Artery Ligation Research Articles

OPTIMIZATION OF OPERATIVE DELIVERY OF WOMEN IN LABOR WITH PLACENTA PREVIA

The aim – to evaluate the effectiveness of preventive ligation of uterine vessels during caesarean section in women with placenta previa.
 Material and Methods. The study was conducted on the basis of the Regional Perinatal Center and Maternity Hospital № 5 (Odessa) for 2000–2020 and performing the main stage of cesarean section after reducing perfusion in the placenta. Uterine ligation was performed after fetal removal. The volume of blood loss, the condition of the mother and fetus were monitored, and perinatal results were analyzed.
 Statistical processing was performed by methods of variance and frequency analysis using Statistica 13.0 software (TIBCO, USA).
 Results. The mean age of pregnant women was 33.4±1.2 years. The clinic of placenta previa during pregnancy was extremely scanty. As a rule, the diagnosis was made during ultrasound monitoring. In 16 (17.7 %) there was repeated bleeding from the genital tract without pain and increased uterine tone, with the development of anemia of moderate severity. Single bleeding was observed in 53 (58.9 %) women.
 Blood loss was 1380±112 ml in group I, 466±34 ml in group II (p<0.05). The frequency of anemia in the postoperative period was 38.0 % and 17.5 %, respectively (p<0.05). All newborns were discharged on the 5-7th day of the postpartum period in satisfactory condition. There were no cases of distress syndrome.
 Conclusions: 1. The method of control of blood loss during placenta previa by ligation of the uterine arteries is effective – blood loss was in group I 1380±112 ml, in group II – 466±34 ml (p<0,05). 2. The frequency of anemia in the postoperative period was 38.0 in group I and 17.5 % in group II (p<0.05).

Lingbao Huxin Pill Alleviates Apoptosis and Inflammation at Infarct Border Zone through SIRT1-Mediated FOXO1 and NF- κ B Pathways in Rat Model of Acute Myocardial Infarction

To investigate whether Lingbao Huxin Pill (LBHX) protects against acute myocardial infarction (AMI) at the infarct border zone (IBZ) of myocardial tissue by regulating apoptosis and inflammation through the sirtuin 1 (SIRT1)-mediated forkhead box protein O1 (FOXO1) and nuclear factor-κ B (NF-κ B) signaling pathways. Six-week-old Wistar rats with normal diet were randomized into the sham, the model, Betaloc (0.9 mg/kg daily), LBHX-L (0.45 mg/kg daily), LBHX-M (0.9 mg/kg daily), LBHX-H (1.8 mg/kg daily), and LBHX+EX527 (0.9 mg/kg daily) groups according to the method of random number table, 13 in each group. In this study, left anterior descending coronary artery (LADCA) ligation was performed to induce an AMI model in rats. The myocardial infarction area was examined using a 2,3,5-triphenyltetrazolium chloride solution staining assay. A TdT-mediated dUTP nick-end labeling (TUNEL) assay was conducted to assess cardiomyocyte apoptosis in the IBZ. The histopathology of myocardial tissue at the IBZ was assessed with Heidenhain, Masson and hematoxylineosin (HE) staining assays. The expression levels of tumor necrosis factor α (TNF-α), interleukin (IL)-6, IL-1 β, and intercellular adhesion molecule-1 were measured using enzyme-linked immunosorbent assays (ELISAs). The mRNA expressions of SIRT1 and FOXO1 were detected by real-time qPCR (RT-qPCR). The protein expressions of SIRT1, FOXO1, SOD2, BAX and NF- κ B p65 were detected by Western blot analysis. The ligation of the LADCA successfully induced an AMI model. The LBHX pretreatment reduced the infarct size in the AMI rats (P<0.01). The TUNEL assay revealed that LBHX inhibited cardiomyocyte apoptosis at the IBZ. Further, the histological examination showed that the LBHX pretreatment decreased the ischemic area of myocardial tissue (P<0.05), myocardial interstitial collagen deposition (P<0.05) and inflammation at the IBZ. The ELISA results indicated that LBHX decreased the serum levels of inflammatory cytokines in the AMI rats (P<0.05 or P<0.01). Furthermore, Western blot analysis revealed that the LBHX pretreatment upregulated the protein levels of SIRT1, FOXO1 and SOD2 (P<0.05) and downregulated NF- κ B p65 and BAX expressions (P<0.05). The RT-qPCR results showed that LBHX increased the SIRT1 mRNA and FOXO1 mRNA levels (P<0.05). These protective effects, including inhibiting apoptosis and alleviating inflammation in the IBZ, were partially abolished by EX527, an inhibitor of SIRT1. LBHX could protect against AMI by suppressing apoptosis and inflammation in AMI rats and the SIRT1-mediated FOXO1 and NF- κ B signaling pathways were involved in the cardioprotection effect of LBHX.

Effect and Mechanism of Lidocaine Pretreatment Combined with Dexmedetomidine on Oxidative Stress in Patients with Intracranial Aneurysm Clipping.

