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.

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.

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.

Bleomycin-induced lung injury in rats selectively abolishes hypoxic pulmonary vasoconstriction: Evidence against a role for platelet-activating factor

1992 ◽  
Vol 82 (3) ◽  
pp. 259-264 ◽  
Author(s):  
David G. McCormack ◽  
David E. Crawley ◽  
Peter J. Barnes ◽  
Timothy W. Evans
Keyword(s):  
Angiotensin Ii ◽  
Lung Injury ◽  
Pressor Response ◽  
Hypoxic Pulmonary Vasoconstriction ◽  
Platelet Activating Factor ◽  
Saline Control ◽  
Lung Weight ◽  
Intratracheal Administration ◽  
Pulmonary Vasoconstriction ◽  
Web 2086

1. The role of platelet-activating factor in the attenuated hypoxic pulmonary vasoconstriction associated with lung injury was evaluated using specific platelet-activating factor antagonists and an isolated perfused lung preparation. 2. Intratracheal bleomycin was administered to rats to produce acute lung injury. Animals received intratracheal saline (control), intratracheal bleomycin or the platelet-activating factor anatagonists BN 52021, WEB 2170 or WEB 2086 before and after bleomycin treatment. Forty-eight hours after intratracheal administration of bleomycin or saline the animals were killed. 3. The increases in pulmonary artery pressure during two periods of hypoxic ventilation and in response to 0.2 μg of angiotensin II were measured. Acetylcholine-induced vasodilatation after pre-constriction with prostaglandin F2α was also measured. To quantify lung injury, the wet/ dry ratio of lung weight was determined. 4. Bleomycin treatment attenuated the first and second hypoxic pressor responses by 93% and 77%, respectively, but not the pressor response to angiotensin II nor the vasodilator response to acetylcholine. BN 52021 plus bleomycin augmented the first hypoxic pressor response compared with bleomycin treatment alone, but the structurally unrelated platelet-activating factor antagonists WEB 2170 and WEB 2086 had no significant effect on the bleomycin-induced attenuation of hypoxic pulmonary vasoconstriction. None of the platelet-activating factor antagonists blocked the increase in the wet/dry lung weight ratio induced by bleomycin. 5. Bleomycin-induced lung injury selectively attenuates hypoxic pulmonary vasoconstriction, an effect that does not appear to be mediated by platelet-activating factor. The mechanism remains to be elucidated, but may involve destruction of the hypoxic ‘sensor’ within the respiratory tract.

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.

Influence of bronchial arterial PO2 on pulmonary vascular resistance

1991 ◽  
Vol 70 (1) ◽  
pp. 405-415 ◽  
Author(s):  
B. E. Marshall ◽  
C. Marshall ◽  
M. Magno ◽  
P. Lilagan ◽  
G. G. Pietra
Keyword(s):  
Vascular Resistance ◽  
Bronchial Artery ◽  
Hypoxic Pulmonary Vasoconstriction ◽  
Pulmonary Arteries ◽  
Vasa Vasorum ◽  
Pulmonary Vasculature ◽  
Mechanically Ventilated ◽  
Bronchial Circulation ◽  
Pulmonary Vasodilation ◽  
Pulmonary Vasoconstriction

In six anesthetized and mechanically ventilated adult sheep, the bronchial artery was perfused with blood from an oxygenator-pump circuit. When the lungs were ventilated with 100% O2 and the bronchial O2 tension (PbrO2) was approximately 600 Torr, the mean of the pulmonary vascular resistances (PVR) measured at the beginning (3.32 +/- 0.29 units) and end (3.17 +/- 0.13 units) of the experiment was 3.24 +/- 0.20 units. When the PbrO2 was changed to 58 +/- 1 Torr, the PVR (2.99 +/- 0.14 units) did not change significantly. However, when the lungs were ventilated with air as PbrO2 was decreased to 91 +/- 4, 77 +/- 3, 56 +/- 2, and 42 +/- 1 Torr, the PVR increased to 3.67 +/- 0.18, 4.03 +/- 0.16, 4.79 +/- 0.19, and 4.71 +/- 0.35 units, respectively. However, when the PbrO2 was decreased further to 26 +/- 1 and 13 +/- 1 Torr, the PVR decreased to 3.77 +/- 0.28 and 3.91 +/- 0.30 units, respectively. In contrast, the bronchial vascular resistance decreased monotonically as PbrO2 decreased. The bronchial circulation supplies vasa vasorum to the walls of all but the smallest pulmonary arteries, and it is therefore suggested that the PO2 of the bronchial circulation is responsible for the bimodal response of the pulmonary vasculature, with stimulation of hypoxic pulmonary vasoconstriction at moderate hypoxemia and of hypoxic pulmonary vasodilation at profound hypoxemia. The physiological and pathophysiological significance of the influence of systemic PO2 on pulmonary vascular tone is discussed.

