Carotid Catheterization and Automated Blood Sampling Induce Systemic IL-6 Secretion and Local Tissue Damage and Inflammation in the Heart, Kidneys, Liver and Salivary Glands in NMRI Mice

Abstract

Automated blood sampling through a vascular catheter is a frequently utilized technique in laboratory mice. The potential immunological and physiological implications associated with this technique have, however, not been investigated in detail. The present study compared plasma levels of the cytokines IL-1β, IL-2, IL-6, IL-10, IL-17A, GM-CSF, IFN-γ and TNF-α in male NMRI mice that had been subjected to carotid artery catheterization and subsequent automated blood sampling with age-matched control mice. Body weight and histopathological changes in the surgical area, including the salivary glands, the heart, brain, spleen, liver, kidneys and lungs were compared. Catheterized mice had higher levels of IL-6 than did control mice, but other cytokine levels did not differ between the groups. No significant difference in body weight was found. The histology revealed inflammatory and regenerative (healing) changes at surgical sites of all catheterized mice, with mild inflammatory changes extending into the salivary glands. Several catheterized mice had multifocal degenerative to necrotic changes with inflammation in the heart, kidneys and livers, suggesting that thrombi had detached from the catheter tip and embolized to distant sites. Thus, catheterization and subsequent automated blood sampling may have physiological impact. Possible confounding effects of visceral damage should be assessed and considered, when using catheterized mouse models.

Ultrasonographic and histological evaluation of the effects of long-term carotid catheterization on cardiac function in NMRI mice

“…Based on the results in the present study, implantation of a carotid catheter with the tip positioned in the proximal brachiocephalic trunk has minimal influence on cardiac and aortic physiology, and does not seem to induce significant histopathological changes in the heart. These results are in contrast to histological analyses obtained in a previous study, 7 where early signs of myocardial degeneration with fibrosis were seen only four days post-catheterization. In this study, catheterized mice were connected to an automated blood sampling device following surgery, and were subjected to computer-driven blood sampling and saline infusions.…”

“…Vascular catheters in mice, however, may be associated with complications that threaten survival, complicate post-surgical catheter maintenance and impair animal welfare. 7,16,23 Thus, further efforts must be made to minimize deleterious effects on the models, and the redundant use of animals in research.…”

“…The specified gender, stock and number of mice were used to test the hypothesis, based on histological analyses and practical experience from previous catheterization studies. 6,7 We generally use outbred NMRI stock in our catheterization studies, as these are commonly used in general biological research. 13 Furthermore, they are genetically uniform in comparison to the wide variability of a species but without lacking genetic diversity, as do the genetically defined inbred mouse strains.…”

Clinical, Physiologic, and Behavioral Evaluation of Permanently Catheterized NMRI Mice

“…Postoperative weight loss, stress, inflammation, and catheter occlusion are frequent complications of catheterization that may compromise animal welfare as well as the use of various mouse models. 24,43,47,48 Therefore, it is still crucial to evaluate the technique critically, because vascular catheterization most often is conducted for long-term purposes. We performed the present study to elucidate whether and to what extent long-term arterial catheterization affected parameters of animal welfare in laboratory mice.…”

“…A recent study suggests that catheterized mice have subclinical pathologic changes in well-vascularized organs, such as the kidneys, liver, and heart, and that cytokine levels increase after surgery and may stay elevated past a 3-d recovery period. 48 Stress is a complex state in the animal, elicited when a stressor stimulates the HPA axis, causing a systemic increase in stress hormones that in turn causes a plethora of physiologic responses. 30,31,37,38 Corticosterone, the main effector hormone of the HPA axis in rodents, is released from the adrenal cortex and can be quantified noninvasively through metabolites excreted in feces.…”