氧化亚氮对大鼠活体心脏的影响：另一种对心脏有预处理作用的吸入性麻醉剂？

Effects of nitrous oxide on the rat heart in vivo: another inhalational anesthetic that preconditions the heart?

作者信息

Weber Nina C, Toma Octavian, Awan Saqib, Frässdorf Jan, Preckel Benedikt, Schlack Wolfgang

机构信息

Department of Anesthesiology, University Hospital of Düsseldorf, Moorenstrasse 5, 40225 Düsseldorf, Germany.

出版信息

Anesthesiology. 2005 Dec;103(6):1174-82. doi: 10.1097/00000542-200512000-00011.

DOI:10.1097/00000542-200512000-00011

PMID:16306729

Abstract

BACKGROUND

For nitrous oxide, a preconditioning effect on the heart has yet not been investigated. This is important because nitrous oxide is commonly used in combination with volatile anesthetics, which are known to precondition the heart. The authors aimed to clarify (1) whether nitrous oxide preconditions the heart, (2) how it affects protein kinase C (PKC) and tyrosine kinases (such as Src) as central mediators of preconditioning, and (3) whether isoflurane-induced preconditioning is influenced by nitrous oxide.

METHODS

For infarct size measurements, anesthetized rats were subjected to 25 min of coronary artery occlusion followed by 120 min of reperfusion. Rats received nitrous oxide (60%), isoflurane (1.4%) or isoflurane-nitrous oxide (1.4%/60%) during three 5-min periods before index ischemia (each group, n = 7). Control animals remained untreated for 45 min. Additional hearts (control, 60% nitrous oxide alone%, and isoflurane-nitrous oxide [0.6%/60%, in equianesthetic doses]) were excised for Western blot of PKC-epsilon and Src kinase (each group, n = 4).

RESULTS

Nitrous oxide had no effect on infarct size (59.1 +/- 15.2% of the area at risk vs. 51.1 +/- 10.9% in controls). Isoflurane (1.4%) and isoflurane-nitrous oxide (1.4%/60%) reduced infarct size to 30.9 +/- 10.6 and 28.7 +/- 11.8% (both P < 0.01). Nitrous oxide (60%) had no effect on phosphorylation (2.3 +/- 1.8 vs. 2.5 +/- 1.7 in controls, average light intensity, arbitrary units) and translocation (7.0 +/- 4.3 vs. 7.4 +/- 5.2 in controls) of PKC-epsilon. Src kinase phosphorylation was not influenced by nitrous oxide (4.6 +/- 3.9 vs. 5.0 +/- 3.8; 3.2 +/- 2.2 vs. 3.5 +/- 3.0). Isoflurane-nitrous oxide (0.6%/60%, in equianesthetic doses) induced PKC-epsilon phosphorylation (5.4 +/- 1.9 vs. 2.8 +/- 1.5; P < 0.001) and translocation to membrane regions (13.8 +/- 13.0 vs. 6.7 +/- 2.0 in controls; P < 0.05).

CONCLUSIONS

Nitrous oxide is the first inhalational anesthetic without preconditioning effect on the heart. However, isoflurane-induced preconditioning and PKC-epsilon activation are not influenced by nitrous oxide.

摘要

背景

关于一氧化二氮对心脏的预处理作用尚未进行研究。这一点很重要，因为一氧化二氮常与已知可对心脏进行预处理的挥发性麻醉剂联合使用。作者旨在阐明：（1）一氧化二氮是否能对心脏起到预处理作用；（2）它如何影响作为预处理核心介质的蛋白激酶C（PKC）和酪氨酸激酶（如Src）；（3）一氧化二氮是否会影响异氟烷诱导的预处理。

方法

为测量梗死面积，对麻醉的大鼠进行25分钟冠状动脉阻塞，随后再灌注120分钟。在指数缺血前的三个5分钟时间段内，大鼠接受一氧化二氮（60%）、异氟烷（1.4%）或异氟烷 - 一氧化二氮（1.4%/60%）（每组，n = 7）。对照动物未接受处理45分钟。另外摘取心脏（对照组、单独使用60%一氧化二氮组，以及异氟烷 - 一氧化二氮[0.6%/60%，等效麻醉剂量]组）用于PKC-ε和Src激酶的蛋白质印迹分析（每组，n = 4）。

结果

一氧化二氮对梗死面积无影响（危险区域面积的59.1±15.2%，对照组为51.1±10.9%）。异氟烷（1.4%）和异氟烷 - 一氧化二氮（1.4%/60%）使梗死面积分别降至30.9±10.6%和28.7±11.8%（均P < 0.01）。一氧化二氮（60%）对PKC-ε的磷酸化（对照组为2.3±1.8，平均光强度，任意单位，一氧化二氮组为2.5±1.7）和转位（对照组为7.0±4.3，一氧化二氮组为7.4±5.2）无影响。Src激酶磷酸化不受一氧化二氮影响（4.6±3.9对5.0±3.8；3.2±2.2对3.5±3.0）。异氟烷 - 一氧化二氮（0.6%/60%，等效麻醉剂量）诱导PKC-ε磷酸化（5.4±1.9对2.8±1.5；P < 0.001）并转位至膜区域（对照组为6.7±2.0，异氟烷 - 一氧化二氮组为13.8±13.0；P < 0.05）。