Development of systemic arterial mechanical properties from infancy to adulthood interpreted by four-element windkessel models.

Aortic impedance data of infants, children and adults (age range 0.8-54 yr), previously reported by others, were interpreted by means of three alternative four-element windkessel models: W4P, W4S, and IVW. The W4P and W4S are derived from the three-element windkessel (W3) by connecting an inertance (L) in parallel or in series, respectively, with the aortic characteristic resistance (Rc). In the IVW, L is connected in series with a viscoelastic windkessel (VW). The W4S and IVW (same input impedance) fit the data best. The W4S, however, suffers from the assumption that Rc is part of total peripheral resistance (Rp). The IVW model offers a new paradigm for interpretation of resistive properties in terms of viscous (Rd) properties of vessel wall motion, distinguished from Rp. Results indicated that rapid reduction of Rd/Rp during early development is functional to modulation of decay time constant (taud) of pressure in diastole, such that normalization over heart period (taud/T) is independent of body size. Estimates of total arterial compliance (C) vs. age were fitted by a bell-shaped curve with a maximum at 33 yr. With body weight (BW) factored out by normalization, the C/BW data scattered about a bell-shaped curve centered at 66 mmHg. Inertance was significantly higher in pediatric patients than in adults, in accordance with a lower cross-sectional area of the vasculature, commensurate to a lower aortic flow. Changes of arterial properties appear functional to control the ratio of pulsatile power to active power and keep arterial efficiency as high as 97% in infants and children.     

Quantification of right ventricular afterload in patients with and without pulmonary hypertension

Right ventricular (RV) afterload is commonly defined as pulmonary vascular resistance, but this does not reflect the afterload to pulsatile flow. The purpose of this study was to quantify RV afterload more completely in patients with and without pulmonary hypertension (PH) using a three-element windkessel model. The model consists of peripheral resistance (R), pulmonary arterial compliance (C), and characteristic impedance (Z). Using pulmonary artery pressure from right-heart catheterization and pulmonary artery flow from MRI velocity quantification, we estimated the windkessel parameters in patients with chronic thromboembolic PH (CTEPH; n = 10) and idiopathic pulmonary arterial hypertension (IPAH; n = 9). Patients suspected of PH but in whom PH was not found served as controls (NONPH; n = 10). R and Z were significantly lower and C significantly higher in the NONPH group than in both the CTEPH and IPAH groups (P < 0.001). R and Z were significantly lower in the CTEPH group than in the IPAH group (P < 0.05). The parameters R and C of all patients obeyed the relationship C = 0.75/R (R(2) = 0.77), equivalent to a similar RC time in all patients. Mean pulmonary artery pressure P and C fitted well to C = 69.7/P (i.e., similar pressure dependence in all patients). Our results show that differences in RV afterload among groups with different forms of PH can be quantified with a windkessel model. Furthermore, the data suggest that the RC time and the elastic properties of the large pulmonary arteries remain unchanged in PH.     

Measurement of total pulmonary arterial compliance using invasive pressure monitoring and MR flow quantification during MR-guided cardiac catheterization

Pulmonary hypertensive disease is assessed by quantification of pulmonary vascular resistance. Pulmonary total arterial compliance is also an indicator of pulmonary hypertensive disease. However, because of difficulties in measuring compliance, it is rarely used. We describe a method of measuring pulmonary arterial compliance utilizing magnetic resonance (MR) flow data and invasive pressure measurements. Seventeen patients with suspected pulmonary hypertension or congenital heart disease requiring preoperative assessment underwent MR-guided cardiac catheterization. Invasive manometry was used to measure pulmonary arterial pressure, and phase-contrast MR was used to measure flow at baseline and at 20 ppm nitric oxide (NO). Total arterial compliance was calculated using the pulse pressure method (parameter optimization of the 2-element windkessel model) and the ratio of stroke volume to pulse pressure. There was good agreement between the two estimates of compliance (r = 0.98, P < 0.001). However, there was a systematic bias between the ratio of stroke volume to pulse pressure and the pulse pressure method (bias = 61%, upper level of agreement = 84%, lower level of agreement = 38%). In response to 20 ppm NO, there was a statistically significant fall in resistance, systolic pressure, and pulse pressure. In seven patients, total arterial compliance increased >10% in response to 20 ppm NO. As a population, the increase did not reach statistical significance. There was an inverse relation between compliance and resistance (r = 0.89, P < 0.001) and between compliance and mean pulmonary arterial pressure (r = 0.72, P < 0.001). We have demonstrated the feasibility of quantifying total arterial compliance using an MR method.     

