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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.

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.

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, 2019 Online supplemental material is available for this article. See also the editorial by Choe in this issue.

Deep-diving California sea lions ( Zalophus californianus ) can maintain arterial hemoglobin saturation ( S O 2 ) above 90% despite lung collapse (lack of gas exchange) and extremely low posterior vena caval S O 2  in the middle of the dive. We investigated anterior vena caval P O 2   and S O 2  during dives of an adult female sea lion to investigate two hypotheses: (1) posterior vena caval S O 2  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 S O 2  during lung collapse. During deep dives, initial anterior vena caval S O 2  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 S O 2  declined during descent and then often increased during ascent. These divergent patterns confirmed that posterior vena caval S O 2  was not representative of the entire venous oxygen store. Prior to and early during descent of deep dives, the high S O 2  values of both the anterior and posterior venae cavae may enhance arterialization of a central venous oxygen store. However, anterior vena caval S O 2  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 S O 2 These findings suggest that maintenance of high arterial S O 2  during deep dives is due to persistence of some gas exchange at depths beyond presumed lung collapse., Competing Interests: Competing interestsThe authors declare no competing or financial interests., (© 2018. Published by The Company of Biologists Ltd.)

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 cm 2 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., (© 2017 by the American Institute of Ultrasound in Medicine.)

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.

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.

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.

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., (Copyright © 2015 International Center for Artificial Organs and Transplantation and Wiley Periodicals, Inc.)

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.

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.

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.

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., (© 2013, Copyright the Authors. Artificial Organs © 2013, International Center for Artificial Organs and Transplantation and Wiley Periodicals, Inc.)

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., (RSNA, 2013.)

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., (Copyright © 2012 Elsevier Ltd. All rights reserved.)

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.

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., (Copyright © 2011 S. Karger AG, Basel.)

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.

The aim of this work was to evaluate the hemodynamic changes in the utero-placental arterial vessels in rabbits (Orictolagus cuniculus) throughout pregnancy as well as those in the umbilical cord, aorta, and caudal vena cava of fetuses to establish their normal reference ranges for systolic peak velocity (SPV), end diastolic velocity (EDV), pulsatility index (PI), and resistance index (RI). The blood flow waveforms were monitored every 4 d in 10 rabbits from Day 10 of pregnancy onward by means of color and pulsed wave Doppler ultrasonography using a 5.5-7.5 MHz microconvex transabdominal probe. The utero-placental blood flow was characterized by steep increases and decrease in the SPV with a slow diastolic wave and relatively high EDV, whereas that of the umbilical artery was discontinuous until Day 22 of pregnancy, when a diastolic waveform was also detectable. From Day 10 to 22 of pregnancy, the fetal aorta blood flow was discontinuous, but thereafter a diastolic peak was measurable. The blood flow of the fetal caudal vena cava was characterized by a systolic peak followed by a small diastolic peak. Throughout the gestation, the SPV and the EDV of maternal and fetal vessels increased (alpha<0.05), whereas the PI and the RI decreased (alpha<0.05), except for the utero-placental vessels. This work confirms that the rabbit could also be a valid experimental animal model to study, by Doppler ultrasonography, functional hemodynamic changes of the fetuses and placenta vessels in both normal and pathophysiologic conditions., (2010 Elsevier Inc. All rights reserved.)

Endothelin receptors (ET(A) and ET(B)) mediate responses to ET-1. ET(B) receptor function seems to differ between a similarly sized arterial and venous pair, the rat vena cava (RVC) and rat thoracic aorta (RA). ET(B) receptors mediate RVC contraction directly, but it is unclear whether ET(B) receptors mediate contraction in RA. Because of these apparent differences in ET(B) receptor-mediated vascular contraction, we hypothesize that relaxant ET(B)-receptor mechanisms in RVC would be different from those in RA. RA and RVC rings were isolated from rats for measurement of isometric contraction. When contracted with prostaglandin F-2alpha (PGF-2alpha) (20 microM), the ET(B) receptor agonist sarafotoxin-6c (S6c) (100 nM) significantly relaxed RA and RVC. N(omega)-Nitro-L-arginine (LNNA) (100 microM) or endothelial denudation abolished relaxation to S6c in RA. By contrast, S6c-induced relaxation of RVC was attenuated but not abolished by LNNA and endothelial denudation. RVC (PGF-2alpha-contracted) relaxed to low concentrations of ET-1, whereas under the same conditions RA responded with contraction. ET-1-induced relaxation in RA was observed only with ET(A) receptor blockade. Vessels from dopamine-beta-hydroxylase-ET(B) transgenic rats, which lack functional ET(B) receptors in the vasculature, were also used. RVC (PGF-2alpha-contracted) from these rats did not relax to ET-1. Thus, although both RA and RVC possess endothelial relaxant ET(B) receptors, RA and RVC differ in that relaxant ET(B) receptors may also be present in smooth muscle of RVC. Moreover, the mechanisms of endothelial cell ET(B) receptor-mediated relaxation in RA and RVC are not the same.

