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BioMed Research International
Volume 2014, Article ID 536510, 6 pages
Research Article

Insulin Preconditioning Elevates p-Akt and Cardiac Contractility after Reperfusion in the Isolated Ischemic Rat Heart

1Department of Anaesthesia, Royal Victoria Hospital, McGill University Health Center, Montreal, QC, Canada H3A 1A1
2Outcomes Research Consortium, Cleveland, OH 44195, USA
3Department of Anesthesiology, Yamanashi University, Yamanashi 409-3821, Japan

Received 13 June 2014; Accepted 1 August 2014; Published 13 August 2014

Academic Editor: M.-Saadeh Suleiman

Copyright © 2014 Tamaki Sato et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.


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.