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Attenuation of circulatory shock and cerebral ischemia injury in heat stroke by combination treatment with dexamethasone and hydroxyethyl starch.

Yang TH, Shih MF, Wen YS, Ho WY, Leu KL, Wang MY, Liu CC - Exp Transl Stroke Med (2010)

Bottom Line: Concentrations of the ischemic and damage markers, dopamine, serotonin, and hydroxyl radical productions in corpus striatum, and the serum levels of interleukin-1 beta, tumor necrosis factor-alpha and malondialdehyde (MDA) were observed during heat stroke.After heat stroke, the rats displayed circulatory shock (arterial hypotension), decreased CBF, increased the serum levels of cytokines and MDA, increased cerebral striatal monoamines and hydroxyl radical productions release, and severe cerebral ischemia and neuronal damage compared with those of normothermic control rats.Our results suggest that the combination of a colloid substance with a volume-expanding effect and an anti-inflammatory agent may provide a better resuscitation solution for victims with heat stroke.

View Article: PubMed Central - HTML - PubMed

Affiliation: Department and Institute of Cosmetic Science, Chia-Nan University of Pharmacy and Science, Tainan 71710, Taiwan. ccliu@mail.chna.edu.tw.

ABSTRACT

Background: Increased systemic cytokines and elevated brain levels of monoamines, and hydroxyl radical productions are thought to aggravate the conditions of cerebral ischemia and neuronal damage during heat stroke. Dexamethasone (DXM) is a known immunosuppressive drug used in controlling inflammation, and hydroxyethyl starch (HES) is used as a volume-expanding drug in cerebral ischemia and/or cerebral injury. Acute treatment with a combined therapeutic approach has been repeatedly advocated in cerebral ischemia experiments. The aim of this study is to investigate whether the combined agent (HES and DXM) has beneficial efficacy to improve the survival time (ST) and heat stroke-induced cerebral ischemia and neuronal damage in experimental heat stroke.

Methods: Urethane-anesthetized rats underwent instrumentation for the measurement of colonic temperature, mean arterial pressure (MAP), local striatal cerebral blood flow (CBF), heart rate, and neuronal damage score. The rats were exposed to an ambient temperature (43 degrees centigrade) to induce heat stroke. Concentrations of the ischemic and damage markers, dopamine, serotonin, and hydroxyl radical productions in corpus striatum, and the serum levels of interleukin-1 beta, tumor necrosis factor-alpha and malondialdehyde (MDA) were observed during heat stroke.

Results: After heat stroke, the rats displayed circulatory shock (arterial hypotension), decreased CBF, increased the serum levels of cytokines and MDA, increased cerebral striatal monoamines and hydroxyl radical productions release, and severe cerebral ischemia and neuronal damage compared with those of normothermic control rats. However, immediate treatment with the combined agent at the onset of heat stroke confers significant protection against heat stroke-induced circulatory shock, systemic inflammation; cerebral ischemia, cerebral monoamines and hydroxyl radical production overload, and improves neuronal damage and the ST in rats.

Conclusions: Our results suggest that the combination of a colloid substance with a volume-expanding effect and an anti-inflammatory agent may provide a better resuscitation solution for victims with heat stroke.

No MeSH data available.


Related in: MedlinePlus

Extracellular levels of dopamine, serotonin, and total production of DHBA. Effects of heat exposure (ambient temperature; Ta = 42°C for 80 min) on extracellular levels of dopamine, serotonin, and total production of dihydroxybenzoic acid (DHBA) of the cerebral corpus striatum in normothermic control rats (open circles), 0.9% NaCl solution (11 ml/kg)-treated (filled circles), DXM (4 mg/kg)-treated (open squares), HES (10%, 11 ml/kg)-treated (filled squares), or the combined agent (DXM+HES)-treated rats (open triangles). The dotted line indicates time of heat stroke onset and drug injection. *P <0.05, compared with normothermic control rats. †P <0.05, compared with saline-treated rats (Ta = 42°C for 80 min). #P <0.05, compared with HES-treated rats (Ta = 42°C for 80 min) (ANOVA followed by Duncan's test).
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Figure 2: Extracellular levels of dopamine, serotonin, and total production of DHBA. Effects of heat exposure (ambient temperature; Ta = 42°C for 80 min) on extracellular levels of dopamine, serotonin, and total production of dihydroxybenzoic acid (DHBA) of the cerebral corpus striatum in normothermic control rats (open circles), 0.9% NaCl solution (11 ml/kg)-treated (filled circles), DXM (4 mg/kg)-treated (open squares), HES (10%, 11 ml/kg)-treated (filled squares), or the combined agent (DXM+HES)-treated rats (open triangles). The dotted line indicates time of heat stroke onset and drug injection. *P <0.05, compared with normothermic control rats. †P <0.05, compared with saline-treated rats (Ta = 42°C for 80 min). #P <0.05, compared with HES-treated rats (Ta = 42°C for 80 min) (ANOVA followed by Duncan's test).