This study aimed to explore the effect and mechanism of lidocaine pretreatment combined with dexmedetomidine on oxidative stress in patients with intracranial aneurysm clipping. Many studies have used various drugs such as lidocaine to explore the effect and mechanism of lidocaine pretreatment. A total of 80 patients with intracranial aneurysm clipping surgery were randomly divided into 4 groups: the single lidocaine group, single dexmedetomidine group, lidocaine combined with dexmedetomidine group, and control group. The thread embolism method was used to establish a stable intracranial aneurysm model of Hashimoto rats. Fifty adult rats were randomly divided into a sham operation group, ligation of the left common carotid artery and bilateral posterior branch of renal artery, lidocaine group, dexmedetomidine group, and lidocaine combined with dexmedetomidine group. The colorimetric method was used to determine the oxidative stress indicators in brain tissue: MDA content, SOD activity, and T-AOC content. The western blot method characterized the protein levels related to oxidative stress: nNOS, iNOS, and NADPH oxidase subunits p22phox, gp91phox, and p47phox. The differences in each index between the groups were statistically significant (P < 0.05). Animal experiment results revealed that the content of MDA in the brain tissue of rats in the LD group was significantly lower than that in the single-drug group and sham group. The T-AOC and SOD concentrations in the LD group were significantly higher than those in the single-drug group and sham group, and the differences between the groups were statistically significant (P < 0.05). The protein expression of the LD group was significantly lower than that of the drug-alone group and model group, and the difference between groups was statistically significant (P < 0.05). To sum up, lidocaine pretreatment combined with dexmedetomidine can effectively maintain the hemodynamic stability of patients with intracranial aneurysm clipping and reduce postoperative oxidative stress response. Its mechanism of action may be related to the inhibition of oxidative stress damage mediated by nNOS, iNOS, and p22phox, gp91phox, and p47phox in the hippocampus. Our study has significant and applicable medical aspects in lidocaine pretreatment combined with dexmedetomidine on oxidative stress in patients.

Abstract 13142: Combined Treatment With Dapagliflozin and Exenatide is More Cardioprotective Than Either Agent Alone in a Non-Diabetic Mouse Model of Ischemia-Reperfusion Injury

Introduction: Sodium-glucose cotransporter 2 inhibitors (SGLT2i) and glucagon-like peptide-1 receptor agonists (GLP-1RA) have individually shown cardiovascular benefits in patients with type 2 diabetes (T2D). SGLT2i also reduced events in patients with reduced ejection fraction heart failure, with or without T2D. However, it is not known whether the cardiovascular effects of SGLT2i and GLP-1RA are through shared or distinct mechanisms, and whether combining these agents would confer additive cardioprotection against ischemia-reperfusion injury (IRI) in the absence of diabetes. Methods &amp; Results: Non-diabetic male C56BL/6-J mice randomized to 7-d treatment with SGLT2i dapagliflozin (Dapa) and/or GLP-1RA exenatide (Ex-4) or vehicle-controls underwent IRI via 30-min left anterior descending (LAD) artery ligation. Analysis of late cardiac remodeling at d-28 post-IRI revealed preserved ejection fraction (EF) in mice treated with Dapa+Ex4 (50±2%; n=12, P&lt;0.05) vs. vehicle-treated controls (36±3; n=11, P&lt;0.05), whereas treatment with Dapa- and Ex-4-alone showed no such benefit. These improvements in LV function were associated with reduced infarct size (%LV) in mice treated with Dapa+Ex4 (17±3; n=8, P&lt;0.001) and Ex-4-alone (29±3; n=10, P&lt;0.05) vs. vehicle-control (44±5; n=10). Metabolome and merged proteome+phosphoproteome analyses revealed systemic and myocardial metabolic modulation following 7-d Dapa+Ex-4 treatment, with distinct enrichment of mitochondrial electron transport chain pathways. Cardiomyocytes isolated from mice treated in vivo for 7-d also showed enhanced aerobic respiration as measured by oxygen consumption rate (OCR;17.6±1.7 pmol/min/μg protein; n=4 mice) compared Dapa- (8.9±0.8; n=3, P&lt;0.001), Ex-4-alone (11.4±0.9; n=3, P&lt;0.01) and vehicle-treated controls (9.5±0.6; n=5, P&lt;0.001). Conclusions: Combined therapy with SGLT2i+GLP-1RA in non-diabetic mice better prevented late cardiac remodeling after IRI compared to either agent alone or vehicle controls. These findings provide rationale for the combined use of these agents in a condition (IRI) for which there remains no approved therapy, and implicate metabolic modulation as a cardioprotective strategy in the absence of diabetes.

