NOS3 deficiency augments hypoxic pulmonary vasoconstriction and enhances systemic oxygenation during one-lung ventilation in mice

2005 ◽  
Vol 98 (2) ◽  
pp. 748-752 ◽  
Author(s):  
Rong Liu ◽  
Oleg V. Evgenov ◽  
Fumito Ichinose
Keyword(s):  
Hypoxic Pulmonary Vasoconstriction ◽  
Left Lung ◽  
Lung Ventilation ◽  
Gas Analysis ◽  
Wild Type ◽  
One Lung Ventilation ◽  
Pulmonary Vasoconstriction ◽  
Arterial Blood ◽  
Deficient Mice

Nitric oxide (NO), synthesized by NO synthases (NOS), plays a pivotal role in regulation of pulmonary vascular tone. To examine the role of endothelial NOS (NOS3) in hypoxic pulmonary vasoconstriction (HPV), we measured left lung pulmonary vascular resistance (LPVR), intrapulmonary shunting, and arterial Po2 (PaO2) before and during left mainstem bronchus occlusion (LMBO) in mice with and without a deletion of the gene encoding NOS3. The increase of LPVR induced by LMBO was greater in NOS3-deficient mice than in wild-type mice (151 ± 39% vs. 109 ± 36%, mean ± SD; P < 0.05). NOS3-deficient mice had a lower intrapulmonary shunt fraction than wild-type mice (17.1 ± 3.6% vs. 21.7 ± 2.4%, P < 0.05) during LMBO. Both real-time PaO2 monitoring with an intra-arterial probe and arterial blood-gas analysis during LMBO showed higher PaO2 in NOS3-deficient mice than in wild-type mice ( P < 0.05). Inhibition of all three NOS isoforms with Nω-nitro-l-arginine methyl ester (l-NAME) augmented the increase of LPVR induced by LMBO in wild-type mice (183 ± 67% in l-NAME treated vs. 109 ± 36% in saline treated, P < 0.01) but not in NOS3-deficient mice. Similarly, systemic oxygenation during one-lung ventilation was augmented by l-NAME in wild-type mice but not in NOS3-deficient mice. These findings indicate that NO derived from NOS3 modulates HPV in vivo and that inhibition of NOS3 improves systemic oxygenation during acute unilateral lung hypoxia.

Effect of anemia on intrapulmonary shunt during atelectasis in rabbits

1995 ◽  
Vol 79 (6) ◽  
pp. 1951-1957 ◽  
Author(s):  
S. Deem ◽  
M. J. Bishop ◽  
M. K. Alberts
Keyword(s):  
Hypoxic Pulmonary Vasoconstriction ◽  
Left Lung ◽  
Blood Gas Analysis ◽  
Gas Analysis ◽  
Blood Gas ◽  
Intrapulmonary Shunt ◽  
Fluorescent Microspheres ◽  
Pulmonary Vasoconstriction ◽  
Arterial Po2 ◽  
Over Time

To elucidate the effects of anemia on intrapulmonary shunt, we studied a model of left lung atelectasis in anesthetized rabbits. In 10 rabbits, isovolemic anemia was produced by sequential hemodilution. Seven control rabbits were followed over time, without hemodilution. Intrapulmonary shunt (Qs/QT) was measured by using blood gas analysis and by quantitation of the percentage of blood flow to the collapsed left lung (QLl/QT) using fluorescent microspheres. In control rabbits, Qs/QT and QLl/QT decreased over time, whereas arterial PO2 increased. In hemodiluted rabbits, there was a trend toward increased Qs/QT and QLl/QT. There were significant differences in the behavior of Qs/QT, QLl/QT, and arterial PO2 between control and hemodiluted rabbits. Hemodynamic parameters, including cardiac output and pulmonary artery pressure, were not different between groups. In a third group of rabbits with pharmacologically induced acidosis but no hemodilution, Qs/QT and QLl/QT decreased over time, and arterial PO2 increased. We conclude that acute isovolemic anemia has a deleterious effect on pulmonary gas exchange, possibly through attenuation of hypoxic pulmonary vasoconstriction.

