Influence of Vessel Distension and Myogenic Tone on Pulmonary Arterial Input Impedance. A Study using a Computer Model of Rabbit Lung

A computer model of the pulmonary arterial (PA) bed of rabbit lungs was designed in order to test experimental observations of changes in PA input impedance and pulsatile hydraulic power (cap.) during increased PA pressure. The computer model was based on a simple 3-component analog representation of single vessels (i.e. resistance, inertance and compliance). 16 generations of arterial vessels, from PA to 60 μm diameter, were combined to calculate PA input impedance. Input impedance was found to mimic closely that observed experimentally. Both venous pressure elevation and arteriolar constriction was found to reduce input impedance and Wp. By combining arteriolar constriction with increased myogenic tone of the larger arteries, Wp was found to show a minimum level at a certain PA pressure, dependent on the degree of arterial stiffening. Wp was found to follow changes in arterial volume and resistance during simulated vasoconstriction. Wp dissipation in arterial vessels was calculated to approx. 50% of total input Wp at physiological pressure conditions, and could be reduced by one half after PA pressure increase from 20 to 50 cm H₂O, despite a concurrent halving of arterial compliance. Arterial vessels smaller than 200 pm diameter were found to have negligible direct influence on PA input impedance.     

Estrogen Preserves Pulsatile Pulmonary Arterial Hemodynamics in Pulmonary Arterial Hypertension

Pulmonary arterial hypertension (PAH) is caused by extensive pulmonary vascular remodeling that increases right ventricular (RV) afterload and leads to RV failure. PAH predominantly affects women; paradoxically, female PAH patients have better outcomes than men. The roles of estrogen in PAH remain controversial, which is referred to as “the estrogen paradox”. Here, we sought to determine the role of estrogen in pulsatile pulmonary arterial hemodynamic changes and its impact on RV functional adaption to PAH. Female mice were ovariectomized and replenished with estrogen or placebo. PAH was induced with SU5416 and chronic hypoxia. In vivo hemodynamic measurements showed that (1) estrogen prevented loss of pulmonary vascular compliance with limited effects on the increase of pulmonary vascular resistance in PAH; (2) estrogen attenuated increases in wave reflections in PAH and limited its adverse effects on PA systolic and pulse pressures; and (3) estrogen maintained the total hydraulic power and preserved transpulmonary vascular efficiency in PAH. This study demonstrates that estrogen preserves pulmonary vascular compliance independent of pulmonary vascular resistance, which provides a mechanical mechanism for ability of estrogen to delay disease progression without preventing onset. The estrogenic protection of pulsatile pulmonary hemodynamics underscores the therapeutic potential of estrogen in PAH.     

The Influence of Pulmonary Blood Flow Rate on Vascular Input Impedance and Hydraulic Power in the Sympathetically and Noradrenaline Stimulated Cat Lung

This study was designed to evaluate the influence of sympathetic nerve stimulation (NS) and α-adrenergic receptor stimulation (αS) on the pulmonary vascular input impedance and hydraulic power output of the right heart during variations of cardiac output (CO). An open chest cat preparation was used and pulsatile pressure and flow in the pulmonary artery were measured by high frequency response transducers. Calculations showed that vascular resistance (VR) was inversely dependent on CO, hut input impedance of the unstimulated lung was not influenced by CO variations. NS or αS increased VR and input impedance significantly, and the relation pulsatile hydraulic power/total hydraulic power (W_p/W_t) increased 40%, indicating that such stimulation has larger relative influence on impedance than on resistance. The reduction of arterial compliance during NS (maximal stimulus) was calculated to be 60%, independent of CO. Input impedance during NS or αS was reduced by CO elevations, probably because the concomitant distension of the arterial bed reduced arterial resistance and inertance. The ratio W_p/CO, which expresses the fraction of pulsatile hydraulic power lost per ml mean arterial flow, was found to be flow dependent both in control and stimulated conditions: W_p/CO was positively correlated to CO in control condition and weakly negatively correlated to CO during stimulation. At high CO the arterial vessels could he stimulated and stiffened without much extra load on the right heart.     