Systemic venous circulation. Waves propagating on a windkessel: relation of arterial and venous windkessels to systemic vascular resistance

Compared with arterial hemodynamics, there has been relatively little study of venous hemodynamics. We propose that the venous system behaves just like the arterial system: waves propagate on a time-varying reservoir, the windkessel, which functions as the reverse of the arterial windkessel. During later diastole, pressure increases exponentially to approach an asymptotic value as inflow continues in the absence of outflow. Our study in eight open-chest dogs showed that windkessel-related arterial resistance was approximately 62% of total systemic vascular resistance, whereas windkessel-related venous resistance was only approximately 7%. Total venous compliance was found to be 21 times larger than arterial compliance (n = 3). Inferior vena caval compliance (0.32 +/- 0.015 ml x mmHg(-1) x kg(-1); mean +/- SE) was approximately 14 times the aortic compliance (0.023 +/- 0.002 ml x mmHg(-1) x kg(-1); n = 8). Despite greater venous compliance, the variation in venous windkessel volume (i.e., compliance x windkessel pulse pressure; 7.8 +/- 1.1 ml) was only approximately 32% of the variation in aortic windkessel volume (24.3 +/- 2.9 ml) because of the larger arterial pressure variation. In addition, and contrary to previous understanding, waves generated by the right heart propagated upstream as far as the femoral vein, but excellent proportionality between the excess pressure and venous outflow suggests that no reflected waves returned to the right atrium. Thus the venous windkessel model not only successfully accounts for variations in the venous pressure and flow waveforms but also, in combination with the arterial windkessel, provides a coherent view of the systemic circulation.     

Estimation of mean molecular weight of Enterobacteriaceae lipopolysaccharides using gas chromatography for determination of fatty acids

In the paper, we propose a method for estimation of the mean molecular weight of lipopolysaccharide, which is important for accuracy of endotoxin activity investigation. In our study, it was assumed that lipid A portion in Enterobacterial lipopolysaccharide is substituted by four 3-hydroxytetradecanoic acid residues. Lipopolysaccharides of S, Ra, Rc and Re chemotypes being laboratory preparations as well as purchased from Sigma were investigated. Fatty acids were determined by of gas chromatography as methyl esters according to the procedure described by Wollenweber and Rietschel. Mean molecular weight was calculated by the formula: MMW = [formula: see text]. A high agreement between the estimated and the theoretical molecular weight values was demonstrated in the case of Salmonella minnesota R595 (Re) LPS preparation. As expected, LPS heterogeneity increase together with enlargement of polysaccharide chain length which is visible in electrophoregrams also. Except for LPS mean molecular weight estimation, the method allows its detection in various preparations and samples, distinguishing of R and S LPS forms as well as the determination of mean length of O-specific chain in lipopolysaccharides which structures are known.     

Direct injury to the bronchial vasculature in anesthetized sheep.

Injury to the bronchial vasculature may contribute to liquid and solute leakage into the lung during noncardiac pulmonary edema. The purpose of this study was to measure changes in hemodynamics, pulmonary mechanics, extravascular lung water, and lung morphometry after selectively injuring the bronchial vasculature in anesthetized sheep. In two groups of seven sheep, we injected oleic acid (0.1 ml/kg) or normal saline directly into the bronchoesophageal artery. We measured systemic and pulmonary arterial pressures, cardiac output, oxygen saturation, pulmonary resistance and compliance, and lung volumes before and 1 and 4 h after injection. The lungs were removed for measurement of extravascular water, histology, and morphometry. Four hours after injection of oleic acid, cardiac output decreased but pulmonary arterial pressure did not change. In addition, pulmonary resistance increased and dynamic compliance and vital capacity decreased. Extravascular lung water was slightly but significantly greater in the oleic acid group. Histological examination showed interstitial edema and leukocytes in airway walls and sloughing of bronchial epithelium but little or no alveolar edema. Morphometric analysis showed significant thickening of airway walls. We conclude that direct injury to the bronchial vasculature increases lung resistance, decreases dynamic compliance, and increases extravascular lung water by the accumulation of an inflammatory infiltrate in airway walls.     

