Endothelium-dependent and -independent hepatic artery vasodilatation is not impaired in a canine model of liver ischemia-reperfusion injury.

We investigated whether hepatic artery endothelium may be the earliest site of injury consequent to liver ischemia and reperfusion. Twenty-four heartworm-free mongrel dogs of either sex exposed to liver ischemia/reperfusion in vivo were randomized into four experimental groups (N = 6): a) control, sham-operated dogs, b) dogs subjected to 60 min of ischemia, c) dogs subjected to 30 min of ischemia and 60 min of reperfusion, and d) animals subjected to 45 min of ischemia and 120 min of reperfusion. The nitric oxide endothelium-dependent relaxation of hepatic artery rings contracted with prostaglandin F2a and exposed to increasing concentrations of acetylcholine, calcium ionophore A23187, sodium fluoride, phospholipase-C, poly-L-arginine, isoproterenol, and sodium nitroprusside was evaluated in organ-chamber experiments. Lipid peroxidation was estimated by malondialdehyde activity in liver tissue samples and by blood lactic dehydrogenase (LDH), serum aspartate aminotransferase (AST) and serum alanine aminotransferase (ALT) activities. No changes were observed in hepatic artery relaxation for any agonist tested. The group subjected to 45 min of ischemia and 120 min of reperfusion presented marked increases of serum aminotransferases (ALT = 2989 +/- 1056 U/L and AST = 1268 +/- 371 U/L; P < 0.01), LDH = 2887 +/- 1213 IU/L; P < 0.01) and malondialdehyde in liver samples (0.360 +/- 0.020 nmol/mgPT; P < 0.05). Under the experimental conditions utilized, no abnormal changes in hepatic arterial vasoreactivity were observed: endothelium-dependent and independent hepatic artery vasodilation were not impaired in this canine model of ischemia/reperfusion injury. In contrast to other vital organs and in the ischemia/reperfusion injury environment, dysfunction of the main artery endothelium is not the first site of reperfusion injury.

Massive tracheal necrosis due to compression by an innominate artery aneurysm associated with a grade IV Chagasic megaesophagus and chronic duodenal ulcer.

A 49-year-old man suffered necrosis of the cephalad tracheal segment due to compression by an innominate artery aneurysm. A peritracheal abscess, a grade IV chagasic megaesophagus, and a duodenal ulcer were also present. The patient underwent a three-stage surgical treatment, and 7 years later he is doing well, and breathing and eating normally.

Does the length of the interposed segment in the Henley procedure influence duodenogastric reflux? An experimental study.

This study assesses duodenogastric reflux (DGR) using 99mTechnetium-diisopropyl iminodiacetic acid in unoperated dogs and in dogs 28 days after a Billroth II gastrectomy and 28 days after the Henley procedure. Fourteen mongrel dogs were divided randomly into two groups of seven each, according to the length of the interposed jejunal segment used (Group A 10 cm; Group B, 20 cm). All dogs were subjected to a Billroth II gastrectomy, followed by the Henley procedure 30 days later. In Group A, DGR was significantly lower in the preoperative period (median, 0.0%; range, 0.0-0.02%) than after gastrectomy (median, 0.13%; range, 0.08-0.70%) and the Henley procedure (median, 0.12%; range, 0.06-0.22%), but did not differ significantly after gastrectomy and jejunal interposition. In Group B, DGR was significantly higher after gastrectomy (median, 0.15%; range, 0.10-0.64%) than in the preoperative period (median, 0.00%; range, 0.00-0.09%) or than after the Henley procedure (median, 0.00%; range, 0.00-0.7%). DGR did not differ significantly between the preoperative period and after Henley procedure. After jejunal interposition, DGR was significantly higher in Group A than in Group B. The Henley procedure is effective in preventing DGR when the interposed segment is 20 cm in length.

The effect of proximal gastric vagotomy plus duodenoplasty on duodenogastric reflux.

