Yogic agnisara increases blood flow in the superior mesenteric artery.

OBJECTIVES: Medieval yoga texts claim that a special exercise of the muscles of the anterior abdominal wall, called agnisara, improves digestive function. Main objective of the study was to demonstrate change in the blood flow through superior mesenteric artery (if any) after performance of agnisara. METHODS: Ultrasound examination of the linear and volumetric indicators of blood flow in the superior mesenteric artery (SMA) before and after performing the agnisara yoga exercise 100 times was carried out in 12 healthy volunteers of both sexes (8 of them women). RESULTS: A significant increase in the diameter of the SMA, peak systolic and diastolic velocities, and blood flow in the superior mesenteric artery after performing the agnisara exercise 100 times was found, which contrasts with the established data on a decrease in splanchnic blood flow in humans in response to normal physical activity. CONCLUSION: Properly performed agnisara increases blood flow to the splanchnic region, registered by the SMA, which should contribute to adequate blood supply to the gastrointestinal tract for successful performance of digestive function.

Effect of meal intake for evaluating hepatic artery by Doppler ultrasonography in liver transplants: Does fasting matter for screening hepatic artery due to hemodynamic changes in splanchnic circulation?

PURPOSE: The aim of this study is to assess the utility of fasting on Doppler ultrasonography findings of hepatic artery in liver transplants. METHODS: Liver transplant patients without vascular abnormalities were prospectively evaluated between December 2017 and January 2020. Doppler sonography was used to describe hemodynamic changes in response to a standard meal. The diameter, peak systolic velocity, blood flow, resistive index (RI) of the main hepatic artery and portal vein peak velocity were measured. RESULTS: The mean hepatic arterial diameter of 44 patients was higher in the fasting group (4.5 mm) than in the postprandial group (3.3 mm) (p < .05). The mean hepatic arterial blood flow decreased (from .276 to .127 L/min) and hepatic arterial RI increased (from .66 to .71) following meal ingestion (p < .05). Hepatic arterial velocity was significantly lower and portal venous velocity was higher after oral intake. CONCLUSION: Meal ingestion has an important effect on hepatic artery Doppler features in liver transplants. Therefore, Doppler ultrasound evaluation should be considered after appropriate fasting due to postprandial responses of liver transplant.

Treatment of refractory ascites: Current strategies and new landscape of non-selective beta-blockers.

Ascites is the fluid accumulation in the peritoneal cavity, and it is the consequence of a wide variety of entities, being liver cirrhosis the most common one. In this kind of patients, the development of ascites results from splanchnic vasodilation; decreased effective circulating volume; the activation of the sympathetic nervous system and the renin-angiotensin-aldosterone system; and a systemic inflammatory process. Its management is diverse and depends on the severity of the hemodynamic disturbance and other clinical manifestations. In recent years, therapeutic strategies have been developed, but they tend to result unconventional, so new evidence demonstrates the advantages of non-selective beta-blockers for the survival rate of patients with end-stage cirrhosis and ascites.

Hemodynamic Influences on Mesenteric Blood Flow in Shock Conditions.

The gastrointestinal (GI) system, is most vulnerable to hypoperfusion among the splanchnic organs. Disturbed perfusion of the mesenteric area may lead to GI dysfunction, cause further injury to the patients and even vital outcomes. However, due to the limitation of detection methods, the hemodynamic influences on mesenteric blood flow in clinical practice are not fully understood. By elucidating the underlying mechanisms, we may be able to recognize disturbed GI perfusion and eventually GI dysfunction at an early phase. Thus, in this review, we will focus on situations where mesenteric blood flow is disturbed due to hemodynamic causes in shock conditions, and the present research status will be discussed. English language articles published before 2020 were identified through a computerized PubMed search using the terms "mesenteric, gastrointestinal, intestinal, splanchnic, blood flow, perfusion" and the cofactors. Relevant publications were retrieved and scanned for additional sources. There were few clinical trials focusing on mesenteric blood flow in shock patients. Most were animal experiments. Based on the best current evidence from these sources, we described the major influences on mesenteric blood flow in the context of physiologic accommodation, disease-related effects and the consequences of medical interventions related to shock conditions. During circulatory shock, sepsis, and medical interventions related to shock treatment, mesenteric blood flow changes and shows different features. We need to carefully consider these issues when making medical decisions, and more work needs to be done on early detection of GI hypoperfusion and its accurate correlation with GI dysfunction.

