Mechanism of Anesthetic Toxicity: Metabolism, Reactive Oxygen Species, Oxidative Stress, and Electron Transfer

Kovacic, Peter; Somanathan, Ratnasamy

doi:10.5402/2011/402906

Cited by 17 publications

(9 citation statements)

References 77 publications

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“…Moreover, these results could support the causative role of the systemic transfer of LA in the suspected shift from pro‐oxidative to antioxidative homeostasis. This shift seems to be linked to the overproduction of ROS and the depleted stores of antioxidant species . Similar results have been reported in the course of myocardial ischemia .…”

Section: Discussionsupporting

confidence: 85%

Electrophysiological, haemodynamic, and mitochondrial alterations induced by levobupivacaine during myocardial ischemia in a pig model: protection by lipid emulsions?

Mamou

Descotes

Chevalier

et al. 2015

Fundamemntal Clinical Pharma

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Accidental intravascular or high-dose injection of local anesthetics (LA) can result in serious, potentially life-threatening complications. Indeed, adequate supportive measures and the administration of lipid emulsions are required in such complications. The study's objectives were threefold: (i) evaluate the myocardial toxicity of levobupivacaine when administered intravenously; (ii) investigate levobupivacaine toxicity on cardiomyocytes mitochondrial functions and cellular structure; (iii) assess the protective effects of a lipid emulsion in the presence or absence of myocardial ischemia. Domestic pigs randomized into two groups of 24 animals each, with either preserved coronary circulation or experimental myocardial ischemia. Six animals from each group received either: (i) single IV injection of saline, (ii) lipid emulsion (Intralipid(®) ), (iii) levobupivacaine, (iv) combination levobupivacaine-Intralipid(®) . Serially measured endpoints included: heart rate, duration of the monophasic action potentials (dMAP), mean arterial pressure, and peak of the time derivative of left ventricular pressure (LV dP/dtmax ). In addition, the following cardiomyocytes mitochondrial functions were measured: reactive oxygen species (ROS) production, oxidative phosphorylation, and calcium retention capacity (CRC) as well as the consequences of ROS production on lipids, proteins, and DNA. IV injection of levobupivacaine induced sinus bradycardia and reduced dMAP and LV dP/dtmax . At the mitochondrial level, oxygen consumption and CRC were decreased. In contrast, ROS production was increased leading to enhanced lipid peroxidation and structural alterations of proteins and DNA. Myocardial ischemia was associated with global worsening of all changes. Intralipid(®) quickly improved haemodynamics. However, beneficial effects of Intralipid(®) were less clear after myocardial ischemia.

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Section: Discussionsupporting

confidence: 85%

Electrophysiological, haemodynamic, and mitochondrial alterations induced by levobupivacaine during myocardial ischemia in a pig model: protection by lipid emulsions?

Mamou

Descotes

Chevalier

et al. 2015

Fundamemntal Clinical Pharma

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“…Although propofol, which is chemically similar to endogenous vitamin E, has been reported to have antioxidant properties [19], no such effects could be confi rmed from this study, and total intravenous anaesthesia with propofol alone was not found to be superior to propofol/sevofl urane anaesthesia in this regard. The plasma concentration of vitamin E decreased after induction to anaesthesia in the propofol group and during anaesthesia in both groups, which might be a consequence of vitamin E consumption due to increased production of ROS during anaesthesia [20]. Naziroǧlu and Günay [21] also reported a signifi cant decrease in serum vitamin E concentrations in healthy dogs anaesthetized with enfl urane.…”

