Pulsatility damping in the microcirculation: Basic pattern and modulating factors.

Blood flow pulsatility is an important determinant of macro- and microvascular physiology. Pulsatility is damped largely in the microcirculation, but the characteristics of this damping and the factors that regulate it have not been fully elucidated yet. Applying computational approaches to real microvascular network geometry, we examined the pattern of pulsatility damping and the role of potential damping factors, including pulse frequency, vascular viscous resistance, vascular compliance, viscoelastic behavior of the vessel wall, and wave propagation and reflection. To this end, three full rat mesenteric vascular networks were reconstructed from intravital microscopic recordings, a one-dimensional (1D) model was used to reproduce pulsatile properties within the network, and potential damping factors were examined by sensitivity analysis. Results demonstrate that blood flow pulsatility is predominantly damped at the arteriolar side and remains at a low level at the venular side. Damping was sensitive to pulse frequency, vascular viscous resistance and vascular compliance, whereas viscoelasticity of the vessel wall or wave propagation and reflection contributed little to pulsatility damping. The present results contribute to our understanding of mechanical forces and their regulation in the microcirculation.

[Acute venous mesenteric ischemia in a young COVID-19 positive subject: a case report]. / Ischémie mésentérique aiguë veineuse chez un jeune sujet COVID-19 positif: à propos d'un cas.

Acute mesenteric ischemia (AMI) is due to a sudden decrease or interruption of mesenteric blood flow resulting in inadequate blood supply to the gastrointestinal tract. This causes ischemic and inflammatory lesions often progressing to necrosis in the absence of appropriate treatment. Vascular insufficiency may arise as a result of embolism or arterial thrombosis or venous thrombosis. We here report a rare case of mesenteric venous ischemia caused by coronavirus disease 2019 (COVID-19) in a 33-year-old man in whom diagnosis was based on ultrasound and, in particular, on computed tomography (CT).

[Designment and application of a novel device for microcirculation viviperception].

The key technology of the device for the viviperception of the animal mesenteric microcirculation is to simulate the celiac environment in the device. The technical requirements of the device for microcirculation viviperception are that the observation box should be able to "keep warm, preserve moisture, continually perfuse, and fix the sample"; and the lighting should be "intense", "convergence", and "cool". After actual application, it was found that the newly designed and developed the device by research personnel of Wannan Medical College for the viviperception of the animal mesenteric microcirculation can meet the technical requirements, which is able to "keep warm, preserve moisture, continually perfuse, and fix the sample", and using LED lamp as the microscope light source is "intense", "convergence", and "cool". This device is ingenious and reasonable in design, stable in technology, convenient in operation, and competent in microcirculation viviperception. It solves the technical problem to simulate the celiac environment for mesenteric microcirculation viviperception. The device provides convenience to observe and study the microcirculation, which is worth to be applicated widely.

Luteolin ameliorates lipopolysaccharide-induced microcirculatory disturbance through inhibiting leukocyte adhesion in rat mesenteric venules.

BACKGROUND: Microcirculatory disturbance is closely associated with multiple diseases such as ischemic and septic stroke. Luteolin (3,4,5,7-tetrahydroxyflavone) is a vascular protective flavonoid present in several dietary foods. However, how luteolin plays a role in microcirculatory disturbance is still unknown. The purpose of this study was to find out the influence of luteolin on the lipopolysaccharide (LPS)-induced microcirculatory disturbance, focusing on its effect on leukocyte adhesion and the underlying mechanism of this effect. METHODS: After injecting LPS into rats, we used an inverted intravital microscope to observe the velocity of red blood cells in venules, numbers of leukocytes adherent to and emigrated across the venular wall, hydrogen peroxide production in venular walls and mast cell degranulation. Intestinal microcirculation blood flow was measured by High-resolution Laser Doppler Perfusion Imaging. Histological changes of small intestine and mesenteric arteries were evaluated. Additionally, cell adhesion stimulated by LPS was tested on EA.hy926 and THP-1 cells. The production of pro-inflammatory cytokines, adhesion molecules and the activation of TLR4/Myd88/NF-κB signaling pathway were determined. RESULTS: The results showed luteolin significantly inhibited LPS-induced leukocyte adhesion, hydrogen peroxide production and mast cell degranulation, and increased intestinal microcirculation blood flow and ameliorated pathological changes in the mesenteric artery and the small intestine. Furthermore, luteolin inhibited the release of pro-inflammatory cytokines, the expression of TLR4, Myd88, ICAM-1, and VCAM-1, the phosphorylation of IκB-α and NF-κB/p65 in LPS stimulated EA.hy926. CONCLUSIONS: Our findings revealed that it is likely that luteolin can ameliorate microcirculatory disturbance. The inhibitory effects of luteolin on the leukocyte adhesion stimulated by LPS, which participates in the development of microcirculatory disturbance, are mediated through the regulation of the TLR4/Myd88/NF-κB signaling pathway.

