Silk fibroin vascular graft: a promising tissue-engineered scaffold material for abdominal venous system replacement.

No alternative tissue-engineered vascular grafts for the abdominal venous system are reported. The present study focused on the development of new tissue-engineered vascular graft using a silk-based scaffold material for abdominal venous system replacement. A rat vein, the inferior vena cava, was replaced by a silk fibroin (SF, a biocompatible natural insoluble protein present in silk thread), tissue-engineered vascular graft (10 mm long, 3 mm diameter, n = 19, SF group). The 1 and 4 -week patency rates and histologic reactions were compared with those of expanded polytetrafluoroethylene vascular grafts (n = 10, ePTFE group). The patency rate at 1 and 4 weeks after replacement in the SF group was 100.0% and 94.7%, and that in the ePTFE group was 100.0% and 80.0%, respectively. There was no significant difference between groups (p = 0.36). Unlike the ePTFE graft, CD31-positive endothelial cells covered the whole luminal surface of the SF vascular graft at 4 weeks, indicating better endothelialization. SF vascular grafts may be a promising tissue-engineered scaffold material for abdominal venous system replacement.

Development of Upright Computed Tomography With Area Detector for Whole-Body Scans: Phantom Study, Efficacy on Workflow, Effect of Gravity on Human Body, and Potential Clinical Impact.

OBJECTIVES: Multiple human systems are greatly affected by gravity, and many disease symptoms are altered by posture. However, the overall anatomical structure and pathophysiology of the human body while standing has not been thoroughly analyzed due to the limitations of various upright imaging modalities, such as low spatial resolution, low contrast resolution, limited scan range, or long examination time. Recently, we developed an upright computed tomography (CT), which enables whole-torso cross-sectional scanning with 3-dimensional acquisition within 15 seconds. The purpose of this study was to evaluate the performance, workflow efficacy, effects of gravity on a large circulation system and the pelvic floor, and potential clinical impact of upright CT. MATERIALS AND METHODS: We compared noise characteristics, spatial resolution, and CT numbers in a phantom between supine and upright CT. Thirty-two asymptomatic volunteers (48.4 ± 11.5 years) prospectively underwent both CT examinations with the same scanning protocols on the same day. We conducted a questionnaire survey among these volunteers who underwent the upright CT examination to determine their opinions regarding the stability of using the pole throughout the acquisition (closed question), as well as safety and comfortability throughout each examination (both used 5-point scales). The total access time (sum of entry time and exit time) and gravity effects on a large circulation system and the pelvic floor were evaluated using the Wilcoxon signed-rank test and the Mann-Whitney U test. For a large circulation system, the areas of the vena cava and aorta were evaluated at 3 points (superior vena cava or ascending aorta, at the level of the diaphragm, and inferior vena cava or abdominal aorta). For the pelvic floor, distances were evaluated from the bladder neck to the pubococcygeal line and the anorectal junction to the pubococcygeal line. We also examined the usefulness of the upright CT in patients with functional diseases of spondylolisthesis, pelvic floor prolapse, and inguinal hernia. RESULTS: Noise characteristics, spatial resolution, and CT numbers on upright CT were comparable to those of supine CT. In the volunteer study, all volunteers answered yes regarding the stability of using the pole, and most reported feeling safe (average rating of 4.2) and comfortable (average rating of 3.8) throughout the upright CT examination. The total access time for the upright CT was significantly reduced by 56% in comparison with that of supine CT (upright: 41 ± 9 seconds vs supine: 91 ± 15 seconds, P < 0.001). In the upright position, the area of superior vena cava was 80% smaller than that of the supine position (upright: 39.9 ± 17.4 mm vs supine: 195.4 ± 52.2 mm, P < 0.001), the area at the level of the diaphragm was similar (upright: 428.3 ± 87.9 mm vs supine: 426.1 ± 82.0 mm, P = 0.866), and the area of inferior vena cava was 37% larger (upright: 346.6 ± 96.9 mm vs supine: 252.5 ± 93.1 mm, P < 0.001), whereas the areas of aortas did not significantly differ among the 3 levels. The bladder neck and anorectal junction significantly descended (9.4 ± 6.0 mm and 8.0 ± 5.6 mm, respectively, both P < 0.001) in the standing position, relative to their levels in the supine position. This tendency of the bladder neck to descend was more prominent in women than in men (12.2 ± 5.2 mm in women vs 6.7 ± 5.6 mm in men, P = 0.006). In 3 patients, upright CT revealed lumbar foraminal stenosis, bladder prolapse, and inguinal hernia; moreover, it clarified the grade or clinical significance of the disease in a manner that was not apparent on conventional CT. CONCLUSIONS: Upright CT was comparable to supine CT in physical characteristics, and it significantly reduced the access time for examination. Upright CT was useful in clarifying the effect of gravity on the human body: gravity differentially affected the volume and shape of the vena cava, depending on body position. The pelvic floor descended significantly in the standing position, compared with its location in the supine position, and the descent of the bladder neck was more prominent in women than in men. Upright CT could potentially aid in objective diagnosis and determination of the grade or clinical significance of common functional diseases.

