Modest protection of early hydrocortisone treatment in a rat model of volume-controlled haemorrhage.
BACKGROUND
Major insults may trigger generalized inflammatory responses that contribute to progressive multiple organ dysfunction. The present study was performed to test the potential of early hydrocortisone treatment to influence these responses as well as organ function following an episode of rapid and profound blood loss.


METHODS
In isoflurane anaesthesia, 35 spontaneously breathing male Sprague-Dawley rats were bled 2.5 ml 100 g-1 body weight over 10 min. Immediately following withdrawal of blood, one group (n = 17) was given 2 mg of hydrocortisone, and the other (n = 18) had the same amount of normal saline. Seventy-five minutes after initiation of bleeding, two-thirds of the blood was retransfused, together with a new injection of hydrocortisone or saline. Thereafter the rats were observed for 2 h. Key mediators of systemic inflammation and plasma markers of organ function and integrity were measured. Internal organs were weighed and scored for visible pathology. Leukocyte infiltration of the liver was counted in a light microscope.


RESULTS
Hydrocortisone reduced the plasma levels of IL-6 (P < 0.05); non-significant reductions of TNF-alpha (P = 0.12) and IL-10 (P = 0.44) were noted. The synthesis of reactive oxygen species in peritoneal cells was unaffected. Relative organ weights and organ injury scores tended to be reduced, but only wet organ weight for the lungs reached statistical significance. Leukocyte infiltration of the liver was equal in both groups. Plasma levels of ALT, AST, alpha-GST and creatinine did not differ significantly between groups. Two of the hydrocortisone treated rats died compared with four controls.


CONCLUSIONS
Early treatment with hydrocortisone had a limited organ protective effect in this model of controlled haemorrhagic shock. Although a general tendency for better outcome in the hydrocortisone group was noted, clear-cut and significant advantages of the treatment were not obtained.
Gundersen
Y
Y
Division of Protection and Material, Norwegian Defence Research Establishment, Kjeller, Norway. yngvar.gundersenffi.no
Vaagenes
P
P
Reistad
T
T
Opstad
P K
PK
D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D015687:Cell Hypoxia; D003345:Corticosterone / Q000097:blood; D006854:Hydrocortisone / Q000627:therapeutic use*; D007962:Leukocytes / Q000502:physiology; D008099:Liver / Q000473:pathology; D008297:Male; D009102:Multiple Organ Failure / Q000517:prevention & control; D009929:Organ Size; D051381:Rats; D017207:Rats, Sprague-Dawley; D012771:Shock, Hemorrhagic / Q000150:complications / Q000188:drug therapy* / Q000503:physiopathology
D003345:Corticosterone; D006854:Hydrocortisone