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Comparison of internal maxillary artery ligation versus embolization for refractory posterior epistaxis.

OBJECTIVE: This study examined the advantages and disadvantages of internal maxillary artery (IMA) ligation versus embolization for the treatment of refractory posterior epistaxis. METHODS: Thirty-nine patients underwent 42 procedures for treatment of posterior epistaxis at the University of Cincinnati Medical Center between 1986 and 1994. Complication rates, failure rates, demographics, and the costs of IMA ligation and embolization were compared. A review of 20 studies published between 1973 and 1995 was done to determine the complication and failure rates of IMA ligation and embolization. Finally, a mail survey was used to determine the availability and use of IMA ligation and embolization by urban and rural otolaryngologists in Ohio. RESULTS: Complication and failure rates of IMA ligation and embolization were similar at our institution. In the literature review, IMA ligation had a higher complication rate, but fewer failures. Although the major complication rates were not significantly different, those associated with embolization were often more serious than those associated with IMA ligation. At our institution, the cost of IMA embolization was significantly lower than the cost of IMA ligation. Only 11% of Ohio otolaryngologists in nonurban areas have embolization available to treat posterior epistaxis. CONCLUSION: IMA ligation is more effective than IMA embolization but may be associated with a higher minor complication rate. The major complications that occur with IMA embolization are often more serious. Although IMA embolization was less expensive at our institution, it is unavailable in most nonurban regions in Ohio. Training in the use of IMA ligation for refractory posterior epistaxis should continue in otolaryngology residency training programs despite the increasing availability of embolization at university training centers.

Academic Medical Centers↗

Effects of endoscopic variceal ligation on systemic and splanchnic hemodynamics in patients with cirrhosis.

It has been shown that patients with cirrhosis and portal hypertension have hyperdynamic systemic and splanchnic circulation. This study was designed to assess how endoscopic variceal ligation may influence systemic and splanchnic hemodynamics. Sixteen patients with cirrhosis and esophageal varices were studied. Cardiac output and flow volume of the portal vein and the superior mesenteric artery were determined by means of duplex Doppler ultrasonography. Mean arterial pressure was also recorded. These hemodynamic measurements were performed before and after initial (3 days after initial session) and repeated (7 days after last session) variceal ligation. No significant changes in cardiac output and mean arterial pressure were found after either initial or repeated variceal ligation. Thus, systemic vascular resistance was not modified. In splanchnic hemodynamics, portal vein blood flow significantly increased after initial variceal ligation (27%, P < 0.01) but it returned to the baseline value after repeated variceal ligation. In contrast, superior mesenteric artery blood flow significantly decreased after initial variceal ligation (17%, P < 0.01) and it returned to the baseline value after repeated variceal ligation. Effect of variceal ligation on splanchnic hemodynamics is transient and variceal ligation has very little effect on systemic circulation. Thus, patients with cirrhosis underwent repeated variceal ligation still have abnormal systemic and splanchnic circulation.

Aged↗

Mesenteric lymph duct ligation provides long term protection against hemorrhagic shock-induced lung injury.

Recently we have shown that ligation of the main mesenteric lymph (MLN) duct prior to an episode of hemorrhagic shock (HS) prevents shock-induced lung injury. Yet, ligation or diversion of intestinal lymph immediately prior to injury is not clinically feasible. Diversion of intestinally derived lymph after injury to protect against secondary insults is possible, but it is not known how long the protective effects of lymph ligation would last. Thus, we tested whether ligation of the MLN duct seven days prior to HS would still be protective. Male Sprague-Dawley rats were subjected to laparotomy with or without MLN duct ligation. Seven days later, half of the sham and actual MLN duct ligated animals randomly were selected to undergo HS (30 mmHG for 90 min). The other half of the animals was subjected to sham shock. Lung permeability, pulmonary myeloperoxidase (MPO) activity, and bronchoalveolar fluid (BALF) protein content were used to determine lung injury. Lymphatic division 7 days prior to HS continued to prevent shock induced lung injury as assessed by a lower Evans Blue dye concentration, BALF protein and MPO activity. In addition, there was no evidence of Patent Blue dye in the previously ligated MLN duct. Since ligation of the main mesenteric lymphatic duct continues to protect against shock-induced lung injury 1 week after duct ligation, it is feasible that lymphatic ligation performed after an injury remains protective against certain secondary insults for at least 1 week.

