Correspondence  |   January 2003
Myocardial Ischemic Preconditioning Decreases Postischemic Oxygen Free Radical Production
Author Affiliations & Notes
  • Yaacov Gozal, M.D.
  • *Department of Anesthesiology and Critical Care Medicine, Hadassah University Hospital, Jerusalem, Israel.
Article Information
Correspondence   |   January 2003
Myocardial Ischemic Preconditioning Decreases Postischemic Oxygen Free Radical Production
Anesthesiology 1 2003, Vol.98, 281. doi:0000542-200301000-00049
Anesthesiology 1 2003, Vol.98, 281. doi:0000542-200301000-00049
To the Editor:—
We read with great interest the article by Müllenheim et al.  1 published in the April 2002 issue of Anesthesiology. They report that the release of free radicals is an important feature of isoflurane-induced myocardial preconditioning. According to recent reports, ischemic preconditioning induces a cascade with the opening of mitochondrial KATPchannels, followed by the generation of free radicals to trigger the preconditioning state. 2 The preconditioning cascade continues with the activation of kinases, if the heart again becomes ischemic. Kersten et al.  3 have shown that isoflurane mimics ischemic preconditioning by the activation of KATPchannels. We have shown that hydroxyl free radicals are released during events of ischemia and reperfusion. 4 These free radicals are known for their harmful effect on the myocardium, both directly, by damaging membranes and enzymes, and indirectly, by initiating the inflammatory process. The release of these hydroxyl radicals could be blocked effectively by halothane, ischemic preconditioning, and by the chelating compound desferral–zinc. 4,5 Isoflurane was found to have only a small, insignificant effect on free radical production. In their study, Müllenheim et al.  1 demonstrated that the use of antioxidants blocked the preconditioning cascade, which might have already been initiated with the opening of KATPchannels by isoflurane. Their in vivo  rabbit model indirectly evaluated postischemic oxygen free radical production, as they measured the preconditioning effect in the presence of scavengers. In our model, however, the release of hydroxyl radicals is identified by 2,3-dihydroxybenzoic acid and 2,5-dihydroxybenzoic acid measurement, the direct product of the interaction between hydroxyl radicals and salicylate given intravenously. 4 This method monitors free radical–related events in vivo  as they are formed in the tissues. Salicylate is a highly effective hydroxyl radical trap, which, upon scavenging the hydroxyl radical, forms the stable adducts 2,3-dihydroxybenzoic acid and 2,5-dihydroxybenzoic acid by hydroxylation reaction.
Thus, during reperfusion and during preconditioning, there are free radical–related events that act in a contradictory manner. This warrants further investigation of free radical–related damage to intracellular organelles and, conversely, of free radical signaling for preconditioning.
Müllenheim J, Ebel D, Frässdorf J, Preckel B, Thämer V, Shlacker W: Isoflurane preconditions myocardium against infarction via release of free radicals. A nesthesiology 2002; 96: 934–40Müllenheim, J Ebel, D Frässdorf, J Preckel, B Thämer, V Shlacker, W
Pain T, Yang XM, Critz SD, Yue Y, Nakano A, Liu GS, Heusch G, Cohen MV, Downey JM: Opening of mitochondrial KATPchannels triggers the preconditioned state by generating free radicals. Circ Res 2000; 87: 460–6Pain, T Yang, XM Critz, SD Yue, Y Nakano, A Liu, GS Heusch, G Cohen, MV Downey, JM
Kersten JR, Schmeling TJ, Pagel PS, Gross GJ, Warltier DC: Isoflurane mimics ischemic preconditioning via  activation of KATPchannels. A nesthesiology 1997; 87: 361–70Kersten, JR Schmeling, TJ Pagel, PS Gross, GJ Warltier, DC
Glantz L, Ginosar Y, Chevion M, Gozal Y, Elami A, Navot N, Kitrossky N, Drenger B: Halothane prevents postischemic production of hydroxyl radicals in the canine heart. A nesthesiology 1997; 86: 440–7Glantz, L Ginosar, Y Chevion, M Gozal, Y Elami, A Navot, N Kitrossky, N Drenger, B
Gozal Y, Chevion M, Raphael J, Drenger B: Ischemic preconditioning, but not isoflurane limits the oxygen free radical production in a rabbit model of myocardial ischemia and reperfusion. A nesthesiology 2001; 95: A677Gozal, Y Chevion, M Raphael, J Drenger, B