Toshihiro Yorozuya⁽¹⁾, Naoto Adachi⁽²⁾, Masao Soutani⁽³⁾, Kazuo Nakanishi⁽⁴⁾, Kentaro Dote⁽⁵⁾, Shigeo Kimura⁽⁶⁾, Takumi Nagaro⁽⁷⁾, Tatsuru Arai^{(8)
(1)(2)(3)(7)(8)}Ehime-university School of Medicine - Japan
^(4)(5)(6)Ehime university School of Medicine - Japan

	[Pharmacology]	[Cardiolovascular Diseases]

DISCUSSION

In the present study, dexamethasone attenuated a hypoxic decrease in the heart ATP concentration. This may be caused by an enhancement of ATP synthesis in the heart or a suppression of ATP consumption in an anaerobic state due to a decrease in the energy requirement. Since the ATP level at 0 minute did not differ between the groups, an increase in the ATP synthesis by dexamethasone is unlikely. Considering its beneficial effect on ischemic cardiac injury, it is conceivable that the agent reduces ATP consumption. In a canine study on myocardial ischemia, a pretreatment with methylprednisolone improved the segmental myocardial function and lactate imbalance, indicating the improvement of energy metabolism in an anaerobic state ⁽⁴⁾. These findings, taken together with the present result, indicate that glucocorticoids contribute to the improvement of ischemic damage by improving local energy metabolism. Glucocorticoids have been shown to increase the plasma glucose level, which may influence energy metabolism. In the current study, the effect of dexamethasone was evaluated by an isolated heart model, using a glucose-free medium. Therefore, it is unlikely that the glucose level affected the current result, although pretreatment with dexamethasone may have affected the intracellular level of glucose prior to hypoxia. Another element specific to glucocorticoids, besides hyperglycemia, seems to have provided the effect to preserve energy. There are some controversial reports that glucocorticoids do not provide protective roles in ischemia-induced change ^(5,6). However, there are differences in the methodology of positive and negative reports such as timing of drug administration, dosage, duration of ischemia, and animal species. Glucocorticoids were administered after ischemic events in most studies that had no beneficial effect. Since glucocorticoids seem to exert an influence on energy metabolism during hypoxia as shown in the current study, post-ischemic treatments may not contribute to the improvement of energy states.

Discussion Board

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[ABSTRACT] [INTRODUCTION] [MATERIAL & METHODS] [RESULTS] [FIGURES] [DISCUSSION] [CONCLUSIONS] [BIBLIOGRAPHY] [Discussion Board]

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	[Pharmacology]	[Cardiolovascular Diseases]

Toshihiro Yorozuya, Naoto Adachi, Masao Soutani, Kazuo Nakanishi, Kentaro Dote, Shigeo Kimura, Takumi Nagaro, Tatsuru Arai
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Last update: 14/01/00