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Blood flow to the active muscles and arterial blood pressure (ABP) increase during dynamic exercise, whereas blood flow to inactive organs (e.g., splanchnic organs and inactive limbs) declines. Aging leads to exaggerated ABP responses to exercise in females, but whether this is related to greater splanchnic vasoconstriction is unknown. This study sought to clarify the effect of aging in females on celiac artery blood flow during dynamic light-intensity exercise. Twelve healthy young females (YF: 20 ± 2 yr, mean ± SD) and 12 healthy older females (OF: 71 ± 4 yr) performed dynamic knee-extension and knee-flexion exercises at 30% of heart rate reserve for 4 min. The absolute changes from baseline (Δ) for mean arterial blood pressure (MAP), celiac artery mean blood flow (celMBF), and celiac vascular conductance (celVC) during exercise were calculated. ABP was measured using an automated sphygmomanometer, and celMBF was recorded by Doppler ultrasonography. The increase in MAP during exercise was greater in OF than in YF (YF: +14 ± 7 mmHg, OF: +24 ± 13 mmHg, P = 0.028). The celMBF decreased during exercise in both groups, but there was no significant difference in the response between YF and OF (YF: −93.0 ± 66.1 mL/min, OF: −89.6 ± 64.0 mL/min, P = 0.951). The celVC also decreased during exercise and remained lower than baseline during exercise. However, the response was not different between YF and OF (YF: −1.8 ± 1.0 mL/min/mmHg, OF: −1.5 ± 0.6 mL/min/mmHg, P = 0.517). These results demonstrate that aging in females has minimal influence on splanchnic artery hemodynamic responses during dynamic light-intensity exercise, suggesting that exaggerated ABP responses during exercise in OF are not due to greater splanchnic vasoconstriction. NEW & NOTEWORTHY: During exercise, the splanchnic arteries vasoconstrict, contributing to blood flow redistribution and the blood pressure response. Blood pressure responses to exercise are exaggerated with aging in females; however, the physiological mechanism responsible has not been clarified. We show that celiac artery blood flow changes during light-intensity dynamic exercise do not differ with age in females. This indicates the exaggerated blood pressure to exercise with aging is likely not due to a difference in splanchnic vasoconstriction. [ABSTRACT FROM AUTHOR]

Abstract Background Elevation of the head of bed (HOB) increases intra-abdominal pressure (IAP), but the effect of body position on abdominal splanchnic perfusion is not clear. The current study aimed to evaluate the effect of body position on the superior mesenteric artery (SMA) and the celiac artery (CA) blood flow by Doppler ultrasound in mechanically ventilated patients with intra-abdominal hypertension (IAH). Methods This prospective cohort study included 53 mechanically ventilated patients with IAH. IAP, hemodynamic variables, and Doppler parameters of the SMA and CA were measured in the supine position. The measurements were repeated after the HOB angle was raised to 15° for 5 min and similarly at HOB angles of 30° and 45°. Finally, the patient was returned to the supine and these variables were re-measured. Results The median (interquartile range, IQR) superior mesenteric artery blood flow (SMABF) decreased from 269 (244–322) to 204 (183–234) mL/min and the median (IQR) celiac artery blood flow (CABF) from 424 (368–483) to 376 (332–472) mL/min (both p

The diagnosis of chronic mesenteric ischaemia is typically based on angiographic findings along with a classic symptomatology. Only a few methods are available for functional testing to establish the diagnosis, such as indirect measurement of the splanchnic blood flow and hepatic vein oxygenation. The present case is a 76-year-old woman with weight loss and intermittent abdominal pain who was clinically suspected of chronic mesenteric ischaemia based on severe stenosis of the celiac artery and superior mesenteric artery. Measurement of the total splanchnic blood flow and hepatic vein oxygenation, however, showed a normal perfusion after meal stimulation, as well as an increased hepatic vein oxygenation, indicating normal flow reserves. This was likely due to a richly developed Riolan’s anastomosis arising from the inferior mesenteric artery. The present case advocates the need for functional testing when diagnosing chronic mesenteric ischaemia.

