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1.
Hroar Piene 《Acta physiologica (Oxford, England)》1976,98(1):54-66
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. 相似文献
2.
Hroar Piene 《Acta physiologica (Oxford, England)》1976,98(1):44-53
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 (Wp/Wt) 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 Wp/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: Wp/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. 相似文献
3.
David J. Farrar George S. Malindzak Jr. George Johnson Jr. 《Annals of biomedical engineering》1978,6(4):413-428
Dynamic pressure-flow diagrams were generated by plotting instantaneous pulsatile pressure versus pulsatile flow measured
2 to 3 cm proximal to a graded arterial stenosis in the dog femoral artery. The slope of the major axis of the diagram was
defined as the pulse impedance (Z
P).Z
p under steady-state and vasodilated conditions was linearly related to the large vessel impedance (Z
l) calculated independently as the average vascular input impedance modulus from 3 to 19 Hz, and linearly related to the hydraulic
resistance of the stenosis. In a separate study,Z
p andZ
l each were shown to be greater in patients with severe femoral artery stenotic atherosclerosis than in control patents, and
unchanged during vasodilation. In addition,Z
p andZ
l were reduced following femoral-to-popliteal bypass procedures. In summary, dynamic pressure-flow diagrams provide an easy-to-obtain
index of the effective vascular hydraulic input impedance in stenotic arteries, and an index of the severity of distal arterial
stenosis.
This research has been supported in part by the North Carolina Heart Association (Grant-in-Aid 1974-75-A-62) and the Environmental
Protection Agency, Chapel Hill, North Carolina. 相似文献
4.
Hroar Piene 《Acta physiologica (Oxford, England)》1976,98(3):295-306
This study aimed to quantify changes of vascular compliance and resistance of the proximal and the peripheral pulmonary arterial vessels when vascular smooth muscle was stimulated. These above vascular characteristics were derived from registrations of pulsatile pressure and flow in the pulmonary artery (PA). An in situ cat lung preparation was used, with the right heart by-passed by a pulsatile blood pump. Vascular input impedance was derived from PA pulsatile pressure and flow recordings, and impedance characteristics were used for calculation of the variables of a simple lumped analog representation of the arterial bed. PA smooth muscle was stimulated by infusions of collagen suspension, by general hypoxia and by nor-adrenaline injections. Collagen caused 40% reduction of vascular compliance (C), no changes in proximal arterial resistance (Rl) and 18076 increase in peripheral vascular resistance (R2). Hypoxia caused 5096 reduced C, 20% increased R1 and 70% increased R2. Noradrenaline caused 20:6 reduced C and 30 % increased R1 and R2. These results, together with results derived from simulation of the observed impedance changes in a computer model of the lung arterial bed, indicated that collagen infusion elicited contraction of small and medium-sized arteries, with increased arterial volume as result of increased distending pressure. Hypoxia and noradrenaline, seemed both to cause contraction of the total arterial bed. This effect being most pronounced during hypoxia. 相似文献
5.
A review of wave mechanics in the pulmonary artery with an emphasis on wave intensity analysis
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J. Su O. Hilberg L. Howard U. Simonsen A. D. Hughes 《Acta physiologica (Oxford, England)》2016,218(4):239-249
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. 相似文献
6.
The paper presents a numerical investigation of the pulsatile blood flow in the detailed arterial vasculatures of a mouse retina using the mathematical model based on frequency domain incorporating an appropriate outlet boundary impedance at the end of the terminal vessels of the arterial trees. The viscosity in the vessels was evaluated considering the Fahraeus-Lindqvist effect, the plasma skimming effect and in vivo viscosity effect in the microcirculation. Comparative studies of the pulsatile circulation were carried out for cases of rigid vessels, constant viscosity, zero and non-zero outlet boundary impedances. In addition, the dependence of the oscillating input impedance at the inlet of the arterial trees on angular frequencies of the oscillation and vessel elasticises was also studied. The study shows that the pressure wave continues in the pre-capillary vessels throughout the retina. In elastic vessels, the amplitude of oscillatory velocity and wall shear stress in larger vessels and in vessels at the periphery region of the retina is amplified. The pulsatile blood flow is significantly influenced by the outlet boundary (or load) impedance which simulates the effect of the capillary and venous vasculatures. The oscillating input impedance at the inlet of the arterial trees is also found to be dependent on the angular frequency and the Young modulus of the vessel segment. Insights into the potential variations of the dynamic responses of the system under retinal pathological condition of arteriosclerosis may be inferred from the findings of the present study. 相似文献
7.