Influence of Moderate Vasoconstriction on the Wave Reflection Properties of the Pulmonary Arterial Bed

Increased transmural pressure in the pulmonary arterial bed may reduce vascular input impedance and reduce hydraulic power linked to pulsatile blood flow. Vascular impedance and pulsatile hydraulic power (Wp) levels of isolated perfused rabbit lungs were compared after similar rises of pulmonary arterial pressure (PAp), induced either by vasoconstriction or by left atrial pressure (LAp) elevation. Resulting Wp levels were significantly smaller after vasoconstriction than LAp elevation. Wp showed a minimum level at physiologic PAp (about 20 cm H₂O) irrespective of the cause of PAp elevation. Pressure pulse wave reflection coefficient (Γ) was calculated for control and test situations, and was found to be approximately doubled after vasoconstriction. Only minor changes in Γ were found after LAP elevation. Accordingly, moderate vasoconstriction (resulting PAp?20 cm H₂O) caused a backward traveling pressure wave of high amplitude, appearing in counter-phase to the forward pressure wave at the input site. The total pressure wave amplitude was thereby markedly lowered, resulting in a reduced Wp level. We assume that this effect of moderate vasoconstriction may be one reason for the existence of vascular smooth muscles in the pulmonary arteries.     

天麻素对动脉血管顺应性以及血流动力学的影响

本文旨在研究天麻素对动脉血管顺应性和血流动力学等的作用。采用改良风箱模型来计算动脉管的顺应性和血管中血流惯性。在静脉注射天麻素前后，分别记录和计算出狗的血压，心输出量，外周阻力，血流惯性以及中央和外周动脉血管的顺应性。结果表明天麻素具有降低血压和外周务管阻力，增加动脉血管中血流惯性，以及中央和外周动脉血管的顺应性等作用。因此，天麻素是一种有效的能够改善由血管顺应性下降所致的高血压－老年性高血压的中     

Role of vascular bed compliance in vasomotor control in human skeletal muscle

The current view of neurogenic vasomotor control in skeletal muscle is based largely on changes in vascular bed resistance. The purpose of this study was to determine to what extent vascular bed compliance may also play a role in this regulation. For this purpose, pressure waveforms (Millar and Finometer) and flow waveforms (Doppler ultrasound) were measured simultaneously in the brachial artery of seven healthy individuals during physiological manoeuvres which were expected to produce non-neurogenic changes in resistance (wrist-cuff occlusion; n = 5) or compliance (arm elevation; n = 6) of the forearm vascular bed. Vascular resistance (R) was calculated from the average flow and pressure values. A lumped Windkessel model was used to obtain vascular bed compliance (C) from these concurrently measured waveforms. Compared with baseline (3.81 +/- 1.59 ml min(-1) mmHg(-1)), wrist occlusion increased R (65 +/- 75%; P < 0.05) with minimal change in C (-15 +/- 16%; n.s.). Compared with the arm in neutral position (0.0075 +/- 0.003 ml mmHg(-1)), elevation of the arm above heart level produced a 86 +/- 41% increase in C (P < 0.05) with little change in R (-5 +/- 11%). In addition, neurogenic changes were assessed during lower body negative pressure (LBNP) and a cold pressor test (CPT; n = 7). Lower body negative pressure induced a 29 +/- 24% increase in R and a 26 +/- 12% decrease in C (both P < 0.05). The CPT induced no consistent change in R but a 22 +/- 7% reduction in C (P < 0.05). It was concluded that vascular bed compliance is an independent variable which should be considered along with vascular bed resistance in the mechanics of vasomotor regulation in skeletal muscle.     

