title: Gender-related difference of sevoflurane postconditioning in isolated rat hearts: focus on phosphatidylinositol-3-kinase/Akt signaling.
abstract: BACKGROUND
  Previous studies have reported that female gender confers cardioprotection against ischemia/reperfusion (I/R) injury, partly because estrogen activates phosphatidylinositol-3-kinase/Akt (PI3K/Akt) pathway. We have previously proven that cardioprotection of sevoflurane postconditioning is mediated by PI3K/Akt pathway in male rats. The purpose of the present study was to determine whether the cardioprotection of sevoflurane postconditioning is influenced by gender, and the role of PI3K/Akt pathway in such gender difference.
  
  
  METHODS
  Isolated hearts from 2-mo-old male and female SD rats were subjected to ischemia for 40 min and reperfusion for 2 h in the Langendorff apparatus, and were randomly assigned to the following groups: no ischemia/reperfusion (CON), ischemia/reperfusion (I/R), I/R+sevoflurane postconditioning (I/R+SPC), I/R+100 nM wortmannin (I/R+WOR), and I/R+SPC+WOR. Postconditioning was performed with administration of 3.0% sevoflurane at the first 10 min of reperfusion. Left ventricular developed pressure (LVDP), left ventricular end-diastolic pressure (LVEDP), and myocardial lactate dehydrogenase (LDH) release were measured. Infarct size was detected by riphenyltetrazolium chloride staining. The protein expression of total Akt (t-Akt) and phosphorylated Akt (Ser(473)) (p-Akt) were determined by Western blot.
  
  
  RESULTS
  The I/R group showed lower LVDP and higher LVEDP than CON group in the same gender during reperfusion period. The LDH release and infarct size were smaller in the female I/R group (P < 0.05 versus male I/R group). Sevoflurane postconditioning markedly improved left ventricular function and decreased LDH, infarct size in the male I/R+SPC group (P < 0.05 versus male I/R group) but not in the female I/R+SPC group. Wortmannin abolished the cardioprotection of sevoflurane postconditioning in the male I/R+SPC+Wort group (P < 0.05 versus male I/R+SPC group), and markedly increased the infarct size and LVEDP and decreased LVDP in female rats. The t-Akt protein expression was no significant difference in all groups. The ratio of p-Akt/t-Akt expression in the male CON group was a little lower than that in the female CON group, but there was no statistical significance. In male rats, the ratio of p-Akt/t-Akt was no difference between CON and I/R group, but it was higher in I/R+SPC group than that in I/R group (P < 0.05). In female rats, the level of p-Akt was markedly increased by I/R, which was markedly higher than that in male I/R group (P < 0.05). However, p-Akt was not different between I/R and I/R+SPC groups. Wortmannin decreased the p-Akt expression in both male and female rats.
  
  
  CONCLUSIONS
  It is concluded that female rat hearts showed greater resistance to I/R injury, and sevoflurane postconditioning developed cardioprotection in male rats but not in female rats. The PI3K/Akt pathway may be involved in the cardioprotection by both sevoflurane postconditioning and gender.
authors.affiliation: Department of Anesthesiology, 2nd Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China.
authors.forename: Zhoupeng
authors.initials: Z
authors.lastname: Zheng
authors.forename: Meijuan
authors.initials: M
authors.lastname: Yang
authors.forename: Fengjiang
authors.initials: F
authors.lastname: Zhang
authors.forename: Jing
authors.initials: J
authors.lastname: Yu
authors.forename: Junkuan
authors.initials: J
authors.lastname: Wang
authors.forename: Leilei
authors.initials: L
authors.lastname: Ma
authors.forename: Yanbo
authors.initials: Y
authors.lastname: Zhong
authors.forename: Lingbo
authors.initials: L
authors.lastname: Qian
authors.forename: Gang
authors.initials: G
authors.lastname: Chen
authors.forename: Lina
authors.initials: L
authors.lastname: Yu
authors.forename: Min
authors.initials: M
authors.lastname: Yan
mesh_terms: D018685:Anesthetics, Inhalation / Q000494:pharmacology*; D000818:Animals; D005260:Female; D066298:In Vitro Techniques; D057775:Ischemic Postconditioning; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D008297:Male; D008738:Methyl Ethers / Q000494:pharmacology*; D015428:Myocardial Reperfusion Injury / Q000517:prevention & control; D019869:Phosphatidylinositol 3-Kinases / Q000502:physiology*; D051057:Proto-Oncogene Proteins c-akt / Q000502:physiology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D000077149:Sevoflurane; D012727:Sex Characteristics; D015398:Signal Transduction / Q000502:physiology*; D016277:Ventricular Function, Left
chemical_list: D018685:Anesthetics, Inhalation; D008738:Methyl Ethers; D000077149:Sevoflurane; D007770:L-Lactate Dehydrogenase; D019869:Phosphatidylinositol 3-Kinases; D051057:Proto-Oncogene Proteins c-akt