Dynamics of cerebral metabolism during moderate hypercapnia.
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Biomedical subjects
Publications and source records attributed to K Kogure.
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Hypocapnia of moderate and extreme degree (Paco2 21.1 and 13.5 torr, respectively)was induced by hyperventilation in rats subjected to the closed system of Lowry inorder to evaluate the effects on utilization rate of cerebral energy metabolites. The tissue levels of high-energy phosphates and calculated intracellular pH did not change, whereas glucose, pyruvate, and lactate increased significantly. The La/Pyratio and NADH/NAD-+ RATIO BOTH INCREASED IN PROPORTION TO THE DEGREE OF HYPOCAPNIA. Utilization rates of glucose, glycogen, and ATP were all significantly reduced by hypocapnia, whereas the utilization rate of phosphocreatine was increased. The rate oftotal high-energy phosphate use was also diminished in proportion to the degree of hypocapnia. The constant value of the energy charge (0.94 plus or minus 0.01) indicates that the energy production rate might also be reduced by hyperventilation; thus the intermediate metabolics and substrates increased. It is concluded that extreme hypocapnia reduces the rate of cerebral energy metabolism significantly.
The effect of sodium cyanate (25, 50, 75, and 100 mg/kg body weight i.p. daily for 10 days) upon cerebral metabolism and the EEG of Wistar rats was studied. This treatment resulted in a dose-related carbamylation of hemoglobin and left shift in the oxygen dissociation curve. Animals receiving the highest dose of cyanate developed a significant systemic metabolic acidosis. In brain there was dose-dependent decrease in phosphocreatine, TCO2 and cytoplasmic NADH/NAD+ ratio, reflecting the calculated drop in intracellular pH. Glucose levels were elevated despite a normal calculated energy charge, which suggests a balanced slowing of the energy-producing and energy-utilizing systems. The higher doses of cyanate produced spontaneous seizure activity on the EEG.
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Oral administration of N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) to hamsters at a concentration of 50-83 μg/ml in the drinking water resulted in a high incidence of tumours in the glandular stomach. Short-term administration of MNNG for 4-6 months resulted in more adenocarcinomata in the glandular stomach than long-term administration for 7-8 months. One case of metastasis of an adenocarcinoma of the glandular stomach to the liver and 2 cases of metastasis to the regional lymph nodes were found. Spindle cell sarcomata in the glandular stomach and adenocarcinomata in the duodenum were also often produced.Oral administration of MNNG at the very high concentration of 500-2000 μg/ml induced a hepatic cell carcinoma, intrahepatic bile duct carcinomata, bile duct cystadenomata and cystic dilatation, and a haemangioma in the liver but no tumour in the glandular stomach.Sequential morphological studies on the glandular stomach of hamsters receiving 50 μg/ml of MNNG in the drinking water showed 3 stages of change of the mucosa. The mucosa became atrophic and eroded in the first 16 weeks. Irregular atypical glands developed at the margins of erosions and proliferation of spindle cells in the submucosa were found after 18 weeks. Spindle cell sarcomata developed in animals after 20 weeks. Adenocarcinomata developed between 25 and 32 weeks.
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