Abstract
Purpose
To investigate the role of the adenosine A1 receptor in the rapid tolerance to cerebral ischemia induced by isoflurane preconditioning.
Methods
Seventy-five rats were randomly assigned into five groups (n = 15 each): Control, 8-cyclopentyl-1,3-dipropulxanthine (DPCPX), Isoflurane, DPCPX+Isoflurane and Vehicle+Isoflurane groups. All animals underwent right middle cerebral artery occlusion (MCAO) for two hours. Isoflurane preconditioning was conducted one hour before MCAO in Isoflurane, DPCPX+Isoflurane and Vehicle+Isoflurane groups by exposing the animals to 1.5% isoflurane in 98% oxygen for one hour. In the Control and DPCPX groups, animals were exposed to 98% oxygen one hour before MCAO for one hour. A selective adenosine A1 receptor antagonist, DPCPX, was administered (0.1 mg·kg-1) 15 min before isoflurane/oxygen exposure in the DPCPX and DPCPX+Isofluranegroups to evaluate the effect of adenosine A1 receptor antagonist on isoflurane preconditioning. Dimethyl sulfoxide, the solvent of DPCPX, was administered (1 mL·kg-1) 15 min before isoflurane exposure in the Vehicle+Isoflurane group. Neurological deficit scores and brain infarct volumes were evaluated 24 hr after reperfusion.
Results
Animals in the Isoflurane and Vehicle+Isoflurane groups developed lower neurological deficit scores and smaller brain infarct volumes than the Control group (P < 0.01). Animals in the DPCPX+Isoflurane group developed higher neurological deficit scores and larger brain infarct volumes than the Isoflurane and Vehicle+Isoflurane groups (P < 0.01).
Conclusion
The present study demonstrates that preconditioning with isoflurane reduces focal cerebral ischemic injury in rats, and the adenosine A1 receptor antagonist (DPCPX) attenuates the neuroprotection induced by isoflurane preconditioning.
Résumé
Objectif
Explorer le rôle des récepteurs de ľadénosine A1 dans la tolérance rapide à ľischémie cérébrale induite par le préconditionnement à ľisoflurane.
Méthode
Nous avons réparti 75 rats en cinq groupes de 15: Témoin, 8-cyclopentyl-1,3-dipropulxanthine (DPCPX), Isoflurane, DPCPX+Isoflurane et Véhicule+Isoflurane. Tous les rats ont subi une occlusion de deux heures de ľartère cérébrale moyenne droite (OACM). Le préconditionnement avec ľisoflurane a été fait une heure avant ľOACM dans les groupes Isoflurane, DPCPX+Isoflurane et Véhicule+Isoflurane par une exposition à un mélange de 1,5 % ďisoflurane et de 98 % ďoxygène pendant une heure. Dans les groupes Témoin et DPCPX, les rats ont été exposés à 98 % ďoxygène une heure avant ľOACM qui a duré une heure. Un antagoniste sélectif des récepteurs de ľadénosine A1, DPCPX, a été administré (0,1 mg·kg-1) 15 min avant ľexposition à ľisoflurane/oxygène dans les groupes DPCPX et DPCPX+Isoflurane pour évaluer ľeffet de ľantagoniste des récepteurs de ľadénosine A1 sur le préconditionnement à ľisoflurane. Le sulfoxyde de diméthyle, le solvant de DPCPX, a été administré (1 mL·kg-1) 15 min avant ľexposition à ľisoflurane dans le groupe Véhicule+Isoflurane. Les scores de déficit neurologique et les volumes ďinfarctus cérébral ont été évalués 24 h après la reperfusion.
Résultats
Dans les groupes Isoflurane et Véhicule+Isoflurane, les scores de déficit neurologique étaient plus bas et les infarctus cérébraux de moindre volume que dans le groupe Témoin (P < 0,01). Dans le groupe DPCPX+Isoflurane, les scores de déficit neurologique étaient plus élevés et les infarctus cérébraux de plus grand volume que dans les groupes Isoflurane et Véhicule+Isoflurane (P < 0,01).
Conclusion
Le préconditionnement avec de ľisoflurane réduit la lésion ischémique cérébrale focale chez les rats et ľantagoniste (DPCPX) des récepteurs de ľadénosine A1 atténue la neuroprotection induite par le préconditionnement à ľisoflurane.
Article PDF
Similar content being viewed by others
Avoid common mistakes on your manuscript.