Reproducibility and Changes in Vena Caval Blood Flow by Using 4D Flow MRI in Pulmonary Emphysema and Chronic Obstructive Pulmonary Disease (COPD): The Multi-Ethnic Study of Atherosclerosis (MESA) COPD Substudy.

BackgroundChronic obstructive pulmonary disease (COPD) is associated with hemodynamic changes in the pulmonary vasculature. However, cardiac effects are not fully understood and vary by phenotype of chronic lower respiratory disease.PurposeTo use four-dimensional (4D) flow MRI for comprehensive assessment of the right-sided cardiovascular system, assess its interrater and intraobserver reproducibility, and examine associations with venous return to the right heart in individuals with chronic COPD and emphysema.Materials and MethodsThe Multi-Ethnic Study of Atherosclerosis COPD substudy prospectively recruited participants who smoked and who had COPD and nested control participants from population-based samples. Electrocardiography and respiratory gated 4D flow 1.5-T MRI was performed at three sites with full volumetric coverage of the thoracic vessels in 2014-2017 with postbronchodilator spirometry and inspiratory chest CT to quantify percent emphysema. Net flow, peak velocity, retrograde flow, and retrograde fraction were measured on 14 analysis planes. Interrater reproducibility was assessed by two independent observers, and the principle of conservation of mass was employed to evaluate the internal consistency of flow measures. Partial correlation coefficients were adjusted for age, sex, race/ethnicity, height, weight, and smoking status.ResultsAmong 70 participants (29 participants with COPD [mean age, 73.5 years ± 8.1 {standard deviation}; 20 men] and 41 control participants [mean age, 71.0 years ± 6.1; 22 men]), the interrater reproducibility of the 4D flow MRI measures was good to excellent (intraclass correlation coefficient range, 0.73-0.98), as was the internal consistency. There were no statistically significant differences in venous flow parameters according to COPD severity (P > .05). Greater percent emphysema at CT was associated with greater regurgitant flow in the superior and inferior caval veins and tricuspid valve (adjusted r = 0.28-0.55; all P < .01), particularly in the superior vena cava.ConclusionFour-dimensional flow MRI had good-to-excellent observer variability and flow consistency. Percent emphysema at CT was associated with statistically significant differences in retrograde flow, greatest in the superior vena cava.© RSNA, 2019Online supplemental material is available for this article.See also the editorial by Choe in this issue.

Anterior vena caval oxygen profiles in a deep-diving California sea lion: arteriovenous shunts, a central venous oxygen store and oxygenation during lung collapse.

