Shouji Naruse

Effects of atrial natriuretic peptide on ischemic brain edema in rats evaluated by proton magnetic resonance method.

We examined the effect of atrial natriuretic peptide on cerebral edema in 96 rats. Forty-four rats were given 30 (n = 11), 120 (n = 26), or 150 (n = 7) micrograms/kg of the peptide intravenously over 24 hours after occlusion of the left middle cerebral artery to induce cerebral ischemia. We then measured the brain water content, the brain sodium and potassium contents, the in vitro proton nuclear magnetic resonance longitudinal (T1) and transverse (T2) relaxation times, and the area of the edematous regions. Compared with saline treatment (n = 39), peptide treatment decreased the brain water content in a dose-dependent manner and decreased the brain sodium content significantly (p less than 0.05). Peptide treatment also suppressed the lengthening of both T1 and T2 in edematous tissue (p less than 0.05 and p less than 0.01, respectively) and reduced the area of the edematous regions observed by magnetic resonance imaging (p less than 0.01). Atrial natriuretic peptide appears to have a pharmacological effect on ischemic brain edema, possibly by suppressing the elevation of water content through regulation of electrolyte transport in the brain.

Proton NMR relaxation times in ischemic brain edema.

The state of water in cerebral ischemia was studied by using the proton nuclear magnetic resonance (1H-NMR) method. Cerebral ischemia was induced experimentally in Mongolian gerbils by unilateral ligation of the common carotid artery. Longitudinal (T1) and transverse (T2) relaxation times of the ischemic brain were measured with a pulse FT-NMR spectrometer and the water content was determined by the wet/dry method. Quantitative analysis of the relaxation times was performed sequentially during the initial 7 hours following ligation and the data were compared with those of brain edema previously reported by S. Naruse in the rat. Characteristic findings in brain ischemia include prolongation of the slow component of T2 and increase in the water content. A quantitative comparison of relaxation rate and water content demonstrates that ischemic brain edema in Mongolian gerbils is different from cytotoxic and vasogenic types of brain edema. When R2 (1/T2) was plotted against the water content, the slope value of ischemia in the gerbil was between the slope values of the TET intoxication and cold injury induced edemas reported previously. From these results, it might be said that ischemic brain edema includes both the cytotoxic and vasogenic types of brain edema. Glycerol was demonstrated to affect brain ischemia by decreasing the water content and by shortening the slow component of T2. By analysis of the relaxation times and water content, we examined the pathophysiological characteristics of water molecules in ischemic brain tissue.

Effects of Atrial Natriuretic Peptide on Brain Oedema: The Change of Water, Sodium, and Potassium Contents in the Brain

We examined the effect of atrial natriuretic peptide (ANP) administration on cerebral oedema in rats. Intravenous ANP infusion with total dose of 120 micrograms/kg and 100 micrograms/kg suppressed the elevation of water and Na contents in left middle cerebral artery (MCA) occluded and cold injured brain tissue, indicating that ANP has a suppressive effect on cerebral oedema. Similar ANP infusion at a low dose of 1 microgram/kg/h for 6 h also resulted in observation of the anti-oedematous effect in both models, with no observable occurrence of the known systemic effects of ANP on systolic blood pressure (SBP), heart rate (HR), hematocrit, or serum electrolyte ion (Na+, K+, Cl-) concentrations. The results thus suggest that the anti-oedematous effect of ANP is attributable to water and Na content control by ANP specific to the damaged tissue, possibly through inhibition of sodium transport. Taken together with a recent study in which it was shown that ANP might inhibit sodium transport in cerebral microvessel, our results suggest that ANP suppresses the development of brain oedema by inhibiting sodium transport and the coupled water influx.

Effects of Atrial Natriuretic Peptide on Ischaemic Brain Oedema Evaluated by the Proton Magnetic Resonance Method

The effect of atrial natriuretic peptide (ANP) on cerebral oedema in rats was examined by magnetic resonance (MR). After occlusion of the left middle cerebral artery (MCA) to induce cerebral ischaemia, rats received continuous infusion of ANP for 24 h at a total dose of 120 micrograms/kg or 150 micrograms/kg. Proton relaxation times (T1 and T2) of excised oedematous tissue were measured in vitro and the area of the oedematous region was determined in vivo by the use of magnetic resonance imaging (MRI). The administration of ANP was found to decrease the lengthening of both T1 and T2 in the oedematous tissues and shown by MRI to decrease the area of the oedematous region, compared with group receiving saline. The topographic observations in vivo suggest that ANP suppress the development of the oedematous region.

Pathophysiological Investigation of Experimental Cerebral Ischaemia Using in vivo 31P-NMR Spectroscopy and 1H-MRI

The cerebral energy metabolism and brain oedema were investigated in three experimental cerebral ischaemia models using 31P-NMR spectroscopy (MRS) and 1H-NMR imaging (MRI) in the same subject animal. These measurements were performed also in experimental brain oedema models and the findings were compared with each other. 31P-MRS showed an ischaemic pattern in all of the cerebral ischaemia models, that is, ATP and PCr peaks decreased, and the Pi peak increased and shifted to a higher resonant frequency. However, 31P-MRS did not show any remarkable change in the brain oedema models. On the other hand, 1H-MRI clearly demonstrated brain oedema in the brain oedema model. In the cerebral ischaemia models, 1H-MRI findings differed depending upon the type of model, namely the most marked brain oedema was detected in the unilateral middle cerebral arterial occlusion model and no marked change was detected in the temporary four vessel occlusion model. It was thought that this difference depended on the severity of the ischaemic insult. Accordingly, the fundamental pathophysiological problem of cerebral ischaemia was the energy metabolism disturbance with the brain oedema being associated with this disturbance but occurring secondarily. However, in the brain oedema model the main pathological change was the increase in tissue water.

Protective Effects of Glycerol and Perfluorochemical in Experimental Cerebral Ischemia Demonstrated by In Vivo 31P-NMR

The treatment of cerebral ischemia has been a matter of concern for some years [12]. Although many drugs have been suggested, there are none that have proved to be definitely superior. Recently, perfluorochemicals (PFCs) with or without the addition of glycerol have been used experimentally as one of the most effective groups of drugs for this condition [2, 10]. However, their mechanism of action is not yet clearly understood. Further studies based on new techniques are necessary to solve this problem.