Masahiro Ohtake

HEPATIC BRANCH VAGOTOMY CAN SUPPRESS LIVER REGENERATION IN PARTIALLY HEPATECTOMIZED RATS

The role of the vagus nerve in liver regeneration after partial hepatectomy was studied by comparing the effects of hepatic branch vagotomy with those of hepatic branch sympathectomy in rats. The liver weight as a percentage of body weight decreased significantly 7 days after vagotomy compared with the controls and this was associated with a reduction in food intake. There was no difference in the liver weights between the control rats and the pair-fed vagotomized rats. Hepatic sympathectomy had no significant effect on the liver weight. The serum scores indicating hepatic function showed no difference between the control and the vagotomized rats except alkaline phosphatase. The concentration of insulin was unchanged. The number of mitotic hepatocytes remained high at 7 days after vagotomy. These observations led us to conclude that the vagus nerve stimulates liver regeneration, and its effect depends on vagal factors directly and specifically.

Inhibition of gastric motility induced by activation of the hypothalamic paraventricular nucleus

Electrical stimulation of the paraventricular nucleus depressed the intragastric pressure of adrenalectomized male rats of which gastric movement had been induced by insulin-hypoglycemia. Electrical stimulation to the pituitary stalk produced a similar response in the pressure, but the response was abolished by bilateral lesion of the paraventricular nucleus. These findings allow us to speculate that the paraventricular nucleus is capable of modulating gastric motility, and suggest that the nucleus has a neural connection between the neurohypophysis and the system relevant to visceral function.

A pharmacological analysis of prostaglandin E1 on portal blood flow after partial hepatectomy in rats.

Portal venous flow (PVF) and portal venous pressure (PVP) were examined after the jugular or portal injection of Prostaglandin E1 (PGE) in rats partially hepatectomized by either 40% or 66%. In the 66% hepatectomized animals, the jugular injection of PGE at 5.0 μg/kg/min produced an increase in PVF concomitant with a fall in systemic arterial pressure (SAP), while PVP remained unchanged. The portal injection of PGE at 0.5 μg/kg/min increased PVF to a level equivalent to that evoked by the jugular injection of 5.0 μg/kg/min PGE, without any change in SAP. PVP was reduced synchronistically with an increase in PVF. The PVF response to a portal injection of PGE at 0.5 μg/kg/min was not reproduced in liver intact rats. These results suggest that PGE is potent in increasing PVF in the partially resected condition of the liver and that the portal vascular bed is involved in this response.

The role of the abdominal sympathetic nervous system in regulating portal venous flow and its functional distribution

The role of the abdominal sympathetic nervous system in regulating portal venous flow (PVF) was examined in anesthetized rats using an ultrasonic volume flowmeter. Electrical stimulation of the hepatic sympathetic branch, given at 10 Hz, 1 ms, 10 s and 12 V, caused approximately a 28 per cent reduction in PVF, which was equivalent to that produced by occlusion of the bilateral carotid arteries for 30 s, without causing any change in the systemic arterial pressure. Stimulation of the major splanchnic nerve decreased PVF, the response being greater by stimulation of the right nerve than by stimulation of the left (p<0.05). Bilateral adrenalectomy shortened the recovery time without changing the magnitude or lateral predominancy. Neither proper hepatic arterial occlusion nor partial hepatectomy affected the response. In the partially hepatectomized animals, stimulation of the hepatic branch did not decrease the splenic flow but decreased the superior mesenteric venous flow (SMVF) and induced a similar response in PVF even when the SMVF was interrupted. An intraportal injection of noradrenaline decreased PVF dose-dependently. These findings indicate that the sympathetic nerve regulates PVF directly, and that there is functional laterality of the regulatory mechanism in the abdominal cavity, which suggests that adrenal factors work together with the nerve that supplies the portal vein.

