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Hemodynamic characterization of chronic bile duct-ligated rats: effect of pentobarbital sodium.

Systemic and splanchnic hemodynamics of the chronic bile duct-ligated rat were characterized by radioactive microspheres. Conscious and pentobarbital sodium-anesthetized, bile duct-ligated and sham-operated rats had cardiac output and regional organ blood flows determined. The conscious bile duct-ligated rat compared with the sham-operated showed a hyperdynamic circulation with an increased cardiac output (153.3 +/- 9.8 vs. 112.6 +/- 6.0 ml/min, P less than 0.005) and portal tributary blood flow (21.32 +/- 1.43 vs. 12.79 +/- 1.47 ml/min, P less than 0.005). Pentobarbital sodium anesthesia induced marked hemodynamic changes in both sham-operated and bile duct-ligated rats. The latter group was especially sensitive to its effects; thus, comparison of cardiac output and portal tributary blood flow between anesthetized bile duct-ligated and sham-operated rats showed no significant differences. We conclude that the rat with cirrhosis due to chronic bile duct ligation is an excellent model for hemodynamic investigations but should be studied in the conscious state, since pentobarbital sodium anesthesia eliminates the hyperdynamic circulation.

Anesthesia, General↗

Vascular ligation response is independent of p107: stressing the role of the related p130.

Recent studies have revealed the role of the pRb family members pRb and p130 in the response to vascular injury. We evaluated the arterial injury response in the absence of p107, a protein that shares a high degree of homology with the injury-controlling p130. Carotid artery ligation and perivascular electric injury of the femoral artery were applied to p107 knockout (p107 -/-) mice, and morphometric analysis was performed 3 wk after ligation and electric injury. Arterial vessels of p107 -/- mice were indistinguishable from controls under basal conditions. After carotid artery ligation the p107 -/- mice (n = 7) did not display an enhanced ligation response compared with controls (n = 9), which was studied over a distance of approximately 450 microm proximal and approximately 200 microm distal from the ligation site, with regard to vessel wall area, neointima area, and lumen area. Corresponding with this, morphometric data obtained from the perivascular electric injury of the femoral artery confirmed the lack of enhanced ligation and injury response in the absence of p107. We conclude that the pRb family member p107 is not a key regulator in vascular injury response. These data, in conjunction with previously reported results, indicate that the control of vascular injury response is not a redundant feature of pRb proteins but primarily specific for p130. Further studies on functional domains of p130 and p107 will help to resolve the pathways in vascular injury response.

Animals↗

Tissue kallikrein increases duration of survival after prolonged coronary artery ligation in hypertensive rats.

There is evidence that the kallikrein-kinin system (KKS) is an important mediator in the regulation of blood pressure, and cardiac and renal hemodynamics. The present study was designed to examine the effect of tissue kallikrein and Trasylol, an inhibitor of tissue kallikrein, on survival time after continuous (prolonged) coronary artery ligation in spontaneously hypertensive rats (SHR). Tissue kallikrein (8 and 16 microg/kg, i.v.) treatment caused significant (p < 0.05) increases in the survival time of SHR as compared with the saline-treated control SHR. Trasylol pretreatment abolished (p < 0.05) the beneficial effect of tissue kallikrein on survival time. The tissue kallikrein treatment resulted in a significant (p < 0.05) reduction in systolic blood pressure (SBP), diastolic blood pressure (DBP) and heart rate (HR) of SHR as compared to the saline-treated control SHR. Trasylol (6 microg/kg) treatment antagonized the effects of tissue kallikrein associated with survival time, SBP, DBP and HR. Ligation of the coronary artery caused a significant (p < 0.001) reduction in the SBP, DBP and HR of SHR, when the mean values were compared between before coronary artery ligation and after coronary artery ligation. However, there was no significant difference (p > 0.05) in SBP, DBP and HR between saline and kallikrein-treated SHR after coronary artery ligation. These findings may suggest that tissue kallikrein is able to act as a cardioprotective agent as demonstrated by an increase in survival time of SHR with prolonged coronary artery ligation.

Animals↗

Contractile responses of pial arterioles in gerbils with unilateral carotid ligation.

