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DNA ligation catalyzed by human topoisomerase II alpha.

The DNA ligation reaction of topoisomerase II is essential for genomic integrity. However, it has been impossible to examine many fundamental aspects of this reaction because ligation assays historically required the enzyme to cleave a DNA substrate before sealing the nucleic acid break. Recently, a cleavage-independent DNA ligation assay was developed for human topoisomerase IIalpha [Bromberg, K. D., Hendricks, C., Burgin, A. B., and Osheroff, N. (2002) J. Biol. Chem. 277, 31201-31206]. This assay overcomes the requirement for DNA cleavage by monitoring the ability of the enzyme to ligate a nicked oligonucleotide in which the 5'-terminal phosphate at the nick has been activated by covalent attachment to the tyrosine mimic, p-nitrophenol. The cleavage-independent ligation assay was used to more fully characterize the DNA ligation activity of human topoisomerase IIalpha. Results suggest that the active site tyrosine contributes little to the catalysis of DNA ligation beyond its primary role as an activating/leaving group. Although arginine 804 (the residue immediately N-terminal to the active site tyrosine) has been proposed to help anchor the 5'-DNA terminus during cleavage, conversion of this residue to alanine had only a modest effect on DNA ligation. Thus, it appears that arginine 804 does not play an essential role in DNA strand joining. In contrast, disruption of base pairing at the 5'-DNA terminus abrogated DNA ligation in the absence of a covalent enzyme-DNA bond. Therefore, it is proposed that base pairing represents a secondary mechanism for aligning the 5'-DNA termini for ligation. Finally, the human enzyme appears to ligate the two scissile bonds of a cleavage site in a nonconcerted fashion.

Antigens, Neoplasm↗

Regulation of tumor necrosis factor-alpha expression by CD40 ligation in BV-2 microglial cells.

Ligation of CD40 has been shown to induce/stimulate the expression of tumor necrosis factor-alpha (TNF-alpha) in microglial cells. This study delineates the mechanism by which CD40 ligation regulates the expression of TNF-alpha in BV-2 microglial cells. There was very little induction of TNF-alpha by ligation of CD40 alone by either cross-linking antibodies against CD40 or recombinant CD40 ligand (CD154). The absence of any increase in TNF-alpha production by CD40 ligation alone even in CD40-overexpressed BV-2 microglial cells suggest that signal transduced by the ligation of CD40 alone is not sufficient for strong induction of TNF-alpha. However, CD40 ligation markedly induced the production of TNF-alpha as well as the expression of TNF-alpha mRNA in interferon-gamma (IFN-gamma)-stimulated BV-2 glial cells. Ligation of CD40 in CD40-overexpressed cells markedly enhanced the expression of TNF-alpha in the presence of IFN-gamma. To understand the mechanism of CD40 ligation-mediated induction/stimulation of TNF-alpha, we investigated the role of nuclear factor-kappaB (NF-kappaB) and C/EBPbeta. IFN-gamma alone was able to induce the activation of NF-kappaB as well as C/EBPbeta. However, CD40 ligation alone in the presence or absence of CD40 overexpression induced the activation of only NF-kappaB and not that of C/EBPbeta, suggesting that the activation of NF-kappaB alone by CD40 ligation is not sufficient to induce the expression of TNF-alpha and that the activation of C/EBPbeta is also necessary for strong induction of TNF-alpha. Consistently, a dominant-negative mutant of p65 (Delta(p65)) and that of C/EBPbeta (DeltaC/EBPbeta) inhibited the expression of TNF-alpha in BV-2 microglial cells stimulated with the combination of IFN-gamma and CD40 ligand. Taken together, these studies suggest that activation of both NF-kappaB and C/EBPbeta is important for strong induction of TNF-alpha and that CD40 ligation regulates the expression of TNF-alpha by modulating the activation of only NF-kappaB but not that of C/EBPbeta.

Animals↗

Mechanisms of impaired hepatic fatty acid metabolism in rats with long-term bile duct ligation.