Abstract 10477: Targeting the Methyltransferase Setd7 Prevents Myocardial Ischemic Injury: A Translational Study

Introduction: Despite appropriate revascularization strategies, a significant number of patients with myocardial infarction (MI) develop ischemic heart failure suggesting that breakthrough therapies are yet to be approved in this setting. Methylation of non-histone proteins is emerging as a central regulatory mechanism in health and disease. The methyltransferase SETD7 has shown to methylate and alter the function of a variety of proteins in vitro, however its function in the heart is poorly understood. Hypothesis: In the present study we sought to determine the role of SETD7 in myocardial ischemic injury. Methods: Experiments were performed in neonatal rat ventricular myocytes (NRVM), SETD7 knockout mice (SETD7-/-) undergoing myocardial ischemia/reperfusion (I/R) injury, rats undergoing permanent left anterior descending (LAD) artery ligation, myocardial samples from patients with and without ischemic cardiomyopathy (ICM) as well as peripheral blood mononuclear cells from patients with ST elevation MI (STEMI) and age-matched healthy controls. Results: We show that SETD7 is activated upon energy deprivation in cultured NRVMs and methylates the Hippo pathway effector YAP, leading to its cytosolic retention and impaired transcription of antioxidant genes. Pharmacological inhibition of SETD7 by (R)-PFI-2 restored YAP nuclear localization thus preventing mitochondrial reactive oxygen species (mtROS) and apoptosis. SETD7 deletion in mice attenuated I/R injury, mtROS and LV dysfunction by restoring YAP-dependent transcriptional programs. SETD7/YAP dysregulation was also observed in rats with permanent LAD ligation and LV specimens from ICM patients. Of note, (R)-PFI-2 treatment prevented titin oxidation and myofilament stiffness in cardiomyocytes isolated from I/R mice and patients with ICM. Finally, SETD7 was upregulated in STEMI patients and its expression negatively correlated with antioxidant genes. Conclusions: In the present study we show that SETD7-dependent methylation of YAP is required for its inactivation, thus leading to myocyte oxidative stress and apoptosis. Therefore, we identified SETD7 as a valid and druggable therapeutic target to protect the heart during ischemia.

Abstract 10495: Mechanism of Cardiac Repair in Rat Myocardial Infarction Model Treated with Extracellular Vesicles from Differentiating Induced Pluripotent Stem Cell-Derived Cardiomyocytes

Introduction: A few reports showed the therapeutic effects of extracellular vesicles (EVs) secreted from induced pluripotent stem cell-derived cardiomyocytes (iPSCM) on animal ischemic cardiomyopathy models. However, the mechanism of the cardiac function restoration after EVs administration remained unclear. Then, this study aimed to identify the mechanism for the restoration of cardiac function after iPSCM-EVs treatment. Methods: We collected EVs from differentiating iPSCM (TnT positive &amp;gt; 80%) culture medium. Comprehensive miRNA-seq and proteome analysis in the EVs were performed. In vitro myocardial contraction assay and wound healing assay, and ex vivo aortic ring assay were performed. In vivo , we designed a rat model of myocardial infarction by left anterior descending artery (LAD) ligation and divided rats into two groups. Two weeks after LAD ligation, iPSCM-EVs (Group EV) or PBS (Group Ctl) were injected peri-infarct zone. We analyzed the sequential cardiac function, histological analysis, and comprehensive RNA sequence analysis of the border zone before the treatment and 3, 7, 14, and 28 days after the treatment (n=5 at each time point in each group). Results: EVs showed the potential of increased myocyte contraction velocity (11±0.7 vs 6.6±0.6 μm/s, mean±SD, p &amp;lt; 0.01) and enhanced endothelial migration in vitro and facilitated angiogenesis (46±6 vs 13±5 sprouting count, p=0.02) ex vivo . In vivo , Group EVs showed higher LVEF (57±5 vs 38±4 % at day28, p &amp;lt; 0.01) and smaller LVDd (6.8±0.3 vs 8.5±0.8 mm at day28, p &amp;lt; 0.01). Histological analysis showed a lower % fibrosis area in Group EV (22±6 vs 12±5 % at day28, p &amp;lt; 0.01) and significantly higher microvascular (vWF positive: 1.7 at day14 and 2.1 times higher at day28) and arterial (vWF and αSMA positive: 4.3 at day14 and 6.2 times higher at day28) density. RNA expression analysis showed the expression of HGF, SDF-1, and IGF-1 increased in Group EVs on day3 and 7. CTGF and collagen 1 increased in Group Ctl on day14 and 28. Conclusions: Intracardiac injection of iPSCM-EVs improved cardiac function in rat MI model via angiogenesis, increased myocyte contraction, and reduced fibrosis. Comprehensive expression analysis suggested the mechanism of action of EVs in cardiac repair.

