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Influence of propofol on the mitochondrial function of colon and liver tissue in healthy rats : Report of an experimental in vitro study

(2019) Buitenhuis, A.J. (Albert)

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).




oai_other:(2019) Burg, M.C. van der
Profylactische trombocytentransfusies bij patiënten met een hemato-oncologische ziekte: werken naar efficiëntere inzet en betere kwaliteit van leven.
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