Mesenteric Artery Flow Research Articles

Doppler ultrasound, a noninvasive tool for the study of mesenteric arterial flow in systemic sclerosis: a cross-sectional study of a patient cohort with review and meta-analysis of the literature.

Gastrointestinal involvement (GI) is a frequent and troublesome complication of systemic sclerosis (SSc), whose etiology is poorly understood, though it is hypothesized that autoimmunity and progressive vasculopathy may play a role. Vasculopathy is considered one of the main pathogenetic pathways responsible for many of the clinical manifestations of SSc, and, therefore, studying the principal splanchnic vessels (i.e., superior mesenteric artery-SMA and inferior mesenteric artery-IMA) with Doppler Ultrasound (DUS) may provide further insights into measuring the progression of vasculopathy, evaluating its possible association with SSc GI symptoms, and determining whether it plays a role in the development or severity of SSc GI disease. A cohort of SSc patients consecutively recruited underwent DUS examination, and associations with GI (UCLA-GIT 2.0 questionnaire) and extraintestinal SSc characteristics were evaluated. Semiquantitative DUS parameters (resistive index-RI and pulsatility index-PI), were applied for splanchnic vessel assessment in SSc patients and healthy subjects (HS). Moreover, a review and meta-analysis of the literature to understand which the values of the main semiquantitative DUS parameters (RI and PI) are both in SSc patients and HS has been conducted. Seventy-eight patients completed DUS examinations and clinical assessments. 30 (39%) were classified as diffuse cutaneous SSc (dcSSC), 35 (45%) as limited cutaneous SSc (lcSSc) and 13 (17%) as sine scleroderma. A significant difference was found both for SMA RI (p for trend = 0.032) and SMA PI (p for trend = 0.004) between patients with sine scleroderma, lcSSc and dcSSc, with lower values observed in the sine scleroderma and lcSSc groups. IMA RI and PI were significantly correlated with GI symptoms such as fecal incontinence (ῥ -0.33, p = 0.008 and ῥ -0.30, p = 0.021, respectively). By multivariate analysis, significant associations were confirmed between SMA RI and SMA PI and mRSS (β 0.248, p = 0.030 and β 2.995, p = 0.004, respectively) and with bosentan (β 0.400, p = 0.003 and β 3.508, p = 0.001, respectively), but not with anticentromere antibody (ACA). No significant differences were found between the weighted median values of SMA RI and SMA PI of SSc patients compared to those of HS that were derived from the meta-analysis of the literature (p = 0.72 and p = 0.64, respectively). This cross-sectional study confirms that the splanchnic vasculature of SSc patients can noninvasively been studied with DUS. Vascular splanchnic involvement correlates with the presence and/or severity of specific clinical features in SSc, including GI. Larger and prospective studies are needed to confirm these preliminary observations and to examine the role of DUS in SSc-risk stratification and GI progression and to obtain definitive data regarding both HS and SSc patients splanchnic DUS parameters.

Cediranib ameliorates portal hypertensive syndrome via inhibition of VEGFR-2 signaling in cirrhotic rats

Portal hypertension (PHT) is a syndrome caused by systemic and portal hemodynamic disturbances with the progression of cirrhosis. However, the exact mechanisms regulating angiogenesis-related responses in PHT remain unclear. Cediranib is a potent inhibitor of vascular endothelial growth factor receptor (VEGFR) tyrosine kinases, exhibiting a greater affinity for VEGFR-2. Liver cirrhosis was induced by common bile duct ligation (BDL) in Sprague–Dawley rats. Sham-operated rats were controls. BDL and sham rats were randomly allocated to receive Cediranib or vehicle after BDL. On the 28th day, portal hypertension related parameters were surveyed. Cediranib treatment could significantly reduce the portal pressure (PP) in BDL rats, while it did not affect the mean arterial pressure (MAP) in sham groups and BDL groups. Cediranib treatment could significantly affect the stroke volume (SV), cardiac output (CO), cardiac index (CI), systemic vascular resistance (SVR), superior mesenteric artery (SMA) flow and SMA resistance in BDL groups and BDL with Cediranib groups. Cediranib treatment could improve the mesenteric vascular remodeling and contractility. Cediranib treatment significantly reduced mesenteric vascular density. And phospho-VEGFR-2 was significantly downregulated by Cediranib. On the other hand, phospho-endothelial Nitric Oxide Synthases (phospho-eNOS) expressions were upregulated. Cediranib not only improved splanchnic hemodynamics, extrahepatic vascular remodeling and vasodilation, but also alleviated intrahepatic fibrosis and collagen deposition significantly. Cediranib treatment could reduce intrahepatic angiogenesis between BDL-vehicle and BDL-Cediranib rats. In conclusion, Cediranib could improve extrahepatic hyperdynamic circulation by inhibiting extrahepatic angiogenesis through inhibition of the VEGFR-2 signaling pathway, portal collateral circulation formation, as well as eNOS-mediated vasodilatation and vascular remodeling, and at the same time, Cediranib improved intrahepatic fibrogenesis and angiogenesis, which together alleviate cirrhotic PHT syndrome.