Abstract 9430: A Novel Soluble Epoxide Hydrolase Peptide Vaccine Attenuates Cardiac Remodeling After Myocardial Infarction Through Angiogenesis

Introduction: Vaccination therapy has long-lasting effects and solves medication non-adherence. However, vaccination therapy on myocardial infarction (MI) has not been developed. Epoxyeicosatrienoic acids (EETs) play an important role in cardio-protective mechanisms through angiogenesis. Here, we developed a soluble epoxide hydrolase (sEH) peptide vaccine to increase the level of EETs and assessed its therapeutic effect for MI-induced heart failure. Hypothesis: We predicted that neovascularization by a sEH vaccine would reduce infract size and prevent post-MI cardiac remodeling. Methods and Results: We made a sEH peptide vaccine based on the amino-acid sequences and administrated the vaccine to rats. ELISA showed that the vaccine induced anti-sEH antibody. Mass spectrometry also confirmed that the vaccine significantly increased blood EETs levels compared to the saline group (P=0.007). We evaluated the effects of the sEH vaccine in the rat model of MI. One week after the left anterior descending artery (LAD) ligation, the vaccinated group significantly suppressed the increase of left ventricular systolic diameter (LVDs) and prevented the decline in left ventricular anterior wall (LVAW), fractional shortening (FS), and ejection function (EF) in echocardiography (P&lt;0.001, P&lt;0.001, P=0.002, and P&lt;0.001 respectively). With the pathological evaluation of the hearts, it was clear that the number of micro-vessels increased in the vaccinated group by immunostaining for CD31 and α-SMA (P=0.015 and P=0.027 respectively). Azan staining showed that infarct-induced fibrosis was lower in the vaccinated group (P=0.029). Western blot showed higher vascular endothelial growth factor (VEGF) expressions of heart muscles in the vaccinated group (P=0.040). Conclusion: The sEH vaccine therapy for MI induces angiogenesis, which promotes reverse cardiac remodeling. This vaccine is expected to be a treatment option to prevent heart failure after MI.

Neurological Deficit and Corrective Effect of Omega-3 Polyunsaturated Fatty Acids in Cerebral Ischemia in Rats: A case-control study

Objectives: It was to assess vasoprotective effects of ω-3 polyunsaturated fatty acids in cerebral ischemia. Materials and methods: The experiments were carried out on 42 male outbred white rats weighing 260 ± 20 g. modeling of cerebral ischemia was carried out under conditions of intravenous thiopental anesthesia (40-50 mg / kg). The studies used models of subtotal, partial and stepwise subtotal cerebral ischemia. The table shows the experimental groups and the number of animals in them. Subtotal cerebral ischemia (SCI) was modeled by simultaneous ligation of both common carotid arteries (CCA). Partial cerebral ischemia (PCI) was modeled by ligating one CCA on the right. Stepwise subtotal CI (SSCI) was performed by sequential ligation of both CCA with an interval of 1 day (subgroup 1), 3 days (subgroup 2), or 7 days (subgroup 3). To study the effects of omega-3 polyunsaturated fatty acids (ω-3 PUFA), animals with CI were injected intragastrically with the drug "Omegamed" (SCI+ω-3 PUFA) at a dose of 5 g / kg body weight for a week. The control group consisted of sham-operated rats of the same sex and weight. Neurological deficits were assessed in the "muscle strength", "swimming test" and "open field" tests after 5-6 hours of the ischemic period. The study was carried out 6 hours after the simulation of the CI. Quantitative continuous data were obtained, which were processed using the licensed computer program Statistica 10.0 for Windows (StatSoft, Inc., USA). Since the experiment used small samples that had an abnormal distribution, the analysis was carried out by methods of nonparametric statistics. Data are presented as Me (LQ; UQ), where Me is the median, LQ is the value of the lower quartile; UQ is the upper quartile value. Differences between groups were considered significant at p &lt;0.05 (Regression Model). Results: With a stepwise bilateral ligation of both common carotid arteries with an interval of 1 day, neurological disorders were most pronounced, which indicates an aggravation of neurological deficit with a reduction in the time between CCA dressings. In rats with SCI, the changes were more pronounced than with PCI, but less than with SCI. The least pronounced changes were noted in the 3rd subgroup (the interval between CCA dressings was 7 days). Studies have shown the dependence of the severity of brain damage in SSCI on the interval between the cessation of blood flow in both CCA. At a 7-day interval between CCA dressings, compensatory mechanisms were activated, which prevented the development of morphological changes and neurological deficits. When CCA was ligated with an interval of 1 day, the degree of neurological deficit was maximal, which indicates insufficient implementation of compensatory mechanisms. Compared with the control group, the rats of the "SCI+ω3-PUFA" group retained neurological deficit, the muscle strength indicator was 86% less (p&lt;0.05), the swimming duration - by 63% (p&lt;0.05), the number of crossed squares - by 55% (p&lt;0.05), the number of washes - by 62% (p&lt;0.05), the number of racks - by 62.5% (p&lt;0.05) and the number of bowel movements - by 60% (p&lt;0.05). However, in comparison with the SCI group, the neurological deficit was less pronounced. There was an increase in muscle strength by 67% (p&lt;0.05), swimming duration by 37.5% (p&lt;0.05) and the number of squares crossed in the open field test by 31% (p&lt;0.05), which indicates the presence of a corrective action in the ω-3 polyunsaturated fatty acids preparation. Conclusion: The introduction of the preparation of ω-3 polyunsaturated fatty acids has a corrective effect in conditions of subtotal cerebral ischemia, contributing to a lesser severity of manifestations of neurological deficit (an increase in muscle strength, duration of swimming and the number of squares crossed in the open field test).

