Splanchnic System Research Articles

Selective monitoring of superior and inferior vena cava drainage flows in bicaval cannulation: Potential clinical benefits of proximal junction placement on the CPB side.

Background: In cardiac surgery, precision and efficiency are crucial, especially in managing venous drainage flows during complex procedures. This practical technique evaluates the benefits of placing the proximal junction on the cardiopulmonary bypass (CPB) side rather than on the surgical table in bicaval cannulation. Bicaval cannulation, involving both the superior vena cava (SVC) and inferior vena cava (IVC), ensures efficient venous return.Practical technique: Placing the junction on the CPB side allows for accurate, real-time control of venous drainage, allowing for swift responses to fluctuations and maintaining stable hemodynamics.Perspectives: This approach could minimize the risk of congestion in the liver, splanchnic system, and cerebral venous return, thereby preventing related complications. Another important potential benefit of this approach could be the ability to closely monitor and manage metabolic demands and oxygen consumption for SVC and IVC. Additionally, EmTec flow technology can be integrated for more precise management.

Hepatic steatosis: additional findings in the splanchnic system on magnetic resonance imaging

Purpose: To document additional findings in the Splanchnic System in patients with hepatosteatosis on clinical MR studies. Materials and Methods: One hundred randomly selected studies of patients with hepatosteatosis who underwent clinical MR studies during a six-month interval were included. Clinical information on the current requisition and prior abdominal studies within one year was recorded. No research or additional investigation into medical records was performed. Statistical analyses were performed. Results: Among 100 patients with hepatosteatosis, there were 59 Females (mean 52.6 years). The presenting complaint was abdominal pain, right upper quadrant, or general pain in 77. Ninety-nine patients showed increased enhancement of the upper GI tract in at least one segment (esophagus and duodenum most commonly). There was a significant association between the subjective grading of hepatosteatosis and bowel enhancement in the Splanchnic System (p=0.00049). Ninety-four were overweight/obese; 23 had pancreatic steatosis; 8 had mesenteric panniculitis. Other findings were recorded. Conclusion: Variable increased enhancement of the upper GI tract was present in almost all patients with hepatosteatosis, and various other abnormalities in the splanchnic system were observed. Hepatosteatosis and inflammation of the upper GI tract may be commonly present together and may be part of a larger picture of splanchnic abnormalities.

Retraction Note: Gastric distension causes changes in heart rate and arterial blood pressure by affecting the crosstalk between vagal and splanchnic systems in anesthetised rats.

Retraction Note: Gastric distension causes changes in heart rate and arterial blood pressure by affecting the crosstalk between vagal and splanchnic systems in anesthetised rats.

Acute Cholecystitis Complicating Cardiac Disease: A Cohort Study From a Tertiary Care Center in Mexico City, Mexico.