Animals↗

[Morphological changes in major pelvic ganglion neurons and histological structure of bladder using rat model of partial urethral ligation].

Ninety six rats were divided into 4 groups (normal control group (N = 4), ligation group (N = 20), ligation-removed group (N = 36), and sham surgery group (N = 36)). The neuronal size of the 4-week ligated rats returned to normal 6 weeks after removal of the ligation. Rats ligated for 7, 11 and 20 weeks also exhibited a significant increase in the mean area but they could not make a complete recovery after removal of ligation for 6 weeks. Only the rats in the 1- and 4-week ligation groups could recover their neuronal size. Area densities of smooth muscle: connective tissue (ADsc ratio) was calculated using Elastica van Gieson staining sections of bladder strips. When ligation was removed, the ratio dropped and became nearly equal to the value of the sham surgery group. Only the 7-week group showed a lower ADsc ratio than the sham surgery group after the ligation was removed. These findings suggest that the reversibility of neuronal hypertrophy might become irreversible when the period of partial urethral ligation persisted beyond 7 weeks. Irreversible hypertrophy of major pelvic ganglion (MPG) neurons might be greatly related with the irreversibly enlarged fibrous bladder which could not show the same ADsc ratio as was seen in the sham surgery groups.

Animals↗

[Morphological change and reversibility of major pelvic ganglion neurons using rat model of partial urethral ligation].

We made partial urethral ligation in female Wistar rats to evaluate the morphological change and the reversibility of the major pelvic ganglion (MPG) neurons before and after partial urethral ligation. Thirty rats were divided into 4 groups; normal control group (N = 3), ligation group (N = 9), release of ligation group (N = 9), and sham-operated group (N = 9). WGA-HRP (horseradish peroxidase with lectin wheat germ agglutinin) was injected into the right side of the bladder 4 days before the MPG neurons were removed. MPG was examined by the axonal tracer method. Rats with partial urethral ligation for 1 week exhibited a significant increase in the size (419.1 +/- 146.0 microns2) of the mean area of MPG neurons as compared to the normal controls (318.0 +/- 118.6 microns2), but they showed a steady decrease in size (304.2 +/- 118.6 microns2) similar to that in the sham-operated group (310.2 +/- 116.3 microns2) 3 weeks after the removal of the ligation. The rats with partial urethral ligation for 7 weeks and 11 weeks also exhibited a significant increase in the mean area (7w; 484.1 +/- 192.6 microns2, 11w; 549.4 +/- 181.3 microns2), but they did not show complete recovery (7w; 383.3 +/- 159.6 microns2, 11w; 549.6 +/- 279.5 microns2) as compared to the sham-operated group (7w; 324.4 +/- 124.9 microns2, 11w; 345.9 +/- 121.7 microns2) after removal of ligation. Only the 1-week ligation group showed recovery in neuronal size. These findings imply that the neuronal hypertrophy might become irreversible when the period of partial urethral ligation persisted beyond 7 weeks.

Animals↗

Cardiovascular effects of propofol during coronary ligation in anesthetized dogs.

