Effects of anesthesia on renal function and metabolism in rats assessed by hyperpolarized <scp>MRI</scp>

Qi, Haiyun; Mariager, Christian Østergaard; Lindhardt, Jakob; Nielsen, Per Mose; Stødkilde-Jørgensen, Hans; Laustsen, Christoffer

doi:10.1002/mrm.27165

Cited by 14 publications

(13 citation statements)

References 44 publications

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“…However, we note that previous work has reported that the lactate to pyruvate ratio is decreased under isoflurane anaesthesia of increasing depth in the brain 100 , heart 101 , and kidney 102 . Additionally, the lactate to pyruvate ratio is altered profoundly following the administration of different anaesthetic agents, with a reduction in the derived metabolic rate constant with increasing depth of anaesthesia from alpha-chloralose to pentobarbital 103 .…”

Section: Discussioncontrasting

confidence: 44%

13C Pyruvate Transport Across the Blood-Brain Barrier in Preclinical Hyperpolarised MRI

Miller

Grist

Serres

et al. 2018

Sci Rep

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Hyperpolarised MRI with Dynamic Nuclear Polarisation overcomes the fundamental thermodynamic limitations of conventional magnetic resonance, and is translating to human studies with several early-phase clinical trials in progress including early reports that demonstrate the utility of the technique to observe lactate production in human brain cancer patients. Owing to the fundamental coupling of metabolism and tissue function, metabolic neuroimaging with hyperpolarised [1-13C]pyruvate has the potential to be revolutionary in numerous neurological disorders (e.g. brain tumour, ischemic stroke, and multiple sclerosis). Through the use of [1-13C]pyruvate and ethyl-[1-13C]pyruvate in naïve brain, a rodent model of metastasis to the brain, or porcine brain subjected to mannitol osmotic shock, we show that pyruvate transport across the blood-brain barrier of anaesthetised animals is rate-limiting. We show through use of a well-characterised rat model of brain metastasis that the appearance of hyperpolarized [1-13C]lactate production corresponds to the point of blood-brain barrier breakdown in the disease. With the more lipophilic ethyl-[1-13C]pyruvate, we observe pyruvate production endogenously throughout the entire brain and lactate production only in the region of disease. In the in vivo porcine brain we show that mannitol shock permeabilises the blood-brain barrier sufficiently for a dramatic 90-fold increase in pyruvate transport and conversion to lactate in the brain, which is otherwise not resolvable. This suggests that earlier reports of whole-brain metabolism in anaesthetised animals may be confounded by partial volume effects and not informative enough for translational studies. Issues relating to pyruvate transport and partial volume effects must therefore be considered in pre-clinical studies investigating neuro-metabolism in anaesthetised animals, and we additionally note that these same techniques may provide a distinct biomarker of blood-brain barrier permeability in future studies.

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Section: Discussioncontrasting

confidence: 44%

13C Pyruvate Transport Across the Blood-Brain Barrier in Preclinical Hyperpolarised MRI

Miller

Grist

Serres

et al. 2018

Sci Rep

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“…The main limitation of this study is the necessity for anesthesia in animal studies, which may alter metabolic measurements . Propofol has been reported to induce transient hyperglycemia in pigs and insulin resistance in rats, and although no data on pigs exist on this, it is possible that the prolonged effect of feeding is the result of the anesthesia used.…”

Section: Discussionmentioning

confidence: 97%

“…The main limitation of this study is the necessity for anesthesia in animal studies, which may alter metabolic measurements. 48 Propofol has been reported to induce transient hyperglycemia in pigs 49 and insulin resistance in rats, 50 and although no data on pigs exist on this, it is possible that the prolonged effect of feeding is the result of the anesthesia used. As such, these results may not be directly translated into human trials, and further research is needed in order to clarify whether the effects of feeding can be replicated in nonanesthetized humans.…”

Section: Study Limitations and Disadvantages Of The Modelmentioning

confidence: 99%

Hyperpolarized [1‐¹³C]pyruvate MRI can image the metabolic shift in cardiac metabolism between the fasted and fed state in a porcine model

