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vol. 14
Experimental research

The effects of ketamine and thiopental used alone or in combination on the brain, heart, and bronchial tissues of rats

Elif Oral Ahiskalioglu, Pelin Aydin, Ali Ahiskalioglu, Bahadir Suleyman, Ufuk Kuyrukluyildiz, Nezahat Kurt, Durdu Altuner, Resit Coskun, Halis Suleyman

Arch Med Sci 2018; 14, 3: 645–654
Online publish date: 2016/06/06
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We compared the side effects of ketamine and thiopental used alone and of a ketamine/thiopental combination dose on the brain,heart, and bronchial tissues of rats.

Material and methods
Three groups received intraperitoneal injections of 30 mg/kg ketamine (K-30); 15 mg/kg thiopental (T-15); or of both in combination (KTSA). These doses were doubled in another set of study groups (K-60, T-30, and KTA groups, respectively). Optimal anesthesia duration was examined in all groups.

Anesthesia did not occur with 30 mg/kg ketamine or 15 mg/kg thiopental. However, when used alone ketamine and thiopental led to oxidative stress in the striatum, heart, and bronchial tissues. Conversely, combined administration of anesthetics and subanesthetic doses were found not to create oxidative stress in any of these areas. The highest level of adrenaline in blood samples collected from the tail veins was measured in the KTA-60, and the lowest amount in the T-30. Creatine kinase activity was highest in the KTA-60 group (p < 0.001). When we compared for all 5 groups to untreated control group; the creatine kinase-MB activities were significiantly different in K-30, T-15 and T-30 (p < 0.001).

The studied doses of ketamine led to oxidative stress by increasing the amount of adrenaline. Thiopental increased oxidative stress with decreases in adrenaline. A longer anesthetic effect with minimal adverse events may be achieved by ketamine and thiopental in combination.