Studies were made in an effort to detect enhanced vasoconstriction ipsilateral to a ligated common carotid artery. No effect of ligation was found on the response to topically administered serotonin, norepinephrine or prostaglandin F2 alpha, in the gerbil in spite of varying a number of parameters, including anesthesia, percent of inspired oxygen, time elapsed following ligation, or body temperature at time of examination. The response was not influenced by the presence or severity of stroke symptoms. A stronger and less specific constrictor, BaCl2, did elicit a difference between the contractile response of ligated and sham operated gerbils. In 13 of the 18 studies, BaCl2 produced a greater constriction in the ligated gerbils, and in 9 of these studies that difference was statistically significant. In only one study was there a statistically significant contrary result. The enhanced contractile response to BaCl2 could not be related to the presence or severity of symptoms or to any other of the variables mentioned above. This suggests that it was probably related to reduced intraluminal pressure distal to the ligation.

Animals↗

Effect of ductus ligation on cardiopulmonary function in premature baboons.

RATIONALE: The role of the patent ductus arteriosus in the development of chronic lung disease in surfactant-treated premature newborns remains unclear. OBJECTIVE: To examine the effects of ductus ligation on cardiopulmonary function and lung histopathology in premature primates. METHODS: Baboons were delivered at 125 d, (term = 185 d) treated with surfactant, and ventilated for 14 d. Serial echocardiograms and pulmonary function tests were performed. Animals were randomized to ligation (n = 12) or no ligation (controls, n = 13) on Day 6 of life. Necropsy was performed on Day 14. RESULTS: Compared with nonligated control animals, ligated animals had lower pulmonary-to-systemic flow ratios, higher systemic blood pressures, and improved indices of right and left ventricular performance. The ligated animals tended to have better compliance and ventilation indices for the last 3 d of the study. There were no differences between the groups in proinflammatory tracheal cytokines (interleukin [IL] 6 and IL-8), static lung compliance, or lung histology. CONCLUSION: Although a persistent patent ductus arteriosus results in diminished cardiac function and increased ventilatory requirements at the end of the second week of life, ligation on Day 6 had no measurable effect on the histologic evolution of chronic lung injury in this 14-d baboon model.

Animals↗

Extrapleural bronchial artery ligation for life-threatening hemoptysis in cystic fibrosis--a case report.

Hemoptyses are common in cystic fibrosis (CF) patients. They range from massive life-threatening (> 240 mL/24 hours) to recurrent minor streaking. Limited pulmonary reserve, potential concurrent chest infection, and the progressive nature of CF pose a high risk to this subgroup. Conservative management and selective bronchial artery embolization (BAE) control most acute episodes, but the recurrence rate is high. The possible need for lung transplantation in future makes an extrapleural approach for bronchial artery ligation desirable. The aim of this study was to assess the role of extrapleural bronchial artery ligation in the treatment of recurrent hemoptysis in CF patients. This is a retrospective analysis of four patients between 1986 and 1999 treated by extrapleural thoracotomy and ligation of bronchial arteries. Indications, surgical experience, and outcome are presented. Three patients underwent unilateral, and one patient bilateral extrapleural thoracotomy (in two separate sessions) for bronchial artery ligation. There were three men and one woman, with a mean age of 26.6 years (range 19-32 years). Indications were failure to stabilize the bronchial arterial catheter for BAE (three cases), recurrence after BAE previously controlled bleeding (one case), and communication with the right costocervical trunk signifying risk to the spinal circulation (one case). The mean follow-up was 68 months (range 3-144 months). There was one death in this series, a patient who was asphyxiated with hemoptysis, requiring ventilation preoperatively. He underwent successful extrapleural thoracotomy for bronchial artery ligation, with no further bleeding but succumbed to severe chest infection and multiorgan failure a few days later. Two patients had recurrent bleeding 12 and 36 months after surgery. Selective bronchial angiography proved the contralateral bronchial arteries to be the culprit. Extrapleural bronchial artery ligation is an effective method of controlling hemoptysis in CF, when BAE has failed. This approach minimizes pleural adhesions and is, therefore, desirable in the future consideration for lung transplantation. In this experience, muscle-sparing thoracotomy and postoperative epidural analgesia significantly improved the postoperative recovery.

Acute Disease↗

Painful neuroma: changes produced in peripheral nerve after fascicle ligation.

Sixteen months after resection of a painful neuroma and fascicle ligation of the proximal nerve segments, the fascicle ligated neural tissue was examined by light and electron microscopy. No significant neuroma formation was found in the fascicle-ligated regions. The distal portion consisted mainly of connective tissue fibroblasts with an absence of neural elements. Maintaining the perineurium intact by fascicle ligation seems to alter significantly axonal regeneration in humans, as is indicated by minimal neuroma formation. Similar findings after fascicle ligation in animals have also been reported. This lack of neuroma formation after resection of a painful neuroma and fascicle ligation may play a significant role in relieving pain in patients with painful neuromas.