Acute hypoxic pulmonary vasoconstriction in conscious dogs decreases renin and is unaffected by losartan

1999 ◽  
Vol 86 (6) ◽  
pp. 1914-1919 ◽  
Author(s):  
Martin O. Krebs ◽  
Willehad Boemke ◽  
Stephan Simon ◽  
Maieli Wenz ◽  
Gabriele Kaczmarczyk
Keyword(s):  
Vascular Resistance ◽  
Sodium Intake ◽  
Minute Ventilation ◽  
Hypoxic Pulmonary Vasoconstriction ◽  
Acute Hypoxia ◽  
Renin Angiotensin System ◽  
Dietary Sodium ◽  
Arterial Oxygen ◽  
Ang Ii ◽  
Pulmonary Vasoconstriction

Acute hypoxic pulmonary vasoconstriction (HPV) may be mediated by vasoactive peptides. We studied eight conscious, chronically tracheostomized dogs kept on a standardized dietary sodium intake. Normoxia (40 min) was followed by hypoxia (40 min, breathing 10% oxygen, arterial oxygen pressures 36 ± 1 Torr) during both control (Con) and losartan experiments (Los; iv infusion of 100 μg ⋅ min−1 ⋅ kg−1losartan). During hypoxia, minute ventilation (by 0.9 l/min in Con, by 1.3 l/min in Los), cardiac output (by 0.36 l/min in Con, by 0.30 l/min in Los), heart rate (by 11 beats/min in Con, by 30 beats/min in Los), pulmonary artery pressure (by 9 mmHg in both protocols), and pulmonary vascular resistance (by 280 and 254 dyn ⋅ s ⋅ cm−5in Con and Los, respectively) increased. Mean arterial pressure and systemic vascular resistance did not change. In Con, PRA decreased from 4.2 ± 0.7 to 2.5 ± 0.5 ng ANG I ⋅ ml−1 ⋅ h−1, and plasma ANG II decreased from 11.9 ± 3.0 to 8.2 ± 2.1 pg/ml. The renin-angiotensin system is inhibited during acute hypoxia despite sympathetic activation. Under these conditions, ANG II AT1-receptor antagonism does not attenuate HPV.

Regional hypoxic pulmonary vasoconstriction in prone pigs

2005 ◽  
Vol 99 (1) ◽  
pp. 363-370 ◽  
Author(s):  
I. R. Starr ◽  
W. J. E. Lamm ◽  
B. Neradilek ◽  
N. Polissar ◽  
R. W. Glenny ◽  
...  
Keyword(s):  
Blood Flow ◽  
Pulmonary Blood Flow ◽  
Hypoxic Pulmonary Vasoconstriction ◽  
Flow Distribution ◽  
Response Patterns ◽  
Mechanically Ventilated ◽  
Oxygen Fraction ◽  
Pulmonary Vasoconstriction ◽  
Initial Difference ◽  
Inspired Oxygen