A fractal continuum model of the pulmonary arterial tree.

The extant morphometric data from the intrapulmonary arteries of dog, human, and cat lungs produce graphs of the log of the vessel number, (N) or length (l) in each level vs. the log of the mean diameter (D) in each level that are sufficiently linear to suggest that a scale-independent self-similar or fractal structure may underlie the observed relationships. These data can be correlated by the following formulas: Nj = a1Dj-beta 1, and lj = a2Dj beta 2, where j denotes the level (order or generation) number measured from the largest vessel at the entrance to the arterial tree to the smallest vessel at the entrance to the capillary bed. With the hemodynamic resistance (R) represented by Rj = 128 microliterj/(Nj pi Dj4) and the vascular volume (Q) by Qj = Nj pi Dj2lj/4, the continuous cumulative distribution of vascular resistance (Rcum) vs. cumulative vascular volume (Qcum) (where Rcum and Qcum represent the total resistance or volume, respectively, upstream from the jth level) can be calculated from [formula: see text] where r = Dj/Dj+1 is a constant independent of j. Analogous equations are developed for the inertance and compliance distributions, providing simple formulas to represent the hemodynamic consequences of the pulmonary arterial tree structure.     

Effects of static and fluctuating airway pressure on intact pulmonary circulation

The direct effects on the pulmonary circulation of static and fluctuation airway pressure were compared in intact close-chest infant lambs with reactive pulmonary vasculature under alpha-chloralose anesthesia. A preparation developed to permit independent ventilation of right and left lungs and independent measurement of right and left lung blood flow was employed to separate direct from indirect effects of unilateral airway pressure changes on pulmonary vascular resistance (PVR). Both static and fluctuating unilateral airway pressure interventions directly elevated ipsilateral PVR. For purposes of comparison mean alveolar pressure (PA) was estimated for both static and fluctuating trials. Fluctuating interventions increased PVR more than did static trials at comparable levels of PA. Substantially less PA was needed to double ipsilateral PVR by fluctuating than by static interventions (16 vs. 26 mmHg, respectively). These data indicate that, in the intact animal with reactive pulmonary vasculature, both PA and the waveform of airway pressure applied can influence PVR.     

Tone-dependent responses to endothelin in the isolated perfused fetal sheep pulmonary circulation in situ

Pulmonary vascular responses to endothelin (ET-1), a peptide derived from endothelial cells in culture, were investigated in the ovine fetus delivered by cesarean section from chloralose-anesthetized ewes with intact umbilical circulation. Circulation to the lower left lobe of the fetal lung was isolated in situ and perfused at constant flow with blood withdrawn from the inferior vena cava. Injection of graded doses of ET-1 into the left pulmonary artery decreased pulmonary arterial perfusion pressure in a dose-related manner. At doses of 100, 300, and 1,000 ng, pulmonary vascular resistance per kilogram body weight (PVR/kg) was decreased 30, 40, and 42%, respectively. However, when fetuses were ventilated with 100% oxygen, 100- and 300-ng doses of ET-1 decreased PVR/kg by 5 and 9%, respectively. In contrast, injection of 1,000 ng of ET-1 resulted in a reversal of the response, and PVR/kg was increased by 70%. Ventilation of the right lung alone resulted in a similar reversal of the vasodilator response to 1,000 ng of ET-1, and a 138% increase in PVR/kg was recorded. These studies demonstrate for the first time that ET-1 has vasodilator activity in the normally high-tone ovine fetal pulmonary circulation. In addition, these results show that ET-1 has vasoconstrictor activity in the newly ventilated low-tone pulmonary vasculature. The present data indicate the pulmonary vascular responses to ET-1 are tone dependent in the ovine fetal pulmonary circulation.     