Under different infusion rates in normal hearts and hearts with coronary ligation, the hemodynamic effects of propofol were measured in a coronary artery ligation model in twelve mongrel dogs. Propofol was given by 10 mg/kg intravenous bolus followed by 30 min infusion in succession with 20 mg/kg/hr, 40 mg/kg/hr and 80 mg/kg/hr in both normal hearts and hearts with coronary ligation. The range of blood concentrations in our study is 2.19 +/- 0.56 microgram/ml to 15.78 +/- 3.31 micrograms/ml. After ligation at 1 cm below first diagonal branch of left anterior descending artery (LAD) obvious cardiovascular changes were seen in a few seconds. However, non-significant hemodynamic changes were demonstrated between pre-ligated and 30 min after ligation. With increasing blood propofol concentrations, there was significant negative correlation (p < 0.01) in mean arterial pressure (MAP), cardiac output (CO) and heart rate (HR) but central venous pressure (CVP) and pulmonary arterial occlusion pressure (PAOP) decreased non-significantly with increasing propofol concentrations in both non-ligated and ligated groups. Propofol infusion up to 80 mg/kg/hr did not decrease MAP, CO and systemic vascular resistance (SVR) further in hearts with coronary ligation than normal hearts in our study. SVR and pulmonary vascular resistance (PVR) changed non-significantly between each groups even in blood concentration as high as 15 micrograms/ml. We conclude that propofol depresses myocardial function associated with increasing blood propofol concentrations despite stable SVR and PVR. The hemodynamic effects of propofol were similar in the normal hearts and hearts with coronary ligation.(ABSTRACT TRUNCATED AT 250 WORDS)

Anesthesia↗

Ligation of nonmatching DNA molecule ends.

T4 DNA ligase can promote the in vitro ligation of blunt DNA ends to ends bearing a 2-nucleotide single-stranded protrusion. This was shown by digestion of plasmids pBR322 and pSP71 with the appropriate restriction enzymes followed by recircularization of the plasmids and transformation of Escherichia coli. It could be ruled out that such nonmatching ligations are due to the presence of contaminating nucleases. The efficiency of ligation is of the same order of magnitude as that obtained with blunt end ligations. The interaction of a number of different combinations of blunt and sticky ends, the latter bearing both 3' and 5' protrusions, was investigated. Ligation of nonmatching ends was shown to take place in all cases. Several ligation junctions were sequenced, showing that during the ligation process the 2-nucleotide protrusion is trimmed away. In two instances the ligation event was accompanied by the specific loss of either 3 or 15 nucleotide pairs as well as the protrusion. An intermolecular ligation involving nonmatching ends was also performed, demonstrating that this form of ligation can be usefully employed in molecular cloning experiments.

Base Sequence↗

Heterotropic effects of chloride on the ligation microstates of hemoglobin at constant water activity.

Dimer-tetramer assembly reactions of the 10 CN-met ligation microstates of hemoglobin (Hb) were analyzed as a function of NaCl concentration while maintaining constant water activity by the addition of compensating sucrose. The assembly free energy for fully ligated cyanomet Hb and for fully oxygenated Hb becomes less favorable by 1.8 kcal when [NaCl] is increased from 0.08 to 0.7 M, whereas that of unligated Hb is practically insensitive to changes in [NaCl]. Values of 1.6 and 0.3 mol chloride release were found for the assembly of fully ligated and deoxy Hb, respectively; i.e., a net release of 1.3 mol chloride is coupled to the ligation of tetramers for both oxygen and cyanomet ligation. The ligation-linked salt component at constant water activity was evaluated to be 1.0 mol for the full oxygenation of the Hb tetramer in agreement with the overall value previously reported. When the detailed salt linkages accompanying all 16 stepwise cyanomet ligation reactions were experimentally resolved, only two "chloride" effects were found. The first chloride effect correlates with the ligation steps, which create tertiary constraint, and the second effect is coupled to the six switchpoints of quaternary T-->R transition. The distribution of these chloride effects agrees closely with predictions of the "symmetry rule mechanism." The total chloride release for CN-met ligation is in good agreement with that for oxygenation. Free energy contributions to assembly and cooperativity arising from the osmotic effects of chloride were found to be small for all ligation species.

Allosteric Regulation↗

Neutral thiol as a proximal ligand to ferrous heme iron: implications for heme proteins that lose cysteine thiolate ligation on reduction.

