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The effect of modification of sympathetic activity on responses to ligation of a coronary artery in the conscious rat.

1 Ligation of a coronary artery was performed in conscious rats whose sympathetic system activity had been altered by various treatments. 2 beta-Adrenoceptor blockade with acute (0.2 mg kg-1 plus 0.1 micrograms kg-1 min-1) or chronic (50-60 mg kg-1 daily for 12 days) propranolol treatment had little effect on arrhythmias, or other responses to ligation. 3 Abrupt withdrawal of chronic propranolol two days before ligation was also without effect. 4 Reduction of sympathetic activity acutely with labetalol (5 mg kg-1), or chronically with adrenomedullectomy and 6-hydroxydopamine treatment, accentuated the adverse effects of ligation. 5 The results of this study suggest that, while activity of the sympathetic system is not detrimental during ligation in the conscious rat, it may be important for survival.

Adrenalectomy↗

Quantitative electroencephalography values of neonates during and after venoarterial extracorporeal membrane oxygenation and permanent ligation of right common carotid artery.

Venoarterial extracorporeal membrane oxygenation (ECMO) in neonates commonly needs neck vessel cannulation leading to ligation of right common carotid artery (RCCA) in some cases. Quantitative electroencephalography (EEG) measurements provide reproducible data of cerebral function. The aim of this case-control study was to test whether ligation of the RCCA results in EEG changes after ECMO weaning. Ten mechanically ventilated neonates not treated with ECMO were eligible as control patients. Seven ECMO patients receiving similar sedoanalgesia were investigated during and after ECMO and RCCA ligation. Dominant frequency, absolute alpha, theta, delta, and total powers of right and left frontocentral and temporooccipital derivations were calculated. Dominant frequency did not differ among groups. Power was found to be significantly decreased in all frequency bands during ECMO. After weaning from ECMO, EEG differences between the ECMO and control groups disappeared in spite of permanent RCCA ligation. It is concluded that ligation of the RCCA per se does not result in quantitative EEG changes.

Carotid Artery, Common↗

Effect of ligation on internal carotid artery blood pressure in horses.

The effect of a single ligature on back pressure in the internal carotid artery was studied in nine horses. In six anesthetized horses, one internal carotid artery was catheterized 2 cm from its origin and blood pressure was recorded continuously. Then the artery was ligated, pressure was recorded again, and the horses were euthanatized. In another three anesthetized horses, indwelling catheters were placed in both internal carotid arteries and a loose ligature was placed proximal to one catheter. After horses recovered from anesthesia, the ligature was tied and blood pressure was recorded in both arteries on that day and 3 days later, then these horses were euthanatized. The anatomy of the cerebral arteries was examined in all nine horses. Blood pressure in the internal carotid arteries did not change after ligation. Subjectively, collateral channels considered most likely to maintain blood pressure in the ligated internal carotid artery were the caudal intercarotid artery and the cerebral arterial circle. We concluded that ligation of the internal carotid artery would not prevent severe hemorrhage from the internal carotid artery in horses with guttural pouch mycosis until the ligated artery thrombosed to the level of the lesion.

Animals↗

Incidence and management of esophageal stricture formation, ulcer bleeding, perforation, and massive hematoma formation from sclerotherapy versus band ligation.