Background Acute cholecystitis (AC) presents as inflammation of the gallbladder, predominantly attributed to gallstones obstructing the cystic duct. Another notable etiology is ischemic cholecystitis, often stemming from severe illnesses that compromise blood flow to the splanchnic system. Individuals with pre-existing cardiovascular conditions or undergoing cardiopulmonary surgery encounter elevated risks of gastrointestinal pathology, leading to heightened morbidity and mortality rates. In these cases, AC stands out as a significant concern, whether it originates from gallstones or is acalculous (ischemic). Methods We conducted a single-center, retrospective cohort study at the National Medical Center in Mexico City, Mexico. We included demographic, clinical, laboratory, preoperative, intraoperative, and postoperative data. Our main objectives were to describe the characteristics of our population and identify predictors of major complications following surgery for AC in patients with heart disease. Results Our study encompassed 18 patients diagnosed with both AC and cardiac disease, with acute myocardial infarction being the leading cause of admission, constituting 38.9% of cases. The clinical presentation was characterized by right hypochondrial pain, observed in all patients, while Murphy's sign was evident in 44.4% of cases. Additionally, various non-specific symptoms were present in varying percentages across the patient cohort. Concerning imaging studies, 88% of our cohort underwent ultrasound (USG), while computed tomography (CT) was utilized in 55% of patients. Among those who had USG, the most prevalent findings were gallbladder wall thickening in 56% and perivesicular fluid in 37.5%. In patients who underwent CT scans, the predominant observations included perivesicular fluid in 66% and perivesicular fat stranding in 55%. In terms of intraoperative findings, gallbladder empyema and necrosis were the most common findings identified in 55.6% of the cases. After surgery, 61.1% had no complications or developed mild complications, while 11.1% experienced moderate to severe complications without resulting in death; the mortality rate was 27.8% in our cohort. Overall, major complications or death were present in 38.9% of our cohort. In the postoperative data analysis, the use of mechanical ventilation and vasopressors showed a significant correlation with increased morbidity and mortality. Conclusions Our study contributes valuable information to the international literature, providing insights into the complications faced by the Mexican population in the context of heart diseases, particularly among patients suffering from cholecystitis. Within individuals with cardiac disease, the occurrence of AC requiring surgical intervention is associated with heightened morbidity and mortality rates, with our cohort experiencing rates as high as 38.9%. Consistent with findings in the international literature, these results underscore the critical importance of continuing the search for novel clinical or laboratory predictors for this high-risk population. While most parameters assessed in this study did not show any correlation with major complications, exceptions were observed in postoperative vasopressors and mechanical ventilation.

Liver support systems and liver transplantation in acute liver failure.

Acute liver failure (ALF) results in a multitude of complications that result in multi-organ failure. This review focuses on the pathophysiological processes and how to manage with these with artificial liver support and liver transplantation (LT). The pathophysiological sequence of events behind clinical deterioration in ALF comes down to two profound consequences of the failing liver. The first is the development of hyperammonemia, as the liver can no longer synthesize urea. The result is that the splanchnic system instead of removing ammonia becomes an ammonia-producing organ system that causes hepatic encephalopathy (HE) and cerebral oedema. The second complication is caused by the necrotic liver cells that release large molecules that originate from degrading proteins, that is damage associated molecular patterns (DAMPs) which causes inflammatory activation of intrahepatic macrophages and an overflow of DAMPs molecules into the systemic circulation resulting in a clinical picture that resembles septic shock. In this context the combined use of continuous renal replacement therapy (CRRT) and plasma exchange are rational and simple ways to remove ammonia and DAMPS molecules. This combination improve survival for ALF patients deemed not appropriate for LT, despite poor prognostic criteria, but also ensure a better stability of vital organs while awaiting LT. The combination of CRRT with albumin dialysis tends to have a similar effect. Currently, the selection criteria for LT for non-paracetamol cases appear robust while the criteria for paracetamol-intoxicated patients have become more unreliable and now consist of more dynamic prognostic systems. For patients that need LT for survival, a tremendous improvement in the post-LT results has been achieved during the last decade with a survival that now reach merely 90% which is mirroring the results seen after LT for chronic liver disease.

Transcatheter heterotopic valve implantation with the TricValve system: focus on preoperative assessment and patient selection.

Nontreated severe symptomatic tricuspid valve regurgitation is associated with significant morbidity and mortality. When a surgical correction is not feasible due to high operative risk, transcatheter treatment of the tricuspid valve has been suggested as an interesting valuable option. Caval valve implantation has been proposed to overcome the tricuspid valve regurgitation mechanism reducing the effect of insufficiency on the splanchnic systems. Given the technical simplicity of the caval valve implantation technique when compared with other transcatheter devices, it is a suitable option for a wide variety of patients. Eligibility criteria and patient selection are still matter of debate. We hereby describe the case of a patient successfully treated with bicaval implants with regard to preoperative assessment.