Deep-diving California sea lions (Zalophus californianus) can maintain arterial hemoglobin saturation (SO2 ) above 90% despite lung collapse (lack of gas exchange) and extremely low posterior vena caval SO2  in the middle of the dive. We investigated anterior vena caval PO2 and SO2  during dives of an adult female sea lion to investigate two hypotheses: (1) posterior vena caval SO2  is not representative of the entire venous oxygen store and (2) a well-oxygenated (arterialized) central venous oxygen reservoir might account for maintenance of arterial SO2  during lung collapse. During deep dives, initial anterior vena caval SO2  was elevated at 83.6±8.4% (n=102), presumably owing to arteriovenous shunting. It remained high until the bottom phase of the dive and then decreased during ascent, whereas previously determined posterior vena caval SO2  declined during descent and then often increased during ascent. These divergent patterns confirmed that posterior vena caval SO2  was not representative of the entire venous oxygen store. Prior to and early during descent of deep dives, the high SO2  values of both the anterior and posterior venae cavae may enhance arterialization of a central venous oxygen store. However, anterior vena caval SO2  values at depths beyond lung collapse reached levels as low as 40%, making it unlikely that even a completely arterialized central venous oxygen store could account for maintenance of high arterial SO2 These findings suggest that maintenance of high arterial SO2  during deep dives is due to persistence of some gas exchange at depths beyond presumed lung collapse.

Vena Cava Responsiveness to Controlled Isovolumetric Respiratory Efforts.

OBJECTIVES: Respirophasic variation of inferior vena cava (IVC) size is affected by large variability with spontaneous breathing. This study aims at characterizing the dependence of IVC size on controlled changes in intrathoracic pressure. METHODS: Ten healthy subjects, in supine position, performed controlled isovolumetric respiratory efforts at functional residual capacity, attaining positive (5, 10, and 15 mmHg) and negative (-5, -10, and -15 mmHg) alveolar pressure levels. The isovolumetric constraint implies that equivalent changes are exhibited by alveolar and intrathoracic pressures during respiratory tasks. RESULTS: The IVC cross-sectional area equal to 2.88 ± 0.43 cm2 at baseline (alveolar pressure = 0 mmHg) was progressively decreased by both expiratory and inspiratory efforts of increasing strength, with diaphragmatic efforts producing larger effects than thoracic ones: -55 ± 15% decrease, at +15 mmHg of alveolar pressure (P < .01), -80 ± 33 ± 12% at -15 mmHg diaphragmatic (P < .01), -33 ± 12% at -15 mmHg thoracic. Significant IVC changes in size (P < .01) and pulsatility (P < .05), along with non significant reduction in the response to respiratory efforts, were also observed during the first 30 minutes of supine rest, detecting an increase in vascular filling, and taking place after switching from the standing to the supine position. CONCLUSIONS: This study quantified the dependence of the IVC cross-sectional area on controlled intrathoracic pressure changes and evidenced the stronger influence of diaphragmatic over thoracic activity. Individual variability in thoracic/diaphragmatic respiratory pattern should be considered in the interpretation of the respirophasic modulations of IVC size.

Blood pooling in extrathoracic veins after glossopharyngeal insufflation.

PURPOSE: Trained breath-hold divers hyperinflate their lungs by glossopharyngeal insufflation (GPI) to prolong submersion time and withstand lung collapse at depths. Pulmonary hyperinflation leads to profound hemodynamic changes. METHODS: Thirteen divers performed preparatory breath-holds followed by apnea with GPI. Filling of extrathoracic veins was determined by ultrasound and magnetic resonance imaging and peripheral extravasation of fluid was assessed by electrical impedance. Femoral vein diameter was measured by ultrasound throughout the easy-going and struggle phase of apnea with GPI in eight divers in a sub-study. RESULTS: After GPI, pulmonary volume increased by 0.8 ± 0.6 L above total lung capacity. The diameter of the superior caval (by 36 ± 17%) and intrathoracic part of the inferior caval vein decreased (by 21 ± 16%), while the diameters of the internal jugular (by 53 ± 34%), hepatic (by 28 ± 40%), abdominal part of the inferior caval (by 28 ± 28%), and femoral veins (by 65 ± 50%) all increased (P < 0.05). Blood volume of the internal jugular, the hepatic, the abdominal part of the inferior caval vein, and the combined common iliac and femoral veins increased by 145 ± 115, 80 ± 88, 61 ± 60, and 183 ± 197%, respectively. In the sub-study, femoral vein diameter increased by 44 ± 33% in the easy-going phase of apnea with GPI, subsequently decreasing by 20 ± 16% during the struggle phase. Electrical impedance remained unchanged over the thigh and forearm, thus excluding peripheral fluid extravasation. CONCLUSIONS: GPI leads to heart and pulmonary vessel compression, resulting in redistribution of blood to extrathoracic capacitance veins proximal to venous valves. This is partially reversed by the onset of involuntary breathing movements.

