DEVELOP OPEN-CHEST 31P MRS MOUSE HEART

这个子项目是许多研究子项目中的一个 由NIH/NCRR资助的中心赠款提供的资源。子项目和 研究者（PI）可能从另一个NIH来源获得了主要资金， 因此可在其他CRISP条目中表示。所列机构为 研究中心，而研究中心不一定是研究者所在的机构。 开发一种快速、稳健和准确的方法来评估小鼠心肌能量学，并证明其适用于获得性和遗传性心脏病小鼠模型。 材料和方法：我们结合表面线圈定位（10 mm直径，1H和31 P之间可调，使用绝热半通射频脉冲）和手术（电灼去除前胸壁），以创建一种开胸方法，用于在12分钟内在4.7T下采集小鼠体内31 P核磁共振（NMR）心脏光谱。检测了正常BALB/c小鼠、心肌梗死（MI）BALB/c小鼠、心肌细胞限制性过氧化物酶体增殖物激活受体δ敲除（KO）（CR-PPARd（-/-））小鼠和对照loxP侧翼的Ppard（Ppard（flox/flox））小鼠。 研究结果：在对照BALB/c小鼠、BALB/c MI小鼠、Ppard小鼠中，（flox/flox）小鼠和PPAR-delta KO小鼠的平均存活率分别为2.13 +/- 0.09（N = 11）、1.35 +/- 0.07 001相对于BALB/c对照）、1.92 +/-0.09（N = 5）和1.31 +/-0.12（N = 5，P < 0.005相对于Ppard（flox/flox）对照）。我们在这些遗传/获得性心脏病模型中观察到的心肌PCr/ATP的显著降低与以前类似的大型动物模型的数据雅阁。未发现来自腔室血液或邻近骨骼肌的NMR信号污染。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. To develop a rapid, robust, and accurate method for assessing myocardial energetics in mice and demonstrate its applicability to mouse models of acquired and genetic heart disease. MATERIALS AND METHODS: We combined surface coil localization (10-mm diameter, tunable between 1H and 31P, using adiabatic half-passage radiofrequency pulses) and surgery (electrocautery removal of anterior chest wall) to create an open-chest method for acquiring in vivo 31P nuclear magnetic resonance (NMR) cardiac spectra from mice at 4.7T within 12 minutes. Normal BALB/c mice, BALB/c with myocardial infarction (MI), cardiomyocyte-restricted peroxisome proliferator-activated receptor-delta knockout (KO) (CR-PPARd(-/-)) and control loxP-flanked Ppard (Ppard(flox/flox)) mice were examined. RESULTS: The mean phosphocreatine (PCr)/adenosine triphosphate (ATP) ratios in control BALB/c mice, BALB/c MI mice, Ppard(flox/flox) mice, and PPAR-delta KO mice were 2.13 +/- 0.09 (N = 11), 1.35 +/- 0.07 (N = 9, P < 0.001 vs. BALB/c control), 1.92 +/- 0.09 (N = 5), and 1.31 +/- 0.12 (N = 5, P < 0.005 vs. Ppard(flox/flox) control), respectively. The significant depression of myocardial PCr/ATP we observed in these genetic/acquired models of heart disease was in accord with previous data from analogous large animal models. No NMR signal contamination from chamber blood or adjacent skeletal muscle was identified.