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Effects of clonidine pre-treatment on bupivacaine and ropivacaine cardiotoxicity in rats

  • S. Gulec (a1), Y. Aydin (a2), K. Uzuner (a2), B. Yelken (a1) and Y. Senturk (a1)...



Background and objective: Clonidine has cardiac and systemic effects that can modify the potentially lethal cardiovascular effects of local anaesthetics. We evaluated the effects of clonidine pre-treatment on cardiotoxicity induced by an infusion of bupivacaine or ropivacaine and the success rate of resuscitation in anaesthetized rats.

Methods: Thirty-two Sprague–Dawley rats (250–300 g) were anaesthetized with thiopental and ketamine. Lung ventilation was maintained mechanically, and the electrocardiograph and invasive blood pressure were recorded continuously. Two separate groups of rats were treated with intravenous clonidine 5 μg kg−1 (n = 16) or saline (n = 16) in a randomized fashion. Fifteen minutes later, each group was randomly subdivided into two equal groups and an infusion of bupivacaine or ropivacaine, 3 mg kg−1 min−1, was given until cardiac arrest (asystole) occurred. The times when the cardiotoxic events (25%, 50% and 75% reduction of arterial pressure and heart rate, first dysrhythmia and asystole, respectively), induced by the local anaesthetic, occurred and the resuscitation outcome scores were recorded.

Results: Clonidine reduced heart rate and arterial pressure (P < 0.01). Clonidine did not alter cardiotoxicity or the success rate of resuscitation in bupivacaine-treated rats. In the ropivacaine group, clonidine increased the 25%, 50% and 75% reduction times of arterial pressure and the 50% and 75% reduction times of heart rate, times to first dysrhythmia and asystole (P < 0.05). Clonidine also increased the success rate of resuscitation in ropivacaine-treated rats (P < 0.05).

Conclusions: Although pre-treatment with clonidine protects the effects of ropivacaine cardiotoxicity and increases the success rate of resuscitation, it does not affect bupivacaine toxicity.


Corresponding author

Correspondence to: Sacit Gulec, Department of Anaesthesiology, Osmangazi University Medical School, Eskisehir, Turkey. E-mail:; Tel: +90 222 2399052; Fax: +90 222 2393774


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Albright GA. Cardiac arrest following regional anaesthesia with etidocaine or bupivacaine. Anesthesiology 1979; 51: 285287.
Reiz S, Haggmark S, Johansson G, Nath S. Cardiotoxicity of ropivacaine – a new amide local anaesthetic agent. Acta Anaesthesiol Scand 1989; 33: 9398.
Gaumann DM, Tassonyi E, Rivest RW, Fathi M, Reverdin AF. Cardiovascular and endocrine effects of clonidine premedication in neurosurgical patients. Can J Anesth 1991; 38: 837843.
Carabine UA, Wright PMC, Moore J. Preanaesthetic medication with clonidine: a dose-response study. Br J Anaesth 1991; 67: 7983.
De la Coussaye JE, Bassoul B, Brugada J, et al. Reversal of electrophysiologic and hemodynamic effects induced by high dose of bupivacaine by the combination of clonidine and dobutamine in anesthetized dogs. Anesth Analg 1992; 74: 703711.
De Kock M, Le Polain B, Henin D, Vandewalle F, Scholtes JL. Clonidine pre-treatment reduces the systemic toxicity of intravenous bupivacaine in rats. Anesthesiology 1993; 79: 282289.
Heath ML. Deaths after intravenous regional anaesthesia. Br Med J 1982; 285: 913914.
Bruguerolle B, Attolini L, Lorec AM, Gantenbein M. Kinetics of bupivacaine after clonidine pretreatment in mice. Can J Anesth 1995; 42: 434437.
Dabadie P, Bendriss P, Erny P, Mazat P. Uncoupling effects of local anaesthetics on rat liver mitochondria. FEBS Lett 1987; 226: 7782.
Chazotte B, Vanderkooi G. Multiples sites of inhibition of mitochondria electron transport by local anaesthetics. Biochim Biophys Acta 1981; 636: 153161.
Karniel M, Beitner N. Local anesthetic induce a decrease in the level of glucose 1,6-bisphospate, fructose 1,6-bisphospate, and ATP, and in the viability of melanoma cells. Mol Genet Metab 2000; 69: 4045.
Sztark F, Tueux O, Erny P, Dabadie P, Mazat JP. Effect of bupivacaine on cellular oxygen consumption and adenine nucleotide metabolism. Anesth Analg 1994; 78: 335339.
Eledjam JJ, de La Coussaye JE, Brugada J, et al. In vitro study on mechanisms of bupivacaine-induced depression of myocardial contractility. Anesth Analg 1989; 69: 732735.
Sztark F, Malgat M, Dabadie P, Mazat JP. Comparison of the effects of bupivacaine and ropivacaine on heart cell mito-chondria bioenergetics. Anesthesiology 1998; 88: 13401349.
Scutari G, Marian M, Nindoli A, et al. Mitochondrial effects of L-ropivacaine, a new local anesthetic. Biochem Pharmacol 1998; 56: 16331637.
Takayanagi I, Onozuka S. Greater tension is developed at the same level of cytosolic Ca2+ concentration in the presence of clonidine, an adrenergic partial agonist, than in the presence of norepinephrine. J Pharmacobiodyn 1989; 12: 781786.
Takayanagi I, Onozuka. Alpha 1-adrenergic partial agonists utilise cytosolic Ca2+ more effectively for contraction in aortic smooth muscle. Can J Physiol Pharmacol 1990; 68: 13291333.
Mio Y, Fukuda N, Kusakari Y, Tanifuji Y, Kurihara S. Bupivacaine attenuates contractility by decreasing sensitivity of myofilaments to Ca2+ in rat ventricular muscle. Anesthesiology 2002; 97: 11681177.
Brown CG, Jenkins J, Werman HA, Van Ligten P, Ashton J, Hamlin RL. The effect of UK14,304-18 (an alpha-2 adrenergic agonist) on myocardial blood flow during cardio-pulmonary resuscitation. Resuscitation 1989; 17: 243250.
Sun S, Weil MH, Tang W, Kamohara T, Klouche K. Alpha-methylnorepinephrine, a selective alpha-2 adrenergic agonist for cardiac resuscitation. J Am Coll Cardiol 2001; 37: 951956.
Kloucke K, Weil MH, Tang W, Povoas H, Kamohara T, Bisera J. A selective alpha-2 adrenergic agonist for cardiac resuscitation. J Lab Clin Med 2002; 140: 2734.
Landry DW, Oliver JA. The pathogenesis of vasodilatory shock. New Engl J Med 2001; 345: 588594.


Effects of clonidine pre-treatment on bupivacaine and ropivacaine cardiotoxicity in rats

  • S. Gulec (a1), Y. Aydin (a2), K. Uzuner (a2), B. Yelken (a1) and Y. Senturk (a1)...


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