Effects of lung recruitment maneuvers using mechanical ventilator on preterm hemodynamics

Background Lung recruitment maneuvers (LRMs) are a strategy to gradually increase mean positive airway pressure (MAP) to expand the alveoli, leading to decreased pulmonary vascular resistance and increased cardiac output (CO). However, the hemodynamic impact of LRM using assist control volume guarantee (AC-VG) ventilator mode done in preterm infants born at 24 to 32 weeks’ gestation, especially in the first 72 hours of life, remains unknown.
 Objective To determine the effect of LRM on right- and left cardiac ventricular output (RVO and LVO), ductus arteriosus (DA) diameter and its pulmonary hypertension (PH) flow pattern, as well as superior mesenteric artery (SMA) flow.
 Method This randomized, controlled, single-blinded clinical trial was performed in 24-32-week preterm neonates with birth weights of >600 grams. Subjects were allocated by block randomization to the LRM and control groups, each containing 55 subjects. We measured RVO, LVO, DA diameter, PH flow pattern, and SMA resistive index (RI) at 1 and 72 hours after mechanical ventilation was applied. We analyzed for hemodynamic differences between the two groups.
 Results During the initial 72 hours of mechanical ventilation, there were no significant differences between the control vs. LRM groups in mean changes of LVO [41.40 (SD 91.21) vs. 15.65 (SD 82.39) mL/kg/min, respectively; (P=0.138)] or mean changes of RVO [65.56 (SD 151.20) vs. 70.59 (SD 133.95) mL/kg/min, respectively; (P=0.859)]. Median DA diameter reduction was -0.08 [interquartile range (IQR) -0.55; 0.14] mm in the control group and -0.10 (IQR -0.17 to -0.01) mm in the LRM group (P=0.481). Median SMA resistive index was 0.02 (IQR -0.16 to 0.24) vs. 0.01(IQR -0.20 to 0.10) in the control vs. LRM group, respectively. There was no difference in proportion of pulmonary hypertension flow pattern at 72 hours (25.4% vs. 20% in the control vs. LRM group, respectively) (P=0.495).
 Conclusion When preterm infants of 24-32 weeks gestational age are placed on mechanical ventilation, LRM gives neither additional hemodynamic benefit nor harm compared to standard ventilator settings.

Transcriptome analysis of mesenteric arterioles changes and its mechanisms in cirrhotic rats with portal hypertension

Portal hypertension (PHT) is a major cause of liver cirrhosis. The formation of portosystemic collateral vessels and splanchnic vasodilation contribute to the development of hyperdynamic circulation, which in turn aggravates PHT and increases the risk of complications. To investigate the changes in mesenteric arterioles in PHT, cirrhotic rat models were established by ligating the common bile ducts. After 4 weeks, the cirrhotic rats suffered from severe PHT and splanchnic hyperdynamic circulation, characterized by increased portal pressure (PP), cardiac output (CO), cardiac index (CI), and superior mesenteric artery (SMA) flow. Mesenteric arterioles in cirrhotic rats displayed remarkable vasodilation, vascular remodeling, and hypocontractility. RNA sequencing was performed based on these findings. A total of 1,637 differentially expressed genes (DEGs) were detected, with 889 up-regulated and 748 down-regulated genes. Signaling pathways related to vascular changes were enriched, including the vascular endothelial growth factor (VEGF), phosphatidylinositol-3-kinase-AKT (PI3K-AKT), and nuclear factor kappa light chain enhancer of activated B cells (NF-κB) signaling pathway, among others. Moreover, the top ten hub genes were screened according to the degree nodes in the protein–protein interaction (PPI) network. Functional enrichment analyses indicated that the hub genes were involved in cell cycle regulation, mitosis, and cellular response to oxidative stress and nitric oxide (NO). In addition, promising candidate drugs for ameliorating PHT, such as resveratrol, were predicted based on hub genes. Taken together, our study highlighted remarkable changes in the mesenteric arterioles of cirrhotic rats with PHT. Transcriptome analyses revealed the potential molecular mechanisms of vascular changes in splanchnic hyperdynamic circulation.

Application of Model-Building Based on Arterial Ultrasound Imaging Evaluation to Predict CHD Risk.