The aim of this work is to evaluate the haemodynamic characteristics of maternal and foetal vessels during normal pregnancy in queens, using colour Doppler and pulsed wave Doppler ultrasonography, in order to obtain information about maternal and foetal circulation. The blood waveforms of the uteroplacental arteries, aorta, caudal cava vein and umbilical cord of the fetuses were recorded weekly in seven healthy pregnant queens. Also, the measurements of peak systolic, end diastolic velocities, resistance and pulsatility indices were carried out. Uteroplacental blood flow was biphasic while the ones of the umbilical artery and aorta were first systolic and then diastolic. The caudal cava vein showed a typical waveform of venous vessels. During gestation the EDV and PSV of foetal vessels increased (alpha<0.05) while the PI and RI of all vessels examined decreased (alpha<0.05) except for the IP of the aorta. The Doppler ultrasonography, also in queens, can be used to evaluate the characteristics of maternal and foetal vessel flow and their progressive changes during pregnancy. This study can be considered the basis for further contribution in diagnosing and monitoring high-risk pregnancies in Veterinary Medicine.

Objective: Transient interruption of the contrast bolus has been described as a physiologic artifact that can sometimes result in poor opacification of the pulmonary arteries on pulmonary CT angiographic studies. To better understand the mechanism underlying this artifact, we used velocity-encoded cine MRI to measure flow in the inferior vena cava (IVC) and superior vena cava (SVC) during respiratory maneuvers., Subjects and Methods: Quantitative measurements of SVC and IVC flow per R-R interval were performed on 10 healthy volunteers (six men, four women; median age, 30 years; range, 25-55 years) with a retrospectively ECG-gated velocity-encoded gradient-echo cine sequence on a 1.5-T MRI unit with axial slices at the level of the diaphragm and just below the azygous vein confluence during free breathing, continuous inspiration, breath-hold at end inspiration, Valsalva maneuver, and breath-hold at end expiration., Results: Median flow during free breathing was 38.9 mL in the SVC and 74.3 mL in the IVC, during continuous inspiration was 43.9 mL in the SVC and 113.7 mL in the IVC, during breath-hold at end inspiration was 31.0 mL in the SVC and 56.1 mL in the IVC, during a Valsalva maneuver was 28.9 mL in the SVC and 53.9 mL in the IVC, and during breath-hold at end expiration was 35.3 mL in the SVC and 61.2 mL in the IVC., Conclusion: MRI measurements showed a significant increase in caval flow during inspiration and a greater relative increase in blood flow in the IVC than in the SVC. For thoracic CT performed with IV contrast enhancement, deep inspiration before scanning leads to a large influx of IVC blood that does not contain contrast medium and dilutes the contrast bolus, causing poor vascular opacification. Avoiding initial inspiration before scanning is suggested as a way to limit the transient interruption of the contrast bolus artifact.

Congenital heart defects with a single functional ventricle, such as hypoplastic left heart syndrome and tricuspid atresia, require a staged surgical approach to separate the systemic and pulmonary circulations. Ultimately, the venous or pulmonary side of the heart is bypassed by directly connecting the vena cava to the pulmonary arteries with a modified t-shaped junction. The Fontan procedure (total cavopulmonary connection, TCPC) completes this process of separation. To date, computational fluid dynamics (CFD) simulations in this low pressure, passive flow, intrathoracic system have neglected the presumed important effects of respiration on physiology and higher "stress" states such as with exercise have never been considered. We hypothesize that incorporating effects of respiration and exercise would provide more realistic estimates of TCPC performance. Time-dependent, 3D blood flow simulations are performed by a custom finite element solver for two patient-specific Fontan models with a novel respiration model, developed to generate physiologic time-varying flow conditions. Blood flow features, pressure, and energy efficiency are analyzed at rest and with increasing flow rates to simulate exercise conditions. The simulations produce realistic pressure and flow data, comparable to that measured by catheterization and echocardiography, and demonstrate substantial increases in energy dissipation (i.e. decreased performance) with exercise and respiration due to increasing intensity of small scale vortices in the flow. As would be expected, these changes are highly dependent on patient-specific anatomy and Fontan geometry. We propose that respiration and exercise should be incorporated into TCPC CFD simulations to provide increasingly realistic evaluations of TCPC performance.

The objective of this study was to investigate venous collapse (VC) related to venous drainage during the use of an extracorporeal life support circuit. A mock circulation was built containing a centrifugal pump and a collapsible vena cava model to simulate VC under controlled conditions. Animal experiments were performed for in vivo verification. Changing pump speed had a different impact on flow during a collapsed and a distended caval vein in both models. Flow measurement in combination with pump speed interventions allows for the detection and quantitative assessment of the degree of VC. Additionally, it was verified that a quick reversal of a VC situation could be achieved by a two-step pump speed intervention, which also proved to be more effective than a straightforward decrease in pump speed.

Smooth muscle myosin heavy chains occur in 2 isoforms, SMA (slow) and SMB (fast). We hypothesized that the SMB isoform is predominant in the faster-contracting rat vena cava compared to thoracic aorta. We compared the time to half maximal contraction in response to a maximal concentration of endothelin-1 (ET-1; 100 nM), potassium chloride (KCl; 100 mM) and norepinephrine (NE; 10 microM). The time to half maximal contraction was shorter in the vena cava compared to aorta (aorta: ET-1 = 235.8 +/- 13.8 s, KCl = 140.0 +/- 33.3 s, NE = 19.8 +/- 2.7 s; vena cava: ET-1 = 121.8 +/- 15.6 s, KCl = 49.5 +/- 6.7 s, NE = 9.0 +/- 3.3 s). Reverse-transcription polymerase chain reaction supported the greater expression of SMB in the vena cava compared to aorta. SMB was expressed to a greater extent than SMA in the vessel wall of the vena cava. Western analysis determined that expression of SMB, relative to total smooth muscle myosin heavy chains, was 12.5 +/- 4.9-fold higher in the vena cava compared to aorta, while SMA was 4.9 +/- 1.2-fold higher in the aorta than vena cava. Thus, the SMB isoform is the predominant form expressed in rat veins, providing one possible mechanism for the faster response of veins to vasoconstrictors., (Copyright (c) 2007 S. Karger AG, Basel.)

