Sensitivity of mononuclear leucocytes to glucocorticoids in elderly hip-fracture patients resistant to suppression of plasma cortisol by dexamethasone.

OBJECTIVE: Elderly women with proximal femur fracture show a prolonged increase in plasma cortisol, which could have undesirable catabolic effects. Suppression of cortisol by dexamethasone is impaired, suggesting resistance to glucocorticoid effects at feedback inhibitory sites. We therefore wished to find out whether peripheral glucocorticoid sensitivity is normal. DESIGN: Peripheral blood mononuclear leucocytes were used as a model tissue. Blood samples were taken from elderly women about 2 weeks after hip fracture and from elderly control women. Each patient was then given 1 mg dexamethasone at 2300 h followed by further sampling at 0800 and 1600 h the next day. METHODS: Glucocorticoid-receptor binding parameters were measured by incubating whole cells with [3H]dexamethasone for 2 h at 37 degrees C. Inhibition of cell proliferation by dexamethasone was assessed by addition of [3H]thymidine to cells cultured for 65 h with concanavalin A. Cortisol and dexamethasone concentrations were measured in the dexamethasone suppression test. RESULTS: As expected, the hip-fracture patients had raised morning cortisol concentrations and impaired suppression by dexamethasone. The cells of the patients had similar numbers of glucocorticoid receptors to those of the control subjects but higher values for Kd (i.e. a lower binding affinity). The cells of the patients incorporated less [3H]thymidine than the control cells in the absence of dexamethasone. The percentage inhibition by a saturating concentration of dexamethasone was unchanged but the concentration giving half-maximal inhibition was decreased (sensitivity was increased) at the higher of the two concanavalin A concentrations used. CONCLUSIONS: These experiments in mononuclear leucocytes give no evidence of peripheral resistance to glucocorticoids in hip-fracture patients with impaired suppression of cortisol by dexamethasone.

Effects of colloidal resuscitation fluids on reticuloendothelial function and resistance to infection after hemorrhage.

The effects of three resuscitation fluids, hydroxyethyl starch (HES), Haemaccel, and fresh autologous blood, on reticuloendothelial system phagocytic and catabolic functions and resistance to infection after 40% hemorrhages in BALB/c mice were studied. The mice, anesthetized with isoflurane, were bled over a 10-min period, left hypovolemic for 30 min, and then resuscitated with their shed blood or the same volume of asanguineous fluid. Normothermia was maintained throughout the experiments. The uptake and catabolism of intravenously injected double-labelled sheep erythrocytes (51Cr-125I-SRBC) in liver and spleen were determined at 1 and 48 h after hemorrhage. No significant changes in the uptake or catabolism of SRBC in liver or spleen were found at 1 h after hemorrhage and resuscitation with any of the fluids. However, at 48 h a significant increase in liver uptake of SRBC was seen in animals resuscitated with either Haemaccel or HES compared to that in animals resuscitated with shed blood or in animals subjected to a sham operation. The increase in liver uptake was accompanied by a small decrease in spleen uptake in animals resuscitated with Haemaccel but not with HES. No great changes in catabolic activity were seen at 48 h, although activity levels tended to be higher in animals resuscitated with Haemaccel. Separate groups of animals were challenged by an intraperitoneal injection with live Escherichia coli at 1 or 48 h after hemorrhage and resuscitation. Sixty-four percent of the animals resuscitated with shed blood survived the challenge with E. coli at 1 h after hemorrhage, whereas only 10 and 0% survival was seen for animals resuscitated with Haemaccel and HES, respectively. At 48 h survival was 80% for shed-blood-resuscitated animals and 60 and 70% for Haemaccel- and HES-resuscitated animals, respectively.

Phagocytic reticuloendothelial function after hemorrhage and resuscitation: modulation by different fluids.

Although the efficacy of colloid resuscitation fluids in restoring cardiovascular status in hemorrhagic shock is accepted, the effect they have on the activity of the reticuloendothelial system (RES) is less clear. As interaction with the RES may be important in determining susceptibility to infections after resuscitation the effects of three such fluids, hydroxyethyl starch, Haemaccel, and fresh autologous blood on RES function after a 40% hemorrhage have been investigated in BALB/C mice. The mice, anesthetized with isoflurane, were bled over a 10 min period, left hypovolemic for 30 min, and then resuscitated with their shed blood or the same volume of asanguineous fluid. Normothermia was maintained throughout the experiments. Whole body phagocytic activity was assessed at 1, 6, 24, 48, and 72 h after the end of hemorrhage by measuring the clearance rate (K) of intravenously injected 51Cr-labeled sheep red blood cells. No significant change in K was found at any time in animals resuscitated with shed blood. However, significant increases in K were found 48 h after resuscitation with Haemaccel. Hepatic uptake of sheep red blood cells was significantly increased at 48 and 72 h in Haemaccel-resuscitated animals compared with hydroxyethyl starch or shed blood resuscitation, whereas spleen uptake decreased at 72 h. Lung uptake was not affected at any time with any fluid. The same volume of Haemaccel had no significant effect either on K or on organ uptake when given to normovolemic animals. The changes in organ uptake after hemorrhage and resuscitation with Haemaccel were partially prevented if animals were resuscitated with Haemaccel plus autologous red cells.

Reticuloendothelial function after hemorrhage and hypothermia.

The effects of hypothermia and hemorrhage, alone and together, on reticuloendothelial system function have been studied in male BALB/c mice anesthetized with isoflurane. Whole body phagocytic activity was assessed at a deep body temperature (Tc) between 30 and 37 degrees C by measuring the clearance rate (K) of intravenously injected 51Cr-labeled sheep red blood cells (SRBC). There was a positive linear relationship between K and Tc. At a Tc of 30 degrees C splenic uptake of 51Cr-SRBC was reduced to approximately 50% of that at 37 degrees C, whilst liver and lung uptake were unaffected by the change in Tc. The hypothermia-induced reduction in K was rapidly reversed by rewarming to normothermia. A hemorrhage of 40% of measured blood volume followed after 30 min by return of the shed blood had no effect on K provided Tc was maintained at 37 degrees C. If Tc was allowed to fall to 30 degrees C during the hemorrhage, K was reduced to the same extent as in control hypothermic animals. There was also a tendency for uptake by liver, as well as spleen, to be reduced. These studies indicate that it is important to pay attention to core temperature when studying the effects of hemorrhage on aspects of reticuloendothelial function, at least in a small-animal model.