Mesenteric Arteriovenous Dysplasia/Vasculopathy Mimicking Crohn's Disease: A Case Report.

Mesenteric arteriovenous vasculopathy (MAVD/V) is an extremely rare and poorly understood disease and its incidence is probably underestimated. It is an uncommon, non-inflammatory and non-atherosclerotic form of mesenteric vascular injury, first reported in 2016, with characteristic histopathologic evidence of fibromuscular dysplasia-like vascular changes. We present the case of a chronically ill 84-year-old female with a 5 year history of recurrent small bowel obstruction, who underwent segmental resection of the small bowel. Intraoperative examination showed bowel stricture with fibrosis, intraluminal pill fragments and creeping mesenteric adipose tissue clinically compatible with Crohn's disease. Histological examination showed acute and chronic mucosal injury characterized by crypt distortion, ulcerations with granulation tissue, pseudo-pyloric metaplasia, areas of fibrosis and serosal adhesions. Multiple blood vessels (including both veins and arteries) demonstrated wall hyalinization, elastic degeneration and non-atherosclerotic luminal occlusion. The pattern of the mucosal injury is, in this case, potentially a consequence of acute and chronic ischemic processes secondary to mesenteric arteriovenous vasculopathy.

Post-treatment with yiqifumai injection and its main ingredients attenuates lipopolysaccharide-induced microvascular disturbance in mesentery and ileum.

OBJECTIVE: To investigate the effect of Yiqifumai injection (YQFM), a compound Chinese medicine, and its main active ingredients on lipopolysaccharide (LPS)-induced microvascular disturbance in mesentery and ileum. METHODS: Rats were infused with LPS (5 mg/kg/h) for 90 min. Thirty minutes after initiation of LPS administration, YQFM (160 mg/kg/h), Rb1 (5 mg/kg/h), Sch (2.5 mg/kg/h), or Rb1+Sch (5 mg/kg/h + 2.5 mg/kg/h) was infused until 90 min. Human umbilical vein endothelial cells (HUVECs) were incubated with LPS (100 ng/ml) for 90 min. YQFM (1 mg/ml), Rb1 (100 µM), Sch (100 µM), or Rb1+Sch (200 µM) was added 30 min after initiation of LPS stimulation. RESULTS: Yiqifumai injection and Rb1+Sch inhibited mesenteric venule hyperpermeability, suppressed microvillar erosion and submucosal edema, and protected claudin-5 from downregulation and interleukin-1ß from upregulation in ileal tissues after LPS. Study in HUVECs confirmed the effect of YQFM and Rb1+Sch on JAM-1 after LPS and revealed a similar effect on other junction proteins. Moreover, YQFM and Rb1+Sch attenuated the dysfunctional energy metabolism and the activation of TLR-4/Src/NF-κB signaling with Rb1 and Sch being partially effective. CONCLUSION: These results demonstrated the beneficial effect of post-treatment with YQFM, which is attributable to its main ingredient Rb1 and Sch, and likely mediated by targeting TLR-4/Src/NF-κB signaling pathway.

[Intraoperative anatomical observation of mesentery morphology of colonic splenic flexure].

