[Effects of hydrocortisone on circulating and intramyocardial inflammatory mediators in severe septic rats with myocardial injury induced by Escherichia coli].
OBJECTIVE
Severe sepsis and septic shock remain the most common cause of death in intensive care units. The main causes of death in sepsis are the cardiac dysfunction and hypotension resistant to cateolamines. The prevalence of relative adrenal insufficiency in severe sepsis and septic shock was estimated at about 32%-51%. Several meta-analysis demonstrated that high-dose glucocorticoids decreased survival during sepsis, while stress doses of corticosteroids may benefit these patients. The exact reason for such widely divergent outcome produced by different doses of corticosteroid is still not understood. Therefore, the study was undertaken to observe the effects of different doses of hydrocortisone (HC) on circulating and intramyocardial inflammatory mediators in severe septic rats with myocardial injury induced by Escherichia coli (E. coli).


METHODS
The model was established by two injections of inactivated E. coli Forty male Wistar rats were randomly divided into five groups: high-dose of HC group (150 mg/kg), medium-dose group (20 mg/kg), low-dose group (6 mg/kg), model group (NS substituted for HC), and control group (NS for E. coli and HC). Each group had eight rats. After 2 hours of treatment, specimens were collected to measure serum cardiac troponin I (cTnI), tumor necrosis factor-alpha (TNF-alpha), interleukin-1beta (IL-1beta), nitric oxide (NO) and total NO synthase (NOS). NO and total NOS in myocardial homogenate were also detected. The expression of inducible NOS (iNOS) of myocytes was investigated.


RESULTS
All the above-mentioned markers in model group significantly higher than those in control group. After HC injection, serum cTnI concentrations in low-dose group decreased to normal values compared to that of model group, while in another two HC groups, the concentrations were higher than those in model group. TNF-alpha level was not significantly influenced. But IL-1beta level declined to normal values, being prominent in low-dose HC group. Neither high-dose nor middle-dose HC could lower serum NO or total NOS, but low-dose HC could greatly inhibit both NO and NOS levels (P < 0.05). There was no significant difference in the level of NO and total NOS of myocardial homogenate between left and right ventricles. There was no iNOS expression by normal myocardium, while the expression in model group was significantly increased. After HC injection, the iNOS expressions by myocardium in three HC groups were weaker than those in model group. The intensity of iNOS signals became weak with the decrease in HC dose.


CONCLUSIONS
Different doses of HC might exert different effects on circulating and intramyocardial inflammatory mediators in severely septic rats with myocardial injury induced by E. coli. Low-dose HC could significantly inhibit such mediators as well as iNOS expression by cardiomyocytes. The results suggest that low dose HC exert protective effect on myocardial injury of severely septic rats.
Wang
Yong-qing
YQ
Department of Pediatric Intensive Care Unit, Beijing Children's Hospital, Capital University of Medical Sciences, Beijing 100045, China.
Fan
Xun-mei
XM
Zhou
Tao
T
Qi
Yu-jie
YJ
Chen
Hui
H
Qian
Su-yun
SY
D000818:Animals; D000893:Anti-Inflammatory Agents / Q000008:administration & dosage / Q000494:pharmacology*; D009202:Cardiomyopathies / Q000188:drug therapy* / Q000276:immunology / Q000378:metabolism; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004926:Escherichia coli / Q000472:pathogenicity; D006854:Hydrocortisone / Q000008:administration & dosage / Q000494:pharmacology*; D053583:Interleukin-1beta / Q000097:blood; D008297:Male; D032342:Muscle Cells / Q000187:drug effects / Q000276:immunology* / Q000378:metabolism*; D009569:Nitric Oxide / Q000097:blood / Q000378:metabolism; D019001:Nitric Oxide Synthase / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D018805:Sepsis / Q000188:drug therapy / Q000276:immunology* / Q000382:microbiology; D016896:Treatment Outcome; D019210:Troponin I / Q000097:blood; D014409:Tumor Necrosis Factor-alpha / Q000097:blood
D000893:Anti-Inflammatory Agents; D053583:Interleukin-1beta; D019210:Troponin I; D014409:Tumor Necrosis Factor-alpha; D009569:Nitric Oxide; D019001:Nitric Oxide Synthase; D006854:Hydrocortisone