A two-dimensional model for the elastic properties of vena cava abdominalis under orthotropic deformation is introduced and tested against the experimental data obtained from six specimen of rat venae cavae by pressurization experiments. The model is based on membrane approximation and suited for vessels where most of the elastic elements are oriented axially, while circumferential contraction is exerted by redirecting axial stress by some network of oblique fibers. For the experimental data considered in this paper, the ratio between axial and circumferential stress depends almost exclusively on the circumferential extension ratio. As a consequence, the mechanical system can be formally decomposed in a kinematic system reacting by axial contraction on circumferential extension without any loss or storage of energy, serially connected to a hyperelastic system acting only in axial direction. Both systems are modeled separately by equations obtained by a purely phenomenological approach with two parameters for each system. This leads to reasonable reproduction of the experimental data. Introducing a correction parameter, which takes into account that the model assumption on the decomposition does not hold exactly, we get better reproduction of data. However, this is paid for by loss of physical rigor and in particular by departing from the assumption of hyperelasticity.

In hypertension, blood vessels exhibit increased reactive oxygen species production that may alter vascular tone. We previously observed that H2O2 contracted rat thoracic vena cava under resting tone and aorta contracted with KCl. In arteries but not veins, H2O2-induced contraction required extracellular Ca2+ influx. Because of this difference in Ca2+ utilization, we hypothesized that signaling pathways mediating H2O2-induced contraction in vena cava under resting tone differed from those mediating H2O2-induced contraction in aorta contracted with KCl. Inhibitors of cyclooxygenase (COX) 1 and 2 (indomethacin, 10 microM), thromboxane A2 (TXA2) receptors [ICI185282 (2RS,4RS,5SR-4-o-hydroxyphenyl-2-trifluoromethyl-1,3-dioxan-5-yl heptenoic acid), 10 microM], p38 mitogen-activated protein kinase (MAPK) [SB203580 (4-[5-(4-fluorophenyl)-2-[4-(methylsulfonyl)phenyl]-1H-imidazol-4-yl]pyridine), 10 microM], extracellular signal-regulated kinase (Erk) [PD98059 (2'-amino-3'-methoxyflavone), 10 microM], src [PP1 (4-amino-5-(4-methylphenyl)-7-(t-butyl)pyrazolo[3,4-d]pyrimidine, 10 microM], and rho kinase [Y27632 (trans-4-[(1R)-1-aminoethyl]-N-4-pyridinylcyclohexanecarboxamide dihydrochloride), 10 microM], significantly reduced H2O2-induced contraction in vena cava under resting tone and aorta after KCl (30 mM) contraction. In contrast, the phosphatidylinositol 3-kinase (PI3-K) inhibitor LY294002 [2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one, 20 microM] did not reduce aortic or venous H2O2-induced contraction. p38 MAPK, Erk MAPK, and src inhibition did not reduce aortic or venous contraction to the TXA2 receptor agonist U46619 (9,11-dideoxy-9alpha,11alpha-methanoepoxy PGF(2alpha), 1 microM), whereas rho kinase inhibition significantly reduced aortic and venous contraction to U46619, and PI3-K inhibition reduced venous contraction to U46619. Our data suggest that, in rat thoracic aorta and vena cava, a COX-derived metabolite is one important mediator of H2O2 contraction, possibly via rho kinase activation, and that H2O2-induced contraction via p38 and Erk MAPK probably occurs independently of TXA2 receptor activation.

The aim of this work is to evaluate the haemodynamic characteristics of maternal and fetal vessels during normal pregnancy in bitches, using Colour and Pulsed wave Doppler ultrasonography, in order to obtain more information about maternal and fetal circulation. The blood waveforms of the uteroplacental arteries, aorta, caudal cava vein and umbilical cord of the fetuses were recorded weekly in 16 pregnant bitches. Also, the measurements of Peak Systolic, End Diastolic Velocities, Resistance and Pulsatility Indices were carried out. Uteroplacental blood flow was biphasic while the ones of the umbilical artery and aorta were first systolic and then diastolic. The cava showed a typical waveform of venous vessels. During gestation the EDV and PSV of fetal vessels increased (alpha<0.05) while the PI and RI of all vessels examined decreased (alpha<0.05) except for the IP of the Aorta. The Doppler ultrasonography was used to study the characteristics of maternal and fetal vessel flow and their progressive changes during pregnancy. This study can be considered a further contribution in diagnosing and monitoring high-risk pregnancies in Veterinary Medicine.

