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Emergency banding ligation versus sclerotherapy for the control of active bleeding from esophageal varices.

Active bleeding varices are a great challenge to endoscopists. In this study, we compared the short-term efficacy and safety of banding ligation with injection sclerotherapy in the arresting of active bleeding from esophageal varices. Seventy-one cirrhotic patients with active variceal bleeding were randomized to receive banding ligation (37 patients) or sclerotherapy (34 patients) immediately after endoscopic examinations. Primary success rate (bleeding stopped for 72 hours) was 97% in the ligation group and 76% in the sclerotherapy group (P = .009). The efficacy of ligation was similar to sclerotherapy in the control of oozing varices (100% vs. 89%, P = .23), whereas ligation was superior to sclerotherapy in the control of spurting varices (94% vs. 62%, P = .012). The requirement of vasoconstrictors after emergency endoscopic treatment was lower in the ligation group than in the sclerotherapy group (11% vs. 41%, P = .007). Treatment failure within 1 month was 8% in the ligation group vs. 30% in the sclerotherapy group (P = .02). Blood transfusion requirements were significantly lower in the ligation group than in the sclerotherapy group (3.2 +/- 1.2 vs. 4.5 +/- 1.8 units, P < .01). Rebleeding rate within 1 month was 17% in the ligation group and 33% in the sclerotherapy group (P = .19). Significant complications were encountered in 5% of the ligation group and 29% of the sclerotherapy group (P = .007). Mortality rates within 1 month were 19% in the ligation group and 35% in the sclerotherapy group (P = .19). Banding ligation and sclerotherapy were comparable in the arresting of oozing varices, whereas ligation was superior to sclerotherapy in the control of spurting varices. Patients treated with ligation required fewer vasoconstrictors and fewer transfusion units than patients treated with sclerotherapy. Furthermore, banding ligation was associated with a lower complication rate than sclerotherapy.

Adult↗

Renal vasoactive mediator generation in portal hypertensive and bile duct ligated rats.

BACKGROUND/METHODS: Vasoactive substances may have a role in the pathogenesis of functional renal abnormalities in patients with cirrhosis. We determined renal vasoactive mediators in rats with portal hypertension since the balance in each part of the kidney between the vasodilator activity of prostaglandin E2 and the vasospastic activity of thromboxane A2, leukotriene B4, leukotriene C4, endothelin-1 and platelet activating factor may determine renal function. Rats with partial portal vein ligation (n = 7), complete bile duct ligation (n = 6) and sham operated (n = 10) were studied. Three weeks following surgery renal function tests, including fractional excretion of sodium [Fe(Na)] were measured. Rats were anesthetized, splenic pulp pressure was measured, kidneys were removed, and cortex, medulla and papilla were separated and homogenized for determination of prostaglandin E2, thromboxane B2, leukotriene B4, leukotriene C4 and endothelin-1 by radioimmunoassay (ng/g) and platelet activating factor activity (pg/10 mg) by platelet aggregation. RESULTS: Pulp pressure was > 13 mmHg in portal vein ligated and bile duct ligated and 6 mmHg in sham operated rats. In bile duct ligated rats there was a 70% decrease in Fe(Na) and a significant decrease in cortical and papillary prostaglandin E2, whereas cortical thromboxane B2 and platelet activating factor activity in the cortex, medulla and papilla were double that of sham operated rats. A similar but insignificant trend of changes was found in portal vein ligated rats. Medullary leukotriene B4 was significantly decreased in bile duct ligated rats. Papillary leukotriene B4 was not detected in bile duct ligated and portal vein ligated rats. Renal leukotriene C4 generation in the three groups was either unchanged (papilla) or beyond detection (cortex and medulla). Medullary and papillary endothelin-1 in portal vein ligated and bile duct ligated rats were 178%-130% higher than in sham operated rats. A significant negative correlation was found between Fe(Na) and cortical and medullary thromboxane B2 generation and medullary platelet activating factor activity. CONCLUSIONS: 1) In bile duct ligated rats enhanced intrarenal generation of thromboxane A2 and platelet activating factor may contribute to decreased renal sodium excretion. 2) The role of decreased intrarenal prostaglandin E2 and increased intrarenal endothelin-1 content in bile duct ligated rats is not yet understood. 3) Renal leukotriene generation is either decreased or undetected in portal vein ligated and bile duct ligated rats.

Animals↗

Mini-detachable snare ligation for the treatment of esophageal varices.