Dysregulated platelet function in COVID-19 patients

More than two year-experience in monitoring patients with severe novel coronavirus disease revealed an increased risk of macroand microcirculatory thrombosis, clinically manifested by heart attack, stroke, thromboses of rare localizations (thrombosis of the hepatic veins, mesenteric veins, cerebral sinuses, portal vein), being the main cause of adverse outcomes. Thromboembolic complications, expressed as sepsis-induced coagulopathy, disseminated intravascular coagulation, venous and arterial thromboembolism, pulmonary embolism, microthrombosis, and thrombotic microangiopathy were noted to affect various organs such as the lungs, heart, kidneys, and brain. Earlier, we showed that hypercoagulability is closely related to inflammatory diseases and hemostasis dysregulation. Endothelial injury and dysfunction have been identified as critical pathways to thrombosis, and other mechanisms occurring in the microvasculature were described such as endothelial activation, cytokine storm, and formation of neutrophil extracellular traps (NETs). However, a role of platelets in severe COVID-19 has not been examined. Platelets are small non-nucleated cells most known as the central mediators of hemostasis. However, upon activation, platelets release a variety of immunomodulatory cytokines and chemokines involved in regulating immune response. Because platelets are involved in both immunity and coagulation, they play a central role in immunothrombosis, a physiological process wherein immune cells induce microthrombogenesis both to prevent spread of pathogens and facilitate their clearance. Moreover, platelets can directly interact with viral receptors including those related to SARS-CoV-2. Platelet dysfunction includes both thrombocytopenia and platelet hyperactivation. It should be noted that persistent thrombocytopenia is usually correlated with mortality being associated with thrombosis of the cerebral sinuses, splanchnic system, autoimmune reactions, as well as with administered heparin and vaccines. Therefore, here we review a role of platelets in the pathogenesis of COVID-19.

α-Adrenergic blockade prevented environmental temperature reduction-induced transient portal pressure surge in cirrhotic and portal hypertensive rats.

Exposure to low temperatures has been associated with increased gastroesophageal variceal bleeding in patients with cirrhosis and portal hypertension; however, the mechanism remains unclear. Therefore, the aim of the present study was to evaluate the impact of environmental temperature reduction on portal hypertension and the role of adrenergic signaling pathways in this phenomenon. Male Sprague-Dawley rats underwent common bile duct ligation or partial portal vein ligation to induce liver cirrhosis and/or portal hypertension. The impacts of acute or chronic changes in environmental temperature were surveyed. The results showed that acute cooling from 25 to 15°C and 5°C increased the portal pressure by 10.6% and 15.5% in cirrhotic rats, and by 22.2% and 36.1% in portal hypertensive rats, respectively. The transient portal pressure surge started shortly after cooling, reached a peak within 5 min and returned to baseline after 10 min. Systemic vascular resistance, mean arterial pressure and splanchnic blood flow increased significantly at the same time. Plasma epinephrine and norepinephrine concentrations, phospholipase C, protein kinase C activity and myosin phosphorylation of peripheral arteries increased significantly in response to cooling. Phentolamine (an α-blocker) but not propranolol (a non-selective β-blocker) dose-dependently inhibited the transient portal pressure surge and aforementioned molecular changes. In conclusion, environmental temperature reduction induced peripheral vasoconstriction via α-adrenergic pathways, and redistribution of blood flow to the splanchnic system led to a surge in transient portal pressure. Treatment with α-adrenergic receptor antagonists may exert additional benefits in controlling portal hypertension, especially on exposure to low temperatures.

A postresection perfusion deficit in the right colon is an independent predictor of perioperative outcome after major hepatectomy

There is a strong interaction between hepatic hemodynamics and perfusion in the splanchnic system. However, little is known about differences in perfusion in different splanchnic compartments and their changes after hepatectomy. Perfusion in various splanchnic compartments (ie, stomach, small intestine, right and left colon, liver) was assessed pre- and post-hepatectomy by intraoperative laser Doppler flowmetry. Differences of splanchnic perfusion between compartments were evaluated by ANOVA, and risk factors of postoperative complications (graded by the comprehensive complication index [CCI]) were analyzed by univariate and multivariate analyses. A prediction model of postoperative complications was developed. A total of 50 and 29 patients with major and minor hepatectomy were enrolled. Splanchnic perfusion at baseline varied significantly across different splanchnic compartments with highest values in the small bowel and right colon (P<.001). Major hepatectomy induced a significant perfusion decrease in the stomach (P=.006), right colon (P<.001) and small bowel (P=.035). A postresection perfusion deficit in the right colon with values below 254 perfusion units (PU) was identified as an independent predictor of clinically relevant complications after major hepatectomy (concordance index: 0.79, 95% CI 0.66-0.87, P=.002). Bootstrap validation confirmed internal validity and excellent calibration. Major hepatectomy causes significant reduction of splanchnic perfusion. An intraoperative posthepatectomy microcirculatory perfusion deficit of the right colon is a strong and independent predictor of clinically relevant postoperative complications after major hepatectomy.