1477 Epistaxis Management During The COVID-19 Pandemic First Wave- Do We Need to Admit Patients with Rapid Rhinos? A Complete Loop Audit

Abstract Introduction Epistaxis is a common ENT emergency, which if management requires nasal-packing, usually results in an inpatient admission. We audited our management of nasal-packing practices in the pre- and intra-pandemic era. Method Review of medical notes including patient demographics, reason for admission, time of admission, bed-day numbers, management plan and 30-day mortality and morbidity (M&amp;M). 1st-cycle- January 2020, 2nd-cycle during the 1st-wave of the COVID-19 pandemic April-June 2020. Change implemented- patients were sent home with their nasal-pack in-situ. Results Pre-pandemic we admitted 100% (n = 15) of patients requiring rapid-rhino (RR) insertion compared to 7% (n = 1) of patients during the 1st-wave with an average age of 69 and 74-years respectively. 67% of patients in each group were on an antiplatelet or anticoagulant. Most common co-morbidities were hypertension (67%v40%), atrial-fibrillation (27%v53%) and cognitive impairment (13%v20%). 60% of patients attended in the out-of-hours period (5pm-8am). There was no difference in M&amp;M. Bed-day average was 3.9-days and 2-days in the first and second groups. In the first group 5 patients (33%) needed arterial ligation with only one (7%) patient in the second group requiring ligation. Conclusions RR insertion and discharge with outpatient follow up is safe with no difference in M&amp;M. Total bed-days were 57v4 bed-days in group one compared to group two, with £222/bed-day (NICE costings statement) the total-price was £12654v£888. We hope that the traditional approach of admitting every patient with RR may be reconsidered as the standard and only required when necessary.

Left atrial geometry in an ovine ischemic mitral regurgitation model: implications for transcatheter mitral valve replacement devices with a left atrial anchoring mechanism

BackgroundTranscatheter mitral valve replacement (TMVR) is a challenging, but promising minimally invasive treatment option for patients with mitral valve disease. Depending on the anchoring mechanism, complications such as mitral leaflet or chordal disruption, aortic valve disruption or left ventricular outflow tract obstruction may occur. Supra-annular devices only anchor at the left atrial (LA) level with a low risk of these complications. For development of transcatheter valves based on LA anchoring, animal feasibility studies are required. In this study we sought to describe LA systolic and diastolic geometry in an ovine ischemic mitral regurgitation (IMR) model using magnetic resonance imaging (MRI) and echocardiography in order to facilitate future research focusing on TMVR device development for (I)MR with LA anchoring mechanisms.MethodsA group of 10 adult male Dorsett sheep underwent a left lateral thoracotomy. Posterolateral myocardial infarction was created by ligation of the left circumflex coronary artery, the obtuse marginal and diagonal branches. MRI and echocardiography were performed at baseline and 8 weeks after myocardial infarction (MI).ResultsSix animals survived to 8 weeks follow-up. All animals had grade 2 + or higher IMR 8 weeks post-MI. All LA geometric parameters did not change significantly 8 weeks post-MI compared to baseline. Diastolic and systolic interpapillary muscle distance increased significantly 8 weeks post-MI.ConclusionsSystolic and diastolic LA geometry do not change significantly in the presence of grade 2 + or higher IMR 8 weeks post-MI. These findings help facilitate future tailored TMVR device development with LA anchoring mechanisms.

Hemorrhoidal surgery in patients with IBD: caution is the parent of safety.

The aim of this study was to evaluate the outcome of hemorrhoidal surgery in patients with inflammatory bowel disease (IBD) undergoing surgery at our center. All adult patients with IBD undergoing hemorrhoidal surgery in our department between November 1, 2013 and July 7, 2020 were included in the study. At the time of surgery, the patients' IBD was in clinical, biological and endoscopic remission, and none of the patients had specific primary anoperineal lesions. We included 25 patients (48% female) with a mean age 48years (± 13.1years). There were 13 cases of CD (52%) and 12 of ulcerative colitis (UC). Pharmacological and instrumental hemorrhoidal treatment had failed in all patients. The CD lesions were exclusively ileal (77%) or ileocolic (23%). The surgical procedures performed for CD were mono-hemorrhoidectomy in three patients (21.4%), tripedicular hemorrhoidectomy in six patients (42.9%), and artery ligations with mucopexy in five patients (35.7%). UC was rectal (16.7%), rectosigmoid (66.7%), or pancolic (16.6%). The surgical procedures performed for UC were a tripedicular hemorrhoidectomy in ten patients (83.3%) and artery ligations with mucopexy in two patients (16.7%). The mean duration of postoperative follow-up was 15.1months. None of the patients was lost to follow-up. The mean time to wound healing after resection was 71.1days (± 21days) for patients with CD and 56.9days (± 6.7days) for patients with UC (p = 0.05). Postoperative complications were reported for four patients with CD (28.8%) and two patients with UC (16.7%). There was no suppuration, stenosis, or anal incontinence sequelae. Hemorrhoidal surgery resulted in a non-negligible frequency of complications in our series of IBD patients, especially in those with CD. Caution is, therefore, still necessary in this patient population.

