TY - JOUR T1 - Gender-related difference of sevoflurane postconditioning in isolated rat hearts: focus on phosphatidylinositol-3-kinase/Akt signaling. AU - Zheng,Zhoupeng, AU - Yang,Meijuan, AU - Zhang,Fengjiang, AU - Yu,Jing, AU - Wang,Junkuan, AU - Ma,Leilei, AU - Zhong,Yanbo, AU - Qian,Lingbo, AU - Chen,Gang, AU - Yu,Lina, AU - Yan,Min, Y1 - 2011/05/17/ PY - 2010/12/23/received PY - 2011/03/13/revised PY - 2011/04/18/accepted PY - 2011/6/28/entrez PY - 2011/6/28/pubmed PY - 2011/10/14/medline SP - e3 EP - 9 JF - The Journal of surgical research JO - J Surg Res VL - 170 IS - 1 N2 - 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. MATERIALS AND 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. SN - 1095-8673 UR - https://www.unboundmedicine.com/medline/citation/21704330/Gender_related_difference_of_sevoflurane_postconditioning_in_isolated_rat_hearts:_focus_on_phosphatidylinositol_3_kinase/Akt_signaling_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0022-4804(11)00415-X DB - PRIME DP - Unbound Medicine ER -