P049 Investigation of Liver Diseases by Ultrasound in Patients With Inflammatory Bowel Disease.

Inflammatory Bowel Disease (IBD), which can be divided into Crohn's Disease (CD) and Ulcerative Colitis (UC), is an immune mediated disease featured by gastrointestinal tract involvement. Hepatic disease, such as non-alcoholic fatty liver disease (NAFLD), cirrhosis, cholelithiasis, hepatic thromboembolic events and primary sclerosing cholangitis (PSC) are some hepatic complications presented by IBD patients. Since these hepatic disorders have a higher prevalence in IBD patients, ultrasonography is a noninvasive low-cost versatile tool, that allows to identify these manifestations at early stages. Therefore, this study aims to analyze the prevalence of hepatic diseases in patients with IBD. A cross-sectional study was performed in a single IBD center, Brazil. This study considered clinical and sociodemographic data of these individuals, besides the evaluation of disease activity, biochemical tests, and liver ultrasound with doppler. Statistical analysis: descriptive, association tests. 71 patients were included, 34 had CD and 37 had UC, mean age 45.32 ± 13.59 years, 63.38% women. Among CD patients, 42.42% have ileocolonic involvement, 50% penetrating behavior and 39.4% perianal involvement. Among patients with UC, most patients have pancolitis (72.22%). Most patients were in clinical (CD: 93.55%, UC: 63.89%) and endoscopic (47.14%) remission. The main medications used were azathioprine (46.48%), infliximab (40.85%), salicylates (28.17%), corticosteroids (16.9%) and adalimumab (11.27%). According to ultrasound, NAFLD was found in 32 (45.07%) patients: 40.63% mild, 40.63% moderate and 18.75% severe. Furthermore, we found a correlation between liver steatosis and blunt liver edge (p < 0.0155). Only 2 patients presented with choledocholithiasis. One patient had features of chronic liver disease such as irregular surface, heterogeneity of a hepatic parenchymal echo and bluntness of the liver edge. No signs of thrombosis were found in portal, splenic or superior mesenteric veins. A higher prevalence of NAFLD was found in patients with IBD, and no signs of thrombosis were found in the splanchnic system.

Terlipressin and the Treatment of Hepatorenal Syndrome: How the CONFIRM Trial Moves the Story Forward

Hepatorenal syndrome (HRS) is a form of acute kidney injury (AKI) occurring in patients with advanced cirrhosis and is associated with significant morbidity and mortality. The pathophysiology underlying HRS begins with increasing portal pressures leading to the release of vasodilatory substances that result in pooling blood in the splanchnic system and a corresponding reduction in effective circulating volume. Compensatory activation of the sympathetic nervous system and the renin-angiotensin-aldosterone system and release of arginine vasopressin serve to defend mean arterial pressure but at the cost of severe constriction of the renal vasculature, leading to a progressive, often fulminant form of AKI. There are no approved treatments for HRS in the United States, but multiple countries, including much of Europe, use terlipressin, a synthetic vasopressin analogue, as a first-line therapy. CONFIRM (A Multi-Center, Randomized, Placebo Controlled, Double-Blind Study to Confirm Efficacy and Safety of Terlipressin in Subjects With Hepatorenal Syndrome Type 1), the third randomized trial based in North America evaluating terlipressin, met its primary end point of showing greater rates of HRS reversal in the terlipressin arm. However, due to concerns about the apparent increased rates of respiratory adverse events and a lack of evidence for mortality benefit, terlipressin was not approved by the Food and Drug Administration (FDA). We explore the history of regulatory approval for terlipressin in the United States, examine the results from CONFIRM and the concerns they raised, and consider the future role of terlipressin in this critical clinical area of continued unmet need.