OBJECTIVES: The aim of this study was to compare the incidence and endoscopic management of esophageal stricture formation, significant ulcer bleeding, massive esophageal hematoma, and perforation resulting from endoscopic band ligation or sclerotherapy of esophageal varices. METHODS: Consecutive esophagogastroduodenoscopies in which band ligation or sclerotherapy was performed for acute or obliterative therapy were entered into a computerized endoscopy database during a 7-yr period. Patients were excluded if they died within 72 h of treatment session from complications unrelated to the procedure. Sclerotherapy was performed using a 25-gauge needle with 1.5% sodium tetradecyl sulfate and banding was primarily performed with a Wilson-Cook 6 or 10 shooter. Complications were assessed at scheduled endoscopy and outpatient clinic visits, review of quality assurance data tallied on a monthly basis, and patient records. RESULTS: Two hundred twenty-one cases of sclerotherapy were performed in 59 patients compared to 110 cases of band ligation in 52 patients. Five patients were excluded because of death within 72 h of the procedure. The incidence of complications from sclerotherapy:banding on a per patient basis included: esophageal stricture formation 25.6%:1.9%, ulcer bleed 25.4%:5.7%, esophageal perforation 2.2%:0%, and massive esophageal hematoma 1.6%:0%. A significant difference in complications between sclerotherapy and band ligation was noted for both stricture formation (p < 0.0005) and ulcer bleeding (p < 0.0001). The majority of ulcer bleeds required no therapeutic intervention, whereas stricture formation required multiple dilation sessions. CONCLUSIONS: Band ligation has a significantly lower incidence of stricture formation and ulcer bleeding compared to sclerotherapy. The majority of complications can be managed with endoscopic interventions.

Databases, Factual↗

Immunohistochemical observation of EGF and NGF in submandibular glands after duct ligation with or without testosterone administration.

Immunohistochemical detection of epidermal growth factor (EGF) and nerve growth factor (NGF) was carried out in duct-ligated submandibular glands (SMG) of mice with or without testosterone treatment. High levels of EGF and NGF were limited to granular convoluted tubule (GCT) cells in normal adult male mice, and reduced levels were evident in the female. After duct ligation, EGF and NGF stainings began to decrease on the 2nd or 3rd day, and by the 10th day, no staining was detectable. Decreasing levels of EGF and NGF following duct ligation, were more pronounced in the male SMG than in the female. Testosterone administration before ligation resulted in decreased EGF and NGF levels of staining; however, staining of sections on the 1st and 3rd day was a little stronger than comparable stained sections of untreated mice. In contrast, testosterone administration after duct ligation showed GCT cells of normal size with some degranulation at 10 days and irregular staining of growth factors with varying degrees of degranulation at 14 days. Histochemical staining for EGF and NGF in this group was marked, as in the normal, until the 10th day with decreasing reactions by the 14th day.

Animals↗

Liver damage induced by bile duct ligation affects CYP isoenzymes differently in rats.

We examined the influence of liver damage induced by bile duct ligation on the activity and the expression of hepatic cytochrome P450 (CYP) 1A, 2B, 2C6, 2C11, 2E1 and 3A2 in male Sprague-Dawley rats. In the ligation group, testosterone 2 alpha-, 16 alpha-, and 6 beta-hydroxylase activities were severely decreased, whereas ethoxyresorufin O-deethylase and progesterone 21-hydroxylase activities relatively remained. Pentoxyresorufin O-deethylase and chlorzoxazone 6-hydroxylase activities were reduced to approximately one thirds those of control. The protein contents of these isoenzymes expressed in hepatic microsomes of the ligation group were decreased to 45%, 32%, 79%, 13%, 58%, and 23% of control for CYP1A, 2B, 2C6, 2C11, 2E1 and 3A2, respectively. The rank order of magnitude of the influence of bile duct ligation on CYP isoenzymes, assessed by the reduction in the enzyme activity and the protein content, corresponded with each other except CYP1A. The reduction of the enzyme activities significantly correlated with the reduction in the protein contents of different isoenzymes. These results suggested that bile duct ligation affected CYP isoenzyme activities and contents with different extent.

Animals↗

Release of insulin in vitro from normal and duct-ligated rat pancreas.