Alkaline reflux gastritis is a clinical syndrome that results from a mucosal injury by duodenal contents. In this study, the amount of duodenogastric reflux was assessed in patients who previously underwent proximal gastric vagotomy (PGV group; n = 11) and PGV plus duodenoplasty (PGV+D group; n = 10) as a treatment for duodenal ulcer. The control group (A) consisted of 11 healthy volunteers without endoscopic abnormalities. A quantitative index of duodenogastric reflux was obtained in each case by determining the percentage of the injected dose of 99mTechnetium-DISIDA that was recovered by continuous aspiration of gastric juice in fasting subjects. In the PGV group, the percentage of administered 99mTechnetium-DISIDA recovered from the stomach (median: 0.69%; range: 0.09%-3.61%) did not differ significantly (P > 0.05) from that of the PGV+D group (median: 0.49%; range: 0.09%-3.91%) and from that of the A group (median: 1.47%; range: 0.22%-3.01%). The results show that proximal gastric vagotomy plus duodenoplasty did not increase duodenogastric reflux.

Lack of correlation between intragastric pressure and early gastric emptying rate after proximal gastric vagotomy.

In order to evaluate the contribution of the impairment of the gastric accommodation to distension to the abnormalities of the gastric emptying of a liquid meal, these functions were evaluated simultaneously in 20 duodenal ulcer patients after proximal gastric vagotomy and in 13 non-operated duodenal ulcer patients. Gastric accommodation was measured by recording intragastric pressure during intragastric instillation of 500 ml 10% dextrose and the gastric emptying of this solution was measured with the double-sample test meal with phenol red as unabsorbable marker. The intragastric volume remaining 10 min after the 500 ml 10% dextrose test meal was significantly (P less than 0.02) smaller in the post-vagotomy patients (range: 60.0 to 580.0 ml; median: 320.0 ml) than in the non-operated patients (range: 220.0 to 540.0 ml; median: 380.0 ml). There was no significant difference between the two groups for the half-life of the test meal in the stomach. Maximal intragastric pressure was significantly higher (P less than 0.02) in post-vagotomy patients (range: 3.3 to 14.5 mmHg; median: 8.7 mmHg) than in non-operated patients (range: 1.8 to 5.5 mmHg; median: 3.8 mmHg). There was no significant correlation between maximal intragastric pressure and volume remaining 10 min after the test meal or half-life values within any group. These results confirm other studies showing that the initial gastric emptying rate of a liquid meal is accelerated and the gastric accommodation to distension is impaired by proximal gastric vagotomy, while overall gastric emptying is not changed.(ABSTRACT TRUNCATED AT 250 WORDS)

Portal flow and mitochondrial function during extrahepatic cholestasis.

This study was designed to determine portal blood flow and mitochondrial and hepatic function during extrahepatic obstruction. Twenty-two male Wistar rats which had undergone bile duct ligation were compared 7 days later to 20 sham-operated controls. Portal flow and mitochondrial respiratory control ratio were reduced by 50% and 35%, respectively (P less than 0.01), and serum alanine-aminotransferase levels increased significantly (P less than 0.01) in the extrahepatic cholestatic group. These results suggest that cholestasis may cause an imbalance between the energy supply and the high demand of the liver leading to a state of partial ischemia.

High chlorpromazine doses and liver function.

The aim of the present study was to evaluate the in vivo effect of high chlorpromazine (CPZ) doses on hepatocellular function. Thirty male Wistar rats weighing 200 to 250 g were divided into two groups: control (C, N = 17), injected ip with saline, and CPZ (N = 13), injected ip with high chlorpromazine doses (initial dose of 30 mg/kg body weight followed by daily doses of 10 mg/kg for 7 days). No significant differences in serum levels of alanine-aminotransferase, alkaline phosphatase and bilirubin or in mitochondrial function (activated and basal respiration and mitochondrial respiration control (activated/basal ratio) were detected between the two groups.

Liver trophism in dogs made diabetic by total pancreatectomy or alloxan administration.