BACKGROUND: We manufactured and studied the usefulness of a newly designed mini-detachable snare in the treatment of esophageal varices. The use of a multiple rubber band ligator, although generally effective and well tolerated, has certain limitations, including high cost, reduced visual field, and inadvertent band release. METHODS: We performed a prospective randomized controlled trial of the use of mini-detachable snare ligation vs. multiple band ligation in patients with recent or active esophageal variceal bleeding. The outcomes assessed were immediate hemostasis and rates of recurrent bleeding, eradication, and recurrence. RESULTS: From March 1997 to October 1998, 103 patients were entered into this trial; 46 underwent mini-detachable snare ligations and 57 multiple band ligations. Among patients with active bleeding, hemostasis was achieved in 6 of 7 (86%) in the mini-detachable snare ligation group and 11 of 13 (85%) in multiple band ligation group. Recurrent bleeding after initial treatment occurred in 2 of 46 (5.5%) in the mini-detachable snare ligation group and 3 of 57 (5.3%) in the multiple band ligation group. Esophageal varices were eradicated or reduced to grade I in 4.8 +/- 2.1 and 4.5 +/- 1.9 sessions in the mini-detachable snare ligation group and multiple band ligation group, respectively. The recurrence rate was 5 of 46 (11%) and 6 of 57 (11%) in the mini-detachable snare ligation group and multiple band ligation group during a follow-up period of 6 and 16 months, respectively. No serious complication occurred in either group. CONCLUSION: The mini-detachable snare is a new device that provides safe and effective treatment for esophageal varices that is comparable to multiple band ligation.

Adolescent↗

Bronchial ligation enhances murine fetal lung development in whole-organ culture.

Evidence exists from both congenital anomalies and animal models that normal fetal lung development is dependent on maintenance of fluid pressure within the developing "airways." Fetal tracheostomy, allowing free egress of airway fluids, results in lung hypoplasia, indicating that some airway distending pressure is required for normal lung development to occur. In contrast, fetal tracheal ligation, which increases fetal airway pressure, reverses lung hypoplasia in animal models. The authors' experiments test the hypothesis that large airway obstruction accelerates the development of murine lungs in vitro in whole-organ culture. Fetuses from time-dated pregnant CD-1 mice at day 14 of gestation were removed (term, 20 days), and the lungs were excised. The left bronchus of each lung was ligated (n = 26), after which the left lung was isolated and cultured at 37 degrees C (95% air, 5% CO2) in BGJb media supplemented with vitamin C and antibiotics. Some fetal lungs were cultured under similar conditions without bronchial ligation (n = 11). After 7 days in culture, the lungs were taken for various analyses. The lungs were fixed in either formaldehyde and processed for paraffin embedding for light microscopic evaluation and morphometric data collection, or were freshly minced and aliquots taken for total protein and DNA content. Several more ligated and unligated lungs were processed for ultrastructural analysis. Morphometric analysis on transverse sections of lungs showed significant differences in the lung tissue size, thickness, epithelial cell height, luminal areas, perimeters, and total number of airspaces (airway + primordial alveolar airspaces). It was evident that bronchial ligation promoted lung development. The ligated lungs displayed thinning of the primordial alveolar walls with cuboidal epithelial cells. The total number of airspaces per field was lower for better developed ligated lungs because of the increased area of airspaces compared with that of the unligated lungs. The dorsoventral tissue thickness (in micrometers) of the ligated lungs was significantly greater than that of the unligated lungs (124.1 +/- 7.0 v 89.6 +/- 8.0); the average outer perimeter of the primordial alveolar airspaces was greater for ligated lungs (404.56 +/- 19.0 microns v 256.85 +/- 17.0 microns). Similarly, the luminal diameter of the spaces of ligated lungs was almost double that of the unligated lungs (38.0 +/- 2.0 microns v 20.3 +/- 2.0 microns), as was the luminal surface area. The morphometric data, which suggest enhanced maturation of the ligated lungs, are supported by results of ultrastructural studies. Ligated lungs had significantly more lamellar bodies. Although total protein and DNA content were greater among the ligated lungs, the protein/DNA ratios did not differ among the groups. The intraluminal pressure (airway pressure) of ligated lungs was 2.9 mm Hg and 3.1 mm Hg at 2 and 4 days in organ culture; the respective pressures for unligated lungs were 1.0 mm Hg and 0.8 mm Hg. These data support the hypothesis that mechanical distending pressure resulting from airway obstruction not only improves pulmonary architecture but also accelerates lung development in vitro. Although these effects have been seen in in vivo models, this is the first proposed in vitro organ culture model. This model may prove to be a powerful tool for the study of molecular mechanisms of mammalian lung development with respect to mechanical and chemical (cytokines, hormones) stimuli.