Hepatic metabolism of fatty acids is impaired in experimental animals with long-term bile duct ligation. To characterize the underlying defects, fatty acid metabolism was investigated in isolated hepatocytes and isolated liver mitochondria from rats subjected to long-term bile duct ligation or sham surgery. After starvation for 24 hr, the plasma beta-hydroxybutyrate concentration was decreased in rats with bile duct ligation as compared with control rats. Production of beta-hydroxybutyrate from butyrate, octanoate and palmitate by hepatocytes isolated from rats subjected to bile duct ligation was also decreased. Liver mitochondria from rats subjected to bile duct ligation showed decreased state 3 oxidation rates for L-glutamate, succinate, duroquinone, and fatty acids but not for ascorbate as substrate. State 3u oxidation rates (uncoupling with dinitrophenol) and activities of mitochondrial oxidases were also decreased in mitochondria from rats subjected to bile duct ligation. Direct assessment of the activities of the subunits of the electron transport chain revealed reduced activities of complex I, complex II and complex III in mitochondria from rats subjected to bile duct ligation. Activities of the beta-oxidation enzymes specific for short-chain fatty acids were all reduced in rats subjected to bile duct ligation. Mitochondrial protein content per hepatocyte was increased by 32% in rats subjected to bile duct ligation compared with control rats. Thus the studies directly demonstrate mitochondrial defects in fatty acid oxidation in rats subjected to bile duct ligation, which explain decreased ketosis during starvation.

3-Hydroxybutyric Acid↗

Rubber band ligation of hemorrhoids and rectal mucosal prolapse in constipated patients.

Rubber band ligation was used in 160 patients with internal hemorrhoids; 43 of them also had rectal anterior mucosal prolapse; 13 had prolapse alone. Two thirds of the patients underwent a single rubber band ligation and one third a double rubber band ligation in one session without anesthesia. Ninety-four required repeated ligations. A follow-up of 25 +/- 16 months (mean +/- SD) was carried out in 153 of them. Rubber band ligation was followed by prolonged bleeding in six patients and severe pain requiring removal of the rubber band in 12 patients. The complication rate decreased significantly (P less than .05) in the last 80 patients. Compared with multiple ligation, single rubber band ligation in one sitting was followed by a lower complication rate (P less than .01). Long-term results were good in 71 percent of the patients. (A formal hemorrhoidectomy was needed within two years in 6 percent.) A significantly lower recurrence rate of 9 percent was noted in those with normal bowel habits, when compared with constipated subjects whose symptoms recurred in 85 percent (P less than .001). Constipation seems to be a predictable factor in worsening the outcome of rubber band ligation. Rubber band ligation is followed by a lower complication rate when performed in a single ligation.

Constipation↗

Bile canalicular barrier function and expression of tight-junctional molecules in rat hepatocytes during common bile duct ligation.

Tight junctions of hepatocytes form the intercellular barrier between the blood circulation and bile flow. We focused on early stages of common bile duct ligation to observe changes in tight junctions without the irreversible changes seen after lengthy ligation. Common bile ducts of 12-week-old male rats were ligated for 6 h because, at this time point, no histological changes were observed. Serum bilirubin and bile acid levels began to increase 3 h after ligation and were restored to the control level immediately after surgical removal of the ligation. To examine the barrier of hapatocytes, horseradish peroxidase was injected via the femoral vein, and bile was collected for the first 10 min. A four-fold elevation of the secretion and concentration was observed in the bile of ligated rats compared with that of control animals. We next examined lanthanum permeability by perfusion fixation of the liver. At 6 h after ligation, both dilation of the bile canaliculi and partial loss of microvilli were commonly observed. There were dense deposits of lanthanum in almost all bile canaliculi of ligated rats. In control animals, neither dilation of the bile canaliculi nor loss of microvilli was detected, and only 44% of bile canaliculi exhibited deposits. An apparent increase of occludin mRNA expression was detected in livers after 6 h ligation, whereas the expression of claudin-1, -2, and -3 was not influenced by ligation. These results indicate that regulation of occludin gene expression is different from that of claudin-1, -2, and -3. The early phase of bile stasis employed in this study is thought to be an indispensable approach for understanding the precise regulation of tight junctions.

Animals↗

Effect of multiple ligations of the external carotid artery and its branches on blood flow in the internal maxillary artery in dogs.