Ligation of the pancreatic duct causes atrophy of the acinar cells but leaves the endocrine tissue intact. In the present study, a partial ligation of the pancreatic duct was performed in the rat, and the in vitro insulin response to glucose was compared from both the atrophic and non-atrophic portions of the pancreas. Subsequent morphological studies of the duct-tied portion of the pancreas indicated a complete lack of acinar cells and a possible neoformation of ducts, fat cells and connective tissue. However, islets were present in normal amounts and appeared well perserved. Measurements of the insulin release in vitro from this ligated pancreatic tissue showed that an increase of the glucose concentrations from 3.3 to 16.7 mmol/1 resulted in a six-fold stimulation. A further two-fold stimulation was seen after addition of theophylline to the high-glucose incubation medium. In addition, only under the latter conditions was there a significantly increased insulin release from both non-atrophic portion of the pancreas and from the pancreas of sham-operated animals. It is concluded that duct ligation does not diminish the glucose sensitivty of rat islet B-cells. Thus, the present study does not support the view proposed previously that islet tissue is functionally of a foetal nature following duct ligation.

Animals↗

Effects of duct ligation on choline acetyltransferase activity in salivary glands of rats.

Duct ligation was found to cause a decrease in the weights of submaxillary and parotid glands examined 3 weeks postoperatively. Choline acetyltransferase activity in ligated glands was compared with that in unligated contralateral glands. The enzyme activity was also measured in the glands from both sides of unoperated control animals. Interference in the assay of choline acetyltransferase by other acetylated compounds was avoided by introducing suitable control incubations. Ligated submaxillary glands showed a small decrease in the activity of choline acetyltransferase both when compared with contralateral glands and with glands of control rats. In parotid glands the enzyme activity was found to be lower only when ligated and contralateral glands were compared. Structural changes in the nerves and reduced traffic of impulses in them may have to be considered as explanations for the reduction in enzyme activity in duct-ligated glands.

Animals↗

Changes in diamine and polyamine metabolism in the duct-ligated submaxillary and sublingual glands of the rat.

Duct-ligation of salivary glands is known to cause disappearance of acini, while ductal elements persist. In the present investigation the duct-ligated submaxillary and sublingual glands increased in weight by 45-60% 3 days postoperatively, while they weighed 48-56 and 63-64% less than their contralateral glands 10 and 21 days postoperatively. In the duct-ligated glands putrescine increased markedly both in terms of total amount and in terms of concentration, while spermidine and spermine decreased; histamine, in terms of concentration, was initially reduced but increased markedly later. As to total amount histamine tended to increase along time. The histamine-forming enzyme, histidine decarboxylase, and the putrescine-forming enzyme, ornithine decarboxylase, showed higher activities in the duct-ligated submaxillary glands than in the contralateral glands. Di- and polyamines and their synthesizing enzymes are considered to increase in growing tissue. The present results of increased amine levels and enzyme activities are discussed in relation to previous findings of ductal goblet cell hyperplasia following duct-ligation and of increases of polyamines in cystic fibrosis.

Animals↗

Day case ligation of patent ductus arteriosus in preterm infants: a 10 year review.

Since 1978, 136 preterm babies received ligation of a patent ductus arteriosus as day cases. A total of 122 babies whose notes were available for review, with a median gestational age of 27 weeks (range 23-35) and median birth weight of 960 g (range 470-2750), were transported distances of up to 80 miles. The median ages at ligation with and without previous medical management with indomethacin were 23 and 15 days, respectively. One hundred and ten (90%) babies were dependent on ventilatory support, but extubation was achieved at a median time of 10 days after ligation, regardless of postnatal age at the time of ligation. There were no deaths associated with the operation, and no complications resulting from transportation. The hospital mortality was 15 (12.3%), and the most important (and significant) adverse factor was a preoperative fractional inspiratory oxygen content greater than 0.3. The results of this study show that day case ligation of the patent ductus arteriosus is safe, and if it is carried out early will reduce the time before extubation and discharge from the intensive care unit.

Birth Weight↗

Reversible regulation of P2Y(2) nucleotide receptor expression in the duct-ligated rat submandibular gland.