Cysteine plays a key role as a metal ligand in metalloproteins. In all well-recognized cases, however, it is the anionic cysteinate that coordinates. Several cysteinate-ligated heme proteins are known, but some fail to retain thiolate ligation in the ferrous state, possibly following protonation to form neutral cysteine. Ligation by cysteine thiol in ferrous heme proteins has not been documented. To establish spectroscopic signatures for such systems, we have prepared five-coordinate adducts of the ferrous myoglobin H94G cavity mutant with neutral thiol and thioether sulfur donors as well as six-coordinate derivatives such as with CO and, when possible, with NO and O(2). A thiol-ligated oxyferrous complex is reported, to our knowledge for the first time. Further, a bis-thioether ferrous H93G model for bis-methionine ligation, as found in Pseudomonas aeruginosa bacterioferritin heme protein, is described. Magnetic CD spectroscopy has been used due to its established ability in axial ligand identification. The magnetic CD spectra of the H93G complexes have been compared with those of ferrous H175CD235L cytochrome c peroxidase to show that its proximal ligand is neutral cysteine. We had previously reported this cytochrome c peroxidase mutant to be cysteinate-ligated in the ferric state, but the ferrous ligand was undetermined. The spectral properties of ferrous liver microsomal cytochrome P420 (inactive P450) are also consistent with thiol ligation. This study establishes that neutral cysteine can serve as a ligand in ferrous heme iron proteins, and that ferric cysteinate-ligated heme proteins that fail to retain such ligation on reduction may simply be ligated by neutral cysteine.

Circular Dichroism↗

The effect of tubal ligation scoring and sterilization counseling on the request for tubal reanastomosis.

OBJECTIVE: The aim of this study is to emphasize the role of counseling methods that are meant to decrease the request for tubal ligation reversal, such as tubal ligation scoring. METHOD: This study covers 389 patients who were admitted for tubal sterilization to Cukurova University, Faculty of Medicine, Obstetrics and Gynecology Department, between 1 January 1990 and 31 December 1999. We have used the 'Tubal ligation score' on these 389 patients. Four hundred and seventeen patients who underwent bilateral Pomeroy type tubal ligation during cesarean section without having undergone tubal ligation scoring in the same time interval, were accepted as the control group. RESULTS: Laparoscopic tubal ligation (with a Yoon ring) was performed on 368 patients who had a score of 6 or higher. Twenty-one patients who got a score of 6 or lower were recounseled and another family planning method was prescribed to them. None of the 368 patients to whom tubal ligation scoring was done previous to laparoscopic tubal ligation returned to our clinic for tubal reanastomosis. Fifteen of the 417 patients (3.6%) in the control group returned to our clinic for tubal reanastomosis. CONCLUSION: Tubal ligation scoring may decrease the ratio of patients who request a tubal ligation reversal.

Counseling↗

Differential induction of nuclear factor-kappaB and activator protein-1 activity after CD40 ligation is associated with primary human hepatocyte apoptosis or intrahepatic endothelial cell proliferation.

CD40, a tumor necrosis factor receptor superfamily member, is up-regulated on intraheptatic endothelial cells (IHEC) and epithelial cells during inflammatory liver disease, and there is evidence that the functional outcome of CD40 ligation differs between cell types. Ligation of CD40 on cholangiocytes or hepatocytes results in induction of Fas-mediated apoptosis, whereas ligation of IHEC CD40 leads to enhanced chemokine secretion and adhesion molecule expression. We now report that differential activation of two transcription factors, nuclear factor-kappaB (NF-kappaB) and activator protein-1 (AP-1), in primary human hepatocytes or IHEC, is associated with and may explain, in part, the different responses of these cell types to CD40 ligation. CD40 ligation induced a rise in NF-kappaB activity in hepatocytes,which peaked at 2 h and returned to baseline by 24 h; however, IHEC CD40 ligation resulted in a sustained up-regulation of NF-kappaB (>24 h). In hepatocytes, CD40 ligation led to sustained up-regulation of AP-1 activity >24 h associated with increased protein levels of RelA (p65), c-Jun, and c-Fos, whereas no induction of AP-1 activity was observed in IHECs. Analysis of mitogen-activated protein kinase phosphorylation (phospho-extracellular signal-regulated kinase 1/2 and phospho-c-Jun NH(2)-terminal kinase 1/2) and expression of inhibitor kappaBalpha were entirely consistent, and thus confirmed the profiles of NF-kappaB and AP-1 signaling and the effects of the selective inhibitors assessed using electrophoretic mobility shift assay or Western immunoblotting. CD40 ligation resulted in induction of apoptosis in hepatocytes after 24 h, but on IHECs, CD40 ligation resulted in proliferation. Inhibition of (CD40-mediated) NF-kappaB activation prevented IHEC proliferation and led to induction of apoptosis. Selective extracellular signal-regulated kinase and c-Jun NH(2)-terminal kinase inhibitors reduced levels of apoptosis in (CD40-stimulated) hepatocytes by approximately 50%. We conclude that differential activation of these two transcription factors in response to CD40 ligation is associated with differences in cell fate. Transient activation of NF-kappaB and sustained AP-1 activation is associated with apoptosis in hepatocytes, whereas prolonged NF-kappaB activation and a lack of AP-1 activation in IHECs result in proliferation.

