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Anesth Analg 2008; 106:1926-
© 2008 International Anesthesia Research Society
doi: 10.1213/01.ane.0000312680.16252.56
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LETTER TO THE EDITOR

Section Editor:
Lawrence Saidman

Additive Cardioprotection by Ethanol and Sevoflurane: Are Sarcolemmal KATP Channels Also Involved?

Paul S. Pagel, MD, PhD

Anesthesia Service; The Clement J. Zablocki Veterans Affairs Medical Center; Milwaukee, Wisconsin; pspagel{at}mcw.edu

To the Editor:

Recently, Kaneda et al. described the additive cardioprotective effects of chronic ethanol consumption and sevoflurane exposure mediated by activation of protein kinase C (PKC), mitochondrial KATP channels (mitoKATP), and endothelial nitric oxide synthase in guinea pig hearts.1 My colleagues and I first identified a role for KATP channels in reductions in myocardial infarct size produced by chronic, intermittent ingestion of small quantities of ethanol in vivo,2 and subsequently demonstrated that both mitoKATP and sarcolemmal KATP channels (sarcKATP) mediate this chronic ethanol-induced preconditioning.3,4 A central role for mitoKATP in preconditioning by volatile anesthetics is well-established,5,6 but recent data also suggest that volatile agents profoundly affect sarcKATP function to produce cardioprotection. Isoflurane stimulated K+ efflux through sarcKATP in patch clamp experiments7 and directly opened sarcKATP by interacting with the nucleotide binding domains of the regulatory sulfonylurea receptor SUR2A (a subunit of sarcKATP) during intracellular acidosis similar to that encountered during ischemia.8,9 The {epsilon} isoform of PKC primed sarcKATP to open in the presence of isoflurane.10 Facilitation of sarcKATP current by isoflurane during reduced intracellular ATP concentrations, such as those encountered during ischemia, was also dependent on PKC-dependent signaling.11 Furthermore, isoflurane preconditioning caused persistent reductions in the sensitivity of the sarcolemmal KATP channel to inhibition by adenine nucleotides.12 SarcKATP was also acted as an effector during isoflurane preconditioning against oxidative stress in ventricular myocytes.13 These in vitro results provided evidence corroborating our previous observations that a selective sarcKATP antagonist abolishes preconditioning by desflurane in dogs.14 Thus, the combined cardioprotective effects of chronic ethanol consumption and administration of sevoflurane before prolonged ischemia and reperfusion may also be mediated by activation of sarcKATP in addition to mitoKATP.

REFERENCES

  1. Kaneda K, Miyamae M, Sugioka S, Okusa C, Inamura Y, Domae N, Kotani J, Figueredo VM. Sevoflurane enhances ethanol-induced cardiac preconditioning through modulation of protein kinase C, mitochondrial KATP channels, and nitric oxide synthase, in guinea pig hearts. Anesth Analg 2008;106:9–16[Abstract/Free Full Text]
  2. Pagel PS, Toller WG, Gross ER, Gare M, Kersten JR, Warltier DC. KATP channels mediate the beneficial effects of chronic ethanol ingestion. Am J Physiol Heart Circ Physiol 2000;279:H2574–H2579[Abstract/Free Full Text]
  3. Pagel PS, Krolikowski JG, Kehl F, Mraovic B, Kersten JR, Warltier DC. Role of mitochondrial and sarcolemmal KATP channels in canine ethanol-induced preconditioning in vivo. Anesth Analg 2002;94:841–8[Abstract/Free Full Text]
  4. Pagel PS, Kersten JR, Warltier DC. Mechanisms of myocardial protection produced by chronic ethanol consumption. Pathophysiology 2004;10:121–9[Medline]
  5. Tanaka K, Ludwig LM, Kersten JR, Pagel PS, Warltier DC. Mechanisms of cardioprotection by volatile anesthetics. Anesthesiology 2004;100:707–21[Web of Science][Medline]
  6. De Hert SG, Turani F, Mathur S, Stowe DF. Cardioprotection with volatile anesthetics: mechanisms and clinical implications. Anesth Analg 2005;100:1584–93[Abstract/Free Full Text]
  7. Kwok WM, Martinelli AT, Fujimoto K, Suzuki A, Stadnicka A, Bosnjak ZJ. Differential modulation of the cardiac adenosine triphosphate-sensitive potassium channel by isoflurane and halothane. Anesthesiology 2002;97:50–6[Web of Science][Medline]
  8. Stadnicka A, Bosjnak ZJ. Isoflurane decreases ATP sensitivity of guinea pig cardiac sarcolemmal KATP channel at reduced intracellular pH. Anesthesiology 2003;98:396–403[Web of Science][Medline]
  9. Bienengraeber M, Warltier DC, Bosnjak ZJ, Stadnicka A. Mechanism of cardiac sarcolemmal adenosine triphosphate-sensitive potassium channel activation by isoflurane in a heterogenous expression system. Anesthesiology 2006;105:534–40[Web of Science][Medline]
  10. Aizawa K, Turner LA, Weihrauch D, Bosjnak 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[Web of Science][Medline]
  11. Turner LA, Fujimoto K, Suzuki A, Stadnicka A, Bosnjak ZJ, Kwok WM. The interaction of isoflurane and protein kinase C-activators on sarcolemmal KATP channels. Anesth Analg 2005;100:1680–6[Abstract/Free Full Text]
  12. Stadnicka A, Marinovic J, Bienengraeber M, Bosnjak ZJ. Impact of in vivo preconditioning by isoflurane on adenosine triphosphate-sensitive potassium channels in the rat heart: lasting modulation of nucleotide sensitivity during early memory period. Anesthesiology 2006;104:503–10[Web of Science][Medline]
  13. Marinovic J, Bosjnak ZJ, Stadnicka A. Distinct roles of sarcolemmal and mitochondial adenosine triphosphate-sensitive potassium channels in isoflurane-induced protection against oxidative stress. Anesthesiology 2006;105:98–104[Web of Science][Medline]
  14. Toller WG, Gross ER, Kersten JR, Pagel PS, Gross GJ, Warltier DC. Sarcolemmal and mitochondrial adenosine triphosphate-dependent potassium (KATP) channels. Mechanism of desflurane-induced cardioprotection. Anesthesiology 2000;92:1731–9[Web of Science][Medline]



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M. Miyamae, S. Sugioka, and V. M. Figueredo
Additive Cardioprotection by Ethanol and Sevoflurane: Are Sarcolemmal KATP Channels Also Involved?
Anesth. Analg., June 1, 2008; 106(6): 1926 - 1927.
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Lippincott, Williams & Wilkins Anesthesia & Analgesia® is published for the International Anesthesia Research Society® by Lippincott Williams & Wilkins with the assistance of Stanford University Libraries' HighWire Press®. Copyright 2006 by the International Anesthesia Research Society. Online ISSN: 1526-7598   Print ISSN: 0003-2999 HighWire Press