Tougaard

Hansen

Laustsen

et al. 2018

Magnetic Resonance in Med

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Purpose Owing to its noninvasive nature, hyperpolarized MRI may improve delineation of myocardial metabolic derangement in heart disease. However, consistency may depend on the changeable nature of cardiac metabolism in relation to whole‐body metabolic state. This study investigates the impact of feeding status on cardiac hyperpolarized MRI in a large animal model resembling human physiology. Methods Thirteen 30‐kg pigs were subjected to an overnight fast, and 5 pigs were fed a carbohydrate‐rich meal on the morning of the experiments. Vital parameters and blood samples were registered. All pigs were then scanned by hyperpolarized [1‐13C]pyruvate cardiac MRI, and results were compared between the 2 groups and correlated with circulating substrates and hormones. Results The fed group had higher blood glucose concentration and mean arterial pressure than the fasted group. Plasma concentrations of free fatty acids (FFAs) were decreased in the fed group, whereas plasma insulin concentrations were similar between groups. Hyperpolarized MRI showed that fed animals had increased lactate/pyruvate, alanine/pyruvate, and bicarbonate/pyruvate ratios. Metabolic ratios correlated negatively with FFA levels. Conclusion Hyperpolarized MR can identify the effects of different metabolic states on cardiac metabolism in a large animal model. Unlike previous rodent studies, all metabolic derivatives of pyruvate increased in the myocardium of fed pigs. Carbohydrate‐rich feeding seems to be a feasible model for standardized, large animal hyperpolarized MRI studies of myocardial carbohydrate metabolism.

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“…It is also associated with hyperthermia and muscle weakness, postoperatively (Maeda, Iranami, & Hatano, 1997). Qi et al (2018) compared the effects of various anesthesia and found that sevoflurane decreases the levels of sodium and insulin, whereas, it suggestively, increases the blood sugar level. Metabolism of sevoflurane in the presence of soda lime, giving compound A (fluoromethyl-2,2 difluoro-1-[trifluoromethyl] vinyl ether; Frink et al, 1992) is found to have nephrotoxic effects, as a consequence of glutathione and cysteine metabolites (Jin, Baillie, Davis, & Kharasch, 1995).…”

Section: Halogenated Anesthesiamentioning

confidence: 99%

Renal effects of general anesthesia from old to recent studies

Alizadeh

Fard

2019

Journal Cellular Physiology

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Various types of anesthesia are being utilized to maintain physiologically secured surgical conditions. Nearly all categories of general anesthesia are characterized by various perioperative and postoperative complications. These shortcomings are important aspects that need to be considered by the anesthesiologist and surgeon before administration of these compounds. The renal effects of anesthesia play an important role in understanding possible systemic changes due to the fact that the kidney has a direct or indirect impact on nearly all the systems of the body. Various studies have been conducted to find out changes in renal parameters and its systemic effects upon administration of the anesthesia and its postoperative repercussions. Besides that, the impaired renal function might have an impact on the excretion of anesthetic metabolites, which can lead to long‐term dysfunction. Patients with a previous history of disease ought to be brought under consideration because these chemicals can ameliorate pre‐existent symptoms. This review is intended to discuss the early and latest studies based on the effects of general anesthesia on the renal system.

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Effects of anesthesia on renal function and metabolism in rats assessed by hyperpolarized MRI

Cited by 14 publications

References 44 publications

13C Pyruvate Transport Across the Blood-Brain Barrier in Preclinical Hyperpolarised MRI

13C Pyruvate Transport Across the Blood-Brain Barrier in Preclinical Hyperpolarised MRI

Hyperpolarized [1‐¹³C]pyruvate MRI can image the metabolic shift in cardiac metabolism between the fasted and fed state in a porcine model

Renal effects of general anesthesia from old to recent studies

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Effects of anesthesia on renal function and metabolism in rats assessed by hyperpolarized MRI

Cited by 14 publications

References 44 publications

13C Pyruvate Transport Across the Blood-Brain Barrier in Preclinical Hyperpolarised MRI

13C Pyruvate Transport Across the Blood-Brain Barrier in Preclinical Hyperpolarised MRI

Hyperpolarized [1‐13C]pyruvate MRI can image the metabolic shift in cardiac metabolism between the fasted and fed state in a porcine model

Renal effects of general anesthesia from old to recent studies

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Hyperpolarized [1‐¹³C]pyruvate MRI can image the metabolic shift in cardiac metabolism between the fasted and fed state in a porcine model