Splanchnic Vein Thrombosis Treatment with Rivaroxaban - a Case Series from the Prospective Dresden Noac Registry (NCT01588119)

Background : Although rivaroxaban is not specifically approved to be used in patients with splanchnic vein thrombosis (SVT), it may offer advantages due the oral intake and the specific pharmacological profile. As a consequence, off-label use of rivaroxaban in single cases has been reported. However, the effectiveness and safety of rivaroxaban in SVT remains to be established.Patients and methods : Using data from the prospective, non-interventional multicentric Dresden NOAC we evaluated a subgroup of patients receiving rivaroxaban for acute or chronic SVT treatment. All patients in the registry undergo long-term follow-up by quarterly phone calls and suspected thromboembolic and bleeding outcome events are centrally adjudicated using standard definitions.Results: Until June 30th 2017, 23 patients receiving rivaroxaban for SVT treatment were enrolled (65% male, median age 56 years). In these, SVT manifested as portal vein thrombosis in 15 cases (65.2%), mesenteric vein thrombosis in 2 (8.7%) and in both localizations in 6 (26.1%) cases. Idiopathic SVT was diagnosed in 78% of cases; 13% had intra- abdominal infections and 9% had cancer (table 1).Median time between diagnosis and initiation of rivaroxaban was 32 days (25th/75th percentile 11.5-125.5 days). Mean exposure time of rivaroxaban was 13 months (range 1-43 months), during which no thromboembolic event occurred. Ten patients had a total of 19 bleeding complications during treatment with rivaroxaban, which (according to International Society of Thrombosis and Haemostasis definition) were minor bleeding in 8 cases, clinically relevant non-major bleeding in 6 and major bleeding in 5 cases (3 x gastrointestinal, 1 x hemorrhoid; 1 x traumatic intracranial bleeding).During follow-up (mean 23 months; range 1-59 months), 7 patients had a scheduled end of rivaroxaban treatment, 2 patients were electively switched to prophylactic dosages of apixaban for long-term secondary prevention and 5 patients had unplanned permanent discontinuation of oral anticoagulation. Five patients died during follow-up (2x traumatic intracranial bleeding, 3 terminal malignant diseases).Detailed information on thrombus burden at baseline and during follow-up was available for 17/23 patients (table 2). Of these, 9 patients initiated rivaroxaban in the first 30 days after SVT diagnosis and demonstrated complete clot resolution in 8 and stable thrombus in 1 case. In contrast, those 8 patients who initiated rivaroxaban later than 30 days were found to have complete resolution or improvement in only two cases and stable thrombus burden without improvement in the remaining 6 cases.Conclusions: Our cohort of 23 consecutive patients currently represents the largest prospectively collected case series of rivaroxaban treatment for SVT. In this cohort treatment with rivaroxaban demonstrated high effectiveness to prevent thromboembolic complications but bleeding complications are common, which is known for SVT patients. Therefore, careful risk-benefit assessments are especially needed in this indication. Early initiation of rivaroxaban resulted in fast thrombus resolution in the majority of cases, whereas late initiation tended to achieve stable clot burden only. A fast SVT resolution with oral direct factor Xa inhibitors may be supported by their first-pass effect, which, compared to LMWH or VKA, should result in high drug concentrations at the site of thrombus in the splanchnic system. It remains to be seen if the fast clot resolution in early initiators of rivaroxaban will reduce late sequelae such as gastrointestinal bleeding from varicose veins, which is the most feared clinical consequence of residual clot in SVT. [Display omitted] DisclosuresMarten:Bayer HealthCare: Honoraria; Daiichi Sankyo: Honoraria. Beyer-Westendorf:Bayer: Honoraria, Research Funding; Pfizer: Honoraria, Research Funding; Daiichi-Sankyo: Honoraria, Research Funding; Boehringer-Ingelheim: Honoraria, Research Funding.

