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Propofol acids fatty

Adéla Krajčová, Nils Gunnar Løvsletten, Petr Waldauf, Vladimír Frič, Moustafa Elkalaf, Tomáš Urban, Michal Anděl, Jan Trnka, G Hege Thoresen, František Duška
OBJECTIVES: Propofol may adversely affect the function of mitochondria and the clinical features of propofol infusion syndrome suggest that this may be linked to propofol-related bioenergetic failure. We aimed to assess the effect of therapeutic propofol concentrations on energy metabolism in human skeletal muscle cells. DESIGN: In vitro study on human skeletal muscle cells. SETTINGS: University research laboratories. SUBJECTS: Patients undergoing hip surgery and healthy volunteers...
December 13, 2017: Critical Care Medicine
Emmanuel Lilitsis, Elisavet Astyrakaki, Evaggelos Blevrakis, Sofia Xenaki, George Chalkiadakis, Emmanuel Chrysos
BACKGROUND: Mitochondria are the energy producing organelles practically in every human cell except erythrocytes. Indeed mitochondria are widespread in high energy requiring organs like brain, heart and muscles. Currently there are no clinical trials supporting with clear evidence which is the most suitable surgical or anesthetic management of a patient with known mitochondrial disease presenting with surgical disorders. This condition poses possible hazardous problems to the medical attention of those patients...
August 29, 2017: BMC Anesthesiology
G J Nieuwenhuijs-Moeke, V B Nieuwenhuijs, M A J Seelen, S P Berger, M C van den Heuvel, J G M Burgerhof, P J Ottens, R J Ploeg, H G D Leuvenink, M M R F Struys
Background: Kidney transplantation is associated with harmful processes affecting the viability of the graft. One of these processes is associated with the phenomenon of ischaemia-reperfusion injury. Anaesthetic conditioning is a widely described strategy to attenuate ischaemia-reperfusion injury. We therefore conducted the Volatile Anaesthetic Protection of Renal Transplants-1 trial, a pilot project evaluating the influence of two anaesthetic regimens, propofol- vs sevoflurane-based anaesthesia, on biochemical and clinical outcomes in living donor kidney transplantation...
May 1, 2017: British Journal of Anaesthesia
G Daş, A Vernunft, S Görs, E Kanitz, J M Weitzel, K-P Brüssow, C C Metges
Experimental setups for physiological research, in which acute operative interventions need to be performed, can require inclusion of general anesthesia (GA), which may interfere or confound with the effects of the experimental factors of interest on measured variables. It was recently shown that the most commonly used sedatives/anesthetics in pigs (e.g., ketamine, xylazine, azaperone) affect physiological responses and thus the primary metabolic readouts have the potential to be confounded. To extend the search for a physiologically-friendly anesthesia regime for such studies, we investigated effects of GA induced by propofol (Prop) or pentobarbital (Pent) or propofol plus isoflurane (Prop + Isof) on plasma concentrations of commonly measured metabolites and hormones...
December 2016: Journal of Animal Science
Claire Allen, Russell Perkins, Bernd Schwahn
BACKGROUND: Medium-chain acyl-CoA dehydrogenase deficiency is the most common genetically determined disorder of mitochondrial fatty acid oxidation. Decompensation can result in hypoglycemia, seizures, coma, and death but may be prevented by ensuring glycogen stores do not become depleted. Perioperative care is of interest as surgery, fasting, and infection may all trigger decompensation and the safety of anesthetic agents has been questioned. Current guidelines from the British Inherited Metabolic Disease Group advise on administering fluid containing 10% glucose during the perioperative period...
January 2017: Paediatric Anaesthesia
M M Welsink-Karssies, J A W Polderman, E J Nieveen van Dijkum, B Preckel, W S Schlack, G Visser, C E Hollak, J Hermanides
Surgery and anesthesia pose a threat to patients with very long-chain acyl-CoA dehydrogenase deficiency (VLCADD), because prolonged fasting, stress, and pain are known risk factors for the induction of metabolic derangement. The optimal perioperative management in these patients is unknown and the use of volatile agents and agents dissolved in fatty acids has been related to postoperative metabolic complications. However, the occurrence of metabolic derangement is multifactorial and depends, amongst others, on the severity of the mutation and residual enzyme activity...
2017: JIMD Reports
Yuichi Hashimoto, Kei Takahashi, Yuko Yamamoto, Tokiko Ogata, Takero Arai, Yasuhisa Okuda
A 34-year-old man with adrenoleukodystrophy (ALD) was scheduled for pump system insertion of intrathecal baclofen therapy under general anesthesia. ALD, a rare genetic disorder, is associated with a total body increase in long chain fatty acids caused by defective degradation, and includes various nervous system abnormalities, muscular weakness, in addition to adrenal insufficiency. He had contracture of the both legs, and muscular weakness of the left hand, and Mallampati class III, but no respiratory disability...