Amputation Stumps↗

Duct ligation and pancreatic islet blood flow in rats: physiological growth of islets does not affect islet blood perfusion.

OBJECTIVES: The aim of this study was to evaluate islet blood-flow changes during stimulated growth of the islet organ without any associated functional impairment of islet function. DESIGN: A duct ligation encompassing the distal two-thirds of the pancreas was performed in adult, male Sprague-Dawley rats. METHODS: Pancreatic islet blood flow was measured in duct-ligated and sham-operated rats 1, 2 or 4 weeks after surgery. In some animals studied 4 weeks after surgery, islet blood flow was also measured also during hyperglycaemic conditions. RESULTS: A marked atrophy of the exocrine pancreas was seen in all duct-ligated rats. Blood glucose and serum insulin concentrations were normal. An increased islet mass was only seen 4 weeks after surgery. No differences in islet blood perfusion were noted at any time point after duct ligation. In both sham-operated and duct-ligated rats islet blood flow was increased during hyperglycaemia; the response was, however, slightly more pronounced in the duct-ligated part of the gland. CONCLUSIONS: Normal, physiological islet growth does not cause any major changes in the islet blood perfusion or its regulation. This is in contrast to findings during increased functional demands on the islets or during deteriorated islet function, when increased islet blood flow is consistently seen.

Animals↗

The effects of tubal ligation on ovum transport in rabbits.

Ovum transport was studied in rabbit oviducts ligated 18 hr after mating in untreated and oestrogen-treated rabbits. Essentially all ova (93.5%) were recovered from the sham-ligated oviducts averaged 46.7%. Recovery of ova in oviducts ligated at the infundibulum and at the uterotubal junction was 100%. It is likely, therefore, that ova were transported prematurely into the uterus from ligated oviducts. Ovum transport through sham-ligated oviducts was significantly retarded by a single injection of oestradiol cyclopentylpropionate (25 or 250 mug) but remained accelerated in ligated oviducts diminished by 60 hr p.c. in untreated rabbits, but was maintained in oestrogen-treated rabbits. Ovum transport through distended oviducts may be accelerated by the passage of oviducal fluid into the uterus.

Animals↗

Increased vascular permeability of developing collateral arteries after femoral artery ligation in rabbits.

Ligation of the main femoral artery is followed by a rapid development of collateral arteries. To detect an increase in vascular permeability of the collateral arteries, colloidal carbon (1 ml/Kg, iv) was injected into 153 rabbits at various times after ligation or sham-ligation of the main femoral artery. These animals were killed later and collateral arteries was dissected. Increase in vascular permeability was identified by the presence of visible carbon deposits on the vascular walls. The carbon deposits were frequently found on the intermediate segments of the collateral system in legs with ligation, but were not found on any arteries either in legs with sham-ligation or in contralateral untouched legs. The increase in vascular permeability was observed in 15 of 17 animals as early as 6 hours, in 32 of 36 animals 1 day but only in 5 of 21 animals 6 to 8 days after ligation. The arterial segments with carbon deposits showed various structural changes such as fragmentation of the internal elastic layer, degeneration of the medial muscle and deposition of fibrinoid material. These results indicate that vascular permeability transiently increases in the intermediate segments of developing collateral arteries. Acute vasodilatation may be responsible for the increase in vascular permeability.

Animals↗

Effects of carbon monoxide inhalation on myocardial infarct size following experimental coronary artery ligation.

This study was conducted to determine whether or not a low concentration of carboxyhemoglobin influences the extent and severity of myocardial ischemia caused by coronary ligation. In 10 dogs, electrograms were recorded from 6 epicardial electrodes mounted on the anterior surface of the left ventricle and distributed over the area normally perfused by the lighted branch of the left anterior descending coronary artery. The magnitude of ST segment elevation of the 6 sites in each animal was determined for 15 min after ligation. This elevation was used as an index of the presence and severity of myocardial ischemic injury. Ligation alone increased sigma ST elevation, summed from 6 sites, from 2.06 +/- 0.34 mV (SEM) to 24.89 +/- 2.14 mV (SEM). Carbon monoxide inhaled prior to ligation increased the severity and extent of ischemic injury and the magnitude of ST segment elevation in the area peripheral to the ischemic area more than did ligation alone. These changes occurred without elevation of heart rate or arterial pressure. It was concluded that a low background concentration of carboxyhemoglobin at the time of ligation increased the extent and severity of myocardial ischemic injury.