Objective: At present, surgeons do not know enough about the mesenteric morphology of the colonic splenic flexure, resulting in many problems in the complete mesenteric resection of cancer around the splenic flexure. In this study, the morphology of the mesentery during the mobilization of the colonic splenic flexure was continuously observed in vivo, and from the embryological point of view, the unique mesenteric morphology of the colonic splenic flexure was reconstructed in three dimensions to help surgeons further understand the mesangial structure of the region. Methods: A total of 9 patients with left colon cancer who underwent laparoscopic radical resection with splenic flexure mobilization by the same group of surgeons in Union Hospital of Fujian Medical University from January 2018 to June 2019 were enrolled. The splenic flexure was mobilized using a "three-way approach" strategy based on a middle-lateral approach. During the process of splenic flexure mobilization, the morphology of the transverse mesocolon and descending mesocolon were observed and reconstructed from the embryological point of view. The lower margin of the pancreas was set as the axis, and 4 pictures for each patient (section 1-section 4) were taken during middle-lateral mobilization. Results: The median operation time of the splenic flexure mobilization procedure was 31 (12-55) minutes, and the median bleeding volume was 5 (2-30) ml. One patient suffered from lower splenic vessel injury during the operation and the bleeding was stopped successfully after hemostasis with an ultrasound scalpel. The transverse mesocolon root was observed in all 9 (100%) patients, locating under pancreas, whose inner side was more obvious and tough, and the structure gradually disappeared in the tail of the pancreatic body, replaced by smooth inter-transitional mesocolon and dorsal lobes of the descending colon. The mesenteric morphology of the splenic flexure was reconstructed by intraoperative observation. The transverse mesocolon was continuous with a fan-shaped descending mesocolon. During the embryonic stage, the medial part (section 1-section 2) of the transverse mesocolon and the descending mesocolon were pulled and folded by the superior mesenteric artery (SMA). Then, the transverse mesocolon root was formed by compression of the pancreas on the folding area of the transverse mesocolon and the descending mesocolon. The lateral side of the transverse mesocolon root (section 3-section 4) was distant from the mechanical traction of the SMA, and the corresponding folding area was not compressed by the tail of the pancreas. The posterior mesangial lobe of the transverse mesocolon and the descending mesocolon were continuous with each other, forming a smooth lobe. This smooth lobe laid flat on the corresponding membrane bed composed of the tail of pancreas, Gerota's fascia and inferior pole of the spleen. Conclusions: From an embryological point of view, this study reconstructs the mesenteric morphology of the splenic flexure and proposes a transverse mesocolon root structure that can be observed consistently intraopertively. Cutting the transverse mesocolon root at the level of Gerota's fascia can ensure the complete resection of the mesentery of the transverse colon.

Mesenteric Vascular Injury in Trauma: An NTDB Study.

BACKGROUND: Although abdominal trauma remains a major cause of morbidity and mortality, there has not been a large-scale multicenter study regarding outcomes in patients who incur mesenteric vascular injuries. The goal of this retrospective analysis was to investigate the factors associated with outcomes in patients with trauma diagnosed with mesenteric vascular injuries. METHODS: A retrospective database analysis was performed on patients who sustained a mesenteric vascular injury (MVI, ICD-9 902.20-902.29) identified by the 2012 National Trauma Data Bank. Data were analyzed to identify differences in hospital length of stay, emergency room (ER) and final hospital disposition, and mortality based on patient age, gender, race, Injury Severity Score (ISS), and injury type (blunt or penetrating). RESULTS: Of the 1,133 total patients included, blunt trauma accounted for 740 (65%) of the injuries, whereas penetrating trauma accounted for 364 of the injuries (32%). Patients with penetrating injuries were 1.43 times more likely to die from their injuries than those suffering from blunt trauma (95% CI 1.04-1.98, P < 0.05). Patients with a higher ISS (>16) were 5.39 times more likely to die from their injuries than those with a lower ISS (95% CI 1.89-15.4, P = 0.002); if ISS was >25, the patient was 15.1 times more likely to die (95% CI 5.5-41.7, P < 0.001). Men were more likely to suffer from penetrating injuries than women (37% vs. 13%, P < 0.001), and African Americans were nearly 4 times more likely to present with penetrating injuries (69% vs 17%, P < 0.001). Age was also associated with mortality as patients >65 years and between 21 and 44 years were more likely to die from their injuries than patients in other age categories. Of the 740 patients with blunt MVIs, 326 (44%) were taken directly from the ER to the operating room (OR) and 306 (41%) to the intensive care unit (ICU), whereas with penetrating MVIs, 311 (85%) were taken to the OR from the emergency department and 18 (5%) to the intensive care unit. Of the 740 blunt MVIs, 115 died (16%), compared with 76 (21%) of the penetrating MVIs (P < 0.001). Injuries to the hepatic and superior mesenteric arteries were associated with higher mortality, with OR 2.03 and 3.03, respectively (P < 0.001). CONCLUSIONS: The presence of mesenteric arterial injury warrants rapid identification and management as these injuries are associated with significant morbidity and mortality, with penetrating mechanism, injury to large mesenteric vessels, and increased ISS associated with increased mortality.

