Changes in rat liver mitochondria under conditions of bilateral subdiaphramatic vagotomy]

A study was made of the changes in the mitochondria of the rat liver under conditions of bilateral subphrenic vagotomy. Two stages in the dynamics of the response of the mitochondrial apparatus to denervation were distingished. During the first stage (0.5-3 days after vagotomy) there occurred reversible functional disturbances of the mitochondria caused by the postoperative stress. The second stage (7 to 60 days after the denervation) was charaterized by more marked structural-functional changes having a number od common features with those seen in hypoxia and being result of vagotomy proper.     

Use of dibunol in pharmacological correction of post-vagotomy hypoxia of digestive organs in rats

1, 7, 14, 30 and 60 days after bilateral sub-diaphragmatic truncal vagotomy tension of oxygen (pO2) in liver, stomach and small intestine (jejunum) was determined. It was demonstrated that vagotomy leads to a decrease of pO2 in all investigated organs 1 day after the operation (such changes were observed in sham-operated rats) and 30 days, in jejunum--after 7 days, in liver--after 14 days, in stomach--after 60 days. Dibunol introduction in vagotomized rats during 29 days (starting from the second day after operation) results in pO2 normalization in all investigated organs.     

The role of the parasympathetic nervous system in regulating the oxygen tension and regional blood flow in the digestive organs of rats

The input of parasympathetic region of vegetative nervous system in regulation of regional blood transfer and maintaining of oxygen balance in organs of rat digestive system has been estimated by measuring oxygen tension (pO2) and the rate of regional blood transfer (RBTR) in liver, gut, and small intestine after 1, 7, 14, 30, and 60 days after vagotomy. Vagotomy was shown to lead to the decrease of pO2 in liver (1, 14, 30 days), gut (1 day), and small intestine (7 and 30 days). At initial postoperation period (1 day), the decrease in pO2 is accompanied by the increase in RBTR (in gut and small intestine), and at late period, by the decrease of RBTR in liver. The correlation between the decrease in pO2 and the decrease in RBTR allows to conclude that the hypoxia developing in liver after vagotomy is of a circulatory nature.     

Effect of vagotomy on permeability processes in the structural components of rat liver]

The method of intravital fluorescence microscopy was used to study permeability by sodium fluoresceine of the structural components of the rat liver 7,21 and 60 days after bilateral subphrenic vagotomy. It was found that vagotomy resulted in a permeability rise both of the liver microvessels and hepatocyte plasma membranes. Later the temporal indices return to the initial levels.     

Effect of the antioxidant dibunol on the course of a neurodystrophic process in the rat pancreas

In experiments on rats using histochemical methods it was postulated that injection of dibunol (ionol) in conditions of subdiaphragmatic vagotomy has a correlative effect on neurodystrophic process in pancreas during the time of observation (7, 14, 30 days postoperation).     

Effect of autonomic denervation on DNA synthesis during liver regeneration after partial hepatectomy

The regulatory role of autonomic nerves in liver regeneration after partial hepatectomy was studied in rats by bilateral subdiaphragmatic vagotomy or splanchnicectomy. 1. In control rats the wet weight of the regenerating liver was restored to approximately 80% of the preoperative weight 72 h after partial hepatectomy. Restoration of the liver weight was significantly impaired in vagotomy rats, but not in splanchnicectomy. Increases in the DNA and protein contents of the regenerating liver were also suppressed by vagotomy. 2. Hepatic DNA synthesis, measured as the incorporation of [methyl-3H]thymidine into DNA at various times after partial hepatectomy, was significantly less in vagotomized rats, and slightly more in splanchnicectomized rats than in control rats. The onset of DNA synthesis triggered by partial hepatectomy was also delayed by vagotomy. 3. The increases in activities of hepatic aspartate transcarbamoylase and thymidine kinase, the key enzymes in synthesis of pyrimidine nucleotides via the de novo and salvage pathways respectively, during liver regeneration, were significantly suppressed and retarded in vagotomized rats. Conversely, splanchnicectomy tended to stimulate these enzyme inductions after partial hepatectomy. 4. During starvation the plasma insulin level decreased after partial hapatectomy in control and vagotomized rats, as in sham-operated rats, but showed a transient increase 6 h after partial hepatectomy in splanchnicectomized rats. It is concluded that vagotomy inhibits and delays DNA synthesis and proliferation of liver cells after partial hepatectomy, whereas splanchnicectomy tends to stimulate these processes. The data also suggest that parasympathetic innervation of the liver may play an important regulatory role in liver regeneration.     