Physically useful measures in current clinical practice refer often to the blood flow rate, that is related to the mean velocity. However, the direct measurement of the latter is currently not possible using a Doppler velocimetry technique. Therefore, the usual approach to calculate the flow rate with this technique consists in measuring the maximum velocity and in estimating the mean velocity, making the hypothesis of parabolic profile that in realistic situations results in strongly inaccurate estimates. In this paper, we propose a different way for estimating the flow rate regarded as a function of maximum velocity and Womersley number. This relation is obtained by fixing a parametrised representation and by evaluating the parameters by means of a least-square approach working on the numerical results of CFD simulations (about 200). Numerical simulations are carried out by prescribing the flow rate, not the velocity profile. In this way, no bias is implicitly induced in prescribing boundary conditions. Validation tests based on numerical simulations show that the proposed relation improves the flow rate estimation.

A minimal closed-loop cardiovascular system (CVS) model has been developed that can simulate ventricular interaction due to both direct interaction through the septum and series interaction through the circulation system. The model is used to simulate canine experiments carried out to study the transient response of the left ventricle due to changes in right ventricle pressures and volumes. The model-simulated trends in left and right ventricle pressures and volumes, septum deflection and arterial flow rates are compared with the experimental results. In spite of the limited physiological data available describing the animals, the model is shown to capture all the transient trends in the experimental data. This is the first known example of a physiological model that can capture all these trends. The model is then used to illustrate the separate effects of direct and series interactions independently. This study proves the value of this modelling method to be used in conjunction with experimental data for delineating and understanding the factors that contribute to ventricular dynamics.

Background: Two randomized prospective studies suggested that ischemic preconditioning (IP) protects the human liver against ischemia-reperfusion injury after hepatectomy performed under continuous clamping of the portal triad. The primary goal of this study was to determine whether IP protects the human liver against ischemia-reperfusion injury after hepatectomy under continuous vascular exclusion with preservation of the caval flow., Study Design: Sixty patients were randomly divided into two groups: with (n=30; preconditioning group) and without (n=30; control group) IP (10 minutes of portal triad clamping and 10 minutes of reperfusion) before major hepatectomy under vascular exclusion of the liver preserving the caval flow. Serum concentrations of aspartate transferase, alanine transferase, glutathione-S-transferase, and bilirubin and prothrombin time were regularly determined until discharge and at 1 month. Morbidity and mortality were determined in both groups., Results: Peak postoperative concentrations of aspartate transferase were similar in the groups with and without IP (851 +/- 1,733 IU/L and 427 +/- 166 IU/L respectively, p=0.2). A similar trend toward a higher peak concentration of alanine transferase and glutathione-S-transferase was indeed observed in the preconditioning group compared with the control group. Morbidity and mortality rates and lengths of ICU and hospitalization stays were similar in both groups., Conclusions: IP does not improve liver tolerance to ischemia-reperfusion after hepatectomy under vascular exclusion of the liver with preservation of the caval flow. This maneuver does not improve postoperative liver function and does not affect morbidity or mortality rates. The clinical use of IP through 10 minutes of warm ischemia in this technique of hepatectomy is not currently recommended.

Computational investigations of flow mixing and oxygen transfer characteristics in an intravenous membrane oxygenator (IMO) are performed by direct numerical simulations of the conservation of mass, momentum, and species equations. Three-dimensional computational models are developed to investigate flow-mixing and oxygen-transfer characteristics for stationary and pulsating balloons, using the spectral element method. For a stationary balloon, the effect of the fiber placement within the fiber bundle and the number of fiber rings is investigated. In a pulsating balloon, the flow mixing characteristics are determined and the oxygen transfer rate is evaluated. For a stationary balloon, numerical simulations show two well-defined flow patterns that depend on the region of the IMO device. Successive increases of the Reynolds number raise the longitudinal velocity without creating secondary flow. This characteristic is not affected by staggered or non-staggered fiber placement within the fiber bundle. For a pulsating balloon, the flow mixing is enhanced by generating a three-dimensional time-dependent flow characterized by oscillatory radial, pulsatile longitudinal, and both oscillatory and random tangential velocities. This three-dimensional flow increases the flow mixing due to an active time-dependent secondary flow, particularly around the fibers. Analytical models show the fiber bundle placement effect on the pressure gradient and flow pattern. The oxygen transport from the fiber surface to the mean flow is due to a dominant radial diffusion mechanism, for the stationary balloon. The oxygen transfer rate reaches an asymptotic behavior at relatively low Reynolds numbers. For a pulsating balloon, the time-dependent oxygen-concentration field resembles the oscillatory and wavy nature of the time-dependent flow. Sherwood number evaluations demonstrate that balloon pulsations enhance the oxygen transfer rate, even for smaller flow rates.

This study examined the nitric oxide (NO) control of the vascular smooth muscle of the ventral abdominal vein and vena cava of the toad, Bufo marinus, by using anatomical and physiological approaches. Nicotinamide adenine di-nucleotide phosphate-diaphorase histochemistry and immunohistochemistry using endothelial nitric oxide synthase (NOS) and neural NOS antibodies produced no evidence for endothelial NOS in the veins, but, neural NOS-immunoreactive perivascular nerves were present. Acetylcholine (10(-5) M) caused a vasodilation in both veins that was endothelium-independent, and which was blocked by the soluble guanylyl cyclase inhibitor, ODQ (10(-5) M). The NOS inhibitors, L-NNA (10(-4) M) and L-NAME (10(-4) M), did not significantly reduce the vasodilatory effect of acetylcholine in the veins; this suggested that the vasodilation was not due to NO. However, in the presence of phenoxybenzamine (10(-7)-10(-8) M), L-NNA significantly reduced the vasodilatory effect of acetylcholine in the veins. This unusual response is due to phenoxybenzamine partially inactivating the muscarinic receptor pool in the veins. In addition, the neural NOS inhibitor, vinyl-L-NIO (10(-5) M), significantly reduced the acetylcholine-mediated vasodilation in the presence of phenoxybenzamine. The results show that in toad veins, nitrergic nerves rather than an endothelial NO system are involved in NO-mediated vasodilation.