Structural and Functional Differences Between Porcine Aorta and Vena Cava.

Elastin and collagen fibers are the major load-bearing extracellular matrix (ECM) constituents of the vascular wall. Arteries function differently than veins in the circulatory system; however as a result from several treatment options, veins are subjected to sudden elevated arterial pressure. It is thus important to recognize the fundamental structure and function differences between a vein and an artery. Our research compared the relationship between biaxial mechanical function and ECM structure of porcine thoracic aorta and inferior vena cava. Our study suggests that aorta contains slightly more elastin than collagen due to the cyclical extensibility, but vena cava contains almost four times more collagen than elastin to maintain integrity. Furthermore, multiphoton imaging of vena cava showed longitudinally oriented elastin and circumferentially oriented collagen that is recruited at supraphysiologic stress, but low levels of strain. However in aorta, elastin is distributed uniformly, and the primarily circumferentially oriented collagen is recruited at higher levels of strain than vena cava. These structural observations support the functional finding that vena cava is highly anisotropic with the longitude being more compliant and the circumference stiffening substantially at low levels of strain. Overall, our research demonstrates that fiber distributions and recruitment should be considered in addition to relative collagen and elastin contents. Also, the importance of accounting for the structural and functional differences between arteries and veins should be taken into account when considering disease treatment options.

Hemodinámica en vena cava y hemorragia durante trombectomía en la cirugía del tumor renal / Vena cava haemodynamics and haemorrhage during thrombectomy in renal tumour surgery

No disponible

An Experimental and Computational Study on the Effect of Caval Valved Stent Oversizing.

Heterotopic implantation of transcatheter tricuspid valve is a new treatment option for tricuspid regurgitation. Transcatheter tricuspid valves are implanted onto the cavoatrial junction in order to avoid the challenging task of anchoring the valve onto the complex tricuspid valve annulus. However, little is known about optimum extent of oversizing of the valved stent in a vena cava. In this study, we implanted valves of the same diameter onto the larger sized inferior vena cava (IVC) and a smaller sized superior vena cava (SVC). The valve in the IVC was oversized by 10.7% while the valve in the SVC was oversized by 21.6%. Finite element analysis was performed (i) to assess the strain on the nitinol stent during manufacturing and deployment; (ii) the stents were deployed in a patient-specific vena cava model and the intramural stress of the vena cava was calculated computationally. These valves were fabricated and placed in a silicone model of a patient-specific right atrium which was part of a mock circulatory system that emulated the patho-physiological flow rate and pressure of a patient with tricuspid regurgitation. Flow measurements were conducted by particle image velocimetry (PIV). It was found that the maximum crimping strain on the nitinol stent was 6.85% which was lower than the critical threshold of 10%. The maximum stress on the vena cava was located at the spot where the hooks met the wall. The maximum stress on the IVC was 0.5098 MPa while the maximum stress on the SVC was 0.7 MPa. The maximum Reynolds shear stress (mRSS) in the vena cava was found to be higher in the IVC than SVC with the highest mRSS being 1741 dynes/cm(2) found in the region of high flow during the peak flow phase. The overtly oversized valve in the SVC did not cause flow disturbances and exhibited mostly laminar flows. The mRSS at the downstream of the vena cava valve and the middle of the atrium remained at low magnitudes. However, velocity fluctuations were high in the IVC in all the time points measured. In conclusion, oversizing the valve may assist anchorage; yet, careful consideration should be taken in choosing the extent of oversizing as it may lead to adverse effects.