Simultaneous development of Crohn's disease and myelodysplastic syndrome progressing to acute myelocytic leukemia in a patient with a normal karyotype

A 28-year-old man developed Crohns disease and myelodysplastic syndrome concurrently. Chromosomal analysis of the bone marrow revealed a normal male karyotype. Subsequently, the myelodysplastic syndrome progressed to acute myelocytic leukemia. Several causes, including the medical treatment for Crohns disease, chromosomal abnormalities, and a common underlying immune dysfunction, have been proposed as pathogenetic factors in the association with Crohns disease of hematologic malignancies. This case suggests that neither medical treatment for Crohns disease nor chromosomal abnormalities are inevitable causes of the development of hematologic malignancies associated with Crohns disease. At present, the cause of the association remains unclear, although the idea of a common immune dysfunction is attractive.

Interaction of glucose signals between the nucleus of the vagus nerve and the portal vein area in the regulation of gastric motility in rats

Intragastric pressures were examined after glucose injection into the nucleus of the vagus nerve (X) of the medulla oblongata or into the portal vein (PV) or both in bilaterally adrenalectomized rats. Ten mM glucose (500 nl) injected into the X or into the PV (25 microliters) decreased gastric pressure associated with insulin-hypoglycemia. Simultaneous injection of glucose into the X and PV produced a reduction in gastric pressure in an additive manner. In addition, a significant fall in gastric pressure was seen when an ineffective concentration of glucose was injected into the X and PV simultaneously. The results suggest that the X and PV signals interact with each other to inhibit gastric motility.

Orally administered prostaglandin E1 derivative can enhance liver regeneration in partially hepatectomized rats

The effect of orally administered 17(S),20-dimethyl-6-oxo prostaglandin E1 (PGE1) methyl ester (OP) on liver regeneration was examined in 66% hepatectomized rats. Administration of OP increased the mitotic index of the hepatocyte 3 days after hepatectomy, and the mitotic index response due to OP was dose dependent. The OP administration had no effect on food intake, but reduced water intake. The serum scores relative to nutrition and hepatic function showed transient change after OP administration, whereas the serum blood urea nitrogen level indicated a slight renal dysfunction with OP. The fat store in the body was transiently reduced. These observations lead us to conclude that orally administered OP is capable of stimulating liver regeneration without serious systemic effects.

d-Glucose anomers in the nucleus of the vagus nerve can depress gastric motility of rats

The infusion of alpha-,beta-, or equilibrated (alpha: 36%; beta: 64%) D-glucose solution in the vicinity of the nucleus of the vagus nerve decreased gastric motility caused by insulin in rats with bilateral adrenalectomy. This effect was not reproduced after vagotomy at the cervical level. Of the 3 forms of D-glucose solution the effect of beta-D-glucose was greatest. The infusion of isotonic NaCl, however, produced no change in the motility. These results suggest that blood beta-D-glucose may predominantly activate a brain mechanism which vagally controls gastric motility at the medullary level.

Gastrin-17 injected into the hypothalamic paraventricular nucleus can induce gastric acid secretion in rats

Injections of picomolar quantities of gastrin-17 into the hypothalamic paraventricular nucleus increased gastric acid output in anesthetized rats. The response was dose-dependent, and it was blocked by atropin and by vagotomy. The same doses, injected intravenously, intraventriculary or into sites far from the nucleus, did not increase the output. Cholecystokinin-8 injected into the nucleus had no effect on the acid output.

Alterations in gastric acid secretion following hepatic vagotomy at a stage of development in rats

The relation of gastric acid secretion to the hepatic vagal section was examined in consideration of developmental stages of a rat. Acid outputs in rats deprived of food for 22 hr before the experiment were estimated with or without insulin. The animals were classified into five groups according to their body weights at the experiments (50, 100, 200, 300 and 400 g). Hepatic vagotomy was effective in decreasing acid output in all of the groups treated with food deprivation and insulin, and it was found that there was a close relationship between the output and glucose concentration in the portal blood. In rats treated only with food deprivation, hepatic vagotomy produced different effects for the five groups; the vagotomy failed to cause acid response when the rats weighed about 300 and 400 g, while in the animals weighing about 50, 100 and 200 g acid outputs were reduced following the vagotomy. It was noted that the sensitivity to hypoglycemia in the acid output was greater in the young rats than the older ones. Results suggest that function of the hepatic vagal nerve may be prominent in modulating acid secretion in an earlier stage of development when the animals are most sensitive to hypoglycemia.