超极化13C核磁共振检测药物引起的心脏代谢快速变化。
Hyperpolarized 13C NMR detects rapid drug-induced changes in cardiac metabolism.
作者信息
Khemtong Chalermchai, Carpenter Nicholas R, Lumata Lloyd L, Merritt Matthew E, Moreno Karlos X, Kovacs Zoltan, Malloy Craig R, Sherry A Dean
机构信息
Advanced Imaging Research Center, University of Texas Southwestern Medical Center, Dallas, Texas, USA.
Department of Chemistry, University of Texas at Dallas, Richardson, Texas, USA.
出版信息
Magn Reson Med. 2015 Aug;74(2):312-9. doi: 10.1002/mrm.25419. Epub 2014 Aug 28.
PURPOSE
The diseased myocardium lacks metabolic flexibility and responds to stimuli differently compared with healthy hearts. Here, we report the use of hyperpolarized 13C NMR spectroscopy to detect sudden changes in cardiac metabolism in isolated, perfused rat hearts in response to adrenergic stimulation.
METHODS
Metabolism of hyperpolarized [1-(13)C]pyruvate was investigated in perfused rat hearts. The hearts were stimulated in situ by isoproterenol shortly after the administration of hyperpolarized [1-(13)C]pyruvate. The hyperpolarized 13C NMR results were corroborated with 1H NMR spectroscopy of tissue extracts.
RESULTS
Addition of isoproterenol to hearts after equilibration of hyperpolarized [1-(13)C]pyruvate into the existing lactate pool resulted in a sudden, rapid increase in hyperpolarized [1-(13)C]lactate signal within seconds after exposure to drug. The hyperpolarized H(13)CO3 (-) and hyperpolarized [1-(13)C]alanine signals were not affected by the isoproterenol-induced elevated cardiac workload. Separate experiments confirmed that the new hyperpolarized [1-(13)C]lactate signal that arises after stimulation by isoproterenol reflects a sudden increase in total tissue lactate derived from glycogen.
CONCLUSION
These results suggest that hyperpolarized pyruvate and 13C MRS may be useful for detecting abnormal glycogen metabolism in intact tissues.
目的
患病心肌缺乏代谢灵活性，与健康心脏相比，对刺激的反应有所不同。在此，我们报告使用超极化13C核磁共振波谱法来检测离体灌注大鼠心脏在肾上腺素能刺激下心脏代谢的突然变化。
方法
在灌注大鼠心脏中研究超极化[1-(13)C]丙酮酸的代谢。在给予超极化[1-(13)C]丙酮酸后不久，用异丙肾上腺素对心脏进行原位刺激。超极化13C核磁共振结果与组织提取物的1H核磁共振波谱结果相互印证。
结果
在超极化[1-(13)C]丙酮酸平衡到现有的乳酸池中后，向心脏中加入异丙肾上腺素，在接触药物后数秒内，超极化[1-(13)C]乳酸信号突然快速增加。超极化H(13)CO3 (-)和超极化[1-(13)C]丙氨酸信号不受异丙肾上腺素诱导的心脏工作负荷增加的影响。单独的实验证实，异丙肾上腺素刺激后出现的新的超极化[1-(13)C]乳酸信号反映了源自糖原的总组织乳酸的突然增加。
结论
这些结果表明，超极化丙酮酸和13C磁共振波谱可能有助于检测完整组织中的异常糖原代谢。
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