One-stage thoracoscopic resection of bilateral bronchiectasis.

To evaluate the results of one-stage thoracoscopic resection of bilateral bronchiectasis. Between June 2009 and December 2020, there were 23 patients selected for one-stage thoracoscopic resection of bilateral bronchiectasis. Their average age was 58.5 (36-73). Female patients were more common, accounting for 17 (74%). Preoperatively, 17 (74%) patients mainly presented with hemoptysis and the other 6 (26%) patients with purulent sputum. In these 23 patients, a total of 121 segments were resected, with an average of 5.26 segments, ranging from 3 to 9 segments. Five of 17 patients with massive hemoptysis underwent ligation of bronchial arteries in addition to lung resections. The average operating time was 271 min, ranging from 145 to 500 min. The average blood loss was 108 ml, ranging from 20 to 600 ml. The average postoperative hospital stay was 8 days, ranging from 3 to 20 days. There was no surgical morbidity or surgical death. Hemoptysis and purulent sputum of all patients was almost controlled after surgery. One-stage thoracoscopic resections of bilateral localized bronchiectasis could be well-tolerated and safe for these selected patients. The one-stage operation could shorten the course of treatment.

Trauma Surgery and War: A Historical Perspective

The aim of this review is to introduce the progress in trauma surgery made during war. In the 16th century, Paré reintroduced ligature of arteries, which had been introduced by Celsus and Galen, instead of cauterization during amputation. Larrey, a surgeon in Napoleon’s military, adapted the “flying artillery” to serve as “flying ambulances” for rapid transport of the wounded. He established rules for the triage of war casualties, treating wounded soldiers according to the seriousness of their injuries and the urgency of medical care. To treat fractures and tuberculosis, Thomas created the “Thomas splint”, which was used to stabilize fractured femurs and prevent infection; in World War I (WWI), use of this splint reduced the mortality of compound femur fractures from 87% to less than 8%. During WWI, Cushing systematized the treatment of head injuries, reducing mortality among head injury patients. Gillies repaired facial injuries, and his experiences became the basis of craniofacial and aesthetic surgery. In WWII, McIndoe discovered that immersion in saline promoted burn healing and improved survival rates, and thus began saline baths and early grafting instead of using tannic acid. A high mortality rate in patients with acute renal failure was noted in WWII and the Korean War. In the Korean War, Teschan used the Kolff-Brigham dialyzer. The first use of medevac with helicopters was the evacuation of three British pilot combat casualties by the US Army in Burma during WWII. As a lotus blooms in the mud, military surgeons have contributed to trauma surgery during wartime.

Energy metabolism and redox status of the glutathione system in experimental brain ischemia and its correction by metabolic neuroprotectors

The changes in the parameters of oxidative stress, energy metabolism, and redox potential of the glutathione system in the rat brain following cerebral ischemia were studied. To correct metabolic disorders, the pantothenic acid derivatives were used in combination with precursors of glutathione biosynthesis and selenium substances.Cerebral ischemia was modeled by ligating the both common carotid arteries in rats for 2 h. Drugs were administered i.p. in the following doses: panthenol – 400 mg/kg, N-acetylcysteine – 150, nanoselen – 1 mg/kg, three times: 1 h before ligation of the carotid arteries, at the time of ligation and 1 hour after ligation. We showed that the development of oxidative stress caused by ischemia is accompanied by the changes in the parameters of energy metabolism and the pentose phosphate pathway in the cerebral hemispheres. Simultaneously, there are a decrease in the GSH level, an increase in the GSSG content, a decrease in the GSH/GSSG ratio, and the activation of enzymes of redox transformations of glutathione.The redox potential of the glutathione system decreases and shifts towards oxidation, while the level of S-glutathionylated proteins increases. Thus, the value of the GSH/GSSG ratio and the protein glutathionylation intensity are the sensitive indicators of the redox potential in the brain tissue and can be used as markers of the extent of changes in the redox balance. The panthenol injection to animals leads to a decrease in the content of free radical oxidation products, violations of oxidative phosphorylation and restoration of thiol-disulfide balance in the brain. When panthenol is administered together with N-acetylcysteine and nanoselen, the corrective effect of panthenol is enhanced.

Abstract P335: Nanoparticle-mediated Delivery Of TT-10 Promotes Myocardial Repair

