scholarly journals The influence of hemoconcentration on hypoxic pulmonary vasoconstriction in acute, prolonged, and lifelong hypoxemia

2021 ◽  
Vol 321 (4) ◽  
pp. H738-H747
Author(s):  
Mike Stembridge ◽  
Ryan L. Hoiland ◽  
Alexandra M. Williams ◽  
Connor A. Howe ◽  
Joseph Donnelly ◽  
...  
Keyword(s):  
Cardiac Output ◽  
Blood Cell ◽  
Hypobaric Hypoxia ◽  
Cell Concentration ◽  
Hypoxic Pulmonary Vasoconstriction ◽  
Pulmonary Vasculature ◽  
Red Cell ◽  
Vascular Response ◽  
Pulmonary Vasoconstriction ◽  
High Altitude Natives

Red blood cell concentration influences the pulmonary vasculature via direct frictional force and vasoactive signaling, but whether the magnitude of the response is modified with duration of exposure is not known. By assessing the pulmonary vascular response to hemodilution in acute normobaric and prolonged hypobaric hypoxia in lowlanders and lifelong hypobaric hypoxemia in Andean natives, we demonstrated that a reduction in red cell concentration augments the vasoconstrictive effects of hypoxia in lowlanders. In high-altitude natives, hemodilution lowered pulmonary vascular resistance, but a compensatory increase in cardiac output following hemodilution rendered PASP unchanged.

Pentobarbital attenuates pulmonary vasoconstriction in isolated sheep lungs

1989 ◽  
Vol 257 (3) ◽  
pp. H898-H903 ◽  
Author(s):  
R. C. Wetzel ◽  
L. D. Martin
Keyword(s):  
Hypoxic Pulmonary Vasoconstriction ◽  
Effective Concentration ◽  
Pulmonary Vasculature ◽  
Vascular Response ◽  
Vascular Responses ◽  
Pulmonary Vasoconstriction ◽  
Wide Range ◽  
Instantaneous Pressure ◽  
Constrictor Response

Pentobarbital sodium is a widely used anesthetic agent that has been demonstrated to attenuate systemic vascular responses to multiple pressors. To determine whether pentobarbital affected pulmonary vasoreactivity we determined the pulmonary vascular response to hypoxia and potassium in isolated in situ perfused sheep lungs. The flow resistive characteristics of the pulmonary vasculature were assessed by determining mean instantaneous pressure-flow relationships over a wide range of flows (20–120 ml.min-1.kg body wt-1) with PIO2 of 200 and 30 Torr, with and without pentobarbital. Pentobarbital attenuated hypoxic pulmonary vasoconstriction (P less than 0.001) in a concentration-dependent fashion (50% effective concentration = 0.42 mM). In addition, the pulmonary constrictor response to potassium was markedly blunted by pentobarbital (P less than 0.001). We conclude that pentobarbital inhibits hypoxic pulmonary vasoconstriction in a concentration-dependent fashion and that this inhibition of pulmonary vasoconstriction in isolated sheep lungs is not specific for hypoxia.

Two temporal components within the human pulmonary vascular response to ∼2 h of isocapnic hypoxia

2005 ◽  
Vol 98 (3) ◽  
pp. 1125-1139 ◽  
Author(s):  
Nick P. Talbot ◽  
George M. Balanos ◽  
Keith L. Dorrington ◽  
Peter A. Robbins
Keyword(s):  
Cardiac Output ◽  
Time Course ◽  
Vascular Tone ◽  
Hypoxic Pulmonary Vasoconstriction ◽  
Initial Response ◽  
Plateau Phase ◽  
Vascular Response ◽  
Pulmonary Vasoconstriction ◽  
End Tidal ◽  
Underlying Processes

The time course of the pulmonary vascular response to hypoxia in humans has not been fully defined. In this investigation, study A was designed to assess the form of the increase in pulmonary vascular tone at the onset of hypoxia and to determine whether a steady plateau ensues over the following ∼20 min. Twelve volunteers were exposed twice to 5 min of isocapnic euoxia (end-tidal Po2 = 100 Torr), 25 min of isocapnic hypoxia (end-tidal Po2 = 50 Torr), and finally 5 min of isocapnic euoxia. Study B was designed to look for the onset of a slower pulmonary vascular response, and, if possible, to determine a latency for this process. Seven volunteers were exposed to 5 min of isocapnic euoxia, 105 min of isocapnic hypoxia, and finally 10 min of isocapnic euoxia. For both studies, control protocols consisting of isocapnic euoxia were undertaken. Doppler echocardiography was used to measure cardiac output and the maximum tricuspid pressure gradient during systole, and estimates of pulmonary vascular resistance were calculated. For study A, the initial response was well described by a monoexponential process with a time constant of 2.4 ± 0.7 min (mean ± SE). After this, there was a plateau phase lasting at least 20 min. In study B, a second slower phase was identified, with vascular tone beginning to rise again after a latency of 43 ± 5 min. These findings demonstrate the presence of two distinct phases of hypoxic pulmonary vasoconstriction, which may result from two distinct underlying processes.

