34°C 治疗性低温对大鼠离体心脏模型中由 PI3K 和一氧化氮介导的缺血/再灌注损伤的心脏保护作用。

Cardioprotective effect of therapeutic hypothermia at 34°C against ischaemia/reperfusion injury mediated by PI3K and nitric oxide in a rat isolated heart model.

机构信息

Department of Emergency Medicine, Hamamatsu University School of Medicine, Japan.

出版信息

Resuscitation. 2012 Feb;83(2):238-42. doi: 10.1016/j.resuscitation.2011.08.013. Epub 2011 Aug 27.

DOI:10.1016/j.resuscitation.2011.08.013

PMID:21875500

Abstract

AIM

Therapeutic hypothermia (TH) is widely used as a cardioprotective treatment for cardiac arrest. TH at 30-32°C during ischaemia and reperfusion has a cardioprotective effect. The aims of the study were to examine whether TH at 34°C with late induction (immediately after the start of reperfusion) has a cardioprotective effect and to determine if this effect is mediated by nitric oxide (NO) and phosphatidylinositol 3'-kinase (PI3K).

METHODS

Langendorff perfusion of Sprague-Dawley rat hearts was initiated at 75 mmHg at 37°C. Left ventricle infarct sizes were evaluated by triphenyltetrazolium chloride staining after Langendorff perfusion in 6 groups (each n=7): control group; ischaemia group, with 34°C TH during ischaemia for 30 min and reperfusion for 180 min; reperfusion group, with 34°C TH induced solely during the reperfusion period; the l-NAME (NO synthase inhibitor), LY294002, and wortmannin (PI3K inhibitors) groups, which were treated similarly to the reperfusion group with the addition of each compound.

RESULTS

TH reduced the left ventricle infarct size from 54.2 ± 14.8% of the control group to 11.9 ± 6.3% (ischaemia group, p<0.001) and to 23.5 ± 10.5% (reperfusion group, p<0.001). l-NAME, LY294002, and wortmannin reversed the cardioprotective effect of TH induced during reperfusion to 42.5 ± 10.6% (p=0.009), 40.9 ± 4.1% (p=0.021), and 51.9±13.0% (p<0.001), respectively. Circulatory temperatures reached 34°C within 5 min in all groups subjected to TH.

CONCLUSIONS

TH of 34°C showed a cardioprotective effect even with late initiation of cooling during reperfusion. The effect was mediated by NO and PI3K.

摘要

目的

治疗性低温（TH）被广泛用作心脏骤停的心脏保护治疗。缺血和再灌注期间 30-32°C 的 TH 具有心脏保护作用。本研究的目的是研究 34°C 的 TH 是否具有延迟诱导（再灌注开始后立即）的心脏保护作用，并确定这种作用是否由一氧化氮（NO）和磷脂酰肌醇 3'-激酶（PI3K）介导。

方法

在 37°C 下以 75mmHg 启动 Sprague-Dawley 大鼠心脏 Langendorff 灌注。通过氯化三苯基四氮唑染色评估 Langendorff 灌注后 6 组（每组 n=7）的左心室梗死面积：对照组；缺血组，缺血期间给予 34°C TH 30min，再灌注 180min；再灌注组，仅在再灌注期间给予 34°C TH；l-NAME（一氧化氮合酶抑制剂）、LY294002 和 wortmannin（PI3K 抑制剂）组，用每种化合物处理与再灌注组相似。

结果

TH 将左心室梗死面积从对照组的 54.2±14.8%降低至 11.9±6.3%（缺血组，p<0.001）和 23.5±10.5%（再灌注组，p<0.001）。l-NAME、LY294002 和 wortmannin 逆转了再灌注期间诱导的 TH 的心脏保护作用，使其恢复至 42.5±10.6%（p=0.009）、40.9±4.1%（p=0.021）和 51.9±13.0%（p<0.001）。所有接受 TH 的组在 5 分钟内循环温度均达到 34°C。