Splanchnic Vein Thrombosis in Acute Pancreatitis and Its Consequences.

Splanchnic vein thrombosis (SVT) is a serious vascular complication that can occur in patients with acute pancreatitis. We assessed the incidence of SVT and its relationship with acute pancreatitis (AP) and associated complications. We carried out a retrospective analysis of medical histories from patients hospitalized with AP in a single surgical center. Histories were acquired from patients with abdominal and pelvic computed tomography scans performed between the 2nd and 3rd day of hospitalization. We assessed the impact and extent of thrombosis over the disease course. We found a strong positive correlation (Cramer's V coefficient = 0.34) between SVT and disease severity. Mortality in the study group was 7.2% (8 patients) of which 5 patients (62.5%) were diagnosed with SVT. We observed an increased incidence of death among patients with thrombosis, with results approaching significance (P = 0.056). In our study, we found that SVT has a negative effect on the course of AP and is associated with more severe disease and increased mortality.

Contribution of Splenic Resistance Arteries to Splanchnic Blood Overflow in Cirrhosis.

BACKGROUND: In liver cirrhosis, a marked splanchnic vasodilation causes an increase in portal blood flow, contributing to the development of portal hypertension. AIM: To evaluate if, in experimental cirrhosis, a different vascular reactivity exists between splenic and mesenteric components of the splanchnic circulation. METHODS: Liver cirrhosis was induced in Sprague Dawley rats by common bile duct ligation. In sections of splenic and superior mesenteric arteries, cumulative dose-response curves were obtained. mRNA expression of endothelial nitric oxide synthase (eNOS), inducible NOS (iNOS), and prostaglandin I2 synthase (PTGIS) was evaluated. RESULTS: In cirrhotic rats, mesenteric but not splenic arteries showed a significant increase in endothelium-dependent relaxation to acetylcholine. In control and cirrhotic rats, COX inhibition alone did not significantly change the response of mesenteric arteries to acetylcholine; after inhibiting also NOS, the relaxation was completely abolished in control but only partially decreased in cirrhotic rats. After the inhibition of COX and NOS, the relaxation to acetylcholine was similarly decreased in splenic arteries from control and cirrhotic animals. The contraction induced by phenylephrine of both mesenteric and splenic arteries was decreased in cirrhotic rats. PTGIS mRNA expression did not differ in splenic and mesenteric arteries from control and cirrhotic rats; in cirrhotic rats, eNOS and iNOS mRNA expression was increased in mesenteric but not in splenic vascular bed. CONCLUSION: In cirrhotic rats, a decreased splenic arterial response to vasoconstrictors, rather than an increased response to vasodilators, contributes to splanchnic vasodilation, while in mesenteric arteries also an increased response to vasodilators secondary to, but not only, eNOS and iNOS overexpression, plays a role.

Association of Splanchnic Vein Thrombosis on Survival: 15-Year Institutional Experience With 1561 Cases.

