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LETTER TO THE EDITOR

When Lack of Addition Really Does Add Up

Anesthesia Service; Clement J. Zablocki Veterans Affairs Medical Center; Milwaukee, WI; paul.pagel{at}va.gov

To the Editor:

Deyhimy et al. recently demonstrated that administration of 2.5% sevoflurane before or after global ischemia and reperfusion reduces infarct size, attenuates creatine kinase release, preserves left ventricular function, and decreases intracellular Na⁺ and Ca²⁺ accumulation in Langendorff perfused isolated rat hearts (1). However, combined sevoflurane pre- and postconditioning did not provide additional cardioprotection as compared with either intervention alone. These findings may be anticipated because the concentration of sevoflurane used before or after global ischemia and reperfusion probably caused near maximal protection against ischemic injury, and thus, the combination of sevoflurane pre- and postconditioning failed to produce any further beneficial effect. There is a limited amount of myocardium that may be salvaged by anesthetic or ischemic pre- or postconditioning (2,3). For example, a 30-min exposure to 1 MAC isoflurane or a 5-min ischemic episode before prolonged coronary artery occlusion and reperfusion produced similar reductions in infarct size in dogs, but the combination of these anesthetic and ischemic preconditioning stimuli did not result in further protection (2). In contrast, combined administration of 0.5 MAC isoflurane (a concentration that did not attenuate myocardial necrosis) and a subthreshold ischemic stimulus during early reperfusion caused reductions in infarct size that were equal in magnitude to 1.0 MAC isoflurane or more intense ischemic postconditioning (3). Anesthetic preconditioning has been shown to be dose related between 0.25 and 1.25 MAC (4). In fact, a lower concentration (2%) of sevoflurane was able to decrease the time threshold of classical ischemic preconditioning (5), conferred an additional beneficial effect during delayed ischemic preconditioning (6), and produced more pronounced reductions in infarct size when administered both before and after coronary artery occlusion in rats in vivo as compared with pre- or postconditioning alone (7). Thus, it seems very likely that the combination of sevoflurane pre- and postconditioning may also have produced additive cardioprotective effects had a lower concentration of the volatile drug been used in the authors’ isolated rat heart model (1).

REFERENCES

1. Deyhimy DI, Fleming NW, Brodkin IG, Liu H. Anesthetic preconditioning combined with postconditioning offers no additional benefit over preconditioning or postconditioning alone. Anesth Analg 2007;105:316–24[Abstract/Free Full Text]
2. Kersten JR, Schmeling TJ, Pagel PS, Gross GJ, Warltier DC. Isoflurane mimics ischemic preconditioning via activation of K_ATP channels. Reduction of myocardial infarct size with an acute memory phase. Anesthesiology 1997;87:361–70[Web of Science][Medline]
3. Chiari PC, Bienengraeber MW, Pagel PS, Krolikowski JG, Kersten JR, Warltier DC. Isoflurane protects against myocardial infarction during early reperfusion by activation of phosphatidylinositol-3-kinase signal transduction: evidence for anesthetic-induced postconditioning in rabbits. Anesthesiology 2005;102:102–9[Web of Science][Medline]
4. Kehl F, Krolikowski JG, Mraovic B, Pagel PS, Warltier DC, Kersten JR. Is isoflurane-induced preconditioning dose related? Anesthesiology 2002;96:675–80[Web of Science][Medline]
5. Toller WG, Kersten JR, Pagel PS, Hettrick DA, Warltier DC. Sevoflurane reduces myocardial infarct size and decreases the time threshold for ischemic preconditioning in dogs. Anesthesiology 1999;91:1437–46[Web of Science][Medline]
6. Mullenheim J, Ebel D, Bauer M, Otto F, Heinen A, Frassdorf J, Preckel B, Schlack W. Sevoflurane confers additional cardioprotection after ischemic late preconditioning in rabbits. Anesthesiology 2003;99:624–31[Web of Science][Medline]
7. Obal D, Dettwiler S, Favoccia C, Scharbatke H, Preckel B, Schlack W. The influence of mitochondrial K_ATP-channels in the cardioprotection of preconditioning and postconditioning by sevoflurane in the rat in vivo. Anesth Analg 2005;101: 1252–60[Abstract/Free Full Text]

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This Article Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Email this article to a colleague Similar articles in this journal Similar articles in Web of Science Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Web of Science (1) Citing Articles via Google Scholar Google Scholar Articles by Pagel, P. S. Search for Related Content PubMed Articles by Pagel, P. S.