scholarly journals Does extracorporeal membrane oxygenation attenuate hypoxic pulmonary vasoconstriction in a porcine model of global alveolar hypoxia?

2020 ◽  
Vol 64 (7) ◽  
pp. 992-1001
Author(s):  
Bernhard Holzgraefe ◽  
Anders Larsson ◽  
Staffan Eksborg ◽  
Håkan Kalzén
Keyword(s):  
Extracorporeal Membrane Oxygenation ◽  
Porcine Model ◽  
Hypoxic Pulmonary Vasoconstriction ◽  
Membrane Oxygenation ◽  
Pulmonary Vasoconstriction ◽  
Alveolar Hypoxia

scholarly journals Impaired hypoxic pulmonary vasoconstriction in a mouse model of Leigh syndrome

2019 ◽  
Vol 316 (2) ◽  
pp. L391-L399 ◽  
Author(s):  
Grigorij Schleifer ◽  
Eizo Marutani ◽  
Michele Ferrari ◽  
Rohit Sharma ◽  
Owen Skinner ◽  
...  
Keyword(s):  
Hypoxic Pulmonary Vasoconstriction ◽  
Pulmonary Inflammation ◽  
Leigh Syndrome ◽  
Arterial Oxygen ◽  
Inborn Errors ◽  
Pulmonary Vasoconstriction ◽  
Progressive Encephalopathy ◽  
Alveolar Hypoxia ◽  
The Impact ◽  
Deficient Mice

Hypoxic pulmonary vasoconstriction (HPV) is a physiological vasomotor response that maintains systemic oxygenation by matching perfusion to ventilation during alveolar hypoxia. Although mitochondria appear to play an essential role in HPV, the impact of mitochondrial dysfunction on HPV remains incompletely defined. Mice lacking the mitochondrial complex I (CI) subunit Ndufs4 ( Ndufs4−/−) develop a fatal progressive encephalopathy and serve as a model for Leigh syndrome, the most common mitochondrial disease in children. Breathing normobaric 11% O2 prevents neurological disease and improves survival in Ndufs4−/− mice. In this study, we found that either genetic Ndufs4 deficiency or pharmacological inhibition of CI using piericidin A impaired the ability of left mainstem bronchus occlusion (LMBO) to induce HPV. In mice breathing air, the partial pressure of arterial oxygen during LMBO was lower in Ndufs4−/− and in piericidin A-treated Ndufs4+/+ mice than in respective controls. Impairment of HPV in Ndufs4−/− mice was not a result of nonspecific dysfunction of the pulmonary vascular contractile apparatus or pulmonary inflammation. In Ndufs4-deficient mice, 3 wk of breathing 11% O2 restored HPV in response to LMBO. When compared with Ndufs4−/− mice breathing air, chronic hypoxia improved systemic oxygenation during LMBO. The results of this study show that, when breathing air, mice with a congenital Ndufs4 deficiency or chemically inhibited CI function have impaired HPV. Our study raises the possibility that patients with inborn errors of mitochondrial function may also have defects in HPV.

Pulmonary hypoxic vasoconstriction: not affected by chemical sympathectomy

1979 ◽  
Vol 46 (3) ◽  
pp. 529-533 ◽  
Author(s):  
C. A. Hales ◽  
D. M. Westphal
Keyword(s):  
Hypoxic Pulmonary Vasoconstriction ◽  
Systemic Blood Pressure ◽  
Lung Perfusion ◽  
Chemical Sympathectomy ◽  
Test Lung ◽  
Systemic Blood ◽  
Pulmonary Vasoconstriction ◽  
Hypoxic Vasoconstriction ◽  
Alveolar Hypoxia ◽  
6 Hydroxydopamine

The influence of chemical sympathectomy with 6-hydroxydopamine (6-OHDA) on regional alveolar hypoxic vasconstriction and on global hypoxic pulmonary vasoconstriction was investigated. In eight dogs a double-lumened endotracheal tube allowed ventilation of one lung with nitrogen as an alveolar hypoxic challenge while ventilation of the other lung with 100% O2 maintained adequate systemic oxygenation. Distribution of perfusion to the two lungs was determined with 133Xe and external counters. Mean perfusion to the test lung was 50.9 +/- 4.9% of total lung perfusion on room air and decreased by 32.4% (P smaller than 0.01) during alveolar hypoxia. Following 6-OHDA the test lung continued to reduce perfusion during alveolar hypoxia by 27.3%. In five dogs global hypoxia induced a 106% increase in pulmonary vascular resistance (PVR) prior to 6-OHDA and a 90% increase in PVR after 6-OHDA. After 6-OHDA no rise in PRV or systemic blood pressure occurred in response to tyramine, confirming effective sympathectomy by the 6-OHDA. Thus, sympathectomy with 6-OHDA failed to substantially block regional alveolar hypoxic vasoconstriction or global hypoxic pulmonary vasconstriction.