Vascular bowel and mesenteric injury in blunt abdominal trauma: a single centre experience.

AIM: To establish common patterns of injury in vascular bowel and mesenteric injury (VBMI) and to identify any factors that may lead to delayed treatment. METHODS AND MATERIALS: Forty-one patients with blunt VBMI presented to the level 1 trauma centre of the The Royal London Hospital over 5 years. Computed tomography (CT) images were reviewed to identify the specific location of injury and additional features such as seatbelt bruising and lumbar hernias. Surgical reports were reviewed to record any pertinent surgical findings at laparotomy. RESULTS: The commonest mechanism of injury was a restrained car occupant involved in a road traffic collision (49%, n=20). The ileocaecal mesenteric vasculature was most frequently injured (41.5%, n=17), followed by the mid ileum (17.1%, n=7). Seatbelt bruising was identified in 80% of restrained car occupants and lumbar hernias in 22% of all patients with VBMI. CONCLUSION: Restrained car occupants involved in road traffic collisions are at increased risk of VBMI with particular susceptibility of the ileocaecal mesentery. This has implications for the reporting radiologist and trauma surgeon in deciding which patients require careful monitoring for the development of delayed bowel ischaemia.

Losartan prevents mesenteric vascular bed alterations in high-fat diet fed rats.

Dysfunction of perivascular adipose tissue of mesenteric bed participates in the pathophysiology of high blood pressure linked to metabolic syndrome. Thus, it might consider a new therapeutic objective to take account in cardiovascular and metabolic diseases. Besides its antihypertensive effect, there is a growing interest on the pleiotropic actions of losartan, an angiotensin II type 1 (AT1) receptor antagonist. The aim of the study was to analyze the actions of losartan treatment on adiposity index and prostanoids release from mesenteric vascular bed and its relationship with blood pressure as well as homeostasis model of assessment of insulin resistance (HOMA-IR) in Sprague-Dawley rats under a high-fat (HF) diet for 8 weeks. Four groups were used: control (C), HF diet (HF, 50%, w/w bovine fat), losartan-treated (CL8, 30mg/kg/body weight/day in the drinking water) and losartan-treated HF diet (HFL, both treatments). A high-fat diet incremented systolic blood pressure, HOMA-IR, adiposity of mesenteric vascular bed and the release of vasoconstrictor prostanoids such as thromboxane (TX) B2 and prostaglandin (PG) F2α as well as PGE2, an inflammatory prostanoid in a context of insulin resistance and hypertension. We found a positive correlation between adiposity index and systolic blood pressure. Also, both parameters are positive correlated with the HOMA IR index. Moreover, we also found that these prostanoids release correlate with systolic blood pressure as well as with mesenteric vascular bed adiposity index. Losartan treatment prevented all these alterations and normalized the PGI2/TXA2 ratio in high-fat fed rats. We conclude that losartan may play beneficial actions on perivascular adipose tissue alterations and endothelial dysfunction through restoration of normal balance of vasoactive substances in this model.

[Reappraisal of the lateral rectal structure].

Colorectal surgeons have focused on the lateral structure of rectum for a long time and lateral ligament is the common term to depict this structure. A better understanding of lateral rectal structure could be beneficial to performing the total mesorectum excision (TME) procedure and protecting patients' urinary, sexual and defecation function. The main controversies focus on two aspects: (1) Does the lateral ligament exist? (2) What dose it contain? Does the middle rectal artery exist? Up to now, anatomic studies have failed to reach consensus on the lateral rectal structure. However, surgeons do find the lateral rectal ligament during surgery and it may be the pathway for lateral lymph node metastasis in rectal cancer. The lateral rectal structure contains the middle rectal artery, nerve branches, lymphatics and adipose fibrous tissue around them. We summarize our clinical experience and conclude that the middle rectal artery appears in lateral ligament constantly but some of them are too small to be easily observed. Therefore, regarding the perspective of membrane anatomy, embryology and surgery, this structure may be more appropriate to be called the "lateral mesorectum". We propose this new term based on the previous literature and our own experience for the readers' reference.