PURPOSE: The effect of occlusion of the external carotid system on blood flow of the internal maxillary artery was investigated in 16 dogs. METHODS: The external carotid system was occluded by ligation or clamping at different levels separately or simultaneously and the blood flow of the internal maxillary artery was measured with an electromagnetic flowmeter before and after each occlusion. RESULTS: The ligation of the external carotid artery below (low ligation) and above (high ligation) the origin of the occipital, lingual, and facial arteries reduced the blood flow by 61.1% and 71.5%, respectively. Low ligation together with ligation of the lingual artery reduced the blood flow by 73.5%. Multiple ligations (high and low ligations combined with ligations of the occipital, lingual, and facial arteries) reduced the blood flow by 81.8%. The internal maxillary artery was sectioned after the multiple ligations, and retrograde flow from the distal segment was studied. The flow was only a trace and could not be measured with the flowmeter. Total blood loss from both ends almost equaled the blood flow of the proximal segment, 18.2% of normal. CONCLUSIONS: Multiple occlusion appears to be the most effective treatment for hemorrhage from the initial part of the internal maxillary artery.

Animals↗

Prediction of immediate ventricular arrhythmias after coronary artery ligation.

OBJECTIVES: Our aim was to test the hypothesis that increased beat to beat morphologic variations in the body surface electrocardiogram (ECG) are associated with fragmented diastolic electrical activity that appears after coronary artery ligation and to correlate the appearance of spontaneous ventricular fibrillation after coronary ligation with the magnitude of the ECG beat to beat variability. BACKGROUND: Unstable and variably delayed electrical activation precedes the development of ventricular fibrillation in dogs with acute ischemia. Detection of these highly variable low amplitude signals from the body surface is currently impossible. We have developed a system designed to measure the degree of beat to beat variability of the ECG. METHODS: With high fidelity electrocardiography, subtle beat to beat ECG morphologic variations were detected in epicardial and body surface electrograms and quantified as the variance of the ECG voltage at specific points of the cardiac cycle. The ratio of the variance at the QRS offset to that of the QRS onset (beat to beat variability index) was then calculated. RESULTS: Ventricular fibrillation developed in 12 of 27 dogs after left anterior descending coronary artery ligation. In 7 of the 12 dogs it occurred immediately (< 15 min) after ligation; in the other 5 it developed late (> 15 min) after ligation. Dogs with subsequently immediate ventricular fibrillation had a significantly higher beat to beat variability index than that of dogs with late or no ventricular fibrillation both before coronary ligation (4.7 +/- 1.4 vs. 1.1 +/- 0.2 and 0.8 +/- 0.1, respectively, p < 0.001) and after ligation (6.4 +/- 2.6, 1.0 +/- 0.6 and 1.2 +/- 0.6, respectively, p < 0.001). In dogs that developed ventricular fibrillation immediately after coronary ligation, the arrhythmia was preceded by fragmented diastolic electrical activity on the epicardial electrogram and a simultaneous increase in the beat to beat morphologic variability of the terminal portion of the body surface ECG QRS complex. CONCLUSIONS: Beat to beat QRS offset morphologic variations appear to be increased before and further increased after coronary artery ligation in dogs that develop ventricular fibrillation immediately after ligation. Increased beat to beat variability index may be associated with the presence of electrophysiologic instability and can predict early ventricular fibrillation.

Analysis of Variance↗

High rate of right ventricular infarction after ligation of mid left anterior descending artery in rats.

BACKGROUND: The left anterior descending artery (LAD) supplies the left ventricle in humans. LAD ligation has been commonly used in rats to induce left ventricular (LV) infarction for research purposes. However, the myocardial supply territories of LAD are not well established in rats. We measured the infarction zone in rats after ligation of the mid-LAD. METHODS: Twenty-four male Sprague-Dawley rats weighing 300-350 g were selected for LAD ligation for the induction of ischemic cardiomyopathy. The surgery was performed under full anesthesia. Left-sided thoracotomy was performed through cuts in the fifth and sixth ribs. Ligation of the LAD was performed 1 to 2 mm distal to a line between the left border of the pulmonary conus and the right border of the left atrial appendage. LAD was ligated after the first diagonal and septal branches. After 24 h, the hearts were removed and stained with Tetrazolium Tetrachloride (TTC) for the detection of infracted areas. RESULTS: Ligation of LAD induces 85% infarction of the right anterior free wall and anterior right ventricular septum and induces 100% infarction of the anterior free wall of the left ventricle and anterior septum. Infarction after LAD ligation extends all the way to the distal of the ligation site down to the apex of the heart. CONCLUSIONS: Mid-LAD ligation after the first septal and diagonal branches causes substantial right ventricular infarction in addition to LV infarct in rats. Therefore, the hemodynamic effect of right ventricle infarct should be considered in research involving LAD ligation in rats.

