Spatial distribution of hypoxic pulmonary vasoconstriction in the supine pig

2004 ◽  
Vol 96 (5) ◽  
pp. 1589-1599 ◽  
Author(s):  
Michael P. Hlastala ◽  
Wayne J. E. Lamm ◽  
Adam Karp ◽  
Nayak L. Polissar ◽  
Ian R. Starr ◽  
...  
Keyword(s):  
Spatial Distribution ◽  
Response Pattern ◽  
Regional Blood Flow ◽  
Hypoxic Pulmonary Vasoconstriction ◽  
Random Order ◽  
Fluorescent Microspheres ◽  
Mechanically Ventilated ◽  
Pulmonary Vasoconstriction ◽  
Supine Posture ◽  
High Altitude Pulmonary Edema

Hypoxic pulmonary vasoconstriction (HPV) serves to maintain optimal gas exchange by decreasing perfusion to hypoxic regions. However, global hypoxia and nonuniform HPV may result in overperfusion of poorly constricted regions leading to local edema seen in high-altitude pulmonary edema. To quantify the spatial distribution of HPV and its response to regional Po2 (PrO2) among small lung regions, five pigs were anesthetized and mechanically ventilated in the supine posture. The animals were ventilated with an inspired O2 fraction (FiO2) of 0.50 and 0.21 and then (in random order) 0.15, 0.12, and 0.09. Regional blood flow (Q̇) and alveolar ventilation (V̇a) were measured by using intravenous infusion of 15 μm and inhalation of 1-μm fluorescent microspheres, respectively. PrO2 was calculated for each piece at each FiO2. Lung pieces differed in their Q̇ response to hypoxia in a manner related to their initial V̇a/Q̇ with FiO2 = 0.21. Reducing FiO2 < 0.15 decreased Q̇ to the initially high V̇a/Q̇ (higher PrO2) regions and forced Q̇ into the low V̇a/Q̇ (dorsal-caudal) regions. Resistance increased in most lung pieces as PrO2 decreased, reaching a maximum resistance when PrO2 is between 40 and 50 Torr. Local resistance decreased at Pro2 < 40 Torr. Pieces were statistically clustered with respect to their relative Q̇ response pattern to each FiO2. Some clusters were shown to be spatially organized. We conclude that HPV is spatially heterogeneous. The heterogeneity of Q̇ response may be related, in part, to the heterogeneity of baseline V̇a/Q̇.

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.

Potentiation of hypoxic pulmonary vasoconstriction by ethyl alcohol in dogs

1978 ◽  
Vol 44 (1) ◽  
pp. 76-80 ◽  
Author(s):  
R. C. Doekel ◽  
E. K. Weir ◽  
R. Looga ◽  
R. F. Grover ◽  
J. T. Reeves
Keyword(s):  
Pressor Response ◽  
Hypoxic Pulmonary Vasoconstriction ◽  
Blood Gases ◽  
Adrenergic Blockade ◽  
Mechanically Ventilated ◽  
Pulmonary Vasoconstriction ◽  
Arterial Blood ◽  
Before And After ◽  
Pressor Activity ◽  
Inhibition Of Prostaglandin Synthesis

Pulmonary and systemic hemodynamics and arterial blood gases were measured in anesthetized and mechanically ventilated dogs before and after oral or intravenous administration of ethanol. Increases in mean pulmonary artery pressure and pulmonary vascular resistance occurred. Platelet antiserum-induced thrombocytopenia inhibition of prostaglandin synthesis with meclofenamate, or alpha-adrenergic blockade did not alter the pulmonary pressor response to ethanol. However, the increase in resistance following ethanol was abolished by hyperoxia and potentiated by hypoxia. Thus, it appears that the effect of ethanol is to augment hypoxic pulmonary vasoconstriction, whereas ethanol per se has no independent pulmonary pressor activity.