缺氧对犬肺循环血流动力学和流变学参数的影响

本文观察了缺氧引起的犬肺循环血流动力学及流变学参数的变化。结果表明：缺氧能显著降低心输出血流量,造成肺动脉高压,经计算获得肺血管阻力明显增加。缺氧还使犬的全血粘度增加,从高、低切变率条件下还原粘度的明显改变上看,这种全血粘度的增加与红细胞刚性指数和聚集指数的上升直接相关。     

Quantification of pulsatility as a function of vascular input impedance: an in vitro study

The physiological benefits of pulsatility generated by ventricular assist device (VAD) support continue to be heavily debated as application of VAD support has been expanded to include destination and recovery therapies. In this study, the relationship between input impedance (Zart) and vascular pulsatility during continuous flow (CF) or pulsatile flow (PF) VAD support was investigated. Hemodynamic waveforms were recorded at baseline failure and with 50%, 75%, and 100% CF or PF VAD support for nine different Zart test conditions (combination of three different resistance and compliance settings) in a mock circulatory system simulating left ventricular failure. High-fidelity hemodynamic pressure and flow waveforms were recorded to calculate mean arterial pressure (MAP), Zart, energy equivalent pressure (EEP), and surplus hemodynamic energy (SHE) as metrics for quantifying vascular pulsatility. MAP and EEP were elevated with increasing resistance whereas SHE was reduced with increasing compliance. Vascular pulsatility was restored with increasing PF VAD support, but diminished by up to 90% with increasing CF VAD support. The nonpulsatile energy component (MAP) of the pressure waveform is dependent on resistance whereas the pulsatile energy component (SHE) is dependent on compliance. The impact of Zart and vascular pulsatility on patient recovery with VAD support warrants further investigation.     

Metabolic control of large-bore arterial resistance vessels,arterioles, and veins in cat skeletal muscle during exercise

The metabolic control of the vascular bed in cat gastrocnemius muscle during exercise was studied with a new technique (Björnberg et al. 1988) permitting continuous and simultaneous recordings of arteriolar and capillary pressures, and of resistances in the following consecutive vascular section: proximal arterial resistance vessels > 25 μm, arterioles < 25 μm, and on the venous side. The study thereby provided quantitative data for resistance and active intrinsic tone in these vascular segments at rest, during graded exercise vasodilatation, and in the post-exercise period. Slight activation of the metabolic control system by low-frequency somatomotor nerve stimulation (light exercise') caused inhibition of intrinsic tone and decreased vascular resistance selectively in the arteriolar section. At increasing workloads, arteriolar resistance was further decreased, but resistance and tone in the proximal arterial resistance vessels and the veins then became clearly reduced as well. This difference in effectiveness of the metabolic control system on the different segments of the vascular bed was expressed quantitatively in terms of a ‘metabolic vasodilator index’. Graded activation of the metabolic control system led to a marked segmental redistribution of intrinsic vascular tone, in turn resulting in an increased pressure drop across the proximal arterial vessels and the veins and a decreased pressure drop over the arterioles. The observed decrease in the pre- to post-capillary resistance ratio caused, at a constant arterial pressure of 100 mmHg, a graded increase in capillary pressure with increasing workloads, at maximum vasodilatation by an average value of 14 mmHg above the resting control value of 15.4 ± 0.6 mmHg. In the post-exercise period, recovery of vascular tone to control was more rapid in the proximal arterial resistance vessels and the veins than in the arteriolar segment.     

Arterial haemodynamics on ventricular hypertrophy in rats with simulated aortic stiffness

Aortic stiffness (AS) exerts significant impact on the cardiovascular risks. We developed a new model to produce AS. The purposes were to evaluate the haemodynamic consequence and to correlate the haemodynamic parameters with the extent of ventricular hypertrophy (VH). We applied silicon gel for embedding of the abdominal and/or thoracic aorta. After 1–4 weeks of AS, the left ventricular weight (LVW), LVW to body weight (BW) ratio (LVW/BW), and the morphological changes in cardiomyotes were quantified for VH. We determined the aortic pressure (AP), stroke volume, cardiac output, total peripheral resistance (TPR), characteristic impedance (Zc), pulse wave reflection (P_b) and pulse wave velocity (PWV). Aortic embedding (AE) increased LVW, LVW/BW, systolic and pulse pressure (PP), Zc, P_b and PWV accompanied by decreases in diastolic pressure and arterial compliance. The magnitude of these haemodynamic and cardiac changes were in an order of combined, thoracic and abdominal AE. Correlation analysis revealed that the VH was well correlated with pulsatile haemodynamics such as Zc, PP, P_b and PWV, while less with steady components (Mean AP and TPR). Our results indicate that pulsatile haemodynamic parameters are significantly elevated after AS. The alterations in pulsatile haemodynamics are the major causes leading to VH.     