Development of the pulmonary vasculature in newborn lambs: structure-function relationships

1991 ◽  
Vol 70 (3) ◽  
pp. 1255-1264 ◽  
Author(s):  
R. P. Michel ◽  
J. B. Gordon ◽  
K. Chu
Keyword(s):  
Light Microscopy ◽  
Hypoxic Pulmonary Vasoconstriction ◽  
Venous Pressure ◽  
Pulmonary Arteries ◽  
Muscle Thickness ◽  
Pulmonary Vasculature ◽  
Pressure Gradients ◽  
Middle Segment ◽  
Pulmonary Vasoconstriction ◽  
Quantitative Light Microscopy

Our objectives were 1) to describe the quantitative light microscopy and ultrastructure of newborn lamb lungs and 2) to correlate hemodynamic changes during normoxia and hypoxia with the morphology. By light microscopy, we measured the percent muscle thickness (%MT) and peripheral muscularization of pulmonary arteries and veins from 25 lambs aged less than 24 h, 2-4 days, 2 wk, and 1 mo. At the same ages, lungs were isolated and perfused in situ and, after cyclooxygenase blockade with indomethacin, total, arterial (delta Pa), middle (delta Pm), and venous pressure gradients at inspired O2 fractions of 0.28 (mild hyperoxia) and 0.04 (hypoxia) were determined with inflow-outflow occlusion. During mild hyperoxia, delta Pa and delta Pm fell significantly between 2-4 days and 2 wk, whereas during hypoxia, only delta Pm fell. The %MT of all arteries (less than 50 to greater than 1,000 microns diam) decreased, and peripheral muscularization of less than 100-microns-diam arteries fell between less than 4 days and greater than 2 wk. Our data suggest that 1) the %MT of arteries determines normoxic pulmonary vascular resistance, because only arterial and middle segment resistance fell, 2) peripheral muscularization is a major determinant of hypoxic pulmonary vasoconstriction, because we observed a fall with age in peripheral muscularization of less than 100-micron-diam arteries and in delta Pm with hypoxia, and 3) the arterial limit of the middle segment defined by inflow-outflow occlusion lies in 100- to 1,000-microns-diam arteries.

Influence of red cell concentration on filtration of blood cell suspensions

Biorheology ◽  
1983 ◽  
Vol 20 (1) ◽  
pp. 29-40 ◽  
Author(s):  
E.A. Schmalzer ◽  
R. Skalak ◽  
S. Usami ◽  
M. Vayo ◽  
S. Chien
Keyword(s):  
Blood Cell ◽  
Cell Concentration ◽  
Cell Suspensions ◽  
Red Cell

Effect of dehydroepiandrosterone on hypoxic pulmonary vasoconstriction: a Ca2+-activated K+-channel opener

1998 ◽  
Vol 274 (2) ◽  
pp. L186-L195 ◽  
Author(s):  
Imad S. Farrukh ◽  
Wei Peng ◽  
Urszula Orlinska ◽  
John R. Hoidal
Keyword(s):  
Hypoxic Pulmonary Vasoconstriction ◽  
Mean Shift ◽  
Pulmonary Vasculature ◽  
K Channel ◽  
Initial Increase ◽  
Cyclic Monophosphate ◽  
Pulmonary Vasoconstriction ◽  
Channel Opener ◽  
Alveolar Hypoxia ◽  
Pulmonary Arterial

In the present study, we investigated the effects of the naturally occurring hormone dehydroepiandrosterone (DHEA) on hypoxic pulmonary vasoconstriction (HPVC) in isolated ferret lungs and on K+ currents in isolated and cultured ferret pulmonary arterial smooth muscle cells (FPSMCs). Severe alveolar hypoxia (3% O2-5% CO2-92% N2) caused an initial increase in pulmonary arterial pressure (Ppa) that was followed by a reversal in pulmonary hypertension. Maintaining alveolar hypoxia caused a sustained secondary increase in Ppa. Pretreating the lungs with the K+-channel inhibitor tetraethylammonium (TEA) caused a small increase in baseline Ppa, potentiated HPVC, and prevented the reversal of HPVC during the sustained alveolar hypoxia. Treating the lungs with DHEA caused a near-complete reversal of HPVC in control lungs and in lungs that were pretreated with TEA. DHEA also reversed the KCl-induced increase in Ppa. In FPSMCs, DHEA caused an adenosine 3′,5′-cyclic monophosphate- and guanosine 3′,5′-cyclic monophosphate-independent increase in activity of the Ca2+-activated K+(KCa) current. In a cell-attached configuration, DHEA caused a mean shift of −22 mV in the voltage-dependent activation of the KCa channel. We conclude that DHEA is a novel KCa-channel opener of the pulmonary vasculature.

