Longitudinal Evaluation of Myocardial Fatty Acid and Glucose Metabolism in Fasted and Nonfasted Spontaneously Hypertensive Rats Using MicroPET/CT.

Longitudinal Evaluation of Myocardial Fatty Acid and Glucose Metabolism in Fasted and Nonfasted Spontaneously Hypertensive Rats Using MicroPET/CT.
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DOI:
10.1177/1536012117724558
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发表时间:
2017-01
期刊:
影响因子:
2.8
通讯作者:
Gullberg GT
Gullberg GT
中科院分区:
医学4区
文献类型:
--
作者:
Huber JS;Hernandez AM;Janabi M;O'Neil JP;Brennan KM;Murphy ST;Seo Y;Gullberg GT

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使用纵向微型正电子发射断层扫描(microPET)/计算机断层扫描(CT)研究,我们量化了自发性高血压大鼠(SHR),左心室肥厚(LVH)模型的心肌代谢和灌注的变化。在正常或禁食条件下,使用长链脂肪酸类似物18 F-氟-6-硫杂十七烷酸(18 F-FTHA)和葡萄糖类似物18 F-氟脱氧葡萄糖(18 F-FDG)定量SHR和Wistar-Kyoto(WKY)正常血压大鼠心脏中的脂肪酸和葡萄糖代谢。我们还使用18F-FDHROL(18F-FDHROL)来研究他们心脏的灌注,而不禁食。大鼠在其生命周期中成像4或5次。使用Combustion建模来估计放射性示踪剂的速率常数。采集血样并分析葡萄糖和游离脂肪酸浓度。在2009-2010年的研究中,SHR的18F-FDHROL洗入速率常数(P = .1)和分布容积(P = .1)没有显著差异,18F-FDG心肌内流速率常数显著高于WKY(P = 4×10−8),18F-FTHA心肌内流速率常数显著低于WKY(P = .007)。在2011-2012年禁食研究期间,SHR显示出显著高于WKY的18F-FDHROL洗入速率常数(P = 5×10−6)和分布容积(P = 3 × 10 − 8),显著高于WKY的18F-FDG心肌内流速率常数(P = 3×10−8),以及18F-FTHA心肌内流速率常数(不显著,P = .1)的趋势。血浆葡萄糖浓度的变化通常与相应的放射性示踪剂流入速率常数变化呈负相关。该研究表明,从首选脂肪酸代谢到增加的葡萄糖代谢与肥大的转变。2011-2012年研究期间灌注增加可能表明SHR LVH模型中有氧代谢增加。
Using longitudinal micro positron emission tomography (microPET)/computed tomography (CT) studies, we quantified changes in myocardial metabolism and perfusion in spontaneously hypertensive rats (SHRs), a model of left ventricular hypertrophy (LVH). Fatty acid and glucose metabolism were quantified in the hearts of SHRs and Wistar-Kyoto (WKY) normotensive rats using long-chain fatty acid analog 18F-fluoro-6-thia heptadecanoic acid (18F-FTHA) and glucose analog 18F-fluorodeoxyglucose (18F-FDG) under normal or fasting conditions. We also used 18F-fluorodihydrorotenol (18F-FDHROL) to investigate perfusion in their hearts without fasting. Rats were imaged at 4 or 5 times over their life cycle. Compartment modeling was used to estimate the rate constants for the radiotracers. Blood samples were obtained and analyzed for glucose and free fatty acid concentrations. SHRs demonstrated no significant difference in 18F-FDHROL wash-in rate constant (P = .1) and distribution volume (P = .1), significantly higher 18F-FDG myocardial influx rate constant (P = 4×10−8), and significantly lower 18F-FTHA myocardial influx rate constant (P = .007) than WKYs during the 2009-2010 study without fasting. SHRs demonstrated a significantly higher 18F-FDHROL wash-in rate constant (P = 5×10−6) and distribution volume (P = 3×10−8), significantly higher 18F-FDG myocardial influx rate constant (P = 3×10−8), and a higher trend of 18F-FTHA myocardial influx rate constant (not significant, P = .1) than WKYs during the 2011–2012 study with fasting. Changes in glucose plasma concentrations were generally negatively correlated with corresponding radiotracer influx rate constant changes. The study indicates a switch from preferred fatty acid metabolism to increased glucose metabolism with hypertrophy. Increased perfusion during the 2011-2012 study may be indicative of increased aerobic metabolism in the SHR model of LVH.
DOI: 10.2967/jnumed.113.120105
发表时间: 2013-11
期刊: Journal of nuclear medicine : official publication, Society of Nuclear Medicine
影响因子: --
作者:
Hernandez AM;Huber JS;Murphy ST;Janabi M;Zeng GL;Brennan KM;O'Neil JP;Seo Y;Gullberg GT
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