Background: Elevation of the head of bed (HOB) increases intra-abdominal pressure (IAP), but the effect of body position on abdominal splanchnic perfusion is not clear. The current study aimed to evaluate the effect of body position on the superior mesenteric artery (SMA) and the celiac artery (CA) blood flow by Doppler ultrasound in mechanically ventilated patients with intra-abdominal hypertension (IAH). Methods: This prospective cohort study included 53 mechanically ventilated patients with IAH. IAP, hemodynamic variables, and Doppler parameters of the SMA and CA were measured in the supine position. The measurements were repeated after the HOB angle was raised to 15° for 5 min and similarly at HOB angles of 30° and 45°. Finally, the patient was returned to the supine and these variables were re-measured. Results: The median (interquartile range, IQR) superior mesenteric artery blood flow (SMABF) decreased from 269 (244–322) to 204 (183–234) mL/min and the median (IQR) celiac artery blood flow (CABF) from 424 (368–483) to 376 (332–472) mL/min (both p<0.0001) while median (IQR) IAP increased from 14(13–16) to 16(14–18) mmHg (p<0.0001) when the HOB angle was changed from 0° to 15°. However, SMABF and CABF were maintained at similar levels from 15° to 30°, despite median (IQR) IAP increased to 17(15–18) mmHg (p = 0.0002). Elevation from 30° to 45° further reduced median (IQR) SMABF from 200(169–244) to 164(139–212) mL/min and CABF from 389(310–438) to 291(241–383) mL/min (both p<0.0001), Meanwhile, median (IQR) IAP increased to 19(18–21) mmHg (p<0.0001). Conclusions: In mechanically ventilated patients with IAH, progressive elevation of the HOB from a supine to semi-recumbent position was associated with a gradual reduction in splanchnic blood flow. However, the results indicate that splanchnic blood flow is not further reduced when the HOB is elevated from 15° to 30°.This study confirms the influence of head-up angle on blood flow of the splanchnic organs and may contribute to the selection of the optimal position in patients with abdominal hypertension. [ABSTRACT FROM AUTHOR]

The diagnosis of chronic mesenteric ischaemia is typically based on angiographic findings along with a classic symptomatology. Only a few methods are available for functional testing to establish the diagnosis, such as indirect measurement of the splanchnic blood flow and hepatic vein oxygenation. The present case is a 76-year-old woman with weight loss and intermittent abdominal pain who was clinically suspected of chronic mesenteric ischaemia based on severe stenosis of the celiac artery and superior mesenteric artery. Measurement of the total splanchnic blood flow and hepatic vein oxygenation, however, showed a normal perfusion after meal stimulation, as well as an increased hepatic vein oxygenation, indicating normal flow reserves. This was likely due to a richly developed Riolan's anastomosis arising from the inferior mesenteric artery. The present case advocates the need for functional testing when diagnosing chronic mesenteric ischaemia. [ABSTRACT FROM AUTHOR]