Eicosanoid production varies by sex in mesenteric ischemia reperfusion injury.

Intestinal ischemia/reperfusion (I/R)-induced injury is an inflammatory response with significant morbidity and mortality. The early inflammatory response includes neutrophil infiltration. However, the majority of rodent studies utilize male mice despite a sexual dimorphism in intestinal I/R-related diseases. We hypothesized that sex may alter inflammation by changing neutrophil infiltration and eicosanoid production. To test this hypothesis, male and female C57Bl/6 mice were subjected to sham treatment or 30 min intestinal ischemia followed by a time course of reperfusion. We demonstrate that compared to male mice, females sustain significantly less intestinal I/R-induced tissue damage and produced significant LTB4 concentrations. Male mice release PGE2. Finally, treatment with a COX-2 specific inhibitor, NS-398, attenuated I/R-induced injury, total peroxidase level, and PGE2 production in males, but not in similarly treated female mice. Thus, I/R-induced eicosanoid production and neutrophil infiltration varies between sexes suggesting that distinct therapeutic intervention may be needed in clinical ischemic diseases.

[Scientific interpretation of membrane anatomy theory and standardized application of membrane anatomy terms].

There has been an upsurge of the theory of membrane anatomy in China, but it is still in the initial stage of establishing preliminary framework. The concept of fasciae in membrane anatomy actually refers to the fasciae constituting the particular plane or the 'holy plane'. Therefore, the membrane anatomy can't simply be defined as the anatomical relationship among fascia. The application of the membrane anatomy is also not just to pursue the avascular plane in the surgical field. Nowadays, nonstandard anatomical terms and diversification of views impede the development of the theory of the membrane anatomy. Fasciae occur in embryonic stage, undergo a series of changes in rotation and fusion, and lose the original features, which bring difficulties in understanding the anatomy of fasciae. In this paper, we restore the origin and continuity of fasciae related to the colorectal surgery by cadaveric study, surgical observation and literature review. Taking the TME for example, we also discuss the core content about the fasciae and plane related to 'mesenteric envelope' and complete mesorectal excision. From the perspective of the fasciae integrity, we illustrate the definitions of important anatomical structure and standardized the terminology of fasciae. To study the origin and architecture of fasciae in the view of embryology, integrity and continuity will contribute to establish the standard theoretical system of membrane anatomy.

[Mesogastrium theory of D2 lymphadenectomy for advanced gastric cancer: cogitation and skills].

D2 lymphadenectomy combined with complete mesentery excision (CME) for advanced gastric cancer in recent years was a hotspot issue in China, while its safety and effectiveness have been proved. According to the Membrane anatomy of the stomach, both surgical approach and mesogastrium interval is particularly important in Laparoscopic radical gastrectomy. We summarized and shared the following clinical experience for medical colleagues. (1) Lymph nodes of right abdominal aorta-No.7,8,9,12-should be resection as an indivisible whole. This integrity tissue above the portal vein was supposed to the end of the dorsal mesentery of stomach and the continuation of Gerota fascia. (2) No.10 (splenic hilar lymph nodes) lymphadenectomy: The surgical approach enters the Gerota fascia between the left gastric artery(LGA) and the left alongside the splenic artery. When the extent of lymphadenectomy performed to cardia and upper margin of the spleen, then the ultrasonic scalpel should excise the lymph node along the splenic artery to the splenic hilum. (3) Esophagogastric junctional cancer: There is no consensus over the type of resection and the extent of lymphadenectomy that could be a standard of care for this category.While we recommended that paraesophageal lymph node dissection and digestive tract reconstruction should be completed in 3D laparoscopy vision. (4) Infracardiac bursa(ICB): Intentional entry into the ICB provides surgeons with a landmark to identify the location of the pleura, and inferior vena cava. (5)The application of endoscopic aspirator with flushing and electrocautery. The CME concept of gastric cancer emphasizes the membrane anatomy theory rather than the regional lymph node. The precision and homogeneity of the D2 procedure therapy of gastric cancer depend on complete mesentery excision, standard the surgical process, or approach. Only in this way can we find the avascular gaps easily and perfectly cover the extent of lymph node dissection required for the D2 procedure.

