Changes in Energy Levels by Dexamethasone in Ischemic Hearts and Brains in Male Mice.

BACKGROUND: Glucocorticoids have been shown to alleviate ischemia-induced myocardial injury, while aggravating neuronal damage caused by ischemia. As energy failure is a predominant factor in cellular viability, we examined the effects of glucocorticoids on energy utilization in the mouse heart and brain. METHODS: Seventy-two male ddY mice were assigned to 1 of 3 groups: saline (S), dexamethasone (a glucocorticoid without mineralocorticoid activity, 5 mg/kg) (D), and metyrapone (a potent inhibitor of the synthesis of glucocorticoids, 100 mg/kg) (M) groups (n=24 in each). Three hours after intraperitoneal administration, all animals were decapitated, and the heads were frozen in liquid nitrogen after 0, 0.5, 1, or 2 minutes (n=6 in each). The hearts were immediately removed and frozen in liquid nitrogen after 0, 5, 10, or 20 minutes of incubation at 37°C (n=6 in each). The concentrations of adenylates and monoamines were determined by high-performance liquid chromatography. RESULTS: In the heart, the adenosine 5'-triphosphate (ATP) concentration did not differ among the 3 groups at 0 minute of ischemia (3 h of S, D, or M treatment). Ischemia for 5 minutes decreased the ATP content to 21% of the basal level in the S group. The ATP decrease was suppressed by either the D or M treatment, such that after 5 minutes ATP levels were 63% and 64% of each basal level, respectively. In the brain, the ATP level in the M group was 62% of that in the S group at 0 minute of ischemia, and the 5'-monophosphate (AMP) level was 276% of that in the S group. Brain dopamine metabolism was facilitated by dexamethasone, and suppressed by metyrapone. CONCLUSIONS: The relationship between effects of glucocorticoids on ischemia-induced changes in energy levels and cellular viability was not clearly elucidated.

[Measurement of external pressure of peroneal nerve tract coming in contact with lithotomy leg holders using pressure distribution measurement system BIG-MAT®].

We investigated external pressure on peroneal nerve tract coming in contact with two kinds of leg holders using pressure distribution measurement system BIG- MAT® (Nitta Corp., Osaka) in the lithotomy position Peak contact (active) pressure at the left fibular head region coming in contact with knee-crutch-type leg holder M® (Takara Belmont Corp., Osaka), which supports the left popliteal fossa, was 78.0 ± 26.4 mmHg. On the other hand, peak contact pressure at the left lateral lower leg region coming in contact with boot-support-type leg holder Bel Flex® (Takara Belmont Corp., Osaka), which supports the left lower leg and foot was 26.3±7.9 mmHg. These results suggest that use of knee-crutch-type leg holder is more likely to induce common peroneal nerve palsy at the fibular head region, but use of boot-support-type leg holder dose not easily induce superficial peroneal nerve palsy at the lateral lower leg region, because capillary blood pressure is known to be 32 mmHg. Safer holders for positioning will be developed to prevent nerve palsy based on the analysis of chronological change in external pressure using BIG-MAT® system during anesthesia.

Suppression of sodium pump activity and an increase in the intracellular Ca2+ concentration by dexamethasone in acidotic mouse brain.

The effects of dexamethasone on adenosine 5'-triphosphatase (ATPase) activity and the intracellular Ca(2+) concentration ([Ca(2+)](i)) were investigated in acidotic mouse brain. Dexamethasone (3 mg/kg, i.p.) or vehicle was administered 3 h before decapitation ischemia, and the brain concentration of adenosine 5'-triphosphate (ATP) was determined 0.5-2 min after ischemia. The effects of dexamethasone (0.3-3 mg/kg, i.p.) on Na(+),K(+)-activated ATPase (Na(+),K(+)-ATPase) and Ca(2+)-ATPase activities were evaluated at pH 7.4 and 6.8. Changes in [Ca(2+)](i) in an acidic medium were determined in hippocampal slices by microfluorometry using rhod-2 acetoxymethyl ester as a Ca(2+) marker, and the effects of dexamethasone (240 microg/l) was evaluated. Decapitation ischemia for 0.5 and 1 min reduced the brain ATP contents to 32% and 16% of the basal level, respectively. Dexamethasone slightly suppressed the extent of the decrease in the ATP level. Although dexamethasone did not affect Na(+),K(+)-ATPase activity at pH 7.4, the activity was suppressed by dexamethasone (3 mg/kg) to 68% at pH 6.8. The activity of Ca(2+)-ATPase was not affected by dexamethasone at either pH 7.4 or pH 6.8. When the pH of the medium of the brain slices was changed from 7.4 to 6.8, almost no increase in [Ca(2+)](i) was observed in the control group. The dexamethasone treatment increased [Ca(2+)](i) in the CA1 field and dentate gyrus immediately after induction of the acidic medium, the effect being significant after 150 s. Because anaerobic glucose metabolism in the early stage of ischemia enhances intracellular lactic acidosis, the findings may suggest a mechanism for the aggravation of ischemic neuronal damage by glucocorticoids.