1. In order to evaluate hepatic trophism in diabetic dogs, an experimental study was carried out on 30 adult mongrel dogs of both sexes weighing 11.9 +/- 1.6 kg, divided into three groups: 1) Controls (C) (N = 10), submitted to partial (30%) hepatectomy; 2) PD Animals (N = 10), submitted to partial hepatectomy plus total pancreatectomy with preservation of the duodenum during the same surgical intervention; 3) and AD Animals (N = 10), submitted to partial and simultaneously made diabetic with alloxan. 2. The animals were submitted to an oral glucose tolerance test (OGTT) one day before and on the 7th day after partial hepatectomy to evaluate the severity of diabetes. During the post-hepatectomy period the fasting glycemia values were similar for both diabetic groups (greater than 200 mg%). During OGTT, blood glucose levels of the diabetic groups peaked at 60 min but were significantly higher for the AD than for the PD group. The difference persisted at 120 and 180 min, but was no longer statistically significant. 3. Liver trophism was evaluated by measuring liver RNA content and the nuclear volume of hepatocytes. Both diabetic groups showed significantly lower RNA contents and absence of nuclear hypertrophy compared to partially hepatectomized controls probably because of the severe diabetes induced in these animals.

Hepatic morphology changes after hepatic artery ligation in extrahepatic cholestasis.

The present study was performed to correlate changes in hepatic morphology with hepatic artery ligation (HAL) in the presence of extrahepatic cholestasis (EHC). The study was conducted on 36 male Wistar rats weighing 350 to 400 g, divided at random into four groups of 9 animals each: group I, sham operation (control); group II, HAL; group III, bile duct ligation (BDL); group IV, HAL plus BDL. After seven days, liver fragments were obtained for morphological study. The relative volume of the bile ducts was I > II < III and III > IV (P < 0.05). These data indicate that arterial irrigation is important for the nutrition of the biliary tree. Seventy-six percent of the animals submitted to HAL plus BDL showed hepatic necrosis. In general, the liver probably becomes more dependent on HA flow in the presence of EHC.

Lack of correlation between the sulfobromophthalein test and fatty liver in diabetic dogs.

The present study was performed to evaluate the correlation between fatty liver and liver function in diabetic dogs. Experimental diabetes was induced in 14 dogs by total pancreatectomy or by alloxan administration, and partial (30%) hepatectomy was performed. Diabetic dogs were compared with control dogs (N = 7) subjected only to partial hepatectomy (30%). Control and diabetic dogs were submitted to the sulfobromophthalein (BSP) liver function test. Serum BSP retention was increased in diabetic dogs but there was no correlation with the extent of fatty infiltration of the liver.

Effect of chlorpromazine and biliary drainage on portal blood flow and mitochondrial function during extrahepatic cholestasis.

The present study examines the effect of chlorpromazine and biliary drainage in cholestatic rats. The time course of portal blood flow was studied 24, 48, and 72 h and seven days after bile duct ligation. Portal blood flow decreased after 72 h. Chlorpromazine reduced biliary hydrostatic pressure in sham-operated control rats, but 24-h obstruction was sufficient to prevent this effect in cholestatic rats. The drug ameliorated the mitochondrial and cell membrane function of cholestatic rats before and after drainage. The data present further support for the role of ischemia in cholestasis.

Contribution of intraoperative biliary manometry for the diagnosis of bile duct stones.

Sixty patients with cholecystitis and gallstones, with and without biliary duct calculi, were submitted to intraoperative biliary manometry and cholangiography. The patients were subdivided into two groups of 30: Group A, without biliary duct calculi, and Group B, with biliary duct calculi. The pathology had been diagnosed before surgery for 24 patients in group B (B1), and for 6 (B2), diagnosis was made on the basis of intraoperative manometry which showed higher pressure values than those encountered in the main bile ducts of patients without calculi, and of intraoperative cholangiography. Choledocotomy, which was performed on all 6 patients, confirmed the presence of calculi. When three successive sequences of pressure measurements were performed on the common bile duct of patients with biliary duct stones there was an increase in pressure at 10, 15 and 20 s from the first compared to the third sequence. Intraoperative manometry suggested the presence of biliary duct calculi, which was confirmed by intraoperative cholangiography in the 20% of patients in group B for whom calculi had not been previously diagnosed, and decreased unnecessary choledocotomy.

