Buitenhuis, A.J. (Albert) (2019) Influence of propofol on the mitochondrial function of colon and liver tissue in healthy rats : Report of an experimental in vitro study. thesis, Medicine.
Full text available on request.Abstract
Introduction: Propofol infusion syndrome (PRIS) is a feared complication of anesthesia from prolonged or high-dose infusion of propofol, which in the clinical setting is used as drug with a lipid containing solvent. It is assumed that PRIS is caused by an altered mitochondrial function. Many studies have researched the influence of propofol on liver-, heart- and musclemitochondria showing, varying results from being either impaired or unaffected. Due to these inconsistent results the question arises, which role plays propofol or the lipid containing solvent agent MCT (medium chain triglycerides)? In addition, while studies on hepatic and muscle mitochondria are plenty, studies on mitochondrial function of the colon are lacking. Research questions: 1. Which role plays MCT on mitochondrial function in hepatic mitochondria and thus in PRIS? 2. Are the effects of propofol on hepatic mitochondria dose dependent? 3. Do the effects of propofol on mitochondrial function differ between hepatic and colonic cells? Method: The experiments were conducted on male Wistar rats, using homogenates of liver and colon. Homogenates were incubated for 3 minutes with three physiological concentrations (50μM, 75μM, 100μM) and one supra-physiological concentration (500μM) of propofol and two different carrier substances dimethyl sulfoxide (DMSO) and MCT. Respiratory rates have been measured using a Clark Type electrode under the presence of complex I or complex II substrate, glutamate & malate or succinate, respectively. The respiratory control index (RCI), as measure of the coupling between the electron transport system (ETS) and the oxidative phosphorylation (OXPHOS), as well as the ADP/O ratio to reflect the efficiency of OXPHOS were calculated. RCI and ADP/O were presented as percentage of the control, which is the measurement of mitochondrial respiration after 3 minutes incubation at room temperature without any substance. Results: 1. MCT only minimally affected hepatic mitochondrial function with a slightly less efficient OXPHOS (control 100%, MCT: ADP/O complex I: 93.7±31.7%, p=0.0271) and mild uncoupling of the ETS (control 100%, MCT: RCI complex II: 87.2±9.8%, p<0.0001). 2. Propofol at the highest dose uncoupled the ETS in hepatic mitochondria in both complexes formulation independent (control 100%, propofol/MCT 500μM: complex I: 66,3±8.7%, p=0.0003, complex II: 75.46±9.18%, p<0.0001; control 100%, propofol/DMSO 500μM: complex I: 29.1±8.8%, p=0.0008, complex II: 49.3±15.5%, p<0.0001), without a significant change of the efficiency of OXPHOS. 3. MCT increased the RCI in complex I in colonic mitochondria (MCT: control 100%, complex I: 123.0±31.6%. p=0.007). Propofol aggravated this effect in both complexes at low concentrations (control: 100%, propofol/MCT 50μM: complex I: 127.2±10.7%, p=0.006, complex II: 136.8±33.9%, p=0.0065; propofol/MCT 100μM: complex I: 131.4±18.7%, p=0.0043). Propofol/DMSO showed only an increased ADP/O index in colonic mitochondria at the highest concentration propofol (control 100%, propofol/DMSO 500μM: complex I 139.4±41.4%, p=0.0026).
| Item Type: | Thesis (Thesis) |
|---|---|
| Supervisor name: | Faculty supervisor: and Thomas Scheeren, Prof. Dr. University of Groningen |
| Supervisor name: | Local supervisor: and Olaf Picker, Prof. Dr. med. and Department: and Anaesthesiology, Heinrich Heine University |
| Faculty: | Medical Sciences |
| Date Deposited: | 25 Jun 2020 10:54 |
| Last Modified: | 25 Jun 2020 10:54 |
| URI: | https://umcg.studenttheses.ub.rug.nl/id/eprint/1459 |
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