Skip to main content

Thank you for visiting You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

Perioperative support reduces mortality of obese BALB/c mice after ovariectomy


The incidence of obesity is on the rise in most western countries and represents major risks to health. Obesity causes complex metabolic dysfunctions and can be associated with a large number of secondary diseases. To investigate causal mechanisms of obesity and develop better options for treatment, researchers study the condition in animal models. In addition to genetically engineered animal models, diet-induced obesity is often used because it occurs similarly in animals as it does in humans. For several types of investigations that use obesity models, investigators must carry out surgical interventions and they frequently encounter severe perioperative complications induced by anesthesia. In an example of this problem, we observed 100% mortality in obese BALB/c mice after ovariectomy, despite no obvious surgical complications. We supposed that a failure to recover from surgery was the primary cause of this increased mortality. Therefore, to support their recovery from surgery we administered atropine to obese mice in order to facilitate blood circulation, and we also increased the oxygen content of the ambient air. With this specific support before and after surgery, we increased the survival rate of obese ovariectomized mice up to 83%. These results confirm the assumption that obesity is a risk factor for the recovery of obese animal models after ovariectomy, and they highlight the need to provide additional interventions for such experimental animals.

Access options

Rent or Buy article

Get time limited or full article access on ReadCube.


All prices are NET prices.

Figure 1: Timeline of the treatment that was administered to obese mice before, during and after surgery.
Figure 2: Perioperative treatment of obese mice.
Figure 3: Body weights of control and obese mice.
Figure 4: Gross depictions of fat mass in mice.
Figure 5: Survival rates of mice that received surgical operations with or without a perioperative treatment regimen.


  1. 1

    WHO. Obesity: preventing and managing the global epidemic. Report of a WHO consultation. World Health Organ. Tech. Rep. Ser. 894, 1–253 (2000).

  2. 2

    Michel, K.E., Fascetti, A. & Delany, S.J. in Applied Veterinary Clinical Nutrition (eds. Fascetti, A. & Delany, S.J.) 109–124 (John Wiley & Sons Ltd., West Sussex, UK, 2012).

    Google Scholar 

  3. 3

    Blüher, M. Adipose tissue dysfunction in obesity. Exp. Clin. Endocrinol. Diabetes 117, 241–250 (2009).

    Article  Google Scholar 

  4. 4

    Trayhurn, P. & Wood, I.S. Signalling role of adipose tissue: adipokines and inflammation in obesity. Biochem. Soc. Trans. 33, 1078–1081 (2005).

    CAS  Article  Google Scholar 

  5. 5

    Blüher, M. Adipokines—removing road blocks to obesity and diabetes therapy. Mol. Metab. 3, 230–240 (2014).

    Article  Google Scholar 

  6. 6

    Bianchini, F., Kaaks, R. & Vainio, H. Overweight, obesity and cancer risk. Lancet Oncol. 3, 565–574 (2002).

    Article  Google Scholar 

  7. 7

    Trentham-Dietz, A. et al. Weight change and risk of postmenopausal breast cancer (United States). Cancer Causes Control 11, 533–542 (2000).

    CAS  Article  Google Scholar 

  8. 8

    MacLean, P.S. et al. A surprising link between the energetics of ovariectomy-induced weight gain and mammary tumor progression in obese rats. Obesity (Silver Spring) 18, 696–703 (2010).

    Article  Google Scholar 

  9. 9

    Mathis, M.R. et al. Patient selection for day case-eligible surgery. Anesthesiology 119, 1310–1321 (2013).

    Article  Google Scholar 

  10. 10

    Brodbelt, D.C., Pfeiffer, D.U., Young, L.E. & Wood, J.L.N. Results of the confidential enquiry into perioperative small animal fatalities regarding risk factors for anesthetic-related death in dogs. J. Am. Vet. Med. Assoc. 233, 1096–1104 (2008).

    Article  Google Scholar 

  11. 11

    Love, L. & Cline, M.G. Perioperative physiology and pharmacology in the obese small animal patient. Vet. Anaesth. Analg. 42, 119–132 (2015).

    Article  Google Scholar 

  12. 12

    Burnside, W.M., Flecknell, P.A., Cameron, A.I. & Thomas, A.A. A comparison of medetomidine and its active enantiomer dexmedetomidine when administered with ketamine in mice. BMC Vet. Res. 9, 48 (2013).

    Article  Google Scholar 

  13. 13

    Taylor, R., Hayes, K.E. & Toth, L.A. Evaluation of an anesthetic regimen for retroorbital blood collection from mice. Contemp. Top. Lab. Anim. Sci. 39, 14–17 (2000).

    CAS  PubMed  PubMed Central  Google Scholar 

  14. 14

    Zuurbier, C.J., Emons, V.M. & Ince, C. Hemodynamics of anesthetized ventilated mouse models: aspects of anesthetics, fluid support, and strain. Am. J. Physiol. Heart Circ. Physiol. 282, H2099–H2105 (2002).

    CAS  Article  Google Scholar 

  15. 15

    Bennett, G.J. Update on the neurophysiology of pain transmission and modulation: focus on the NMDA-receptor. J. Pain Symptom Manage. 19, S2–S6 (2000).