Improvement in Oxygenation by Phenylephrine and Nitric Oxide in Patients with Adult Respiratory Distress Syndrome 

1997 ◽  
Vol 87 (1) ◽  
pp. 18-25 ◽  
Author(s):  
Elana B. Doering ◽  
C. William Hanson ◽  
Daniel J. Reily ◽  
Carol Marshall ◽  
Bryan E. Marshall
Keyword(s):  
Nitric Oxide ◽  
Respiratory Distress Syndrome ◽  
Respiratory Distress ◽  
Adult Respiratory Distress Syndrome ◽  
Distress Syndrome ◽  
Hypoxic Pulmonary Vasoconstriction ◽  
Random Order ◽  
Pulmonary Vasoconstriction ◽  
Arterial Blood ◽  
Inhaled No

Background Inhaled nitric oxide (NO), a selective vasodilator, improves oxygenation in many patients with adult respiratory distress syndrome (ARDS). Vasoconstrictors may also improve oxygenation, possibly by enhancing hypoxic pulmonary vasoconstriction. This study compared the effects of phenylephrine, NO, and their combination in patients with ARDS. Methods Twelve patients with ARDS (PaO2/FIO2 &lt;le&gt; 180; Murray score &lt;me&gt; 2) were studied. Each patient received three treatments in random order: intravenous phenylephrine, 50-200 micrograms/min, titrated to a 20% increase in mean arterial blood pressure; inhaled NO, 40 ppm; and the combination (phenylephrine+NO). Hemodynamics and blood gas measurements were made during each treatment and at pre- and posttreatment baselines. Results All three treatments improved PaO2 overall. Six patients were "phenylephrine-responders" (delta PaO2 &gt; 10 mmHg), and six were "phenylephrine-nonresponders." In phenylephrine-responders, the effect of phenylephrine was comparable with that of NO (PaO2 from 105 +/- 14 to 132 +/- 14 mmHg with phenylephrine, and from 110 +/- 14 to 143 +/- 19 mmHg with NO), and the effect of phenylephrine+NO was greater than that of either treatment alone (PaO2 from 123 +/- 13 to 178 +/- 23 mmHg). In phenylephrine-nonresponders, phenylephrine did not affect PaO2, and the effect of phenylephrine+NO was not statistically different from that of NO alone (PaO2 from 82 +/- 12 to 138 +/- 28 mmHg with NO; from 84 +/- 12 to 127 +/- 23 mmHg with phenylephrine+NO). Data are mean +/- SEM. Conclusions Phenylephrine alone can improve PaO2 in patients with ARDS. In phenylephrine-responsive patients, phenylephrine augments the improvement in PaO2 seen with inhaled NO. These results may reflect selective enhancement of hypoxic pulmonary vasoconstriction by phenylephrine, which complements selective vasodilation by NO.

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.

scholarly journals Almitrine as a non ventilatory strategy to improve intrapulmonary shunt in COVID-19 patients

2020 ◽  
Author(s):  
MARIE REINE LOSSER ◽  
COLINE LAPOIX ◽  
BENOIT CHAMPIGNEULLE ◽  
MATTHIEU DELANNOY ◽  
JEAN FRANCOIS PAYEN ◽  
...  
Keyword(s):  
Hypoxic Pulmonary Vasoconstriction ◽  
Dose Effect ◽  
Pharmacological Intervention ◽  
Severe Hypoxemia ◽  
Intrapulmonary Shunt ◽  
Ventilatory Strategy ◽  
Control Series ◽  
Mechanically Ventilated ◽  
Pulmonary Vasodilation ◽  
Pulmonary Vasoconstriction

In severe COVID-19 pulmonary failure, hypoxia is mainly related to pulmonary vasodilation with altered hypoxic pulmonary vasoconstriction (HPV). Besides prone positioning, other non-ventilatory strategies may reduce the intrapulmonary shunt. This study has investigated almitrine, a pharmacological option to improve oxygenation. Patients and Method. A case control series of 17 confirmed COVID-19 mechanically ventilated patients in prone or supine positioning was collected: 10 patients received two doses of almitrine (4 and 12 mcg/kg/min) at 30-45 min interval each, and were compared to 7 control COVID-matched patients conventionally treated. The end-point was the reduction of intra-pulmonary shunt increasing the PaO2 and ScvO2. Results Patients were male (59%) with median (25th, 75th percentiles) age of 70 (54-78) years and a BMI of 29 (23-34). At stable mechanical ventilatory settings, PaO2 (mmHg) at FiO2 1 (135 (85, 195) to 214 (121, 275); p = 0.06) tended to increase with almitrine. This difference was significant when the best PaO2 between the 2 doses was used : 215 (123,294) vs baseline (p = 0.01). A concomitant increase in ScvO2 occurred ((73 (72, 76) to 82 (80, 87); p = 0.02). Eight over 10 almitrine-treated patients increased their PaO2, with no clear dose-effect. During the same time, the controls did not change PaO2. In conclusion, in early COVID-19 with severe hypoxemia, almitrine infusion is associated with improved oxygenation in prone or supine positioning. This pharmacological intervention may offer an alternative and/or an additional effect to proning and might delay or avoid more demanding modalities such as ECMO.