Haft JW Bull JL Rose R Katsra J Grotberg JB Bartlett RH Hirschl RB 《ASAIO journal (American Society for Artificial Internal Organs : 1992)》2003,49(1):35-40
Matching the impedance of an artificial lung for pulmonary replacement to native pulmonary impedance is important in preventing right ventricular dysfunction. A lumped-parameter theoretical model and bench-top experiments were used to investigate the effect of a prototype compliance chamber on input impedance. The bench-top simulation consisted of a pulsatile flow generator, a prototype compliance chamber, and a low resistance artificial lung connected in series. Effective compliance was varied using pneumatic compression. The theoretical model considered a similar circuit with resistors before and after a compliance element. The bundle flow pulsatility (flow amplitude divided by average flow) and input impedance were calculated in the theoretical and experimental models. More compliance and lower upstream resistance result in lower bundle flow pulsatility and reduced first harmonic impedance. Matching the time scale of the circuit to the period of pulsatile flow also reduces impedance. The bench-top circuit demonstrated an optimal chamber pressure at which first harmonic impedance is reduced by 80%. The prototype compliance chamber in series with the artificial lung more closely matches native pulmonary impedance. The lumped-parameter model and the bench-top simulation will aid in the design and testing of compliance chamber modifications to improve its efficiency. 相似文献
8.
To study pulsatile pressure-flow rate relationships in the intact pulmonary vascular network of mice, we developed a protocol for measuring pulmonary vascular resistance and impedance in isolated, ventilated, and perfused mouse lungs. We used pulmonary emboli to validate the effect of vascular obstruction on resistance and impedance. Main pulmonary artery and left atrial pressures and pulmonary vascular flow rate were measured under steady and pulsatile conditions in the lungs of C57BL/6J mice (n = 6) before and after two infusions with 25 μm-diameter microspheres (one million per infusion). After the first and second embolizations, pulmonary artery pressures increased approximately two-fold and three and a half-fold, respectively, compared to baseline, at a steady flow rate of 1 ml/min (P < 0.05). Pulmonary vascular resistance and 0 Hz impedance also increased after the first and second embolizations for all flow rates tested (P < 0.05). Frequency-dependent features of the pulmonary vascular impedance spectrum were suggestive of shifts in the major pulmonary vascular reflection sites with embolization. Our results demonstrate that pulmonary artery pressure, resistance, and impedance magnitude measured in this isolated lung setup changed in ways consistent with in vivo studies in larger animals and humans and demonstrate the usefulness of the isolated, ventilated, and perfused mouse lung for investigating steady and pulsatile pressure-flow rate relationships. 相似文献
9.
Aiping Liu Timothy Hacker Jens C. Eickhoff Naomi C. Chesler 《Annals of biomedical engineering》2017,45(3):632-643
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. 相似文献
10.
In 11 pigs under general endotracheal anaesthesia, the time-domain method of determining the pulmonary arterial input impedance
was compared with the frequency-domain equivalent under normal conditions as well as acute pulmonary hypertension induced
by glass microspheres. The time-domain methods of determining the pulmonary arterial compliance C and pulmonary vascular bed
resistance Rp compared favourably with the frequency-domain equivalent (r=0·744, n=60, p<0·001 and r=0·906, n=60, p<0·001, respectively),
even at mean pulmonary artery pressures (MPAP) of 35 mmHg and above. A consistent and everincreasing difference between characteristic
impedance Zo(ω), estimated by averaging input impedance modulus values over a selected frequency range, and its time domain equivalent
Ro with increasing MPAP was shown to be the cause of the poor fit between the measured and remodelled pulmonary blood flow.
