51. Changes in Energy Levels by Dexamethasone in Ischemic Hearts and Brains in Male Mice
- Author
-
Toshihiro Yorozuya, Naoto Adachi, Chikara Namba, Kentaro Dote, Kazuo Nakanishi, and Takumi Nagaro
- Subjects
Male ,Adenosine monophosphate ,medicine.medical_specialty ,Cardiotonic Agents ,mice ,Traumatic brain injury ,brain ,Myocardial Ischemia ,Ischemia ,dexamethasone ,heart ,ischemia ,Body Temperature ,Cerebral edema ,chemistry.chemical_compound ,Adenosine Triphosphate ,Internal medicine ,medicine ,Animals ,Biogenic Monoamines ,Enzyme Inhibitors ,adenosine 5′-triphosphate ,Muscle, Skeletal ,Dexamethasone ,Brain Chemistry ,Cardioprotection ,Metyrapone ,business.industry ,medicine.disease ,Adenosine Monophosphate ,Adenosine Diphosphate ,Anesthesiology and Pain Medicine ,Endocrinology ,chemistry ,Laboratory Investigation ,Surgery ,Neurology (clinical) ,dopamine ,Energy Metabolism ,business ,Injections, Intraperitoneal ,Glucocorticoid ,medicine.drug - Abstract
The cardioprotective effects of glucocorticoids in the acute setting of ischemia/reperfusion have been experimentally demonstrated in animals1–7 and humans.8 Although the mechanisms underlying glucocorticoid cardioprotection are not known with certainty, glucocorticoids are reported to preserve cellular function in ischemia thereby prolonging the period of myocardial viability. In previous studies, glucocorticoids were reported to improve lactate imbalance and prevent the leakage of intracellular enzymes caused by myocardial ischemia.6,7 At the same time, deleterious effects of glucocorticoids on ischemia-induced neuronal damage have been shown in various animal models, despite the ability of glucocorticoids to alleviate cerebral edema caused by traumatic brain injury and hemorrhage.9–13 Further, steroids are not indicated for traumatic brain injury in humans, as they do not improve clinical outcomes.14 Because adenosine 5′-triphosphate (ATP) provides energy to maintain membrane functional integrity in both the heart and brain, and ATP depletion precedes loss of cellular viability, the different effects of the agents in ATP utilization in the heart and brain during ischemia could well explain differences in ischemia-induced organ injury. In the present study, therefore, we investigated the effect of dexamethasone, a glucocorticoid without mineralocorticoid activity, on ischemia-induced reduction of ATP in the mouse heart and brain. In addition, we examined the effect of metyrapone, a potent inhibitor of the synthesis of glucocorticoids, to assess the role of endogenous glucocorticoids. We hypothesized that ATP levels would be diminished in neuronal tissue subjected to dexamethasone and improved in cardiac tissue subjected to dexamethasone. In contrast, ATP levels would be improved in neuronal tissue subjected to metyrapone and diminished in cardiac tissue subjected to metyrapone.
- Published
- 2015
- Full Text
- View/download PDF