Use of Input Impedance to Determine Changes in the Resistance of Arterial Vessels at Different Levels in Feline Femoral Bed

In many studies, the functional state of vessels of different caliber was determined by fitting the lumped parameters of a mathematical model of the bed in order to fit the vascular input impedance (Z _in) data. However, reliability of the results obtained in such a way remains uncertain. In this study, we employed a mathematical model with seven lumped parameters and Z _in experimental data to analyze the distribution of resistance across the arterial bed of the hind limb in anesthetized cats, to test reliability of this distribution and to describe the process of ascending arterial dilation followed occlusion of iliac artery. The vascular bed was divided into three segments: large arteries, medium-sized arterial vessels and precapillary resistance vessels together with venous part of the bed. Based on the data of Z _in measured in a wide frequency range (from 0 to 150 Hz) we showed that pharmacologically induced constriction and dilation of the arterial microvessels were reflected in the model by the changes in the resistance of distal precapillary vessels only, whereas the local constriction or dilation of femoral and iliac arteries as well as artificial stenosis of the femoral artery resulted exclusively in the changes of the resistance describing the state of large arteries. Using the input impedance method we could demonstrate and quantitatively describe the process of ascending arterial dilation during the post-occlusion (reactive) hyperemia. All these results prove that the model of vascular bed with seven lumped elements used in combination with input hydraulic impedance data can be an effective tool permitted to quantitatively analyze the functional state of arterial vessels of different caliber and to describe the changes in resistance of arterial vessels during vascular reactions.     

Impact of Acute Pulmonary Embolization on Arterial Stiffening and Right Ventricular Function in Dogs

Pulmonary hypertension (PH) can impact right ventricular (RV) function and alter pulmonary artery (PA) stiffness. The response of the RV to an acute increase in pulmonary pressure is unclear. In addition, the relation between total pulmonary arterial compliance and local PA stiffness has not been investigated. We used a combination of right heart catheterization (RHC) and magnetic resonance imaging (MRI) to assess PA stiffening and RV function in dogs before and after acute embolization. We hypothesized that in moderate, acute PH the RV is able to compensate for increased afterload, maintaining adequate coupling. Also, we hypothesized that in the absence of PA remodeling the relative area change in the proximal PA (RAC, a noninvasive index of local area strain) correlates with the total arterial compliance (stroke volume-to-pulse pressure ratio). Our results indicate that, after embolization, RV function is able to accommodate the demand for increased stroke work without uncoupling, albeit at the expense of a reduction of efficiency. In this acute model, RAC showed excellent correlation with total arterial compliance. We used this correlation to assess PA pulse pressure (PP) from noninvasive MRI measurements of stroke volume and RAC. We demonstrated that in acute pulmonary embolism MRI estimates of PP are remarkably close to measurements from RHC. These results, if confirmed in chronic PH and clinically, suggest that monitoring of PH progression by noninvasive methods may be possible.     

True Arterial System Compliance Estimated From Apparent Arterial Compliance

A new method has been developed to estimate total arterial compliance from measured input pressure and flow. In contrast to other methods, this method does not rely on fitting the elements of a lumped model to measured data. Instead, it relies on measured input impedance and peripheral resistance to calculate the relationship of arterial blood volume to input pressure. Generally, this transfer function is a complex function of frequency and is called the apparent arterial compliance. At very low frequencies, the confounding effect of pulse wave reflection disappears, and apparent compliance becomes total arterial compliance. This study reveals that frequency components of pressure and flow below heart rate are generally necessary to obtain a valid estimate of compliance. Thus, the ubiquitous practice of estimating total arterial compliance from a single cardiac cycle is suspect under most circumstances, since a single cardiac cycle does not contain these frequencies. © 2000 Biomedical Engineering Society. PAC00: 8719Uv, 8719Rr     

A review of wave mechanics in the pulmonary artery with an emphasis on wave intensity analysis

