Effects of adenosine on ischaemia–reperfusion injury associated with rat pancreas transplantation

Pi, Felip; Badosa, Francisco; Solà, Anna; Catafau, J.R.; Xaus, Carme; Prats, Neus; Gelpí, E.; Hotter, Georgina

doi:10.1046/j.0007-1323.2001.01866.x

Cited by 11 publications

(7 citation statements)

References 35 publications

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“…The observed superior ATP level in UW‐preserved HLEC might have been caused by the presence of adenosine in this solution. Regarding the efficacy of adenosine to maintain a high intracellular ATP level during ischemia and reperfusion, our findings were in accordance with results from UW in liver and pancreas transplantation 28, 29. The immediate utilization and access of adenosine to maintain ATP in UW caused an extreme rise in the ATP level in comparison to the warm control with culture medium.…”

Section: Discussionsupporting

confidence: 88%

UW is superior to Celsior and HTK in the protection of human liver endothelial cells against preservation injury

Janssen

Broelsch

2004

Liver Transpl

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Celsior solution (CS), a new preservation solution in thoracic organ transplantation, was evaluated for its efficacy in cold preservation of human liver endothelial cells (HLEC) and was compared to University of Wisconsin solution (UW) and histidine-tryptophan-ketoglutarate solution (HTK, Custodiol). HLEC cultures were preserved at 4°C in CS, UW, and HTK, for 2, 6, 12, 24, and 48 hours, with 6 hours of reperfusion. Levels of lactate dehydrogenase (LDH), 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT), and adenosine 5-triphosphate (ATP) were measured after each interval of ischemia and the respective phase of reperfusion. Preservation injury of HLEC as measured by LDH release, intracellular ATP level, and MTT reduction were overall significantly (P < .01, P < .01, P < .05, respectively) lower in UW than in CS and HTK. CS demonstrates a modest superiority to HTK in HLEC preservation. Furthermore, cold preservation remains the main cause of preservation injury of HLEC regardless of the preservation solution used. Additionally, the maintenance of a high intracellular ATP level of HLEC after ischemia and reperfusion, as shown by UW, could be taken as a beneficial effect, particularly in long-term ischemia. In conclusion, our cell culture model reveals the order of efficacy to protect HLEC against preservation injury as: UW ӷ CS > HTK. (Liver

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Section: Discussionsupporting

confidence: 88%

UW is superior to Celsior and HTK in the protection of human liver endothelial cells against preservation injury

Janssen

Broelsch

2004

Liver Transpl

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“…Consequently, the high ATP level in UW-preserved HLECs was entirely caused by the adenosine provided in the solution. This interpretation of our data was supported by a rat pancreas transplantation study with UW which also ruled out endogenous adenosine as a significant factor in maintaining a high ATP level during ischemia [25].…”

Section: Discussionsupporting

confidence: 73%

Value of Energy Substrates in HTK and UW to Protect Human Liver Endothelial Cells against Ischemia and Reperfusion Injury

Janssen¹,

Janssen²,

Broelsch³

2004

Eur Surg Res

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Adenosine 5′-triphosphate (ATP) depletion is a major cause of cellular injury during ischemia and reperfusion in organ transplantation. Therefore, histidine-tryptophan-ketoglutarate solution (HTK; α-ketoglutarate) and University of Wisconsin solution (UW; adenosine) were supplied with energy substrates to achieve graft viability. Nevertheless, their efficacy for maintaining the ATP level, particularly in human liver endothelial cells, was uncertain. Furthermore, it is of interest whether a high ATP level is beneficial in human liver endothelial cell viability. We used human liver endothelial cells between the 3rd and 6th passages in a cell culture model. Human liver endothelial cells were exposed to hypothermic preservation (4°C) in HTK and UW for 2, 6, 12, 24 and 48 h with subsequent reperfusion of 6 h. ATP and lactate dehydrogenase (LDH) were measured after each interval. In comparison to HTK, UW demonstrates a statistically significantly higher level of ATP after each interval of ischemia (p < 0.001) and reperfusion (p < 0.002). Additionally, UW-preserved human liver endothelial cells exceed the ATP level of the warm control during all intervals of ischemia. The loss of cell viability (LDH) was statistically significantly higher after ischemia (p < 0.01) and reperfusion (p < 0.01) in HTK than in UW except after the interval of 48 h. In conclusion, adenosine was more effective than α-ketoglutarate in maintaining a high ATP level in human liver endothelial cells after ischemia and reperfusion. Different pathways of energy substrate utilization were a contributing factor. The beneficial effect of the higher ATP level caused by adenosine to human liver endothelial cell viability was limited to 24 h of ischemia. Beyond this ischemia time we could not prove a favorable impact of adenosine on human liver endothelial cells.

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“…Apart from its antioxidative potential, UW was designed to overcome the lack of substrates during the cold ischaemic period. Adenosine, for instance, led to a better regeneration of ATP during the first 60–120 min after reperfusion in several studies [41–43]. This was also shown in the harvested organs after 90 min of reperfusion in our series.…”

Section: Discussionsupporting

confidence: 86%

In vivoquantification of oxygen-free radical release in experimental pancreas transplantation

Neeff

Dobschuetz

Sommer

et al. 2008

Transplant International

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Summary Reactive oxygen species (ROS) were drawn to the attention in the setting of organ transplantation when the ‘injury hypothesis’ postulated a link between oxidative stress and the activation of the innate immunity of the recipient. While the occurrence of ROS during organ transplantation is undoubted, their onset and magnitude remain largely unknown. We therefore measured ROS using a novel cyclic hydroxylamine spin probe CMH (1‐hydroxy‐3‐ methoxycarbonyl‐2,2,5,5‐tetramethylpyrrolidine) during syngeneic experimental pancreas transplantation in rats in vivo. Organs were subjected to two different cold preservation methods [University of Wisconsin preservation solution (UW) or normal saline] for 18 h. During the first 90 min of reperfusion, samples were collected and analysed using electron paramagnetic resonance signalling. Isolated blood‐free perfused organs (IPO) were used for comparison. Analysis showed that it is feasible to detect ROS using CMH spin probes. While IPO organs displayed a very early ROS release, there was no ROS increase in the UW preserved group compared to NaCl. These findings were in line with conventional markers of organ damage such as serum lactate, glucose, potassium as well as tissue ATP levels. CMH spin probes might become a useful tool for the in vivo animal testing of antioxidative substances in models of solid organ transplantation.

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Effects of adenosine on ischaemia–reperfusion injury associated with rat pancreas transplantation

Abstract: Adenosine in the preservation solution may enhance the inflammatory response in rat pancreas transplantation.

Cited by 11 publications

References 35 publications

UW is superior to Celsior and HTK in the protection of human liver endothelial cells against preservation injury

UW is superior to Celsior and HTK in the protection of human liver endothelial cells against preservation injury

Value of Energy Substrates in HTK and UW to Protect Human Liver Endothelial Cells against Ischemia and Reperfusion Injury

In vivoquantification of oxygen-free radical release in experimental pancreas transplantation

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