Acute abdominal vagotomy reduces drinking to peripheral but not central angiotensin II

Rats were tested two or three days after bilateral abdominal vagotomy or a laparotomy control procedure for their drinking responses to subcutaneous (1 mg-kg-1) or intracerebroventricular (100 ng) injections of angiotensin II. Vagotomy delayed the initiation of drinking and decreased 60-min water intake after subcutaneous, but not after intracerebroventricular, angiotensin II. This is the shortest postoperative interval in which the decrease in drinking after systemic injection of angiotensin II by abdominal vagotomy has been observed. The failure of vagotomy to decrease the response to intracerebroventricular angiotensin II demonstrates that the deficit after subcutaneous injection was not a nonspecific effect of recent vagotomy. These results, therefore, suggest that the abdominal vagus is necessary for normal drinking in response to circulating angiotensin II. Furthermore, the selective and acute onset of the deficit is consistent with the loss of a specific, rather than tonic facilitatory, vagal mechanism for drinking after elevation of circulating angiotensin II levels. Finally, the results imply that the physiological mechanisms which mediate the drinking responses to central and peripheral angiotensin are not identical.     

Characteristics of liver regeneration after vagotomy

Peculiarities of a reparative process in the hepatic parenchyma have been studied after toxic effect of CCl4, at vagotomy in 1, 2 and 4 weeks after the operation. Appearance of a more massive lesion and decreasing regeneration of the vagotomized liver have been revealed. The proliferative activity of hepatocytes, normal and after vagotomy has a principally similar character and is described as a curve with two picks, having its maximum on the 2nd and the 5th-6th days after xenobiotic administration. The intensity of the hepatocyte proliferative activity in the denervated liver essentially surpasses that in the control and decreases, as the area of the parenchymal lesion decreases in the latest time after the operation.     

NADPH-diaphorase activity in the nodose ganglion of normal and vagotomized guinea-pigs

The activity and distribution of reduced nico-tinamide adenine dinucleotide phosphate diaphorase (NADPH-diaphorase) in the nodose ganglion of normal and vagotomized guinea-pigs were examined by light and electron microscopy. Light microscopy confirmed a remarkable increase in the number of NADPH-diaphorase-reactive neurons in the nodose ganglion following unilateral cervical vagotomy. The increase was present at 5 days but became more prominent at 10 days and was sustained until at least 30 days after vagotomy when compared with the non-lesioned side. The NADPH-diaphorase reaction product was associated with the membrane of the rough endoplasmic reticulum, Golgi apparatus, mitochondria and nucleus of the nodose neurons. In animals killed 5 days post-operation, there was no noticeable degeneration in the nodose neurons. However, at 10 days, the mitochondria in some neurons appeared swollen and vacuolated with disrupted cristae. These changes were accentuated in some nodose neurons 20 and 30 days after vagotomy but there was no evidence of cell death. All the degenerating neurons exhibited NADPH-diaphorase activity. The increase in NADPH-diaphorase activity in the neuronal somata after vagotomy suggests that the enzyme is involved in either the retrograde degeneration or the recovery of the lesioned neurons. Received: 15 June 1995 / Accepted: 15 February 1996     

Vagotomy enhances experimental metastases of 4THMpc breast cancer cells and alters substance P level

We have previously demonstrated that inactivation of capsaicin-sensitive sensory neurons enhances lung and heart metastases of breast carcinoma. Because a significant part of sensory innervation of lung tissue is supplied by the vagus nerve, we here examined the effects of unilateral mid-cervical vagotomy in the metastases of 4THMpc breast carcinoma and tissue Substance P (SP) levels. Balb-c mice were injected orthotopically with 4THMpc cells 1 week after vagotomy. Animals were sacrificed 27-30 days after injection of 4THMpc cells and the extent of metastases was determined. Unilateral vagotomy, right or left significantly increased the lung, liver and kidney metastases without altering the growth rate of the primary tumor. Heart metastases were increased only following left vagotomy. The changes in SP levels were somewhat surprising such that vagotomy actually increased while sham-operation decreased SP levels in lung. The effect of sham-operation was reversed by unilateral vagotomy demonstrating that vagal activity decreases total SP levels in the lung. Increased SP levels might be due to decreased degradation of the peptide. Presence of the tumor markedly increased SP level in the lung, which was more prominent in vagotomized animals. These results provide evidence that vagal activity may protect against metastatic disease.     

