title: Insulin preconditioning elevates p-Akt and cardiac contractility after reperfusion in the isolated ischemic rat heart.
abstract: Insulin induces cardioprotection partly via an antiapoptotic effect. However, the optimal timing of insulin administration for the best quality cardioprotection remains unclear. We tested the hypothesis that insulin administered prior to ischemia provides better cardioprotection than insulin administration after ischemia. Isolated rat hearts were prepared using Langendorff method and divided into three groups. The Pre-Ins group (Pre-Ins) received 0.5 U/L insulin prior to 15 min no-flow ischemia for 20 min followed by 20 min of reperfusion. The Post-Ins group (Post-Ins) received 0.5 U/L insulin during the reperfusion period only. The control group (Control) was perfused with KH buffer throughout. The maximum of left ventricular derivative of pressure development (dP/dt(max)) was recorded continuously. Measurements of TNF-α and p-Akt in each time point were assayed by ELISA. After reperfusion, dP/dt(max) in Pre-Ins was elevated, compared with Post-Ins at 10 minutes after reperfusion and Control at all-time points. TNF-α levels at 5 minutes after reperfusion in the Pre-Ins were lower than the others. After 5 minutes of reperfusion, p-Akt was elevated in Pre-Ins compared with the other groups. Insulin administration prior to ischemia provides better cardioprotection than insulin administration only at reperfusion. TNF-α suppression is possibly mediated via p-Akt leading to a reduction in contractile myocardial dysfunction.
authors.affiliation: Department of Anaesthesia, Royal Victoria Hospital, McGill University Health Center, Montreal, QC, Canada H3A 1A1 ; Outcomes Research Consortium, Cleveland, OH 44195, USA.
authors.forename: Tamaki
authors.initials: T
authors.lastname: Sato
authors.affiliation: Department of Anaesthesia, Royal Victoria Hospital, McGill University Health Center, Montreal, QC, Canada H3A 1A1 ; Outcomes Research Consortium, Cleveland, OH 44195, USA.
authors.forename: Hiroaki
authors.identifier: 0000-0002-8817-3904
authors.initials: H
authors.lastname: Sato
authors.affiliation: Department of Anesthesiology, Yamanashi University, Yamanashi 409-3821, Japan.
authors.forename: Takeshi
authors.identifier: 0000-0003-2849-9360
authors.initials: T
authors.lastname: Oguchi
authors.affiliation: Department of Anesthesiology, Yamanashi University, Yamanashi 409-3821, Japan.
authors.forename: Hisashi
authors.initials: H
authors.lastname: Fukushima
authors.affiliation: Department of Anaesthesia, Royal Victoria Hospital, McGill University Health Center, Montreal, QC, Canada H3A 1A1.
authors.forename: George
authors.identifier: 0000-0003-4488-6168
authors.initials: G
authors.lastname: Carvalho
authors.affiliation: Department of Anaesthesia, Royal Victoria Hospital, McGill University Health Center, Montreal, QC, Canada H3A 1A1.
authors.forename: Ralph
authors.identifier: 0000-0001-5009-1543
authors.initials: R
authors.lastname: Lattermann
authors.affiliation: Outcomes Research Consortium, Cleveland, OH 44195, USA ; Department of Anesthesiology, Yamanashi University, Yamanashi 409-3821, Japan.
authors.forename: Takashi
authors.identifier: 0000-0002-5307-5968
authors.initials: T
authors.lastname: Matsukawa
authors.affiliation: Department of Anaesthesia, Royal Victoria Hospital, McGill University Health Center, Montreal, QC, Canada H3A 1A1 ; Outcomes Research Consortium, Cleveland, OH 44195, USA.
authors.forename: Thomas
authors.initials: T
authors.lastname: Schricker
mesh_terms: D000818:Animals; D003326:Coronary Circulation / Q000187:drug effects; D006339:Heart Rate / Q000187:drug effects; D066298:In Vitro Techniques; D007328:Insulin / Q000494:pharmacology*; D019157:Ischemic Preconditioning, Myocardial; D008297:Male; D009200:Myocardial Contraction / Q000187:drug effects*; D015428:Myocardial Reperfusion Injury / Q000201:enzymology* / Q000473:pathology / Q000503:physiopathology*; D010766:Phosphorylation / Q000187:drug effects; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism*; D017208:Rats, Wistar; D013997:Time Factors; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D007328:Insulin; D014409:Tumor Necrosis Factor-alpha; D051057:Proto-Oncogene Proteins c-akt