scholarly journals Functional Pathophysiology of SARS-CoV-2 Induced Acute Lung Injury and Clinical Implications

2021 ◽  
Author(s):  
Nader M. Habashi ◽  
Luigi Camporota ◽  
Louis A. Gatto ◽  
Gary F. Nieman
Keyword(s):  
Hypoxic Pulmonary Vasoconstriction ◽  
Renin Angiotensin System ◽  
Lung Weight ◽  
Angiotensin System ◽  
Mechanically Ventilated ◽  
Pulmonary Vasoconstriction ◽  
Ventilation Strategies ◽  
Pressure Release Ventilation ◽  
Ventilation Perfusion Ratio ◽  
Standard Ventilation

The worldwide pandemic caused by the SARS-CoV-2 virus has resulted in over 84,407,000 cases with over 1,800,000 deaths when this paper was submitted, with comorbidities such as gender, race, age, body mass, diabetes, and hypertension greatly exacerbating mortality. This review will analyze the rapidly increasing knowledge of COVID-19 induced lung pathophysiology. Although controversial, the acute respiratory distress syndrome (ARDS) associated with COVID-19 (CARDS) seems to present as two distinct phenotypes: Type-L and Type-H. The 'L' refers to Low elastance, ventilation/perfusion ratio, lung weight, and recruitability, and the 'H' refers to High pulmonary elastance, shunt, edema, and recruitability. However, the LUNG SAFE and ESICM Trials Groups has shown that ~13% of the mechanically ventilated non-COVID-19 ARDS patients have the Type-L phenotype. However, other studies have shown that CARDS and ARDS respiratory mechanics overlap and that standard ventilation strategies apply to these patients. The mechanisms causing alterations in pulmonary perfusion could be caused by some combination of: 1) renin-angiotensin system (RAS) dysregulation, 2) thrombosis caused by loss of endothelial barrier, 3) endothelial dysfunction causing loss of hypoxic pulmonary vasoconstriction (HPV) perfusion control, and 4) hyper-perfusion of collapsed lung tissue that has been directly measured and supported by a computational model. A flow chart has been constructed highlighting the need for personalized and adaptive ventilation strategies, such as the time controlled adaptive ventilation (TCAV) method to set and adjust the airway pressure release ventilation (APRV) mode, which recently was shown effective at improving oxygenation and reducing FiO2, vasopressors, and sedation in COVID-19 patients.

Endotoxemia increases relative perfusion to dorsal-caudal lung regions

2001 ◽  
Vol 90 (4) ◽  
pp. 1508-1515 ◽  
Author(s):  
Anthony J. Gerbino ◽  
William A. Altemeier ◽  
Carmel Schimmel ◽  
Robb W. Glenny
Keyword(s):  
Spatial Distribution ◽  
Acute Lung Injury ◽  
Gas Exchange ◽  
Lung Injury ◽  
Vascular Response ◽  
Regional Ventilation ◽  
Fluorescent Microspheres ◽  
Mechanically Ventilated ◽  
Ventilation And Perfusion ◽  
Time Point

Changes in the spatial distribution of perfusion during acute lung injury and their impact on gas exchange are poorly understood. We tested whether endotoxemia caused topographical differences in perfusion and whether these differences caused meaningful changes in regional ventilation-to-perfusion ratios and gas exchange. Regional ventilation and perfusion were measured in anesthetized, mechanically ventilated pigs in the prone position before and during endotoxemia with the use of aerosolized and intravenous fluorescent microspheres. On average, relative perfusion halved in ventral and cranial lung regions, doubled in caudal lung regions, and increased 1.5-fold in dorsal lung regions during endotoxemia. In contrast, there were no topographical differences in perfusion before endotoxemia and no topographical differences in ventilation at any time point. Consequently, endotoxemia increased regional ventilation-to-perfusion ratios in the caudal-to-cranial and dorsal-to-ventral directions, resulting in end-capillary Po 2 values that were significantly lower in dorsal-caudal than ventral-cranial regions. We conclude that there are topographical differences in the pulmonary vascular response to endotoxin that may have important consequences for gas exchange in acute lung injury.