Not all fluid overloads are the same: some practical considerations for better decongestion

Not all fluid overloads are the same: some practical considerations for better decongestion

Differential Mesenteric Venous and Arterial Vascular Reactivity to Adenosine between Rats, Dogs, Mini‐pigs, and Human

It is well established that adenosine induces arterial vasodilation in various vascular beds. However, its effect on the venous circulation is still largely unknown. The splanchnic system receives approximately 25% of cardiac output (CO) and contains approximately 20% of total blood volume. Mesenteric (part of splanchnic system, o. d. 150–250 μm) arteries (MA) and their adjacent veins (MV) from rats, dogs, mini‐pigs and humans were isolated and mounted on a myograph (DMT Technology, USA). Vessels were preconstricted with 1 μM phenylephrine (PE) for arteries and prostaglandin F2α (PGF2α) for veins. Cumulative concentrations of 5’‐N‐Ethylcarboxamidoadenosine (NECA, 10−11 – 10−5 M), a non‐specific adenosine agonist, were applied and evaluated. Tension development was normalized to the tension induced by PE/PGF2α as %. NECA induced a concentration dependent arterial vasodilation in all 3 animals and human MA (Fig. 1). The effects were very similar in all 3 animals (maximum of 91.09±10.94% to 93.88±1.93%), however human responses were less pronounced (maximum of 59.14±4.61%). Interestingly, veins from all species responded to NECA very differently (Fig. 2). MVs from rats were the only vessels that constricted strongly in response to NECA (182.94±17.52% of pre‐constriction), which has not been previously reported (Figs. 2– 3). NECA induced vasodilation in MV from the other species varied. NECA induced vasodilation in MV from dogs were similar to MA at high concentrations (Fig. 6, 10−8 M and above). However, MV from mini‐pig (Fig. 5) and human (Fig. 6) responses were minimal (Fig. 2, maximum of 24.56±14.67% in mini‐pig and 33.54±9.61% relaxation in human) compared to 92.93±2.26% relaxation in dogs. In conclusion, although mesenteric arterial vascular reactivity responds similarly to adenosine among species, mesenteric venous vascular reactivity responses varied greatly to adenosine among species. MVs from rats were the only vessel constricted strongly in response to NECA. Caution is advised when choosing animal models for studying vascular reactivity.Figure 1Figure 2Figure 3Figure 4Figure 5Figure 6

Tromboza splanhničkih vena kao rijedak uzrok akutnog abdominalnog bola

Cilj: Prikazati slučaj pacijenta s akutnim abdominalnim bolom kojemu je dijagnosticirana tromboza splanhničkog venskog sustava, a uzrok je naknadno dokazana mijeloproliferativna bolest uz JAK2 V617F varijantu sekvence. Prikaz slučaja: 44-godišnji pacijent primljen je u hitnu medicinsku službu zbog akutizacije paraumbilikalnog bola koji je trajao 10-ak dana. U laboratorijskim nalazima bile su povišene vrijednosti alfa amilaze i upalnih parametara, zbog čega je pacijent hospitaliziran. Nativna snimka abdomena i ultrazvuk abdomena pokazivali su meteorizam tankog i debelog crijeva. Zbog nejasne dijagnoze učinjena je i kompjutorizirana tomografija (CT) abdomena koja je pokazala samo zamućeno mezenterijalno masno tkivo u korijenu mezenterija. Trećeg dana hospitalizacije zbog intenzivnijih bolova, koji nisu popustili ni na opiodne analgetike, učinjen je kontrolni CT abdomena koji je pokazivao trombozu v. portae, v. mesentericae superior i v. lienalis. Navedene promjene bile su praćene zadebljanjem stijenke tankog crijeva u smislu kongestije i raslojavanja stijenke, ali bez znakova jasne ishemije, te parcijalnim poremećajima perfuzije jetre uz prisutnost ascitesa. U terapiju je uveden niskomolekularni heparin u punoj dozi uz acetilsalicilnu kiselinu, a zbog dodatnog pogoršanja stanja sa znakovima paralitičkog ileusa i progresijom ishemijskih promjena tankog crijeva učinjena je hitna laparotomija. Za vrijeme hospitalizacije, hematološkom obradom dokazana je JAK2 V617F varijanta sekvence i mijeloproliferativna bolest koja je etiološki čimbenik tromboze portalnog sustava i ishemije crijeva. Zaključak: Uzrok akutnog bola u trbuhu može rijetko biti i tromboza splahničkog sustava, koja u kratkom vremenskom periodu može dovesti do životno ugrožavajućeg stanja. Akutno nastalu trombozu splanhničkog venskog sustava nužno je liječiti antikoagulantnom terapijom, a ako taj način liječenja ne pokaže zadovoljavajuće rezultate, nužan je kirurški zahvat. Dokazana mijeloproliferativna bolest uz JAK2 V617F varijantu sekvence mogući je etiološki čimbenik splanhničke venske tromboze kod mlađih pacijenata.

