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Experimental fetal tracheal ligation prevents the pulmonary hypoplasia associated with fetal nephrectomy: possible application for congenital diaphragmatic hernia.

Pulmonary hypoplasia has a definite clinical impact in a variety of congenital diseases such as renal dysplasia and congenital diaphragmatic hernia. These diseases have in common inadequate growth and development of fetal lungs. Previous reports have demonstrated increased lung growth with in utero tracheal ligation. The purpose of this study was to determine if lung growth can be accelerated in the setting of experimental pulmonary hypoplasia. Ninety-five-day gestation fetal sheep were divided into four experimental groups: nephrectomy, nephrectomy with tracheal ligation, tracheal ligation alone, and sham-operated control animals. Animals were delivered near term and their lungs inflation fixed at 25 cm H2O. Total alveolar number (Alv#), total alveolar surface area (AlvSA), and lung volume to body weight ratios (LV:BW) were determined for apical and basilar segments of each animal and then averaged. Total lung DNA and protein content were also analyzed. The nephrectomy group had smaller lungs than control animals with decreased Alv#, AlvSA, and LV:BW. In contrast, nephrectomy with tracheal ligation produced large lungs which had increased Alv#, AlvSA, and LV:BW when compared with both the nephrectomy and the control group (P < .01). Total lung DNA and protein concentrations were both markedly elevated in the tracheally obstructed groups. However, the DNA/protein ratios remained constant in all four groups, suggesting that lung growth had occurred through cell multiplication. Photomicrographs of the lung demonstrated a histologically immature appearance in the nephrectomy group and a histologically mature appearance in the tracheally obstructed groups.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Effects of portacaval shunt and hepatic artery ligation on liver surface oxygen tension and effective hepatic blood flow.

Liver surface oxygen tension (LSOT) and nutrient hepatic blood flow (NHBF) were measured in rats 1 hr and 1 week after sham operation, portacaval shunt (PCS), and hepatic artery ligation (HAL). LSOT was measured using a heated Clark electrode (37 deg) and was expressed as percentage of rectus muscle O2 tension to correct for changes in systemic oxygenation. Nutrient hepatic blood flow (NHBF) was measured using steady-state, low-dose galactose clearance pharmacokinetics. Acutely, we found a close correlation between LSOT and nutrient hepatic blood flow after both hepatic artery ligation and portacaval shunt. At one week after hepatic artery ligation, LSOT and nutrient hepatic blood flow made parallel increases. However, 1 week after portacaval shunt, LSOT increased while nutrient hepatic blood flow remained reduced. The divergence in these results between the two methods of producing hepatic hypoperfusion, implies that LSOT recovers via a different mechanism after portacaval shunt. Recovery of LSOT at one week probably reflects normalization of hepatic O2 delivery after hepatic artery ligation and impaired oxygen utilization after portacaval shunt.

Animals↗

Common bile duct ligation in rabbit: a new model of acute cholecystitis description of histology and bile analysis.

The early stages of acute cholecystitis have been difficult to investigate due to the animal models developed and utilized over the past 60 years. A new model of animal acute cholecystitis induced by common bile duct ligation in the rabbit for 1 to 4 days produces histologic changes which are nearly identical to acute human cholecystitis. These changes include subserosal edema, hemorrhage, white cell infiltration, and dilatation of lymphatics. An inflammation scoring system is described with a range from 0 (not present) to 11 (the most severe). The inflammation score was 2 +/- 0.7 in control rising to 6.3 +/- 1.2 at 1 day of ligation and increasing further with time of duct ligation (P less than 0.01 all groups compared to control). Analysis of bile lithogenic index and concentrations of cholesterol, bile acids, and phospholipids showed no differences among control and experimental groups. Our findings show that the model of rabbit common bile duct ligation produces a histologic picture identical to human cholecystitis without chemical or physical manipulation of the gallbladder or significant changes in the bile lithogenic index.

Acute Disease↗

Left ventricular dysfunction following ligation of the ductus arteriosus in the preterm baboon.