Hypoxic Pulmonary Vasoconstriction

2012 ◽  
Vol 92 (1) ◽  
pp. 367-520 ◽  
Author(s):  
J. T. Sylvester ◽  
Larissa A. Shimoda ◽  
Philip I. Aaronson ◽  
Jeremy P. T. Ward
Keyword(s):  
Hypoxic Pulmonary Vasoconstriction ◽  
Pulmonary Vessels ◽  
Pulmonary Vasoconstriction ◽  
Neonatal Life ◽  
High Altitude Pulmonary Edema ◽  
Alveolar Hypoxia ◽  
Pulmonary Arterial ◽  
Pulmonary Arterial Smooth Muscle ◽  
Isolated Lungs

It has been known for more than 60 years, and suspected for over 100, that alveolar hypoxia causes pulmonary vasoconstriction by means of mechanisms local to the lung. For the last 20 years, it has been clear that the essential sensor, transduction, and effector mechanisms responsible for hypoxic pulmonary vasoconstriction (HPV) reside in the pulmonary arterial smooth muscle cell. The main focus of this review is the cellular and molecular work performed to clarify these intrinsic mechanisms and to determine how they are facilitated and inhibited by the extrinsic influences of other cells. Because the interaction of intrinsic and extrinsic mechanisms is likely to shape expression of HPV in vivo, we relate results obtained in cells to HPV in more intact preparations, such as intact and isolated lungs and isolated pulmonary vessels. Finally, we evaluate evidence regarding the contribution of HPV to the physiological and pathophysiological processes involved in the transition from fetal to neonatal life, pulmonary gas exchange, high-altitude pulmonary edema, and pulmonary hypertension. Although understanding of HPV has advanced significantly, major areas of ignorance and uncertainty await resolution.

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.

Leukotriene inhibitors do not block hypoxic pulmonary vasoconstriction in dogs

1987 ◽  
Vol 62 (5) ◽  
pp. 1808-1813 ◽  
Author(s):  
D. P. Schuster ◽  
D. R. Dennis
Keyword(s):  
Blood Flow ◽  
Pulmonary Blood Flow ◽  
Pressor Response ◽  
Hypoxic Pulmonary Vasoconstriction ◽  
Lower Lobe ◽  
Left Lower Lobe ◽  
The Other ◽  
Pulmonary Vasoconstriction ◽  
Other Hand ◽  
Alveolar Hypoxia

We studied whether intravenously administered inhibitors of leukotriene synthesis (diethylcarbamazine, DEC) or end-organ effect (FPL-55712) would change the distribution of regional pulmonary blood flow (rPBF) caused by left lower lobe (LLL) alveolar hypoxia in dogs. Both drugs failed to alter rPBF. In addition, the pressor response to whole-lung hypoxia was not blocked by an FPL-55712 infusion. On the other hand, nitroprusside, as a nonspecific vasodilator also administered intravenously, was able to partially reverse the effects of LLL hypoxia on rPBF. Thus our data do not support a role for leukotriene mediation of hypoxic pulmonary vasoconstriction in dogs.

Effects of active vasoconstriction and total flow on perfusion distribution in the rabbit lung

1997 ◽  
Vol 273 (4) ◽  
pp. R1465-R1473 ◽  
Author(s):  
Yoshitaka Oyamada ◽  
Masaaki Mori ◽  
Ichiro Kuwahira ◽  
Takuya Aoki ◽  
Yukio Suzuki ◽  
...  
Keyword(s):  
Lung Tissue ◽  
Flow Rate ◽  
Hypoxic Pulmonary Vasoconstriction ◽  
Total Flow ◽  
Rabbit Lung ◽  
Pulmonary Vasoconstriction ◽  
Hypoxic Vasoconstriction ◽  
Lower Lung ◽  
Alveolar Hypoxia ◽  
Lung Base