Apoptosis↗

Effects of aspirin and prostacyclin on arrhythmias resulting from coronary artery ligation and on infarct size.

1 The effects of pretreatment with aspirin, and of prostacyclin (PGI(2)) infusions, on responses to myocardial ischaemia and infarction produced by ligation of a coronary artery were investigated in conscious rats.2 Surgical preparation, under halothane anaesthesia, consisted of implanting exteriorized aortic and jugular cannulae, ECG leads and a polypropylene/polyethylene occluder for the left anterior descending coronary artery. Ligation of the coronary artery was performed six to nine days after surgery.3 Aspirin pretreatment consisted of 100 mg/kg given intravenously 1 or 36 h before ligation. PGI(2) infusions (10-400 ng kg(-1) min(-1), i.v.) were begun 2 min before ligation and continued for 4 h afterwards.4 ECG, blood pressure, heart rate and arrhythmias were recorded starting 30 min before, and continuing for 4 h after, ligation. Twenty-four hours after ligation, in surviving animals, the heart was removed for estimation of occluded and infarcted zones.5 Some treatments provided antiarrhythmic and other protection in the first 30 min post-ligation. By 4 and 24 h post-ligation, protective effects were lost.6 Both aspirin pretreatment and low doses of prostacyclin reduced arrhythmias occurring within 30 min of ligation. The highest dose of prostacylin (400 ng kg(-1) min(-1)) was arrhythmogenic.7 None of the treatments influenced the amount of cardiac tissue occluded or infarcted by ligation.8 The conclusions from this study in conscious rats were that acute aspirin pretreatment and low doses of infused prostacyclin have limited beneficial actions which are mainly confined to the earliest post-ligation period.

Animals↗

cAMP response element-binding protein activation in ligation preconditioning in neonatal brain.

Perinatal hypoxic-ischemic (HI) brain injury is a major cause of permanent neurological dysfunction in children. An approach to study the treatment of neonatal HI encephalopathy that allows for neuroprotection is to investigate the states of tolerance to HI. Twenty-four-hour carotid-artery ligation preconditioning established by delaying the onset of hypoxia for 24 hours after permanent unilateral carotid ligation rats markedly diminished the cerebral injury, however, the signaling mechanisms of this carotid-artery ligation preconditioning in neonatal rats remain unknown. Ligation of the carotid artery 24 hours before hypoxia provided complete neuroprotection and produced improved performance on the Morris water maze compared with ligation performed 1 hour before hypoxia. Carotid artery ligation 6 hours before hypoxia produced intermediate benefit. The 24-hour carotid-artery ligation preconditioning was associated with a robust and sustained activation of a transcription factor, the cAMP response element-binding protein (CREB), on its phosphorylation site on Ser133. Intracerebroventricular infusions of antisense CREB oligodeoxynucleotides significantly reduced the 24-hour carotid-artery ligation-induced neuroprotection effects by decreasing CREB expressions. Pharmacological activation of the cAMP-CREB signaling with rolipram 24 hours before hypoxia protected rat pups at behavioral and pathological levels by sustained increased CREB phosphorylation. This study suggests that 24-hour carotid-artery ligation preconditioning provides important mechanisms for potential pharmacological preconditioning against neonatal HI brain injury.

Analysis of Variance↗

Atrial natriuretic peptide in portal vein-ligated rats: alterations in cardiac production, plasma level and glomerular receptor density and affinity.

