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Sci Rep. 2018 Dec 11;8(1):17774. doi: 10.1038/s41598-018-35631-w.

Bretschneider solution-induced alterations in the urine metabolome in cardiac surgery patients.

Lee CC1,2, Hsieh YJ3, Chen SW2,4, Fu SH3, Hsu CW3, Wu CC3,5,6, Han W7, Li Y7, Huan T7, Chang YS3,6,8, Yu JS3,9,10, Li L11, Chang CH12,13, Chen YT14,15,16,17.

Author information

1
Kidney Research Center, Department of Nephrology, Chang Gung Memorial Hospital, Linkou branch, College of Medicine, Chang Gung University, Guishan, Taoyuan, Taiwan.
2
Graduate Institute of Clinical Medical Sciences, College of medicine, Chang Gung University, Guishan, Taoyuan, Taiwan.
3
Molecular and Medicine Research Center, Chang Gung University, Guishan, Taoyuan, Taiwan.
4
Department of cardiothoracic and vascular surgery, Chang Gung Memorial Hospital, Linkou branch, College of Medicine, Chang Gung University, Guishan, Taoyuan, Taiwan.
5
Department of Medical Biotechnology and Laboratory Science, Chang Gung University, Guishan, Taoyuan, 33302, Taiwan.
6
Department of Otolaryngology-Head & Neck Surgery, Chang Gung Memorial Hospital at Linkou, Guishan, Taoyuan, 33305, Taiwan.
7
Department of Chemistry, University of Alberta, Edmonton, AB, T6G2G2, Canada.
8
Graduate Institute of Biomedical Sciences, Chang Gung University, Guishan, Taoyuan, 33302, Taiwan.
9
Liver Research Center, Chang Gung Memorial Hospital at Linkou, Guishan, Taoyuan, 33305, Taiwan.
10
Department of Cell and Molecular Biology, Chang Gung University, Guishan, Taoyuan, 33302, Taiwan.
11
Department of Chemistry, University of Alberta, Edmonton, AB, T6G2G2, Canada. liang.li@ualberta.ca.
12
Kidney Research Center, Department of Nephrology, Chang Gung Memorial Hospital, Linkou branch, College of Medicine, Chang Gung University, Guishan, Taoyuan, Taiwan. franwisandsun@gmail.com.
13
Graduate Institute of Clinical Medical Sciences, College of medicine, Chang Gung University, Guishan, Taoyuan, Taiwan. franwisandsun@gmail.com.
14
Kidney Research Center, Department of Nephrology, Chang Gung Memorial Hospital, Linkou branch, College of Medicine, Chang Gung University, Guishan, Taoyuan, Taiwan. ytchen@mail.cgu.edu.tw.
15
Molecular and Medicine Research Center, Chang Gung University, Guishan, Taoyuan, Taiwan. ytchen@mail.cgu.edu.tw.
16
Department of Biomedical Sciences, College of Medicine, Chang Gung University, Guishan, Taoyuan, Taiwan. ytchen@mail.cgu.edu.tw.
17
Graduate Institute of Biomedical Sciences, College of Medicine, Chang Gung University, Guishan, Taoyuan, Taiwan. ytchen@mail.cgu.edu.tw.

Abstract

The development of Bretschneider's histidine-tryptophan-ketoglutarate (HTK) cardioplegia solution represented a major advancement in cardiac surgery, offering significant myocardial protection. However, metabolic changes induced by this additive in the whole body have not been systematically investigated. Using an untargeted mass spectrometry-based method to deeply explore the urine metabolome, we sought to provide a holistic and systematic view of metabolic perturbations occurred in patients receiving HTK. Prospective urine samples were collected from 100 patients who had undergone cardiac surgery, and metabolomic changes were profiled using a high-performance chemical isotope labeling liquid chromatography-mass spectrometry (LC-MS) method. A total of 14,642 peak pairs or metabolites were quantified using differential 13C-/12C-dansyl labeling LC-MS, which targets the amine/phenol submetabolome from urine specimens. We identified 223 metabolites that showed significant concentration change (fold change > 5) and assembled several potential metabolic pathway maps derived from these dysregulated metabolites. Our data indicated upregulated histidine metabolism with subsequently increased glutamine/glutamate metabolism, altered purine and pyrimidine metabolism, and enhanced vitamin B6 metabolism in patients receiving HTK. Our findings provide solid evidence that HTK solution causes significant perturbations in several metabolic pathways and establish a basis for further study of key mechanisms underlying its organ-protective or potential harmful effects.

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