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Activation of Akt and cardioprotection against reperfusion injury are maximal with only five minutes of sevoflurane postconditioning in isolated rat hearts |
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| Authors: | Yuan-yuan Yao Man-hua Zhu Feng-jiang Zhang Chuan-yun Wen Lei-lei Ma Wen-na Wang Can-can Wang Xian-bao Liu Li-na Yu Ling-bo Qian Jian-an Wang Min Yan |
| Institution: | 1. Department of Anesthesiology, the Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, 310009, China 2. Jiangsu Province Key Laboratory of Anesthesiology, Xuzhou Medical College, Xuzhou, 221002, China 3. Department of Cardiology, the Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, 310009, China 4. Department of Physiology, Zhejiang Medical College, Hangzhou, 310035, China |
| Abstract: | It had been proved that administration of sevoflurane for the first two minutes of reperfusion effectively protects the heart against reperfusion injury in rats in vivo. Our aim was to investigate the duration of effective sevoflurane administration and its underlying mechanism in isolated rat hearts exposed to global ischemia/reperfusion (I/R) injury. Adult male Sprague-Dawley rats were randomly divided into six groups (n=12): a sham-operation group, an I/R group, and four sevoflurane postconditioning groups (S2, S5, S10, and S15). In the S2, S5, S10, and S15 groups, the duration times of sevoflurane administration were 2, 5, 10, and 15 min after the onset of reperfusion, respectively. The isolated rat hearts were mounted on the Langendorff system, and after a period of equilibrium were subjected to 40 min global ischemia and 120 min reperfusion. Left ventricular (LV) hemodynamic parameters were monitored throughout each experiment and the data at 30 min of equilibrium and 30, 60, 90, and 120 min of reperfusion were analyzed. Myocardial infarct size at the end of reperfusion (n=7 in each group) and the expression of myocardial phosphorylated Akt (p-Akt) after 15-min reperfusion were determined in a duplicate set of six groups of rat hearts (n=5 in each group). Compared with the I/R group, the S5, S10, and S15 groups had significantly improved left ventricular end-diastolic pressure (LVEDP), left ventricular developed pressure (LVDP), and the maximal rate of rise or fall of the LV pressure (±dP/dt max), and decreased myocardial infarct size (P<0.05), but not the S2 group. After 15 min of reperfusion, the expression of p-Akt was markedly up-regulated in the S5, S10, and S15 groups compared with that in the I/R group (P<0.05), but not in the S2 group. Sevoflurane postconditioning for 5 min was sufficient to activate Akt and exert maximal cardioprotection against I/R injury in isolated rat hearts. |
| Keywords: | Sevoflurane postconditioning Ischemia/reperfusion (I/R) injury Cardioprotection Duration of administration Akt |
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