Two-Layer Method: Does it Have a Beneficial Effect Compared with Simple Preservation in University of Wisconsin Solution?

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