Ligation of the main excretory duct of the rat submandibular gland (SMG) produces a pronounced atrophy that is reversed upon ligature removal. Based on previous studies by our group and others suggesting that P2Y(2) nucleotide receptors are upregulated in response to tissue damage, we hypothesized that P2Y(2) receptor activity and mRNA levels would increase after duct ligation and return to control levels after ligature removal. Our results support this hypothesis. Intracellular Ca(2+) mobilization in response to the P2Y(2) receptor agonist UTP in SMG cells was increased significantly after ligation periods of 1.5 to 7 days, whereas no significant response was observed in the contralateral, nonligated gland. P2Y(2) receptor mRNA, as measured by semiquantitative RT-PCR, increased about 15-fold after 3 days of ligation. These increases reverted to control levels by 14 days after ligature removal. In situ hybridization revealed that the changes in P2Y(2) receptor mRNA abundance occurred mostly in acinar cells, which also were more adversely affected by ligation, including an increase in the appearance of apoptotic bodies. These findings support the idea that P2Y(2) receptor upregulation may be an important component of the response to injury in SMG and that recovery of normal physiological function may signal a decreased requirement for P2Y(2) receptors.

Animals↗

A novel model of cryoinjury-induced myocardial infarction in the mouse: a comparison with coronary artery ligation.

Mouse myocardial infarction (MI) models are frequently used research tools. The most commonly applied model is coronary artery ligation. However, coronary ligation often gives rise to apical aneurysmatic infarcts of variable size. Other infarct models include cryoinfarction, which produces reproducible infarcts of the anterior wall. Thus far, this model has not been extensively described in mice. Therefore, we developed a murine cryoinfarction model and compared it with coronary ligation. Studies were performed under isoflurane anesthesia with a follow-up of 4 and 8 wk. Cryoinfarction was induced using a 2- or 3-mm cryoprobe. Two-dimensional guided M-mode echocardiography was used to assess fractional shortening and left ventricular (LV) dimensions at baseline and end point. At end point, hemodynamics were assessed using a 1.4-Fr Millar catheter. Pressure-diameter relations were constructed by combining echocardiography and hemodynamic data. Histological and morphometric analyses of infarct and remote areas were performed. At 4 wk, 3-mm cryoinfarction resulted in decreased LV fractional shortening as well as decreased global LV contractility and relaxation, which was comparable with coronary ligation. No adverse remodeling was observed at this time point, in contrast with the ligation model. However, progressive LV remodeling occured between 4 and 8 wk after cryoinfarction with a further decline in hemodynamic parameters and LV pump function. Histologically, cryoinfarction resulted in highly reproducible, transmural, cone-shaped infarcts with reperfusion at the macrovascular level. These results indicate that the cryoinfarction model represents the anterior myocardial infarct with modest adverse remodeling and may thus be representative for infarcts encountered in clinical practice.

Animals↗

bFGF increases collateral blood flow in aged rats with femoral artery ligation.

We tested the hypothesis that aged animals are as responsive as the young adult animals in expanding collateral vasculature under a similar treatment of basic fibroblast growth factor (bFGF). Two age groups of male Fischer 344 rats (11 mo old; n = 32, 23 mo old; n = 43) weighing approximately 385 g were subdivided into normal, acute ligation [femoral artery (FA) ligated 3 days before blood flow (BF) measurement] or ligated groups for 16 days and received recombinant human bFGF intra-arterial infusion at doses of 0, 0.5, 5, and 50 microg x kg(-1) x day(-1). BF was determined with (85)Sr- and (141)Ce-labeled microspheres during treadmill running at 15 and 20 m/min at 15% grade. Blood pressure (BP) values were approximately 149 and approximately 163 mmHg (p < 0.05); heart rates were approximately 496 and approximately 512 beats/min in the aged and young adult groups during running, respectively. Maximal collateral BF values were confirmed by no additional BF increase in the calf muscle at the higher speed. Ligation of the FA for 3 days reduced the BF reserve to the calf muscle by approximately 90%. Calf muscle BF was modestly greater (10 ml x min(-1) x 100 g(-1)) by 16 days in the carrier group. bFGF infusion expanded collateral BF in a dose-dependent manner with an increase of 33 and 42 ml x min(-1) x 100 g(-1) (P < 0.001) in the 5 and 50 microg x kg(-1) x day(-1) bFGF groups, respectively. Aged animals showed similar BF improvements as observed with the adult groups in response to ligation surgery and bFGF treatment. Our data indicate that the aged rats (approximately 23 mo old) remain responsive to exogenous bFGF induced in developing collateral-dependent BF as the young adult (approximately 11 mo old) controls. This suggests that the influence of bFGF in expanding collateral BF should not be preempted in the aged group, the population most affected by peripheral arterial insufficiency.