Airway Obstruction↗

Prospective randomized trial of endoscopic sclerotherapy versus variceal band ligation for esophageal varices: influence on gastropathy, gastric varices and variceal recurrence.

BACKGROUND/AIMS: Endoscopic variceal ligation and endoscopic sclerotherapy are both recommended for the prevention of variceal rebleeding. To compare their efficacy, their influence on gastric varices and the development of portal gastropathy, 95 patients with variceal bleeding were studied. METHODS: The patients were randomized to receive weekly endoscopic sclerotherapy using alcohol (n=48) or endoscopic variceal ligation (n=47). The endoscopic sclerotherapy and endoscopic variceal ligation groups were comparable in etiology, severity of liver disease and grade of varices. RESULTS: In the arrest of acute bleed, endoscopic sclerotherapy and endoscopic variceal ligation were comparable (86% vs. 80%, p=ns). Endoscopic variceal ligation as compared to endoscopic sclerotherapy, obliterated esophageal varices in fewer sessions (4.1+/-1.2 vs. 5.2+/-1.8, p<0.01) and a shorter time (4.4+/-1.3 vs. 6.9+/-3.4 wk, p<0.01). Three (6.4%) patients bled after endoscopic variceal ligation and 10 (20.8%) after endoscopic sclerotherapy (p<0.05). The actuarial percentage of variceal recurrence during a follow-up of 8.5+/-4.4 months, was higher after endoscopic variceal ligation than endoscopic sclerotherapy (28.7% vs 7.5%, p<0.05). Esophageal stricture formation after endoscopic sclerotherapy occurred in five (10.4%) patients, but in none after endoscopic variceal ligation. Significantly more patients developed gastropathy after endoscopic sclerotherapy than ligation (20.5% vs. 2.3%; p=0.02). Endoscopic sclerotherapy (52%) and endoscopic variceal ligation (59%) were equally effective in obliterating the lesser curve gastric varices. Six patients died: three in each group. CONCLUSIONS: (i) Endoscopic sclerotherapy and endoscopic variceal ligation were equally effective in controlling acute bleed; (ii) endoscopic ligation achieved variceal obliteration faster and in fewer treatment sessions; (iii) endoscopic variceal ligation had a significantly lower rate of development of portal gastropathy and rebleeding, (iv) while both techniques influenced gastric varices equally, there was significantly higher esophageal variceal recurrence after endoscopic variceal ligation than sclerotherapy.

Adult↗

Comparison of endoscopic variceal ligation and nadolol plus isosorbide-5-mononitrate in the prevention of first variceal bleeding in cirrhotic patients.

BACKGROUND: Both drug therapy and banding ligation are widely used in the prevention of first variceal bleeding. This study compared the efficacy and safety of band ligation vs. combination of beta-blocker and nitrate for the prevention of first bleeding in patients with cirrhosis and high-risk esophageal varices. METHODS: A total of 61 patients with cirrhosis with moderate or severe esophageal varices associated with red color signs but without history of variceal bleeding were randomized to band ligation (30 patients) or treatment with nadolol plus isosorbide-5-mononitrate (ISMN) (31 patients). In the ligation group, multiband ligator with 4 elastic bands was applied during each session. Ligation was repeated at intervals of 4 weeks until variceal obliteration was achieved. In the combination group, the dose of nadolol was sufficient to reduce the pulse rate by 25%. ISMN 1 tablet 20 mg qd or bid was administered. RESULTS: Both groups were similar in baseline characteristics. In the ligation group, variceal obliteration was achieved in 24 patients (80%), at a mean of 3.2 +/- 0.9 ligation sessions and 11.7 +/- 3.2 elastic bands. In the combination group, the mean daily doses of nadolol and ISMN administered were 40 +/- 14 mg and 40 +/- 12 mg, respectively. During a median follow-up of approximately 23 months, 5 patients (17%) in the ligation group and 8 patients (26%) in the combination group had upper-gastrointestinal bleeding (p = 0.53). Esophageal variceal bleeding occurred in 3 patients (10%) in the ligation group and 6 (19%) in the combination group (p = 0.42). By multivariate Cox analysis, presence of ascites was the only factor predictive of variceal bleeding. Minor complications were noted in 5 patients (17%) in the ligation group and 3 (10%) in the combination group (p = 0.47). Eight patients in the ligation group and 6 in the combination group died (p = 0.49). One (3%) patient in the ligation group and 3 (10%) in the combination group died of uncontrollable variceal bleeding. CONCLUSION: Our preliminary results suggest that endoscopic variceal ligation is similar to the combination of nadolol plus ISMN with regard to effectiveness and safety in the prevention of first variceal bleeding in patients with cirrhosis.