Animals↗

Experimental studies on the influence of simultaneous ligation of the bile and pancreatic ducts upon gastric acid secretion and gut hormones.

The influence of simultaneous ligation of the bile and pancreatic ducts on gastric acid secretion and gut hormones, particularly gastrin and secretin, was studied in 5 dogs with a Heidenhain pouch. In addition, the pH of the duodenal content was measured in 2 dogs with a duodenal fistula. Tests in response to a test meal were done during the control and observation periods. In all of the 5 dogs the mean 24 hr-acid output from the Heindenhain pouches showed a significant increase from 199 to 564%. Plasma gastrin levels during the fasting showed no significant change, but the peak response to the test meal significantly decreased from 83.6 +/- 4.4 pg/ml (mean +/- S.E.) before the ligation to 42.1 +/- 4.2 pg/ml after the ligation. Plasma secretin levels were significantly elevated after the ligation both during fasting and after the test meal. The pH of the duodenal contents after the test meal was lower after the ligation than before. These results suggest that gastric hypersecretion induced by the simultaneous ligation of the common bile and pancreatic ducts is not related simply to release of gastrin, and further hypersercretinemia may depend on gastric hypersecretion.

Animals↗

Ureteral ligation prevents the haemodynamic effect of frusemide in pentobarbitol anaesthetised horses.

Frusemide reduces pulmonary vascular pressures in resting horses and attenuates exercise-induced increases in these pressures in exercising horses. The mechanism underlying these effects of frusemide is unclear. We tested the hypothesis that the haemodynamic effects of frusemide are dependent on diuresis by examining the effect of frusemide in anaesthetised horses in which diuresis was prevented by ligation of ureters. Twenty four horses were assigned randomly to one of 4 treatments: 1) frusemide (1 mg/kg bwt i.v.) and intact ureters; 2) frusemide and ligated ureters; 3) saline placebo and ligated ureters; and 4) frusemide and phenylbutazone (4.4 mg/kg bwt i.v. 12 h and 15 min before frusemide) and ligated ureters. Frusemide administration to anaesthetised horses with intact ureters increased plasma total protein concentration and reduced mean right atrial, pulmonary artery and aortic pressures. There was no significant effect of frusemide administration on haemodynamic variables or plasma total protein concentration in horses with ligated ureters. The combination of frusemide and phenylbutazone increased mean right atrial, pulmonary artery and aortic pressures in horses with ligated ureters. This study demonstrates that, in anaesthetised horses, the haemodynamic effect of frusemide is dependent upon diuresis. We interpret these results as providing further evidence that the haemodynamic effect of frusemide in horses is attributable to a reduction in plasma and blood volume.

Adjuvants, Anesthesia↗

Bacterial translocation after mesenteric ligation in dogs.

These experiments were designed to determine the relationship between translocation of Escherichia coli and viability of ischemic small bowel. Twenty beagles were gavaged with 14C-labeled E. coli at two time intervals (3 and 24 h) prior to ligation of the blood supply to a 40-cm segment of ileum. Mesenteric lymph node (MLN) biopsies and bacterial cultures of the peritoneal fluid, peripheral arterial blood, and splanchnic venous blood were taken immediately prior to ligation and 24 h later both before and after the ischemic bowel was resected and anastomosed. Biopsies of each resection margin were taken to measure translocation of E. coli into the bowel wall. Several hemodynamic hemodynamic parameters were also measured before and 24 h after ligation. Seven of the 20 dogs died of further bowel necrosis. In survivors A-alpha DO2 was significantly decreased 24 h after mesenteric ligation vs. preligation, whereas in dogs that died DO2 was significantly increased after ligation vs. preligation. The incidence of mesenteric venous cultures positive for E. coli was significantly higher 24 h after ligation vs. preligation. However, there was no correlation between survival and the incidence of positive E. coli cultures in the blood or peritoneal fluid. Mean MLN counts were significantly higher in dogs gavaged at 3 h vs. those gavaged 24 h prior to laparotomy. However, there was no correlation between survival and translocation into either the bowel wall or MLN at either time interval. Viability of ischemic small bowel in this canine model was not affected by translocation of E. coli. Hemodynamic parameters that are altered during the course of sepsis also did not correlate with survival.

Animals↗

The protective effect of allopurinol on cholestatic liver injury induced by bile duct ligation.

