Emulsified isoflurane induces postconditioning against myocardial infarction via JAK-STAT pathway

Background: The authors investigated the cardioprotection afforded by postconditioning with intravenous infusion of emulsified isoflurane in a rat model in vivo and determined the role of Janus kinase (JAK)-signal transducer and activator of transcription (STAT) pathway in such procedure.

Materials and methods: Rats were subjected to a 30-min coronary artery occlusion followed by a 120-min reperfusion. Postconditioning was achieved by inhalation of 1 minimum alveolar concentration isoflurane or intravenous infusion of emulsified isoflurane (8% vol/vol) during the last 3 min of coronary artery occlusion and the first 5 min of reperfusion. AG490 was used to inhibit the activity of JAK2. Infarct size was determined by triphenyltetrazolium chloride staining. Expressions of JAK2, STAT1, and STAT3 were measured by Western blot.

Results: Infarct size was significantly reduced from 51.6% ± 7.6% in the control group to 29.8% ± 7.0% in rats postconditioned with inhalation of isoflurane (P < 0.01). A powerful infarct-sparing effect was also induced by postconditioning with intravenous infusion of emulsified isoflurane (33.7% ± 5.6% versus control group, P < 0.01). Pretreatment with AG490 abolished the anti-infarct effects conducted by either inhalation of isoflurane (44.1% ± 7.1% versus control group, P > 0.05) or intravenous infusion of emulsified isoflurane (51.4% ± 6.8% versus control group, P > 0.05). Compared with the control group, postconditioning with inhalation of isoflurane or infusion of emulsified isoflurane remarkably enhanced the expression of phosphorylation of JAK2 Tyr(1007)/Tyr(1008) and STAT3 Tyr(705), but not phosphorylation of STAT1 Tyr(701).

Conclusions: Postconditioning with intravenous infusion of emulsified isoflurane induces powerful cardioprotection, which is mediated, at least in part, by activating JAK-STAT pathway.