Objective Atherosclerotic is a chronic systemic disease that may occur in multiple vascular beds, including the carotid arteries, renal arteries, lower limb arteries, and cerebral vessels. Coronary atherosclerosis shares similar risk factors, pathogenesis, and pathophysiological basis with the atherosclerotic lesions of arteries at these sites. Arterial ultrasound assessment data were used to explore the correlation of atherosclerotic disease with CHD lesions and their severity and the number of lesion branches, as well as to evaluate its value in predicting CHD risk, in combination with traditional risk factors. Methods A total of 363 inpatients with suspected CHD in the Department of Cardiology of the First Hospital of Harbin Medical University from November 2017 to June 2021 were selected. Patient clinical data, blood biochemical examination results, and ultrasound examination of neck vessels, abdominal arteries, and limb arteries were collected to obtain atherosclerosis assessment data. We then compared the differences between the CHD group and the control group, analyzed their correlation with CHD lesions and severity and the number of lesion branches, and evaluated the correlation with the coronary Gensini score. After adjustment for traditional risk factors, logistic regression was applied to analyze the relationship between arterial ultrasound assessment data and the risk of CHD. In addition, ROC plots were drawn to evaluate the risk of arterial ultrasound assessment data, combined with traditional risk factors, to predict CHD. Results With regard to abnormal blood biochemical index values, differences in lipids, HDL-C, FIB, CK-MB, hs-cTnI, BNP, and GGT were found between the CHD group and the control group. Carotid plaque count, abdominal aortic flow velocity, inferior mesenteric artery flow velocity, classification of the number of stenotic branches of abdominal aortic branch arteries, lower-extremity-artery plaque count, degree of lower-extremity-artery stenosis, and lower-extremity-artery AS were risk factors for arterial ultrasound assessment data of CHD. Carotid plaque count, carotid artery AS, inferior mesenteric artery flow velocity, abdominal aortic flow velocity, abdominal aortic plaque count, abdominal aortic branch artery stenosis branch classification, lower-extremity-artery plaque count, lower-extremity-artery stenosis branch classification, degree of lower-extremity-artery stenosis, and lower-extremity-artery AS, combined with traditional risk factors, were mostly more effective than traditional risk factor models in predicting CHD, its severity, and the number of branch lesions; moreover, the predictive value was higher. Specifically, carotid plaque count, carotid AS, lower-extremity-artery AS, the degree of stenosis of lower-extremity arteries, and abdominal aortic branch artery stenosis branch classification can be used as predictor variables for CHD risk. Among these variables, the carotid plaque count can be used as an independent predictor of CHD. Conclusion The incidence of arterial intima–media thickening (IMT), plaques, and stenosis can provide a reference for understanding the pattern of systemic atherogenesis and the distribution of atherosclerosis.

Cardiovascular Mapping in Cirrhosis From the Compensated Stage to Hepatorenal Syndrome: A Magnetic Resonance Study.

Arterial vasodilation and hyperdynamic circulation are considered hallmarks of the pathophysiological mechanisms of decompensation in cirrhosis. However, detailed characterization of peripheral, splanchnic, renal, and cardiac hemodynamic have not previously been published in a spectrum from healthy stage to advanced decompensated liver disease with hepatorenal syndrome-acute kidney injury (HRS-AKI). We included 87 patients with cirrhosis and 27 healthy controls in this prospective cohort study. The population comprised patients with compensated cirrhosis (n = 27) and decompensated cirrhosis (n = 60); patients with decompensated cirrhosis were further separated into subsets of responsive ascites (33), refractory ascites (n = 16), and HRS-AKI (n = 11). We measured portal pressure and assessed regional blood flow by magnetic resonance imaging. Patients with compensated cirrhosis experienced higher azygos venous flow and higher hepatic artery flow fraction of cardiac index than controls ( P < 0.01), but other flow parameters were not significantly different. Patients with decompensated cirrhosis experienced significantly higher cardiac index ( P < 0.01), higher superior mesenteric artery flow ( P = 0.01), and lower systemic vascular resistance ( P < 0.001) compared with patients with compensated cirrhosis. Patients with HRS-AKI had the highest cardiac output and lowest renal flow of all groups ( P < 0.01 and P = 0.02, respectively). Associations of single hemodynamic parameters were stronger with model for end-stage liver disease than with portal pressure. The regional cardiocirculatory changes seem closely linked to clinical symptoms with 3 distinguished hemodynamic stages from compensated to decompensated cirrhosis and, finally, to HRS-AKI. The attenuated renal perfusion despite high cardiac output in patients with HRS-AKI challenges the prevailing pathophysiological hypothesis of cardiac dysfunction as a causal factor in HRS-AKI. Finally, magnetic resonance imaging seems an accurate and reliable noninvasive method to assess hemodynamics and has potential as a diagnostic tool in patients with cirrhosis.

Long-term dioxin exposure promotes systemic endothelial damage and diastolic cardiac dysfunction in mice