    CAS  Article  Google Scholar 

  16. 16

    Maze, M. & Tranquilli, W. Alpha-2 adrenoceptor agonists: defining the role in clinical anesthesia. Anesthesiology 74, 581–605 (1991).

    CAS  Article  Google Scholar 

  17. 17

    Sinclair, M.D. A review of the physiological effects of alpha2-agonists related to the clinical use of medetomidine in small animal practice. Can. Vet. J. 44, 885–897 (2003).

    CAS  PubMed  PubMed Central  Google Scholar 

  18. 18

    Brock, K.A. Preanaesthetic use of atropine in small animals. Aust. Vet. J. 79, 24–25 (2001).

    CAS  Article  Google Scholar 

  19. 19

    Baker, N.J., Schofield, J.C., Caswell, M.D. & McLellan, A.D. Effects of early atipamezole reversal of medetomidine-ketamine anesthesia in mice. J. Am. Assoc. Lab. Anim. Sci. 50, 916–920 (2011).

    CAS  PubMed  PubMed Central  Google Scholar 

  20. 20

    Veilleux-Lemieux, D., Castel, A., Carrier, D., Beaudry, F. & Vachon, P. Pharmacokinetics of ketamine and xylazine in young and old Sprague-Dawley rats. J. Am. Assoc. Lab. Anim. Sci. 52, 567–570 (2013).

    CAS  PubMed  PubMed Central  Google Scholar 

  21. 21

    Cruz, J.I., Loste, J.M. & Burzaco, O.H. Observations on the use of medetomidine/ketamine and its reversal with atipamezole for chemical restraint in the mouse. Lab. Anim. 32, 18–22 (1998).

    CAS  Article  Google Scholar 

  22. 22

    Cheymol, G. Effects of obesity on pharmacokinetics implications for drug therapy. Clin. Pharmacokinet. 39, 215–231 (2000).

    CAS  Article  Google Scholar 

  23. 23

    Hanley, M.J., Abernethy, D.R. & Greenblatt, D.J. Effect of obesity on the pharmacokinetics of drugs in humans. Clin. Pharmacokinet. 49, 71–87 (2010).

    CAS  Article  Google Scholar 

  24. 24

    Guh, D.P. et al. The incidence of co-morbidities related to obesity and overweight: a systematic review and meta-analysis. BMC Public Health 9, 88 (2009).

    Article  Google Scholar 

  25. 25

    Steier, J., Lunt, A., Hart, N., Polkey, M.I. & Moxham, J. Observational study of the effect of obesity on lung volumes. Thorax 69, 752–759 (2014).

    Article  Google Scholar 

  26. 26

    Salome, C.M., King, G.G. & Berend, N. Physiology of obesity and effects on lung function. J. Appl. Physiol. 108, 206–211 (2010).

    Article  Google Scholar 

  27. 27

    Mosing, M. et al. Oxygenation and ventilation characteristics in obese sedated dogs before and after weight loss: a clinical trial. Vet. J. 198, 367–371 (2013).

    CAS  Article  Google Scholar 

  28. 28

    Wang, Z., Li, L., Zhao, H., Peng, S. & Zuo, Z. Chronic high fat diet induces cardiac hypertrophy and fibrosis in mice. Metabolism 8, 917–925 (2015).

    Article  Google Scholar 

  29. 29

    Callaghan, L.C. & Walker, J.D. An aid to drug dosing safety in obese children: development of a new nomogram and comparison with existing methods for estimation of ideal body weight and lean body mass. Anaesthesia 70, 176–182 (2015).

    CAS  Article  Google Scholar 

  30. 30

    Cortínez, L.I. et al. Performance of propofol target-controlled infusion models in the obese: pharmacokinetic and pharmacodynamic analysis. Anesth. Analg. 119, 302–310 (2014).

    Article  Google Scholar 

  31. 31

    Lemmens, H.J. Perioperative pharmacology in morbid obesity. Curr. Opin. Anaesthesiol. 23, 485–491 (2010).

    Article  Google Scholar 

  32. 32

    Sankaralingam, S., Kim, R.B. & Padwal, R.S. The impact of obesity on the pharmacology of medications used for cardiovascular risk factor control. Can. J. Cardiol. 31, 167–176 (2015).

    Article  Google Scholar 

  33. 33

    Jones, P., Dauger, S. & Peters, M.J. Bradycardia during critical care intubation: mechanisms, significance and atropine. Arch. Dis. Child. 97, 139–144 (2012).

    Article  Google Scholar 

Download references


We thank Anette Molzahn for her support during the development of the atropine injection regimen. The study was supported by the Danone Foundation, Haar, Germany.

Author information



Corresponding author

Correspondence to Laura Mattheis.

Ethics declarations

Competing interests

The authors declare no competing financial interests.

Rights and permissions

Reprints and Permissions

About this article

Verify currency and authenticity via CrossMark

Cite this article

Mattheis, L., Jung, JS., Hiebl, B. et al. Perioperative support reduces mortality of obese BALB/c mice after ovariectomy. Lab Anim 45, 262–267 (2016).

Download citation


Quick links

Nature Briefing

Sign up for the Nature Briefing newsletter — what matters in science, free to your inbox daily.

Get the most important science stories of the day, free in your inbox. Sign up for Nature Briefing