Heereveld, D.N. van (2017) Metformin postconditioning during isolated renal machine perfusion in a porcine slaughterhouse model. thesis, Medicine.
Full text available on request.Abstract
BACKGROUND: Machine perfusion is a preservation method that shows many benefits over traditional cold storage and allows for the addition of therapeutic substances. Metformin is a therapeutic substance that reduces radical oxygen species production due its effects on mitochondrial respiration. We aim to assess whether metformin reduces ischemia-reperfusion injury and improves renal function when a therapeutic dose is added during perfusion. The primary outcome parameter is creatinine clearance as a measure of renal function. Urine output, fractional sodium excretion, flow rates, oxygen consumption and ATP, LDH and TBARS concentrations are also analyzed. METHODS: Twelve porcine kidneys obtained from the slaughterhouse are included in this study. After 30 minutes of warm ischemia, all kidneys were preserved using 3 hours of oxygenated hypothermic machine perfusion (HMP). 4 hours of oxygenated normothermic machine perfusion (NMP) are used as reperfusion model. Six kidneys will be treated with metformin during HMP and NMP, whilst six kidneys from earlier perfusions will function as controls. In this experiment, another research group will analyze metformin excretion during (sub) toxic concentrations of the drug. To this aim gradually increasing metformin infusion is given in the treatment group during NMP, reaching toxic concentrations after 2 hours. RESULTS: Mean creatinine clearance rates were lower in treatment group at all time points and significantly lower after 150 minutes of NMP, when toxic concentrations of metformin were reached. Urine production rates were significantly lower in the treatment group after an hour of NMP. Oxygen consumption was significantly lower in the treatment group after 3 hours of NMP. Mean TBARS concentrations were insignificantly lower in the treatment group before toxic concentrations of metformin were reached and insignificantly higher afterwards. Fractional sodium excretion, flow rates, ATP and LDH concentrations were comparable for the treatment and the control group. CONCLUSION: We did not find a beneficial effect of metformin postconditioning during machine perfusion on renal function or ischemia-reperfusion injury.
| Item Type: | Thesis (Thesis) |
|---|---|
| Supervisor name: | Faculty supervisor: and Leuvenink, prof. dr. H.G.D. and Second supervisors: and Venema, L.H. MSc and and and Posma R.A.BSc and University Medical Center Groningen and Department of Surgery: Surgical Research Laboratory |
| Faculty: | Medical Sciences |
| Date Deposited: | 25 Jun 2020 11:05 |
| Last Modified: | 25 Jun 2020 11:05 |
| URI: | https://umcg.studenttheses.ub.rug.nl/id/eprint/2532 |
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