Mentions: Male Spraque-Dawley rats weighing between 300 and 350 g were obtained from the National Science Council of Republic of China (Taiwan). Between experiments the animals were housed individually at an ambient temperature of 24 ± 1°C with a 12-h light-dark cycle, with the lights being switched on at 0600 h. Animal chow and water were allowed ad libitum. All protocol were approved by the Animal Ethics Committee of the Chia-Nan University of Pharmacy and Science, Tainan, Taiwan (approbated no. CN-IACUC-94007) in accordance with the Guide for the Care and Use of Laboratory Animals of the National Institutes of Health and the guidelines of the Animal Welfare Act. Adequate anesthesia was maintained to abolish the corneal reflex and pain reflexes by tail-pinching throughout all experiments (approximately 8 hr) by a single intraperitoneal dose of urethane (1.4 g.kg-1 b.w., i.p.). At the end of the experiments, control rats (and any rats that had survived heat stroke) were killed with an overdose of urethane. One hundred thirty-eight rats were used in this study. Fifty-three rats of 138 were used for examining in Table 1, Figure 1 and 2 (three premature deaths during heat stroke induction and two premature deaths during animal surgery). Forty-three rats of 138 were used for examining in Table 2 (three premature deaths during heat stroke induction). Forty-two rats of 138 were used for examining in Figure 3 and 4 (two premature deaths during heat stroke induction). No premature deaths during anesthesia.


Attenuation of circulatory shock and cerebral ischemia injury in heat stroke by combination treatment with dexamethasone and hydroxyethyl starch.

Yang TH, Shih MF, Wen YS, Ho WY, Leu KL, Wang MY, Liu CC - Exp Transl Stroke Med (2010)

Extracellular levels of dopamine, serotonin, and total production of DHBA. Effects of heat exposure (ambient temperature; Ta = 42°C for 80 min) on extracellular levels of dopamine, serotonin, and total production of dihydroxybenzoic acid (DHBA) of the cerebral corpus striatum in normothermic control rats (open circles), 0.9% NaCl solution (11 ml/kg)-treated (filled circles), DXM (4 mg/kg)-treated (open squares), HES (10%, 11 ml/kg)-treated (filled squares), or the combined agent (DXM+HES)-treated rats (open triangles). The dotted line indicates time of heat stroke onset and drug injection. *P <0.05, compared with normothermic control rats. †P <0.05, compared with saline-treated rats (Ta = 42°C for 80 min). #P <0.05, compared with HES-treated rats (Ta = 42°C for 80 min) (ANOVA followed by Duncan's test).
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC2959042&req=5