2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) is the most toxic and persistent organic pollutant that bioaccumulates in the body through the food chain. The toxicity of TCDD is mediated by the activation of aryl hydrocarbon receptor (AHR), a transcription factor regulating detoxification enzyme expression. Although human exposure to TCDD has been shown to be associated with increased risk of cardiovascular disease and deaths, the impact of TCDD exposure on the heart at cellular and molecular levels remains poorly understood. To assess the cardiac and vascular stress response to long-term TCDD exposure in mice. Height-week-old C57BL/6N male mice were exposed for 12 months to low-dose TCDD (4 μg/kg, once per week) or vehicle by oral gavage. One-year TCDD exposure did not affect body weight or arterial pressure in mice, but cardiac mass index was increased. Echocardiographic analysis showed that long-term TCDD exposure led to diastolic LV dysfunction with preserved ejection fraction. Diastolic LV dysfunction was confirmed by PV loop analysis showing an increased diastolic stiffness with preserved systolic contractility in TCDD-exposed mice. Using permeabilized cardiac myofibers, we showed that chronic TCDD administration alters cardiac mitochondrial energetics and increases ROS production. Confocal imaging and q-PCR analysis revealed that AHR is expressed in the mouse heart, especially in endothelial cells that respond better than cardiomyocytes to TCDD exposure. Cardiac MRI showed decreased LV perfusion in TCDD-exposed mice. This was associated with a loss of endothelium-mediated relaxation responses to acetylcholine and to flow in mesenteric arteries of TCDD-exposed mice. In parallel, en face microscopy revealed profound disruptions of endothelial adherens junctions in the aorta of mice after TCDD exposure. These data demonstrate severe cardiac and systemic endothelial dysfunction upon TCDD exposure. This endothelial dysfunction was associated with a metabolic adaptation of endothelial cells, as assessed by the enhanced mitochondrial oxidative phosphorylation in TCDD-exposed primary muscle endothelial cells. Long-term exposure to TCDD promotes endothelial dysfunction and diastolic LV impairment, possibly through an increased oxidative stress and disrupted mitochondrial bioenergetics in both endothelial cells and cardiomyocytes.

Effectiveness and Power of Abdominal Ultrasonography in the Assessment of Crohn's Disease Activity: Comparison with Clinical, Endoscopic, and CT Enterography Findings.

Non-invasive methods play an important role in clinical assessment of Crohn's disease. Recent studies have highlighted the effectiveness and reliability of intestinal ultrasonography. We aimed to examine the relationship between intestinal ultrasonography and the clinical, endoscopic, and computed tomography enterography findings, and to assess the activity of Crohn's disease. This was a 1-year prospective study involving patients diagnosed with Crohn's Disease. Clinical and endoscopic activity indi- ces, and intestinal ultrasonography and computed tomography enterography findings were evaluated. Intestinal wall thickness, mes- enteric inflammation, lymphadenopathy, and complications were evaluated by intestinal ultrasonograpy and computed tomography enterography, while the superior mesenteric artery flow velocity, resistive index, and Limberg score were assessed by Doppler intestinal ultrasonography. Seventy-nine patients with Crohn's disease were included. A significant correlation was found between intestinal wall thick- ness, mesenteric inflammation, and complications in intestinal ultrasonography and computed tomography enterography (P = .0001). According to the receiver operating curve analysis, the intestinal wall thickness, and mesenteric inflammation were correlated with the Crohn's Disease Activity Index, Harvey-Bradshaw Index, and SES-CD scores (P < .05), and they were very effective in distinguishing active from inactive disease. According to the Crohn's Disease Activity Index and SES-CD scores, Doppler flow velocity of the superior mesenteric artery was significantly higher in the active group than in the inactive group (P < .05). The Limberg score was very consistent with the Crohn's Disease Activity Index, Harvey-Bradshaw Index , and the results of the Simple Endoscopic Score for Crohn's Disease (P < .0001). Our study showed that intestinal ultrasonography is an effective and reliable method for assessment of Crohn's disease activity compared to clinical, endoscopic, and CTE findings.

The effects of vasopressors with and without dobutamine on haemodynamics, metabolism and gut injury during endotoxic shock in rabbits. Acontrolled study.

Vasopressors increase arterial pressure but they may have deleterious effects on mesenteric blood flow. We aimed to evaluate the response of gut biomarkers and superior mesenteric blood flow to different vasopressors with and without dobutamine. Thirty New Zealand rabbits were included and randomly allocated to 5 groups: group A- sham group; group B - norepinephrine; group C - norepinephrine plus dobutamine; group D - vasopressin; and group E - vasopressin plus dobutamine. Mean arterial pressure (MAP) target was greater than 60 mmHg. Endotoxic shock was induced by intra-venous injection of lipopolysaccharide (LPS) in four of the five groups. Aortic blood flow (Qao), superior mesenteric artery flow (QSMA) and lactate were measured after LPS injection. Enterocyte damage was evaluated by measurements of serum citrulline and intestinal fatty acid-binding protein (I-FABP) after 4 h. The largest reduction in Qao occurred in group D (64 ± 17.3 to 38 ± 7.5 mL min-1; P = 0.04). QSMA also declined significantly in groups D and E and remained lower than in the other groups over 4 h (group D - baseline: 65 ± 31; 1 h: 37 ± 10; 2 h: 38 ± 10; 3 h: 46 ± 26; and 4 h: 48 ± 15 mL min-1; P < 0.005; group E - baseline: 73 ± 14; 1 h: 28 ± 4.0; 2 h: 37 ± 6.4; 3 h: 40 ± 11; and 4 h: 48 ± 11; P < 0.005; all in mL min-1). Serum citrulline was significantly lower in groups D (P = 0.014) and E (P = 0.019) in comparison to group A. The fluid administration regimen was similar in all groups. Vasopressin seems to negatively impact gut enterocyte function during endotoxic shock despite the association of an inodilator and adequate fluid replacement.