Adult↗

Carotid ligation for the treatment of carotid artery aneurysms. Pre- and peroperative studies of the cerebral blood flow with an intravenous isotope technique.

Carotid ligation was performed in a series of 30 consecutive cases of infraclinoid aneurysms, of which 6 had not ruptured, and 9 cases of supraclinoid aneurysms. Fifteen of the ruptured aneurysms were operated on before, and 18 after, the eleventh day after bleeding. The internal carotid artery was primarily ligated in four cases, with two deaths, and in one case lasting hemiparesis occurred. In the rest of the cases, the common carotid artery was primarily ligated without operative mortality. After varying intervals, the internal carotid artery was ligated both in the neck and intracranially in 25 cases. In three cases late complications occurred due to embolus and thrombosis, resulting in one death. In four cases there were transient symptoms caused by insufficient cerebral circulation. The cerebral circulation was investigated in 23 cases using an intravenous isotope technique before and after ligation of the common carotid artery. In each of the cases the circulatory values were sufficient, with a slight diminishing of the flow on the ligated side. After ligation of the internal carotid artery at a later stage the flow in both hemispheres increased. This finding has been interpreted as being due to the interruption by internal carotid ligation of the retrograde internal carotid flow that occurs after common carotid ligation. In five cases aorto-cervical angiography was performed some months after ligation of the common carotid artery, and in four a retrograde flow in the internal carotid artery on the ligated side was shown. In accordance with the results obtained suggestions are made for carotid ligation in the treatment of carotid aneurysms not accessible for neck ligation.

Adult↗

Endoscopic ligation vs. nadolol in the prevention of first variceal bleeding in patients with cirrhosis.

BACKGROUND: The value of band ligation for prevention of the first episode of variceal bleeding has not been fully evaluated. This study compared the efficacy and safety of band ligation vs. treatment with a beta-blocker for the prophylactic prevention of first bleeding in patients with cirrhosis and high-risk esophageal varices. METHODS: A total of 100 patients with cirrhosis and endoscopically determined high-risk esophageal varices but no history of bleeding were randomized to band ligation (50 patients) or treatment with nadolol (50 patients). In the ligation group, two to 4 elastic bands were deployed during each session. Ligation was repeated at intervals of 3 to 4 weeks until variceal obliteration was achieved. In the nadolol group, the dose of the drug, administered once daily, was sufficient to reduce the pulse rate by 25%. RESULTS: In the ligation group, variceal obliteration was achieved in 41 patients (82%), at a mean of 2.7 (1.1) ligation sessions. In the nadolol group, the mean daily dose of nadolol administered was 60 (20) mg. During follow-up (median approximately 22 months), 10 patients (20%) in the ligation group and 16 (32%) in the nadolol group had upper-GI bleeding (p=0.23). Esophageal variceal bleeding occurred in 5 patients (10%) in the ligation group and 9 (18%) in the nadolol group (p=0.31). By multivariate Cox analysis, Child-Pugh class was the only factor predictive of variceal bleeding. Minor complications were noted in 9 patients (18%) in the ligation group and 4 (8%) in the nadolol group (p=0.35). No serious complication was encountered. Twelve patients in the ligation group and 11 in the nadolol group died (p=0.62). One patient in the ligation group and 3 in the nadolol group died from uncontrollable variceal hemorrhage. CONCLUSIONS: Variceal ligation is as effective and as safe as treatment with nadolol for prevention of first variceal bleeding in patients with cirrhosis.

Adult↗

The impact of internal spermatic artery ligation during laparoscopic varicocelectomy on recurrence rate and short post operative outcome.

OBJECTIVE: To prospectively compare the recurrence rate and short postoperative outcome after randomized laparoscopic varix ligation with internal spermatic artery (ISA) preservation versus laparoscopic varix ligation with ISA ligation. MATERIAL AND METHODS: Twenty-five patients with 35 varicocele who required varix ligation for infertility in 13 patients, scrotal pain in 15 patients and scrotal swelling in 2 patients who underwent one of two procedures: laparoscopic varix ligation with ISA prservation (Group A) or laparoscopic varix ligation with ISA ligation (Group B) were postoperatively evaluated for short post operative outcome and underwent percutaneous spermatic venograms to detect recurrence. Fisher's Exact Test was used for statistical analysis. RESULTS: Recurrence through parallel collaterals was noted in 39% and 5.9% in Group A and Group B respectively as demonstrated on percutaneous spermatic venous venography (PSV) (statistically significant p = 0.0408). Preoperative pain completely resolved in all patients in Group B and persisted in 45% in Group A. However, this was not statistically significant (p = 0.088). No testicular atrophy or hydrocele formation was noted in either group. CONCLUSIONS: Laparoscopic varix ligation with ISA ligation has lower recurrence rate than laparoscopic varix ligation without ISA ligation and may provide better varicocele related pain control with no increase in hydrocele or testicular atrophy rate. We recommend ISA ligation routinely during laparoscopic varix ligation.