The atrial natriuretic peptide hormonal system is altered to a variable degree in patients with cirrhosis. Portal pressure and portal-systemic shunting are also varied in cirrhosis. We used a portal vein-ligated rat model with predictable portal hypertension to study the effects of portal hypertension alone on the atrial natriuretic peptide hormonal system. Sham-operated rats were used as controls. Mean portal pressure was significantly increased in portal vein-ligated rats (portal vein-ligated rats, 21.7 +/- 0.74 cm H2O; sham-operated rats, 13.7 +/- 0.47 cm H2O; p less than 0.0001). Plasma atrial natriuretic peptide decreased 50% in the portal vein-ligated rats (p less than 0.0001). Atrial natriuretic peptide messenger RNA level was decreased by 40% to 60% in the left and right atria and in the ventricles of portal vein-ligated rats (p less than 0.05 for each chamber). Only one class of glomerular binding site was identified by competitive binding studies. The atrial natriuretic peptide glomerular receptor density increased in the portal vein-ligated rats (portal vein-ligated rats, 1,660 +/- 393; sham-operated 725 +/- 147 fmol/mg protein, p less than 0.02), whereas affinity decreased (portal vein-ligated, 1.69 +/- 0.49; sham-operated, 0.55 +/- 0.12 nmol/L, p less than 0.02). No difference was seen in the amount of cyclic GMP generated by atrial natriuretic peptide stimulation in isolated glomeruli from portal vein-ligated and sham-operated rats.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

[Ear to retina time and ophthalmodynamometry after ligation of the common carotid artery in rabbits (author's transl)].

Unilateral ligation of the common carotid artery was performed in rabbits. Before ligation, immediately thereafter, and 6 weeks later the ophthalmic artery pressure was determined and at the same time a synchronous measurement of the ear to retina time was done on both sides. The results were statistically analyzed (Tables 1-4). Ligation of the right common carotid artery resulted in a highly significant difference in systolic ophthalmic artery pressure between the two eyes of 16.4 mm Hg, and in diastolic pressure one of 13.0 mm Hg. After ligation of the left similar pressure differences of (systolic) 17.8 mm Hg and (diastolic) 15.2 mm Hg were shown. During the following 6 weeks these differences decreased considerably, to 41.5% and 29.2% after ligation on the right and to 33.5% and 36.6% after ligation on the left. The ear to retina time was markedly prolonged on the side of the ligation. This resulted in a highly significant side difference of 0.42 s immediately after ligation on the right common carotid artery and 0.4 s immediately after ligation on the left side. After 6 weeks these differences were only slightly reduced, to 80% and 72.7% respectively. These animal experiments demonstrate clearly that an acute occlusion of one common carotid artery in rabbits can easily be diagnosed by ophthalmodynamometry as well as by synchronous measurement of the ear to retina time. In chronic occlusions determination of the ear to retina time is superior to pressure measurement. This is of particular interest since in these experiments an ophthalmodynamometric method was used that is much superior to the clinical method of ophthalmodynamometry.

Animals↗

Effect of glutamine and bile acid on hepatocyte apoptosis after bile duct ligation in the rat.

Apoptosis is an important process in a wide variety of biologic systems. Cholestasis, or impaired bile formation, occurs in a wide variety of human liver diseases. Retention and accumulation of toxic hydrophobic bile salts in hepatocytes may cause hepatocyte toxicity by inducing apoptosis. In addition, the translocation of bacteria and endotoxin, well documented in patients with obstructive jaundice, contribute to the induction of hepatocyte apoptosis. We hypothesized that oral bile acid replacement, glutamine administration, or both can attenuate or abolish hepatocyte apoptosis. Male Sprague-Dawley rats weighing 250 to 300 g were randomized to four groups (10 in each group). Group 1 underwent a sham operation and was simultaneously treated with normal saline. Group 2 underwent common bile duct (CBD) ligation and was simultaneously treated with normal saline. Group 3 underwent CBD ligation and was simultaneously treated with oral glutamine. Group 4 underwent CBD ligation and was simultaneously treated with oral bile acid replacement. After 3 days (n = 5) and 7 days (n = 5), liver tissues were harvested for histopathologic analysis and apoptosis measurements. When compared with the sham operation group, significantly increased hepatocyte apoptosis and ductular proliferation occurred after CBD ligation for either 3 or 7 days. After administration of either glutamine or bile acid, the increased hepatocyte apoptosis and ductular proliferation after CBD ligation for 3 days were significantly diminished. However, both failed to diminish the changes after CBD ligation for 7 days. Significantly increased hepatocyte apoptosis and ductular proliferation occurred after CBD ligation. The administration of either glutamine or bile acid effectively diminished the hepatocyte apoptosis and ductular proliferation after CBD ligation for 3 days, whereas both failed to show the same effect after CBD ligation for 7 days.