Background Previous studies regarding survival in patients with splanchnic vein thrombosis (SVT) are limited. This study measured overall survival in a large cohort of SVTs through linkage to population-based data. Methods and Results Using a previously derived text-search algorithm, we screened the reports of all abdominal ultrasound and contrast-enhanced computed tomography studies at The Ottawa Hospital over 14 years. Screen-positive reports were manually reviewed by at least 2 authors to identify definite SVT cases by consensus. Images of uncertain studies were independently reviewed by 2 radiologists. One thousand five hundred sixty-one adults with SVT (annual incidence ranging from 2.8 to 5.9 cases/10 000 patients) were linked with population-based data sets to measure the presence of concomitant cancer and survival status. Thrombosis involved multiple veins in 314 patients (20.1%), most commonly the portal vein (n=1410, 90.3%). Compared with an age-sex-year matched population, patients with SVT had significantly reduced survival in particular with local cancer (adjusted relative excess risk for recent cases 12.0 [95% CI, 9.8-14.6] and for remote cases 9.7 [7.7-12.2]), distant cancer (relative excess risk for recent cases 5.7 [4.5-7.3] and for remote cases 5.4 [4.4-6.6]), cirrhosis (relative excess risk 8.2 [5.3-12.7]), and previous venous thromboembolism (relative excess risk 3.8 [2.4-6.0]). One hundred fifty (23.9%) of patients >65 years of age were anticoagulated within 1 month of diagnosis. Conclusions SVT is more common than expected. Most patients have cancer and the portal vein is by far the most common vein involved. Compared with the general population, patients with SVT had significantly reduced survival, particularly in patients with concomitant cancer, cirrhosis, and previous venous thromboembolic disease. Most elderly patients did not receive anticoagulant therapy.

Hyponatremia in Cirrhosis: An Update.

Hyponatremia is frequently seen in patients with ascites secondary to advanced cirrhosis and portal hypertension. Although not apparent in the early stages of cirrhosis, the progression of cirrhosis and portal hypertension leads to splanchnic vasodilation, and this leads to the activation of compensatory mechanisms such as renin-angiotensin-aldosterone system (RAAS), sympathetic nervous system, and antidiuretic hormone (ADH) to ameliorate low circulatory volume. The net effect is the avid retention of sodium and water to compensate for the low effective circulatory volume, resulting in the development of ascites. These compensatory mechanisms lead to impairment of the kidneys to eliminate solute-free water in decompensated cirrhosis. Nonosmotic secretion of antidiuretic hormone (ADH), also known as arginine vasopressin, further worsens excess water retention and thereby hyponatremia. The management of hyponatremia in this setting is a challenge as conventional therapies for hyponatremia including fluid restriction and correction of hypokalemia are frequently inefficacious. In this review, we discuss the pathophysiology, complications, and various treatment modalities, including albumin infusion, selective vasopressin receptor antagonists, or hypertonic saline for patients with severe hyponatremia and those awaiting liver transplantation.

Exercise and intestinal permeability: another form of exercise-induced hormesis?

Regular aerobic exercise has numerous benefits on human physiology, arguably by serving as a hormetic stressor resulting in positive adaptations over time. It has long been known that aerobic exercise at a variety of intensities and durations induces intestinal permeability, which is a feature of many pathologies of the gastrointestinal tract and metabolic diseases. Given the health benefits of exercise, it seems unlikely that intestinal permeability induced by exercise outweighs the positive adaptations. In fact, a growing body of evidence suggests adoption of exercise regimens lasting weeks to months improves indicators of intestinal permeability. In this brief review, we summarize factors contributing to acute exercise-induced intestinal permeability and what is known about chronic exercise and the gut barrier. Additionally, we outline known and theoretical adaptations of the gut to chronic exercise that may explain emerging reports that exercise improves markers of gut integrity.

Impact of habituated dietary protein intake on fasting and postprandial whole-body protein turnover and splanchnic amino acid metabolism in elderly men: a randomized, controlled, crossover trial.