To determine whether oxygen free radicals are responsible for the pathogenesis of the cholestasis induced by ligation of common bile duct (CBD) variables which reflect the hepatic function in the serum, the amount of superoxide radical production, and xanthine oxidase(XO) activity were studied. The activity of serum alanine aminotransferase, bilirubin level in the serum and the amount of superoxide radical production were lower in a CBD ligation with allopurinol treated group than in a CBD ligation without allopurinol treated group. Abnormalities of the microscopic structures were reduced in a CBD ligation with allopurinol treated group than in a CBD ligation without allopurinol treated group. Allopurinol, an inhibitor of XO, prevented the hepatic damage induced by CBD ligation through the inhibition of XO. These experiments demonstrate that oxygen free radicals are responsible for the pathogenesis of the cholestatic liver.

Allopurinol↗

Different expression of positive and negative regulators of hepatocyte growth in growing and shrinking hepatic lobes after portal vein branch ligation in rats.

Portal vein branch embolization is often performed before hepatectomy to prevent postoperative liver failure. It is, however, still not clear how the embolized lobe shrinks and the non-embolized lobe proliferates in counterbalance. We investigated the expression of positive and negative regulators of hepatocyte growth to clarify the mechanisms of liver growth and atrophy in a rat portal vein ligation (PVL) model compared with partial hepatectomy (PH). A significant increase in DNA synthesis within the non-ligated lobe reached a peak at 36 h, a delay of 12 h as compared with PH, while no increase occurred in the ligated lobe. Expression of hepatocyte growth factor mRNA remarkably increased in the non-ligated growing lobe between 6 and 24 h, but was only slightly elevated in the ligated shrinking lobe. Contrarily, negative regulators of hepatocyte proliferation, such as TGF-beta1 and IL-1beta, were strongly expressed in the ligated shrinking lobe. Thus, the changes of portal venous flow and/or pressure caused by PVL may contribute to induction of different kinds of growth factors between the ischemic and non-ischemic lobes; these factors possibly regulate liver regeneration and atrophy after PVL.

Animals↗

[Postoperative results of ligation of crura penis for impotence with corporal veno-occlusive insufficiency].

We performed ligation of the crura penis for 34 impotents with corporal veno-occlusive insufficiency without arterial insufficiency and neural dysfunction from October 1987 to April 1991. Ages ranged from 24 to 72 (52.6 +/- 12.7) years old and follow up period was from 1 to 41 (17.7 +/- 12.6) months. For six patients ligation of the crura only was performed, for 22 ligation of the crura and deep dorsal vein (DDV) as well was performed at the same time, and for 6 crural ligation was performed after ligation of DDV. These operations required less than one hour and there were no severe complications. The postoperative results at 1 month were as follows: Excellent (sufficient spontaneous erection was recovered); 18, Improved (complete erection with intracavernous papaverine injection was achieved); 13, and Failure; 3. Erectile function was maintained only in 50% of the 18 pts. graded excellent. Ninety percent of the 31 patients graded either excellent or improved could maintain erectile function after 40 months with papaverine injection. Venous surgeries could not be a primary treatment for correcting the outflow abnormalities (of the veins). So it is conceivable that failure or recurrence could occur during a long follow up period. We concluded that crural ligation was acceptable as the first line treatment for erectile dysfunction due to corporal veno-occlusive insufficiency because of its relative non-invasiveness compared to other venous surgeries.

Adult↗

Short- and long-term results of endoscopic variceal ligation for esophageal varices compared with injection sclerotherapy.

We assessed the efficacy and safety of endoscopic therapy for esophageal varices in Japanese patients comparing the results of ligation therapy performed in 101 patients with those of sclerotherapy with paravariceal injection of polidocanol in 40 patients. Both therapies were effective in controlling active hemorrhages. Hemostasis rates at the first endoscopic session were 100% in both groups and rebleeding rates were 40.0% in the sclerotherapy and 29.6% in the ligation group. Variceal eradication was achieved equally in both groups in approximately 90% of the patients. However, the ligation achieved eradication more quickly in fewer endoscopic sessions than did the sclerotherapy (mean; 2.1 vs. 3.7 sessions, P < 0.01). Complications such as rebleeding and intramural hematomas were less common in the ligation group. These results indicate some advantages of the ligation over the sclerotherapy. A disadvantage of the ligation therapy is that recurrence occurs more quickly than in the sclerotherapy, although the difference was not statistically significant.

Endoscopy↗