By analysing a time-domain estimate of the pulmonary characteristic impedance Ro(C, Rp, t), it was demonstrated that the characteristic impedance was dependent on C. Ro is therefore not an accurate representation of the characteristic impedance, especially under conditions of acute pulmonary
hypertension. Ro (C, Rp, t) should therefore be calculated instead. 相似文献
11.
Our experimental study was undertaken to determine the effect of bilateral novocaine vagosympathetic block (VSB) on central hemolymphodynamic and regional hemodinamic in lesser circulation. Follow-up period lasted for 4 hours. No statistically significant arterial pressure changes were detected. Studies of stroke index (SI) and general peripheral vascular resistance (GPVR) changes indentified the development of two responses: (1) a 60% SI decline and PVR increase were accompanied with elevation (mean 37%) of volumetric lymph flow rate within 15-30 min following VSB: (2) there was only a 40% SI elevation and GPVR decline. Rheopulmographic findings detected the reduction of volumetric pulmonary blood flow following VSB, and the decline of both pulmonary tissue-filling and venous bed capacity demonstrated by a significant fall of diastolic wave amplitude within 30 min following VSB. Histologic findings verified the reduction in pulmonary blood-filling following VSB. 相似文献
12.
Alexey Yu. Naumov Sergey A. Balashov Arthur M. Melkumyants 《Annals of biomedical engineering》2014,42(8):1644-1657
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. 相似文献
13.
Clinical achievements of impedance analysis 总被引:1,自引:1,他引:0
Mitchell GF 《Medical & biological engineering & computing》2009,47(2):153-163
Various models and derived measures of arterial function have been proposed to describe and quantify pulsatile hemodynamics
in humans. A major distinction can be drawn between lumped models based on circuit theory that assume infinite pulse wave
velocity versus distributed, propagative models based on transmission line theory that acknowledge finite wave velocity and
account for delays, wave reflection, and spatial and temporal pressure gradients within the arterial system. Although both
approaches have produced useful insights into human arterial pathophysiology, there are important limitations of the lumped
approach. The arterial system is heterogeneous and various segments respond differently to cardiovascular disease risk factors
including advancing age. Lumping divergent change into aggregate summary variables can obscure abnormalities in regional arterial
function. Analysis of a limited number of summary variables obtained by measuring aortic input impedance may provide novel
insights and inform development of new treatments aimed at preventing or reversing abnormal pulsatile hemodynamics. 相似文献
14.
Professor R. Burattini K. B. Campbell 《Medical & biological engineering & computing》1999,37(3):366-376
This paper reviews the analytical expressions for in-phase and quadrature aortic power components associated with the real and imaginary parts of aortic input admittance, respectively. It is shown that active power Wact, and its steady, Wstdy, and pulsatile, Wpuls, components logically follow from in-phase power. Reactive power follows from quadrature power only for sinusoidal signals. The definition of reactive power indexes for real aortic pressures and flows requires extreme care. The link between overall arterial properties and pressure power components (and indexes) is investigated, making use of a three-element windkessel model and ascending aortic pressure and flow data taken from eight anaesthetised dogs, under basal state and after treatment with a vasoconstrictor (methoxamine). Seven dogs are normotensive in the baseline state (NBA cases, n = 7), the average (+/- SE) of mean pressure being 86.5 +/- 5.2 mmHg. The eighth dog has a baseline mean pressure of 134 mmHg and is considered to be hypertensive. The two experimental cases from this dog are grouped with those from the other seven dogs after vasoconstriction, to form the NVC + H group (n = 9). On average, fitting the model to the experimental data yields a 100% increase (p < 0.05) in total peripheral resistance, a 63% decrease (p < 0.01) in total arterial compliance and a 10% decrease (p > 0.05) in aortic characteristic impedance, from the NBA group to the NVC + H. Correspondingly, the peak-to-peak amplitude of quadrature power shows a 69% increase (p < 0.02). Wact, Wstdy, and Wpuls show a 28% increase (p > 0.05), a 40% increase (p < 0.02) and a 43% decrease (p > 0.05), respectively. Energetic efficiency of the arterial system, Eart = 1 - (Wpuls/Wact), increases by 8% (p < 0.02). From analysis of the estimates of power components and arterial parameters in relation to low-frequency phase angles of aortic impedance, it is concluded that the decrease in total arterial compliance with increasing pressure reduces the power lost in pulsation. This happens at the expense of an increase in quadrature power and absolute values of related reactive power indexes. 相似文献
15.