In Vitro Investigation of the Hemodynamics of Transcatheter Heterotopic Valves Implantation in the Cavo-Atrial Junction.

Severe tricuspid regurgitation (TR) is life-threatening but is often undertreated. Many patients with severe TR are denied heart valve replacement surgery because their old age or comorbidities predispose them to a higher risk of surgical complications associated with open-heart surgery. With the advent of transcatheter technology, it is now possible to deliver the valve to the desired location without the need for open-heart surgery. However, presently, there is no commercially available transcatheter tricuspid valve. This may be due to the complex tricuspid valve anatomy, which lacks an anchorage zone for the percutaneous valves. In view of this drawback, we have recently developed and tested two percutaneous caval heart valves that are designed to deploy at the vena cava and atrium junction. The hemodynamic characteristics of these valves are tested in a mock circulatory system with patient-specific silicone atrium and vena cava, which emulates the physiological pressure and flow conditions at the right side of the human heart. Particle imaging velocimetry results showed that flow velocity and the associated Reynolds shear stress (RSS) and the turbulent kinetic energy (TKE) downstream of the valves increased after the implantation of the valves. A maximum flow velocity of 0.94 m/s was observed at the region downstream of the percutaneous valve at the superior vena cava (SVC). Maximum RSS value of 2076.1 dynes/cm(2) was observed downstream of the valve at the inferior vena cava during the deceleration phase while maximum TKE measured was 572.6 J/m(3) at the upstream of the valve in the SVC during the peak flow phase. While these values appear high, they are significantly lower than those reported in prosthetic mitral and aortic valves. Hence, caval stented valves can be potentially considered as a minimally invasive option to treat TR.

Acute effect of static exercise on the cardiovascular system: assessment by cardiovascular magnetic resonance.

PURPOSE: The acute effect of static exercise on the global dynamics of the cardiovascular system is poorly understood. The use of cardiovascular magnetic resonance (CMR) may be useful for evaluating this effect. METHODS: A total of 12 healthy individuals underwent CMR imaging at rest and while performing a maximal sustained static exercise (weight elevation with both legs). We analyzed the effects on left and right ventricular function, ascending aorta dynamics, and venous capacitance using standard cine and phase-contrast sequences. RESULTS: We observed excellent reproducibility in the measurements of the images obtained at rest as well as during static exercise. During exercise, we observed reduced left (-35 ± 8 %, p < 0.001) and right (-44 ± 9 %, p < 0.001) ventricle end-diastolic volumes, reduced left (-35 ± 16 %, p < 0.001) and right (-43 ± 8 %, p < 0.001) ventricle end-systolic volumes (both with a significantly greater reduction in the right ventricle), a reduced superior vena cava cross-sectional area (-20 ± 17 %, p = 0.003), and increased left ventricle wall thickness. We estimated that there was an increase in left ventricle contractility. There were no significant changes in the left and right ventricular ejection fractions. During exercise, we noted a tendency toward decreased aortic distensibility and a reduction of ascending aorta systolic expansion. CONCLUSIONS: In healthy individuals, an acute maximal static exercise produced a reduction in the left ventricle, right ventricle, and superior vena cava volumes as well as signs of increased aortic stiffness without increasing left ventricular systolic wall stress. CMR is feasible and useful in evaluating the hemodynamic effects of static exercise.

Generation and characterization of feline arterial and venous endothelial cell lines for the study of the vascular endothelium.