Validation of an automated determination of pulmonary resistance by electrical subtraction.

An analog computer to determine dynamic pulmonary compliance (C) and pulmonary resistance (R) on a breath-by-breath basis was tested in guinea pigs and dogs. C was determined by dividing volume by transpulmonary pressure at instants of zero flow. R was determined by the method of electrical subtraction at predetermined flows. In both species the computer outputs and the results of direct analysis were in close agreement. In guinea pigs, the device reliably followed the rapid three- to fourfold changes in C and R resulting from histamine infusion. In unanesthetized dogs, the dispersion and mean values of C and R were similar by the two methods.     

Effects of acute Rho kinase inhibition on chronic hypoxia-induced changes in proximal and distal pulmonary arterial structure and function

Hypoxic pulmonary hypertension (HPH) is initially a disease of the small pulmonary arteries. Its severity is usually quantified by pulmonary vascular resistance (PVR). Acute Rho kinase inhibition has been found to reduce PVR toward control values in animal models, suggesting that persistent pulmonary vasoconstriction is the dominant mechanism for increased PVR. However, HPH may also cause proximal arterial changes, which are relevant to right ventricular (RV) afterload. RV afterload can be quantified by pulmonary vascular impedance, which is obtained via spectral analysis of pulsatile pressure-flow relationships. To determine the effects of HPH independent of persistent pulmonary vasoconstriction in proximal and distal arteries, we quantified pulsatile pressure-flow relationships before and after acute Rho kinase inhibition and measured pulmonary arterial structure with microcomputed tomography. In control lungs, Rho kinase inhibition decreased 0 Hz impedance (Z?), which is equivalent to PVR, from 2.1 ± 0.4 to 1.5 ± 0.2 mmHg·min·ml?1 (P < 0.05) and tended to increase characteristic impedance (Z(C)) from 0.21 ± 0.01 to 0.22 ± 0.01 mmHg·min·ml?1. In HPH lungs, Rho kinase inhibition decreased Z? (P < 0.05) without affecting Z(C). Microcomputed tomography measurements performed on lungs after acute Rho kinase inhibition demonstrated that HPH significantly decreased the unstressed diameter of the main pulmonary artery (760 ± 60 vs. 650 ± 80 μm; P < 0.05), decreased right pulmonary artery compliance, and reduced the frequency of arteries of diameter 50-100 μm (both P < 0.05). These results demonstrate that acute Rho kinase inhibition reverses many but not all HPH-induced changes in distal pulmonary arteries but does not affect HPH-induced changes in the conduit arteries that impact RV afterload.     

A new parasitological index for the estimation of peculiarities of the relationships between parasite and its host, and biotope of the host

A new parasitological index (hostal-topical index) for the estimation of the degree of ectoparasite's relationship with its host and biotope of the host is proposed: [formula: see text], where [formula: see text]--hostal-topical index; n--amount of ectoparasites of the given species on the given host species in the biotope; N--amount of ectoparasites of all species from the given taxonomic group on the given host species in the biotope; n1--amount of hosts of the given species in the biotope; N1--amount of hosts of all species from the given taxonomic group in the biotope; n2--amount of ectoparasites of the given species in the biotope; N2--amount of ectoparasites of all species from the given taxonomic group in the biotope. Values [formula: see text] < 0.1 indicate that there is a distinct relationship with the biotope in spite of the host; values fallen into the range 0.1 < [formula: see text] < 0.5 indicate a moderate relationship with the biotope through the host; values [formula: see text] > 0.5 indicate a significant relationship with the host. By means of this index we have analyzed peculiarity of several parasitic species of fleas and gamasid mites to their hosts, biotopes, and biotope through the host. As it was found on the materials from different native zones and subzones of the Omsk Region (Western Siberia, Russia), values of the hostal-topical index for polyhostal parasitic species are lesser than those for oligohostal species. Values of this index can be different for the same species in the different native zones and subzones as well as in the different biotopes of the same native zone (subzone).     

