Metabolomic Profile of Rat Lung Tissue after Death: Effect of Delayed Post-Mortem O2-Ventilation

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• 作者：T. Egan¹ ; B. Dong¹ ; A. Tikunov² ; C. Semelka² ; P.-F. Kuan³ ; J. Macdonald²
• 刊名：The Journal of Heart and Lung Transplantation
• 出版年：2013
• 出版时间：April, 2013
• 年：2013
• 卷：32
• 期：4_supp_S
• 页码：S296-S297
• 全文大小：88 K

文摘

| Figures/TablesFigures/Tables

Purpose

Retrieving lungs from Category 1 non-heart-beating donors (NHBDs) for transplant (LTX) requires a mandatory period of ischemia. NHBDs can be ventilated before retrieval. In earlier studies, O2-vent of a NHBD delayed cell death, and improved function after LTX. ¹H Nuclear Magnetic Resonance Spectroscopy (NMR-spec) identifies all metabolites in an organ. We characterized lung metabolic phenotype with NMR-spec.

Methods and Materials

To simulate failed resuscitation in the field (Category 1 NHBD), 6 rats were anesthetized, ventilated briefly with 100 % O2 via tracheotomy, sacrificed, then the trachea was clamped. After rapid sternotomy, the right upper lobe was ligated, excised, and flash frozen. Inflated but non-vent lobes from 3 rats were ligated and excised hourly x 4. 3 rats were ventilated 1 hr after death with 100 % O2 for 1 hr to simulate O2-vent of a NHBD after consent for lung retrieval. NMR spectra were analyzed with Principal Component Analysis and Orthogonal Partial Least Squares Discriminant Analysis.

Results

Of nearly 50 metabolites detected by ¹H NMR spec, changes were observed in 23 over 4 hr. Glycolysis persists, more in non-vent lungs. Krebs cycle activity is higher in vent lungs, perhaps due to motion redistributing metabolites.

Conclusions

NMR-spec can define changes in the lung metabolome due to ischemia. O2-vent of a NHBD started 1 hr after death changes the lung metabolome resulting in more Krebs cycle activity. NMR-spec may identify biomarkers of function, or therapeutic targets to administer to NHBDs.

Metabolites
Pathways	Metabolites	Ventilated	Non-Vent
Krebs (TCA) Cycle	Succinate, Glutamine	?
Krebs (TCA) Cycle	Glutamate	?	¡ý
Glycolysis	Glucose	¡ý	¡ý
Glycolysis	Lactate, Alanine
¦Â-Oxidation/Ketone Bodies	Acetate, ¦Â-hydroxybutyrate	¡ý	¡ý
Phospholipid Intermediates	Choline, Phosphocholine, Glycerophsophocholine
Nucleotide energy	ATP/ADP	¡ý	¡ý
Nucleotide degradation	AMP, Inosine, Xanthine, Hypoxanthine
Osmolytes/GSH degradation	Taurine
Amine acceptor	Arginine	?
Amino Acids	Leucine, Valine, Isoleucine, Glycine