Hiroshi Ito Ken-ichi Yamakoshi Akio Yamada 《Medical & biological engineering & computing》1976,14(4):373-378
By perfusing the aorta and the pulmonary artery of dogs with a controlled sinusoidal or pulsatile flow, the source of the transthoracic impedance variation and the relationship between the actual blood volume flow and the stroke volume value calculated by Kubicek's impedance method s.v.z were investigated. The results are as follows: (a) the main component of the transthoracic impedance waveform from which the s.v.z value is calculated originates from the systemic blood flow rather than from the pulmonary blood flow; (b) not the absolute but the relative value of the stroke volume can be calculated by Kubicek's equation; and (c) the s.v.z value is greatly affected by the hydraulic frequency of the actual sinusoidal blood flow. 相似文献
16.
Chen HI Hsieh NK Chang HR Hu CT 《Pflügers Archiv : European journal of physiology》2008,455(4):595-606
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 (Pb) and pulse wave velocity (PWV). Aortic embedding (AE) increased LVW, LVW/BW, systolic and pulse pressure (PP), Zc, Pb 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, Pb 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. 相似文献
17.
The relationship between wave reflections and ventricular-vascular coupling has been the subject of considerable speculation.
Since we have previously shown that low-dose nitroprusside infusion improved ventricular-vascular coupling (as evidenced by
increases in cardiac output and in aortic and pulmonary arterial total external power) in patients with severe left ventricular
failure and secondary pulmonary hypertension, we chose to examine the changes in their aortic and pulmonary arterial wave
reflections in this study. Wave reflection indexes examined included [1] calculated backward and forward pressure waves and
the ratio of their magnitudes (reflection factor), [2] the reflection coefficient spectrum obtained by taking the ratios of
the corresponding Fourier harmonics of the backward and forward waves, [3] two terminal reflection coefficients calculated
as Γ
t
=(R-Z
c
)/R+Z
c
) where Z is characteristic impedance and R is either total resistance or vascular resistance, and [4] the difference between
the maximum and minimum impedance moduli for frequencies of 4 to 15 Hz. In the systemic vasculature, nitroprusside produced
large reductions in the elevated vascular resistances and decreased aortic reflections as indexed by the reflection factor
and by both terminal reflection coefficients. In contrast, however, no significant changes were found in the pulmonary artery
wave reflection indexes despite large reductions in the pulmonary resistances.
Supported in part by Grant #P-50-HL17655 from the National Institutes of Health Ischemic Heart Disease Specialized Center
on Research.
Dr. Brin is a recipient of a Public Health Service Clinical Investigator Award (HL-01028) from the National Heart, Lung, and
Blood Institute.
Dr. Yin was a recipient of a Frank T. McClure Fellowship from the Johns Hopkins University Applied Physics Laboratory. 相似文献
18.