IN VIVO SYNTHESIS OF STABLE RNA WITHIN THE RAT NODOSE GANGLIA FOLLOWING VAGOTOMY

Abstract— We have investigated the in vivo synthesis of stable RNA in the rat nodose ganglia following unilateral vagotomy. Incorporation of precursor into rRNA, and possibly tRNA, in the injured ganglion increases rapidly after vagotomy, reaching twice the normal value at 2 days post-crush. In contrast to this, incorporation within the uninjured colateral ganglion decreases to about 65% of normal values after 4 days. But, by 7 days, both ganglia appear to be returning to their normal levels. One phase of DNA synthesis is detected in the injured ganglion, at days 1 and 2. while two phases are found in the contralateral ganglion, at days 2 and 34.     

A histochemical analysis of the enzymes of the enterocyte transport and bioenergetics in rat small intestine after vagotomy and dibunol administration

It was shown that the vagotomy leads to the elevation of the activity of alkaline phosphatase (AP) 7 days after the operation and to the decrease of its activity 30 days after the operation, and to the decrease of the activity of succinic dehydrogenase (SDG) 7 and 30 days after the operation. Introduction of dibunol leads to normalization of these disturbances of the activity of AP and SDG induced by vagotomy.     

Importance of vagal afferents in determining ventilation in newborn rats

We studied the effect of acute bilateral vagotomy on ventilation and ventilatory pattern in rats. In 1- to 6-day-old unanesthetized rats, vagotomy resulted in a substantial decrease (38%) in ventilation during air breathing. After vagotomy there was a threefold increase in tidal volume (VT), inspiratory time (TI) doubled, and expiratory time (TE) was six times longer. When studied under isoflurane anesthesia, newborn rats showed decreases in ventilation similar to that observed without anesthesia, whereas anesthetized adult rats had no consistent changes in ventilation. Adult and newborn rats had nearly identical proportionate increases in VT and TI after vagotomy, but TE lengthened to a greater extent in the newborns. Additionally, we demonstrated a significant decrease in ventilation when 100% O2 rather than air was supplied to nonvagotomized unanesthetized newborn rats. Ventilation decreased by 19% after vagotomy under hyperoxic conditions. We conclude that vagal afferent input, probably of pulmonary mechanoreceptor origin, provides positive feedback to respiration in newborn rats and that newborn rats greater than 24 h old also have a degree of peripheral chemoreceptor drive during air breathing.     

Distribution of glucose-6-phosphatase activity in normal,hyperplastic, and preneoplastic rat liver

The significance of glucose-6-phosphatase (G6P) expression by bile duct-like cells proliferating during hepatocarcinogenesis in the histogenesis of hepatocellular carcinoma is not clear. To this end, we measured the histochemical and biochemical activity of G6P in normal rat liver, and in rat livers in which bile duct-like proliferation was induced by either hyperplastic (bile duct ligation for 14 days or feeding alpha-naphthylisothiocyanate for 28 days) or neoplastic (feeding a choline-devoid diet containing 0.1% ethionine for 60 days) regimens. In normal, hyperplastic, and preneoplastic livers, G6P histochemical activity was confined to the hepatocytes; proliferated bile duct-like cells, like normal bile ducts, did not display visible G6P staining. When the enzyme activity was determined biochemically, however, hydrolysis of glucose-6-phosphate was observed in both parenchymal and nonparenchymal liver cells isolated from all experimental animals. In elutriated nonparenchymal fractions, G6P activity was directly proportional to the number of cells positive for gamma-glutamyl transpeptidase and cytokeratin no. 19 (markers of bile duct cells) and inversely proportional to the number of cells positive for vimentin (marker of mesenchymal cells). These results indicate that, while by light microscopy hepatic G6P histochemical activity is detectable only in the hepatocytes, the biochemical activity is also expressed in proliferating bile duct-like cells. However, the nonparenchymal activity is observed during both neoplastic and hyperplastic liver growth, thus indicating that the presence of this enzyme in bile duct-like cells proliferating during hepatocarcinogenesis should not necessarily be construed as supporting their stem cell nature nor their neoplastic commitment.     