The pharmaceutical product TT-10 increases cardiomyocyte proliferation and survival by upregulating nuclear levels of Yes-associated protein (Yap) and the expression of Yap-targeted genes. When evaluated in a mouse model of myocardial infarction (MI), intraperitoneal TT-10 administration was associated with improvements in infarct size and cardiac function one week after treatment, but functional parameters progressively declined at later time points [1]. Here, we tested our hypothesis that the potency of TT-10 for myocardial repair could be increased by loading it into poly-lactic-co-glycolic acid nanoparticles (NPs) before intramyocardial administration. Mice were treated with injections of DPBS (n=9), empty nanoparticles (Empty-NPs, n=8), TT-10 solution (TT-10-sol, n=8), or TT-10-loaded NPs (TT-10-NPs, n=9) immediately after MI was induced via permanent ligation of the coronary artery. Cardiac function was assessed via transthoracic echocardiography, infarct size via histological Fast-Green staining, cardiac hypertrophy via measures of the heart-weight:bodyweight (HW:BW) ratio, cardiomyocyte proliferation via staining for Ki67 and phosphorylated histone 3 (PH3), and apoptosis via TUNEL. In vitro assessments confirmed that TT-10 was released from the TT-10-NPs for up to four weeks, and that the NPs were taken up by cultured cardiomyocytes. One and four weeks after MI induction and treatment, measures of left-ventricular (LV) ejection fraction (EF) and fractional shortening (FS) were significantly greater in TT-10-NP animals than in the TT-10-sol, Empty-NP, or DPBS groups; LV EF and FS also remained stable in the TT-10-NP group, while measurements in all other groups worsened (but not significantly) (LV EF at Week 4: TT-10-sol vs TT-10-NPs; 22.25 ± 1.474 vs 43.95 ± 1.884, p&lt;0.05), between the two time points. TT-10-NP treatment was also associated with significantly smaller (by ~20%, p&lt;0.05) infarcts and significantly lower HW:BW ratios at Week 4; with significantly greater proportions of Ki67 + , PH3 + , and nuclear-Yap + cardiomyocytes at Week 1; and with significant declines in TUNEL + cardiomyocytes 72 hours after MI and treatment. Thus, NP-mediated delivery of TT-10 results in the efficacy of both the magnitude and durability of the benefits associated with promotion of myocyte proliferation in a mouse MI model. [1] H. Hara, N. Takeda, M. Kondo, M. Kubota, T. Saito, J. Maruyama, et al., Discovery of a Small Molecule to Increase Cardiomyocytes and Protect the Heart After Ischemic Injury, JACC Basic Transl Sci, 3 (2018) 639-653.

Therapeutic effects of moxibustion on neonatal mice with hypoxia-ischemia brain injury

Objective: To investigate the effects of moxibustion on the behavioral performance, brain morphological structure of mice with hypoxia-ischemia brain injury and to explore its mechanisms. Methods: One hundred and six ICR mice were randomly divided into three groups, sham group (n=23), model group (n=46) and moxibustion-treated group (n=37). Neonatal hypoxic-ischemia brain injury was induced by ligation of common carotid artery followed by hypoxia (8% oxygen, 100 min), and pups in the moxibustion-treated group were administered suspended moxibustion on the Dazhui points (GV14) at a height of approximately 2 cm over a hairless area of the skin once a day for 4 days (i.e. at 2, 24, 48 and 72 hours after hypoxia-ischemia procedure). Behavioral tests were used to evaluate behavioral performance. HE staining was used to observe brain morphological structure. Western blot was used to detect the expression of SOD2 protein, and spectrophotometry was used to determine the content of MDA in the ipsilateral brain. Results: Mouse pups in sham group showed that the behavioral performance was normal, the brain tissue cells were densely and neatly arranged, the expression of SOD2 and the level of MDA in the brain tissues were normal. Compared with sham group, mouse pups in the HI model group exhibited a significant longer latency to complete the righting reflex, geotaxis reflex, cliff avoidance (P＜0.05) and a marked shorter latency to complete the grip test (P＜0.05); and the HI model group had dramatic brain morphological changes showing missing regions, decreased expression of SOD2 protein (P＜0.05) and increased level of MDA in the brain. Compared with HI model group, mouse pups in the moxibustion-treated group exhibited a significant shorter latency to complete the righting reflex, geotaxis reflex, cliff avoidance test (P＜0.05) and a marked longer latency to complete the grip test (P＜0.05); and the moxibustion-treated group had less brain morphological changes, increased expression of SOD2 protein (P＜0.05) and decreased level of MDA in the brain (P＜0.05) . Conclusion: Moxibustion could improve behavioral performance and attenuate hypoxia-ischemia brain injury, which might be related to increasing the expression of SOD2 protein and decreasing the content of MDA, thus enhancing the anti-oxidative ability.

A rare case of sigmoid colon cancer in which the lower limbs received collateral blood flow from the inferior mesenteric artery owing to peripheral artery disease

