| Effects of Nitric Oxide Synthase Inhibitior on Energy Metabolism in Acute Ischemic-Reperfused Cat Brain: Investigated by 31P and 1H Magnetic Resonance Spectroscopy. |
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Eun Ha Suk, Pyung Hwan Park, Kun Ho Lim, Jung Hee Lee, Tae Hwan Lim |
1Department of Anesthesiology, NMR Laboratory, Asan Medical Center, College of Medicine, Ulsan University, Seoul, Korea.
2Department of Diagnotic Radiology, Asan Medical Center, College of Medicine, Ulsan University, Seoul, Korea. |
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| Abstract |
BACKGROUND
The effects of the inhibitor of nitric oxide synthase (NOS) in cerebral ischemia have been debated.
Recently, it has been suggested that it depends on the amount of the inhibitor used. Therefore, this study was carried out to evaluate the effects of the NOS in the acute ischemia-reperfusion of the cat model using variable amounts of the inhibitor.
METHODS
Nineteen cats were divided into 3 groups: group 1 (n = 6), 10 mg/kg of N-nitro-L-arginine methyl ester (L-NAME); group 2 (n = 7), 0.5 mg/kg; group 3 (n = 6), control group. Incomplete global cerebral ischemia was induced by ligation of both carotid arteries with arterial hypotension (-40 mmHg) for 30 minutes followed by 3 hours of reperfusion. The NOS inhibitor (L-NAME), was injected intraperitoneally 5 minutes before reperfusion. 31P and 1H MR spectroscopy were performed. A series of spectra was acquired in the time intervals before ligation, during ischemia, and after reperfusion.
RESULTS
Phosphocreatine/inorganic phosphate (PCr/Pi) ratios for group 1 were significantly lower than for groups 2 and 3 (P < 0.05), and there was no significant difference between groups 2 and 3. Lactate/N-acetyl aspartate (Lac/NAA) and lactate/creatine (Lac/Cr) ratios at 180 minutes after reperfusion were higher for group 1 than for groups 2 and 3 (P < 0.05). There were no significant differences in pH and lactate/choline (Lac/Cho) ratios among the 3 groups.
CONCLUSIONS
It is demonstrated that the effect of the NOS inhibitor is dosage dependent. A high dose (10 mg/kg) of L-NAME seems to have an adverse effect on recovery of the ischemia, but a low dose (0.5 mg/kg) seems to have no effect. |
| Key Words:
Brain: ischemia; Pharmacology: L-NAME; nitric oxide synthase inhibitor |
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