BACKGROUND: Efficacy of protein absorption and subsequent amino acid utilization may be reduced in the elderly. Higher protein intakes have been suggested to counteract this. OBJECTIVES: We aimed to elucidate how habituated amounts of protein intake affect the fasted state of, and the stimulatory effect of a protein-rich meal on, protein absorption, whole-body protein turnover, and splanchnic amino acid metabolism. METHODS: Twelve men (65-70 y) were included in a double-blinded crossover intervention study, consisting of a 20-d habituation period to a protein intake at the RDA or a high amount [1.1 g · kg lean body mass (LBM)-1 · d-1 or >2.1 g · kg LBM-1 · d-1, respectively], each followed by an experimental trial with a primed, constant infusion of D8-phenylalanine and D2-tyrosine. Arterial and hepatic venous blood samples were obtained after an overnight fast and repeatedly 4 h after a standardized meal including intrinsically labeled whey protein concentrate and calcium-caseinate proteins. Blood was analyzed for amino acid concentrations and phenylalanine and tyrosine tracer enrichments from which whole-body and splanchnic amino acid and protein kinetics were calculated. RESULTS: High (compared with the recommended amount of) protein intake resulted in a higher fasting whole-body protein turnover with a resultant mean ± SEM 0.03 ± 0.01 µmol · kg LBM-1 · min-1 lower net balance (P < 0.05), which was not rescued by the intake of a protein-dense meal. The mean ± SEM plasma protein fractional synthesis rate was 0.13 ± 0.06%/h lower (P < 0.05) after habituation to high protein. Furthermore, higher fasting and postprandial amino acid removal were observed after habituation to high protein, yielding higher urea excretion and increased phenylalanine oxidation rates (P < 0.01). CONCLUSIONS: Three weeks of habituation to high protein intake (>2.1 g protein · kg LBM-1 · d-1) led to a significantly higher net protein loss in the fasted state. This was not compensated for in the 4-h postprandial period after intake of a meal high in protein.This trial was registered at clinicaltrials.gov as NCT02587156.

Causal Relationship between Celiac Stenosis and Pancreaticoduodenal Artery Aneurysm: Interpretation by Simulation Using an Electric Circuit.

Pancreaticoduodenal artery (PDA) aneurysm and celiac artery (CA) stenosis are rare diseases in themselves. Interestingly, however, there are more cases documented in the literature in which these two disease entities occurred together than could be coincidental, and CA stenosis has been suggested as the provocative condition in developing PDA aneurysm. This study is aimed at examining the causal relationship between CA stenosis and PDA aneurysm by simulating the splanchnic circulation with an electric circuit. A patient with multiple PDA aneurysms and collaterals with CA stenosis was treated in our institution using hybrid techniques. The patient's pre- and postoperative status was simulated using an electric circuit, and the two possible scenarios were tested for compatibility: the stenosis-first scenario vs. the aneurysm-first scenario. The simulation was performed in two ways: using Simulink® software (MATLAB® Release 2018b) and actual circuit construction on a breadboard. The stenosis-first scenario showed that as the CA stenosis progresses, the blood flow through PDA increases, favoring the development of an aneurysm and/or collaterals if the artery was already compromised by a weakening condition. On the other hand, the aneurysm-first scenario also showed that if the aneurysm or collaterals developed first, the aneurysm will steal the blood flow through the CA, causing it to collapse if the artery was already compromised by increased wall tension. Contrary to the common belief, this study showed that in patients suffering from concurrent CA stenosis and PDA aneurysm, either condition could develop first and predispose the development of the other. The simulation of splanchnic blood flow with an electric circuit provides a useful tool for analyzing rare vascular diseases that are difficult to provoke in clinical and animal studies.

Effects of Proximal and Distal Enteral Glucose Infusion on Cardiovascular Response in Health and Type 2 Diabetes.

