Longitudinal evaluation of left ventricular substrate metabolism, perfusion, and dysfunction in the spontaneously hypertensive rat model of hypertrophy using small-animal PET/CT imaging.
Longitudinal evaluation of left ventricular substrate metabolism, perfusion, and dysfunction in the spontaneously hypertensive rat model of hypertrophy using small-animal PET/CT imaging.
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DOI：
10.2967/jnumed.113.120105
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发表时间：
2013-11
期刊：
影响因子：
--
通讯作者：
Gullberg GT
中科院分区：
文献类型：
--
作者：
Hernandez AM;Huber JS;Murphy ST;Janabi M;Zeng GL;Brennan KM;O'Neil JP;Seo Y;Gullberg GT
心肌代谢和灌注成像是了解心力衰竭生理后果的重要工具。我们使用PET成像来检查18 F-FDG和14（R，S）-18 F-fluoro-6-thia-heptadecanoic acid（18 F-FTHA）作为葡萄糖和脂肪酸（FA）的类似物的纵向动力学，以量化作为左心室肥大（LVH）和衰竭模型的自发性高血压大鼠（SHR）的代谢底物转移。心肌灌注和左心室功能也进行了研究，使用新开发的放射性示踪剂18 F-氟二氢鱼藤醇（18 F-FDHROL）。纵向动态心电图门控小动物PET/CT研究进行了8 SHR和8血压正常的Wistar-Kyoto（WKY）大鼠在其生命周期。我们测定了18F-FDG和18F-FTHA（分别为KiFDG和KiFTHA）的心肌内流速率常数和18F-FDHROL（K1 FDHROL）的洗入速率常数。18F-FDHROL数据还用于量化左心室射血分数（LVEF）和舒张末期容积（EDV）。抽取血液样本以独立测量葡萄糖、胰岛素和游离脂肪酸（FFA）的血浆浓度。与年龄无关，SHR的KiFDG和KiFTHA高于WKY大鼠（分别为P < 3 × 10−8和0.005）。当模型组合时，KiFDG随年龄的降低是明显的（P = 0.034）。SHR的K1 FDHROL（P < 5 × 10−6）高于对照组，两种模型均无年龄依赖性趋势（P = 0.058）。SHR的血浆葡萄糖浓度低于对照组（P < 6 × 10−12），WKY大鼠的血浆葡萄糖浓度呈年龄依赖性升高（P < 2 × 10−5）。SHR的血浆胰岛素浓度高于对照组（P < 3 × 10−3），当模型组合时呈年龄依赖性下降（P = 0.046）。模型间FFA水平相似（P = 0.374），但仅在SHR中随年龄增加（P < 7 × 10−6）。SHR在8个月时表现出心肌底物利用的改变，其特征是葡萄糖和FA利用增加。在20个月时，SHR具有LVH，其特征为LVEF降低和EDV增加，同时维持较高的葡萄糖和相似的FA利用率（与WKY大鼠相比），这表明衰竭心脏中能量底物的适应不良。SHR中K1 FDHROL升高可能反映了肥厚心脏中氧耗量升高和毛细血管密度降低。从我们的研究结果来看，代谢变化似乎先于SHR模型中LVH进展的机械变化。
Myocardial metabolic and perfusion imaging is a vital tool for understanding the physiologic consequences of heart failure. We used PET imaging to examine the longitudinal kinetics of 18F-FDG and 14(R,S)-18F-fluoro-6-thia-heptadecanoic acid (18F-FTHA) as analogs of glucose and fatty acid (FA) to quantify metabolic substrate shifts with the spontaneously hypertensive rat (SHR) as a model of left ventricular hypertrophy (LVH) and failure. Myocardial perfusion and left ventricular function were also investigated using a newly developed radiotracer 18F-fluorodihydrorotenol (18F-FDHROL). Longitudinal dynamic electrocardiogram-gated small-animal PET/CT studies were performed with 8 SHR and 8 normotensive Wistar-Kyoto (WKY) rats over their life cycle. We determined the myocardial influx rate constant for 18F-FDG and 18F-FTHA (KiFDG and KiFTHA, respectively) and the wash-in rate constant for 18F-FDHROL (K1FDHROL). 18F-FDHROL data were also used to quantify left ventricular ejection fraction (LVEF) and end-diastolic volume (EDV). Blood samples were drawn to independently measure plasma concentrations of glucose, insulin, and free fatty acids (FFAs). KiFDG and KiFTHA were higher in SHRs than WKY rats (P < 3 × 10−8 and 0.005, respectively) independent of age. A decrease in KiFDG with age was evident when models were combined (P = 0.034). The SHR exhibited higher K1FDHROL (P < 5 × 10−6) than the control, with no age-dependent trends in either model (P = 0.058). Glucose plasma concentrations were lower in SHRs than controls (P < 6 × 10−12), with an age-dependent rise for WKY rats (P < 2 × 10−5). Insulin plasma concentrations were higher in SHRs than controls (P < 3 × 10−3), with an age-dependent decrease when models were combined (P = 0.046). FFA levels were similar between models (P = 0.374), but an increase with age was evident only in SHR (P < 7 × 10−6). The SHR exhibited alterations in myocardial substrate use at 8 mo characterized by increased glucose and FA utilizations. At 20 mo, the SHR had LVH characterized by decreased LVEF and increased EDV, while simultaneously sustaining higher glucose and similar FA utilizations (compared with WKY rats), which indicates maladaptation of energy substrates in the failing heart. Elevated K1FDHROL in the SHR may reflect elevated oxygen consumption and decreased capillary density in the hypertrophied heart. From our findings, metabolic changes appear to precede mechanical changes of LVH progression in the SHR model.
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DOI：
10.2967/jnumed.109.068205
发表时间：
2010-05-01
期刊：
Journal of nuclear medicine : official publication, Society of Nuclear Medicine
影响因子：
--
作者：
Taegtmeyer H
通讯作者：
Taegtmeyer H
影响因子：
9.8
作者：
PAOLISSO, G;GAMBARDELLA, A;DONOFRIO, F
通讯作者：
DONOFRIO, F
DOI：
10.1016/s0735-1097(02)01967-8
发表时间：
2002-07-17
影响因子：
24
作者：
Dávila-Román, VG;Vedala, G;Gropler, RJ
通讯作者：
Gropler, RJ
影响因子：
3.1
作者：
Szymanski, Mariusz K.;Kruizinga, Silvana;Slart, Riemer H. J. A.
通讯作者：
Slart, Riemer H. J. A.
影响因子：
10.8
作者：
Dodd MS;Ball DR;Schroeder MA;Le Page LM;Atherton HJ;Heather LC;Seymour AM;Ashrafian H;Watkins H;Clarke K;Tyler DJ
通讯作者：
Tyler DJ