BACKGROUND: The in vitro culture of endothelial cells (ECs) is an indispensable tool for studying the role of the endothelium in physical and pathological conditions. Primary ECs, however, have a restricted proliferative lifespan which hampers their use in long-term studies. The need for standardized experimental conditions to obtain relevant and reproducible results has increased the demand for well-characterized, continuous EC lines that retain the phenotypic and functional characteristics of their non-transformed counterparts. RESULTS: Primary feline ECs from aorta and vena cava were successfully immortalized through the successive introduction of simian virus 40 large T (SV40LT) antigen and the catalytic subunit of human telomerase (hTERT). In contrast to the parental ECs, the transformed cells were able to proliferate continuously in culture. Established cell lines exhibited several inherent endothelial properties, including typical cobblestone morphology, binding of endothelial cell-specific lectins and internalization of acetylated low-density lipoprotein. In addition, the immortalization did not affect the functional phenotype as demonstrated by their capacity to rapidly form cord-like structures on matrigel and to express cell adhesion molecules following cytokine stimulation. CONCLUSION: The ability to immortalize feline ECs, and the fact that these cells maintain the EC phenotype will enable a greater understanding of fundamental mechanisms of EC biology and endothelial-related diseases. Furthermore, the use of cell lines is an effective implementation of the 3-R principles formulated by Russel and Burch.

Network interactions within the canine intrinsic cardiac nervous system: implications for reflex control of regional cardiac function.

The aims of the study were to determine how aggregates of intrinsic cardiac (IC) neurons transduce the cardiovascular milieu versus responding to changes in central neuronal drive and to determine IC network interactions subsequent to induced neural imbalances in the genesis of atrial fibrillation (AF). Activity from multiple IC neurons in the right atrial ganglionated plexus was recorded in eight anaesthetized canines using a 16-channel linear microelectrode array. Induced changes in IC neuronal activity were evaluated in response to: (1) focal cardiac mechanical distortion; (2) electrical activation of cervical vagi or stellate ganglia; (3) occlusion of the inferior vena cava or thoracic aorta; (4) transient ventricular ischaemia, and (5) neurally induced AF. Low level activity (ranging from 0 to 2.7 Hz) generated by 92 neurons was identified in basal states, activities that displayed functional interconnectivity. The majority (56%) of IC neurons so identified received indirect central inputs (vagus alone: 25%; stellate ganglion alone: 27%; both: 48%). Fifty per cent transduced the cardiac milieu responding to multimodal stressors applied to the great vessels or heart. Fifty per cent of IC neurons exhibited cardiac cycle periodicity, with activity occurring primarily in late diastole into isovolumetric contraction. Cardiac-related activity in IC neurons was primarily related to direct cardiac mechano-sensory inputs and indirect autonomic efferent inputs. In response to mediastinal nerve stimulation, most IC neurons became excessively activated; such network behaviour preceded and persisted throughout AF. It was concluded that stochastic interactions occur among IC local circuit neuronal populations in the control of regional cardiac function. Modulation of IC local circuit neuronal recruitment may represent a novel approach for the treatment of cardiac disease, including atrial arrhythmias.

Dual-pump support in the inferior and superior vena cavae of a patient-specific fontan physiology.

The implementation of simultaneous mechanical cavopulmonary assistance having blood pumps located in both of the vena cavae is investigated as an approach to treating patients with an ailing Fontan physiology. Identical intravascular blood pumps are employed to model the hemodynamic support of a patient-specific Fontan. Pressure flow characteristics, energy gain calculations, and blood damage analyses are assessed for each model. The performance of the dual-support scenario is compared to conditions of mechanical support in the inferior vena cava only and to a nonsupported cavopulmonary circuit. The blood pump in the superior vena cava generates pressures ranging from 1 to 22 mm Hg for flow rates of 1-4 L/min at operating speeds of 1250-2500 rpm. The blood pump in the inferior vena cava produces pressures at levels approximately 20% lower. The blood pumps positively augment the hydraulic energy in the total cavopulmonary connection circuit as a function of flow rate and rotational speed. Scalar stress levels and fluid residence times are at acceptable levels. Damage indices for the dual-support case, however, are elevated slightly above 3.5%. These results suggest that concurrent, mechanical assistance of the inferior vena cava and superior vena cava in Fontan patients has the potential to be beneficial, but additional studies are needed to further explore this approach.