Distribution of glucose-6-phosphatase activity in normal, hyperplastic, and preneoplastic rat liver.

The significance of glucose-6-phosphatase (G6P) expression by bile duct-like cells proliferating during hepatocarcinogenesis in the histogenesis of hepatocellular carcinoma is not clear. To this end, we measured the histochemical and biochemical activity of G6P in normal rat liver, and in rat livers in which bile duct-like proliferation was induced by either hyperplastic (bile duct ligation for 14 days or feeding alpha-naphthylisothiocyanate for 28 days) or neoplastic (feeding a choline-devoid diet containing 0.1% ethionine for 60 days) regimens. In normal, hyperplastic, and preneoplastic livers, G6P histochemical activity was confined to the hepatocytes; proliferated bile duct-like cells, like normal bile ducts, did not display visible G6P staining. When the enzyme activity was determined biochemically, however, hydrolysis of glucose-6-phosphate was observed in both parenchymal and nonparenchymal liver cells isolated from all experimental animals. In elutriated nonparenchymal fractions, G6P activity was directly proportional to the number of cells positive for gamma-glutamyl transpeptidase and cytokeratin no. 19 (markers of bile duct cells) and inversely proportional to the number of cells positive for vimentin (marker of mesenchymal cells). These results indicate that, while by light microscopy hepatic G6P histochemical activity is detectable only in the hepatocytes, the biochemical activity is also expressed in proliferating bile duct-like cells. However, the nonparenchymal activity is observed during both neoplastic and hyperplastic liver growth, thus indicating that the presence of this enzyme in bile duct-like cells proliferating during hepatocarcinogenesis should not necessarily be construed as supporting their stem cell nature nor their neoplastic commitment.     

Five- to Eight-year Results of Truncal Vagotomy and Pyloroplasty for Duodenal Ulcer

From January 1963 to December 1965 inclusive 192 men with duodenal ulcer were treated by elective truncal vagotomy and pyloroplasty with one death. Ten subsequent deaths were due to causes unrelated to the ulcer or operation, and 17 patients became untraceable. The remaining 164 patients have been followed up for five to eight years. The late results have been compared with those obtained in a previous study of patients five to eight years after truncal vagotomy and gastroenterostomy, truncal vagotomy and antrectomy, and subtotal gastrectomy respectively for duodenal ulcer.Of the various postgastric operation syndromes early dumping, late dumping, bilious vomiting, and diarrhoea were all less frequent, but not significantly so, after vagotomy and pyloroplasty than after vagotomy and gastroenterostomy.Recurrent ulceration was commoner after vagotomy and pyloroplasty than after all the other operations, the incidence of proved and suspected recurrent ulcers being respectively 6·7 and 7·3% after vagotomy and pyloroplasty, but only 2·5 and 5·9% after vagotomy and gastroenterostomy, 0 and 5·2% after vagotomy and antrectomy, and 0·9 and 3·7% after subtotal gastrectomy. The differences between vagotomy and pyloroplasty and vagotomy and antrectomy or subtotal gastrectomy are statistically significant, but those between vagotomy and pyloroplasty and vagotomy and gastroenterostomy are not.Overall assessment (Visick grading) of the outcome gave poorer results after vagotomy and pyloroplasty than after any other operation, with 14% of category IV cases after vagotomy and pyloroplasty, 11% after vagotomy and gastroenterostomy, 8% after vagotomy and antrectomy, and 6% after subtotal gastrectomy—differences that are significant between vagotomy and pyloroplasty and vagotomy and antrectomy or subtotal gastrectomy but not between vagotomy and pyloroplasty and vagotomy and gastroenterostomy.In the light of these findings it is suggested that truncal vagotomy and pyloroplasty has not lived up to expectations and its place as the currently most popular procedure in the elective surgical treatment of duodenal ulcer should be reconsidered.     