Section: Discussionmentioning

confidence: 90%

Influence of sevoflurane or propofol anaesthesia on oxidative stress parameters in dogs with early-stage myxomatous mitral valve degeneration. A preliminary study

et al. 2018

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The aim of this study was to investigate the effects of total intravenous anaesthesia with propofol and anaesthesia induced with propofol and maintained with sevoflurane on oxidative stress parameters in dogs with early-stage myxomatous mitral valve degeneration (MMVD). Sixteen client-owned dogs with early stage MMVD that required periodontal treatment were included in the study. After induction with propofol, anaesthesia was maintained with propofol (group P) or sevoflurane (group PS). Blood samples for determination of vitamin E, superoxide dismutase, glutathione peroxidase and malondialdehyde were collected before premedication, 5 and 60 minutes and 6 hours after induction to anaesthesia. There were no significant differences between groups in any of the oxidative stress parameters at each sampling time. Compared to basal values, vitamin E concentration decreased significantly during anaesthesia in both groups and glutathione peroxidase activity increased 60 minutes after induction to anaesthesia in PS group. Anaesthesia with propofol or with propofol and sevoflurane did not have any significant impact on oxidative stress parameters in dogs with early stage MMVD. In terms of oxidative stress, both protocols may be equally safely used in dogs with early stage MMVD.

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“…In the plasma of healthy men, vitamin E represents up to 75% of ACL [16,17]. A decrease in vitamin E (total tocopherol) during anaesthesia was demonstrated in dogs with MMVD [18], healthy dogs [19] and people [20,21], as well as a decrease in alpha tocopherol in people [22,23].Metabolism of anaesthetics and changes in tissue oxygenation during anaesthesia promote increased formation of ROS, which affects antioxidant defence system [7,24,25].…”

Section: Discussionmentioning

confidence: 99%

Antioxidant capacity of lipid- and water-soluble antioxidants in dogs with subclinical myxomatous mitral valve degeneration anaesthetised with propofol or sevoflurane

Tomsič

Svete

Nemec

et al. 2020

Preprint

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Background: Antioxidants located in both the hydrophilic and lipophilic compartments of plasma act as a defence system against reactive oxygen species (ROS). . Excessive production of ROS during anaesthesia affects the antioxidant capacity of plasma and may result in oxidative stress. The aim of this study was to evaluate the antioxidant capacity of lipid- (ACL) and water-soluble (ACW) antioxidants in client-owned dogs diagnosed with periodontal disease and early-stage myxomatous mitral valve degeneration (MMVD) and anaesthetised for a dental procedure with propofol and sevoflurane or with propofol only. Results: Dogs with MMVD were anaesthetised with propofol and sevoflurane (MMVD/PS, n = 8) or with propofol only (MMVD/P, n = 10). Dogs with no evidence of MMVD (PS, n = 12) were anaesthetised with propofol and sevoflurane. Blood samples for determination of ACL and ACW were collected before and 5 minutes, 60 minutes and 6 hours after induction to anaesthesia. In dogs with MMVD and anaesthetised with propofol and sevoflurane, ACL was significantly higher at all sampling times when compared to control dogs. Compared to basal values, only anaesthesia maintained with propofol significantly increased ACL at 60 minutes in dogs with MMVD. In dogs with MMVD and anaesthetised with propofol, ACW increased after induction to anaesthesia and remained elevated up to 6 hours after anaesthesia. Compared to basal values, anaesthesia maintained with sevoflurane significantly increased ACW only at 60 minutes in both dogs with and without MMVD.The only difference between propofol and propofol/sevoflurane anaesthesia in dogs with MMVD was significantly higher ACW at 60 minutes after induction to anaesthesia in the propofol group. Conclusions: Regarding antioxidant capacity, propofol could be a better choice than sevoflurane for anaesthesia of dogs with early-stage MMVD, although further studies are necessary to clarify the advantage of this antioxidant capacity.

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Mechanism of Anesthetic Toxicity: Metabolism, Reactive Oxygen Species, Oxidative Stress, and Electron Transfer

Cited by 17 publications

References 77 publications

Electrophysiological, haemodynamic, and mitochondrial alterations induced by levobupivacaine during myocardial ischemia in a pig model: protection by lipid emulsions?

Electrophysiological, haemodynamic, and mitochondrial alterations induced by levobupivacaine during myocardial ischemia in a pig model: protection by lipid emulsions?

Influence of sevoflurane or propofol anaesthesia on oxidative stress parameters in dogs with early-stage myxomatous mitral valve degeneration. A preliminary study

Antioxidant capacity of lipid- and water-soluble antioxidants in dogs with subclinical myxomatous mitral valve degeneration anaesthetised with propofol or sevoflurane

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