Arteries↗

A prospective, randomized trial of sclerotherapy versus ligation in the management of bleeding esophageal varices.

We conducted a prospective, randomized trial comparing sclerotherapy and ligation in 120 patients with acute bleeding of esophageal varices. All the patients were cirrhotic, 59 received sclerotherapy, and 61 received ligation. Treatment was repeated regularly until the varices were obliterated. The mean follow-up period was 295 +/- 120 days and 310 +/- 105 days for the sclerotherapy and ligation groups, respectively. The control of active bleeding was 12/15 (80%) in the sclerotherapy group and 18/19 (94%) in the ligation group (P = .23). The numbers of treatment sessions required to achieve variceal obliteration were 6.5 +/- 1.2 in the sclerotherapy group and 3.8 +/- 0.4 in the ligation group (P < .001). Recurrent bleeding from the gastrointestinal tract was 51% in the sclerotherapy group compared with 33% in the ligation group (P < .05). Recurrent bleeding from esophageal varices was 36% in the sclerotherapy group and 11% in the ligation group (P < .01). However, bleeding from ectopic varices and congestive gastropathy was less common in the sclerotherapy group (7%) than in the ligation group (18%) (P = .05). Significant complications were encountered in 19% of the sclerotherapy group and in 3.3% of the ligation group (P < .01). Comparison of Kaplan-Meier estimates of time to death of both groups showed a significantly lower mortality in the ligation group (P = .011). Both sclerotherapy and ligation can effectively arrest active bleeding from esophageal varices. However, ligation is more effective than sclerotherapy in decreasing the risk of rebleeding from esophageal varices with fewer complications. Ligation can also achieve obliteration of esophageal varices more rapidly than sclerotherapy.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Prophylactic banding ligation of high-risk esophageal varices in patients with cirrhosis: a prospective, randomized trial.

BACKGROUND/AIMS: Injection sclerotherapy has been used to prevent the first episode of variceal hemorrhage, but the results are controversial. The value of banding ligation in the prophylaxis of the first episode of variceal bleeding has not yet been completely evaluated. This study was conducted to determine whether prophylactic banding ligation is beneficial for cirrhotic patients with high-risk esophageal varices. METHODS: A total of 127 cirrhotic patients with endoscopically-assessed high-risk esophageal varices but no history of bleeding were randomized to undergo banding ligation (64 patients) or to serve as controls (63 patients). Ligation was performed at 3-week intervals until variceal obliteration was obtained. RESULTS: During a median follow-up of 29 months, 14 patients (21.8%) in the ligation group and 22 patients (34.9%) in the control group experienced upper gastrointestinal bleeding (p = 0.15). Variceal bleeding occurred in eight patients (12.5%) in the ligation group and 14 patients (22.2%) in the control group (p = 0.22). Blood transfusion requirements were fewer in the EVL group than in the control group (0.6+/-0.4 units vs. 1.2+/-0.8 units, p<0.001). Furthermore, variceal bleeding was significantly reduced in Child-Pugh class B patients treated with ligation compared with the control group (p<0.05). Sixteen patients (25%) in the ligation group and 23 patients (36.5%) in the control group died. Comparison of Kaplan-Meier estimates of time to death for the two groups did not show significant differences (p = 0.19). More patients died of uncontrollable variceal bleeding in the control group (7 patients, 11%) than in the ligation group (3 patients, 4.7%) (p = 0.15). CONCLUSIONS: Although prophylactic ligation did not significantly reduce the first episode of bleeding from esophageal varices in cirrhotic patients with high-risk esophageal varices, a subgroup of patients (Child-Pugh class B) had a reduced frequency of the first episode of esophageal variceal bleeding after prophylactic banding ligation. Furthermore, there was a trend of reducing mortality from variceal bleeding in patients receiving prophylactic ligation. Prophylactic ligation is a promising treatment, but requires further investigation.

Constriction↗

Resistance to sliding of self-ligating brackets versus conventional stainless steel twin brackets with second-order angulation in the dry and wet (saliva) states.