Explants of rat inferior vena cava embedded in collagen gel and cultured under serum-free conditions produced microvascular outgrowths composed of endothelial cells and pericytes. Exogenous vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (bFGF) dose-dependently stimulated angiogenesis and induced the formation of complex networks of highly branched microvessels. VEGF and the VEGF/bFGF combination also promoted pericyte recruitment. Medium conditioned by untreated vena cava cultures contained endogenous VEGF, and a blocking antibody against VEGF significantly reduced the spontaneous angiogenic response of the explants. Vena cava explants exhibited a greater capacity to form neovessels than aortic rings when tested in parallel cultures from the same animal. When compared with aorta-derived microvessels, neovessels of vena cava origin were longer and had fewer pericytes. Vena cava-aorta cocultures produced extensive anastomosing networks of microvessels, which were primarily contributed by the venous explants. Because of its florid angiogenesis and exquisite sensitivity to angiogenic factor stimulation, the vena cava model may provide novel insights into the regulation of the angiogenic process, which typically initiates from the venous side of the vascular bed. Combined with the aortic ring model, this new assay may also enhance our understanding of the mechanisms of anastomosis formation between the arterial and the venous circulations., (Copyright 2005 S. Karger AG, Basel.)

The value of ultrasonography was evaluated in 85 dogs and 17 cats presented with a clinically suspected portosystemic shunt (PSS). A PSS was confirmed in 50 dogs and nine cats (single congenital extrahepatic in 42, single congenital intrahepatic in 11, and multiple acquired in six). Six dogs and one cat had hepatic microvascular dysplasia, and 29 dogs and seven cats had a normal portal system. Ultrasonography was 92% sensitive, 98% specific, and had positive and negative predictive values of 98% and 89%, respectively, in identifying PSS, with an overall accuracy of 95%. When a PSS was identified with ultrasonography, extrahepatic, intrahepatic, and multiple acquired PSS could be correctly differentiated in 53/54 patients (98%). The combination of a small liver, large kidneys, and uroliths had positive and negative predictive values of 100% and 51% for the presence of a congenital PSS in dogs. The portal vein/aorta (PV/Ao) and portal vein/caudal vena cava (PV/ CVC) ratios were smaller in animals with extrahepatic PSSs compared with animals with microvascular dysplasia, intrahepatic PSSs and those without portal venous anomalies (P<0.001). All dogs and cats with a PV/Ao ratio of < or = 0.65 had an extrahepatic PSS or idiopathic noncirrhotic portal hypertension. Dogs and cats with PV/Ao and PV/CVC ratios of > or = 0.8 and > or = 0.75, respectively, did not have an extrahepatic PSS. Reduced or reversed portal flow was seen in four of four patients with multiple acquired PSSs secondary to portal hypertension. The presence of turbulence in the caudal vena cava of dogs had positive and negative predictive values of 91% and 84%, respectively, for the presence of any PSS terminating into that vein.

Diagnostic testing in patients with congenital heart disease is usually performed supine and at rest, conditions not representative of their typical hemodynamics. Upright exercise measurements of blood flow may prove valuable in the assessment of these patients, but data in normal subjects are first required. With the use of a 0.5-T open magnet, a magnetic resonance-compatible exercise cycle, and cine phase-contrast techniques, time-dependent blood flow velocities were measured in the right (RPA), left (LPA), and main (MPA) pulmonary arteries and superior (SVC) and inferior (IVC) vena cavae of 10 healthy 10- to 14-yr-old subjects. Measurements were made at seated rest and during upright cycling exercise (150% resting heart rate). Mean blood flow (l/min) and reverse flow index were computed from the velocity data. With exercise, RPA and LPA mean flow increased 2.0 +/- 0.5 to 3.7 +/- 0.7 (P < 0.05) and 1.6 +/- 0.4 to 2.9 +/- 0.8 (P < 0.05), respectively. Pulmonary reverse flow index (rest vs. exercise) decreased with exercise as follows: MPA: 0.014 +/- 0.012 vs. 0.006 +/- 0.006 [P = not significant (NS)], RPA: 0.005 +/- 0.004 vs. 0.000 +/- 0.000 (P < 0.05), and LPA: 0.041 +/- 0.019 vs. 0.014 +/- 0.016 (P < 0.05). SVC and IVC flow increased from 1.5 +/- 0.2 to 1.9 +/- 0.6 (P = NS) and 1.6 +/- 0.4 to 4.9 +/- 1.3 (P < 0.05), respectively. A 56/44% RPA/LPA flow distribution at both rest and during exercise suggests blood flow distribution is dominated by distal pulmonary resistance. Reverse flow in the MPA appears to originate solely from the LPA while the RPA is in relative isolation. During seated rest, the SVC-to-IVC venous return ratio is 50/50%. With light/moderate cycling exercise, IVC flow increases by threefold, whereas SVC remains essentially constant.