Administration, Oral↗

Glutathione status in liver and plasma during development of biliary cirrhosis after bile duct ligation.

We do not know much about the changes that occur in reduced (GSH) and oxidized (GSSG) glutathione in the development of liver cirrhosis. Therefore, we investigated the glutathione redox system during development of liver cirrhosis after bile-duct ligation in rats. We compared the GSH and GSSG content of liver and plasma between bile-duct-ligated rats and sham-operated controls 6 and 24 h and 5, 15, 23, and 38 days after operation. Compared to controls (x +/- SD: 6.07 +/- 0.52 mumol/g wet wt.), liver GSH significantly increased 24 h (+ 37%) and 5 days (+ 53%) after bile-duct ligation. Thereafter, GSH continuously declined to 4.25 +/- 0.64 mumol/g (-31%; P < 0.001) at the end of the observation period after 38 days. The GSH turnover in 5-day bile-duct-ligated rats with high GSH concentrations was not significantly different than in sham-operated controls (16 nmol/min per g after bile-duct ligation and 15 nmol/min per g in controls). GSSG (211 +/- 42 nmol/g wet wt. in controls) was significantly lower 6 and 24 h after bile-duct ligation (-34% and -43%, respectively). Thereafter, GSSG increased and was about 100% higher than in controls after 23 and 38 days. The relation of GSSG to GSH in liver continuously increased from 3.4 to 20.5% after bile-duct ligation. The course of plasma GSH (9.57 +/- 0.79 mumol/l) paralleled hepatic GSH on a lower level: + 14% at day 5, -41% at day 15 and -51% at the end of the observation period. Plasma GSSG (0.99 +/- 0.31 mumol/l) was inversely related to liver GSSG: there were increased concentrations early after bile duct ligation (day 5: + 91%) and reduced concentrations (-44%) at the end of the observation period. Dynamic changes of the glutathione status occur in the development of liver cirrhosis after bile-duct ligation. These changes are consistent with increased oxidative stress in the liver and a deficit of transporting GSSG from the cells into plasma.

Animals↗

Does level of ligation influence results in a murine biliary obstruction model?

BACKGROUND: Despite advances in perioperative management, patients with extrahepatic biliary obstruction still experience a high rate of complications and death after surgery. The rat is commonly used as an experimental animal for research in obstructive jaundice. Ligation of the rat bile duct high in the liver hilum is assumed to produce a more severe model of biliary obstruction than low ligation. The differences are attributed to the ability of the rat bile duct to dilate. Differences in level of ligation may, thus, explain some discrepancies between studies. MATERIALS AND METHODS: To test this hypothesis, female Lewis rats underwent high ligation (HL), low ligation (LL), and sham celiotomy. Colloidal carbon clearance, bilirubin, total serum bile acids, and hematocrit were measured 12 days later. Liver and spleen weight, presence or absence of ascites, infection, and adequacy of ligation were noted and the liver was processed for routine histology and electron microscopy. RESULTS: Although bilirubin levels were higher after HL than after LL, liver and spleen weight, total serum bile salts, and phagocytic constants K and alpha were not different between these two groups. Gross, histologic, and ultrastructural appearance did not differ between HL and LL groups. CONCLUSION: High ligation causes greater hyperbilirubinemia than low ligation, but does not alter other parameters including phagocytic constants. The present study does not confirm the hypothesis that HL creates a more severe model than LL; therefore, it is unlikely that differences in level of ligation explain variability in results between studies.

Animals↗