The frictional properties of conventional stainless steel brackets that were coupled with rectangular stainless steel archwires and ligated with stainless steel ligature wires and the frictional properties of closed self-ligating brackets coupled with the same archwires were compared in terms of second-order angulation. The slides of these self-ligating brackets passively restrained the archwires within the slots. As a control, the frictional properties of the opened self-ligating brackets, which were ligated with stainless steel ligature wires, were measured. The resistance to sliding of the conventional brackets and the opened self-ligating brackets were measured at ligation forces ranging from 200 to 600 cN and at angles from -9 degrees to 9 degrees. The resistances to sliding of the closed self-ligating brackets were measured at the same angles, but no external ligation forces were applied. In the passive configuration, the conventional brackets exhibited similar frictional resistance as the opened self-ligating brackets, whereas the closed self-ligating brackets exhibited no friction. In the active configuration, all brackets exhibited increased resistance to sliding as the angulation increased. At all angles, the resistances to sliding of the closed self-ligating brackets were lower than those of the conventional brackets because of the absence of a ligation force when the slide restrained the archwire.

Dental Stress Analysis↗

Expression of gastrin and transforming growth factor-alpha during duct to islet cell differentiation in the pancreas of duct-ligated adult rats.

In adult rats islet cell neogenesis can be stimulated by partial duct ligation. Duct to islet cell differentiation is thought to be regulated by growth factors such as gastrin and transforming growth factor-alpha (TGF alpha). To test this hypothesis, we examined the expression of gastrin and TGF alpha at the mRNA and protein level in pancreatic tissue following partial duct ligation. Pancreatic specimens were investigated on days 3, 5, 7 and 14 after duct ligation by means of non-isotopic in situ hybridization, immunocytochemistry and Western blotting. Gastrin mRNA was strongly expressed in newly developed duct-like cell structures in the ligated tail portion of the pancreas before the period of pronounced islet cell neogenesis (days 5 and 7), and immunostaining for gastrin peptides was positive at days 5-7. In the non-ligated head portion and in control pancreases, gastrin was not expressed. Expression of TGF alpha was found to be increased in the ligated tail portion of the pancreas on day 3 and particularly on day 5, while there was no enhanced signal in the non-ligated part. Western blotting revealed two different TGF alpha isoforms (18 kDa and 42 kDa) in the ligated tail part and three isoforms (18 kDa, 24 kDa and 42 kDa) in the non-ligated head part and in untreated pancreases. The induction of gastrin and TGF alpha expression preceded the peak in the bromodeoxyuridine pulse labelling index of beta cells, known from a previous study to occur on day 7. We conclude that pancreas duct ligation induces the overexpression of gastrin and TGF alpha in the first days following ligation. Since ductal cells are known to give rise to endocrine cells after duct ligation, gastrin and TGF alpha may play a role as growth factors in islet neogenesis.

Animals↗

Characterization of mechanisms causing hypoalbuminemia in rats with long-term bile duct ligation.

Albumin kinetics and albumin synthesis were studied in rats with chronic bile duct ligation and compared with pair-fed control rats. The plasma albumin concentration was significantly reduced in bile duct ligated rats as compared to control rats, averaging 35 +/- 1 vs 40 +/- 2 g/l after 2 weeks and 28 +/- 3 vs 38 +/- 5 g/l after 4 weeks of bile duct ligation. Two weeks after bile duct ligation, the transcapillary escape rate of albumin was increased by 60% in bile duct ligated rats, whereas the plasma volume was unchanged. Albumin synthesis expressed as a fraction of total liver protein synthesis, as assessed by the 'flooding' dose method using [3H]phenylalanine, was decreased by 46% in bile duct ligated rats. However, absolute albumin synthesis expressed per 100 g body weight was not different from control rats. Four weeks after bile duct ligation, the transcapillary escape rate of albumin was no longer different, whereas the plasma volume was increased by 38% in bile duct ligated rats. At this time point, albumin synthesis as a fraction of total liver protein synthesis was decreased by 60% in bile duct ligated rats, and absolute albumin synthesis expressed per 100 g body weight averaged 80 +/- 8 vs 53 +/- 12 mg/(day x 100 g) in control and bile duct ligated rats (p < 0.05). The hepatic steady-state levels of albumin mRNA determined by Northern blot analysis were decreased in bile duct ligated rats at both 2 and 4 weeks after surgery. The studies suggest that reduced plasma albumin concentrations in bile duct ligated rats are caused by increased capillary permeability and lack of compensatory increase in albumin synthesis 2 weeks, and by increased plasma volume and decreased albumin synthesis 4 weeks after surgery.