CONTEXT: Exposure of the small intestine to nutrients frequently leads to marked reductions in blood pressure (BP) in type 2 diabetes (T2DM). It remains unclear whether the region of the gut exposed to nutrients influences postprandial cardiovascular responses. OBJECTIVE: To evaluate the cardiovascular responses to proximal and distal small intestinal glucose infusion in health and T2DM. DESIGN: Double-blind, randomized, crossover design. SETTING: Single center in Australia. PATIENTS: 10 healthy subjects and 10 T2DM patients. INTERVENTIONS: Volunteers were studied on 2 occasions, when a transnasal catheter was positioned with infusion ports opening 13 cm and 190 cm beyond the pylorus. A 30-g bolus of glucose was infused into either site and 0.9% saline into the alternate site over 60 minutes. MAIN OUTCOME MEASURES: BP, heart rate (HR), and superior mesenteric artery (SMA) blood flow were measured over 180 minutes. RESULTS: Systolic BP was unchanged in response to both infusions in health, but decreased in T2DM, with a greater reduction after proximal versus distal infusion (all P ≤ .01). The increment in HR did not differ between treatments in health, but was greater after distal versus proximal infusion in T2DM (P = .02). The increases in SMA blood flow were initially greater, but less sustained, with proximal versus distal infusion in health (P < .001), a pattern less evident in T2DM. CONCLUSIONS: In T2DM, postprandial hypotension may be mitigated by diversion of nutrients from the proximal to the distal small intestine.

Oximetría esplácnica en neonatos pequeños para la edad gestacional en relación con el estudio doppler prenatal / Splanchnic oximetry in small for gestational age neonates in relation to prenatal doppler study

INTRODUCCIÓN: El estudio del doppler fetal permite identificar la etiología placentaria y clasificar su gravedad en aquellos neonatos pequeños para la edad gestacional. Existen estudios que relacionan estos datos doppler con alteraciones en el flujo intestinal del recién nacido, pero su relación con los datos de oximetría intestinal ha sido poco estudiada. OBJETIVO: Evaluar si existe relación entre los datos doppler prenatales y los datos de oximetría abdominal en los niños pequeños para su edad gestacional. MATERIAL Y MÉTODOS: Estudio prospectivo observacional en neonatos > 32 semanas con un peso al nacer < P10. Se clasificó la gravedad de la insuficiencia placentaria según criterios de doppler prenatal. Se monitorizó la oximetría esplácnica durante los 3 primeros días de vida y se realizó un análisis comparativo de los datos oximétricos según la afectación doppler prenatal. RESULTADOS: Se evaluaron 53 pacientes. Se observaron diferencias significativas en la rSO2 media entre los pacientes con fallo placentario moderado o grave y aquellos con doppler prenatal normal o levemente alterado: 42 ± 10 vs. 71,3 ± 10 (p < 0,001). Estas diferencias se mantuvieron durante los 3 primeros días de vida. Se identificaron patrones tipo de oximetría esplácnica según el grado de insuficiencia placentaria. CONCLUSIONES: Existe correlación entre el doppler fetal y el patrón de oximetría esplácnica durante los primeros días de vida. Los neonatos con insuficiencia placentaria moderada o grave presentan unos registros de oximetría abdominal más alterados, por lo que podría ser una técnica útil para evaluar el grado de insuficiencia placentaria y el riesgo de intolerancia oral en los neonatos pequeños para la edad gestacional

INTRODUCTION: Among small for gestational age neonates, foetal Doppler enables the identification of placental insufficency aetiology and the classification of severity in small for gestational age neonates. There are studies that associate the Doppler data with alterations in the intestinal flow of the newborn, but its relationship with intestinal oximetry has been little studied. OBJECTIVE: To assess whether there is a relationship between prenatal Doppler data and abdominal oximetry in small for gestational age neonates MATERIAL AND METHODS: A prospective observational study carried out on neonates >32 weeks with a birth weight < P10. The severity of placental insufficiency was classified according to prenatal Doppler criteria. Splanchnic oximetry was monitored during the first three days of life and a comparative analysis of the oximetry data was performed according to the prenatal Doppler alteration severity. RESULTS: A total of 53 patients were evaluated. Significant differences were observed in the mean regional oximetry (rSO2) between patients with moderate or severe placental failure and those with normal or slightly altered prenatal Doppler: 42 ± 10 vs. 71.3 ± 10 (P < .001). These differences were maintained during the first 3 days of life. Standard patterns of splanchnic oximetry were identified depending on the degree of placental insufficiency. CONCLUSIONS: There is a correlation between the foetal Doppler and the splanchnic oximetry pattern during the first days of life. Neonates with moderate or severe placental insufficiency have more altered abdominal oximetry patterns, making it a useful technique to evaluate the degree of placental insufficiency and the risk of oral intolerance in small for gestational age neonates

