In vivo mouse cardiac hyperpolarized magnetic resonance spectroscopy
In vivo mouse cardiac hyperpolarized magnetic resonance spectroscopy
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DOI：
10.1186/1532-429x-15-19
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发表时间：
2013-02-18
影响因子：
6.4
通讯作者：
Tyler, Damian J.
中科院分区：
文献类型：
--
作者：
Dodd, Michael S.;Ball, Vicky;Tyler, Damian J.
背景：心脏代谢的改变伴随着许多心脏疾病。心脏超极化磁共振波谱（MRS）的出现，通过动态核极化（DNP），使在体内发生的心肌梗死，肥大和糖尿病的结果代谢变化的理解。然而，迄今为止进行的所有心脏研究都集中在大鼠和较大的动物上，而通过研究心脏病的转基因小鼠模型可以获得更多的信息。翻译从大鼠到小鼠是具有挑战性的，部分原因是心脏大小减少（1/10）和增加的心率（50%）在小鼠相比，大鼠。方法和结果：在这项研究中，我们已经调查了在体内代谢的[1-C-13]丙酮酸在小鼠心脏。为了证明该方法检测丙酮酸脱氢酶（PDH）通量变化的灵敏度，进行了两种充分表征的PDH调节方法：禁食过夜和输注二氯乙酸钠（DCA）。禁食导致PDH通量减少85%，而DCA输注使PDH通量增加123%。三个常用的对照小鼠品系进行比较，揭示显着的代谢strains.Conclusions之间的差异：我们已经成功地证明了一个超极化DNP协议，调查在患病小鼠心脏内的体内改变。该技术提供了优于现有体外技术的显著优势，因为它减少了动物数量并降低了生物学变异性。因此，[1-C-13]丙酮酸可用于提供转基因小鼠的体内心脏代谢谱。
Background: Alterations in cardiac metabolism accompany many diseases of the heart. The advent of cardiac hyperpolarized magnetic resonance spectroscopy (MRS), via dynamic nuclear polarization (DNP), has enabled a greater understanding of the in vivo metabolic changes that occur as a consequence of myocardial infarction, hypertrophy and diabetes. However, all cardiac studies performed to date have focused on rats and larger animals, whereas more information could be gained through the study of transgenic mouse models of heart disease. Translation from the rat to the mouse is challenging, due in part to the reduced heart size (1/10th) and the increased heart rate (50%) in the mouse compared to the rat.Methods and Results: In this study, we have investigated the in vivo metabolism of [1-C-13] pyruvate in the mouse heart. To demonstrate the sensitivity of the method to detect alterations in pyruvate dehydrogenase (PDH) flux, two well characterised methods of PDH modulation were performed; overnight fasting and infusion of sodium dichloroacetate (DCA). Fasting resulted in an 85% reduction in PDH flux, whilst DCA infusion increased PDH flux by 123%. A comparison of three commonly used control mouse strains was performed revealing significant metabolic differences between strains.Conclusions: We have successfully demonstrated a hyperpolarized DNP protocol to investigate in vivo alterations within the diseased mouse heart. This technique offers a significant advantage over existing in vitro techniques as it reduces animal numbers and decreases biological variability. Thus [1-C-13] pyruvate can be used to provide an in vivo cardiac metabolic profile of transgenic mice.