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Mean duration of ISO, KX and MMF anaesthesia. Anaesthesias were divided in different anaesthetic stages. Induction time (time from application to loss of righting reflex), time of non-surgical tolerance (time from loss of righting reflex until loss of all measured reflexes), time of surgical tolerance (time from loss of all measured reflexes till regain of one reflex), wake-up period (time from regaining one reflex till regain of righting reflex). After 40 minutes ISO delivery was terminated and MMF was reversed with AFN.
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Background
This study investigated effects on cardiovascular parameters during anaesthesia with isoflurane (ISO, 2¿3 Vol%), ketamine-xylazine (KX, 100 mg¿kg¿1¿+¿5 mg¿kg¿1) or a combination of medetomidine-midazolam-fentanyl (MMF, 0.15 mg¿kg¿1¿+¿2.0 mg¿kg¿1¿+¿0.005 mg¿kg¿1) in rats throughout induction, maintenance and recovery from anaesthesia. Rat...
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Citations
... They also increase diuresis and natriuresis by centrally reducing the production of antidiuretic hormone (ADH) [8], by blocking the peripheral effects of ADH in renal tubules [9] and by increasing the concentration of natriuretic peptide in plasma [10]. Despite these potential adverse effects of medetomidine, the combination of medetomidine, midazolam and fentanyl has been suggested to provide reliable sedation in rats [11][12][13]. However, it has also been recognised that anaesthesia procedures may have profound effects on plasma metabolite and hormone concentrations in experimental rats [14]. ...
Background
Alpha2-adrenoceptor agonists (α 2 -agonists) are widely used in animals as sedatives and for pre-anaesthetic medication. Medetomidine has often been given subcutaneously (SC) to rats, although its absorption rate is slow and the individual variation in serum drug concentrations is high via this route. In addition, α 2 -agonists have various effects on metabolic and endocrine functions such as hypoinsulinaemia, hyperglycaemia and diuresis. Vatinoxan is a peripherally acting α 2 -adrenoceptor antagonist that, as a hydrophilic molecule, does not cross the blood-brain barrier in significant quantities and thus alleviates peripheral cardiovascular effects and adverse metabolic effects of α 2 -agonists. Aim of this study was to evaluate the effects of vatinoxan on sedation, blood glucose concentration, voiding and heart and respiratory rates and arterial oxygen saturation in rats sedated with subcutaneous medetomidine, midazolam and fentanyl.
Results
Onset of sedation and loss of righting reflex occurred significantly faster with vatinoxan [5.35 ± 1.08 (mean ± SD) versus 12.97 ± 6.18 min and 6.53 ± 2.18 versus 14.47 ± 7.28 min, respectively]. No significant differences were detected in heart and respiratory rates and arterial oxygen saturation between treatments. Blood glucose concentration (18.3 ± 3.6 versus 11.8 ± 1.2 mmol/L) and spontaneous urinary voiding [35.9 (15.1–41.6), range (median) versus 0.9 (0–8.0) mL /kg/min] were significantly higher without vatinoxan.
Conclusions
Acceleration of induction of sedation, alleviation of hyperglycaemia and prevention of profuse diuresis by vatinoxan may be beneficial when sedating rats for clinical and experimental purposes with subcutaneous medetomidine, midazolam and fentanyl.
... Animals were anaesthetized using (50 mg/kg IP ketamine HCl 23 and 5 mg/kg IP xylazine 24 ), and a bleomycin solution was administered through endotracheal (OP) catheter intubation of the lung with the assistance of auroscope (to aid in the visualization of the vocal cords and laryngeal opening). The rodents were hung on the intubation platform using incisors on the wire. ...
This study investigated the therapeutic benefits of para-hydroxycinnamic acid in mice with bleomycin-induced lung fibrosis. Forty male BALB/c mice were randomly assigned to four groups: normal, which received 0.9% normal saline; induced, which received a single dose of bleomycin (5 mg/kg) by oropharyngeal challenge; pirfenidone-treated; and para-hydroxycinnamic acid-treated, which challenged with bleomycin and received a daily oral dose of 300 and 50 mg/kg, respectively, from day 7 to day 21. Tissue pro-fibrotic and inflammatory cytokines, oxidative indicators, pulmonary histopathology, immunohistochemistry of fibrotic proteins and the assessment of gene expression by RT-qPCR were evaluated on day 22 after euthanizing animals. Pirfenidone and para-hydroxycinnamic acid managed to alleviate the fibrotic endpoints by statistically improving the weight index, histopathological score and reduced expression of fibrotic-related proteins in immune-stained lung sections, as well as fibrotic markers measured in serum samples. They also managed to alleviate tissue levels of oxidative stress and inflammatory and pro-fibrotic mediators. para-Hydroxycinnamic acid enhanced the expression of crucial genes associated with oxidative stress, inflammation and fibrosis in vivo. para-Hydroxycinnamic acid has demonstrated similar effectiveness to pirfenidone, suggesting it could be a promising treatment for fibrotic lung conditions by inhibiting the TGF-β1/Smad3 pathway or through its anti-inflammatory and antioxidant properties.