Animals↗

White ball appearance in endoscopic ligation of bleeding esophageal varices.

BACKGROUND: Endoscopic variceal ligation is useful in the control of bleeding from esophageal varices. However, confirmation of ligation precisely at the site of bleeding is usually difficult when treating massive variceal bleeding. Characteristic endoscopic findings that appeared when ligation was performed at the site of bleeding are reported in this article. METHODS: Emergency endoscopic variceal ligation was performed in 14 patients with active bleeding from esophageal varices. Endoscopic findings after variceal ligation at the site of bleeding were compared with those at sites without bleeding. RESULTS: Active bleeding ceased just after endoscopic ligation at the site of bleeding in all patients. After ligation of the bleeding site of the varix, an unusual white-colored ball-like appearance (white ball appearance) was observed in all patients. This finding was markedly different from the purple-colored ball-like appearance that is usually observed after ligation of a varix at a site without bleeding. CONCLUSIONS: White ball appearance was a characteristic finding that appeared after ligation of a varix at the site of bleeding. This finding may be useful in the confirmation of successful ligation of a varix at its bleeding site.

Emergency Treatment↗

Prevalence of paraesophageal varices and gastric varices in patients achieving variceal obliteration by banding ligation and by injection sclerotherapy.

BACKGROUND: The impact of banding ligation and injection sclerotherapy on paraesophageal varices and gastric varices has received scarce attention. We conducted a study using endoscopic ultrasound (EUS) to visualize paraesophageal varices and gastric varices in patients who underwent sclerotherapy and banding ligation. METHODS: Patients with esophageal variceal bleeding whose varices were obliterated by ligation (44 patients) and by sclerotherapy (35 patients) were enrolled. EUS was used to compare the prevalences of paraesophageal varices and gastric varices between the treatment groups. The correlation between paraesophageal varices and esophageal variceal recurrence and recurrent bleeding was assessed. RESULTS: The prevalence of paraesophageal varices was 86% in the ligation group compared with 51% in the sclerotherapy group (p = 0.002). The prevalence of gastric varices was slightly higher in the ligation group than in the sclerotherapy group (43% vs. 26%, p = 0.18). Esophageal varices recurred in 70% of the ligation group and 43% of the sclerotherapy group (p = 0.04). Patients in both groups with more severe paraesophageal varices had a significantly higher rate of variceal recurrence (p = 0.002 in ligation group and p = 0.001 in sclerotherapy group). Bleeding recurred in 6 patients in the ligation group and 4 patients in the sclerotherapy group. All patients with recurrent bleeding had paraesophageal varices. The rate of recurrent bleeding was significantly higher in patients with paraesophageal varices (p < 0.0001). CONCLUSIONS: EUS was helpful in the imaging of paraesophageal and gastric varices after sclerotherapy or banding ligation. Paraesophageal varices were more frequently noted in patients undergoing ligation. The presence of paraesophageal varices may predict the recurrence of esophageal varices and recurrent bleeding.

Endosonography↗

The sequence of vessel ligation affects tumor release into the circulation.