Nitroglycerin (glyceryl trinitrate, GTN) relaxes blood vessels primarily via activation of the soluble guanylyl cyclase (sGC)/cGMP/cGMP-dependent protein kinase (cGK-I) pathway. Although the precise mechanism of sGC activation by GTN in the vascular wall is unknown, the mediatory role of nitric oxide (NO) has been postulated. We tested the GTN/NO hypothesis in different types of isolated rat and rabbit blood vessels using two novel approaches: (1) EPR spin trapping using colloid Fe(DETC)2 and (2) analysis of cGK-I-dependent phosphorylation of the vasodilator-stimulated phosphoprotein at Ser239 (P-VASP). For comparison, another organic nitrate, isosorbide dinitrate (ISDN), and endothelium-dependent vasodilator, calcium ionophore A23187, were tested. We found a marked discrepancy between GTN's strong vasoactivity (vasodilation and augmentation of P-VASP) and its poor NO donor properties. In aortas precontracted with phenylephrine, GTN, ISDN, and A23187 induced nearly full relaxations (>80%) and doubling of vascular P-VASP content at concentrations of 100 nmol/L, 100 micromol/L, and 1 micromol/L, respectively. GTN applied in vasorelaxant concentrations (10 to 1000 nmol/L) did not significantly increase the basal vascular NO production, in contrast to ISDN and A23187. The absence of GTN-derived NO was confirmed in rabbit vena cava and renal artery. A significant increase in vascular NO formation was observed only at suprapharmacological GTN concentrations (>10 micromol/L). The concentration dependency of NO formation from GTN was comparable to that of ISDN, although the latter exhibits 100-folds lower vasorelaxant potency. We conclude that GTN activates the sGC/cGMP/cGK-I pathway and induces vasorelaxation without intermediacy of the free radical NO. The full text of this article is available online at http://www.circresaha.org.

Tolerance to positive vertical acceleration (Gz) gravitational stress is reduced when positive Gz stress is preceded by exposure to hypogravity, which is called the "push-pull effect." The purpose of this study was to test the hypothesis that baroreceptor reflexes contribute to the push-pull effect by augmenting the magnitude of simulated hypogravity and thereby augmenting the stimulus to the baroreceptors. We used eye-level blood pressure as a measure of the effectiveness of the blood pressure regulatory systems. The approach was to augment the magnitude of the carotid hypertension (and the hindbody hypotension) when hypogravity was simulated by head-down tilt by mechanically occluding the terminal aorta and the inferior vena cava. Sixteen anesthetized Sprague-Dawley rats were instrumented with a carotid artery catheter and a pneumatic vascular occluder cuff surrounding the terminal aorta and inferior vena cava. Animals were restrained and subjected to a control gravitational (G) profile that consisted of rotation from 0 Gz to 90 degrees head-up tilt (+1 Gz) for 10 s and a push-pull G profile consisting of rotation from 0 Gz to 90 degrees head-down tilt (-1 Gz) for 2 s immediately preceding 10 s of +1 Gz stress. An augmented push-pull G profile consisted of terminal aortic vascular occlusion during 2 s of head-down tilt followed by 10 s of +1 Gz stress. After the onset of head-up tilt, the magnitude of the fall in eye-level blood pressure from baseline was -20 +/- 1.3, -23 +/- 0.7, and -28 +/- 1.6 mmHg for the control, push-pull, and augmented push-pull conditions, respectively, with all three pairwise comparisons achieving statistically significant differences (P < 0.01). Thus augmentation of negative Gz stress with vascular occlusion increased the magnitude of the push-pull effect in anesthetized rats subjected to tilting.

We have used incremental stress-strain curves to study the mechanical behavior of porcine aorta, carotid artery, and vena cava. Elastic and viscous stress-strain curves are composed of low and high strain regions that are approximately linear. Analysis of the low strain behavior is consistent with previous studies that suggest that the behavior is dominated by the behavior of elastic fibers, and that the collagen and elastic fibers are in parallel networks. At high strain, the behavior is different than that of skin where it is dominated by the behavior of the collagen fibers. The high strain behavior is consistent with a series arrangement of the collagen and smooth muscle; however, the arrangement of smooth muscle and collagen may be different in aorta than in the other vessels studied. It is concluded that the mechanical behavior of the vessel wall differs from the behavior of other extracellular matrices that do not contain smooth muscle. Our results indicate that at least some of the collagen fibrils in the media are in series with smooth muscle cells and this collagen-smooth muscle network is in parallel with parallel networks of collagen and elastic tissue in aorta, carotid artery, and vena cava. It is concluded that the series arrangement of collagen and smooth muscle may be important in mechanochemical transduction in vessel walls and that the exact quantity and arrangement of these components may differ in different vessels.

Background: The use of animals in medical research raises both ethical and economic concerns. Validated in vitro models allow extensive device testing prior to in vivo studies which limits the numbers of animals required to reach conclusions regarding efficacy and safety., Materials and Methods: In vitro studies were conducted in a vena caval simulator (ECU) to evaluate characteristics of filter performance: ability to capture emboli, resistance to vertical movement from lateral forces, resistance to vertical movement from mass impact, and ability to maintain caval flow. These tests are used to select candidate filters for in vivo studies. In vivo filter studies are conducted in an ovine model with filters placed into the vena cava from a jugular or femoral vein approach. At intervals, the animals are sacrificed and both cava and device are evaluated for thrombogenicity, thrombus resolution, and mechanical integrity. Radiographs, intravascular ultrasound, and histology are used to determine outcome., Results: During the 6-year period from 1993 to 1999, 11 vena caval filter types were evaluated. In each case, it was possible to select a single prototype for in vivo study on the basis of four tests. An investigational device was developed that was comparable to the marketed devices with respect to clot capture (P = 0.001), superior to the Greenfield in resistance to movement (P = 0.001), and superior to the VenaTech and Simon Nitinol relative to volume loading (P = 0.01). Problems with metal fatigue prevented clinical development., Conclusion: An integrative system of in vitro and in vivo studies allows efficient evaluation of IVC filters and identifies design characteristics associated with clinical functioning. Evaluation over time is essential to determine safety as well as efficacy.