We analyzed the effects of hypoxic vasoconstriction and total flow on the distribution of pulmonary perfusion in 38 isolated left rabbit lungs perfused under zone 3 conditions. Lungs were suspended in an upright position, oriented to the apicobasal line. Distributions of regional perfusion rates (RPR) along the vertical and horizontal axes were determined using nonradioactive microspheres labeled with heavy metal elements, which were detectable with X-ray fluorescence spectrometry. Changing the O2 concentration of a respirator and an extracorporeal membrane oxygenator independently, respective influences of active vasoconstriction induced by alveolar hypoxia and pulmonary artery hypoxia (PA hypoxia) on the RPR distribution were examined at a flow rate of 0.4 ml ⋅ min−1 ⋅ g wet lung tissue−1. To analyze the effects of changes in total flow, we investigated the RPR distribution at a perfusion rate of 1.2 ml ⋅ min−1 ⋅ g wet lung tissue−1. The RPR distribution in the absence of hypoxia was inhomogeneous and was augmented in the lower lung fields, whereas alveolar hypoxia shifted the RPR upward and significantly diminished the RPR in the lung base. RPR distributions along the horizontal axes under alveolar hypoxia conditions demonstrated that remarkable hypoxic pulmonary vasoconstriction (HPV) takes place in medial regions at the lung base. PA hypoxia altered the RPR distribution in qualitatively the same manner as alveolar hypoxia. Increased flow rate augmented the RPR in the lung, except in the dorsobasal region. These results suggest that the occurrence of HPV and the vascular conductance are not uniform throughout the lung.

Hypoxic pulmonary vasoconstriction

2007 ◽  
Vol 43 ◽  
pp. 61-76 ◽  
Author(s):  
A. Mark Evans
Keyword(s):  
Smooth Muscle ◽  
Cell Activation ◽  
Calcium Release ◽  
Hypoxic Pulmonary Vasoconstriction ◽  
Pulmonary Arteries ◽  
Right Heart Failure ◽  
Cell Types ◽  
Pulmonary Vasoconstriction ◽  
Alveolar Hypoxia ◽  
Different Cell Types

HPV (hypoxic pulmonary vasoconstriction) is the critical and distinguishing characteristic of the arteries that feed the lung. In marked contrast, systemic arteries dilate in response to hypoxia to meet the metabolic demands of the tissues they supply. Physiologically, HPV contributes to ventilation–perfusion matching in the lung by diverting blood flow to oxygen-rich areas. However, when alveolar hypoxia is global, as in diseases such as emphysema and cystic fibrosis, HPV leads to HPH (hypoxic pulmonary hypertension) and right heart failure. HPV is driven by the intrinsic response to hypoxia of two different cell types, namely the pulmonary arterial smooth muscle and endothelial cells. These are representatives of a group of specialized cells, commonly referred to as oxygen-sensing cells, which are defined by their acute sensitivity to relatively small changes in PO2 and have evolved to monitor oxygen supply and alter respiratory and circulatory function, as well as the capacity of the blood to transport oxygen. Upon exposure to hypoxia, mitochondrial oxidative phosphorylation is inhibited in all such cells and this, in part, mediates cell activation. In the case of pulmonary arteries, constriction is triggered via: (i) calcium release from the smooth muscle sarcoplasmic reticulum and consequent store-depletion-activated calcium entry into the smooth muscle cells and, (ii) the modulation of transmitter release from the pulmonary artery endothelium, which leads to further constriction of the smooth muscle by increasing the sensitivity of the contractile apparatus to calcium.

Stability of alveolar hypoxic vasoconstriction with intermittent hypoxia

1980 ◽  
Vol 49 (5) ◽  
pp. 846-850 ◽  
Author(s):  
M. A. Miller ◽  
C. A. Hales
Keyword(s):  
Hypoxic Pulmonary Vasoconstriction ◽  
Lung Perfusion ◽  
Double Lumen ◽  
Double Lumen Endotracheal Tube ◽  
Pulmonary Vasoconstriction ◽  
Group I ◽  
Hypoxic Vasoconstriction ◽  
Anesthetized Dogs ◽  
Alveolar Hypoxia ◽  
Group Ii

Repeated intermittent global hypoxia has been reported to markedly enhance hypoxic pulmonary vasoconstriction in dogs. We have reexamined this phenomenon but with intermittent unilateral alveolar hypoxia, avoiding complications of systemic hypoxemia. Fifteen anesthetized dogs were intubated with a double-lumen endotracheal tube, allowing separate ventilation of one lung with 100% N2 as a hypoxic challenge and the other lung with 100% O2 to maintain adequate systemic oxygenation. Distribution of lung perfusion was determined with intravenous 133Xe and external chest detectors. Each dog alternately breathed air or the unilateral alveolar hypoxia combination for 15 min each for a total of 12 hypoxic challenges or 6 h. Two groups emerged on the basis of the strength of their vasoconstrictor responses to successive hypoxic challenge. In group I (n = 6), perfusion to the hypoxic lung decreased 29% with the first challenge and decreased comparably with successive challenges. In group II, vasoconstriction was initially weak with perfusion decreasing only 5%, but perfusion decreased further with time alone (n = 5) or successive challenges (n = 4), falling 35% on the 12th challenge (comparable to group I). Delayed achievement of hypoxic vasoconstriction in group II may be secondary to a vasodilating prostanoid that disappears with time.

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