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

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

Glycyrrhizin Attenuates Portal Hypertension and Collateral Shunting via Inhibition of Extrahepatic Angiogenesis in Cirrhotic Rats.

Portal hypertension develops along with liver cirrhosis then induces the formation of portal-systemic collaterals and lethal complications. Extrahepatic angiogenesis plays an important role. Glycyrrhizin has been found to exhibit anti-angiogenic features, which leads to its extensive use. However, the relevant effects of glycyrrhizin on liver cirrhosis and portal hypertension have not been evaluated. This study thus aimed to investigate the impact of glycyrrhizin on portal hypertension-related derangements in cirrhotic rats. Male Sprague-Dawley rats received bile duct ligation (BDL) to induce cirrhosis or sham operation as control. The rats were subdivided to receive glycyrrhizin (150 mg/kg/day, oral gavage) or vehicle beginning on the 15th day post operation, when BDL-induced liver fibrosis developed. The effects of glycyrrhizin were determined on the 28th day, the typical timing of BDL-induced cirrhosis. Glycyrrhizin significantly reduced portal pressure (p = 0.004). The splanchnic inflow as measured by superior mesenteric arterial flow decreased by 22% (p = 0.029). The portal-systemic collateral shunting degree reduced by 30% (p = 0.024). The mesenteric angiogenesis and phospho-VEGFR2 protein expression were also downregulated (p = 0.038 and 0.031, respectively). Glycyrrhizin did not significantly influence the liver biochemistry data. Although glycyrrhizin tended to reverse liver fibrosis, statistical significance was not reached (p = 0.069). Consistently, hepatic inflow from portal side, hepatic vascular resistance, and liver fibrosis-related protein expressions were not affected. Glycyrrhizin treatment at the stage of hepatic fibrosis still effectively attenuated portal hypertension and portosystemic collateral shunting. These beneficial effects were attributed to, at least in part, the suppression of mesenteric angiogenesis by VEGF signaling pathway downregulation.

Superior Mesenteric Artery Blood Flow in Parenterally Fed Versus Enterally Fed Preterm Infants.

The aim of the study was to compare superior mesenteric artery (SMA) flow in premature infants with parenteral and enteral nutrition. A prospective study was conducted on 2 groups of preterm infants with gestational age of 280/7 to 366/7 weeks: group 1 did not qualify for early enteral feeds and received parenteral nutrition (PN), and group 2 received early enteral feeding. SMA peak systolic velocity (PSV), end diastolic velocity (EDV), and pulsatility index (PI) were measured using Doppler ultrasound before starting feeds at day 1 and at day 5. The study recruited 40 infants; 20 in each group. At baseline, PSV, EDV, and PI did not differ between groups. At day 5, enteral nutrition was associated with significant increases in PSV (91.53 ± 29.15 vs 65.49 ± 19.18, P = 0.003) and EDV (15.91 ± 7.01 vs 11.65 ± 5.58, P = 0.026) and a decrease in PI (1.28 ± 0.40 vs 2.48 ± 0.83, P < 0.001). Regression analysis to control for confounders showed enterally fed infants to have increased PSV (adjusted odds ratio [aOR] = 25.45; 95% confidence interval [CI]: 8.53-42.38, P = 0.004) and EDV (aOR 8.630; 95% CI: 2.987-14.273, P = 004) and decreased PI (aOR = -1.133; 95% CI: -1.603 to -0.664, P < 0.001). Infants in the PN group later developed more frequent feeding intolerance when compared with the enterally fed group (65% vs 15%, respectively, P < 0.001). In preterm neonates, early EF is associated with increased SMA blood flow, decreased vascular intestinal resistance, and less frequent incidence of feeding intolerance.

Real-time bedside management and titration of partial resuscitative endovascular balloon occlusion of the aorta without an arterial line: Good for pressure, not for flow!

Partial resuscitative endovascular balloon occlusion of the aorta (pREBOA) attempts to minimize ischemia/reperfusion injury while controlling hemorrhage. There are little data on optimal methods to evaluate and titrate partial flow, which typically requires invasive arterial line monitoring. We sought to examine the use of a miniaturized handheld digital pressure device (COMPASS; Mirador Biomedical, Seattle, WA) for pREBOA placement and titration of flow. Ten swine underwent standardized hemorrhagic shock. Carotid and iliac pressures were monitored with both arterial line and COMPASS devices, and flow was monitored by aortic and superior mesenteric artery flow probes. Partial resuscitative endovascular balloon occlusion of the aorta was inflated to control hemorrhage for 15 minutes before being deflated to try targeting aortic flow of 0.7 L/min (using only the COMPASS device) by an operator blinded to the arterial line pressures and aortic flow. Correlations between COMPASS and proximal/distal arterial line were evaluated, as well as actual aortic flow. There was strong correlation between the distal mean arterial pressure (MAP) and the distal COMPASS MAP (r = 0.979, p < 0.01), as well as between the proximal arterial line and the proximal COMPASS on the pREBOA (r = 0.989, p < 0.01). There was a significant but weaker correlation between the distal compass MAP reading and aortic flow (r = 0.47, p < 0.0001), although it was not clinically significant and predicted flow was not achieved in a majority of the procedures. Of 10 pigs, survival times ranged from 10 to 120 minutes, with a mean survival of 50 minutes, and 1 pig surviving to 120 minutes. Highly reliable pressure monitoring is achieved proximally and distally without arterial lines using the COMPASS device on the pREBOA. Despite accurate readings, distal MAPs were a poor indicator of aortic flow, and titration based upon distal MAPs did not provide reliable results. Further investigation will be required to find a suitable proxy for targeting specific aortic flow levels using pREBOA.