The Lymphatic Headmaster of the Mast Cell-Related Splanchnic Inflammation in Portal Hypertension

Portal hypertension is a common complication of liver disease, either acute or chronic. Consequently, in chronic liver disease, such as the hypertensive mesenteric venous pathology, the coexisting inflammatory response is classically characterized by the splanchnic blood circulation. However, a vascular lymphatic pathology is produced simultaneously with the splanchnic arterio-venous impairments. The pathological increase of the mesenteric venous pressure, by mechanotransduction of the venous endothelium hyperpressure, causes an inflammatory response involving the subendothelial mast cells and the lymphatic endothelium of the intestinal villi lacteal. In portal hypertension, the intestinal lymphatic inflammatory response through the development of mesenteric-systemic lymphatic collateral vessels favors the systemic diffusion of substances with a molecular pattern associated with damage and pathogens of intestinal origin. When the chronic hepatic insufficiency worsens the portal hypertensive inflammatory response, the splanchnic lymphatic system transports the hyperplasied intestinal mast cells to the mesenteric lymphatic complex. Then, an acquired immune response regulating a new hepato-intestinal metabolic scenario is activated. Therefore, reduction of the hepatic metabolism would reduce its key centralized functions, such as the metabolic, detoxifying and antioxidant functions which would try to be substituted by their peroxisome activity, among other functions of the mast cells.

The beneficial effects of curcumin in cirrhotic rats with portal hypertension.

In liver cirrhosis with portal hypertension, the uneven distribution of vasoactive substances leads to increased intrahepatic vascular resistance and splanchnic vasodilatation. Angiogenesis also induces increased portal inflow and portosystemic collaterals. The collaterals may induce lethal complications such as gastroesophageal variceal hemorrhage, but the therapeutic effect of vasoconstrictors is still suboptimal due to poor collateral vasoresponsivenss. Curcumin has aroused much attention for its antifibrosis, vasoactive, and anti-angiogenesis actions. However, whether it affects the aforementioned aspects is unknown. Liver cirrhosis was induced by common bile duct ligation (CBDL) in Sprague–Dawley rats. Sham-operated rats were controls. CBDL and sham rats were randomly allocated to receive curcumin (600 mg/kg per day) or vehicle since the 15th day after BDL. On the 29th day, portal hypertension related parameters were surveyed. Portosystemic collateral in situ perfusion was performed to evaluate vascular activity. Chronic curcumin treatment decreased portal pressure (PP), cardiac index (CI) and increased systemic vascular resistance (SVR) in cirrhotic rats. In splanchnic system, curcumin decreased superior mesenteric artery (SMA) flow and increased SMA resistance. Mesenteric angiogenesis was attenuated by curcumin. Acute administration of curcumin significantly induced splanchnic vasoconstriction. The mesenteric protein expressions of p-endothelial nitric oxide synthase (eNOS), cyclooxygenase (COX) 2 (COX2), vascular endothelial growth factor (VEGF), p-VEGF receptor 2 (VEGFR2), and p-Erk were down-regulated. In collateral system, curcumin decreased portosystemic shunting and induced vasoconstriction. In conclusion, chronic curcumin administration in cirrhotic rats ameliorated portal hypertension related hemodynamic derangements and portosystemic collaterals. Curcumin also attenuated splanchnic hyperdynamic circulation by inducing vasoconstriction through inhibition of eNOS activation and by decreasing mesenteric angiogenesis via VEGF pathway blockade.