... Animals were anesthetized using (50mg/kg IP ketamine HCl 37 and 5 mg/kg IP xylazine 38 ), and a bleomycin solution was administered through endotracheal (oropharyngeal) catheter intubation of the lung with the assistance of Auroscope (to aid in the visualization of the vocal cords and laryngeal opening). Mice were positioned on the intubation platform, hanging them by their incisors placed on the wire. ...
This study aimed to investigate the potential anti-fibrotic activity of vinpocetine in an experimental model of pulmonary fibrosis by bleomycin and in the MRC-5 cell line. Pulmonary fibrosis was induced in BALB/c mice by oropharyngeal aspiration of a single dose of bleomycin (5 mg/kg). The remaining induced animals received a daily dose of pirfenidone (as a standard anti-fibrotic drug) (300 mg/kg/PO) and vinpocetine (20 mg/kg/PO) on day 7 of the induction till the end of the experiment (day 21). The results of the experiment revealed that vinpocetine managed to alleviate the fibrotic endpoints by statistically improving (P ≤ 0.05) the weight index, histopathological score, reduced expression of fibrotic-related proteins in immune-stained lung sections, as well as fibrotic markers measured in serum samples. It also alleviated tissue levels of oxidative stress and inflammatory and pro-fibrotic mediators significantly elevated in bleomycin-only induced animals (P ≤ 0.05). Vinpocetine managed to express a remarkable attenuating effect in pulmonary fibrosis both in vivo and in vitro either directly by interfering with the classical TGF-β1/Smad2/3 signaling pathway or indirectly by upregulating the expression of Nrf2 enhancing the antioxidant system, activating PPAR-γ and downregulating the NLRP3/NF-κB pathway making it a candidate for further clinical investigation in cases of pulmonary fibrosis.
... In comparison with physiological values without anaesthesia, heart rate and mean blood pressure were less impacted with isoflurane-maintained anaesthesia compared with ketamine-xylazine. These results highlight the cardiodepressant effect of ketamine-xylazine and are consistent with studies which reported that isoflurane had lower haemodynamic effects with respect to ketamine-xylazine anaesthesia [31][32][33] . Blood glucose levels were also less impacted with isoflurane-maintained anaesthesia than by ketamine-xylazine, which is consistent with previous findings demonstrating hyperglycaemia and reduced plasma insulin levels with ketamine-xylazine 34,35 . ...
Anaesthetics are used daily in human and veterinary medicine as well as in scientific research. Anaesthetics have an impact on cell homeostasis especially through modulation of protein post-translational modifications. O-GlcNAcylation, a ubiquitous post-translational modification, plays a role in many biological processes. The aims of this study were to evaluate whether (1) anaesthesia influences O-GlcNAcylation and (2) its stimulation affects physiological parameters. Male Wistar rats (n = 38) were anaesthetized with ketamine-xylazine or isoflurane. They randomly received either an intravenous injection of Ringer's lactate or NButGT (10mg/kg) in order to increase O-GlcNAcylation levels. One hour after induction of anaesthesia, haemodynamic parameters and plasmatic markers were evaluated. Heart, brain and lungs were harvested and O-GlcNAcylation levels and O-GlcNAc-related enzymes were evaluated by western blot. Cardiac and pulmonary O-GlcNAcylation levels and cardiac, cerebral and pulmonary O-GlcNAc associated enzyme expression were not impacted with anaesthesia. Compared with ketamine-xylazine, isoflurane had a lower impact on blood pressure, heart rate and glycaemia. Pharmacological stimulation of O-GlcNAcylation by NButGT did not affect the physiological parameters. This study offers unprecedented insights into the regulation of O-GlcNAcylation and O-GlcNAc related enzymes during anaesthesia. Pharmacological stimulation of O-GlcNAcylation over a 1-h period did not disrupt the physiological balance in healthy anaesthetized rats.