Mean pulmonary arterial pressure and pulmonary vascular resistance (PVR) remain the most common haemodynamic measures to evaluate the severity and prognosis of pulmonary hypertension. However, PVR only captures the non‐oscillatory component of the right ventricular hydraulic load and neglects the dynamic compliance of the pulmonary arteries and the contribution of wave transmission. Wave intensity analysis offers an alternative way to assess the pulmonary vasculature in health and disease. Wave speed is a measure of arterial stiffness, and the magnitude and timing of wave reflection provide information on the degree of impedance mismatch between the proximal and distal circulation. Studies in the pulmonary artery have demonstrated distinct differences in arterial wave propagation between individuals with and without pulmonary vascular disease. Notably, greater wave speed and greater wave reflection are observed in patients with pulmonary hypertension and in animal models exposed to hypoxia. Studying wave propagation makes a valuable contribution to the assessment of the arterial system in pulmonary hypertension, and here, we briefly review the current state of knowledge of the methods used to evaluate arterial waves in the pulmonary artery.     

Influence of central and peripheral changes on the hydraulic input impedance of the systemic arterial tree

The input impedance of the systemic arterial tree of the dog has been computed by Fourier analysis. It was shown that a distance between pressure and flow transducers of less than 2 cm results in appreciable errors which manifest themselves mainly in the phase of the input impedance. The input impedance for controls, occlusions at various locations in the aorta, and an increase and decrease of peripheral resistance were studied. For the same experiments, the total arterial compliance was calculated from the peripheral resistance of the diastolic aortic-pressure curve. The characterstic impedance of the ascending aorta was also estimated. The impedance in the control situation may be modelled by means of a 3-element Windkessel consisting of a peripheral resistance and (total) arterial compliance, together with a resistance equal to the characteristic impedance of the aorta. The occlusions of the aorta show that blockage at (and beyond) the trifurcation do not result in a detectable change in input impedance, except for a slight increase of the peripheral resistance. The more proximal an aortic occlusion, the more effect it has on the pattern of the input impedance. When the aorta is occluded at the diphragm, or higher, the single (uniform) tube appears to be a much better model than the Windkessel. Occlusion of one or both carotid arteries increases the mean pressure; consequently not only the peripheral resistance increases but also the total arterial compliance decreases. The Windkessel with increased peripheral resitance and decreased compliance is again a good model. After a sudden release of occlusion of the aorta, the arterial system has a low peripheral resistance and may also be modelled by the Windkessel.     

Constant flow- vs. constant pressure-perfusion for studies of pulmonary vasoactive responses

We have compared the pulmonary vascular responses to a standardized hypoxic vasoconstrictor stimulus (F_1,0,2=0.02) obtained during 1) constant volume inflow, with pulmonary arterial pressure as the dependent variable, and 2) constant inflow pressure, with flow as the dependent variable. Isolated rat lungs were perfused at different baseline transvascular pressures. The experimental arrangement allowed changes between the two types of perfusion. Hypoxia at constant pressure perfusion gave a higher percentage rise in pulmonary vascular resistance (PVR) at all pressure levels. This advantage was however, more than offset by the finding that a) vascular closure (total or partial) often occurred, particularly below arterial pressure of 3 kPa, making detection of graded responses impossible, and b) the control situation was rarely regained. Responses obtained during constant flow were less reduced by elevations in baseline transvascular pressure, and the control situation was rapidly and completely regained. The observation that hypoxic vascular closure may occur in the pulmonary vascular bed supports the hypothesis that high altitude edema is caused by precapillary occlusion of a major part of the vascular bed, thereby subjecting still perfused regions to very high pressures and flow.     