We evaluated the effect of early closure of the patent ductus arteriosus (PDA) on cardiac performance in a preterm baboon model of hyaline membrane disease. Eleven baboon fetuses were delivered at 75% gestation, resuscitated, and treated with conventional ventilation. The animals were divided into two groups, and underwent left thoracotomy at 2 hr of age. Group 1 (N = 5) had ductal infiltration with formalin to maintain ductal patency. Group 2 (N = 6) had ductal ligation. Hemodynamic parameters were compared between groups before and after surgical intervention. Examination of cardiovascular function was performed at intervals over a 24-hr period using two-dimensional, M-mode, and pulsed Doppler echocardiography. Ventricular performance was significantly worse in the ligation animals as demonstrated by reduced left and right ventricular outputs and reduced left ventricular shortening. However, pulmonary disease and arterial blood gases were not different. Early ligation was also associated with significantly increased systemic vascular resistance. We conclude that early ductal ligation leads to impaired ventricular performance in the premature primate. We hypothesize that the PDA may protect the immature ventricle by preventing pressure overload during adaptation to postnatal life.

Animals↗

Effect of portal branch ligation on polyamine metabolism in rat liver.

The activity of ornithine decarboxylase and the intracellular concentrations of putrescine and spermidine in the non-ligated lobes of the liver increased after portal branch ligation. These changes were followed by increased [3H]thymidine uptake into the acid-insoluble fraction of the liver. The induction of ornithine decarboxylase and changes in intracellular polyamines are important biochemical events in liver regeneration, so our results suggest that portal branch ligation causes formation of some stimuli that trigger liver regeneration. Changes were less with ligation than with partial hepatectomy.

Animals↗

Magnetic resonance imaging of canine salivary glands after ductal ligation and stimulation by pilocarpine.

We performed magnetic resonance imaging in six dogs after submandibular ductal ligation on one side, followed by secretory stimulation with intraperitoneal injection of pilocarpine (5 mg/kg). On the images obtained after ductal ligation but before stimulation, there was no significant change in signal intensity on either side. After injection of pilocarpine the signal intensity of the ligated gland increased significantly (p less than 0.01) in T2-weighted images and nonsignificantly in inversion recovery images, and remained constant in T1-weighted images. Significant (p less than 0.01) volume increases of the glands after ligation and stimulation were measured for the T1, T2, and inversion recovery protocols. These findings likely reflect the retention of saliva caused by pilocarpine stimulation and the absence of drainage through the obstructed duct. The results indicate that the T2-weighted images obtained after pilocarpine stimulation may be useful for studying patients with disturbance of major salivary gland function and may provide an objective basis for the noninvasive diagnosis of unilateral stenosis.

Animals↗

Cecal ligation and puncture is associated with pulmonary injury in the rat: role of cyclooxygenase pathway products.

The present studies evaluated the role cyclooxygenase products play in bacterial sepsis induced pulmonary injury in the rat. Lung injury was assessed by determining the pulmonary capillary filtration coefficient (Kf) and the lung lavage protein concentration four and 18 hours after cecal ligation and puncture. Four hours after cecal ligation, the Kf was unchanged from control, however, by 18 hours, the Kf was increased 171% (p < .05). Similarly, lung lavage protein levels were unchanged four hours after cecal ligation but were significantly (p < .05) elevated at 18 hours. On the other hand, pulmonary lavage immunoreactive thromboxane B2 (iTXB2) levels were increased both four and 18 hours after the initiation of sepsis. In order to determine if cyclooxygenase products played a role in the sepsis associated lung injury, ibuprofen was administered prior to cecal ligation. Ibuprofen pretreatment prevented the sepsis associated increase in both Kf and lung lavage protein concentration. These studies suggest that bacterial sepsis in the rat is associated with pulmonary injury and that early administration of ibuprofen ameliorates this damage.

Animals↗

Coronary artery ligation in anesthetized rats as a method for the production of experimental dysrhythmias and for the determination of infarct size.