Hypoxic pulmonary vasoconstriction (HPV) is known to affect regional pulmonary blood flow distribution. It is unknown whether lungs with well-matched ventilation (V̇)/perfusion (Q̇) have regional differences in the HPV response. Five prone pigs were anesthetized and mechanically ventilated (positive end-expiratory pressure = 2 cmH2O). Two hypoxic preconditions [inspired oxygen fraction (FiO2) = 0.13] were completed to stabilize the animal's hypoxic response. Regional pulmonary blood Q̇ and V̇ distribution was determined at various FiO2 (0.21, 0.15, 0.13, 0.11, 0.09) using the fluorescent microsphere technique. Q̇ and V̇ in the lungs were quantified within 2-cm3 lung pieces. Pieces were grouped, or clustered, based on the changes in blood flow when subjected to increasing hypoxia. Unique patterns of Q̇ response to hypoxia were seen within and across animals. The three main patterns (clusters) showed little initial difference in V̇/Q̇ matching at room air where the mean V̇/Q̇ range was 0.92–1.06. The clusters were spatially located in cranial, central, and caudal portions of the lung. With decreasing FiO2, blood flow shifted from the cranial to caudal regions. We determined that pulmonary blood flow changes, caused by HPV, produced distinct response patterns that were seen in similar regions across our prone porcine model.

Effects of renovascular hypertension on rat adrenal zona glomerulosa

1978 ◽  
Vol 36 (2) ◽  
pp. 582-583
Author(s):  
G. Mazzocchi ◽  
P. Rebuffat ◽  
C. Robba ◽  
P. Vassanelli ◽  
G. G. Nussdorfer
Keyword(s):  
Renovascular Hypertension ◽  
Left Kidney ◽  
Renin Angiotensin System ◽  
Plasma Renin ◽  
Zona Glomerulosa ◽  
Ultrastructural Changes ◽  
Albino Rats ◽  
Left Renal Artery ◽  
Angiotensin System ◽  
And Control

It is well known that the rat adrenal zona glomerulosa steroidogenic activity is controlled by the renin-angiotensin system. The ultrastructural changes in the rat zona glomerulosa cells induced by renovascular hypertension were described previously, but as far as we are aware no correlated biochemical and morphometric investigations were performed.Twenty adult male albino rats were divided into 2 experimental groups. One group was subjected to restriction of blood flow to the left kidney by the application of a silver clip about the left renal artery. The other group was sham-operated and served as a control. Renovascular hypertension developed in about 10 days: sistolic blood pressure averaged 165 ± 6. 4 mmHg, whereas it was about 110 ± 3. 8 mmHg in the control animals. The hypertensive and control rats were sacrificed 20 days after the operation. The blood was collected and plasma renin activity was determined by radioimmunological methods. The aldosterone concentration was radioimmunologically assayed both in the plasma and in the homogenate of the left capsular adrenal gland.

Vascular adaptations to hypoxia: molecular and cellular mechanisms regulating vascular tone

2007 ◽  
Vol 43 ◽  
pp. 105-120 ◽  
Author(s):  
Michael L. Paffett ◽  
Benjimen R. Walker
Keyword(s):  
Vascular Tone ◽  
Cellular Proliferation ◽  
Hypoxic Pulmonary Vasoconstriction ◽  
Hypoxia Inducible Factor ◽  
Systemic Circulation ◽  
Cellular Mechanisms ◽  
Hypoxia Inducible Factor 1 ◽  
Pulmonary Vasoconstriction ◽  
Adaptive Mechanisms ◽  
Adaptive Processes

Several molecular and cellular adaptive mechanisms to hypoxia exist within the vasculature. Many of these processes involve oxygen sensing which is transduced into mediators of vasoconstriction in the pulmonary circulation and vasodilation in the systemic circulation. A variety of oxygen-responsive pathways, such as HIF (hypoxia-inducible factor)-1 and HOs (haem oxygenases), contribute to the overall adaptive process during hypoxia and are currently an area of intense research. Generation of ROS (reactive oxygen species) may also differentially regulate vascular tone in these circulations. Potential candidates underlying the divergent responses between the systemic and pulmonary circulations may include Nox (NADPH oxidase)-derived ROS and mitochondrial-derived ROS. In addition to alterations in ROS production governing vascular tone in the hypoxic setting, other vascular adaptations are likely to be involved. HPV (hypoxic pulmonary vasoconstriction) and CH (chronic hypoxia)-induced alterations in cellular proliferation, ionic conductances and changes in the contractile apparatus sensitivity to calcium, all occur as adaptive processes within the vasculature.

Sign in / Sign up

Export Citation Format

Share Document