Aging↗

Inhibition of transmembrane K transfer in ureter-ligated dogs infused with KCl.

In anuric dogs loaded with K by infusion with 2 meq KCl/kg per h until prelethal hyperkalemic cardiotoxicity appears, the extent of transmembrane K transfer depends on the origin of the anuria. Animals with bilateral ureter ligation transfer a mean of 1.2 meq/kg to intracellular fluid, while those with bilateral nephrectomy transfer more than 2.5 times as much (3.1 meq/kg). Further, if dogs with functioning kidneys are ureter ligated or nephrectomized after approximately 45 min of K loading, K transfer ultimately falls as infusion continues. The fall is precipitate and over 90% in ligated animals; but it is gradual, and only 10% in those that are nephrectomized. Finally, K transfer, because of the absence of insulin, is negligible in K-loaded pancreatectomized dogs with bilateral ureter ligation, but fairly substantial in pancreatectomized animals with bilateral nephrectomy. The data suggest that ureter ligation and hyperkalemia activate a renal mechanism that interferes with the transfer of infused K to intracellular fluid. The mechanism may involve the renin-angiotensin II-aldosterone system to a limited degree.

Animals↗

Early adaptations in collateral and microvascular resistances after ligation of the rat femoral artery.

Collateral and microvascular (including feed artery) resistances in the rat hindlimb were determined immediately or 1 wk after ligation of the femoral artery. Collateral-to-microvascular resistance ratios were determined from in vivo pressure measurements proximal and distal to the ligation. Microvascular resistance was 32 +/- 2.5 and 41 +/- 1.5% of the total collateral-dependent vasculature in acutely and chronically ligated limbs, respectively, and decreased 20% in both groups during reactive hyperemia. Minimum resistances of collateral vessels and the microcirculation arising from arterial branches proximal and distal to the ligation were determined by using a modification of the standard hindquarter perfusion technique for determining maximum vascular conductance. One week postligation, minimum total hindquarter resistance was decreased by a reduction in the resistance of the collaterals (approximately 50%) and microcirculation (approximately 33%) proximal to the ligation. The results suggest that the microvasculature distal to the occlusion is able to increase flow by dilation both initially and at 1 wk postligation but that collateral adaptations are primarily responsible for decreases in the minimum total resistance of the collateral-dependent region.

Adaptation, Physiological↗

Fat absorption and metabolism in bile duct ligated rats.