April 2016: Masui. the Japanese Journal of Anesthesiology
J-C Devaud, M M Berger, A Pannatier, F Sadeghipour, P Voirol
BACKGROUND & AIMS: An altered lipid profile is common among intensive care unit (ICU) patients, but evidence regarding the impact of different fatty acid (FA) emulsions administered to patients requiring parenteral nutrition (PN) is scarce. This study aimed to compare the plasma triglycerides (TG) response to two types of commercial lipid emulsions: a structured mixture of long- and medium-chain triglycerides (LCT/MCT) or LCTs with n-9 FA (LCT+) in ICU patients. METHODS: In this retrospective observational study conducted in a multidisciplinary ICU: two groups were defined by the type of emulsion used...
April 2017: Clinical Nutrition: Official Journal of the European Society of Parenteral and Enteral Nutrition
Xinhua Yao, Yalan Li, Mingzhe Tao, Shuang Wang, Liangqing Zhang, Jiefu Lin, Zhengyuan Xia, Hui-Min Liu
The anesthetic propofol confers cardioprotection against myocardial ischemia-reperfusion injury (IRI) by reducing reactive oxygen species (ROS). However, its cardioprotection on patients is inconsistent. Similarly, the beneficial effect of tight glycemic control during cardiac surgery in patients has recently been questioned. We postulated that low glucose (LG) may promote ROS formation through enhancing fatty acid (FA) oxidation and unmask propofol cardioprotection during IRI. Rat hearts were isolated and randomly assigned to be perfused with Krebs-Henseleit solution with glucose at 5...
2015: Journal of Diabetes Research
Mei Qin, Zachary Zeidler, Kristen Moulton, Leland Krych, Zengyan Xia, Carolyn B Smith
Silencing the gene FMR1 in fragile X syndrome (FXS) with consequent loss of its protein product, FMRP, results in intellectual disability, hyperactivity, anxiety, seizure disorders, and autism-like behavior. In a mouse model (Fmr1 knockout (KO)) of FXS, a deficit in performance on the passive avoidance test of learning and memory is a robust phenotype. We report that drugs acting on the endocannabinoid (eCB) system can improve performance on this test. We present three lines of evidence: (1) Propofol (reported to inhibit fatty acid amide hydrolase (FAAH) activity) administered 30 min after training on the passive avoidance test improved performance in Fmr1 KO mice but had no effect on wild type (WT)...
September 15, 2015: Behavioural Brain Research
Aibek E Mirrakhimov, Prakruthi Voore, Oleksandr Halytskyy, Maliha Khan, Alaa M Ali
Propofol infusion syndrome is a rare but extremely dangerous complication of propofol administration. Certain risk factors for the development of propofol infusion syndrome are described, such as appropriate propofol doses and durations of administration, carbohydrate depletion, severe illness, and concomitant administration of catecholamines and glucocorticosteroids. The pathophysiology of this condition includes impairment of mitochondrial beta-oxidation of fatty acids, disruption of the electron transport chain, and blockage of beta-adrenoreceptors and cardiac calcium channels...
2015: Critical Care Research and Practice
Paolo Ascenzi, Loris Leboffe, Alessandra di Masi, Viviana Trezza, Gabriella Fanali, Magda Gioia, Massimo Coletta, Mauro Fasano
The hydrolysis of 4-nitrophenyl esters of hexanoate (NphOHe) and decanoate (NphODe) by human serum albumin (HSA) at Tyr411, located at the FA3-FA4 site, has been investigated between pH 5.8 and 9.5, at 22.0°C. Values of Ks, k+2, and k+2/Ks obtained at [HSA] ≥ 5×[NphOXx] and [NphOXx] ≥ 5×[HSA] (Xx is NphOHe or NphODe) match very well each other; moreover, the deacylation step turns out to be the rate limiting step in catalysis (i.e., k+3 < k+2). The pH dependence of the kinetic parameters for the hydrolysis of NphOHe and NphODe can be described by the acidic pKa-shift of a single amino acid residue, which varies from 8...
2015: PloS One
Coert J Zuurbier, Anneke Koeman, Sander M Houten, Markus W Hollmann, Wouter J Florijn
The role of anesthetics in animal research models is crucial, yet often ignored, and is almost never the primary focus of examination. Here, we investigated the impact of anesthetic regimens on different parameters of hemodynamics (blood pressure (BP) and heart rate (HR)), metabolism (glucose, insulin, and free fatty acids (FFA)), and inflammation (IL-6 and TNF-α) in two frequently used mouse strains (C57BL/6 and FVB). All animals were at a similar surgical plane of anesthesia, mechanically ventilated, and monitored for 60 min...