硝普钠对动物血管力学参数的影响

有研究表明硝普钠具有增加动脉顺应性的趋势和降低外周阻力的作用,但是硝普钠对血管中血流惯性的影响却不统一。本文以Coldwyn等建立的动脉系改良风箱力学模型为主要研究方法对动物动脉血管顺应性(包括中央和外周顺应性),血流惯性和外周阻力等进行了研究,并建立了动脉系总阻抗的公式。然后评价硝普钠对总阻抗的影响以及总阻抗做为一种血管力学参数的灵敏性。实验结果表明:硝普钠具有统计学意义地增加外周血管的顺应性(P<0.05);有增加中央动脉顺应性和血流惯性的趋性;并能降低外周阻力和动脉系总阻抗(P<0.05)。结果还表明动脉系总阻抗是一种灵敏度高的血管力学参数。因此,硝普钠能影响血管参数,对外周血管顺应性和血管总阻抗的作用尤其明显。     

Arterial pressure-blood flow relations during limb elevation in man

The effect of local arterial hypotension upon blood flow was studied in 13 healthy humans. Blood flow was measured by the local 133Xe washout technique in the calf or foot region. Changes in arterial pressure was achieved by elevation of the leg above heart level, while the subject rested in supine position. In papaverine-infiltrated subcutaneous tissue, local arterial pressure and blood flow was linearly related. In subcutaneous and skeletal muscle tissue with normal vasomotor tone, blood flow remained constant during a decrease in regional arterial pressure of 30 mmHg--autoregulation of blood flow. Blood flow ceased in vasoparalysed tissue as well as in tissue with normal vasomotor tone, when the local diastolic arterial pressure was reduced to zero. The elevated foot showed signs of vascular ischaemia during these conditions. When the vessels in the ischaemic foot were distended by inflating a femur cuff to a pressure level above the diastolic blood pressure beneath the cuff, the colour of the foot changed into bluish-red and a substantial blood flow was recorded. It is concluded, that the arteries-arterioles seemed to be collapsed with blood flow cessation, when the diastolic portion of a pulsatile inflow pressure was reduced to zero. Vascular distension seemed to reopen the arterial-arteriolar collapse, and during these conditions the vascular bed offered only little resistance to the systolic peak injection.     

Intestinal O2 consumption and 86Rb extraction during arterial hypoxia

Earlier reports indicated that arterial hypoxia not only dilated intestinal resistance vessels but also increased capillary filtration coefficients. The latter finding was interpreted as reflecting an increased number of perfused capillaries. Because both increased blood flow and increased capillary density would tend to maintain tissue oxygenation in spite of arterial hypoxia, the main purpose of this paper was to determine how effectively intestinal O2 utilization is maintained during arterial hypoxia. Therefore, I perfused isolated loops of canine small bowel at constant arterial pressure. Under this condition, reducing arterial PO2 to a mean value of 46 +/- 2.4 mmHg caused blood flow to increase to 146% of control, and O2 consumption was kept within 26% of control. In gut loops perfused at constant blood flow, arterial hypoxia depressed O2 uptake still further, but measurements of 86Rb extraction confirmed that the density of the perfused capillary bed increased. Thus, the responses of both resistance and exchange vessels tend to maintain O2 delivery to intestinal tissue during arterial hypoxia.     

Effect of BQ123 on vasoconstriction as a result of either hypoxia or endothelin-1 in perfused rat lungs

A possible role of endothelin (ET)-1 in mediating hypoxic pulmonary vasoconstriction (HPV) was examined by comparing haemodynamic differences between ET-1-induced vasoconstriction and HPV in isolated perfused rat lungs. An ET_A receptor antagonist (BQ123) was also employed to assess the effects of ET-1. The pulmonary arterial pressure (Ppa) was significantly increased by alveolar hypoxia (3% O₂) and by ET-1 (5 nM). The pulmonary microvascular pressure was not changed by hypoxia, but increased more than two-fold by ET-1 (P < 0.01). Hypoxia significantly increased pulmonary arterial resistance (P < 0.01) while ET-1 significantly increased pulmonary venous resistance (P < 0.01), and slightly increased arterial resistance. Lung weight was increased by ET-1 and decreased by hypoxia, accompanied by similar Ppa responses in both cases. BQ123 (10^-6 m and 10^-5 m ) did not influence the changes in Ppa and lung weight induced by hypoxia or angiotensin II (0.3 μg). BQ123 did, however, suppress (P < 0.05) the increase in Ppa and lung weight induced by 5 nM ET-1. Thus, it appears unlikely that ET-1 is involved in changes in pulmonary vascular tone during acute HPV.