Methane Exhalation Can Monitor the Microcirculatory Changes of the Intestinal Mucosa in a Large Animal Model of Hemorrhage and Fluid Resuscitation.

Background: Internal hemorrhage is a medical emergency, which requires immediate causal therapy, but the recognition may be difficult. The reactive changes of the mesenteric circulation may be part of the earliest hemodynamic responses to bleeding. Methane is present in the luminal atmosphere; thus, we hypothesized that it can track the intestinal circulatory changes, induced by hemorrhage, non-invasively. Our goal was to validate and compare the sensitivity of this method with an established technique using sublingual microcirculatory monitoring in a large animal model of controlled, graded hemorrhage and the early phase of following fluid resuscitation.Materials and Methods: The experiments were performed on anesthetized, ventilated Vietnamese minipigs (approval number: V/148/2013; n = 6). The animals were gradually bled seven times consecutively of 5% of their estimated blood volume (BV) each, followed by gradual fluid resuscitation with colloid (hydroxyethyl starch; 5% of the estimated BV/dose) until 80 mmHg mean arterial pressure was achieved. After each step, macrohemodynamic parameters were recorded, and exhaled methane level was monitored continuously with a custom-built photoacoustic laser-spectroscopy unit. The microcirculation of the sublingual area, ileal serosa, and mucosa was examined by intravital videomicroscopy (Cytocam-IDF, Braedius).Results: Mesenteric perfusion was significantly reduced by a 5% blood loss, whereas microperfusion in the oral cavity deteriorated after a 25% loss. A statistically significant correlation was found between exhaled methane levels, superior mesenteric artery flow (r = 0.93), or microcirculatory changes in the ileal serosa (ρ = 0.78) and mucosa (r = 0.77). After resuscitation, the ileal mucosal microcirculation increased rapidly [De Backer score (DBS): 2.36 ± 0.42 vs. 8.6 ± 2.1 mm−1], whereas serosal perfusion changed gradually and with a lower amplitude (DBS: 2.51 ± 0.48 vs. 5.73 ± 0.75). Sublingual perfusion correlated with mucosal (r = 0.74) and serosal (r = 0.66) mesenteric microperfusion during the hemorrhage phase but not during the resuscitation phase.Conclusion: Detection of exhaled methane levels is of diagnostic significance during experimental hemorrhage as it indicates blood loss earlier than sublingual microcirculatory changes and in the early phase of fluid resuscitation, the exhaled methane values change in association with the mesenteric perfusion and the microcirculation of the ileum.

Impairment of Flow-Sensitive Inwardly Rectifying K+ Channels via Disruption of Glycocalyx Mediates Obesity-Induced Endothelial Dysfunction.

To determine if endothelial dysfunction in a mouse model of diet-induced obesity and in obese humans is mediated by the suppression of endothelial Kir (inwardly rectifying K+) channels. Approach and Results: Endothelial dysfunction, observed as reduced dilations to flow, occurred after feeding mice a high-fat, Western diet for 8 weeks. The functional downregulation of endothelial Kir2.1 using dominant-negative Kir2.1 construct resulted in substantial reductions in the response to flow in mesenteric arteries of lean mice, whereas no effect was observed in arteries of obese mice. Overexpressing wild-type-Kir2.1 in endothelium of arteries from obese mice resulted in full recovery of the flow response. Exposing freshly isolated endothelial cells to fluid shear during patch-clamp electrophysiology revealed that the flow-sensitivity of Kir was virtually abolished in cells from obese mice. Atomic force microscopy revealed that the endothelial glycocalyx was stiffer and the thickness of the glycocalyx layer reduced in arteries from obese mice. We also identified that the length of the glycocalyx is critical to the flow-activation of Kir. Overexpressing Kir2.1 in endothelium of arteries from obese mice restored flow- and heparanase-sensitivity, indicating an important role for heparan sulfates in the flow-activation of Kir. Furthermore, the Kir2.1-dependent component of flow-induced vasodilation was lost in the endothelium of resistance arteries of obese humans obtained from biopsies collected during bariatric surgery. We conclude that obesity-induced impairment of flow-induced vasodilation is attributed to the loss of flow-sensitivity of endothelial Kir channels and propose that the latter is mediated by the biophysical alterations of the glycocalyx.