Pulmonary vascular impedance vs. resistance in hypoxic and hyperoxic dogs: effects of propofol and isoflurane

1993 ◽  
Vol 74 (5) ◽  
pp. 2188-2193 ◽  
Author(s):  
P. Ewalenko ◽  
C. Stefanidis ◽  
A. Holoye ◽  
S. Brimioulle ◽  
R. Naeije
Keyword(s):  
Hypoxic Pulmonary Vasoconstriction ◽  
Pulmonary Vasculature ◽  
Hemodynamic Changes ◽  
Vascular Effects ◽  
Intravenous Anesthesia ◽  
Mean Pulmonary Arterial Pressure ◽  
Vascular Impedance ◽  
Pulmonary Vasoconstriction ◽  
Pulmonary Arterial ◽  
The Time Domain

The pulmonary vascular effects of inhaled anesthetics have been reported variably. We compared the effects of intravenous anesthesia (propofol) and inhalational anesthesia (isoflurane) on multipoint mean [pulmonary arterial pressure (Ppa)-pulmonary arterial occluded pressure (PpaO)]/cardiac output (Q) plots and on pulmonary vascular impedance (PVZ) spectra in eight dogs alternatively ventilated in hyperoxia [inspired O2 fraction (FIO2) 0.4] and in hypoxia (FIO2 0.1). Q was altered by a manipulation of venous return. During propofol, hypoxia increased (Ppa-PpaO) by an average of 2–3 mmHg over the entire range of Q studied, from 1 to 2.5 l.min-1 x m-2. This hypoxic pulmonary vasoconstriction (HPV) was associated with insignificant changes in PVZ. Decreasing Q in hypoxia and hyperoxia did not affect PVZ. Compared with propofol, isoflurane decreased (Ppa-PpaO) by an average of 2–5 mmHg at all levels of Q studied in both hypoxia and hyperoxia but did not affect HPV. During isoflurane anesthesia, 0 Hz PVZ was lower (P < 0.01) in hypoxia, but otherwise the PVZ spectrum was not different from that recorded during propofol anesthesia. We conclude that, in dogs, 1 degree general anesthesia with isoflurane alone decreases pulmonary vascular tone without inhibition of HPV and that 2 degrees pressure/Q plots in the time domain are more sensitive than those in the frequency domain to subtle hemodynamic changes induced by hypoxia or isoflurane at the periphery of the pulmonary vasculature.

Abstract 2616: Role of the Soluble Epoxide Hydrolase in Hypoxic Pulmonary Vasoconstriction and Pulmonary Vascular Remodeling

Circulation ◽  
2008 ◽  
Vol 118 (suppl_18) ◽  
Author(s):  
Benjamin Keserü ◽  
Beate Fisslthaler ◽  
Ingrid Fleming
Keyword(s):  
Vascular Remodeling ◽  
Epoxide Hydrolase ◽  
Chronic Hypoxia ◽  
Hypoxic Pulmonary Vasoconstriction ◽  
Soluble Epoxide Hydrolase ◽  
Pulmonary Vasculature ◽  
Resistance Arteries ◽  
Pulmonary Vascular Remodeling ◽  
Pulmonary Vasoconstriction

The soluble epoxide hydrolase (sEH), which is expressed in pulmonary artery smooth muscle cells, metabolizes cytochrome P450 (CYP) epoxygenase-derived epoxyeicosatrienoic acids (EETs) to their less active diols. Preliminary findings indicate a role of the sEH on hypoxic pulmonary vasoconstriction (HPV) and a vasoconstrictor role of EETs in the pulmonary vasculature. Here we assessed the influence of hypoxia on the expression of the sEH, acute HPV and pulmonary vascular remodeling. In lungs from wild-type mice (WT), exposure to hypoxia (FiO 2 = 0.1) for 21 days decreased the expression of the sEH by 70% (RT-PCR), and increased the number of partially and fully muscularised resistance arteries (by 3-fold). In isolated lungs, pre-exposure to chronic hypoxia significantly increased baseline perfusion pressures (1.3-fold) and potentiated the acute HPV (1.5-fold). While an sEH inhibitor (1-adamantyl-3-cyclohexylurea; ACU) potentiated acute HPV in lungs from mice maintained in normoxic conditions, it had no effect on HPV in lungs from mice exposed to hypoxia. The EET antagonist, 14,15-EEZE, abolished the sEH inhibitor-dependent increase in acute HPV in normoxic lungs. Under normoxic conditions the muscularization of small pulmonary arteries was greater in lungs from sEH −/− mice than in lungs from WT mice and chronic hypoxia further increased the number of fully and partially muscularized arteries in these animals. sEH −/− mice also displayed an enhanced acute HPV (1.5-fold), compared to that observed in WT mice and chronic exposure to hypoxia did not further potentiate acute HPV. Taken together, these data indicate that the sEH is involved in hypoxia-induced pulmonary vascular remodeling and hypoxic pulmonary vasoconstriction.

