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猪缺血再灌注模型中胰岛素和钾对心肌的保护作用。

Myocardial protection of insulin and potassium in a porcine ischemia-reperfusion model.

作者信息

Oates Aris, Nubani Reem, Smiley Jeremy, Kistler Laura, Hughey Scott, Theiss Peter, Perez-Tamayo R Anthony, Eiferman Daniel, Lonchyna Vassyl, Higgins Robert S

机构信息

Department of Cardiovascular Surgery, Rush University Medical Center, Chicago, IL 60612, USA.

出版信息

Surgery. 2009 Jul;146(1):23-30. doi: 10.1016/j.surg.2009.03.028.

Abstract

BACKGROUND

We previously evaluated cardioprotective effects of glucose-insulin-potassium (GIK) in a porcine ischemia-reperfusion model; our results showed less myocardial pH decrease during ischemia and reperfusion and faster normalization of ATP and glucose during reperfusion. The proposed protective mechanism was facilitation of glucose transport for myocardial metabolism. The objective of this study was to assess the impact of insulin-potassium (IK) alone on myocardial metabolism.

METHODS

Male swine received continuous infusion of IK (IK group, n = 10), GIK (GIK group, n = 10), or standard lactated Ringer's (LR) solution (controls, n = 10). Induction of 20 minutes of ischemia in the left anterior descending (LAD) artery distribution was followed by 20 minutes of reperfusion. Real-time biosensors recorded pH and glucose levels in ischemic and nonischemic beds. Myocardial biopsies in the distribution of the LAD assessed ATP levels. Groups were compared using the Kruskal-Wallis and Mann-Whitney tests.

RESULTS

Real-time data are presented as percent change from baseline. At less than 10 minutes of ischemia, the average pH change was less for the IK group than the LR group (0.03% +/- 0.21% vs -2.06% +/- 1.23%; P = .001), and the pH change in the IK group was similar to the GIK group. After 10 minutes of ischemia and during the first 10 minutes of reperfusion, the IK group experienced pH changes that were similar to the LR group. Biopsies after 20 minutes of ischemia and 20 minutes of reperfusion showed less of a decline in ATP levels for the IK group compared to the LR group. Glucose at all time points demonstrated no statistically significant differences.

CONCLUSION

IK infusion alone demonstrates cardioprotective effects during early ischemia; however, compared to GIK infusion after 20 minutes of ischemia and reperfusion, myocardial pH and glucose levels were not sustained. Although insulin may facilitate glucose transport during ischemia, additional glucose in combination with IK enhances myocardial protection during reperfusion. This finding suggests that GIK enhancement during acute ischemia-reperfusion may improve myocardial protection.

摘要

背景

我们之前在猪缺血再灌注模型中评估了葡萄糖 - 胰岛素 - 钾(GIK)的心脏保护作用;我们的结果显示,在缺血和再灌注期间心肌pH值下降较少,且再灌注期间ATP和葡萄糖更快恢复正常。提出的保护机制是促进葡萄糖转运以进行心肌代谢。本研究的目的是评估单独使用胰岛素 - 钾(IK)对心肌代谢的影响。

方法

雄性猪持续输注IK(IK组,n = 10)、GIK(GIK组,n = 10)或标准乳酸林格氏液(对照组,n = 10)。在左前降支(LAD)动脉分布区域诱导20分钟缺血,随后进行20分钟再灌注。实时生物传感器记录缺血和非缺血区域的pH值和葡萄糖水平。在LAD分布区域进行心肌活检以评估ATP水平。使用Kruskal - Wallis和Mann - Whitney检验对各组进行比较。

结果

实时数据以相对于基线的百分比变化表示。在缺血少于10分钟时,IK组的平均pH值变化小于LR组(0.03%±0.21%对 - 2.06%±1.23%;P = 0.001),且IK组的pH值变化与GIK组相似。缺血10分钟后及再灌注的前10分钟,IK组的pH值变化与LR组相似。缺血20分钟和再灌注20分钟后的活检显示,IK组的ATP水平下降幅度小于LR组。所有时间点的葡萄糖水平均无统计学显著差异。

结论

单独输注IK在早期缺血期间表现出心脏保护作用;然而,与缺血和再灌注20分钟后输注GIK相比,心肌pH值和葡萄糖水平未得到维持。尽管胰岛素可能在缺血期间促进葡萄糖转运,但额外的葡萄糖与IK联合可增强再灌注期间的心肌保护。这一发现表明,急性缺血再灌注期间增强GIK可能改善心肌保护。

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