Cecal ligation and puncture with total parenteral nutrition: a clinically relevant model of the metabolic, hormonal, and inflammatory dysfunction associated with critical illness.
BACKGROUND
Standard rat cecal ligation and puncture (CLP) results in only transient hyperglycemia, making an examination of the effects of glucoregulatory agents, such as insulin, on the morbidity and mortality of CLP problematic. Accordingly, we sought to develop a model of rat CLP with prolonged hyperglycemia through continuous infusion of total parenteral nutrition (TPN) post CLP.


METHODS
Polyethylene catheters were implanted into the femoral vein of female Sprague Dawley rats (245-265 g) which were subsequently subjected to CLP. TPN was initiated at different intervals following CLP, and mortality, bacteremia, blood glucose, hormonal, and inflammatory responses were monitored.


RESULTS
Without TPN, CLP resulted in significantly lower blood glucose at 22 h post CLP. In contrast, CLP rats receiving TPN exhibited significant prolonged hyperglycemia that was responsive to insulin treatment. Mortality and hyperglycemia tended to increase with puncture size in CLP TPN rats, with early initiation of TPN leading to poorer outcome. There were time-dependent differences in bacteremia and mortality based on time of TPN initiation. Levels of insulin, leptin, and glucagon were significantly elevated in CLP TPN rats, as were many inflammatory markers. Organ damage was evident as early as 12 h post CLP and blood cell kinetics indicated significantly depressed neutrophil and lymphocyte counts.


CONCLUSIONS
Our results indicate that addition of TPN to CLP provides a clinically relevant animal model of critical illness with associated hyperglycemia that may provide utility for the testing of glucoregulatory and other therapeutic modalities.
Heuer
Josef G
JG
Biotechnology Discovery Research, Eli Lilly and Company, Lilly Corporate Center, Indianapolis, Indiana 46285, USA. heuer_josef_g@lilly.com
Bailey
Dianna L
DL
Sharma
Ganesh R
GR
Zhang
Tonghai
T
Ding
Chunjin
C
Ford
Amy
A
Stephens
Eddie J
EJ
Holmes
Kimberly C
KC
Grubbs
Renee L
RL
Fynboe
Kelly A
KA
Chen
Yun-Fei
YF
Jakubowski
Joseph A
JA
D000818:Animals; D016470:Bacteremia / Q000209:etiology; D001777:Blood Coagulation; D002432:Cecum; D016638:Critical Illness / Q000401:mortality; D016207:Cytokines / Q000378:metabolism; D004195:Disease Models, Animal; D004700:Endocrine System Diseases / Q000209:etiology; D004867:Equipment Design; D005260:Female; D006728:Hormones / Q000378:metabolism; D006943:Hyperglycemia / Q000097:blood / Q000209:etiology; D007107:Immune System / Q000503:physiopathology; D007249:Inflammation / Q000209:etiology; D007328:Insulin / Q000494:pharmacology; D008026:Ligation; D008659:Metabolic Diseases / Q000209:etiology; D009339:Needles; D010289:Parenteral Nutrition, Total; D011677:Punctures / Q000295:instrumentation; D051381:Rats; D017207:Rats, Sprague-Dawley; D013997:Time Factors
D016207:Cytokines; D006728:Hormones; D007328:Insulin