Successful Transplantation after Long-term Preservation of Dog Hearts

Möllhoff, T.; Sukehiro, S; Belle, H. Van; Aken, Hugo Van; Flameng, Willem

doi:10.1097/00000542-199208000-00012

Cited by 7 publications

(2 citation statements)

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“…More important, R75231 can be added to the preservation solution to prevent further degradation of adenosine during cold storage and/or given to the recipient immediately before reperfusion to inhibit adenosine uptake by the erythrocytes and to delay its washout from ischemic tissues. The beneficial effect of the last approach has been shown in canine heart preservation and transplantation (29,46,47), and further study is being conducted at our laboratory using a canine liver transplantation model. In summary, preischemic administration of the nucleoside transport inhibitor, R75231, attenuated postreperfusion liver injury, apparently from the positive effect of augmented endogenous adenosine.…”

Section: Discussionmentioning

confidence: 96%

Attenuation of Ischemic Liver Injury by Augmentation of Endogenous Adenosine1,2

Todo

Zhu²,

Zhang³

et al. 1997

Transplantation

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Hepatic grafts from non-heartbeating donors may alleviate the organ shortage, but they inherently suffer from warm ischemia. In the present study, we tested our hypothesis that augmentation of endogenous adenosine by inhibition of nucleoside transport with R75231 attenuates ischemic liver injury. Adult female beagle dogs underwent 2-hr hepatic vascular exclusion with venovenous bypass. R75231 was given to the animals by continuous intravenous infusion for 30 min before ischemia at a dose of 0.1 mg/kg (Group 2, n=6), 0.05 mg/kg (Group 3, n=6), or 0.025 mg/kg (Group 4, n=6). Nontreated animals were used as the control (Group 1, n= 10). Animal survival, hepatic tissue blood flow, liver function, and histopathology were analyzed. Two-week animal survival was 30% in Group 1, 83% in Group 2, 100% in Group 3, and 100% in Group 4. Postreperfusion hepatic tissue blood flow was markedly improved by the treatment. Treatment significantly attenuated liver enzyme release, lipid peroxidation, and changes in adenine nucleotides and purine catabolites. Structural abnormality of the liver after reperfusion was markedly improved by R75231 treatment, showing better architecture and less neutrophil infiltration. Preischemic administration of a nucleoside transport inhibitor ameliorated ischemic liver injury due to the positive effects of augmented endogenous adenosine, and is applicable clinically when the liver is procured from a controlled non-heartbeating donor.

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Section: Discussionmentioning

confidence: 96%

Attenuation of Ischemic Liver Injury by Augmentation of Endogenous Adenosine1,2

Todo

Zhu²,

Zhang³

et al. 1997

Transplantation

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“…The hearts were excised, immersed in 4°C cold KrebsHenseleit buffer (KHB), mounted on a modified Langendorff apparatus, and perfused at 37°C with KHB in a nonrecirculated, retrograde manner at the aortic root. After 15 min of normoxic perfusion at a constant pressure of 50 mm Hg using KHB as perfusion solution, six hearts in each of the four storage groups were flushed for 5 min with one of the following oxygenated 4°C-cold test solutions (table 1) via a side arm of the aortic cannula: (1) HTK (Custodiol ® ) was provided by Dr. F. Köhler Chemie, Alsbach-Hähnlein, Germany, (2) STH, (3) NIH and (4) KHB, used for simple hypothermic storage, were prepared as described [6][7][8][9]. All chemicals used were of analytical quality.…”

Section: Methodsmentioning

confidence: 99%

Comparison of the Solutions of Bretschneider, St. Thomas’ Hospital and the National Institutes of Health for Cardioplegic Protection during Moderate Hypothermic Arrest

et al. 1998

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We evaluated three cardioplegic solutions, Bretschneider’s cardioplegic solution (HTK), St. Thomas’ Hospital solution (STH) and the solution of the National Institutes of Health (NIH), a solution with added nitroglycerin and lidocaine, for their ability to minimize ischemia-reperfusion injury in a working rat heart model. After cardioplegic arrest at 4°C and subsequent 45 min of ischemic storage at 25°C the function recovery of hearts was examined during 1 h of normothermic crystalloid reperfusion using Krebs-Henseleit buffer as perfusion medium. We noted a significantly better preservation of the maximum (+dp/dt_max) and minimum (–dp/dt_max) velocity of pressure development and a significantly higher coronary flow with the use of HTK (2,657 mm Hg/s, 2,122 mm Hg/s, 17 ml/min) compared to STH (1,600 mm Hg/s, p < 0.05; 1,591 mm Hg/s, p < 0.05; 11 ml/min, p < 0.05), and an intermediate level of preservation of hemodynamic parameters with NIH (2,149 mm Hg/s, 1,766 mm Hg/s, 12 ml/min). Concerning the cardiac output, however, no major difference was found between the HTK (41 ml/min), the STH (34 ml/min) and the NIH group (36 ml/min). The decay of the myocardial energy charge was significantly lower in both the HTK and the NIH group as compared with conservation in STH solution. Lactate was lowest in the HTK group, CK and LDH releases in the effusate remained lowest after HTK and NIH preservation. The data of this study suggest that HTK and NIH most perfectly reduce the impairment of myocardial function and provide better myocardial protection during ischemic arrest at 25°C and superior recovery compared to STH solution.

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Adenosine uptake inhibitors

Noji

Karasawa

Kusaka

2004

European Journal of Pharmacology

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Adenosine is a purine nucleoside and modulates a variety of physiological functions by interacting with cell-surface adenosine receptors. Under several adverse conditions, including ischemia, trauma, stress, seizures and inflammation, extracellular levels of adenosine are increased due to increased energy demands and ATP metabolism. Increased adenosine could protect against excessive cellular damage and organ dysfunction. Indeed, several protective effects of adenosine have been widely reported (e.g., amelioration of ischemic heart and brain injury, seizures and inflammation). However, the effects of adenosine itself are insufficient because extracellular adenosine is rapidly taken up into adjacent cells and subsequently metabolized. Adenosine uptake inhibitors (nucleoside transport inhibitors) could retard the disappearance of adenosine from the extracellular space by blocking adenosine uptake into cells. Therefore, it is expected that adenosine uptake inhibitors will have protective effects in various diseases, by elevating extracellular adenosine levels. Protective or ameliorating effects of adenosine uptake inhibitors in ischemic cardiac and cerebral injury, organ transplantation, seizures, thrombosis, insomnia, pain, and inflammatory diseases have been reported. Preclinical and clinical results indicate the possibility of therapeutic application of adenosine uptake inhibitors.

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Successful Transplantation after Long-term Preservation of Dog Hearts

Cited by 7 publications

References 0 publications

Attenuation of Ischemic Liver Injury by Augmentation of Endogenous Adenosine1,2

Attenuation of Ischemic Liver Injury by Augmentation of Endogenous Adenosine1,2

Comparison of the Solutions of Bretschneider, St. Thomas’ Hospital and the National Institutes of Health for Cardioplegic Protection during Moderate Hypothermic Arrest

Adenosine uptake inhibitors

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