June 2014: Experimental Biology and Medicine
Arnaud Vincent Vanlander, Juergen Guenther Okun, Annick de Jaeger, Joél Smet, Elien De Latter, Boel De Paepe, Georges Dacremont, Birgitte Wuyts, Bert Vanheel, Peter De Paepe, Philippe Germaine Jorens, Niels Van Regenmortel, Rudy Van Coster
BACKGROUND: Propofol is a short-acting intravenous anesthetic agent. In rare conditions, a life-threatening complication known as propofol infusion syndrome can occur. The pathophysiologic mechanism is still unknown. Some studies suggested that propofol acts as uncoupling agent, others suggested that it inhibits complex I or complex IV, or causes increased oxidation of cytochrome c and cytochrome aa3, or inhibits mitochondrial fatty acid metabolism. Although the exact site of interaction is not known, most hypotheses point to the direction of the mitochondria...
February 2015: Anesthesiology
Charlotte Redshaw, Catherine Stewart
Very long-chain acyl-coenzyme A dehydrongenase deficiency (VLCADD) is a rare disorder of fatty acid metabolism that renders sufferers susceptible to hypoglycemia, liver failure, cardiomyopathy, and rhabdomyolysis. The literature about the management of these patients is hugely conflicting, suggesting that both propofol and volatile anesthesia should be avoided. We have reviewed the literature and have concluded that the source papers do not support the statements that volatile anesthetic agents are unsafe. The reports on rhabdomyolysis secondary to anesthesia appear to be due to inadequate supply of carbohydrate not volatile agents...
November 2014: Paediatric Anaesthesia
Julie M Martin, Melanie B Gillingham, Cary O Harding
The medication propofol, commonly used for anesthesia, has been avoided in patients with mitochondrial fatty acid oxidation disorders (FAODs) due to concerns that it contains long-chain fatty acids (LCFAs), and because of reports of severe side effects in some critically ill patients receiving high-dose propofol infusions that mimic some of the symptoms regularly found in FAOD patients. In this secondary analysis, we examined the outcomes of 8 children with long-chain 3-hydroxyacyl CoA dehydrogenase (LCHAD) deficiency or trifunctional protein (TFP) deficiency who were repeatedly sedated for an electroretinogram (ERG) as part of a longitudinal study of the progression of chorioretinopathy commonly found in this population...
June 2014: Molecular Genetics and Metabolism
Coert J Zuurbier, Anneke Koeman, Sander M Houten, Markus W Hollmann, Wouter J Florijn
The role of anesthetics in animal research models is crucial, yet often ignored, and is almost never the primary focus of examination. Here, we investigated the impact of anesthetic regimens on different parameters of hemodynamics (blood pressure (BP) and heart rate (HR)), metabolism (glucose, insulin, and free fatty acids (FFA)), and inflammation (IL-6 and TNF-α) in two frequently used mouse strains (C57BL/6 and FVB). All animals were at a similar surgical plane of anesthesia, mechanically ventilated, and monitored for 60 min...
June 2014: Experimental Biology and Medicine
Maki Shinohara, Yohsuke Hirose, Aiji Boku, Keiji Richard Kimura, Yoshinari Morimoto, Hitoshi Niwa
Adrenoleukodystrophy (ALD) is a genetic disorder with demyelination of the central nervous system and adrenal insufficiency. A 24-year-old man with ALD was scheduled for dental treatment under general anesthesia. He was diagnosted as having ALD at the age of 5. Past medical history included recurrent cervical cellulitis, adrenal insufficiency, mental retardation, muscle weakness and seizure disorder. General anesthesia was induced using betamethasone as a steroid cover, sevoflurane and nitrous oxide-oxygen and maintained with sevoflurane and nitrous oxide-oxygen...
January 2014: Masui. the Japanese Journal of Anesthesiology
Azmat A Khan, Ahmad Husain, Mumtaz Jabeen, Jamal Mustafa, Mohammad Owais
The present study enumerates the synthesis, spectroscopic characterization, and evaluation of anticancer potential of esters of two n-9 fatty acids viz., oleic acid (OLA) and ricinoleic acid (RCA) with 2,4- or 2,6-diisopropylphenol. The synthesis strategy involved esterification of the hydroxyl group of diisopropylphenol (propofol) to the terminal carboxyl group of n-9 fatty acid. The synthesized propofol-n-9 conjugates having greater lipophilic character were tested initially for cytotoxicity in-vitro. The conjugates showed specific growth inhibition of cancer cell lines whereas no effect was observed in normal cells...
October 2012: Lipids
Zarazuela Zolkipli, Mary Sherlock, William D Biggar, Glenn Taylor, Jamie S Hutchison, Arie Peliowski, Benjamin A Alman, Simon C Ling, Ingrid Tein
A 15 year old boy with SMA type II underwent spinal fusion and suffered a mitochondrial Reye-like catabolic crisis 4 days postop with hypoketotic hypoglycemia, lactic acidaemia, hyperammonemia and liver failure, with 90% coagulative necrosis and diffuse macro- and microvesicular steatosis, requiring orthotopic liver transplantation. This crisis responded in part to mitochondrial therapy and anabolic rescue. He made a dramatic sustained neurological recovery, though his post-transplant liver biopsies revealed micro- and macrosteatosis...
September 2012: European Journal of Paediatric Neurology: EJPN
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