A metabonomic approach to early prognostic evaluation of experimental sepsis.
OBJECTIVE
Early prognostic evaluation of sepsis is an attractive strategy to decrease the mortality of septic patients, but presently there are no satisfactory approaches. Our goal is to establish an early, rapid and efficient approach for prognostic evaluation of sepsis.


METHODS
Forty-five septic rats, induced by cecal ligation and puncture, were divided into surviving (n=23) and nonsurviving group (n=22) on day 6. Serum samples were obtained from septic and sham-operated rats (n=25) at 12h after surgery. HPLC/MS assays were performed to acquire serum metabolic profiles, and radial basis function neural network (RBFNN) was employed to build predictive model for prognostic evaluation of sepsis.


RESULTS
Principle component analysis allows a clear discrimination of the pathologic characteristics among rats from surviving, nonsurviving and sham-operated groups. Six metabolites related to the outcome of septic rats were then structurally identified, which included linolenic acid, linoleic acid, oleic acid, stearic acid, docosahexaenoic acid and docosapentaenoic acid. A RBFNN model was built upon the metabolic profile data from rat serum, and a high predictive accuracy over 94% was achieved.


CONCLUSIONS
HPLC/MS-based metabonomic approach combined with pattern recognition permits accurate outcome prediction of septic rats in the early stage. The proposed approach has advantages of rapid, low-cost and efficiency, and is expected to be applied in clinical prognostic evaluation of septic patients.
Xu
Ping-bo
PB
Department of Anaesthesia, Changhai Hospital, Second Military Medical University, Shanghai 200433, PR China.
Lin
Zhong-ying
ZY
Meng
Hai-bing
HB
Yan
Shi-kai
SK
Yang
Yun
Y
Liu
Xin-ru
XR
Li
Jin-bao
JB
Deng
Xiao-ming
XM
Zhang
Wei-dong
WD
D000818:Animals; D002851:Chromatography, High Pressure Liquid; D008297:Male; D013058:Mass Spectrometry; D008660:Metabolism / Q000502:physiology*; D025341:Principal Component Analysis; D011379:Prognosis; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley; D018805:Sepsis / Q000097:blood / Q000378:metabolism*; D013047:Specific Pathogen-Free Organisms