Integrity of liver inner mitochondrial membrane in rats with extrahepatic cholestasis.

To investigate the effect of extrahepatic cholestasis on integrity of the inner mitochondrial membrane, a study was conducted on two groups of rats: sham-operated control animals (N = 10) and rats subjected to extrahepatic cholestasis (EHC, N = 10) by double ligation of the hepatic duct. The animals were observed for 7 days and then sacrificed. The EHC group presented significantly higher serum levels of alanine aminotransferase, total bilirubins and alkaline phosphatase than the controls (P less than 0.01). Basal mitochondrial respiration (state IV), analyzed separately using either alpha-ketoglutarate or alpha-ketoglutarate + pyruvate as substrates, was similar in the two groups (P greater than 0.01). ADP-activated respiration, state III, diminished significantly in the EHC group. The results show that the decrease in mitochondrial function that has been reported by several investigators to occur in EHC is due to mitochondrial alterations not related to the ability of these organelles to maintain the proton gradient, since the inner mitochondrial membrane continued to be energized throughout the observation period.

Effect of hepatic artery ligation in rats with chronic extrahepatic cholestasis.

Because of the liver's dependence on arterial blood to exert its metabolic functions in cirrhosis of the liver, with or without thrombosis of the portal vein, the interruption of hepatic arterial flow for the palliative treatment of malignant tumors of the liver is counterindicated. However, the effects of arterial devascularization on the cholestatic liver are not fully understood. The objective of the present study was to investigate hepatic alterations due to hepatic artery ligation in rats with chronic extrahepatic cholestasis. Serum alkaline phosphatase, bilirubin and alanine aminotransferase were measured in rats 3 h after sham operation (group A, N = 29) or ligation of the hepatic artery (group B, N = 29). Alanine aminotransferase activity was significantly higher (P less than 0.05) in group B, demonstrating acute hepatocellular damage in animals with chronic extrahepatic cholestasis.

Heparin-induced increase in plasma and serum gamma-glutamyl transpeptidase activity.

gamma-Glutamyl transpeptidase (GGT) activity may be a sensitive index of hepatobiliary dysfunction. GGT activity, however, has been shown to be affected by several factors in different clinical situations. The present study was designed to determine the effect of heparin on serum and plasma GGT activity. Blood samples were collected from 15 normal male Wistar rats weighing 200-250 g for the determination of GGT activity in plasma prepared with heparin (group P(H), N = 10), in serum (group S, N = 15) and in serum with heparin added (group S + H, N = 10). GGT activity was 45.1 +/- 9.5 U/l (mean +/- SD) for serum compared with 161.2 +/- 46.1 U/l for serum plus heparin and 93.3 +/- 30.9 U/l for plasma prepared with heparin. The mean for each group was significantly different from the means for the other groups. These data demonstrate that GGT activity measurements should be made on serum in the absence of heparin, which produces elevated results.

Serum gamma-glutamyl transpeptidase in chronic extrahepatic cholestasis.

Studies in the literature have shown the inhibitory action of bilirubin on serum gamma-glutamyl transpeptidase (GGT) activity. In spite of this, GGT is a sensitive diagnostic indicator, comparable to alkaline phosphatase for the diagnosis of chronic extrahepatic cholestasis (CEHC). To evaluate the relationship of bilirubin, alkaline phosphatase (AP) activity and GGT activity in CEHC we studied 30 patients with CEHC divided into two groups: A, 14 male and female subjects with serum bilirubin levels of 2 to 10 mg/dl, and B, 16 male and female subjects with serum bilirubin levels of 10.1 to 44 mg/dl. Serum GGT activity was measured by diluting serum samples 1:5 and 1:10. GGT values were equivalent in the two groups, there was no correlation between bilirubin and GGT (r = +0.179, P less than 0.01), and there was a significant correlation between GGT and AP (r = +0.627, P less than 0.01). The present results show that, if GGT inhibition by bilirubin did occur, this inhibition was not sufficient to prevent the increase in serum GGT levels and that the sensitivity of GGT as a marker for CEHC is similar to that of alkaline phosphatase.