OBJECTIVE: Whether the sequence of pulmonary vein and artery ligation in pulmonary lobectomy for carcinoma affects intraoperative hematogenous cancer cell dissemination is not known. We examined whether vessel ligation sequence affects the presence of circulating cancer cells as reflected by carcinoembryonic antigen messenger ribonucleic acid. METHODS: We assayed for the transcripts of carcinoembryonic antigen messenger ribonucleic acid by reverse-transcriptase polymerase chain reaction in peripheral blood taken before, during, and after operation from 30 patients with non-small-cell lung cancer who underwent a curative lobectomy and from six patients with limited-stage small-cell lung cancer who were treated initially with chemotherapy followed by lobectomy. Each patient was randomly assigned before the operation to have either pulmonary vein ligation or pulmonary artery ligation first. Blood taken from 10 patients with interstitial pulmonary fibrosis who underwent an open lung biopsy and 41 healthy subjects served as a control. RESULTS: No control samples were positive for transcripts. Sixteen of the preoperative blood samples from the 30 patients with non-small-cell cancers were positive. Of these 16, eight samples remained positive even after lobectomy was performed; the remaining eight samples (four in each ligation group) became negative. Of the 14 initially negative samples (seven in each ligation group), nine samples became positive during the operation. Such conversion during the operation was more common with arterial ligation first (six patients, 85.7%) than with venous ligation first (three patients, 42.9%). Samples from all six patients with small-cell cancer were positive before the operation, and five of six samples remained positive after the operation. CONCLUSIONS: Many patients with non-small-cell lung cancer have systemic disease even when they were thought to have resectable tumors. Ligating the pulmonary vein before ligating the artery may lessen intraoperative hematogenous dissemination. Most small-cell lung cancers represent systemic disease even when considered resectable.

Aged↗

Recurrence of esophageal varices following endoscopic treatment and its impact on rebleeding: comparison of sclerotherapy and ligation.

BACKGROUND/AIMS: Endoscopic variceal ligation is superior to sclerotherapy because of its lower rebleeding and complication rates. However, ligation is not without drawbacks due to a higher tendency to variceal recurrence. We conducted a randomized cohort study to delineate the long-term history of variceal recurrence following ligation and sclerotherapy, and to clarify the impact of recurrence on rebleeding and on the consumption of endoscopic treatment resources. METHODS: Two hundred cirrhotic patients with esophageal variceal bleeding were randomized to undergo maintenance endoscopic variceal sclerotherapy or ligation. RESULTS: One hundred and forty-one patients achieved variceal eradication and were regularly followed up for 2.2 to 6.7 (mean: 5.1 +/- 1.2) years. The demographic data, hepatic reserve, bleeding severity, and endoscopic features of both sclerotherapy (n=70) and ligation (n=71) showed no difference. Forty (57.1%) patients who underwent sclerotherapy experienced 58 recurrences of esophageal varices, in contrast to the 46 (64.8%) patients who underwent ligation and experienced 81 episodes of recurrence. Kaplan-Meier analysis showed that within 2 years variceal recurrence was more frequent for ligation than sclerotherapy, and the difference decreased thereafter. Multiple recurrence appeared more common with ligation (1/2/3/4/5 episodes of recurrence: 46/23/8/3/1 vs. 40/14/3/1/0, p=0.08). On multifactorial analysis, the endoscopic treatment method and red wale markings were the two factors determining variceal recurrence. Rebleeding from recurrent esophageal varices was unusual and showed no difference between the two groups (7/58 vs. 6/81, p>0.05). Rebleeding from gastric varices was more common after eradication by sclerotherapy (7/19 vs. 1/16, p=0.085) than by ligation. The number of sessions required for eradication of recurrent varices was no different between the two groups. CONCLUSIONS: Early recurrence and multiple recurrence of esophageal varices are more likely in patients undergoing endoscopic ligation, compared to sclerotherapy; however, the recurrence did not lead to a higher risk of rebleeding or require more endoscopic treatment.

Aged↗

In utero percutaneous umbilical cord ligation in the management of complicated monochorionic multiple gestations.