Animals↗

Carotid artery and jugular vein ligation with and without hypoxia in the rat.

A continuing concern about the use of extracorporeal membrane oxygenation (ECMO) is the cannulation of the common carotid artery or the internal jugular vein. The authors investigated the changes that might occur in the brain with neck vessel ligation in the normal and the hypoxic rat. Two groups of 60 rats each were studied. The first group was divided into three subgroups of 20 animals each. Subgroup 1 (HH) was hypoxic both 24 hours before and 24 hours after operation. Subgroup 2 (HN) (the ECMO model) was hypoxic before operation and recovered for 24 hours in room air. Subgroup 3 (NN) underwent the entire procedure in room air. For each oxygen environment, four different operations were performed: carotid artery ligation, jugular vein ligation, carotid artery and jugular vein ligation, and dissection of the vessels without ligation (sham). Thus each subgroup was further divided into four sub-subgroups based on the operation performed. Rats were again anesthetized after a 24-hour recovery period and killed using low, blunt cervical dislocation. In the first group of 60 rats, the skull was opened and the brain was carefully removed from the cranial vault and placed in a fixative. The brains were placed in a small magnetic resonance imaging (MRI) head coil in groups of five and scans were obtained to provide T1 and T2 images that correlated with histological sections. MRI scans were reviewed in random, blinded fashion by an imager unaware of how these animals had been treated. The brains were then sectioned coronally at six corresponding levels: frontal, mid and posterior cerebrum, midbrain, pons, and medulla. Histological examination was performed in blinded fashion. The number of lesions (usually ischemic as noted by a decrease in the number of neurons) was totaled for each area of the brain. There were no differences that were consistent or statistically significant in the MR images of brains removed from the head, although it would appear that rats with jugular vein and carotid artery ligation were relatively protected. In the HN group jugular vein ligation was worst, and adding carotid artery ligation was best. In the histological studies the NN group had significantly more lesions than the HH group (P < .01). The second group of 60 rats was divided and treated as the first group in all respects except that MRI was conducted immediately after death on intact heads, and no histological studies were performed. This was done to control for lesions that might have been produced by removal of the brains from the skulls. In this group all findings were right sided. One animal in the HN group showed midcerebral white matter edema after jugular and carotid ligation. Focal anterior cerebral edema was seen in another animal (HH) after isolated carotid ligation. An occipital infarct was found in one animal (HH) after both carotid and jugular ligation. The authors conclude that neck vessel ligation in the hypoxic or normoxic rat causes only occasional and sporadic brain injury much as is seen clinically in newborn ECMO patients.

Animals↗

Surgical left atrial appendage ligation is frequently incomplete: a transesophageal echocardiograhic study.

OBJECTIVES: This study sought to determine the incidence of incomplete ligation of the left atrial appendage (LAA) during mitral valve surgery. BACKGROUND: Ligation of the LAA to prevent future thromboembolic events is commonly performed during mitral surgery. However, success in completely excluding the appendage from the circulation has never been systematically assessed. METHODS: Using transesophageal Doppler echocardiography, we studied 50 patients who underwent mitral valve surgery and ligation of the LAA. Thirty patients were studied immediately postoperative, and 20 patients were studied 6 days to 13 years after surgery. Incomplete ligation was detected by demonstrating a color jet traversing the separation between the left atrial body and appendage. RESULTS: Transesophageal echocardiography detected incomplete LAA ligation in 18 of 50 (36%) patients. The incidence of incomplete ligation was not significantly different between patients studied immediately postoperative and patients studied at various times after surgery. Type of mitral surgery (repair vs. replacement), operative approach (sternotomy vs. port access), left atrial size or degree of mitral regurgitation did not significantly correlate with the incidence of incomplete appendage ligation. However, the power to detect a significant difference in left atrial size was only 64%. Spontaneous echo contrast or thrombus was identified within appendages in 9 of 18 (50%) patients with incomplete ligation, while 4 of these 18 (22%) patients had thromboembolic events. CONCLUSIONS: Surgical LAA ligation is frequently incomplete. The similar incidence of incomplete ligation detected immediately postoperative and at various times thereafter suggest that this results from an intraoperative phenomenon rather than from gradual dehiscence of sutures over years. The incidence of incomplete left atrial ligation was unrelated to type of surgery, surgical approach, left atrial size or degree of mitral regurgitation. Residual communication between the incompletely ligated appendage and the left atrial body may produce a milieu of stagnant blood flow within the appendage and be a potential mechanism for embolic events.