... At the end of the experiment, all rats were terminated, and surgery was performed to remove the liver after blood samples were obtained by puncturing the heart with a 23G needle while being anesthetized with ketamine and xylazine at doses of 100 mg/kg and 5 mg/kg. 24 The guidelines for the welfare of laboratory animals by the Research Ethical Committee of Universitas Padjajaran refer to American Veterinary Medical Association (AVMA) guidelines for the Euthanasia of Animals: 2020 Edition and National Research Council of the National Academies, Guide for the Care and Use of Laboratory Animals (Eight Edition), 2011, approved this research with approval number 1009/UN6.KEP/EC/2020. ...
Background: No drug with a liver antifibrotic effect for treating non-alcoholic fatty liver disease (NAFLD) has been approved. Physalis angulata Linn., better known to Indonesian as ciplukan, has natural abilities in various metabolic and inflammatory diseases. This study aims to determine the effect of ethyl acetate fraction of P. angulata in the NAFLD rat model by examining alanine aminotransferase (ALT), cholesterol levels, and liver histopathological features, which are methods to evaluate the course of the disease and the potential antifibrotic effect.Method: This research is an in vivo study on male Wistar rats conducted at the Animal Laboratory, Faculty of Medicine, Universitas Padjadjaran, from September to November 2020. Rats were grouped randomly into seven groups of 5 each. The NAFLD models were created by giving a diet containing 20% margarine for four weeks. The intervention groups were given vitamin E, ethyl acetate fraction of P. angulata, and both combinations. The statistical analysis examined differences in each group based on their histopathological features, ALT, and cholesterol levels.Results: Histopathological results in the group given P. angulata at a dose of 0.32 mg resembled normal liver, and the ALT level was similar to vitamin E. The administration of P. angulata at 0.16 mg dose improved cholesterol levels.Conclusions: P. angulata ethyl acetate fraction at a dose of 0.32 mg improved the histopathological and serum ALT levels in the NAFLD rat model, which could be the basis for the mechanism of P. angulata's antifibrotic ability in NAFLD conditions.
... At the end of the experiment, all rats were terminated, and surgery was performed to remove the liver after blood samples were obtained by puncturing the heart with a 23G needle while being anesthetized with ketamine and xylazine at doses of 100 mg/kg and 5 mg/kg. 24 The guidelines for the welfare of laboratory animals by the Research Ethical Committee of Universitas Padjajaran refer to American Veterinary Medical Association (AVMA) guidelines for the Euthanasia of Animals: 2020 Edition and National Research Council of the National Academies, Guide for the Care and Use of Laboratory Animals (Eight Edition), 2011, approved this research with approval number 1009/UN6.KEP/EC/2020. ...
Background: No drug with a liver antifibrotic effect for treating non-alcoholic fatty liver disease (NAFLD) has been approved. Physalis angulata Linn., better known to Indonesian as ciplukan, has natural abilities in various metabolic and inflammatory diseases. This study aims to determine the effect of ethyl acetate fraction of P. angulata in the NAFLD rat model by examining alanine aminotransferase (ALT), cholesterol levels, and liver histopathological features, which are methods to evaluate the course of the disease and the potential antifibrotic effect.Method: This research is an in vivo study on male Wistar rats conducted at the Animal Laboratory, Faculty of Medicine, Universitas Padjadjaran, from September to November 2020. Rats were grouped randomly into seven groups of 5 each. The NAFLD models were created by giving a diet containing 20% margarine for four weeks. The intervention groups were given vitamin E, ethyl acetate fraction of P. angulata, and both combinations. The statistical analysis examined differences in each group based on their histopathological features, ALT, and cholesterol levels.Results: Histopathological results in the group given P. angulata at a dose of 0.32 mg resembled normal liver, and the ALT level was similar to vitamin E. The administration of P. angulata at 0.16 mg dose improved cholesterol levels.Conclusions: P. angulata ethyl acetate fraction at a dose of 0.32 mg improved the histopathological and serum ALT levels in the NAFLD rat model, which could be the basis for the mechanism of P. angulata's antifibrotic ability in NAFLD conditions.
... In rabbits [35] and cats [36], isoflurane induced tachycardia that appeared mainly attributable to an additional vagal withdrawal [35]. In rats, Albrecht et al. also observed a significant increase in heart rate under 2-4% isoflurane [38]. However, Yang et al. observed a significant decrease in heart rate, blood pressure and cardiac function in rats when isoflurane concentrations increased from 0.5 to 1%, 1.5%, 2% and 3% [39]. ...