The study was designed to report our experience with in utero percutaneous umbilical cord ligation for selective feticide in pre-viable, abnormal, monochorionic multiple gestations. The selection criteria prior to offering percutaneous umbilical cord ligation included normal anatomy in the other fetus(es), normal karyotype and polyhydramnios, or uterine contractions. The procedure was performed under combined endoscopic and sonographic guidance. Fifteen patients were referred for evaluation and possible treatment. Two patients were excluded because of misdiagnosis. The mean gestational age at the time of the procedure was 21 weeks (range 16-25 weeks). There were ten acardiac twins, one discordant twin with acrania, and two cases of twin-twin transfusion syndrome with a hydropic twin. Percutaneous umbilical cord ligation was accomplished in 11/13 (84%) cases. An average of 8.5 weeks (range 0-18.5 weeks) was gained after percutaneous umbilical cord ligation, and five of 11 patients delivered at or after 30 weeks. Seven of 11 patients undergoing ligation procedures had living children. Premature rupture of membranes occurred within 3 weeks in 4/13 (30%) of cases. In utero fetal demise remote from the procedure occurred in three ligated patients undergoing ligation, in two of which intraoperative bleeding occurred. One fetus with cystic fibrosis died in the newborn period. Percutaneous umbilical cord ligation is an evolving alternative technique for the management of abnormal monochorionic multiple gestations. The advantages of percutaneous umbilical cord ligation over other approaches include complete extravascular interruption of the blood flow in all vessels of the cord. This may prevent postmortem feto-fetal hemorrhage or possible embolic phenomena that may result in death of the normal twin, as seen with intravascular techniques. Percutaneous umbilical cord ligation prior to spontaneous death of a co-twin may also avert the neurological and other complications that may occur in the surviving twin. Technological advances should decrease the observed complications and improve the success rate of the procedure.

Diseases in Twins↗

Survival after high or low ligation of the inferior mesenteric artery during curative surgery for rectal cancer.

In an attempt to determine whether "high ligation" of the inferior mesenteric artery during surgery for cancer of the rectum and rectosigmoid confers any significant 5-year survival advantage over "low ligation," the outcome of 1370 patients was reviewed. There were 784 patients in whom the inferior mesenteric artery was ligated below the origin of the left colic artery (low ligation) and 586 in whom it was ligated above this level (high ligation). The distribution of histologic grades of the tumors and incidence of venous invasion were similar in both groups. Five-year follow-up was complete in 98.5%. No difference in the crude or age-corrected 5-year survival was found for patients with Dukes A, B, C overall, or C1 tumors, whether having had a low or high ligation. In hopes of identifying a population that benefited from high ligation, C1 patients were further subgrouped according to tumor location and number of involved lymph nodes. However, in no such subgroup was any significant high ligation advantage seen. In conclusion, high ligation of the inferior mesenteric artery has not been found to improve 5-year survival in patients with cancer of the rectum or rectosigmoid.

Aged↗

Long-term follow-up of brachial artery ligation in children.

Ligation of the brachial artery in the antecubital fossa in children can be performed without limb loss, but the effect on subsequent limb growth is unknown. From 1969 to 1974, brachial artery ligation for insertion of a Scribner shunt was performed in 27 patients with a mean age of 8.4 years (range, 3 to 15 years). We examined 11 patients, all with functional renal transplants, a mean of 15.8 years (range, 13 to 18 years) after ligation. Nine patients had unilateral ligation and two had bilateral ligation. The patients were examined for arm length and circumference, resting blood pressure at the wrist, neurologic function of the arm, and exercise tolerance. A significant difference in resting arterial pressures in the ligated extremity was uniformly noted (mean systolic pressure 106 mmHg versus 123 mmHg in 7 patients, p less than 0.01). Although no patient specifically complained of problems with the ligated side, six of nine patients with unilateral ligation experienced arm discomfort on stress testing. There was no significant difference in limb circumference or length between the ligated and unligated extremity. Ligation of the brachial artery in growing children with renal disease caused diminished resting pressure and mildly decreased exercise tolerance but did not lead to limb loss or subsequent growth abnormalities.

Adolescent↗

Effect of segmental artery ligation on the blood supply of the thoracic spinal cord during anterior spinal surgery: a quantitative histomorphological fresh cadaver study.