Gastric distension causes changes in heart rate and arterial blood pressure by affecting the crosstalk between vagal and splanchnic systems in anesthetised rats.

Various hindbrain nuclei have been demonstrated to be involved in the control of the cardiovascular reflexes elicited by both non-noxious and noxious gastric distension, through parasympathetic and sympathetic activation. The different role played by the branches of autonomic nervous system in exerting these effects and their crosstalk in relation to low-/high-pressure distension rate has not been examined yet. Therefore, in the present work, monolateral and bilateral vagotomy and splanchnicotomy were performed in anesthetised rats to analyse the involvement of hindbrain nuclei in haemodynamic changes caused by gastric distension at high (80mmHg) and low (15mmHg) pressure. The analysis of c-Fos expression in neuronal areas involved in cardiovascular control allowed us to examine their recruitment in response to various patterns of gastric distension and the crosstalk between vagal and splanchnic systems. The results obtained show that the low-pressure (non-noxious) gastric distension increases both heart rate and arterial blood pressure. In addition, the vagus nerve and hindbrain nuclei, such as nucleus ambiguous, ventrolateral medulla and lateral reticular nucleus, appear to be primarily involved in observed responses. In particular, we have found that although vagus nerve plays a central role in exerting those cardiovascular reflex changes at low gastric distension, for its functional expression an intact splanchnic system is mandatory. Hence, the absence of splanchnic input attenuates pressor responses or turns them into depressor responses. Instead at high-pressure (noxious) gastric distension, the splanchnic nerve represents the primary component in regulating the reflex cardiovascular effects.

Markers of erythrocyte turnover are linked to liver cirrhosis stage

Background: Rheological stasis in the splanchnic system could induce erythrocyte sequestration and lysis during liver cirrhosis. Markers of erythrocyte turnover might therefore respond to the severity of portal hypertension. Hence, we investigated the relation between cirrhosis stage and glycated hemoglobin (HbA1c), as HbA1c derives from a chemical reaction which dependents on the lifespan of erythrocytes.

Dietary protein in urea cycle defects: How much? Which? How?

Dietary recommendations for patients with urea cycle disorders (UCDs) are designed to prevent metabolic decompensation (primarily hyperammonaemia), and to enable normal growth. They are based on the ‘recommended daily intake’ guidelines, on theoretical considerations and on local experience.A retrospective dietary review of 28 patients with UCDs in good metabolic control, at different ages, indicates that most patients can tolerate a natural protein intake that is compatible with metabolic stability and good growth. However, protein aversion presents a problem in many patients, leading to poor compliance with the prescribed daily protein intake. These patients are at risk of chronic protein deficiency. Failing to recognise this risk, and further restricting protein intake because of persistent hyperammonaemia may aggravate the deficiency and potentially lead to episodes of metabolic decompensation for which no clear cause is found. These patients may need on-going supplementation with essential amino acids (EAA) to prevent protein malnutrition.Current recommendations for the management of acute metabolic decompensation include cessation of protein intake whilst increasing energy (calorie) intake in the first 24h. We have found that plasma concentrations of all EAA are low at the time of admission to hospital for metabolic decompensation, with correlation between low EAA concentrations, particularly branched-chain amino acids, and hyperammonaemia. Thus, supplementation with EAA should be considered at times of metabolic decompensation.Finally, it would be advantageous to treat patients in metabolic decompensation through enteral supplementation, whenever possible, because of the contribution of the splanchnic (portal-drained viscera) system to protein retention and metabolism.