New Findings: What is the central question of this study?Increased work of breathing and the accumulation of metabolites have neural and cardiovascular consequences through a respiratory muscle‐induced metaboreflex. The influence of the respiratory muscle‐induced metaboreflex on splanchnic blood flow in humans remains unknown.What is the main finding and its importance?Coeliac artery blood flow decreased gradually during inspiratory resistive breathing, accompanied by a progressive increase in arterial blood pressure. It is possible that the respiratory muscle‐induced metaboreflex contributes to splanchnic blood flow regulation. The purpose of this study was to clarify the effect of increasing inspiratory muscle work on coeliac artery blood flow. Eleven healthy young males completed the study. The subjects performed voluntary hyperventilation with or without inspiratory resistance (loading or non‐loading trial; tidal volume of 40% of vital capacity and breathing frequency of 20 breaths/min). The loading trial was conducted with inspiratory resistance (40% of maximal inspiratory pressure) and was terminated when the subjects could no longer maintain the target tidal volume or breathing frequency. The non‐loading trial was conducted without inspiratory resistance and was of the same duration as the loading trial. Arterial blood pressure was recorded using finger photoplethysmography, and coeliac artery blood flow was measured using Doppler ultrasound. Mean arterial blood pressure increased gradually during the loading trial (mean ± SD; from 89.0 ± 10.8 to 103.9 ± 17.3 mmHg) but not in the non‐loading trial (from 88.7 ± 5.9 to 90.4 ± 9.9 mmHg). Coeliac artery blood flow and coeliac vascular conductance decreased gradually during the loading trial (from 601.2 ± 155.7 to 482.6 ± 149.5 mL/min and from 6.9 ± 2.2 to 4.8 ± 1.7 mL/min/mmHg, respectively) but were unchanged in the non‐loading trial (from 630.7 ± 157.1 to 635.6 ± 195.7 mL/min and from 7.1 ± 1.8 to 7.2 ± 2.9 mL/min/mmHg, respectively). These results show that increasing inspiratory muscle work affects splanchnic blood flow regulation, and we suggest that this might be mediated by the inspiratory muscle‐induced metaboreflex. [ABSTRACT FROM AUTHOR]

Background and Aims: Intraabdominal hypertension (IAH) is poorly diagnosed condition that cause splanchnic hypoperfusion and abdominal organs ischemia and can lead to multiple organ failure. There are no scientific data regarding effect of intraabdominal pressure (IAP) on splanchnic circulation in children. Material and Methods: Ninety-four children after surgery for appendicular peritonitis were enrolled in the study. After IAP measurement children were included in one of two groups according IAP levels: “without IAH” (n = 51) and “with IAH” (n = 43). Superior mesenteric artery (SMA) and portal vein (PV) blood flows (BFSMA, BFPV, mL/min) were measured, and SMA and PV blood flow indexes (BFISMA, BFIPV, ml/min*m2) and abdominal perfusion pressure (APP) were calculated in both groups. Results: Median BFISMA and BFIPV in group “with IAH” were lower by 54.38% (P < 0.01) and 63.11% (P < 0.01) respectively compared to group “without IAH”. There were strong significant negative correlation between IAP and BFISMA (rs = –0.66; P < 0.0001), weak significant negative correlation between IAP and BFIPV (rs = –0.36; P = 0.0001) in group “with IAH” and weak significant negative correlation between IAP and BFISMA (rs = –0.30; P = 0.0047) in group “without IAH”. There were no statistically significant correlations between IAP and BFIPV in group “without IAH”, between BFISMA and APP in both groups and between BFIPV and APP in both groups. Conclusion: Elevated IAP significantly reduces splanchnic blood flow in children with appendicular peritonitis. BFISMA and BFIPV negatively correlate with IAP in these patients. There is no correlation between BFISMA/BFIPV and APP in children with IAH due to appendicular peritonitis.

Background: Acute mesenteric ischaemia (AMI) is a surgical emergency which has an associated high mortality. The mainstay of active treatment includes early surgical intervention, with resection of non-viable bowel, and revascularisation of the ischaemic bowel where possible. Due to the physiological insult of AMI however, perioperative care often involves critical care and the use of vasoactive agents to optimise end organ perfusion. A number of these vasoactive agents are currently available with varied mechanism of action and effects on splanchnic blood flow. However, specific guidance on which is the optimal vasoactive drug to use in these settings is limited. This systematic review aimed to evaluate the current evidence comparing vasoactive drugs in AMI. Methods: A systematic search of Ovid Medline, Ovid Embase, Cochrane CENTRAL and the Cochrane Database of Systematic Review was performed on the 5th of November 2020 to identify randomised clinical trials comparing different vasoactive agents in AMI on outcomes including mortality. The search was performed through the Royal College of Surgeons of England (RCSEng) search support library. Results were analysed using the Rayyan platform, and independently screened by four investigators. Results: 614 distinct papers were identified. After screening, there were no randomised clinical trials meeting the inclusion criteria. Conclusions: This review identifies a gap in literature, and therefore recommends an investigation into current practice and clinician preference in relation to vasoactive agents in AMI. Multicentre randomised controlled trials comparing these medications on clinical outcomes will therefore be required to address this question.