[Thinking of the application of membrane anatomy in gastric cancer surgery after neoadjuvant therapy].

The standard treatment for advanced gastric cancer remains surgery-based comprehensive treatment. The D2 radical surgery has made outstanding contributions to the standarlization of gastric cancer surgery, which has improved patients' prognosis and quality of life. In recent years, neoadjuvant chemotherapy has achieved a certain effect on the treatment of advanced gastric cancer. With the continuous development of the concept of membrane anatomy in gastric cancer surgery, new surgical challenges have also been raised. For patients after neoadjuvant therapy, there is heated controversy in the possibility of completing radical gastrectomy with membrane anatomical concept for gastric cancer. We believe that if neoadjuvant therapy pushes mesenteric cancer cell back into the mesentery, theoretically membrane anatomy combined with neoadjuvant therapy is beneficial to the treatment efficacy of advanced gastric cancer. However, membrane anatomy has two important problems when combined with neoadjuvant therapy: (1) After neoadjuvant chemotherapy, there are varying degrees of edema around the stomach tissue, which will affect the visualization of anatomic planes. In addition, because the patients' coagulation function is damaged to a certain extent, it is difficult to avoid bleeding or minimize bleeding during the operation. Therefore, it is still controversial whether the patients with gastric cancer after neoadjuvant chemotherapy can undergo radical gastrectomy with membrane anatomy. (2) For patients with complete pathological remission, whether to obtain the maximum rate of pathological remission through intensive neoadjuvant therapy, or to obtain the survival benefit of patients with membrane anatomy surgery in clinic is still controversial. Faced with these confusions, multi-center clinical researches on the application of membrane anatomy surgery after neoadjuvant therapy is the only solution.

[Better understanding of interfacial planes in colorectal cancer surgery and the value of small vessels on fascia in the identification of interfacial planes].

The introduction of total mesorectal excision and wider use of laparoscopic surgery pushed the field of colorectal surgery into an era of interfasical dissection. The Japanese suggestion of fascial arrangement of the trunk in a multilaminar, symmetrical and parallel way helps in better understanding of fascial relationship and interfascial planes surrounding the colon and the rectum. However, different interpretations of the multilayer retroperitoneal fascial relationship, complexity of fascial structures within the pelvis and dense adhesion between two apposed fasciae at special points make it still challenging for the surgeon to decide on the precise interfascial plane for colorectal mobilization. Small vessels on fasica propria of the rectum and various retroperitoneal fascia, especially ureterohypogastric fascia show distinctive features. The root of small vessels on fascia propria of the rectum helps to identify the anterolateral and posterolateral interfascial plane in the middle and low rectum. The longitudinal trajectory of small vessel on ureterohypogastric fascia and scarcity interfascial vascular communication between mesocolic and retroperitoneal fascia help the surgeon to find and stay in the interfacial plane during colorectal mobilization. More knowledge of fascial and interfascial plane will certainly help achieve better mesocolic mesorectal integrity and reduce the risk of injuries to autonomic nerves. More anatomical, histological and embryological studies are warranted with respect to relationship between small vessels and fasciae.

[Controversy and consideration of high and low ligation of inferior mesenteric artery in radical resection of rectal cancer].

Radical resection is one of the most important treatment for rectal cancer, which requires not only removal of adequate bowel and mesorectum around the tumor, but also thorough lymphadenectomy. Besides, postoperative complications are surgeons' concerns as well. According to different ways to manage inferior mesenteric artery, procedures could be divided into two groups: inferior mesenteric artery (IMA) high ligation and low ligation, which lead to various outcomes of the extent of lymph nodes dissection, survival, preservation of intestinal blood supply, incidence of anastomotic leakage, and postoperative functions including defecation function, urinary function and sexual function. Author believes that for those patients with clinical stage T1, low ligation and D2 lymph nodes dissection could be considered. However, for patients with locally advanced carcinomas (clinical stage T2+or N+), especially suspicious metastasis of lymph nodes around IMA root, high ligation and D3 lymph node dissection is suggested to ensure en bloc resection. As for those patients with high risks for compromised intestinal blood supply, preservation of left colic artery plus D3 lymph nodes dissection might be a feasible way. Intraoperative indocyanine green fluorescent imaging might play a role in quality control of lymphadenectomy.