Association of Bolus Feeding With Splanchnic and Cerebral Oxygen Utilization Efficiency Among Premature Infants With Anemia and After Blood Transfusion.

Importance: The pathogenesis of transfusion-associated necrotizing enterocolitis remains elusive. Splanchnic hypoperfusion associated with packed red blood cell transfusion (PRBCT) and feeding has been implicated, but studies of splanchnic tissue oxygenation with respect to feeding plus PRBCT are lacking. Objective: To investigate the oxygen utilization efficiency of preterm gut and brain challenged with bolus feeding during anemia and after transfusion using near-infrared spectroscopy. Design, Setting, and Participants: This prospective cohort study conducted from September 1, 2014, to November 30, 2016, at a tertiary neonatal intensive care unit included 25 hemodynamically stable infants with gestational age less than 32 weeks, birth weight less than 1500 g, and postmenstrual age younger than 37 weeks. Data analysis was performed from August 1, 2017, to October 31, 2018. Exposures: Infants received PRBCT (15 mL/kg for 4 hours) and at least 120 mL/kg daily of second hourly bolus feedings. Main Outcomes and Measures: Splanchnic fractional tissue oxygen extraction (FTOEs) and cerebral fractional tissue oxygen extraction (FTOEc) measures were made during 75-minute feeding cycles that comprised a 15-minute preprandial feeding phase (FP0) and 4 contiguous 15-minute postprandial feeding phases (FP1, FP2, FP3, and FP4; each 15 minutes long). The intraindividual comparisons of feeding-related changes were evaluated during the pretransfusion epoch (TE0: 4 hours before onset of transfusion) and 3 TEs after transfusion (TE1: first 8 hours after PRBCT completion; TE2: 9-16 hours after PRBCT completion; and TE3: 17-24 hours after PRBCT completion). Results: Of 25 enrolled infants (13 [52%] female; median birth weight, 949 g [interquartile range {IQR}, 780-1100 g]; median gestational age, 26.9 weeks [IQR, 25.9-28.6 weeks]; median enrollment weight, 1670 g [IQR, 1357-1937 g]; and median postmenstrual age, 34 weeks [IQR, 32.9-35 weeks]), 1 infant was excluded because of corrupted near-infrared spectroscopy data. No overall association was found between FTOEs and FPs in a multivariable repeated-measures model that accounted for transfusion epochs (primary analysis approach) (FP0: mean estimate, 11.64; 95% CI, 9.55-13.73; FP1: mean estimate, 12.02; 95% CI, 9.92-14.11; FP2: mean estimate, 12.77; 95% CI, 10.68-14.87; FP3: mean estimate, 12.54; 95% CI, 10.45-14.64; FP4: mean estimate, 12.98; 95% CI, 10.89-15.08; P = .16 for the FP association). However exploratory analyses of postprandial changes in FTOEs undertaken for each transfusion epoch separately found evidence of increased postprandial FTOEs during TE1 (mean [SD] FTOEs, 10.55 [5.5] at FP0 vs 13.21 [5.96] at FP4, P = .046). The primary and exploratory analyses found no association between FTOEc and feeding phases, suggesting that cerebral oxygenation may be protected. Conclusions and Relevance: The findings suggest that enteral feeding may be associated with gut ischemia and potentially transfusion-associated necrotizing enterocolitis. The postprandial changes in FTOEs appear to warrant further investigation in larger randomized studies.