Structure of the O-specific polysaccharide chain of Yersinia aldovae lipopolysaccharide]

O-specific polysaccharide has been isolated on mild hydrolysis of lipopolysaccharide from Yersinia aldovae and shown to consist of 2-acetamido-2-deoxy-D-glucose, D-glucose, 2-acetamido-2-deoxy-D-galactose, and 3,6-dideoxy-3- [(R)-3-hydroxybutyramido]-D-galactose in molar ratio 2:2:1:1. Acid hydrolysis, methylation, solvolysis with anhydrous hydrogen fluoride, 1H and 13C NMR studies indicated the polysaccharide to be composed of hexasaccharide repeating units of the following structure: [formula see text].     

Population structure and genetic heterogeneity in the Upper Markham Valley of New Guinea.

An analysis is presented of the standardized Wahlund's variances (f) in gene frequencies of the ABO, Rh and MNS blood group systems among 19 villages of the Atsera isolate of the upper Markham Valley, Papua New Guinea. In the past, there has been some disagreement over the relative importance of population structure and natural selection in the determination of these variances. The Lewontin-Krakauer test is presented as a means of resolving this disagreement. According to this test, selectively neutral variation in gene frequencies should generate essentially homogeneous values of f for all loci, a homogeneity which can be tested by comparing the value of (formula: see text) to a theoretical (formula: see text) expected when variations in (formula: see text) are due solely to sampling error. The observed value of (formula: see text) for the Atsera isolate is 2.9 x 10(-5), which is not significantly different from the expected values that range from 1.23 x 10(-5) to 2.46 x 10(-5) depending on the constant used in calculating (formula: see text). Therefore it appears that nonselective aspects of population structure such as genetic drift and intervillage migration are responsible for the recorded genetic variation in this isolate.     

Effects of blood flow on lung ACE kinetics: evidence for microvascular recruitment.

The parameter Amax/Km (product of reactant enzyme mass in perfused microvessels and the constant kcat/Km), calculated from in vivo assays of pulmonary endothelial ectoenzymes (e.g., angiotensin-converting enzyme, ACE), can provide estimates of the perfused pulmonary microvascular surface area (PMSA) in the absence of enzyme dysfunction. We examined the relationship between PMSA and pulmonary blood flow (Qb) in anesthetized rabbits placed on total heart bypass, using [3H]benzoyl-Phe-Ala-Pro (BPAP) as the ACE substrate. When Qb was increased from 250 to 1,100 ml/min, at zone 3 conditions, pulmonary arterial pressure increased, pulmonary vascular resistance (PVR) decreased, and Amax/Km increased linearly, reflecting increasing PMSA. When only the left lung was perfused, increasing Qb from 250 to 636 +/- 17 ml/min (the last value representing fully recruited and/or distended vascular bed), PVR decreased, while Amax/Km increased. When Qb was further increased to 791 +/- 44 ml/min, both PVR and Amax/Km remained unchanged, confirming the lack of additional changes in PMSA. We conclude that Amax/Km provides a sensitive indication of PMSA, because it 1) increases with increasing Qb and decreasing PVR, 2) reaches a maximum at Qb values that correspond to the minimal values in PVR, and 3) like PVR, did not change with further increases in Qb. Compared with predicted changes in PMSA produced by either microvascular recruitment alone or distension alone, our data indicate that recruitment is a larger contributor to the observed increase in PMSA.     

Increased pulmonary vascular resistance and defective pulmonary artery filling in caveolin-1-/- mice