BACKGROUND: Bile excretion is obstructed in children with extrahepatic bile duct atresia (EHBA) resulting in fat malabsorption and disturbed lipid metabolism. AIM: Investigate if the bile duct ligated rat exhibits similar deviations as patients with EHBA under different feeding conditions. METHODS: 6 bile duct ligated Wistar rats and 12 matched paired controls were randomised over 3 feeding groups. Rats were killed 16 or 30 days postsurgery. Faeces, blood and livers were collected. Fat absorption was evaluated, markers for cholestasis and the fatty acid composition of serum phospholipids (PL) and cholesterol esters (CE) were determined. Fatty acid desaturation activities in liver microsomes were measured. RESULTS: Cholestatic bile duct ligated rats have a lower fat absorption coefficient and a lower fraction of 18:2n-6 and 18:3n-3 in serum triglycerides than their controls. This demonstrates that bile duct ligated rats suffer from fat malabsorption. In contrast to the observations in serum triglycerides, 18:2n-6 and 18:3n-3 were not reduced in serum PL and CE of cholestatic rats. Overflow of 18:2n-6 rich biliary PL in the general circulation could contribute to this observation. In agreement with what was found in man, serum PL of cholestatic rats have a higher 16:0/18:0 ratio, increased monoenes and reduced unsaturated fatty acids. However, no differences were observed in microsomal desaturation activities. CONCLUSION: Cholestatic bile duct ligated rats exhibit similar deviations in serum fatty acid composition as found in patients with EHBA, therefore they can be used as a model for this human disease.

Animals↗

Cecal ligation and puncture as a model of sepsis in the rat: influence of the puncture size on mortality, bacteremia, endotoxemia and tumor necrosis factor alpha levels.

BACKGROUND: Cecal ligation and puncture is a widely used experimental model of sepsis. AIM OF THE STUDY: The present study was aimed to evaluate the influence of the size of the cecal puncture on mortality, bacteremia, endotoxemia and plasma TNF-alpha levels. MATERIALS AND METHODS: Female Sprague-Dawley rats underwent cecal ligation and puncture, divided into the following groups, defined by the diameter of the cecal puncture: 0.5-cm blade incision (n = 25), 13-gauge (n = 25), 16-gauge (n = 25), 18-gauge puncture (n = 25) and 4 punctures with a 22-gauge needle (n = 25). A sham operation was performed in another 25 rats. Three animals of each group were sacrificed 5 h after the procedure for blood cultures as well as determination of plasma endotoxin and TNF-alpha. The remaining animals were followed up for a week after cecal ligation and puncture for evaluation of mortality. RESULTS: Five hours after cecal ligation and puncture, bacteremia was present in all animals, independently of the puncture size. Endotoxemia and plasma TNF levels tended to increase along with the diameter of the cecal puncture. Mortality gradually increased with the puncture size, from 27% with a 22-gauge needle to 95% with the blade incision. CONCLUSIONS: The severity of sepsis obtained with cecal ligation and puncture in rats can be easily modulated varying the size of the puncture.

Animals↗

Plasma membrane fluidity during regeneration and atrophy of the rat liver following portal branch ligation.

Dynamic changes in liver plasma membrane fluidity caused by regeneration and atrophy were assessed in rats following portal branch ligation (PBL). The portal branch, which perfuses 70% of the liver, was ligated with 5-0 prolene, and liver plasma membranes were isolated by ultracentrifugation. The membrane fluorescence polarization was measured as an index of membrane fluidity using 1,6-diphenyl-1,3,5-hexatriene (DPH) as the probe dye. In nonligated lobes, a significant decrease in fluorescence polarization was observed 12 and 24 h after PBL (0.171 +/- 0.004, p < 0.01 and 0.165 +/- 0.005, p < 0.001, respectively) as compared to the controls (0.181 +/- 0.002). The fluorescence polarization values then gradually returned to near control levels. In contrast, in the ligated lobes, the fluorescence polarization had increased by 12 hours after PBL (0.196 +/- 0.002, p < 0.01), and remained significantly elevated (p < 0.01) for up to 1 week after PBL, gradually returning to control levels within 3 weeks. The membrane composition was also evaluated by analyzing the cholesterol/phospholipid (C/P) ratio. A significant increase in the C/P ratio was detected in the ligated lobes 12 h and 3 days after PBL, but there was no significant difference in fluorescence polarization values between nonligated lobes and controls. These results suggest that alterations in membrane fluidity play an important role in the regenerative and atrophic processes of the liver following portal branch ligation.

Animals↗