Tricht, Isa Maria van (2024) The influence of warm ischaemic injury on the effect of vasoactive drugs during renal normothermic machine perfusion. thesis, Medicine.
Full text available on request.Abstract
Normothermic machine perfusion (NMP) could serve as a platform to assess the viability of deceased-donor kidneys prior to transplantation. However, it remains unclear which parameters are indicative of sufficient viability during renal NMP, as the ex vivo physiology of kidneys is incompletely understood. Recent research demonstrated responsiveness, comparable to a normal in vivo response, of kidneys to pharmacological stimuli during NMP. Hence, viability assessment could be done through observation of renal responses to administered compounds. As the integrity of the renal vasculature is of utmost importance for proper kidney function after transplantation, this study compared the differences in renal vasomotor response to bolus administrations of the vasoactive compounds epoprostenol, dopamine, sodium nitroprusside (SNP), acetylcholine, norepinephrine, and verapamil in kidneys subjected to either 30 or 60 minutes of warm ischaemia (WI), during 4 hours of NMP. The renal blood flow (RBF) changed significantly in response to acetylcholine (35.12 ± 37.54 and 30.55 ± 29.88 mL/min/100g, P < 0.05 for both groups), norepinephrine (71.94 ± 27.20 and 52.17 ± 17.30 mL/min/100g, P < 0.001 for both groups) and verapamil (73.51 ± 31.59 and 49.54 ± 16.33 mL/min/100g, P < 0.01 for both groups) in the 30 and 60 minute WI group respectively, but this response did not differ between both groups (P = 0.4, P = 0.068, and P = 0.054, resp.). No response was observed after administration of epoprostenol and SNP in both groups. There was a significant decrease in RBF after administration of dopamine in kidneys subjected to 30 minutes of WI (37.41 ± 18.58 mL/min/100g, P < 0.05), but not in kidneys subjected to 60 minutes of WI (17.32 ± 7.51 mL/min/100g, P = 0.25), and this difference in renal response between both groups was significant (P < 0.05). Furthermore, the pH was significantly lower during NMP in the 60-minute WI group (an arterial pH of 7.44 ± 0.03 in the 30-minute WI group vs. 7.38 ± 0.03 in the 60-minute WI group, P < 0.01), and the same was true for renal oxygen consumption (2.87 ± 0.34 mLO₂/min/100g in the 30 minute WI group vs. 2.27 ± 0.28 mLO₂/min/100g in the 60 minute WI group, P < 0.01). In conclusion, this study suggests that the renal vascular response to dopamine, as well as decreased rates of oxygen consumption and pH, could serve as objective indicators of warm ischaemic damage during renal normothermic machine perfusion.
| Item Type: | Thesis (UNSPECIFIED) |
|---|---|
| Supervisor name: | Moers, Cyril |
| Faculty: | Medical Sciences |
| Date Deposited: | 20 Jan 2025 12:24 |
| Last Modified: | 20 Jan 2025 12:24 |
| URI: | https://umcg.studenttheses.ub.rug.nl/id/eprint/3792 |
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