STUDY DESIGN: Human cadaver quantitative morphometric analysis of the blood vessels in the spinal cord after ligation of segmental arteries. OBJECTIVES: To investigate the effect of ligation of segmental arteries on the quantity and density of the blood vessels in the spinal cord. SUMMARY OF BACKGROUND DATA: Ligation of segmental arteries is often used in the anterior approach for correction scoliosis. However, whether or not segmental artery ligation is liable to deny the spinal cord an adequate blood supply, thus leading to paraplegia, still remains controversial. METHODS: Eleven fresh cadavers were divided into control, unilateral, and bilateral groups. For the unilateral and bilateral groups, 5 segmental vertebral arteries (T7-T11) were ligated unilaterally and bilaterally, respectively. Then, the number and density of blood vessels at different levels in the 3 groups were measured. RESULTS: Compared to that of the corresponding level in the control group, the number of blood vessels at T5 to L1 all decreased in the ligation groups. And significant differences were found at T8 (82.80 +/- 16.36), T10 (77.80 +/- 19.80), and T11 (99.20 +/- 14.85) levels, compared to those of the corresponding levels in the control group: T8 (175.80 +/- 8. 31), T9 (176.40 +/- 32. 33), T10 (171.40 +/- 9. 73), and T11 (189.20 +/- 15. 92). Further decrease was found at each corresponding level in the bilateral group, and significant differences were found at T8 (65.80 +/- 15.55), T9 (24.80 +/- 13.43), T10 (0), T11 (0), and T12 (0) levels. Similar results were obtained with regard to the density of blood vessels. Significant differences were found at T11 (1.246 +/- 0.112) and L1 (1.349 +/- 0.109) in the unilateral group, and T9 (0.260 +/- 0.088), T10 (0), T11 (0), T12 (0), and L1 (0.147 +/- 0.117) in the bilateral group compared to those of the corresponding levels in the control group: T9 (1.810 +/- 0.202), T10 (1.833 +/- 0.175), T11 (2.308 +/- 0.335), T12 (2.510 +/- 0.617), and L1 (2.193 +/- 0.033). CONCLUSIONS: This study suggests that the more levels the ligation encompasses, the higher the risk of spinal cord damage. Therefore, caution should be taken when several segmental arteries are to be ligated in the clinical setting. What is more, bilateral ligation, which is worse than unilateral ligation, can lead to a significant decrease in the number and density of blood vessels of the spinal.

Adolescent↗

Skeletal muscle ventricles: full versus half aortic ligation.

BACKGROUND: Skeletal muscle ventricles have been shown to provide effective aortic diastolic counterpulsation in an experimental model. Construction has included full ligation of the thoracic aorta. The authors sought to determine if these muscle pumps could function effectively without fully ligating the aorta. METHODS: Skeletal muscle ventricles were constructed in two groups of dogs. Group 1 had their aortas fully ligated (n = 10) while group 2 had their aortas narrowed by 50% (n = 10). The animals were followed for 10 weeks. RESULTS: There was no significant difference in femoral diastolic augmentation at implant or at 10 weeks (19.1% +/- 9.9% in group 1 [full ligation] versus 16.3% +/- 10.2% in group 2 [half ligation] p = 0.502). Survival to 10 weeks was significantly better in group 1 (full ligation). Nine of 10 animals in this group survived versus 4 of 10 in group 2 (p = 0.019). Two animals survived in the half ligation group with effective augmentation and without thrombus formation. CONCLUSION: Both models produce effective diastolic counterpulsation. Survival was decreased in this model using half ligation, and survival without complication was observed in 2 of 10 animals. Currently the overall results are better with the full aortic ligation model. However, design modifications will probably result in an effective model of diastolic counterpulsation without full aortic ligation.

Animals↗

Distribution of extracellular potassium and electrophysiologic changes during two-stage coronary ligation in the isolated, perfused canine heart.

We studied the relation between [K+]o and the electrophysiologic changes during a "Harris two-stage ligation," which is an occlusion of a coronary artery, preceded by a 30-minute period of 50% reduction of flow through the artery. This two-stage ligation has been reported to be antiarrhythmic. Local direct current electrograms and [K+]o signals from up to 48 intramural sites were simultaneously recorded in isolated, perfused dog hearts. A second period of one-stage ligation was compared with a consecutive two-stage ligation because reproducibility in [K+]o and electrophysiologic changes are established only after the first period of ischemia. In control experiments, no difference was found between the second and third period of one-stage ligation in the electrophysiologic changes and in increases in [K+]o. After complete occlusion during two-stage ligation, activation block in the ischemic tissue occurred about 6 minutes earlier than during one-stage ligation, but the average potassium concentration at which block occurred was identical. This [K+]o during total ischemia was achieved earlier during two-stage ligation than during one-stage ligation. No indication was found for a large decrease of intracellular potassium content during the period of low flow perfusion. Early activation block may explain the previously reported reduced incidence of ventricular fibrillation during two-stage ligation.

Animals↗