Caval blood flow distribution in patients with Fontan circulation: quantification by using particle traces from 4D flow MR imaging.

PURPOSE: To validate the use of particle traces derived from four-dimensional (4D) flow magnetic resonance (MR) imaging to quantify in vivo the caval flow contribution to the pulmonary arteries (PAs) in patients who had been treated with the Fontan procedure. MATERIALS AND METHODS: The institutional review boards approved this study, and informed consent was obtained. Twelve healthy volunteers and 10 patients with Fontan circulation were evaluated. The particle trace method consists of creating a region of interest (ROI) on a blood vessel, which is used to emit particles with a temporal resolution of approximately 40 msec. The flow distribution, as a percentage, is then estimated by counting the particles arriving to different ROIs. To validate this method, two independent observers used particle traces to calculate the flow contribution of the PA to its branches in volunteers and compared it with the contribution estimated by measuring net forward flow volume (reference method). After the method was validated, caval flow contributions were quantified in patients. Statistical analysis was performed with nonparametric tests and Bland-Altman plots. P < .05 was considered to indicate a significant difference. RESULTS: Estimation of flow contributions by using particle traces was equivalent to estimation by using the reference method. Mean flow contribution of the PA to the right PA in volunteers was 54% ± 3 (standard deviation) with the reference method versus 54% ± 3 with the particle trace method for observer 1 (P = .4) and 54% ± 4 versus 54% ± 4 for observer 2 (P = .6). In patients with Fontan circulation, 87% ± 13 of the superior vena cava blood flowed to the right PA (range, 63%-100%), whereas 55% ± 19 of the inferior vena cava blood flowed to the left PA (range, 22%-82%). CONCLUSION: Particle traces derived from 4D flow MR imaging enable in vivo quantification of the caval flow distribution to the PAs in patients with Fontan circulation. This method might allow the identification of patients at risk of developing complications secondary to uneven flow distribution. SUPPLEMENTAL MATERIAL: http://radiology.rsna.org/lookup/suppl/doi:10.1148/radiol.12120778/-/DC1.

Reverse-mode Na+/Ca2+ exchange is an important mediator of venous contraction.

The Na(+)/Ca(2+) exchanger (NCX) is a bi-directional regulator of cytosolic Ca(2+), causing Ca(2+) efflux in forward-mode and Ca(2+) influx in reverse-mode. We hypothesized that reverse-mode NCX is a means of Ca(2+) entry in rat aorta (RA) and vena cava (RVC). NCX protein in RA and RVC was confirmed by immunoprecipitation. To assess NCX function, isometric contraction and intracellular Ca(2+) was measured in RA and RVC rings in response to low extracellular Na(+), endothelin-1 (ET-1), and KCl, in the presence or absence of the NCX antagonist KB-R7943. In RVC, low extracellular Na(+) caused vasoconstriction and an increase in intracellular Ca(2+) that was attenuated by 10µM KB-R7943. KB-R7943 (10 µM) attenuated maximal contraction to ET-1 in RVC (53 ± 9% of control), but not RA (91±1% of control). KB-R7943 (10 µM) reduced the maximal contraction to KCl in RA (48 ± 5%) and nearly abolished it in RVC (9 ± 2%), suggesting that voltage-dependent Ca(2+) influx may be inhibited by KB-R7943 as well. However, the L-type Ca(2+) channel inhibitor nifedipine (1 µM) did not alter ET-1-induced contraction. Our findings suggest that reverse-mode NCX is an important mechanism of Ca(2+) influx in RVC but not RA, especially during ET-1-induced contraction. Also, the effects of KB-R7943 on ET-1-induced contraction of RA and RVC are predominantly mediated by reverse-mode NCX inhibition and not due to off-target inhibition of Ca(2+) channels.