The type and magnitude of changes in blood flow in the anterior (cranial) and posterior (caudal) caval veins and shifts in the mean right atrial pressure induced by catecholamines (epinephrine and norepinephrine) were studied in acute experiments on cats. It was found that irrespective of right atrial pressure shifts, the increase in the blood flow in the anterior vena cava was more pronounced than in the posterior vena cava and was determined by blood redistribution due to more pronounced increase in vascular resistance in the abdominal aorta basin.

Unlabelled: Hepatic vascular exclusion (HVE) combines portal triad clamping and occlusion of the inferior vena cava. Although HVE has been performed for major liver resections during the last 2 decades, little is known about the mechanisms that explain its satisfactory hemodynamic tolerance. Consequently, we performed a comprehensive study of both hemodynamic and hormone responses to HVE. Twenty-two patients who underwent liver resection for secondary tumors developed in noncirrhotic livers were prospectively studied. Heart rate, arterial blood pressure, pulmonary artery pressure, mixed venous saturation, cardiac output, and left ventricular dimensions determined by transesophageal echocardiography were monitored in HVE patients. Blood concentrations of arginine vasopressin (AVP), epinephrine, norepinephrine, dopamine, and atrial natriuretic peptide and plasma renin activity (PRA) were measured before clamping; 5, 15, and 30 min after clamping; and 15 min after unclamping. Hemodynamic response to HVE was characterized by a significant (P < 0.05) decrease in left ventricular dimensions, fractional area change, and pulmonary artery pressure. We also observed a marked decrease in cardiac output (50%) and an increase in heart rate and systemic vascular resistance. After unclamping, there was peripheral vasodilation, assessed by a significant decrease in systemic vascular resistance from the preclamping value to unclamping. An acute and sustained increase in AVP and norepinephrine that returned to baseline after unclamping and the absence of modification in PRA concentrations were noted. The marked decrease in venous return that characterizes HVE is compensated for by an increase in vascular resistance secondary to an important activation of the AVP and sympathetic systems. The PRA system does not play an important role in maintaining arterial blood pressure during HVE., Implications: Hemodynamic and hormonal responses to the acute interruption of caval venous return to the heart were investigated in patients undergoing liver resection with hepatic vascular exclusion. A compensatory role for arginine vasopressin and sympathetic systems that provoked increased vascular resistance was demonstrated.

Phosphodiesterase (PDE) type 4 is the predominant PDE isozyme in polymorphonuclear leukocytes (PMN) and plays a key role in the regulation of PMN activation. The aim of this study was to examine the effect of a PDE type 4 inhibitor, rolipram, on the functional changes and the retention of PMN in the lung. In vitro, F-actin content and L-selectin and CD11b expression of PMN stimulated by N-formyl-Met-Leu-Phe were measured by flow cytometry. PMN deformability was evaluated using silicon microchannels. Rolipram reduced the increase of F-actin and CD11b but did not change the decrease of L-selectin. Rolipram inhibited the increase of the transit time of PMN through the microchannel. We evaluated the retention of PMN in the lung in vivo by infusing labeled blood into the vena cava and examining the recovery into aortic root samples in rabbits. Rolipram inhibited the retention of stimulated PMN in the lung. In conclusion, a PDE type 4 inhibitor, rolipram, reduces the retention of PMN in the lung by reducing deformability change and CD11b upregulation of PMN.

Phase-contrast magnetic resonance (MR) imaging is a well-known but undervalued method of obtaining quantitative information on blood flow. Applications of this technique in cardiovascular MR imaging are expanding. According to the sequences available, phase-contrast measurement can be performed in a breath hold or during normal respiration. Prospective as well as retrospective gating techniques can be used. Common errors in phase-contrast imaging include mismatched encoding velocity, deviation of the imaging plane, inadequate temporal resolution, inadequate spatial resolution, accelerated flow and spatial misregistration, and phase offset errors. Flow measurements are most precise if the imaging plane is perpendicular to the vessel of interest and flow encoding is set to through-plane flow. The sequence should be repeated at least once, with a high encoding velocity used initially. If peak velocity has to be estimated, flow measurement is repeated with an adapted encoding velocity. The overall error of a phase-contrast flow measurement comprises errors during prescription as well as errors that occur during image analysis of the flow data. With phase-contrast imaging, the overall error in flow measurement can be reduced to less than 10%, an acceptable level of error for routine clinical use., (Copyright RSNA, 2002)