ACG Clinical Guideline: disorders of the hepatic and mesenteric circulation

Disorders of the mesenteric, portal, and hepatic veins and mesenteric and hepatic arteries have important clinical consequences and may lead to acute liver failure, chronic liver disease, noncirrhotic portal hypertension, cirrhosis, and hepatocellular carcinoma. Although literature in the field of vascular liver disorders is scant, these disorders are common in clinical practice, and general practitioners, gastroenterologists, and hepatologists may benefit from expert guidance and recommendations for management of these conditions. These guidelines represent the official practice recommendations of the American College of Gastroenterology. Key concept statements based on author expert opinion and review of literature and specific recommendations based on PICO/GRADE analysis have been developed to aid in the management of vascular liver disorders. These recommendations and guidelines should be tailored to individual patients and circumstances in routine clinical practice.

Patterns of splenic arterial enhancement on computed tomography scan are related to portal venous hypertension.

OBJECTIVES: We have previously shown that patterns of splenic arterial enhancement on computed tomography scan change following liver transplantation. We suggested that this is related to changes in portal venous pressure. The aim of this study was to see if similar patterns occur in patients with and without portal hypertension and in patients before and after portal systemic shunts (transjugular portosystemic shunts). METHODS: We evaluated contrast enhanced computed tomography scans in patients being evaluated for liver disease and compared those from patients with and without portal hypertension. In addition we evaluated patients who had computed tomography scans before and after transjugular portosystemic shunts shunts. Splenic arterial enhancement was evaluated using Hounsfield units (pixel counts). RESULTS: Twenty-four patients with clinically significant portal hypertension were compared to 91 without. Mean splenic pixel count was significantly lower in patients with clinically significant portal hypertension (88.2 ± 17.7 vs. 115.2 ± 21.0; m ± SD, P < 0.01). Computed tomography scans were available in 18 patients pre- and post-transjugular portosystemic shunts. Pixel counts were significantly higher in the post-transjugular portosystemic shunts scans (99.7 ± 20.9 vs. 88.9 ± 26.3; P < 0.05). CONCLUSION: This study supports the hypothesis that changes in portal venous pressure are related to changes in splenic arterial enhancement. We suggest that this reflects changes in the splenic micro-circulation. This mechanism may be part of the innate immune response and may also be important in the pathogenesis of hypersplenism.

A hybrid discrete-continuum approach for modelling microcirculatory blood flow.

In recent years, biological imaging techniques have advanced significantly and it is now possible to digitally reconstruct microvascular network structures in detail, identifying the smallest capillaries at sub-micron resolution and generating large 3D structural data sets of size >106 vessel segments. However, this relies on ex vivo imaging; corresponding in vivo measures of microvascular structure and flow are limited to larger branching vessels and are not achievable in three dimensions for the smallest vessels. This suggests the use of computational modelling to combine in vivo measures of branching vessel architecture and flows with ex vivo data on complete microvascular structures to predict effective flow and pressures distributions. In this paper, a hybrid discrete-continuum model to predict microcirculatory blood flow based on structural information is developed and compared with existing models for flow and pressure in individual vessels. A continuum-based Darcy model for transport in the capillary bed is coupled via point sources of flux to flows in individual arteriolar vessels, which are described explicitly using Poiseuille's law. The venular drainage is represented as a spatially uniform flow sink. The resulting discrete-continuum framework is parameterized using structural data from the capillary network and compared with a fully discrete flow and pressure solution in three networks derived from observations of the rat mesentery. The discrete-continuum approach is feasible and effective, providing a promising tool for extracting functional transport properties in situations where vascular branching structures are well defined.

Gender differences in vascular reactivity of mesenteric arterioles in portal hypertensive and non-portal hypertensive rats.