... The first placed and longest anaesthetized mouse therefore might adapt its thermoregulation to lower ambient temperatures despite the bed heated at 37 °C. Albrecht et al. reported a drop in blood temperature to 36.6 °C in rats during the sixth isoflurane anaesthesia of 40 min duration within three weeks [38]. Therefore, it might be possible that a slight cooling of animals with time promoted vasoconstriction and partly contributed to a reduced RBF. ...
Background
The influence of anaesthetic depth and the potential influence of different anaesthetic beds and thus different handling procedures were investigated in 86 severe combined immunodeficient (SCID) mice using semi-stationary dynamic single photon emission computed tomography (SPECT) for kidney scintigraphy. Therefore, isoflurane concentrations were adjusted using respiratory rate for low (80–90 breath/min) and deep anaesthesia (40–45 breath/min). At low anaesthesia, we additionally tested the influence of single bed versus 3-mouse bed hotel; the hotel mice were anaesthetized consecutively at ~ 30, 20, and 10 min before tracer injections for positions 1, 2, and 3, respectively. Intravenous [99mTc]Tc-MAG3 injection of ~ 28 MBq was performed after SPECT start. Time-activity curves were used to calculate time-to-peak (Tmax), T50 (50% clearance) and T25 (75% clearance).
Results
Low and deep anaesthesia corresponded to median isoflurane concentrations of 1.3% and 1.5%, respectively, with no significant differences in heart rate (p = 0.74). Low anaesthesia resulted in shorter aortic blood clearance half-life (p = 0.091) and increased relative renal tracer influx rate (p = 0.018). A tendency toward earlier Tmax occurred under low anaesthesia (p = 0.063) with no differences in T50 (p = 0.40) and T25 (p = 0.24). Variance increased with deep anaesthesia. Compared to single mouse scans, hotel mice in position 1 showed a delayed Tmax, T50, and T25 (p < 0.05 each). Furthermore, hotel mice in position 1 showed delayed Tmax versus position 3, and delayed T50 and T25 versus position 2 and 3 (p < 0.05 each). No difference occurred between single bed and positions 2 (p = 1.0) and 3 (p = 1.0).
Conclusions
Deep anaesthesia and prolonged low anaesthesia should be avoided during renal scintigraphy because they result in prolonged blood clearance half-life, delayed renal influx and/or later Tmax. Vice versa, low anaesthesia with high respiratory rates of 80–90 rpm and short duration (≤ 20 min) should be preferred to obtain representative data with low variance.
... Table 1) confirms published data that both types of anesthesia influence the cardiovascular system differently. [28][29][30][31] In the case of volatile anesthetic ISO, our control APW-Ps for systolic BP, diastolic BP, and heart rate were similar, but the pulse BP was lower as that reported by Albrecht et al. 29 (Table 1). Our values are higher in comparison to published data from rats in which 3% ISO decreased myocardial contractility, BP, and heart rate and impaired left ventricular diastolic function. ...
... Table 1) confirms published data that both types of anesthesia influence the cardiovascular system differently. [28][29][30][31] In the case of volatile anesthetic ISO, our control APW-Ps for systolic BP, diastolic BP, and heart rate were similar, but the pulse BP was lower as that reported by Albrecht et al. 29 (Table 1). Our values are higher in comparison to published data from rats in which 3% ISO decreased myocardial contractility, BP, and heart rate and impaired left ventricular diastolic function. ...
... 5,6,10,11,[39][40][41][42] Unfortunately, it is not fully known which signaling pathway(s) are influenced by these anesthetics. [28][29][30][31]33 If it is known, we might speculate what changes in APW-Ps reflect particular pathway(s). ...
Background
Information obtained from arterial pulse waveforms (APW) can be useful for characterizing the cardiovascular system. To achieve this, it is necessary to know the detailed characteristics of APWs in different states of an organism, which would allow APW parameters (APW‐Ps) to be assigned to particular (patho)physiological conditions. Therefore, our work aimed to characterize 35 APW‐Ps in rats under the influence of isoflurane (ISO) and Zoletil/xylazine (ZO/XY) anesthesia and to study the effect of root extract from Acanthopanax senticosus (ASRE) in these anesthetic conditions.
Methods
The right jugular vein of anesthetized rats was cannulated for the administration of ASRE and the left carotid artery for the detection of APWs from which 35 APW‐Ps were evaluated.