Coronary artery ligation in anesthetized rats was assessed as a method for the production of experimental dysrhythmias and for the determination of infarct size. Following occlusion of the left main coronary artery, very marked ventricular dysrhythmias occurred in two distinct phases, an early and a late phase, at 0-30 minutes and at 1 1/2--4 hours after ligation respectively. Infarct size was measured at 4 hours after ligation using nitroblue tetrazolium to stain for the depletion of two cytoplasmic enzymes, lactate dehydrogenase and NADPH diaphorase. In this model, lignocaine (10 mg/kg plus an infusion of 5 mg/kg/hr) and ORG 6001 (10 mg/kg plus an infusion of 2.5 mg/kg/hr) had marked antidysrhythmic activity but neither drug influenced infarct size. The model, because of its simplicity, reproducibility, and low cost, should be useful for the screening of potential antidysrhythmic agents and may also be used to determine infarct size following coronary artery ligation.

Androstanols↗

Elevated mitochondrial gene expression during rat liver regeneration after portal vein ligation.

We explored the molecular basis of mitochondrial energy production during rat liver regeneration after portal vein ligation. Ligation of the left branch of the portal vein induces an increase in the weight of the nonligated lobe, counterbalancing the reduced weight of the ligated lobe. Using this model, we investigated changes in mitochondrial DNA-binding proteins, mitochondrial DNA, and mitochondrial messenger RNA (mRNA) in rat hepatocytes of the nonligated lobes. The amount of mitochondrial DNA-binding protein increased maximally (200% to 300% of the preoperative level) at 12 hours after the operation, before an increase (390%) in mitochondrial DNA content at 24 hours, and parallel to an increase (240%) in mitochondrial mRNA levels at 12 hours. These results suggest that the energy supply for liver regeneration is achieved through enhancement of mitochondrial DNA replication as well as transcription, in which the mitochondrial DNA-binding proteins probably play regulatory roles. We also found that in the nonligated lobes, mRNA levels of hepatocyte growth factor increased to a detectable level only 12 hours after the operation. These molecular biochemical data help explain why preoperative portal vein embolization, which is a modification of portal vein branch ligation, is an effective method to prevent posthepatectomy liver failure.

Animals↗

The prevalence and impact of pain after day-care tubal ligation surgery.

Empirical data from controlled studies using standardized, reliable measures on the amount and quality of pain after laparoscopic tubal ligation and the consequences of this pain on the activities of daily living are extremely scarce. In a study of 54 women admitted to a day-care unit for this procedure, validated measures were utilized to assess the incidence, intensity and duration of pain after tubal ligation (McGill Pain Questionnaire) and the impact of pain on the activities of daily living (Modified Functional Assessment Inventory). Psychological measures (Brief Symptom Inventory, Kranz Health Opinion Survey, and the State-Trait Anxiety Inventory) were employed to test their use as possible predictors for pain, analgesic usage and the time taken to resume a normal activity level after tubal ligation surgery. The results showed that pain is a significant problem after tubal ligation although pain rating scores over the 7-day study period were lower than those reported after major abdominal surgery. Eighty-five percent of our sample reported that pain and/or fatigue impacted on their recovery and contributed to an average delay of return to normal activity level of 4.4 days, not including the day of surgery. The psychological measures did not prove to be strong predictors of postoperative pain, time of return to normal activity level or analgesic usage. The most powerful predictor of return to normal activity was the total amount of pain experienced, as measured by the McGill Pain Questionnaire, during the 7 day post-operative period.

Activities of Daily Living↗

Antiarrhythmic properties of specific inhibitors of sarcoplasmic reticulum calcium ATPase in the isolated perfused rat heart after coronary artery ligation.

