A respiratory‐gated micro‐<scp>CT</scp> comparison of respiratory patterns in free‐breathing and mechanically ventilated rats

Ford, Nancy L.; McCaig, Lynda; Jeklin, Andrew T.; Lewis, James F.; Veldhuizen, Ruud A. W.; Holdsworth, David W.; Drangova, Maria

doi:10.14814/phy2.13074

Cited by 8 publications

(8 citation statements)

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“…Supplemental oxygen provided via nose cone or mask is reported in only few other papers [29, 30], sometimes during only anaesthetic induction [7]. To the best of our knowledge, only few papers mention the importance of oxygen, which matches our findings: Ford et al stated that it is important to monitor vital parameters during anaesthesia because, especially for injectable anaesthetics, hypoxia is specified as a threat [15]. The authors used oxygen inhalation through a nose cone to prevent hypoxia.…”

Section: Discussionsupporting

confidence: 75%

Oxygen inhalation improves postoperative survival in ketamine-xylazine anaesthetised rats: An observational study

et al. 2019

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ObjectiveA simple but reliable and safe anaesthetic procedure is required for surgical interventions in small rodents. Combined ketamine and xylazine injections are often used in rats for less invasive surgery, possibly with spontaneous breathing and without airway management. However, there are important pitfalls to be avoided by special precautions and monitoring, as shown subsequently.Study designObservational study.AnimalsTwenty-four anaesthetic procedures for bile duct ligation, sham operation or carotid artery dilatation in 20 male Sprague-Dawley rats, preoperatively weighing between 440 and 550 g.MethodsIntolerable high mortality rates occurred in the first 7 postoperative days while establishing a new experimental model in rats using ketamine-xylazine anaesthesia. Rats were spontaneously breathing ambient air during the first 12 surgeries without airway management. An observed high mortality rate in these animals led to a change in the trial protocol: the insufflation of 2 litres of oxygen per minute via nose cone during the following 12 rat surgeries. Retrospective comparison of the outcome (without oxygen vs. with oxygen insufflation) was conducted.ResultsThe perioperative mortality rate could be significantly reduced from 58% (7/12) to 17% (2/12) (p = 0.036) by oxygen insufflation via nose cone. Significantly different levels of intraoperative oxygen saturation (SpO2; 89 ± 4% [without oxygen] vs. 97 ± 0.5% [with oxygen], p < 0.0001), but no significant differences in heart rate (HR; 267 ± 7 beats minute–1 [bpm] [without oxygen] vs. 266 ± 6 bpm [with oxygen], p = 0.955) were observed.Conclusions and clinical relevanceIn summary, rats under ketamine-xylazine anaesthesia are susceptible to hypoxia. This may lead to increased delayed mortality related to hypoxia induced lung failure. Apparently, this is an underestimated problem. We highly recommend using additional oxygen insufflation in spontaneously breathing rats under ketamine-xylazine anaesthesia with basic monitoring such as measurement of oxygen saturation.

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Section: Discussionsupporting

confidence: 75%

Oxygen inhalation improves postoperative survival in ketamine-xylazine anaesthetised rats: An observational study

et al. 2019

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“…The volume of each compartment was normalized and expressed in the percentage of total lung volume for all CT scans. Mean Lung Attenuation (MLA) was also extracted from each rescaled HU image at the end of the expiratory phase to quantify the content of air (also known as Functional Residual Capacity (FRC) [ 16 , 17 ] and tissue in the lung, following the equations: …”

Section: Methodsmentioning

confidence: 99%

Pivotal role of micro-CT technology in setting up an optimized lung fibrosis mouse model for drug screening