Inhibitory effect of different anticoagulants on gamma-glutamyl transpeptidase activity.

Increased gamma-glutamyl transpeptidase (GGT) levels have been observed in patients with several types of liver diseases. However, since GGT activity can be inhibited or increased by several substances, the interpretation of these increased levels should be made with caution. The present study was designed to determine plasma GGT activity in blood samples obtained from 24 adult volunteers (13 males and 11 females aged 20 to 40 years) with the use of three different anticoagulants, i.e., ethylenediaminetetraacetic acid (EDTA), calcium fluoride and calcium citrate, and to compare it with GGT activity in serum obtained from the same blood samples. Serum GGT activity was significantly higher than plasma GGT activity (P less than 0.001) and significantly higher in men than in women (P less than 0.05), though plasma GGT activity was similar for both sexes.

Serum transaminase levels in the acute phase of chronic extrahepatic cholestasis.

Serum alanine aminotransferase (ALT) and serum aspartate aminotransferase (AST) levels are normal or discretely increased in rats with chronic extrahepatic cholestasis (CEHC). During the acute phase (first 72 h after biliary obstruction), however, serum transaminase values are quite elevated due to a mechanism not yet fully elucidated. Thus, this is a good experimental model, not involving hepatocellular necrosis, for the study of serum ALT and AST levels during the acute phase of CEHC. Male Wistar rats (250-350 g) were divided into two groups: group A (N = 60) was submitted to sham operation for bile duct ligation (BDL), and group B (N = 60) was submitted to BDL. Thirty and 120 min after BDL there was a 1.5-fold increase in both serum ALT and AST levels compared to sham-operated rats (P less than 0.05). Serum ALT levels were higher than AST levels as early as 30 min after BDL and the highest serum values for both transaminases were observed at 360 min which was also the last value measured. Serum AST levels increased 120 min after BDL, with no further significant increases thereafter.

Effect of hepatic artery ligation on liver metabolism in rats.

The rat is an experimental model of orthotopic liver transplant that does not need arterial revascularization of the transplanted liver. The objective of the present study was to investigate the effect of hepatic artery ligation on hepatic metabolism in rats. After 2, 3 or 24 h of hepatic artery ligation, no significant differences in serum levels of alanine aminotransferase were observed. Bile flow decreased significantly 3 h after arterial ligation (P less than 0.05) and returned to normal after 24 h (P less than 0.05).

[Quantitative evaluation of the duodenogastric reflux after cholecystectomy and transduodenal sphincteroplasty: experimental study in dogs]. / Avaliação quantitativa do refluxo duodenogástrico após colecistectomia e esfincteroplastia transduodenal: estudo experimental em cães.

The role of cholecystectomy and transduodenal sphincteroplasty on duodenogastric reflux (DGR) is still controversial. PURPOSE--To assess the effect of cholecystectomy alone, transduodenal sphincteroplasty alone and cholecystectomy combined with transduodenal sphincteroplasty on bile reflux into the stomach. METHODS--40 dogs were divided into four groups: control group (C) (n = 12), cholecystectomy group (Co) (n = 10), transduodenal sphincteroplasty group (Es) (n = 10) and cholecystectomy plus transduodenal sphincteroplasty group (Co+Es) (n = 8). A quantitative index of DGR was obtained in each case by determining the percentage of the intravenously injected 99m Technetium-DISIDA that was recovered in the gastric juice. RESULTS--The DGR was significantly higher in Co+Es group (mean: 2.26 +/- 2.69%) than in the C group (mean: 0.23 +/- 0.26%), and the Co group (mean: 1.52 +/- 1.77%) and the Es group (mean: 1.23 +/- 1.23%) (p < 0.05). The DGR did not differ significantly between C, Co and Es groups (p > 0.05). CONCLUSION--The results shows that only cholecystectomy plus sphincteroplasty increases duodenogastric reflux.