Is Chronobiology of Internal Environment Important for “In Vivo” Rat Experiments?

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Is Chronobiology of Internal Environment Important for “In Vivo” Rat Experiments?

Journal Title: Journal of Anesthetic Research and Pain Medicine - Year 2018, Vol 3, Issue 1

Abstract

At the end of the 18th and early 19th century, the white rat became the most commonly used experimental animal in biomedical research because it was recognized as the preeminent model of the mammalian system. Currently, rat models are widely used not only because of their low costs but also for their ability to mimic several human pathologies. These models are used to analyze basic physiological mechanisms, for preclinical and toxicological studies, and/or the evaluation of therapeutic approaches [3, 2]. Rats are also useful model animals for studying acid-base balance, especially in relation to the cardiovascular and respiratory systems [3]. The design and development of experimental, in vivo, chronobiological animal models may help reveal some of the relationships between circadian rhythms and biological function, which is sometimes exceedingly difﬁcult to study in humas. Popilskis et al. (2008) referred to the fact that “nonhuman primates are important models for a wide variety of biomedical and behavioural research because of their close phylogenetic relationship to humans and they are useful models for experimental surgical studies” [1]. However, in the the design and development of such chronobiological in vivo rat models, several problems may be encountered. First is the fact that homeostatic regulatory mechanisms are not eliminated; therefore, the responses of the animal as a whole are only a reflection of these mechnisms at a particular time of day. Second is that the circadian rhythms of the observed function itself are not accounted for. Finally, the initial state of the internal environment and the parameters of the function being observed―after the induction of general anaesthesia―are often not considered. In vivo experiments require the use of appropriate anaesthesia, which should be selected according to their particular effect on the organism. Moreover, an increasing number of rat and mice studies have acknowledged that the toxicity and efﬁcacy of some anaesthetic agents ﬂuctuate in circadian dependence. Nevertheless, anaesthesia has played an important role in ensuring humane surgical/interventions in experimental animals, particularly in long-term in vivo protocols requiring animal survival. Presently, anaesthetic practice is primarily based on physiology. The importance of the application of physiological principles in anaesthesia has been reaffirmed and emphasizes the need for progress in systemic physiology [4]. The key role of homeostatic maintainance in all living organisms is not at odds with the observation that various biological parameters are dynamic mainly related to cardiovascular and respiratory systems. Changes in the functional efficiency of these systems lead to changes in acid-base balance and, vice versa, changes in acid-base parameters affect the functional state of these systems. Similarly, changes in acid-base balance also reflect 24 h fluctuations in respiratory and cardiovascular functions. Therefore, reference values for acid-base balance as well as ion concentration can cause problems because they reflect the current state of the organism at a given time. Results are often compared with average reference values, and often regardless of their dependence on the circadian rhythm, what may be the potential risk of experimental design. If acid-base balance and ion concentrations change in circadian dependence, circadian changes under general anesthesia may be of interest. From this point of view, we investigated chronobiological aspects of the status of acid-base balance and plasma ion concentrations in arterial blood (i.e., existence of possible circadian variations) under pentobarbital (P), ketamine/xylazine (K/X), and zoletil (Z) anaesthesia in spontaneously breathing rats. After summarizing the results from the analysis of acid-base balance parameters and ions, we concluded that there are differences in the final status of the rat internal environment, and that depends on the LD cycle and on the type of anaesthesia (table 1). This should be taken into account and experiments should start with a normal range of acid-base balance. Even at the beginning of the experiment, the altered internal environment may affect the activity of systems whose functions are primarily dependent on acid-base balance. P anaesthesia is not the most appropriate type of general anaesthesia to use in chronobiological rat models. It is likely to produce a more acidic environment than K/X and Z anaesthesias and, although an LD difference in P anaesthesia was not recorded, the pH values were the lowest in both light parts of the rat regimen day compared with K/X and Z anaesthesias. It means that it is not possible to monitor periodic changes in the functions of individual systems that are primarily dependent on changes in extracellular pH. As a result, P probably and immediately reduces either the activity of the buffer systems or inhibits the regulatory mechanisms associated with the maintenance of isohydria, independently of the LD cycle. In this regard, K/X and Z anaesthesias may be more appropriate for general anaesthesia because the arterial pH varies within the range of isohydria. This assumption is only valid if the rat experiments are performed under K/X and Z anaesthesia in the dark (i.e., active) parts of the day.

Authors and Affiliations

Dr. Pavol Svorc

Keywords

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EP ID EP275899
DOI 10.28967/jarpm.2018.01.18001
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