Background: Acute mesenteric ischaemia (AMI) is a surgical emergency which has an associated high mortality. The mainstay of active treatment includes early surgical intervention, with resection of non-viable bowel, and revascularisation of the ischaemic bowel where possible. Due to the physiological insult of AMI however, perioperative care often involves critical care and the use of vasoactive agents to optimise end organ perfusion. A number of these vasoactive agents are currently available with varied mechanism of action and effects on splanchnic blood flow. However, specific guidance on which is the optimal vasoactive drug to use in these settings is limited. This systematic review aimed to evaluate the current evidence comparing vasoactive drugs in AMI. Methods: A systematic search of Ovid Medline, Ovid Embase, Cochrane CENTRAL and the Cochrane Database of Systematic Review was performed on the 5th of November 2020 to identify randomised clinical trials comparing different vasoactive agents in AMI on outcomes including mortality. The search was performed through the Royal College of Surgeons of England (RCSEng) search support library. Results were analysed using the Rayyan platform, and independently screened by four investigators. Results: 614 distinct papers were identified. After screening, there were no randomised clinical trials meeting the inclusion criteria. Conclusions: This review identifies a gap in literature, and therefore recommends an investigation into current practice and clinician preference in relation to vasoactive agents in AMI. Multicentre randomised controlled trials comparing these medications on clinical outcomes will therefore be required to address this question.

Background and Aims: Intraabdominal hypertension (IAH) is poorly diagnosed condition that cause splanchnic hypoperfusion and abdominal organs ischemia and can lead to multiple organ failure. There are no scientific data regarding effect of intraabdominal pressure (IAP) on splanchnic circulation in children. Material and Methods: Ninety-four children after surgery for appendicular peritonitis were enrolled in the study. After IAP measurement children were included in one of two groups according IAP levels: "without IAH" (n = 51) and "with IAH" (n = 43). Superior mesenteric artery (SMA) and portal vein (PV) blood flows (BFSMA, BFPV, mL/min) were measured, and SMA and PV blood flow indexes (BFISMA, BFIPV, ml/min*m2) and abdominal perfusion pressure (APP) were calculated in both groups. Results: Median BFISMA and BFIPV in group "with IAH" were lower by 54.38% (P < 0.01) and 63.11% (P < 0.01) respectively compared to group "without IAH". There were strong significant negative correlation between IAP and BFISMA (rs = –0.66; P < 0.0001), weak significant negative correlation between IAP and BFIPV (rs = –0.36; P = 0.0001) in group "with IAH" and weak significant negative correlation between IAP and BFISMA (rs = –0.30; P = 0.0047) in group "without IAH". There were no statistically significant correlations between IAP and BFIPV in group "without IAH", between BFISMA and APP in both groups and between BFIPV and APP in both groups. Conclusion: Elevated IAP significantly reduces splanchnic blood flow in children with appendicular peritonitis. BFISMA and BFIPV negatively correlate with IAP in these patients. There is no correlation between BFISMA/BFIPV and APP in children with IAH due to appendicular peritonitis. [ABSTRACT FROM AUTHOR]

Objective: Meal ingestion is followed by a redistribution of blood flow (BF) within the splanchnic region contributing to nutrient absorption, insulin secretion and glucose disposal, but factors regulating this phenomenon in humans are poorly known. The aim of the present study was to evaluate the organ-specific changes in BF during a mixed-meal and incretin infusions. Design: A non-randomized intervention study of 10 healthy adults to study splanchnic BF regulation was performed. Methods: Effects of glucose-dependent insulinotrophic polypeptide (GIP) and glucagon-like peptide 1 (GLP-1) infusions and mixed-meal were tested in 10 healthy, glucose tolerant subjects using PET-MRI multimodal imaging technology. Intestinal and pancreatic BF and blood volume (BV) were measured with 15O-water and 15O-carbon monoxide, respectively. Results: Ingestion of a mixed-meal led to an increase in pancreatic and jejunal BF, whereas duodenal BF was unchanged. Infusion of GIP and GLP-1 reduced BF in the pancreas. However, GIP infusion doubled blood flow in the jejunum with no effect of GLP-1. Conclusion: Together, our data suggest that meal ingestion leads to increases in pancreatic BF accompanied by a GIP-mediated increase in jejunal but not duodenal blood flow.

