title: Effects of nitrous oxide on the rat heart in vivo: another inhalational anesthetic that preconditions the heart?
abstract: BACKGROUND
  For nitrous oxide, a preconditioning effect on the heart has yet not been investigated. This is important because nitrous oxide is commonly used in combination with volatile anesthetics, which are known to precondition the heart. The authors aimed to clarify (1) whether nitrous oxide preconditions the heart, (2) how it affects protein kinase C (PKC) and tyrosine kinases (such as Src) as central mediators of preconditioning, and (3) whether isoflurane-induced preconditioning is influenced by nitrous oxide.
  
  
  METHODS
  For infarct size measurements, anesthetized rats were subjected to 25 min of coronary artery occlusion followed by 120 min of reperfusion. Rats received nitrous oxide (60%), isoflurane (1.4%) or isoflurane-nitrous oxide (1.4%/60%) during three 5-min periods before index ischemia (each group, n = 7). Control animals remained untreated for 45 min. Additional hearts (control, 60% nitrous oxide alone%, and isoflurane-nitrous oxide [0.6%/60%, in equianesthetic doses]) were excised for Western blot of PKC-epsilon and Src kinase (each group, n = 4).
  
  
  RESULTS
  Nitrous oxide had no effect on infarct size (59.1 +/- 15.2% of the area at risk vs. 51.1 +/- 10.9% in controls). Isoflurane (1.4%) and isoflurane-nitrous oxide (1.4%/60%) reduced infarct size to 30.9 +/- 10.6 and 28.7 +/- 11.8% (both P < 0.01). Nitrous oxide (60%) had no effect on phosphorylation (2.3 +/- 1.8 vs. 2.5 +/- 1.7 in controls, average light intensity, arbitrary units) and translocation (7.0 +/- 4.3 vs. 7.4 +/- 5.2 in controls) of PKC-epsilon. Src kinase phosphorylation was not influenced by nitrous oxide (4.6 +/- 3.9 vs. 5.0 +/- 3.8; 3.2 +/- 2.2 vs. 3.5 +/- 3.0). Isoflurane-nitrous oxide (0.6%/60%, in equianesthetic doses) induced PKC-epsilon phosphorylation (5.4 +/- 1.9 vs. 2.8 +/- 1.5; P < 0.001) and translocation to membrane regions (13.8 +/- 13.0 vs. 6.7 +/- 2.0 in controls; P < 0.05).
  
  
  CONCLUSIONS
  Nitrous oxide is the first inhalational anesthetic without preconditioning effect on the heart. However, isoflurane-induced preconditioning and PKC-epsilon activation are not influenced by nitrous oxide.
authors.affiliation: Department of Anesthesiology, University Hospital of Düsseldorf, Moorenstrasse 5, 40225 Düsseldorf, Germany.
authors.forename: Nina C
authors.initials: NC
authors.lastname: Weber
authors.forename: Octavian
authors.initials: O
authors.lastname: Toma
authors.forename: Saqib
authors.initials: S
authors.lastname: Awan
authors.forename: Jan
authors.initials: J
authors.lastname: Frässdorf
authors.forename: Benedikt
authors.initials: B
authors.lastname: Preckel
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Schlack
mesh_terms: D000679:Amygdala / Q000502:physiology*; D018685:Anesthetics, Inhalation / Q000494:pharmacology*; D000818:Animals; D001362:Avoidance Learning / Q000187:drug effects; D000077335:Desflurane; D018690:Excitatory Amino Acid Agonists / Q000633:toxicity; D006221:Halothane / Q000494:pharmacology; D006930:Hyperalgesia / Q000139:chemically induced / Q000523:psychology; D007530:Isoflurane / Q000031:analogs & derivatives / Q000494:pharmacology; D008297:Male; D008568:Memory / Q000187:drug effects*; D008738:Methyl Ethers / Q000494:pharmacology*; D016202:N-Methylaspartate / Q000633:toxicity; D051381:Rats; D017207:Rats, Sprague-Dawley; D000077149:Sevoflurane
chemical_list: D018685:Anesthetics, Inhalation; D018690:Excitatory Amino Acid Agonists; D008738:Methyl Ethers; D000077149:Sevoflurane; D016202:N-Methylaspartate; D000077335:Desflurane; D007530:Isoflurane; D006221:Halothane