OBJECTIVES: The hypothesis tested was that sequestration of calcium by the sarcoplasmic reticulum and internal calcium oscillations may play a role in the genesis of ischemic and reperfusion ventricular arrhythmias. BACKGROUND: Previous data suggest that inhibition of the release of intracellular calcium from the sarcoplasmic reticulum by ryanodine may prevent ventricular fibrillation. METHODS: The isolated Langendorff perfused rat heart was treated with two specific inhibitors of the calcium ATPase pump of the sarcoplasmic reticulum (thapsigargin [10(-6) mol/liter] or cyclopiazonic acid [10(-7) mol/liter]) for 5 min before left anterior descending coronary artery ligation was performed. One group of hearts was subject to 30 min of coronary artery ligation, and ischemic arrhythmias were monitored. In a second group, the incidence of reperfusion arrhythmias was measured after 10, 15, 20, 25 and 30 min of coronary artery ligation. RESULTS: Thapsigargin treatment during ischemia and reperfusion decreased the incidence of reperfusion ventricular fibrillation after 10 min of coronary artery ligation from 67% (n = 6) to 0% (n = 6) (p < 0.05), after 15 min from 81% (n = 16) to 25% (n = 20) (p < 0.002) and after 20 min of ischemia from 90% (n = 10) to 46% (n = 13) (p < 0.05). Thapsigargin treatment also decreased the incidence of ischemic ventricular fibrillation from 83% (n = 12) to 0% (n = 12) (p < 0.002). Cyclopiazonic acid treatment during ischemia and reperfusion likewise decreased the incidence of ischemic and reperfusion arrhythmias. CONCLUSIONS: The highly specific inhibitors of the calcium uptake pump of the sarcoplasmic reticulum--thapsigargin and cyclopiazonic acid--have antifibrillatory properties in the isolated perfused rat heart. They appear to act by restriction of calcium oscillations between the sarcoplasmic reticulum and the cytosol.

Animals↗

The protective effect of thromboxane synthetase inhibitor UK 38485 against bile duct ligation induced liver injury.

In order to elucidate the relation between tissue eicosanoids and liver injury due to bile duct obstruction, we have examined the effects of iloprost, a stable analogue of prostaglandin I2 (PGI2), and UK 38485 (UK), an inhibitor of thromboxane synthetase, on prostaglandin E2 (PGE2) and leukotriene C4(LTC4) in guinea pig liver. 56 male guinea pigs were divided into the following groups: (i) sham operations (SHAM), (ii) bile duct ligated (BDL) group, (iii) guinea pigs given UK (5 micrograms/kg body wt intraperitoneally 10 min, 8 h and 16 h after bile duct ligation), and (iv) guinea pigs treated with iloprost (ILO) (2 micrograms/kg body wt intraperitoneally 10 min, 8 h and 16 h after bile duct ligation). Liver damage was assessed by blind quantitation of liver cell necrosis. Bile duct ligation caused an increase in tissue PGE2-like activity and a decrease LTC4-like activity. But the most pronounced elevation of PGE2-like activity was observed in ILO treated group. The LTC4-like activity level improved significantly in the UK-treated BDL group compared with the BDL only and ILO treated animals. Also, UK was found to be beneficial in preventing the liver cell necrosis due to cholestasis. It is concluded that the ratio of PGE2/LTC4 in liver is a valuable marker for cholestatic injury.

Animals↗

Bile-pancreatic juice exclusion increases cholinergic M3 and CCK-A receptor expression and interleukin-6 production in ligation-induced acute pancreatitis.

BACKGROUND: Using an original model, the Donor Rat Model, we showed that bile-pancreatic juice (BPJ) exclusion from gut exacerbates ligation-induced acute pancreatitis in rats. We also showed that muscarinic cholinergic M3 and CCK-A receptor expression is induced following duct ligation. Increased receptor number potentially could exacerbate cytokine production. We hypothesize that BPJ exclusion is responsible for M3 and CCK-A receptor induction and increased interleukin-6 (IL-6) production. METHODS: M3 and CCK-A receptor expression and IL-6 production were compared in rat pancreata 1 to 3 hours after duct ligation with or without BPJ replacement. RESULTS: Our studies showed that BPJ replacement attenuates duct ligation-induced increases in M3 and CCK-A receptor expression and IL-6 production. CONCLUSIONS: In this model, BPJ exclusion from gut induces M3 and CCK-A receptor expression and increases IL-6 production. In this experimental corollary of gallstone pancreatitis, BPJ exclusion from gut may play a key role in the mechanism of disease pathogenesis.

Analysis of Variance↗

Are laparoscopic staplers effective for ligation of large intraabdominal arteries?