The incretin hormone glucose-dependent insulinotropic polypeptide (GIP) potentiates glucose-stimulated insulin secretion, and affects ß-cell turnover. This study aimed at evaluating if some of the beneficial effects of GIP on glucose homeostasis can be explained by modulation of islet blood flow. Anesthetized Sprague-Dawley rats were infused intravenously with different doses of GIP (10, 20, or 60 ng/kg*min) for 30 min. Subsequent organ blood flow measurements were performed with microspheres. In separate animals, islets were perfused ex vivo with GIP (10-6-10-12 mol/L) during normo- and hyperglycemia and arteriolar responsiveness was recorded. The highest dose of GIP potentiated insulin secretion during hyperglycemia, but had no effect in normoglycemic rats. The highest GIP concentration decreased blood perfusion of whole pancreas, pancreatic islets, duodenum, colon, liver and kidneys. The decrease in blood flow was unaffected by ganglion blockade or adenosine receptor inhibition. In contrast to this, in single perfused islets GIP induced a dose-dependent arteriolar dilation. Thus, high doses of GIP exert a direct dilatory effect on islet arterioles in isolated islets, but induce a generalized vasoconstriction in splanchnic organs, including the whole pancreas and islets, in vivo. The latter effect is unlikely to be mediated by adenosine, the autonomic nervous system, or endothelial mediators. [ABSTRACT FROM AUTHOR]

Following a meal, a transient increase in splanchnic blood flow occurs that can result in increased exposure to orally administered high-extraction drugs. Typically, physiologically based pharmacokinetic (PBPK) models have incorporated this increase in blood flow as a time-invariant fed/fasted ratio, but this approach is unable to explain the extent of increased drug exposure. A model for the time-varying increase in splanchnic blood flow following a moderate- to high-calorie meal (TV- Q ) was developed to describe the observed data for healthy individuals. This was integrated within a PBPK model and used to predict the contribution of increased splanchnic blood flow to the observed food effect for two orally administered high-extraction drugs, propranolol and ibrutinib. The model predicted geometric mean fed/fasted AUC and C ratios of 1.24 and 1.29 for propranolol, which were within the range of published values (within 1.0-1.8-fold of values from eight clinical studies). For ibrutinib, the predicted geometric mean fed/fasted AUC and C ratios were 2.0 and 1.84, respectively, which was within 1.1-fold of the reported fed/fasted AUC ratio but underestimated the reported C ratio by up to 1.9-fold. For both drugs, the interindividual variability in fed/fasted AUC and C ratios was underpredicted. This suggests that the postprandial change in splanchnic blood flow is a major mechanism of the food effect for propranolol and ibrutinib but is insufficient to fully explain the observations. The proposed model is anticipated to improve the prediction of food effect for high-extraction drugs, but should be considered with other mechanisms. [ABSTRACT FROM AUTHOR]