ketamine, thiopental, cardiotoxicity, neurotoxicity, oxidative stress

Trevor AJ, Miller RD. General anesthetic. In: General Anesthetics. Basic and Clinical Pharmacology. 7th ed. Bg K (eds). Connecticut, Appleton & Lange 1998; 409-23.
Reves J, Flezzani P, Kissin I. Pharmacology of intravenous anesthetic induction drugs. In: Cardiac Anesthesia. Kaplan J (ed). Elsevier 1987; 125.
Aydogmus MT, Türk HS, Oba S, Gokalp O. A comparison of different proportions of a ketamine-propofol mixture administered in a single injection for patients undergoing colonoscopy. Arch Med Sci 2015; 11: 570-6.
Rang H, Dale M, Ritter J, Gardner P. General Anesthetic Agents. Pharmacology. Churchil Livingstone, New York 1995.
Aksoy M, Ince I, Ahiskalioglu A, et al. The suppression of endogenous adrenalin in the prolongation of ketamine anesthesia. Med Hypotheses 2014; 83: 103-7.
Cadet JL. Free radical mechanisms in the central nervous system: an overview. Int J Neurosci 1988; 40: 13-8.
Jesberger JA. Oxygen free radicals and brain function. Int J Neurosci 1991; 57: 1-17.
Lohr JB. Oxygen radicals and neuropsychiatric illness: some speculations. Arch Gen Psychiatry 1991; 48: 1097-104.
De Oliveira L, Spiazzi CM, Bortolin T, et al. Different sub-anesthetic doses of ketamine increase oxidative stress in the brain of rats. Prog Neuropsychopharmacol Biol Psychiatry 2009; 33: 1003-8.
Ahiskalioglu A, Ince I, Aksoy M, et al. Comparative investigation of protective effects of metyrosine and metoprolol against ketamine cardiotoxicity in rats. Cardiovasc Toxicol 2015; 15: 336-44.
Faug YZ, Yang S, Wu G. Free radicals, antioxidants, and nutrition. Nutrition 2002; 18: 872-87.
Wang XL, Wang J. Endothelial nitric oxide synthase gene sequence variations and vascular disease. Mol Genet Metab 2000; 70: 241-51.
White JM, Ryan CF. Pharmacological properties of ketamine. Drug Alc Review 1996; 15: 145-55.
Lau TT, Zed PJ. Does ketamine have a role in managing severe exacerbation of asthma in adults? Pharmacotherapy 2001; 21: 1100-6.
Gaines 3rd G, Rees D. Anesthetic considerations for electroconvulsive therapy. South Med J 1992; 85: 469-82.
Aksoy M, Ahiskalioglu A, Ince I, et al. The relation between the effect of a subhypnotic dose of thiopental on claw pain threshold in rats and adrenalin, noradrenalin and dopamine levels. Exp Anim Tokyo 2015; 64: 391-6.
Kavanagh B, Ryan M, Cunningham A. Myocardial contractility and ischaemia in the isolated perfused rat heart with propofol and thiopentone. Can J Anaesth 1991; 38: 634-9.
Ely EW, Margolin R, Francis J, et al. Evaluation of delirium in critically ill patients: validation of the Confusion Assessment Method for the Intensive Care Unit (CAM-ICU). Crit Care Med 2001; 29: 1370-9.
Ebert TJ, Kanitz DD, Kampine JP. Inhibition of sympathetic neural outflow during thiopental anesthesia in humans. Anesth Analg 1990; 71: 319-26.
Kurt A, Isaoglu U, Yilmaz M, et al. Biochemical and histological investigation of famotidine effect on postischemic reperfusion injury in the rat ovary. J Pediatr Surg 2011; 46: 1817-23.
Bradford MM. A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein-dye binding. Anal Biochem 1976; 72: 248-54.
Ohkawa H, Ohishi N, Yagi K. Assay for lipid peroxides in animal tissues by thiobarbituric acid reaction. Anal Biochem 1979; 95: 351-8.
Sedlak J, Lindsay RH. Estimation of total, protein-bound, and nonprotein sulfhydryl groups in tissue with Ellman’s reagent. Anal Biochem 1968; 25: 192-205.
Carlberg I, Mannervik B. Glutathione reductase. Meth Enzymol 1985; 113: 484-90.
Lawrence RA, Burk RF. Glutathione peroxidase activity in selenium-deficient rat liver. Biochem Biophys Res Commun 1976; 71: 952-8.
Bories PN, Bories C. Nitrate determination in biological fluids by an enzymatic one-step assay with nitrate reductase. Clin Chem 1995; 41: 904-7.
Moshage H, Kok B, Huizenga JR, Jansen P. Nitrite and nitrate determinations in plasma: a critical evaluation. Clin Chem 1995; 41: 892-6.
Coskun R, Turan MI, Turan IS, Gulapoglu M. The protective effect of thiamine pyrophosphate, but not thiamine, against cardiotoxicity induced with cisplatin in rats. Drug Chem Toxicol 2014; 37: 290-4.
Botrè F, Pavan A. Enhancement drugs and the athlete. Phys Med Rehabil Clin N Am 2009; 20: 133-48.
Wieczerzak M, Kudłak B, Namieśnik J. Environmentally oriented models and methods for the evaluation of drug × drug interaction effects. Crit Rev Anal Chem 2015; 45: 131-55.
Polat B, Suleyman H, Sener E, Akcay F. Examination of the effects of thiamine and thiamine pyrophosphate on doxorubicin-induced experimental cardiotoxicity. J Cardiovasc Pharm 2014, doi: 10.1177/1074248414552901.
Suleyman H, Cadirci E, Albayrak A, et al. Comparative study on the gastroprotective potential of some antidepressants in indomethacin-induced ulcer in rats. Chem Biol Interact 2009; 180: 318-24.
Zheng X, Zhou J, Xia Y. The role of TNF-alpha in regulating ketamine-induced hippocampal neurotoxicity. Arch Med Sci 2015; 11: 1296-302.
Yeum KJ, Russell RM, Krinsky NI, Aldini G. Biomarkers of antioxidant capacity in the hydrophilic and lipophilic compartments of human plasma. Arch Biochem Biophys 2004; 430: 97-103.
Weber G. The pathophysiology of reactive oxygen intermediates in the central nervous system. Med Hypotheses 1994; 43: 223-30.
Ko YY, Jeong YH, Lim DY. Influence of ketamine on catecholamine secretion in the perfused rat adrenal medulla. Korean J Physiol Pharmacol 2008; 12: 101-9.
Shibuta S, Varathan S, Mashimo T. Ketamine and thiopental sodium: individual and combined neuroprotective effects on cortical cultures exposed to NMDA or nitric oxide. Br J Anaesth 2006; 97: 517-24.
Sigola L. Adrenaline inhibits macrophage nitric oxide production through beta1 and beta2 adrenergic receptors. Immunology 2000; 100: 359-63.
Dawson VL, Dawson TM. Physiological and toxicological actions of nitric oxide in the central nervous system. Adv Pharmacol (San Diego, Calif) 1994; 34: 323-42.
Bouloumié A, Bauersachs J, Linz W, et al. Endothelial dysfunction coincides with an enhanced nitric oxide synthase expression and superoxide anion production. Hypertension 1997; 30: 934-41.
Schlaich MP, Socratous F, Hennebry S, et al. Sympathetic activation in chronic renal failure. J Am Soc Nephrol 2009; 20: 933-9.
Parvin R, Akhter N. Protective effect of tomato against adrenaline-induced myocardial infarction in rats. Bangladesh Med Res Coun Bul 2008; 34: 104-8.
Snyder S. Nitric oxide: first in a new class of neurotransmitters. Science 1992; 257: 494-6.
Loscalzo J, Welch G. Nitric oxide and its role in the cardiovascular system. Progress Cardiovasc Dis 1995; 38: 87-104.
Hirota K, Ohtomo N, Hashimoto Y, et al. Effects of thiopental on airway calibre in dogs: direct visualization method using a superfine fibreoptic bronchoscope. Br J Anaesth 1998; 81: 203-7.
Marín J, Rodríguez-Martínez MA. Role of vascular nitric oxide in physiological and pathological conditions. Pharmacol Therap 1997; 75: 111-34.
Barnes PJ. Nitric oxide and airway disease. Ann Med 1995; 27: 389-93.
Khatri SB, Ozkan M, McCarthy K, Laskowski D, Hammel J, Dweik RA. Alterations in exhaled gas profile during allergen-induced asthmatic response. Am J Respir Crit Care Med 2001; 164: 1844-8.
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