OBJECTIVES: To evaluate ligation of aortoiliac arteries with laparoscopic staplers in order to develop specifically designed staplers. METHODS: Cadaveric study. Seven human cadaver aortas were stapled using EndoGIA60 staplers. Efficiency was evaluated macroscopically and on a hydrodynamic bench. Clinical study. Twelve patients had ligation of 14 large abdominal arteries (aorta: nine, iliac artery: four, hepatic artery: one) using a laparoscopic stapler. Stapling efficiency was judged on peroperative clinical and postoperative CT scan criteria. RESULTS: Cadaveric study. Stapling was performed perfectly on four moderately calcified aortas, without leakage with a pulsatile pressure of >250 mmHg. For three aortas with severe calcification, stapling was not efficient and major leakage occurred. Clinical study. Stapling appeared clinically efficient on all arteries but one aorta: this severely calcified aorta was ligated conventionally. The staplers are not easy to use due to their shape and their lack of articulation. After a mean follow-up of 31.3 months, all the other stapled arteries were effectively ligated. CONCLUSION: The commercially available staplers can be used securely on moderately calcified arteries but stapling of severely calcified arteries should be avoided. These devices should be redesigned to facilitate their use in vascular surgery.

Aged↗

Uterine artery ligation for treatment of pregnant women with uterine leiomyomas who are undergoing cesarean section.

OBJECTIVE: To evaluate the therapeutic effects of uterine artery ligation for pregnant women with uterine leiomyomas, who are undergoing cesarean section. DESIGN: Prospective clinical study without randomization. SETTING: University-affiliated tertiary referral center. PATIENT(S): Forty-eight women with uterine leiomyomas undergoing cesarean section for obstetric reasons were enrolled into the study. Diagnosis was established with ultrasound before or during early pregnancy. INTERVENTION(S): Ligation of the bilateral uterine arteries was performed immediately after closure of the uterine incision wound. MAIN OUTCOME MEASURE(S): Blood loss during cesarean section, dominant leiomyoma size, and future surgical intervention for symptomatic leiomyoma. RESULT(S): Twenty-six (54%) of 48 patients underwent uterine artery ligation during cesarean section (group I), and 22 (46%) received cesarean section only (group II). The average follow-up time was 38.5 months. The average blood loss during surgery was 254 +/- 92.3 mL for group I and 278 +/- 160.5 mL for group II. Hemoglobin on the first postoperative day was 11.2 +/- 0.9 g/dL for group I and 10.4 +/- 1.1 g/dL for group II. One patient in group II required blood transfusion due to hemorrhage. Two patients (7.7%) in group I and 9 (40.9%) in group II underwent myomectomy or hysterectomy for symptomatic leiomyomas within 6-38 months after cesarean section. Reductions in the dominant myoma size (average: 45%) were demonstrated in group I patients postoperatively. Four patients (15.4%) in group I and three (13.6%) in group II had a repeat cesarean section during the follow-up period. CONCLUSION(S): Uterine artery ligation appears to be a promising method for treating pregnant women with uterine leiomyomas, who are undergoing cesarean section, because it is able to reduce postpartum blood loss and minimize the necessity of future surgery. Fertility is apparently not compromised by this treatment, which offers obstetricians with another choice between observation and myomectomy for pregnant women with leiomyomas who are undergoing cesarean section.

Adult↗

Endoscopic resection with hypertonic saline-solution-epinephrine injection plus band ligation for large pedunculated or semipedunculated gastric polyp.

BACKGROUND: Endoscopic resection of pedunculated polyps with heads 1 cm or greater in diameter presents a risk of bleeding. To minimize this complication, we performed endoscopic resection with hypertonic saline-solution-epinephrine injection plus band ligation and evaluated its safety and effectiveness. METHODS: Seventeen patients with 20 pedunculated or semipedunculated polyps with heads 1 cm or greater in diameter were treated with this technique. Conventional upper-GI endoscope, hypertonic saline-solution and epinephrine, sclerotherapy needle, and endoscopic band ligator device are needed for the procedure. OBSERVATIONS: All lesions were easily and safely resected. During this procedure, a band ligation chamber proved to be satisfactory for accurate recognition of a postpolypectomy ulcer under good visual control. No hemorrhage, perforation, or other complication occurred as a result of the use of this technique. The histologic resection margin was affected by nonneoplastic components in 6 of 20 lesions. Follow-up endoscopy 1 week later revealed a small, shallow ulcer without residual polyp in all lesions. CONCLUSIONS: This preliminary study suggests that endoscopic resection with hypertonic saline-solution-epinephrine injection plus band ligation is a simple and effective method for the prevention of polypectomy-associated bleeding. Prospective trials, including randomized controlled studies, are required to evaluate the suitability of this modality for wide clinical use.