BackgroundColorectal cancer and peripheral artery disease are common conditions in older adults and may coexist in this population. Lymph node dissection along the inferior mesenteric artery is a vital procedure in cases of left-sided colorectal cancer. However, the inferior mesenteric artery may show a collateral blood pathway in rare cases of peripheral artery disease. We report a case of advanced sigmoid colon cancer in which the lower limbs received inferior mesenteric artery flow owing to asymptomatic peripheral artery disease. The possibility of catastrophic lower-limb ischemia because of complete mesenteric excision with ligation of the inferior mesenteric artery was a matter of concern in this case.Case presentationA 73-year-old man with asymptomatic peripheral artery disease was diagnosed with stage IIIB advanced sigmoid colon cancer. Angiography using a balloon-occlusion catheter revealed that his lower limbs received prominent inferior mesenteric artery blood flow through a collateral pathway. Therefore, interventional radiologists and cardiovascular surgeons evaluated the indications for endovascular stents or bypass grafts. The patient also had dilated cardiomyopathy, so the cardiovascular physicians evaluated his tolerance in the worst-case scenario of a colorectal anastomotic leak. The patient underwent axillofemoral artery bypass and two-stage laparoscopic sigmoid colectomy without anastomosis. The postoperative course was uneventful, and he resumed his job within a month after the resection.ConclusionsAlthough collateral flow from the inferior mesenteric artery is rare in patients with peripheral artery disease, a few case reports have described fatal lower-limb ischemia following anterior resection. The perioperative multidisciplinary evaluation enabled us to understand the patient’s condition and risks, and allowed successful cancer treatment without ischemia of the lower limbs.

Effectiveness of uterine tamponade devices for refractory postpartum haemorrhage after vaginal birth: a systematic review.

ObjectivesTo evaluate uterine tamponade devices’ effectiveness for atonic refractory postpartum haemorrhage (PPH) after vaginal birth and the effect of including them in institutional protocols.Search strategyPubMed, EMBASE, CINAHL, LILACS, POPLINE, from inception to January 2021.Study selectionRandomised and non‐randomised comparative studies.OutcomesComposite outcome including surgical interventions (artery ligations, compressive sutures or hysterectomy) or maternal death, and hysterectomy.ResultsAll included studies were at high risk of bias. The certainty of the evidence was rated as very low to low. One randomised study measured the effect of the condom‐catheter balloon compared with standard care and found unclear results for the composite outcome (relative risk [RR] 2.33, 95% CI 0.76–7.14) and hysterectomy (RR 4.14, 95% CI 0.48–35.93). Three comparative studies assessed the effect of including uterine balloon tamponade in institutional protocols. A stepped wedge cluster randomised controlled trial suggested an increase in the composite outcome (RR 4.08, 95% CI 1.07–15.58) and unclear results for hysterectomy (RR 4.38, 95% CI 0.47–41.09) with the use of the condom‐catheter or surgical glove balloon. One non‐randomised study showed unclear effects on the composite outcome (RR 0.33, 95% CI 0.11–1.03) and hysterectomy (RR 0.49, 95% CI 0.04–5.38) after the inclusion of the Bakri balloon. The second non‐randomised study found unclear effects on the composite outcome (RR 0.95, 95% CI 0.32–2.81) and hysterectomy (RR 1.84, 95% CI 0.44–7.69) after the inclusion of Ebb or Bakri balloon.ConclusionsThe effect of uterine tamponade devices for the management of atonic refractory PPH after vaginal delivery is unclear, as is the role of the type of device and the setting.Tweetable abstractUnclear effects of uterine tamponade devices and their inclusion in institutional protocols for atonic refractory PPH after vaginal delivery.

Epistaxis

Epistaxis, also known as nosebleeds, is a commonly treated condition in medicine and especially otolaryngology. 1 in 200 emergency room visits are due to acute epistaxis, with a higher frequency during the winter and among young children and the elderly. A strong understanding of the etiology, anatomy, and available therapeutic options is necessary for optimal management of epistaxis.1,2 This review contains 11 figures, 5 tables, 1 video, and 66 references. Keywords: epistaxis, nose bleed, nasal packing, hemostasis, nasal cauterization, arterial ligation, arterial embolization, hereditary hemorrhagic telangiectasias

Hypoxia - as a Possible Regulator of the Activity of Epicardial Mesothelial Cells After Myocardial Infarction.

Aim To study the effect of hypoxia on the activity of epithelial-mesenchymal transition (EMT) in epicardial cells, which provides formation of a specialized microenvironment.Material and methods This study used a model of experimental myocardial infarction created by ligation of the anterior descendent coronary artery. The activity of epicardial cells after a hypoxic exposure was studied with the hypoxia marker, pimonidazole, bromodeoxyuridine, immunofluorescent staining of heart cryosections, and in vitro mesothelial cell culture.Results The undamaged heart maintained the quiescent condition of mesothelial cells and low levels of their proliferation, extracellular matrix protein production, and of the EMT activity. Acute ischemic injury induced moderate hypoxia in the epicardial/subepicardial region. This caused a global rearrangement of this region due to the initiation of EMT in cells, changes in the cell composition, and accumulation of extracellular matrix proteins. We found that the initiation of EMT in mesothelial cells may result in the formation of smooth muscle cell precursors, fibroblasts, and a population of Sca-1+ cardiac progenitor cells, which may both participate in construction of new blood vessels and serve as a mesenchymal link for the paracrine support of microenvironmental cells. In in vitro experiments, we showed that 72‑h hypoxia facilitated activation of EMT regulatory genes, induced dissembling of intercellular contacts, cell uncoupling, and increased cell plasticity.Conclusion The epicardium of an adult heart serves as a "reparative reserve" that can be reactivated by a hypoxic exposure. This creates a basis for an approach to influence the epicardium to modulate its activity for regulating reparative processes.