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Ischaemic preconditioning but not isoflurane prevents post-ischaemic production of hydroxyl radicals in a canine model of ischaemia–reperfusion

Published online by Cambridge University Press:  13 April 2005

Y. Gozal
Affiliation:
Hadassah University Hospital, Hebrew University Faculties of Medicine and Dental Medicine, Department of Anesthesiology and CCM, Jerusalem, Israel
M. Chevion
Affiliation:
Hadassah University Hospital, Hebrew University Faculties of Medicine and Dental Medicine, Department of Cellular Biochemistry and Human Genetics, Jerusalem, Israel
A. Elami
Affiliation:
Hadassah University Hospital, Hebrew University Faculties of Medicine and Dental Medicine, Department of Cardiothoracic Surgery, Jerusalem, Israel
E. Berenshtein
Affiliation:
Hadassah University Hospital, Hebrew University Faculties of Medicine and Dental Medicine, Department of Cellular Biochemistry and Human Genetics, Jerusalem, Israel
N. Kitrossky
Affiliation:
Hadassah University Hospital, Hebrew University Faculties of Medicine and Dental Medicine, Department of Cellular Biochemistry and Human Genetics, Jerusalem, Israel
B. Drenger
Affiliation:
Hadassah University Hospital, Hebrew University Faculties of Medicine and Dental Medicine, Department of Anesthesiology and CCM, Jerusalem, Israel
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Extract

Summary

Background and objective: Isoflurane has been shown to mimic ischaemic preconditioning (IPC). The protective effect of IPC, or applying isoflurane or perfusion with the ‘push-pull’ complex zinc–desferrioxamine (Zn–DFO) in the canine heart, was investigated.

Methods: Thirty minutes after salicylate administration (100 mg kg−1) the heart was exposed. All dogs were subjected to a 10 min left anterior descending artery occlusion followed by 2 h of reperfusion. In Group I (n = 9) isoflurane (2.5%) was administered 10 min prior to and during ischaemia. In Group II (n = 8), IPC was elicited by 5 min coronary artery occlusion, followed by 5 min of reperfusion, prior to the 10 min ischaemia. In Group III (n = 9) Zn–DFO (2.5 mg kg−1) was given 10 min prior to ischaemia. The effects of these interventions were compared to control (n = 10). Coronary sinus blood concentrations of salicylate, 2,3-dihydroxybenzoic acid (DHBA), lactate, pH and oxygen content were monitored.

Results: In the control group, 2,3-DHBA increased by 32% above the pre-ischaemic value (P < 0.05). In contrast, in the IPC hearts, a significant decrease in the production of 2,3-DHBA was observed (40% lower than baseline, P < 0.01). In the isoflurane group only a 13% (and non-significant) decrease was noticed. In the Zn–DFO group a 33% decrease was found (P < 0.01). The increase in lactate concentrations in the IPC and Zn–DFO groups was significantly smaller than that of control and isoflurane groups.

Conclusions: IPC protected the heart against the deleterious effects of reperfusion, possibly by amelioration of the level of oxygen-derived reactive species, and the complete inhibition of reactive hydroxyl radical production. Isoflurane did not prove to be as effective in reducing the free radical damage.

