Comparison of Combined and Distinct Ketamine/Xylazine Anesthesia on Gene Receptors of Angiotensin 2 in Pigeons Heart Tissue

Subject Areas : Pharmacology and toxicology

leila derakhshan ¹ , seyed morteza razaghi manesh ² , Simin Yaghoubiani ³ , Melina Daghighian ⁴

1 - Department of Pathobiology, Faculty of Veterinary Medicine, Islamic Azad University, Shushtar Branch, Shushtar, Iran
2 - Department of Pathobiology, Faculty of Veterinary Medicine, Islamic Azad University, Shushtar Branch, Shushtar, Iran
3 - 2- Graduated of Veterinary Medicine Faculty, Islamic Azad University, Shushtar Branch, Shushtar, Iran
4 - 3- Doctor of Veterinary Medicine Student, Faculty of Veterinary Medicine, Islamic Azad University, Shushtar Branch, Shushtar, Iran

Received: 2025-09-01 Accepted : 2025-09-01 Published : 2025-09-02

Keywords: Ketamine, Xylazine, AGTR1, Anesthesia, Renin-Angiotensin-Aldosterone System (RAAS),

Abstract :

The Renin-angiotensin-aldosterone system (RAAS) plays a crucial role in regulating blood pressure and maintaining electrolyte balance. Dysregulation of this system during the anesthetic process can lead to blood pressure instability, affecting the efficacy and safety of anesthetic protocols. Given the widespread use of the ketamine-xylazine combination in anesthesia, it is essential to accurately assess its effects on the RAAS system and related indices, including the expression level of the AGTR1 gene in cardiac tissue.

This research investigates the effect of the ketamine-xylazine combination on AGTR1 gene expression in the cardiac tissue of pigeons. The primary aim of this study is to analyze how this drug combination influences the RAAS and blood pressure fluctuations during anesthesia, as well as to improve anesthetic protocols to mitigate blood pressure instability.

Twenty healthy, adult domestic pigeons (males and females) with an average weight of 150 to 300 grams and aged 1 to 3 years were selected. The birds were randomly divided into four groups. Different doses of ketamine and xylazine were injected intramuscularly into the left pectoral muscle.

Based on the findings, the ketamine-xylazine combination did not produce significant changes in AGTR1 gene expression.

The ketamine-xylazine combination can be recommended as an effective method for anesthesia in birds. These results provide a better understanding of the effects of these drugs on the RAAS system and pave the way for improving anesthetic protocols in veterinary medicine.

References:

1. SHEARER WM. The evolution of premedication. British journal of anaesthesia. 1960;32(11):554-62.
2. Sheen MJ, Chang F-L, Ho S-T. Anesthetic premedication: new horizons of an old practice. Acta Anaesthesiologica Taiwanica. 2014;52(3):134-42.
3. Buxton DW. The use of scopolamine, morphine, atropine, and similar drugs by hypodermic injection before inhalation anaesthesia. SAGE Publications; 1911.
4. Beecher HK. PREANESTHETIC MEDICATION: GUEST EDITORIAL. Journal of the American Medical Association. 1955;157(3):242-3.
5. Metkus TS, Suarez-Pierre A, Crawford TC, Lawton JS, Goeddel L, Dodd-o J, et al. Diastolic dysfunction is common and predicts outcome after cardiac surgery. Journal of Cardiothoracic Surgery. 2018;13(1):67.
6. Rhodes DR, Ateeq B, Cao Q, Tomlins SA, Mehra R, Laxman B, et al. AGTR1 overexpression defines a subset of breast cancer and confers sensitivity to losartan, an AGTR1 antagonist. Proceedings of the National Academy of Sciences. 2009;106(25):10284-9.
7. Occhieppo VB, Basmadjian OM, Marchese NA, Silvero MJ, Rodríguez A, Armonelli S, et al. AT1‐R is involved in the development of long‐lasting, region‐dependent and oxidative stress‐independent astrocyte morphological alterations induced by Ketamine. European Journal of Neuroscience. 2020;54:5705 - 16.
8. Oh E, Kim JY, Cho Y, An H, Lee N, Jo H, et al. Overexpression of angiotensin II type 1 receptor in breast cancer cells induces epithelial-mesenchymal transition and promotes tumor growth and angiogenesis. Biochimica et biophysica acta. 2016;1863 6 Pt A:1071-81.
9. Pipkin FB, Waldron BA. Ketamine Hypertension and the Renin-Angiotensin System. Clinical and Experimental Hypertension Part A: Theory and Practice. 1983;5(6):875-83.
10. Durrani U, Ashraf M, Khan M. A comparison of the clinical effects associated with xylazine, ketamine, and a xylazine-ketamine cocktail in pigeons (Columba livia). Turkish Journal of Veterinary and Animal Sciences. 2009;33:413-7.
11. Antonaccio MJ, Robson RD, Kerwin LJ. Evidence for increased vagal tone and enhancement of baroreceptor reflex activity after xylazine (2-(2,6-dimethylphenylamino)-4-H-5,6-dihydro-1,3-thiazine) in anesthestized dogs. European journal of pharmacology. 1973;23 3:311-6.
12. Baumgartner C, Bollerhey M, Ebner JK, Laacke-Singer L, Schuster T, Erhardt W. Effects of ketamine-xylazine intravenous bolus injection on cardiovascular function in rabbits. Canadian journal of veterinary research = Revue canadienne de recherche veterinaire. 2010;74 3:200-8.
13. KAZDAĞLI HÖ, HASAN FEHMİ; ÖZBEK, MUSTAFA; ALPAY, ŞÜHEDA; and ALENBEY, MÜRÜVVET Classical heart rate variability and non-linear heart rate analysis in mice under Na-Pentobarbital and Ketamine/Xylazine anesthesia. Turkish Journal of Medical Sciences. 2022;52(3):858-69.
14. Picollo C, Serra A, Levy R, Antonio E, Santos Ld, Tucci P. Hemodynamic and thermoregulatory effects of xylazine-ketamine mixture persist even after the anesthetic stage in rats. Arquivo Brasileiro de Medicina Veterinária e Zootecnia. 2012;64:860-4.
15. Struck MB, Andrutis KA, Ramirez HE, Battles AH. Effect of a short-term fast on ketamine-xylazine anesthesia in rats. J Am Assoc Lab Anim Sci. 2011;50(3):344-8.
16. Sotoudeh N, Namavar MR. Optimisation of ketamine-xylazine anaesthetic dose and its association with changes in the dendritic spine of CA1 hippocampus in the young and old male and female Wistar rats. Veterinary Medicine and Science. 2022;8(6):2545-52.