Caveolin-1, the structural and signaling protein of caveolae, is an important negative regulator of endothelial nitric oxide synthase (eNOS). We observed that mice lacking caveolin-1 (Cav1(-/-)) had twofold increased plasma NO levels but developed pulmonary hypertension. We measured pulmonary vascular resistance (PVR) and assessed alterations in small pulmonary arteries to determine the basis of the hypertension. PVR was 46% greater in Cav1(-/-) mice than wild-type (WT), and increased PVR in Cav1(-/-) mice was attributed to precapillary sites. Treatment with NG-nitro-l-arginine methyl ester (l-NAME) to inhibit NOS activity raised PVR by 42% in WT but 82% in Cav1(-/-) mice, indicating greater NO-mediated pulmonary vasodilation in Cav1(-/-) mice compared with WT. Pulmonary vasculature of Cav1(-/-) mice was also less reactive to the vasoconstrictor thromboxane A2 mimetic (U-46619) compared with WT. We observed redistribution of type I collagen and expression of smooth muscle alpha-actin in lung parenchyma of Cav1(-/-) mice compared with WT suggestive of vascular remodeling. Fluorescent agarose casting also showed markedly decreased density of pulmonary arteries and artery filling defects in Cav1(-/-) mice. Scanning electron microscopy showed severely distorted and tortuous pulmonary precapillary vessels. Thus caveolin-1 null mice have elevated PVR that is attributed to remodeling of pulmonary precapillary vessels. The elevated basal plasma NO level in Cav1(-/-) mice compensates partly for the vascular structural abnormalities by promoting pulmonary vasodilation.     

Distribution of pulmonary vascular pressure as a function of perinatal age in lambs

The distribution of pulmonary vascular resistance (PVR) with respect to compliance was determined using vascular occlusion in isolated lungs from lambs at five ages, from 2 wk before birth to 1 mo of age. The major change in PVR occurred in the pressure gradient across the middle compliant region (delta Pm), which dropped sharply at birth, remained low for 2 wk, and increased at 1 mo. Pulmonary vasoreactivity also varied with ages. Lungs at 0-4 days did not respond to hypoxia and responded poorly to prostaglandin F2 alpha (PGF2 alpha). In contrast, lungs at 13-33 days had significant increases in delta Pm and the gradient across relatively indistensible arterial vessels during hypoxia and increases in all gradients with PGF2 alpha. Ventilation of fetal lungs reduced PVR, mainly because of a 50% reduction in delta Pm. Our results demonstrate that the magnitude and distribution of PVR relative to compliance varied as a function of perinatal age and that pulmonary vasoreactivity depended on postnatal age. The major effect of ventilating fetal lungs was on the middle region.     

Bounds and inequalities relating h-index, g-index, e-index and generalized impact factor: an improvement over existing models

In this paper, we describe some bounds and inequalities relating h-index, g-index, e-index, and generalized impact factor. We derive the bounds and inequalities relating these indexing parameters from their basic definitions and without assuming any continuous model to be followed by any of them. We verify the theorems using citation data for five Price Medalists. We observe that the lower bound for h-index given by Theorem 2, [formula: see text], g ≥ 1, comes out to be more accurate as compared to Schubert-Glanzel relation h is proportional to C(2/3)P(-1/3) for a proportionality constant of 1, where C is the number of citations and P is the number of papers referenced. Also, the values of h-index obtained using Theorem 2 outperform those obtained using Egghe-Liang-Rousseau power law model for the given citation data of Price Medalists. Further, we computed the values of upper bound on g-index given by Theorem 3, g ≤ (h + e), where e denotes the value of e-index. We observe that the upper bound on g-index given by Theorem 3 is reasonably tight for the given citation record of Price Medalists.     

Comparative in vitro study of bileaflet and tilting disk valve behavior in the pulmonary position

A study of mechanical heart valve behavior in the pulmonary position as a function of pulmonary vascular resistance is reported for the St. Jude Medical bileaflet (SJMB) valve and the MedicalCV Omnicarbon (OTD) tilting disk valve. Tests were conducted in a pulmonic mock circulatory system and impedance was varied in terms of system pulmonary vascular resistance (PVR). An impedance spectrum was found using instantaneous pulmonary artery pressure and flow rate curves. Both valves fully opened and closed at and above a nominal PVR of 3.0 mmHg/L/min. The SJMB valve was prone to leaflet bounce at closure, but otherwise completely closed, at settings above and below this nominal setting. At PVR values at and below 2.0 mmHg/L/min, the SJMB valve exhibited two types of leaflet aberrant behavior: single leaflet only closure while the other leaflet fluttered, and incomplete closure where both leaflets flutter but neither remain fully closed. The OTD valve fully opened and closed to a PVR value of 1.6 mmHg/L/min. At lower values, the valve did not close. Valves designed for the left heart can show aberrant behavior under normal conditions as pulmonary valves.