Type
Original Article
Copyright
© 2005 European Society of Anaesthesiology

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References

Warltier DC, Al-Wathiqui MH, Kampine JP, Schmeling WT. Recovery of contractile function of stunned myocardium in chronically instrumented dogs is enhanced by halothane or isoflurane. Anesthesiology 1988; 69: 552565.Google Scholar
Marijic J, Stowe DF, Turner LA, et al. Differential protective effects of halothane and isoflurane against hypoxia and reoxygenation injury in the isolated guinea pig heart. Anesthesiology 1990; 73: 976983.Google Scholar
Luss H, Meissner A, Rolf N, et al. Biochemical mechanism(s) of stunning in conscious dogs. Am J Physiol 2000; 279: H176H184.Google Scholar
Kanaya N, Kobayashi I, Nakayama M, et al. ATP sparing effect of isoflurane during ischaemia and reperfusion of the canine heart. Br J Anaesth 1995; 74: 563568.Google Scholar
Kanaya N, Fujita S. The effects of isoflurane on regional myocardial contractility and metabolism in ‘stunned’ myocardium in acutely instrumented dogs. Anesth Analg 1994; 79: 447454.Google Scholar
Kersten JR, Orth KG, Pagel PS, et al. Role of adenosine in isoflurane-induced cardioprotection. Anesthesiology 1997; 86: 11281139.Google Scholar
Kersten JR, Lowe D, Hettrick DA, et al. Glyburide, a KATP channel antagonist, attenuates the cardioprotective effects of isoflurane in stunned myocardium. Anesth Analg 1996; 83: 2733.Google Scholar
Kersten JR, Schmeling TJ, Hettrick DA, et al. Mechanism of myocardial protection by isoflurane: role of adenosine triphosphate-regulated potassium (KATP) channels. Anesthesiology 1996; 85: 794807.Google Scholar
Kersten JR, Schmeling TJ, Pagel PS, et al. Isoflurane mimics ischemic preconditioning via activation of KATP channels. Anesthesiology 1997; 87: 361370.Google Scholar
Chevion M, Jiang Y, Har-El R, et al. Copper and iron are mobilized following myocardial ischemia: possible predictive criteria for tissue injury. Proc Nat Acad Sci 1993; 90: 11021106.Google Scholar
Chevion M. A site-specific mechanism for free radical induced biological damage: the essential role of redox-active transition metals. Free Radic Biol Med 1988; 5: 2737.Google Scholar
Chevion M. Protection against free radical-induced and transition metal-mediated damage: the use of ‘pull’ and ‘push’ mechanisms. Free Radic Res Comms 1991; 12–13: 691–696.Google Scholar
Karwatowska-Prokopczuk E, Czarnowska E, Beresewicz A. Iron availability and free radical induced injury in the isolated ischaemic/reperfused rat heart. Cardiovasc Res 1992; 26: 5866.Google Scholar
Samuni AM, Afeworki M, Stein W, et al. Multifunctional antioxidant activity of HBED iron chelator. Free Radic Biol Med 2001; 30: 170177.Google Scholar
Berenshtein E, Vaisman B, Goldberg-Langerman C, et al. Roles of ferritin and iron in ischemic preconditioning of the heart. Mol Cell Biochem 2002; 234–235: 283292.Google Scholar
Floyd RA, Henderson R, Watson JJ, Wong PK. Use of salicylate with high pressure liquid chromatography and electrochemical detection (LCED) as a sensitive measure of hydroxyl free radicals in adriamycin treated rats. Free Radic Biol Med 1986; 2: 1318.Google Scholar
Onodera T, Ashraf M. Detection of hydroxyl radicals in the post-ischemic reperfused heart using salicylate as a trapping agent. J Mol Cell Cardiol 1991; 23: 365370.Google Scholar
Halliwell B, Kaur H, Ingelman-Sundberg M. Hydroxylation of salicylate as an assay for hydroxyl radicals: a cautionary note. Free Radic Biol Med 1991; 10: 439441.Google Scholar
Glantz L, Ginosar Y, Chevion M, et al. Halothane prevents postischemic production of hydroxyl radicals in the canine heart. Anesthesiology 1997; 86: 440447.Google Scholar
Simpson PJ, Lucchesi BR. Free radicals and myocardial ischemia and reperfusion injury. J Lab Clin Med 1987; 110: 1330.Google Scholar
Opie LH. Reperfusion injury and its pharmacologic modification. Circulation 1989; 80: 10491062.Google Scholar
Pain T, Yang XM, Critz SD, et al. Opening of mitochondrial KATP channels triggers the preconditioned state by generating free radicals. Circ Res 2000; 87: 460466.Google Scholar
Bolli R, Patel BS, Zhu WX, et al. The iron chelator desferrioxamine attenuates postischemic ventricular dysfunction. Am J Physiol 1987; 253: H1372H1380.Google Scholar
Karck M, Tanaka S, Berenshtein E, et al. The ‘push-pull’ mechanism to scavenge redox active transition metals: a novel concept in myocardial protection. J Thorac Cardiovasc Surg 2001; 121: 11691178.Google Scholar
Kashimoto S, Kume M, Ikeya K, Kumazawa T. Effects of sevoflurane and isoflurane in the post-ischaemic reperfused heart. Eur J Anaesthesiol 1998; 15: 553558.Google Scholar