Adult↗

Mechanisms of gastric acid secretion after pylorus and oesophagus ligation in the rat.

1. The effect of vagotomy on gastric acid secretion was studied in chronic gastric fistula rats at various times after denervation. In these rats basal and pentagastrin-induced acid output was permanently reduced. Thus, the magnitude of the acid response to pentagastrin in the conscious fistula rat is dependent upon an intact vagus. 2. The acid response to pylorus ligation in vagally intact rats was unaffected by drainage of the stomach and therefore not caused by distension. Bilateral vagotomy, performed simultaneously with the ligation, completely abolished acid secretion, while unilateral vagotomy reduced the acid output by half. Hence, in innervated rats, an intact vagal impulse flow appears to be essential for the acid response to pylorus ligation. When the pylorus ligation was performed 2-8 weeks after truncal vagotomy, the acid output showed a progressive return towards pre-denervation values. In the denervated rats the acid response to pylorus ligation was blocked by drainage of the stomach and therefore probably caused by distension, a mechanism which is independent of the vagal impulse flow. 3. The response to pylorus ligation in innervated rats was blocked by atropine and chlorisondamine but not by metiamide. In the denervated rats, the response to pylorus ligation was blocked by all three drugs. 4. Following ligation of both the pylorus and the oesophagus the acid response was poor. With drainage of the oesophagus the acid response was much enhanced, suggesting that oesophageal distension inhibits acid secretion. In the vagotomized rat the poor acid response to oesophageal + pyloric ligation could not be overcome by drainage of the oesophagus. In the innervated rat gastric distension could overcome the inhibition induced by oesophageal ligation. Also in chronically, but not in acutely vagotomized rats, gastric distension brought about a good acid response. Conceivably, gastric reflex mechanisms can activate acid secretion through vagal and/or intramural pathways. Both in innervated and denervated rats the response to gastric distension was inhibited by atropine, chlorisondamine and metiamide. 5. The results suggest that in the innervated rat vago-vagal reflexes are important for the gastric hypersecretion following ligation of the pylorus, and for the acid response to gastric distension following ligation of the pylorus and oesophagus. In the chronically vagotomized rat local intramural reflexes elicited by gastric distension are responsible for the acid response.

Animals↗

Gastric acid response to pylorus ligation in rats: is gastrin or histamine involved?

1. Pylorus ligation stimulated the acid output in vagally intact rats. The serum gastrin concentration and the gastric mucosal histamine content were not affected. The gastric histidine decarboxylase activity was initially slightly elevated and then greatly reduced (12-20 hr after ligation).2. Pylorus ligation stimulated the acid output in chronically, but not in acutely, vagotomized rats. Chronic vagotomy raises the serum gastrin concentration, the gastric histamine content and histidine decarboxylase activity. The serum gastrin concentration was further raised by pylorus ligation. The histamine content was initially lowered but returned to preligation values after 20 hr. The histidine decarboxylase activity first decreased, but increased to very high levels 5-6 hr after ligation. Twelve hours after ligation it was lower than before ligation.3. Following pylorus ligation pentagastrin and histamine stimulated the acid output in vagally intact and in acutely vagotomized but not in chronically vagotomized rats. By contrast, pentagastrin raised the histidine decarboxylase activity in vagally intact and in chronically vagotomized, but not in acutely vagotomized rats.4. The two major populations of endocrine cells of the oxyntic gland area (ECL cells and A-like cells) are argyrophil, store histamine and are capable of taking up exogenous DOPA and of decarboxylating it to dopamine which is retained in the cytoplasm for several hours. As evidenced by light and fluorescence microscopy pylorus ligation did not affect their argyrophilia or their ability to produce and store dopamine.5. Pylorus ligation caused ultrastructural changes in the gastrin cells of the pyloric gland area and in the histamine-storing ECL and A-like cells of the oxyntic gland area. The two endocrine cell types in the oxyntic gland area were enlarged by pylorus ligation, more so after 16 hr than after 4 hr. The size of the gastrin cells seemed unaffected. In all three cell types pylorus ligation reduced the number of cytoplasmic granules. There was no increase in the Golgi area or in the endoplasmic reticulum in any of the endocrine cell types of the oxyntic gland area. It appears unlikely that the ultrastructural changes of the ECL and A-like cells reflect an increased rate of histamine mobilization.6. The acid response to pylorus ligation probably reflects neuronal reflex mechanisms exclusively. There is no evidence that gastrin or histamine released from gastric endocrine cells mediate the response.

Animals↗