P189 Use of transabdominal ultrasonography for the evaluation of Crohn’s disease activity

Abstract Background Ileocolonoscopy is accepted as the gold standard method for the diagnosis of Crohn’s disease (CD). However, there are cases where it is inadequate due to being invasive, failure to allow endoscopic exploration of the small intestine, and failure to show the extraintestinal pathologies. In the present study, it is aimed to compare clinical, endoscopic scores and computerised tomography enterography (CTE) findings with transabdominal ultrasonography (TAUS) findings in order to evaluate the activity of CD. Methods The study included 79 patients diagnosed with CD. Crohn’s Disease Activity Index (CDAI) and Harvey Bradshaw Index (HBI) were used for the evaluation of the clinical activities of the patients. The patients with CDAI equal to 150 and more and HBI equal to 5 points and more were assessed as clinically active. Colonoscopic disease activity was assessed by The Simple Endoscopic Score for Crohn’ disease (SES-CD), SES-CD score of 3 and higher was defined as endoscopically active. In the evaluation of CTE and TAUS, the measurement of the thickness of the intestinal wall above 3 mm was accepted as pathological. Abscess, mass, fistula and ileus were evaluated as complications. Superior mesenteric artery (SMA) flow velocity was assessed by Color Doppler US. Limberg score was graded from Grades 0 to 4 for Doppler TAUS. Results Of the patients, 57 (72.1%) were male and 22 (27.8%) were female. Age average of the patients was 37.5 years (17–64) and the mean duration of disease was 48.6 months (0–240 months). Increase in the wall thickness in CTE and TAUS, detection of inflammation and complication in mesenteric fatty planes were found to be highly significant (p ˂ 0.0001). Wall thickness increase sensitivity level of TAUS according to CTE was 82%, specificity level was 97%, sensitivity level of the inflammation finding in mesenteric fatty planes was measured as 80%, and specificity level as 95%. A significant correlation was found between the wall thickness increase in CTE and TAUS and inflammation in mesenteric fatty planes via CDAI, HBI and SES-CD scoring (p ˂ 0.05). In addition, there was a significant relationship between the presence of lymphadenopathy in CTE in active patients according to HBI (p ˂ 0.05). According to the CDAI and SES-CD scores, Doppler flow velocity of SMA was significantly higher in the active group than the inactive group (p ˂ 0.05). CDAI, HBI and SES-CD results were found highly significant via the Limberg Scoring results (p &amp;lt; 0.0001). Conclusion In the current study, it is shown that TAUS is a diagnostic tool as effective as CTE in the evaluation of CD activity. In addition, it is an important finding that the flow velocity of SMA increases as correlated with inflammation via the Doppler feature of TAUS.

Natural history of isolated type II endoleaks in patients treated by fenestrated-branched endovascular repair for pararenal and thoracoabdominal aortic aneurysms

ObjectiveType II endoleaks (T2ELs) are common after endovascular aneurysm repair (EVAR), but little is known about their natural history in patients treated by fenestrated-branched EVAR (F/BEVAR). We sought to evaluate the natural history of isolated T2EL after F/BEVAR for pararenal aortic aneurysms (PRAs) and thoracoabdominal aortic aneurysms (TAAAs). MethodsConsecutive patients enrolled in a prospective nonrandomized study to investigate F/BEVAR for PRAs and TAAAs at a single institution (2014-2017) were identified. Computed tomography angiography images at discharge and during follow-up were reviewed. Patients with ≥12 months of follow-up were included and divided in two groups for comparison based on the presence or absence of T2ELs. Patients with any non-T2ELs were excluded. Multivariable logistic regression was used to assess factors associated with T2EL occurrence. Primary outcomes were absolute and relative sac diameter change and sac diameter increase >5 mm. Secondary outcomes included overall survival, aorta-related death, reinterventions, and conversion or rupture. ResultsThere were 184 patients (136 male [74%]) with PRAs (n = 70 [38%]) and TAAAs (n = 114 [62%]) with an average age of 74 ± 7 years included. Isolated T2ELs were seen in 76 patients (41%); of these, 71 T2ELs (93%) were primary. Patients with T2ELs were more likely to have larger aneurysms (mean baseline diameter, 66 ± 8 mm vs 63 ± 8 mm; P = .01), patent inferior mesenteric artery (66% vs 32%; P < .001), and more lumbar arteries (mean, 6 ± 1 vs 4 ± 1; P < .001). In the multivariable analysis, these were all independently associated with T2EL occurrence. Of all T2ELs, only 18 (24%) resolved spontaneously during a mean follow-up of 31 ± 15 months. Mean absolute sac diameter reduction for patients without T2ELs and with T2ELs, at 12 and 36 months, was 10.2 ± 5.9 mm vs 2.6 ± 6.4 mm and 16.3 ± 7.3 mm vs 5.7 ± 11.3 mm, respectively (P < .001). For the same groups, the mean percentage sac diameter reduction at 12 and 36 months was 16.4% ± 9.4% vs 3.8% ± 9.8% and 26.4% ± 11.6% vs 8.8% ± 17.7%, respectively (P < .001). Overall, 13 patients showed sac increase >5 mm, and all these instances were recorded in the T2EL group; 8 required reintervention. T2ELs were not associated with decreased overall survival, freedom from aorta-related death, or freedom from any reintervention. ConclusionsIsolated T2ELs are common after F/BEVAR for PRAs and TAAAs, usually seen early; they are most often associated with inferior mesenteric or lumbar artery flow and tend to persist in follow-up. Their presence is associated with impaired sac shrinkage and risk of sac growth with subsequent need for secondary interventions. Although not associated with decreased overall survival or loss of freedom from aorta-related death, T2ELs require serial imaging surveillance.