Physiological aspects of high-altitude pulmonary edema

2005 ◽  
Vol 98 (3) ◽  
pp. 1101-1110 ◽  
Author(s):  
Peter Bärtsch ◽  
Heimo Mairbäurl ◽  
Marco Maggiorini ◽  
Erik R. Swenson
Keyword(s):  
Pulmonary Edema ◽  
High Altitude ◽  
Hypoxic Pulmonary Vasoconstriction ◽  
Right Heart Catheterization ◽  
Lung Edema ◽  
Heart Catheterization ◽  
Edema Formation ◽  
Pulmonary Vasoconstriction ◽  
Large Molecular Weight ◽  
High Altitude Pulmonary Edema

High-altitude pulmonary edema (HAPE) develops in rapidly ascending nonacclimatized healthy individuals at altitudes above 3,000 m. An excessive rise in pulmonary artery pressure (PAP) preceding edema formation is the crucial pathophysiological factor because drugs that lower PAP prevent HAPE. Measurements of nitric oxide (NO) in exhaled air, of nitrites and nitrates in bronchoalveolar lavage (BAL) fluid, and forearm NO-dependent endothelial function all point to a reduced NO availability in hypoxia as a major cause of the excessive hypoxic PAP rise in HAPE-susceptible individuals. Studies using right heart catheterization or BAL in incipient HAPE have demonstrated that edema is caused by an increased microvascular hydrostatic pressure in the presence of normal left atrial pressure, resulting in leakage of large-molecular-weight proteins and erythrocytes across the alveolarcapillary barrier in the absence of any evidence of inflammation. These studies confirm in humans that high capillary pressure induces a high-permeability-type lung edema in the absence of inflammation, a concept first introduced under the term “stress failure.” Recent studies using microspheres in swine and magnetic resonance imaging in humans strongly support the concept and primacy of nonuniform hypoxic arteriolar vasoconstriction to explain how hypoxic pulmonary vasoconstriction occurring predominantly at the arteriolar level can cause leakage. This compelling but as yet unproven mechanism predicts that edema occurs in areas of high blood flow due to lesser vasoconstriction. The combination of high flow at higher pressure results in pressures, which exceed the structural and dynamic capacity of the alveolar capillary barrier to maintain normal alveolar fluid balance.

scholarly journals Inhaled nitric oxide alters the distribution of blood flow in the healthy human lung, suggesting active hypoxic pulmonary vasoconstriction in normoxia

2015 ◽  
Vol 118 (3) ◽  
pp. 331-343 ◽  
Author(s):  
Amran K. Asadi ◽  
Rui Carlos Sá ◽  
Nick H. Kim ◽  
Rebecca J. Theilmann ◽  
Susan R. Hopkins ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Blood Flow ◽  
Spatial Heterogeneity ◽  
Human Lung ◽  
Regional Blood Flow ◽  
Hypoxic Pulmonary Vasoconstriction ◽  
Inhaled Nitric Oxide ◽  
Spatiotemporal Variability ◽  
Healthy Human ◽  
Pulmonary Vasoconstriction

Hypoxic pulmonary vasoconstriction (HPV) is thought to actively regulate ventilation-perfusion (V̇a/Q̇) matching, reducing perfusion in regions of alveolar hypoxia. We assessed the extent of HPV in the healthy human lung using inhaled nitric oxide (iNO) under inspired oxygen fractions (FiO2) of 0.125, 0.21, and 0.30 (a hyperoxic stimulus designed to abolish HPV without the development of atelectasis). Dynamic measures of blood flow were made in a single sagittal slice of the right lung of five healthy male subjects using an arterial spin labeling (ASL) MRI sequence, following a block stimulus pattern (3 × 60 breaths) with 40 ppm iNO administered in the central block. The overall spatial heterogeneity, spatiotemporal variability, and regional pattern of pulmonary blood flow was quantified as a function of condition (FiO2× iNO state). While spatial heterogeneity did not change significantly with iNO administration or FiO2, there were statistically significant increases in Global Fluctuation Dispersion,(a marker of spatiotemporal flow variability) when iNO was administered during hypoxia (5.4 percentage point increase, P = 0.003). iNO had an effect on regional blood flow that was FiO2dependent ( P = 0.02), with regional changes in the pattern of blood flow occurring in hypoxia ( P = 0.007) and normoxia ( P = 0.008) tending to increase flow to dependent lung at the expense of nondependent lung. These findings indicate that inhaled nitric oxide significantly alters the distribution of blood flow in both hypoxic and normoxic healthy subjects, and suggests that some baseline HPV may indeed be present in the normoxic lung.

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