Maassen, H. (2019) Inducing a hypometabolic state during normothermic machine perfusion by adding hydrogen sulphide in an isolated perfusionporcine kidney; a pre-clinical study for the application in renal transplantation. thesis, Medicine.
Full text available on request.Abstract
Introduction Hydrogen sulphide (H2S) causes a hibernation like state in small mammals and isolated perfused rat kidneys. In this study, we investigated if it is possible to induce a reversible hypometabolic state in porcine kidneys during normothermic machine perfusion by adding H2S compared to controls. Because of the similarities in anatomy and physiology, porcine kidneys are very useful for pre-clinical studies. Methods Ten porcine kidneys were evaluated in an isolated perfusion system. The experimental group (n=5) received one bolus H2S of 100 ppm, administrated during normothermic machine perfusion (NMP), and was compared to a control group (n=5). The experimental NMP period lasted 3 hours, after a standardized hypothermic machine perfusion (HMP) of 4 hours. Oxygen consumption and tissue ATP levels were measured as reflection of the metabolic rate. To assess short-term damage, ASAT and LDH levels were measured and kidneys were studied for histology. A linear mixed model was used for statistical analysis for the repeated measurements. Results Oxygen consumption decreased with 61% from 409,4 O2*ml/min/gr to 159,6 O2*ml/min/gr after the administration of H2S. The oxygen consumption was significantly different between the control group (mean 443,3 O2*ml/min/gr SE 39,88) and the H2S group (mean 159,6 O2*ml/min/gr SE 30,90) (p<0.001). ATP levels were borderline significantly different between the two groups (P=0.053). ASAT and LDH levels were not significantly different between the groups (P=0.612 and P= 0.754). Moreover, no difference was seen at the histologic level. Conclusion A reversible hypometabolic state was induced in porcine kidneys during normothermic machine perfusion by adding hydrogen sulphide to the perfusion medium. The method was considered successful because a decrease in oxygen consumption was observed in the absence of short-term damage. This makes H2S a very promising therapeutic intervention for the future during renal transplantation.
| Item Type: | Thesis (Thesis) |
|---|---|
| Supervisor name: | Coester, Dr. A.M. and Hofker, Drs. H.S. and Department of Surgery, Section Kidney Transplantation and University Medical Center Groningen, Netherlands |
| Faculty: | Medical Sciences |
| Date Deposited: | 25 Jun 2020 10:42 |
| Last Modified: | 25 Jun 2020 10:42 |
| URI: | https://umcg.studenttheses.ub.rug.nl/id/eprint/336 |
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