Abstract

Simple SummaryFunctional hemodialysis access is essential for the survival of patients with end-stage renal disease. Although various guidelines recommend autologous arteriovenous fistula as the first choice for hemodialysis, it is still the Achilles heel for patients. Several in vivo models have been used to study and improve the mechanisms of vascular remodeling of arteriovenous fistula. However, some models have the disadvantage of having anatomical features or a hemodynamic profile different from that of the arteriovenous fistula in humans. In the presented cervical arteriovenous fistula model, these disadvantages were eliminated. It resembles the human physiology and is an ideal animal model for arteriovenous fistula research. Moreover, in order to understand the impact of this model on animal welfare, the distress of this new animal model was analyzed. Body weight, faecal corticosterone metabolites, burrowing activity, nesting behaviour and distress scores were analysed after fistula creation and during the following three weeks. The physiological, behavioural, and neuroendocrine assessments all indicated that this model causes only moderate distress to the animals. This not only meets the need for animal ethics but also improves the quality of scientific research. Therefore, this cervical model is suitable for arteriovenous fistula research and should be used more frequently in the future.The welfare of laboratory animals is a consistent concern for researchers. Its evaluation not only fosters ethical responsibility and addresses legal requirements, but also provides a solid basis for a high quality of research. Recently, a new cervical arteriovenous model was created in mice to understand the pathophysiology of arteriovenous fistula, which is the most commonly used access for hemodialysis. This study evaluates the distress caused by this new animal model. Ten male C57B6/J mice with cervical arteriovenous fistula were observed for 21 days. Non-invasive parameters, such as body weight, faecal corticosterone metabolites, burrowing activity, nesting activity and distress scores were evaluated at each time point. Six out of ten created arteriovenous fistula matured within the observation time as defined by an increased diameter. The body weight of all animals was reduced after surgery but recovered within five days. In addition, the distress score was significantly increased during the early time point but not at the late time point after arteriovenous fistula creation. Neither burrowing activity nor nesting behaviour were significantly reduced after surgical intervention. Moreover, faecal corticosterone metabolite concentrations did not significantly increase. Therefore, the cervical murine arteriovenous fistula model induced moderate distress in mice and revealed an appropriate maturation rate of the fistulas.

Highlights

  • As vascular access for hemodialysis, all academic guidelines suggest autologous arteriovenous fistula (AVF) as the first option [1,2]

  • None of these models mimics the anatomical characteristics of AVF in hemodialysis patients, which determines the hemodynamic profile within the fistula

  • The analysis of multiple distress parameters, such as body weight, Faecal corticosterone metabolites (FCMs), burrowing activity, nesting activity and a distress score, demonstrated that this model in mice can be established without causing severe distress

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Summary

Introduction

As vascular access for hemodialysis, all academic guidelines suggest autologous arteriovenous fistula (AVF) as the first option [1,2]. AVFs were created between the aorta and the inferior cava vein in a side-to-side manner [5] or by anastomosis of the common carotid artery to the jugular vein in an end-to-end manner [6]. None of these models mimics the anatomical characteristics of AVF in hemodialysis patients, which determines the hemodynamic profile within the fistula. This is very important because the blood flow dynamics have an important impact on AVF maturation and dysfunction [7]. It is not known what distress the model induces in the experimental animals

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