BACKGROUND: Portal hypertension (PHT) is primarily caused by an increase in resistance to portal outflow and secondarily by an increase in splanchnic blood flow. Vascular hyporeactivity both in systemic circulation and in the mesenteric artery plays a role in the hyperdynamic circulatory syndrome. AIM: To explore gender differences and the role of endogenous sex hormones in PHT and vascular reactivity of mesenteric arterioles in rats. METHODS: Cirrhosis and PHT were established by subcutaneous injection of carbon tetrachloride (CCl4) in both male and female integral and castrated rats (ovariectomized [OVX] in female rats, orchiectomy [ORX] in male rats). The third-order branch of the mensenteric artery was divided and used to measure vascular reactivity to vasoconstrictors. RESULTS: No significant difference in portal pressure was observed between integral and castrated male PHT rats (15.2 ± 2.1 mmHg vs 16.7 ± 2.7 mmHg, P > 0.05). The portal pressure in integral female PHT rats was lower than that in OVX female PHT rats (12.7 ± 2.7 mmHg vs 16.5 ± 2.4 mmHg, P < 0.05). In PHT rats, the concentration response curves of the mesenteric arterioles to norepinephrine were shifted to the right, and the maximal responses (Emax) values were decreased and effective concentrations causing half maximum responses (EC50) values were increased, compared to those of non-PHT rats, both in male and female rats. Compared to non-PHT integral male rats, the sensitivity of the mesenteric arterioles of non-PHT ORX male rats to norepinephrine was decreased (P > 0.05). However, there was no difference between integral and ORX male rats with PHT. In integral female PHT rats, the concentration response curves were shifted to the left (P < 0.05), and the Emax values were increased and EC50 values were decreased compared to OVX female PHT rats. CONCLUSION: Clear gender differences were observed in mesenteric vascular reactivity in CCl4-induced cirrhotic and PHT rats. Conservation of estrogen can retain the sensitivity of the mesenteric arterioles to vasoconstrictors and has a protective effect on splanchnic vascular function in PHT.

Periodicity, time constants of drainage, and the mechanical determinants of peak cardiac output during exercise.

To analyze mechanical adaptations that must occur in the cardiovascular system to reach the high cardiac outputs known to occur at peak aerobic performance, we adapted a computational model of the circulation by adding a second parallel venous compartment as proposed by August Krogh in 1912. One venous compartment has a large compliance and slow time constant of emptying; it is representative of the splanchnic circulation. The other has a low compliance and fast time constant of emptying and is representative of muscle beds. Fractional distribution between the two compartments is an important determinant of cardiac output. Parameters in the model were based on values from animal and human studies normalized to a 70 kg male. The baseline cardiac output was set at 5 L/min, and we aimed for 25 L/min at peak exercise with a fractional flow to the peripheral-muscle region of 90%. Finally, we added the equivalent of a muscle pump. Adjustments in circuit and cardiac parameters alone increased cardiac output to only 15.6 L/min because volume accumulated in the muscle compartment and limited a higher cardiac output. Addition of muscle contractions decompressed the muscle region and allowed cardiac output to increase to 23.4 L/min. The pulsatility of blood flow imposes important constraints on the adaptations of cardiac and circulatory functions because it fixes the times for filling and emptying. Flow is further limited by the limits of cardiac filling on each beat. Muscle contractions play a key role by decompressing volume that would otherwise accumulate in the muscle vasculature and by decreasing the time for stroke return to the right ventricle.NEW & NOTEWORTHY We used a computational model of the circulation and previous human and animal data to model mechanical changes in the heart and circulation that are needed to reach the known high cardiac output at peak aerobic exercise. Key points are that time constants of drainage of circulatory compartments put limits on peak flow in a pulsatile system. Muscle contractions increase the rate of return to the heart and by doing so prevent accumulation of volume in the muscle compartment and greatly increase circulatory capacity.