Aged↗

Laparoscopic-assisted vaginal hysterectomy with uterine artery ligation through retrograde umbilical ligament tracking.

STUDY OBJECTIVE: To evaluate the clinical outcomes of uterine artery ligation through retrograde tracking of the umbilical ligament (RUL) in laparoscopic-assisted vaginal hysterectomy (LAVH). DESIGN: Prospective study (Canadian Task Force classification II-3). SETTING: University-affiliated hospital. PATIENTS: Two hundred twenty-five women with myomas or adenomyosis. INTERVENTION: Laparoscopic-assisted vaginal hysterectomy with uterine artery identification and ligation through RUL. MEASUREMENTS AND MAIN RESULTS: The median age of the patients was 46 years, and the median weight of the extirpated uteri was 340 g, with 26.2% of uteri weighing more than 500 g. The median operation time was 135 minutes, and the median blood loss was 50 mL. The median intramuscular meperidine requirements were 1 ampoule (50 mg), and the median hospital stay was 3 days. It took approximately 10 minutes from identification of the umbilical ligament to ligation of the uterine artery. Uterine weight of 500 g or more required a significantly longer operation time compared with uteri weighing less than 500 g (164 min vs 127 min median, p <.001), and there was more blood loss (100 mL vs 50 mL median, p <.001). There were no differences in the median intramuscular meperidine requirements or hospital stay between the two groups. No blood transfusion was needed in either group, even in patients with a uterine weight of more than 1000 g. By regression analysis, uterine weight was significantly related to blood loss and operation time. A linear relationship was found among uterine weight, operation time, and blood loss: Uterine weight = 87.589 + 1.881 x operation time + 0.48 x blood loss (R = 0.531, F = 35.694, degrees of freedom 184, p <.001). No complications related to RUL were observed, although two bladder injuries related to severe pelvic adhesion with endometriosis and previous cesarean section occurred. CONCLUSION: Minimal blood loss and a low complication rate were noted in LAVH by uterine artery ligation through RUL. This technique should be a valid approach, especially in patients in whom minimal blood loss must be achieved.

Adult↗

A behavioral model of neuropathic pain induced by ligation of the common peroneal nerve in mice.

UNLABELLED: Different laboratory animal models of neuropathic pain that replicate pathophysiological changes in patients have been developed. In most animal models of neuropathic pain, both sensory and motor nerves are injured. Thus, animals usually show both abnormal sensory and motor responses. Assessment of the sensory system is likely to be affected by the motor defects, although motor functions have not been evaluated in previous neuropathic pain models. An ideal neuropathic pain model to assess behavioral nociceptive responses in animals is one without affecting motor function and without muscle injury. Here, we report a novel mouse model of neuropathic pain with normal motor functions. Ligation of the common peroneal nerve near the head of fibula was performed by a less invasive procedure. Long-lasting behavioral allodynia and thermal hyperalgesia was observed in mice after the ligation. Furthermore, behavioral allodynia is resistant to morphine treatment at 5 mg/kg body weight, as reported in some cases of neuropathic pain. Standard rotarod test analysis confirmed intact motor functions. Our results show that ligation of the common peroneal nerve can be used as an efficacious mouse model for assessing behavioral nociceptive responses in neuropathic pain. PERSPECTIVE: Tests to assess behavioral responses in a neuropathic pain model depend on intact motor functions. Here we report a less invasive procedure to ligate common peroneal nerve of leg to induce neuropathic pain with least motor defects.

Analgesics, Opioid↗