The purpose of this study was to clarify the effect of sex and menstrual cycle phase on celiac artery blood flow during dynamic exercise in healthy young humans. Eleven healthy young females (21 ± 2 yr, means ± SD) and 10 males (23 ± 3 yr) performed dynamic knee-extension and -flexion exercises at 30% of heart rate reserve for 4 min. The percent changes from baseline (Δ) for mean arterial blood pressure (MAP), mean blood flow (celMBF) in the celiac artery, and celiac vascular conductance (celVC) during exercise were calculated. Arterial blood pressure was measured using an automated sphygmomanometer, and celiac artery blood flow was recorded by Doppler ultrasonography. Female subjects performed the exercise test in the early follicular phase (EF) and in the midluteal phase (ML) of their menstrual cycle. The increase in MAP during exercise was not significantly ( P > 0.05) different between sexes or between menstrual cycle phases (ΔMAP, EF in females: +16.6 ± 6.4%, ML in females: +20.2 ± 11.7%, and males: +19.9 ± 12.2%). The celMBF decreased during exercise in each group, but the response was not significantly ( P > 0.05) different between sexes or between menstrual cycle phases (ΔcelMBF, EF in females: -24.6 ± 15.5%, ML in females: -25.2 ± 18.7%, and males: -29.2 ± 4.0%). The celVC decreased during dynamic exercise in each group, with no significant ( P > 0.05) difference in the responses between sexes or between menstrual cycle phases (ΔcelVC, EF in females: -38.3 ± 15.0%, ML in females: -41.5 ± 19.1%, and males: -43.4 ± 7.2%). These results suggest that sex and menstrual cycle phase have minimal influence on hemodynamic responses in the splanchnic artery during dynamic moderate-intensity exercise in young healthy individuals. NEW & NOTEWORTHY During dynamic exercise, splanchnic organ blood flow is reduced from resting values. Whether sex and menstrual cycle phase influence splanchnic blood flow responses during exercise remains unknown. We show that the decrease in celiac artery blood flow during dynamic leg exercise does not differ between young females and males or between menstrual cycle phases. In young individuals, sex and menstrual cycle have minimal influence on splanchnic artery hemodynamic responses during dynamic moderate-intensity leg exercise.

Introduction. The incidence of acute pancreatitis (AP) in the world has increased over the last years, mainly due to alcohol consumption. The increasing of the AP severity is characterized by pancreatic necrosis, local complications and systemic organ dysfunction and is about 20.0% of all cases of AP. Despite the successes of intensive care, early mortality from AP remains high. The main component in the pathogenesis of acute pancreatitis is the transition from local to the system inflammation that causes the increasing of the disease severity. Changes of microcirculation and endothelial dysfunction are an important step on the way from the mild to severe course of the disease. Aim. To determine the pathogenetic role of proinflammatory cytokines, adrenal molecules and E-selectin in the occurrence of vascular disorders and organ dysfunction in patients with acute necrotic pancreatitis. Materials and methods. The study involved 53 AP patients (28 – severe, 25 – mild). We measured interleukin-6, interleukin-18, ICAM-1 and E-selectin in the blood plasma. Flow in the visceral arteries was assessed with the help of the Doppler sonography. Organ dysfunction was evaluated on the SOFA scale. The severity of pancreatitis in patients was determined according to the criteria of J. H. C. Ranson. Results. Patients with AP during the hospitalization showed an increase of the levels of IL-6 and IL-18 in 12.11 and 2.02 times, respectively. However, a differentiated assessment of the individual forms of AP revealed a significant increase in both proinflammatory cytokines only in the case of acute necrotic pancreatitis, whereas IL-18 was not significantly elevated in patients with edematous pancreatitis. At the same time, the mean values ​​of IL-6 and IL-18 in patients with acute necrotic pancreatitis significantly exceeded the indicators of patients with pulmonary hypertension in 4.25 and 1.84 times, respectively. It has been established that proinflammatory cytokines mediate the damage of organs by their action on the endothelium of blood vessels and leukocytes by the increasing of the expression of adrenal molecules, which in turn leads to rolling, adhesion, aggregation and transmigration of leukocytes in the involved tissues. Cytokines stimulate endothelial cell membrane and cause the increased synthesis of selectin that bind to leukocytes through the appropriate receptors. This leads to roller leukocytes on the walls of postcapillary venules. The activation of intercellular adhesion molecules (ICAM) and vascular cell adhesion molecules (VCAM) on endothelial cells promotes the adhesion of leukocytes to vascular endothelium and their tissue transmigration. Inflammation cells respond to initial events by releasing enzymes and active forms of oxygen that cause damage of the tissues. Conclusions. It was determined that the levels of proinflammatory cytokines and adhesion molecules increase in the blood of AP patients. Their level correlates with the organ dysfunction and disturbances in splanchnic blood flow.