Role of endogenous nitric oxide in endotoxin-induced alteration of hypoxic pulmonary vasoconstriction in mice

2005 ◽  
Vol 289 (2) ◽  
pp. H823-H831 ◽  
Author(s):  
Fabian Spöhr ◽  
Annemiek J. M. Cornelissen ◽  
Cornelius Busch ◽  
Martha M. Gebhard ◽  
Johann Motsch ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Hypoxic Pulmonary Vasoconstriction ◽  
No Production ◽  
Wild Type ◽  
Pulmonary Vasodilation ◽  
Congenital Deficiency ◽  
Pulmonary Vasoconstriction ◽  
Vasoconstrictor Response ◽  
Endogenous Nitric Oxide ◽  
Deficient Mice

Pulmonary vasoconstriction in response to alveolar hypoxia (HPV) is frequently impaired in patients with sepsis or acute respiratory distress syndrome or in animal models of endotoxemia. Pulmonary vasodilation due to overproduction of nitric oxide (NO) by NO synthase 2 (NOS2) may be responsible for this impaired HPV after administration of endotoxin (LPS). We investigated the effects of acute nonspecific ( NG-nitro-l-arginine methyl ester, l-NAME) and NOS2-specific [l- N6-(1-iminoethyl)lysine, l-NIL] NOS inhibition and congenital deficiency of NOS2 on impaired HPV during endotoxemia. The pulmonary vasoconstrictor response and pulmonary vascular pressure-flow (P-Q) relationship during normoxia and hypoxia were studied in isolated, perfused, and ventilated lungs from LPS-pretreated and untreated wild-type and NOS2-deficient mice with and without l-NAME or l-NIL added to the perfusate. Compared with lungs from untreated mice, lungs from LPS-challenged wild-type mice constricted less in response to hypoxia (69 ± 17 vs. 3 ± 7%, respectively, P < 0.001). Perfusion with l-NAME or l-NIL restored this blunted HPV response only in part. In contrast, LPS administration did not impair the vasoconstrictor response to hypoxia in NOS2-deficient mice. Analysis of the pulmonary vascular P-Q relationship suggested that the HPV response may consist of different components that are specifically NOS isoform modulated in untreated and LPS-treated mice. These results demonstrate in a murine model of endotoxemia that NOS2-derived NO production is critical for LPS-mediated development of impaired HPV. Furthermore, impaired HPV during endotoxemia may be at least in part mediated by mechanisms other than simply pulmonary vasodilation by NOS2-derived NO overproduction.

Lung Isolation

2018 ◽  
Author(s):  
Bryan Hierlmeier ◽  
Vanetta Levesque ◽  
Henrique Vale
Keyword(s):  
Thoracoscopic Surgery ◽  
Hypoxic Pulmonary Vasoconstriction ◽  
Lung Ventilation ◽  
Double Lumen Tube ◽  
Lung Protective Ventilation ◽  
One Lung Ventilation ◽  
Double Lumen ◽  
Lung Isolation ◽  
Pulmonary Vasoconstriction ◽  
Protective Strategies

Lung isolation is being used more frequently in adult patients due to increasing incidence of thoracoscopy and video-assisted thoracoscopic surgery. There are several indications for lung isolation and one-lung ventilation (OLV) during surgery. Isolation is usually achieved by double-lumen endotracheal tubes or use of some type of bronchial blocker system. The initiation of OLV frequently leads to hypoxemia, the management of which should be stepwise. Additionally, clinical outcomes are significantly improved with the use of lung protective strategies during OLV. This review covers the use of few of the most common lung isolation devices, management of OLV using lung protective ventilation strategies, and management of oxygenation and hypoxemia during OLV. This review contains 12 figures, 6 tables, and 36 references. Key Words: bronchial blockers, double-lumen tube, uninvent, hypoxemia, hypoxic pulmonary vasoconstriction, one lung ventilation, positive end expiratory pressure, tracheal anatomy, lung isolation

Congenital NOS2 deficiency prevents impairment of hypoxic pulmonary vasoconstriction in murine ventilator-induced lung injury

2007 ◽  
Vol 293 (5) ◽  
pp. L1300-L1305 ◽  
Author(s):  
Rong Liu ◽  
Yukako Hotta ◽  
Amanda R. Graveline ◽  
Oleg V. Evgenov ◽  
Emmanuel S. Buys ◽  
...  
Keyword(s):  
Lung Injury ◽  
Tidal Volume ◽  
Hypoxic Pulmonary Vasoconstriction ◽  
Left Lung ◽  
Arterial Oxygen Tension ◽  
Arterial Oxygen ◽  
Lung Edema ◽  
Wild Type ◽  
Ventilator Induced Lung Injury ◽  
Pulmonary Vasoconstriction