References
Murry CE, Jennings RB, Reimer KA. Preconditioning with ischemia: a delay of lethal cell injury in ischemic myocardium. Circulation 1986; 74: 1124–36.
Kitagawa K, Matsumoto M, Tagaya M, et al. ‘Ischemic tolerance’ phenomenon found in the brain. Brain Res 1990; 528: 21–4.
Bordet R, Deplanque D, Maboudou P, et al. Increase in endogenous brain superoxide dismutase as a potential mechanism of lipopolysaccharide-induced brain ischemic tolerance. J Cereb Blood Flow Metab 2000; 20: 1190–6.
Ginis I, Schweizer U, Brenner M, et al. TNF-alpha pretreatment prevents subsequent activation of cultured brain cells with TNF-alpha and hypoxia via ceramide. Am J Physiol 1999; 276: C1171–83.
Ohtsuki T, Ruetzler CA, Tasaki K, Hallenbeck JM. Interleukin-1 mediates induction of tolerance to global ischemia in gerbil hippocampal CA1 neurons. J Cereb Blood Flow Metab 1996; 16: 1137–42.
Mackensen GB, Nellgard B, Miura Y, et al. Sympathetic ganglionic blockade masks beneficial effect of isoflurane on histologic outcome from near-complete forebrain ischemia in the rat. Anesthesiology 1999; 90: 873–81.
Roscoe AK, Christensen JD, Lynch C III. Isoflurane, but not halothane, induces protection of human myocardium via adenosine A1 receptors and adenosine triphosphate -sensitive potassium channels. Anesthesiology 2000; 92: 1692–701.
Aizawa K, Turner LA, Weihrauch D, Bosnjak ZJ, Kwok WM. Protein kinase C-epsilon primes the cardiac sarcolemmal adenosine triphosphate-sensitive potassium channel to modulation by isoflurane. Anesthesiology 2004; 101: 381–9.
Xiong L, Zheng Y, Wu M, et al. Preconditioning with isoflurane produces dose-dependent neuroprotection via activation of adenosine triphosphate-regulated potassium channels after focal cerebral ischemia in rats. Anesth Analg 2003; 96: 233–7.
Gassmayr S, Stadnicka A, Suzuki A, Kwok WM, Bosnjak ZJ. Isoflurane sensitizes the cardiac sarcolemmal adenosine triphosphate-sensitive potassium channel to pinacidil. Anesthesiology 2003; 98: 114–20.
Longa EZ, Weinstein PR, Carlson S, Cummins R. Reversible middle cerebral artery occlusion without craniectomy in rats. Stroke 1989; 20: 84–91.
Tatlisumak T, Takano K, Carano RA, Miller LP, Foster AC, Fisher M. Delayed treatment with an adenosine kinase Inhibitor, GP683, attenuates infarct size in rats with temporary middle cerebral artery occlusion. Stroke 1998; 29: 1952–8.
Kersten JR, Schmeling TJ, Pagel PS, Gross GJ, Warltier DC. Isoflurane mimics ischemic preconditioning via activation of KATP channels. Reduction of myocardial infarct size with an acute memory phase. Anesthesiology 1997; 87: 361–70.
Kapinya KJ, Lowl D, Futterer C, et al. Tolerance against ischemic neuronal injury can be induced by volatile anesthetics and is inducible NO synthase dependent. Stroke 2002; 33: 1889–98.
Engelhard K, Werner C, Reeker W, et al. Desflurane and isoflurane improve neurological outcome after incomplete cerebral ischaemia in rats. Br J Anaesth 1999; 83: 415–21.
Russell GB, Graybeal JM. Differences in anesthetic potency between Sprague-Dawley and Long-Evans rats for isoflurane but not nitrous oxide. Pharmacology 1995; 50: 162–7.
Mackensen GB, Nellgard B, Kudo M, Sheng H, Pearlstein RD, Warner DS. Periischemic cerebral blood flow (CBF) does not explain beneficial effects of isoflurane on outcome from near-complete forebrain ischemia in rats. Anesthesiology 2000; 93: 1102–6.
Nakamura M, Nakakimura K, Matsumoto M, Sakabe T. Rapid tolerance to focal cerebral ischemia in rats is attenuated by adenosine A1 receptor antagonist. J Cereb Blood Flow Metab 2002; 22: 161–70.
Perez-Pinzon MA, Born JG. Rapid preconditioning neuroprotection following anoxia in hippocampal slices: role of the K+ATP channel and protein kinase C. Neuroscience 1999; 89: 453–9.