The Effects of a Whey Protein and Guar Gum-Containing Preload on Gastric Emptying, Glycaemia, Small Intestinal Absorption and Blood Pressure in Healthy Older Subjects.

A whey protein/guar gum preload reduces postprandial glycaemia in type 2 diabetes through slowing gastric emptying. However, gastric emptying has previously been assessed using a stable isotope breath test technique, which cannot discriminate between slowing of gastric emptying and small intestinal absorption. This preload also may be useful in the management of postprandial hypotension. We evaluated the effects of a whey protein/guar preload on gastric emptying, glucose absorption, glycaemic/insulinaemic and blood pressure (BP) responses to an oral glucose load. Eighteen healthy older participants underwent measurements of gastric emptying (scintigraphy), plasma glucose and insulin, glucose absorption, superior mesenteric artery (SMA) flow, BP and heart rate (HR) after ingesting a 50 g glucose drink, with or without the preload. The preload reduced plasma glucose (p = 0.02) and serum 3-O-methylglucose (3-OMG) (p = 0.003), and increased plasma insulin (p = 0.03). There was no difference in gastric emptying or BP between the two days. The reduction in plasma glucose on the preload day was related to the reduction in glucose absorption (r = 0.71, p = 0.002). In conclusion, the glucose-lowering effect of the preload may relate to delayed small intestinal glucose absorption and insulin stimulation, rather than slowing of gastric emptying.

Postprandial Vascular Dysfunction Is Associated With Raised Blood Pressure and Adverse Left Ventricular Remodeling in Adolescent Adiposity.

Left ventricular hypertrophy (LVH) is a major risk factor for cardiovascular disease, including heart failure. Although linked to obesity and hypertension, its pathogenesis is multifactorial. Blunted postprandial sympathetic regulation of gut blood flow has been observed in overweight animals and suggested as a promotor of hypertension and LVH. We hypothesized that blunted postprandial superior mesenteric blood flow responses would be more common in overweight humans and associated with increased blood pressure and LVH. Left ventricular dimensions and hemodynamic responses to a standardized high-calorie liquid meal were measured in healthy adolescents (n=82; 39 overweight/obese) by magnetic resonance imaging. Covariates such as body mass index, blood pressure, Tanner score, and an index of insulin resistance were included in multiple regression models to examine the independent associations of mesenteric flow response with blood pressure status and LVH. Food ingestion increased cardiac output (Δmean, 0.45 [SD, 0.62] L·min-1; P=3.8×10-8) and superior mesenteric artery flow (Δmean, 0.76 [SD, 0.35] L·min-1; P=4.2×10-31). A blunted mesenteric flow response was associated with increased left ventricular mass (B=-12.7 g·m-2.7 per L·min-1·m-0.92; P=6×10-5) and concentric LVH (log likelihood, -9.9; P=0.001), independently of known determinants of LVH, including body mass index. It was also associated with elevated systolic blood pressure (B=-18.0 mm Hg per L·min-1·m-0.92; P=0.001), but this link did not explain the association with left ventricular mass. Postprandial mesenteric vascular dysfunction is associated with LVH and hypertension, independently of common risk factors for those conditions. These findings highlight a new, independent marker of cardiovascular risk in the young.

Glucagon-like peptide-2 mobilizes lipids from the intestine by a systemic nitric oxide-independent mechanism.

To test the hypothesis that gut hormone glucagon-like peptide-2 (GLP-2) mobilizes intestinal triglyceride (TG) stores and stimulates chylomicron secretion by a nitric oxide (NO)-dependent mechanism in humans. In a randomized, single-blind, cross-over study, 10 healthy male volunteers ingested a high-fat formula followed, 7 hours later, by one of three treatments: NO synthase inhibitor L-NG -monomethyl arginine acetate (L-NMMA) + GLP-2 analogue teduglutide, normal saline + teduglutide, or L-NMMA + placebo. TG in plasma and lipoprotein fractions were measured, along with measurement of blood flow in superior mesenteric and coeliac arteries using Doppler ultrasound in six participants. Teduglutide rapidly increased mesenteric blood flow and TG concentrations in plasma, in TG-rich lipoproteins, and most robustly in chylomicrons. L-NMMA significantly attenuated teduglutide-induced enhancement of mesenteric blood flow but not TG mobilization and chylomicron secretion. GLP-2 mobilization of TG stores and stimulation of chylomicron secretion from the small intestine appears to be independent of systemic NO in humans.