Introduction: Atrial fibrillation is the most common cardiac arrhythmia. In ablation procedures, identification of the reentrant pathways is vital. This has proven difficult because of the complex morphology of the atria. The purpose of this study was to ascertain the role of specific anatomic structures on reentry induction and maintenance., Method and Results: A computationally efficient, morphologically realistic, computer model of the atria was developed that incorporates its major structural features, including discrete electrical connections between the right and left atria, physiologic fiber orientation in three dimensions, muscle structures representing the crista terminalis (CT) and pectinate muscles, and openings for the veins and AV valves. Reentries were induced near the venous openings in the left and right atria, the mouth of the coronary sinus, and the free wall of the right atrium. The roles of certain muscular structures were ascertained by selectively removing the structures and observing how the propagation of activity was affected., Conclusion: (1) The muscular sheath of the coronary sinus acts as a pathway for a reentrant circuit and stabilizes any circuits that utilize the isthmus near the inferior vena cava. (2) Poor trans-CT coupling serves to stabilize flutter circuits. (3) Wall thickness is an important factor in the propagation of electrical activity, especially in the left atrium. (4) The openings of the inferior and superior venae cavae form natural anatomic anchors that make reentry easier to initiate by allowing for smaller ectopic beats to induce reentry.

Objective: To investigate whether a decrease in cardiac output of >or=50% after vena cava clamping is associated with an increase in perioperative morbidity or mortality in patients undergoing orthotopic liver transplantation without venovenous bypass., Design: Retrospective, clinical study., Participants: Patients undergoing elective orthotopic liver transplantation without venovenous bypass (n = 172)., Interventions: None., Measurements and Main Results: In 82 patients (group 1), the decrease in cardiac output after vena cava clamping was >or=50%; in 90 patients (group 2), the decrease was <50%. Hemodynamics during surgery and perioperative morbidity and mortality were compared between group 1 and group 2 patients. Mean arterial pressure during the anhepatic phase was not significantly different between groups, but cardiac output and mixed venous oxygen saturation were significantly lower in group 1 patients. Perioperative mortality, need for postoperative renal replacement therapy, postoperative serum creatinine levels, and graft function were not different between groups., Conclusion: A >50% reduction in cardiac output after vena cava clamping is not associated with an increase in perioperative morbidity and mortality when compared with patients with a less pronounced reduction in cardiac output. These results question the common practice of basing the indication for venovenous bypass during the anhepatic phase on a reduction in cardiac output of >50% after a trial of vena cava clamping., (Copyright 2001 by W.B. Saunders Company.)

A line of block between the vena cava and the crista terminalis (CT) region is important for atrial flutter (AFL), but whether it is fixed or functional is controversial. To test the hypothesis that conduction across the CT normally occurs, but when block occurs in this region it is functional, we analyzed atrial activation during right and left atrial pacing (cycle lengths of 500--130 ms), AFL, and atrial fibrillation in 15 dogs with sterile pericarditis and 7 normal dogs. Electrograms from 396 right, left, and septal atrial sites were simultaneously recorded. Activation across the CT occurred during atrial pacing, AFL, and atrial fibrillation. Activation wave fronts from the right to the left atrium and vice versa traveled over several routes, including Bachmann's bundle and inferior to the inferior vena cava, as well as across the CT. In these models, there is no fixed conduction block across the CT, and when block in the CT region occurs, as during AFL, it is functional.

Discrete stretch of the caval-atrial junction decreases the activity of vasopressin-secreting neurons in the supraoptic nucleus (SON). The perinuclear zone (PNZ) of the SON is necessary for inhibition of vasopressin neurons following an increase in blood pressure. To determine whether the PNZ is necessary for cardiopulmonary regulation of vasopressin neurons, male rats received three unilateral injections of the excitotoxin ibotenic acid (n = 9) or phosphate-buffered saline vehicle (n = 10) into the PNZ. Extracellular activity of antidromically identified phasic vasopressin neurons in the ipsilateral SON was recorded. Of the 26 neurons recorded from vehicle-injected rats 26 were inhibited by an increase in blood pressure and 22 of those neurons were sensitive to caval-atrial distension. Of the neurons recorded from PNZ-lesion rats, only 12 of 29 were inhibited by an increase in blood pressure (P < 0.05), and only 11 neurons were sensitive to caval-atrial stretch (P < 0.05). Functional lesion of the PNZ significantly attenuates both arterial and cardiopulmonary baroreceptor-mediated inhibition of supraoptic vasopressin neurons, suggesting that the PNZ is a necessary component of both pathways.

A proper measurement of splanchnic metabolism involves sampling blood from the hepatic vein without backflow contamination of blood from the caval vein. We have investigated the potential problem of caval backflow in human volunteers with an indwelling hepatic vein catheter by sampling blood with different amounts of suction on the syringe (ie, sampling speeds). We also investigated the potential problem in pigs in which a balloon catheter was inserted in the hepatic vein. Pure hepatic vein samples were obtained with the balloon inflated and compared with samples obtained from the same catheter in the conventional manner. In overnight fasted humans, drawing blood samples from the hepatic vein with minimal suction ("slow" drawing) resulted in glucose values 9.6% higher than drawing the samples with greater suction ("fast" drawing). The calculated arterial-venous balance across the splanchnic bed was 4.8 times greater with "slow" blood drawing as compared with "fast" drawing. Values obtained from the pigs showed no concentration differences between pure hepatic vein samples and "slow" drawing from the hepatic vein. The current study indicates that it is possible to obtain a "true" hepatic vein sample, but backflow from the caval vein is a potential pitfall that can have a physiologically significant impact on calculated balance data.