Effect of tidal volume and anesthetic agent on airway responsiveness to histamine

Dose-response relationships for bronchoconstriction in response to aerosal histamine were assessed before and after vagotomy in 11 dogs anesthetized with barbiturates and in 9 dogs anesthetized with alpha-chloralose-urethan. The dose-response relationships following vagotomy were assessed during spontaneous ventilation and during muscular paralysis and mechanical ventilation with tidal volume (VT) similar to each animal's VT prior to vagotomy. After vagotomy the spontaneous VT of both groups increased but the VT of the alpha-chloralose-urethan group was significantly less than that of the barbiturate group. The histamine responsiveness of the animals anesthetized with barbiturates was significantly greater during mechanical ventilation when VT was reduced to prevagotomy levels compared with during spontaneous ventilation. In contrast, the histamine responsiveness of the alpha-chloralose-urethan group was not significantly changed by reducing VT to prevagotomy levels. In six other dogs anesthetized with pentobarbital sodium and studied after vagotomy, responsiveness to histamine aerosol during controlled ventilation with breaths of prevagotomy VT was greater than responsiveness during mechanical ventilation with large volume breaths given immediately afterward. Thus the magnitude of VT of dogs after vagotomy may influence airway responsiveness, and the influence of anesthetic agents on airway responsiveness after vagotomy may in part be due to their effects on VT. Furthermore, bronchodilation accompanying large volume ventilation persists after vagotomy, suggesting that it is not exclusively mediated by changes in parasympathetic activity.     

Use of chemiluminescence analysis in the determination of the activity of hepatic antichalone and chalone

Partially purified antichalone and chalone from the liver of the mammals possess significant antiradical activity revealed by the chemiluminiscent analysis in the system capable of generating free radicals. Chemiluminiscent damping degree is proportional to the quantity of antichalone and chalone in the system. During the first three days the activity of antichalone is increased, while that of chalone in decreased in the liver of partially hepatectomized rats. In 14 days after partial hepatectomy the activity of both antichalone and chalone decreased, but their ratio is normalized. Thus, the regeneration of the liver in different periods after the operation takes place when the condition of antichalone/chalone system in the organ is unequal.     

Effects of abdominal vagotomy on serum LH concentrations in female rats

Vagotomy on the morning of pro-oestrus did not prevent the pro-oestrous LH surge and rats became oestrous on the following day. However, vagotomized rats then exhibited a period of acyclicity which lasted for 20.4 +/- 1.3 (s.e.m.) days. Food intake and body weight also declined after vagotomy. During the first week after vagotomy, afternoon LH surges generally did not occur, a pattern which was similar in animals pair fed with vagotomized rats. However, pair-fed rats showed oestrous cycles while vagotomized rats were acyclic. At 7 days after vagotomy, LH surges were induced by oestradiol benzoate and progesterone treatment of ovariectomized rats. Vagotomy suppressed the post-ovariectomy increase in serum LH at 7 and 21 days after surgery. These results, combined with those of other studies, suggest impairment of LH release in vagotomized rats.     

Alkaline phosphatase distribution in the inferior vagal ganglion of the cat following vagotomy

Summary The object of this study was to demonstrate sites of alkaline phosphatase activity within the cellular elements of the inferior vagal (nodosal) ganglion of the cat and chronologically observe and describe alterations in enzyme activity following vagotomy.In control tissues alkaline phosphatase activity was localized to the wall of perineuronal blood vessels and the satellite cell cytoplasm which envelops the neuronal perikarya. In the experimental tissues alkaline phosphatase activity was increased in the above locations during the first 20 days following vagotomy then gradually decline to approximate control levels by 60 days post-operatively.The functional significance of changes in alkaline phosphatase activity occurring within an altered metabolic environment induced by vagotomy is discussed.Part of a dissertation submitted in partial fulfillment of the requirements for the degree Doctor of PhilosophySupported by Public Health Service Fellowship 1-Fl-GM-33, 597-01 from the National Institutes of Health