Patient-specific simulations and measurements of the magneto-hemodynamic effect in human primary vessels.

This paper investigates the main characteristics of the magneto-hemodynamic (MHD) response for application as a biomarker of vascular blood flow. The induced surface potential changes of a volunteer exposed to a 3 T static B0 field of a magnetic resonance imaging (MRI) magnet were measured over time at multiple locations by an electrocardiogram device and compared to simulation results. The flow simulations were based on boundary conditions derived from MRI flow measurements restricted to the aorta and vena cava. A dedicated and validated low-frequency electromagnetic solver was applied to determine the induced temporal surface potential change from the obtained 4D flow distribution using a detailed whole-body model of the volunteer. The simulated MHD signal agreed with major characteristics of the measured signal (temporal location of main peak, magnitude, variation across chest and along torso) except in the vicinity of the heart. The MHD signal is mostly influenced by the aorta; however, more vessels and better boundary conditions are needed to analyze the finer details of the response. The results show that the MHD signal is strongly position dependent with highly variable but reproducibly measurable distinguished characteristics. Additional investigations are necessary before determining whether the MHD effect is a reliable reference for location-specific information on blood flow.

Normal reference ranges of ductus venosus Doppler indices in the period from 14 to 40 weeks' gestation.

OBJECTIVE: To construct reference ranges of ductus venosus (DV) Doppler indices in normal singleton pregnancies. METHODS: A cross-sectional study was conducted on low-risk singleton pregnancies with accurate gestational age, and normal fetuses were enrolled into the study. Measurements of DV Doppler indices were determined by experienced sonographers. Poor quality images were excluded. RESULTS: A total of 640 fetuses underwent DV measurements, ranging from 13 to 30 for each gestational week. The relationship between gestational age and DV Doppler indices was not linear. The best-fit regression equations are as follows: preload index = (5.061 - 0.4882) × exp (-0.211 × GA) + 0.4882; peak velocity index for veins = (7.498 - 0.5609) × exp (-0.2184 × GA) + 0.5609; pulsatility index for veins = (17.9 - 0.6053) × exp (-0.2512 × GA) + 0.6053; systolic/atrial wave ratio = (300 - 2.124) × exp (-0.3649 × GA) + 2.124. Notably, during the period from 14 to 20 weeks' gestation, all of the four indices rapidly decreased and they were relatively stable or slightly decreased after that. The nomogram tables for various percentile ranges were constructed. CONCLUSION: A nomogram for DV Doppler indices for each gestational week during the period from 14 to 40 weeks' gestation was established. These reference ranges may be a useful non-invasive tool for evaluation of fetal cardiac function.

Contribution of splanchnic and musculocutaneous vascular compartments to the formation of blood flow volume in the vena cava posterior during catecholamine treatment.

Studies by electromagnetic flowmetry in acute experiments on cats under conditions of the open thoracic cage and artificial ventilation of the lungs showed that 64% of venous return via the vena cava posterior was realized at the expense of the splanchnic and 36% due to the musculocutaneous vessels (abdominal basin of the caudal vein). Epinephrine (20 µg/kg) increased the contribution of the splanchnic venous blood flow to the increase in the blood flow in the vena cava posterior and reduced the contribution of the musculocutaneous veins throughout the entire duration of systemic reactions: 84% of the blood flow increase in the vena cava posterior was due to the splanchnic and just 16% due to the musculocutaneous blood flow. Norepinephrine (10 µg/kg) resulted in a phase-wise involvement of the studied compartments in blood flow increase in the vena cava posterior. During the initial period of systemic reactions (coinciding with the maximum systemic BP rise) the contribution of the musculocutaneous compartment was 13% higher, while later (by the time of the maximum elevation of venous blood flow in the studied compartments) the contribution of splanchnic veins predominated constituting 89% of venous blood flow in the vena cava posterior. These results indicate that venous blood flow increase in the splanchnic vessels largely determined the formation of changes in the vena cava posterior blood flow in response to catecholamines.