HALOTHANE, CARDIAC OUTPUT, AND HYPOXIC PULMONARY VASOCONSTRICTION

1984 ◽  
Vol 61 (3) ◽  
pp. A482-A482
Author(s):  
F. L. Miller ◽  
L. Chen ◽  
C. Alexander ◽  
W. Sedrak ◽  
C. Marshall ◽  
...  
Keyword(s):  
Cardiac Output ◽  
Hypoxic Pulmonary Vasoconstriction ◽  
Pulmonary Vasoconstriction

scholarly journals Oxygen sensing and signal transduction in hypoxic pulmonary vasoconstriction

2015 ◽  
Vol 47 (1) ◽  
pp. 288-303 ◽  
Author(s):  
Natascha Sommer ◽  
Ievgen Strielkov ◽  
Oleg Pak ◽  
Norbert Weissmann
Keyword(s):  
Signal Transduction ◽  
Calcium Channels ◽  
Transient Receptor Potential ◽  
Oxygen Sensing ◽  
Hypoxic Pulmonary Vasoconstriction ◽  
Transient Receptor Potential Channels ◽  
Pulmonary Vasculature ◽  
Experimental Conditions ◽  
Pulmonary Vasoconstriction ◽  
Alveolar Hypoxia

Hypoxic pulmonary vasoconstriction (HPV), also known as the von Euler–Liljestrand mechanism, is an essential response of the pulmonary vasculature to acute and sustained alveolar hypoxia. During local alveolar hypoxia, HPV matches perfusion to ventilation to maintain optimal arterial oxygenation. In contrast, during global alveolar hypoxia, HPV leads to pulmonary hypertension. The oxygen sensing and signal transduction machinery is located in the pulmonary arterial smooth muscle cells (PASMCs) of the pre-capillary vessels, albeit the physiological response may be modulatedin vivoby the endothelium. While factors such as nitric oxide modulate HPV, reactive oxygen species (ROS) have been suggested to act as essential mediators in HPV. ROS may originate from mitochondria and/or NADPH oxidases but the exact oxygen sensing mechanisms, as well as the question of whether increased or decreased ROS cause HPV, are under debate. ROS may induce intracellular calcium increase and subsequent contraction of PASMCsviadirect or indirect interactions with protein kinases, phospholipases, sarcoplasmic calcium channels, transient receptor potential channels, voltage-dependent potassium channels and L-type calcium channels, whose relevance may vary under different experimental conditions. Successful identification of factors regulating HPV may allow development of novel therapeutic approaches for conditions of disturbed HPV.

Analysis of flow resistance in the pulmonary arterial circulation: Implications for hypoxic pulmonary vasoconstriction

2021 ◽  
Author(s):  
David Walter Johnson ◽  
Tuhin K. Roy ◽  
Timothy W. Secomb
Keyword(s):  
Essential Role ◽  
Scaling Laws ◽  
Hypoxic Pulmonary Vasoconstriction ◽  
Pulmonary Arteries ◽  
Blood Oxygenation ◽  
Pulmonary Vasculature ◽  
Arterial Circulation ◽  
Pulmonary Vasoconstriction ◽  
Hypoxic Vasoconstriction ◽  
Pulmonary Arterial

Hypoxic pulmonary vasoconstriction (HPV) plays an essential role in distributing blood in the lung to enhance ventilation-perfusion matching and blood oxygenation. In this study, a theoretical model of the pulmonary vasculature is used to predict the effects of vasoconstriction over specified ranges of vessel diameters on pulmonary vascular resistance (PVR). The model is used to evaluate the ability of hypothesized mechanisms of HPV to account for observed levels of PVR elevation during hypoxia. The vascular structure from pulmonary arteries to capillaries is represented using scaling laws. Vessel segments are modeled as resistive elements and blood flow rates are computed from physical principles. Direct vascular responses to intravascular oxygen levels have been proposed as a mechanism of HPV. In the lung, significant changes in oxygen level occur only in vessels less than 60 μm in diameter. The model shows that observed levels of hypoxic vasoconstriction in these vessels alone cannot account for the elevation of PVR associated with HPV. However, the elevation in PVR associated with HPV can be accounted for if larger upstream vessels also constrict. These results imply that upstream signaling by conducted responses to engage constriction of arterioles plays an essential role in the elevation of PVR during HPV.

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