Perez-Pinzon MA, Born JG, Centeno JM. Calcium and increase excitability promote tolerance against anoxia in hippocampal slices. Brain Res 1999; 833: 20–6.
Tanaka K, Weihrauch D, Ludwig LM, Kersten JR, Pagel PS, Warltier DC. Mitochondrial adenosine triphosphate -regulated potassium channel opening acts as a trigger for isoflurane-induced preconditioning by generating reactive oxygen species. Anesthesiology 2003; 98: 935–43.
Zaugg M, Lucchinetti E, Spahn DR, Pasch T, Schaub MC. Volatile anesthetics mimic cardiac preconditioning by priming the activation of mitochondrial KATP channels via multiple signaling pathways. Anesthesiology 2002; 97: 4–14.
Yoshida M, Nakakimura K, Cui YJ, Matsumoto M, Sakabe T. Adenosine A1 receptor antagonist and mitochondrial ATP-sensitive potassium channel blocker attenuate the tolerance to focal cerebral ischemia in rats. J Cereb Blood Flow Metab 2004; 24: 771–9.
Speechly-Dick ME, Grover GJ, Yellon DM. Does ischemic preconditioning in the human involve protein kinase C and the ATP-dependent K+ channel? Studies of contractile function after simulated ischemia in an atrial in vitro model. Circ Res 1995; 77: 1030–5.
Hiraide T, Katsura K, Muramatsu H, Asano G, Katayama Y. Adenosine receptor antagonists cancelled the ischemic tolerance phenomenon in gerbil. Brain Res 2001; 910: 94–8.
Reichelt ME, Willems L, Molina JG, et al. Genetic deletion of the A1 adenosine receptor limits myocardial ischemic tolerance. Circ Res 2005; 96: 363–7.
Cleveland JC Jr, Meldrum DR, Rowland RT, Banerjee A, Harken AH. Adenosine preconditioning of human myocardium is dependent upon the ATP-sensitive K+ channel. J Mol Cell Cardiol 1997; 29: 175–82.
Phillis JW, Goshgarian HG. Adenosine and neurotrauma: therapeutic perspectives. Neurol Res 2001; 23: 183–9.
Deckert J, Gleiter CH. Adenosine-an endogenous neuroprotective metabolite and neuromodulator. J Neural Transm Suppl 1994; 43: 23–31.
Von Lubitz DK, Beenhakker M, Lin RC, et al. Reduction of postischemic brain damage and memory deficits following treatment with the selective adenosine A1 receptor agonist. Eur J Pharmacol 1996; 302: 43–8.
Von Lubitz DK, Lin RC, Bischofberger N, et al. Protection against ischemic damage by adenosine amine congener, a potent and selective adenosine A1 receptor agonist. Eur J Pharmacol 1999; 369: 313–7.
Dolphin AC, Archer ER. An adenosine agonist inhibits and a cyclic AMP analogue enhances the release of glutamate but not GABA from slices of rat dentate gyrus. Neurosci Lett 1983; 43: 49–54.
Toller WG, Montgomery MW, Pagel PS, Hettrick DA, Warltier DC, Kersten JR. Isoflurane-enhanced recovery of canine stunned myocardium: role for protein kinase C? Anesthesiology 1999; 91: 713–22.
Matsuoka Y, Okazaki M, Takata K, et al. Endogenous adenosine protects CA1 neurons from kainic acidinduced neuronal cell loss in the rat hippocampus. Eur J Neurosci 1999; 11: 3617–25.
Wardas J. Neuroprotective role of adenosine in the CNS. Pol J Pharmacol 2002; 54: 313–26.
Thiyagarajan M, Sharma SS. Neuroprotective effect of curcumin in middle cerebral artery occlusion induced focal cerebral ischemia in rats. Life Sci 2004; 74: 969- 85.
Yamamoto S, Yang G, Zablocki D, et al. Activation of Mst1 causes dilated cardiomyopathy by stimulating apoptosis without compensatory ventricular myocyte hypertrophy. J Clin Invest 2003; 111: 1463–74.
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Liu, Y., Xiong, L., Chen, S. et al. Neuroanesthesia and Intensive Care Isoflurane tolerance against focal cerebral ischemia is attenuated by adenosine A1 receptor antagonists. Can J Anesth 53, 194–201 (2006). https://doi.org/10.1007/BF03021827
Accepted:
Issue Date:
DOI: https://doi.org/10.1007/BF03021827