Peter A. L. Gaehtgens 《Pflügers Archiv : European journal of physiology》1970,316(2):140-151
Summary The transmission of arterial pressure and flow pulse through the mesenteric vascular bed was studied in 18 experiments on cats. Pressures were measured in the superior mesenteric artery and in small mesenteric veins, red blood cell flow velocities in mesenteric microvessels smaller than 60 diameter. Venous pressures were found to show heart beat synchronous oscillatory components of 0.2–0.5mmHg amplitude. Venous pressure pulses were delayed in time in comparison to the arterial pressure pulses: mean transit times varied between 85 and 110 msec. Blood flow velocities in arterioles and venules were generally pulsatile, the amplitude of the arteriolar pulses averaging 52.5% of mean velocity, of the venular pulses 32.5%. The velocity pulses were found to be similar in shape as flow pulses in larger arteries. Infusion of vasoactive drugs showed transmission of arterial pulses to be inversely dependent upon vascular resistance. It is concluded that the concept of complete damping of the arterial pulse during the passage of blood through the intestinal vascular bed cannot be maintained. Two different mechanisms of pulse transmission are discussed: direct hydraulic transmission through the capillary network and transmission across the vascular wall from the arteriole to the venule.Supported by USPHS Grant HE-08977. 相似文献
19.
R. KETTUNEN J. TIMISJRVI P. SAUKKO M. KOSKELA 《Acta physiologica (Oxford, England)》1983,118(3):209-214
Immediate circulatory reactions to acute intragastric ethanol administration were studied by a catheterization technique in spontaneously breathing dogs. Diluted ethanol was given in a dosage of 1 g/kg in test group I (n = 11), and 2 g/kg in group II (n = 10). The control group (n = 14) received only water. The highest blood ethanol concentration was 0.90 ± 0.07 mg/ml (mean ± SE) in group I, and 1.97 ± 0.10 mg/ml in group II. Heart rate and cardiac output increased (p < 0.001), but stroke volume, mean aortic blood pressure and right atrial blood pressure remained practically unchanged. Systemic vascular resistance decreased. Mean pulmonary arterial blood pressure increased markedly in both test groups (p < 0.001) while pulmonary arterial wedge pressure did not change. The pulmonary arterial resistance increased (p xyl 0.01). Changes in respiratory rate or volume and arterial pO2 were negligible in group I, but respiratory minute volume decreased in group II. In conclusion, ethanol in concentrations 0.5 to 2.0 mg/ml increased resistance in the pulmonary arterial tree, indicating pulmonary arterial vasoconstriction, but reduced systemic vascular resistance, thus putting a concept of peripheral vasodilation in favour. 相似文献
20.
Fiona Murray Paul A. Insel Jason X.-J. Yuan 《Respiratory physiology & neurobiology》2006,151(2-3):192
High altitude pulmonary edema (HAPE) is a potentially fatal complication in response to exposure to low O2 at high altitudes. Hypoxia, by causing pulmonary vasoconstriction, increases pulmonary vascular resistance and pulmonary arterial pressure, both of which are features in the pathogenesis of HAPE. Uneven hypoxic pulmonary vasoconstriction is thought to be responsible for increased capillary pressure and leakage, resulting in edema. O2-sensitive ion channels are known to play pivotal roles in determining vascular tone in response to hypoxia. K+, Ca2+ and Na+ channels are ubiquitously expressed in both endothelial and smooth muscle cells of the pulmonary microvasculature, subfamilies of which are regulated by local changes in PO2. Hypoxia reduces activity of voltage-gated K+ channels and down-regulates their expression leading to membrane depolarization, Ca2+ influx in pulmonary artery smooth muscle cells (by activating voltage-dependent Ca2+ channels) and vasoconstriction. Hypoxia up-regulates transient receptor potential channels (TRPC) leading to enhanced Ca2+ entry through receptor- and store-operated Ca2+ channels. Altered enrichment of ion channels in membrane microdomains, in particular in caveolae, may play a role in excitation–contraction coupling and perhaps in O2-sensing in the pulmonary circulation and thereby may contribute to the development of HAPE. We review the role of ion channels, in particular those outlined above, in response to low O2 on vascular tone and pulmonary edema. Advances in the understanding of ion channels involved in the physiological response to hypoxia should lead to a greater understanding of the pathogenesis of HAPE and perhaps in the identification of new therapies. 相似文献