Figure 2: Extracellular levels of dopamine, serotonin, and total production of DHBA. Effects of heat exposure (ambient temperature; Ta = 42°C for 80 min) on extracellular levels of dopamine, serotonin, and total production of dihydroxybenzoic acid (DHBA) of the cerebral corpus striatum in normothermic control rats (open circles), 0.9% NaCl solution (11 ml/kg)-treated (filled circles), DXM (4 mg/kg)-treated (open squares), HES (10%, 11 ml/kg)-treated (filled squares), or the combined agent (DXM+HES)-treated rats (open triangles). The dotted line indicates time of heat stroke onset and drug injection. *P <0.05, compared with normothermic control rats. †P <0.05, compared with saline-treated rats (Ta = 42°C for 80 min). #P <0.05, compared with HES-treated rats (Ta = 42°C for 80 min) (ANOVA followed by Duncan's test).
Mentions: Male Spraque-Dawley rats weighing between 300 and 350 g were obtained from the National Science Council of Republic of China (Taiwan). Between experiments the animals were housed individually at an ambient temperature of 24 ± 1°C with a 12-h light-dark cycle, with the lights being switched on at 0600 h. Animal chow and water were allowed ad libitum. All protocol were approved by the Animal Ethics Committee of the Chia-Nan University of Pharmacy and Science, Tainan, Taiwan (approbated no. CN-IACUC-94007) in accordance with the Guide for the Care and Use of Laboratory Animals of the National Institutes of Health and the guidelines of the Animal Welfare Act. Adequate anesthesia was maintained to abolish the corneal reflex and pain reflexes by tail-pinching throughout all experiments (approximately 8 hr) by a single intraperitoneal dose of urethane (1.4 g.kg-1 b.w., i.p.). At the end of the experiments, control rats (and any rats that had survived heat stroke) were killed with an overdose of urethane. One hundred thirty-eight rats were used in this study. Fifty-three rats of 138 were used for examining in Table 1, Figure 1 and 2 (three premature deaths during heat stroke induction and two premature deaths during animal surgery). Forty-three rats of 138 were used for examining in Table 2 (three premature deaths during heat stroke induction). Forty-two rats of 138 were used for examining in Figure 3 and 4 (two premature deaths during heat stroke induction). No premature deaths during anesthesia.

Bottom Line: Concentrations of the ischemic and damage markers, dopamine, serotonin, and hydroxyl radical productions in corpus striatum, and the serum levels of interleukin-1 beta, tumor necrosis factor-alpha and malondialdehyde (MDA) were observed during heat stroke.After heat stroke, the rats displayed circulatory shock (arterial hypotension), decreased CBF, increased the serum levels of cytokines and MDA, increased cerebral striatal monoamines and hydroxyl radical productions release, and severe cerebral ischemia and neuronal damage compared with those of normothermic control rats.Our results suggest that the combination of a colloid substance with a volume-expanding effect and an anti-inflammatory agent may provide a better resuscitation solution for victims with heat stroke.

View Article: PubMed Central - HTML - PubMed

Affiliation: Department and Institute of Cosmetic Science, Chia-Nan University of Pharmacy and Science, Tainan 71710, Taiwan. ccliu@mail.chna.edu.tw.

ABSTRACT

Background: Increased systemic cytokines and elevated brain levels of monoamines, and hydroxyl radical productions are thought to aggravate the conditions of cerebral ischemia and neuronal damage during heat stroke. Dexamethasone (DXM) is a known immunosuppressive drug used in controlling inflammation, and hydroxyethyl starch (HES) is used as a volume-expanding drug in cerebral ischemia and/or cerebral injury. Acute treatment with a combined therapeutic approach has been repeatedly advocated in cerebral ischemia experiments. The aim of this study is to investigate whether the combined agent (HES and DXM) has beneficial efficacy to improve the survival time (ST) and heat stroke-induced cerebral ischemia and neuronal damage in experimental heat stroke.

Methods: Urethane-anesthetized rats underwent instrumentation for the measurement of colonic temperature, mean arterial pressure (MAP), local striatal cerebral blood flow (CBF), heart rate, and neuronal damage score. The rats were exposed to an ambient temperature (43 degrees centigrade) to induce heat stroke. Concentrations of the ischemic and damage markers, dopamine, serotonin, and hydroxyl radical productions in corpus striatum, and the serum levels of interleukin-1 beta, tumor necrosis factor-alpha and malondialdehyde (MDA) were observed during heat stroke.

Results: After heat stroke, the rats displayed circulatory shock (arterial hypotension), decreased CBF, increased the serum levels of cytokines and MDA, increased cerebral striatal monoamines and hydroxyl radical productions release, and severe cerebral ischemia and neuronal damage compared with those of normothermic control rats. However, immediate treatment with the combined agent at the onset of heat stroke confers significant protection against heat stroke-induced circulatory shock, systemic inflammation; cerebral ischemia, cerebral monoamines and hydroxyl radical production overload, and improves neuronal damage and the ST in rats.

Conclusions: Our results suggest that the combination of a colloid substance with a volume-expanding effect and an anti-inflammatory agent may provide a better resuscitation solution for victims with heat stroke.

No MeSH data available.


Related in: MedlinePlus