Khalajzeyqami

Grandi²,

Ferrini³

et al. 2022

PLoS ONE

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Idiopathic pulmonary fibrosis (IPF) is a progressive disease with no curative pharmacological treatment. The most used animal model of IPF for anti-fibrotic drug screening is bleomycin (BLM)-induced lung fibrosis. However, several issues have been reported: the balance among disease resolution, an appropriate time window for therapeutic intervention and animal welfare remain critical aspects yet to be fully elucidated. In this study, C57Bl/6 male mice were treated with BLM via oropharyngeal aspiration (OA) following either double or triple administration. The fibrosis progression was longitudinally assessed by micro-CT every 7 days for 4 weeks after BLM administration. Quantitative micro-CT measurements highlighted that triple BLM administration was the ideal dose regimen to provoke sustained lung fibrosis up to 28 days. These results were corroborated with lung histology and Bronchoalveolar Lavage Fluid cells. We have developed a mouse model with prolonged lung fibrosis enabling three weeks of a curative therapeutic window for the screening of putative anti-fibrotic drugs. Moreover, we have demonstrated the pivotal role of longitudinal micro-CT imaging in reducing the number of animals required per experiment in which each animal can be its own control. This approach permits a valuable decrease in costs and time to develop disease animal models.

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“…Changes in respiratory system parameters over time were expected to happen in this experimental model. We did not induce a primary lung injury, but anaesthetic drugs, like ketamine, xylazine and isoflurane, induces hypoventilation, specifically, a reduction in V t 24–28. The observed variation in regional strain during the observation period could be explained by this mechanism, even if FRC did not change.…”

Section: Discussionmentioning

confidence: 93%

Mapping regional strain in anesthetised healthy subjects during spontaneous ventilation

et al. 2019

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IntroductionBreathing produces a phenomenon of cyclic deformation throughout life. Biomechanically, deformation of the lung is measured as strain. Regional strain recently started to be recognised as a tool in the study of lung pathophysiology, but regional lung strain has not been studied in healthy subjects breathing spontaneously without voluntary or pharmacological control of ventilation. Our aim is to generate three-dimensional (3D) regional strain and heterogeneity maps of healthy rat lungs and describe their changes over time.MethodsMicro-CT and image-based biomechanical analysis by finite element approach were carried out in six anaesthetised rats under spontaneous breathing in two different states, at the beginning of the experiment and after 3 hours of observation. 3D regional strain maps were constructed and divided into 10 isovolumetric region-of-interest (ROI) in three directions (apex to base, dorsal to ventral and costal to mediastinal), allowing to regionally analyse the volumetric strain, the strain progression and the strain heterogeneity. To describe in depth these parameters, and systematise their report, we defined regional strain heterogeneity index [1+strain SD ROI(x)]/[1+strain mean ROI(x)] and regional strain progression index [ROI(x)−mean of final strain/ROI(x)−mean of initial strain].ResultsWe were able to generate 3D regional strain maps of the lung in subjects without respiratory support, showing significant differences among the three analysed axes. We observed a significantly lower regional volumetric strain in the apex sector compared with the base, with no significant anatomical systematic differences in the other directions. This heterogeneity could not be identified with physiological or standard CT methods. There was no progression of the analysed regional volumetric strain when the two time-points were compared.DiscussionIt is possible to map the regional volumetric strain in the lung for healthy subjects during spontaneous breathing. Regional strain heterogeneity and changes over time can be measured using a CT image-based numerical analysis applying a finite element approach. These results support that healthy lung might have significant regional strain and its spatial distribution is highly heterogeneous. This protocol for CT image acquisition and analysis could be a useful tool for helping to understand the mechanobiology of the lung in many diseases.

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A respiratory‐gated micro‐CT comparison of respiratory patterns in free‐breathing and mechanically ventilated rats

Cited by 8 publications

References 36 publications

Oxygen inhalation improves postoperative survival in ketamine-xylazine anaesthetised rats: An observational study

Oxygen inhalation improves postoperative survival in ketamine-xylazine anaesthetised rats: An observational study

Pivotal role of micro-CT technology in setting up an optimized lung fibrosis mouse model for drug screening

Mapping regional strain in anesthetised healthy subjects during spontaneous ventilation

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