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多参数活体心脏磁共振成像显示,尽管神经元型一氧化氮合酶基因敲除小鼠的β-肾上腺素能功能反应严重减弱,但其灌注储备仍正常。

Multi-parameter in vivo cardiac magnetic resonance imaging demonstrates normal perfusion reserve despite severely attenuated beta-adrenergic functional response in neuronal nitric oxide synthase knockout mice.

作者信息

Vandsburger Moriel H, French Brent A, Helm Patrick A, Roy Rene Jack, Kramer Christopher M, Young Alistair A, Epstein Frederick H

机构信息

Department of Biomedical Engineering, University of Virginia, Charlottesville, VA 22908, USA.

出版信息

Eur Heart J. 2007 Nov;28(22):2792-8. doi: 10.1093/eurheartj/ehm241. Epub 2007 Jun 30.

Abstract

AIMS

The role of neuronal nitric oxide synthase (nNOS) in regulating contractile function remains controversial, and in regulating myocardial perfusion is uninvestigated. We used magnetic resonance imaging (MRI) to phenotype nNOS(-/-) and wild-type (WT) mice regarding left ventricular (LV) structure, baseline function, beta-adrenergic responsiveness, and perfusion reserve.

METHODS AND RESULTS

Cine MRI showed higher LV mass to end-diastolic volume ratio (2.3 +/- 0.2 mg/microL nNOS(-/-) vs. 1.7 +/- 0.1 mg/microL WT; P=0.032) and LV ejection fraction (64.9 +/- 2.1% nNOS(-/-) vs. 55.8 +/- 1.1% WT; P = 0.003) in nNOS(-/-). Myocardial tagging demonstrated similar baseline systolic circumferential strain (Ecc) in nNOS(-/-) and WT. With dobutamine, the normal change in Ecc was nearly absent in nNOS(-/-) (-0.5 +/- 0.3% nNOS(-/-) vs. -2.2 +/- 0.3% WT; P = 0.001), and the systolic strain rate (dEcc/dt) response to dobutamine seen in WT was reduced in nNOS(-/-) (-29 +/- 13%/s nNOS(-/-) vs. -106+/-16%/s WT; P = 0.001). Diastolic strain rate increased significantly with dobutamine only in WT. Arterial spin labelling showed that baseline perfusion and perfusion reserve with either dobutamine or an adenosine receptor agonist are normal in nNOS(-/-).

CONCLUSION

MRI provides non-invasive in vivo evidence that nNOS does not play a role in basal contractile function or myocardial perfusion, but is required for increasing cardiac inotropy and lusitropy upon beta-adrenergic stimulation.

摘要

目的

神经元型一氧化氮合酶(nNOS)在调节收缩功能中的作用仍存在争议,且其在调节心肌灌注方面尚未得到研究。我们使用磁共振成像(MRI)对nNOS基因敲除(nNOS(-/-))小鼠和野生型(WT)小鼠的左心室(LV)结构、基线功能、β-肾上腺素能反应性及灌注储备进行表型分析。

方法与结果

电影MRI显示,nNOS(-/-)小鼠的左心室质量与舒张末期容积比更高(nNOS(-/-)为2.3±0.2mg/μL,WT为1.7±0.1mg/μL;P = 0.032),左心室射血分数也更高(nNOS(-/-)为64.9±2.1%,WT为55.8±1.1%;P = 0.003)。心肌标记显示nNOS(-/-)小鼠和WT小鼠的基线收缩期圆周应变(Ecc)相似。使用多巴酚丁胺时,nNOS(-/-)小鼠Ecc的正常变化几乎消失(nNOS(-/-)为-0.5±0.3%,WT为-2.2±0.3%;P = 0.001),且nNOS(-/-)小鼠对多巴酚丁胺的收缩期应变率(dEcc/dt)反应降低(nNOS(-/-)为-29±13%/s,WT为-106±16%/s;P = 0.001)。仅在WT小鼠中,多巴酚丁胺使舒张期应变率显著增加。动脉自旋标记显示,nNOS(-/-)小鼠的基线灌注以及使用多巴酚丁胺或腺苷受体激动剂后的灌注储备均正常。

结论

MRI提供了非侵入性的体内证据,表明nNOS在基础收缩功能或心肌灌注中不起作用,但在β-肾上腺素能刺激时增加心脏收缩性和舒张性方面是必需的。

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