Hypoxic pulmonary vasoconstriction (HPV) preserves systemic arterial oxygenation during lung injury by diverting blood flow away from poorly ventilated lung regions. Ventilator-induced lung injury (VILI) is characterized by pulmonary inflammation, lung edema, and impaired HPV leading to systemic hypoxemia. Studying mice congenitally deficient in inducible nitric oxide synthase (NOS2) and wild-type mice treated with a selective NOS2 inhibitor, l- N6-(1-iminoethyl)lysine (l-NIL), we investigated the contribution of NOS2 to the impairment of HPV in anesthetized mice subjected to 6 h of either high tidal volume (HVT) or low tidal volume (LVT) ventilation. HPV was estimated by measuring the changes of left lung pulmonary vascular resistance (LPVR) in response to left mainstem bronchus occlusion (LMBO). LMBO increased the LPVR similarly in wild-type, NOS2−/−, and wild-type mice treated with l-NIL 30 min before commencing 6 h of LVT ventilation (96% ± 30%, 103% ± 33%, and 80% ± 16%, respectively, means ± SD). HPV was impaired in wild-type mice subjected to 6 h of HVT ventilation (23% ± 16%). In contrast, HPV was preserved after 6 h of HVT ventilation in NOS2−/− and wild-type mice treated with l-NIL either 30 min before or 6 h after commencing HVT ventilation (66% ± 22%, 82% ± 29%, and 85% ± 16%, respectively). After 6 h of HVT ventilation and LMBO, systemic arterial oxygen tension was higher in NOS2−/− than in wild-type mice (192 ± 11 vs. 171 ± 17 mmHg; P < 0.05). We conclude that either congenital NOS2 deficiency or selective inhibition of NOS2 protects mice from the impairment of HPV occurring after 6 h of HVT ventilation.

Hypoxic Pulmonary Vasoconstriction

2015 ◽  
Vol 122 (4) ◽  
pp. 932-946 ◽  
Author(s):  
Andrew B. Lumb ◽  
Peter Slinger
Keyword(s):  
Hypoxic Pulmonary Vasoconstriction ◽  
Lung Ventilation ◽  
Second Phase ◽  
Lung Pathology ◽  
Regional Ventilation ◽  
One Lung Ventilation ◽  
Intravenous Anesthetic ◽  
Anesthetic Drugs ◽  
Pulmonary Vasoconstriction ◽  
Ventilation And Perfusion

Abstract Hypoxic pulmonary vasoconstriction (HPV) represents a fundamental difference between the pulmonary and systemic circulations. HPV is active in utero, reducing pulmonary blood flow, and in adults helps to match regional ventilation and perfusion although it has little effect in healthy lungs. Many factors affect HPV including pH or Pco2, cardiac output, and several drugs, including antihypertensives. In patients with lung pathology and any patient having one-lung ventilation, HPV contributes to maintaining oxygenation, so anesthesiologists should be aware of the effects of anesthesia on this protective reflex. Intravenous anesthetic drugs have little effect on HPV, but it is attenuated by inhaled anesthetics, although less so with newer agents. The reflex is biphasic, and once the second phase becomes active after about an hour of hypoxia, this pulmonary vasoconstriction takes hours to reverse when normoxia returns. This has significant clinical implications for repeated periods of one-lung ventilation.

Time course of hypoxic pulmonary vasoconstriction after endotoxin infusion in unanesthetized sheep

1991 ◽  
Vol 70 (5) ◽  
pp. 2120-2125 ◽  
Author(s):  
J. L. Theissen ◽  
H. M. Loick ◽  
B. B. Curry ◽  
L. D. Traber ◽  
D. N. Herndon ◽  
...  
Keyword(s):  
Blood Flow ◽  
Cardiac Output ◽  
Time Course ◽  
Hypoxic Pulmonary Vasoconstriction ◽  
Left Lung ◽  
Arterial Blood Flow ◽  
Endotoxin Infusion ◽  
Pulmonary Vasoconstriction ◽  
Arterial Blood ◽  
Time Period

Endotoxin [lipopolysaccharide (LPS)] has been reported to reduce hypoxic pulmonary vasoconstriction and thus increases venous admixture. The time course of this failure of pulmonary blood flow regulation was investigated in six chronically instrumented unanesthetized sheep after infusion of Escherichia coli LPS (1 microgram/kg). The change in left pulmonary arterial blood flow (LPBF, ultrasonic transit time) in response to unilateral lung hypoxia (10 min of N2 alternately to the left and right lungs) was compared before and at various time intervals after the administration of LPS. During baseline conditions, LPBF was 33% of total cardiac output and decreased to 15% when the left lung was ventilated with a hypoxic gas mixture. One hour after endotoxin infusion, LPBF remained at 33% of total cardiac output yet only decreased to 28% during the hypoxic challenge. The response to one-lung hypoxia was still significantly depressed 10 h post-LPS administration. It is concluded that hypoxic pulmonary vasoconstriction is almost completely abolished for a prolonged time period after a small dose of LPS.

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