Insulin addition after ischemia improves recovery of function equal to ischemic preconditioning in rat heart
Insulin addition after ischemia improves recovery of function equal to ischemic preconditioning in rat heart
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DOI：
10.1007/s00395-003-0414-y
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发表时间：
2003-09-01
影响因子：
9.5
通讯作者：
Doenst, T
中科院分区：
文献类型：
--
作者：
Fischer-Rasokat, U;Beyersdorf, F;Doenst, T
缺血预处理（IPC）被认为是改善缺血耐受性的最有效机制。我们已经证明，在再灌注期间添加胰岛素可以改善离体大鼠工作心脏的功能恢复。我们在此比较这两种机制在改善缺血后功能恢复中的相对重要性。方法用含葡萄糖(5 mmol/l) +油酸（0.4 mmol/l）的Krebs-Henseleit缓冲液灌注离体工作大鼠心脏20 min，缺血15 min，再灌注35 min。IPC是通过缺血5分钟后再灌注10分钟来实现的。再灌注开始时是否添加胰岛素（1 mU/ml）。Wortmannin （WM, 3 μ mol/l）是一种磷脂酰肌醇3-激酶抑制剂，从实验开始就存在或不存在于灌注液中。在实验结束时，我们测量了[2-H-3]葡萄糖的葡萄糖摄取，心脏功率和组织代谢物含量。结果缺血前心肌功率为7.17 ~ 10.4 mW。缺血后，心功率恢复到65.7±3.8%（对照组）。胰岛素显著提高康复（96.3 +/- 10.8%,p < 0.05）。IPC的回收率为86.2 +/- 6.2%,p < 0.05)。胰岛素和IPC的影响无相加性（回收率为83.4±6.2%,p < 0.05）。WM完全抑制了胰岛素和IPC的作用（分别为69.5 +/- 3.3,72.0 +/- 6.9）。基础葡萄糖摄取范围为2.53 ~ 3.46 μ mol/gdry，缺血后WM的存在显著降低。结论胰岛素是改善缺血后收缩功能的有效工具。缺血后添加胰岛素对恢复的改善可能通过与缺血预处理类似的机制介导。
Background Ischemic preconditioning (IPC) is considered the most potent mechanism to improve ischemia tolerance. We have demonstrated that insulin addition during reperfusion improves recovery of function in the isolated working rat heart. We herein compare the relative importance of these two mechanisms in improving recovery of postischemic function. Methods Isolated working rat hearts were perfused with Krebs-Henseleit buffer containing glucose (5 mmol/l) plus oleate (0.4 mmol/l) for 20 min and were then subjected to 15 min of ischemia followed by 35 min of reperfusion. IPC was achieved by an ischemic period of five minutes followed by 10 minutes of reperfusion before ischemia. Insulin (1 mU/ml) was or was not added at the beginning of reperfusion. Wortmannin (WM, 3 mumol/l), an inhibitor of phosphatidylinositol 3-kinase, was or was not present in the perfusate from the beginning of the experiments. We measured glucose uptake with [2-H-3]glucose, cardiac power and tissue metabolite content at the end of the experiments. Results Cardiac power before ischemia ranged from 7.17 to 10.4 mW. After ischemia, cardiac power recovered to 65.7 +/- 3.8% (Control). Insulin significantly improved recovery (96.3 +/- 10.8%, p < 0.05 vs. Control). This effect was also achieved by IPC (recovery 86.2 +/- 6.2%, p < 0.05). The effects of insulin and IPC were not additive (recovery 83.4 +/- 6.2%, p < 0.05). WM fully inihibited the effects of both insulin and IPC (69.5 +/- 3.3, 72.0 +/- 6.9, respectively). Basal glucose uptake ranged from 2.53 to 3.46 mu mol/gdry, and was significantly lower after ischemia in the presence of WM. Conclusions Insulin is a potent tool to improve postischemic contractile function. The improvement of recovery afforded by insulin added after ischemia may be mediated through a similar mechanism as ischemic preconditioning.