Results
We obtained data on 35 APW‐Ps, which significantly depended on the anesthesia, and thus, they characterized the cardiovascular system under these two conditions. ASRE transiently modulated all 35 APW‐Ps, including a transient decrease in systolic and diastolic blood pressure (BP) and heart rate or increases in pulse BP, d P /d t max , and systolic and diastolic areas. Whereas the transient effects of ASRE were similar, the extract had prolonged disturbing effects on the cardiovascular system in rats under ZO/XY but not under ISO anesthesia. This negative effect can result from the disturbance caused by ZO/XY anesthesia on the cardiovascular system.
Conclusions
We characterized 35 APW‐Ps of rats under ISO and ZO/XY anesthesia and found that ASRE contains compounds that can modulate the properties of the cardiovascular system, which significantly depended on the status of the cardiovascular system. This should be considered when using ASRE as a nutritional supplement by individuals with cardiovascular problems.
... However, in our hands, this resulted in unstable anesthesia, which made the subsequent intratracheal instillation very difficult. In addition, this protocol resulted in long recovery times as reported before [2], and also animal death. Subsequently, we switched to a Ketalar, Domitor, and Fentanyl-based anesthetic protocol [1]. ...
Background
The inducible Kras/p53 lung adenocarcinoma mouse model, which faithfully recapitulates human disease, is routinely initiated by the intratracheal instillation of a virus-based Cre recombinase delivery system. Handling virus-based delivery systems requires elevated biosafety levels, e.g., biosafety level 2 (BSL-2). However, in experimental animal research facilities, following exposure to viral vectors in a BSL-2 environment, rodents may not be reclassified to BSL-1 according to standard practice, preventing access to small animal micro-computed tomography (micro-CT) scanners that are typically housed in general access areas such as BSL-1 rooms. Therefore, our goal was to adapt the protocol so that the Cre-induced KP mouse model could be handled under BSL-1 conditions during the entire procedure.
Results
The Kras-Lox-STOP-Lox-G12D/p53 flox/flox (KP)-based lung adenocarcinoma mouse model was activated by intratracheal instillation of either an adenoviral-based or a gutless, adeno-associated viral-based Cre delivery system. Tumor growth was monitored over time by micro-CT. We have successfully substituted the virus-based Cre delivery system with a commercially available, gutless, adeno-associated, Cre-expressing vector that allows the KP mouse model to be handled and imaged in a BSL-1 facility. By optimizing the anesthesia protocol and switching to a microscope-guided vector instillation procedure, productivity was increased and procedure-related complications were significantly reduced. In addition, repeated micro-CT analysis of individual animals allowed us to monitor tumor growth longitudinally, dramatically reducing the number of animals required per experiment. Finally, we documented the evolution of tumor volume for different doses, which revealed that individual tumor nodules induced by low-titer AAV-Cre transductions can be monitored over time by micro-CT.
Conclusion
Modifications to the anesthesia and instillation protocols increased the productivity of the original KP protocol. In addition, the switch to a gutless, adeno-associated, Cre-expressing vector allowed longitudinal monitoring of tumor growth under BSL-1 conditions, significantly reducing the number of animals required for an experiment, in line with the 3R principles.
... At the end of the study, the rabbits were intra-muscularly injected with ketamine/xylazine mixture (35 + 5mg/kg) to anesthetize them (24). The aorta, liver and kidney were removed from the scari ed animals and immersed into training for future investigation. ...
Inflammation control is becoming a critical strategy for atherosclerosis management, because inflammation is involved in plaque progression. In this regard, a biomimetic strategy using cell membrane-coated nanoparticles has some promising advantages. In the study, a RBC membrane-based nanoghost containing Glyburide (Glibenclamide) was prepared using an extrusion method. The hydrodynamic size and zeta potential of the nanoghost were changed compared to PLGA nanoparticles. In addition, a nanoghost with a diameter and shell size of 125nm and 8.3nm was obtained based on the TEM measurement. The fabricated nanoghost was not only hemocompatible but also was biocompatible. According to RT-PCR assay, the expression levels of inflammatory genes including NLRP3, IL-1β, IL-18 caspase1, 8 and 9 were decreased. In accordance with in vitro anti-inflammation properties, total foam cells, total surface area in tunica intima and population of CD14 + cells were decreased in the rabbit model of atherosclerosis upon nanoghost treatment, compared to positive control. Furthermore, macrophages in aorta sections exhibited M1 to M2 polarization. In general, the development of Glyburide-loaded nanoghost can be considered as a potential therapeutic for controlling the progression and inflammation of atherosclerotic plaque.
