Hypoxia has a greater effect than exercise on the redistribution of pulmonary blood flow in swine

2007 ◽  
Vol 103 (6) ◽  
pp. 2112-2119 ◽  
Author(s):  
Susan R. Hopkins ◽  
Axel Kleinsasser ◽  
Susan Bernard ◽  
Alex Loeckinger ◽  
Eric Falor ◽  
...  
Keyword(s):  
Blood Flow ◽  
Pulmonary Blood Flow ◽  
Strenuous Exercise ◽  
Exercise Tests ◽  
Fluorescent Intensity ◽  
Pulmonary Capillaries ◽  
High Altitude Pulmonary Edema ◽  
Specific Pathogen ◽  
Pulmonary Arterial ◽  
Maximal Shift

Strenuous exercise combined with hypoxia is implicated in the development of high-altitude pulmonary edema (HAPE), which is believed to result from rupture of pulmonary capillaries secondary to high vascular pressures. The relative importance of hypoxia and exercise in altering the distribution of pulmonary blood flow (PBF) is unknown. Six chronically catheterized specific pathogen-free Yorkshire hybrid pigs (25.5 ± 0.7 kg, means ± SD) underwent incremental treadmill exercise tests in normoxia (FiO2 = 0.21) and hypoxia (FiO2 = 0.125, balanced order), consisting of 5 min at 30, 60, and 90% of the previously determined V̇o2max. At steady state (∼4 min), metabolic and cardiac output data were collected and fluorescent microspheres were injected over ∼30 s. Later the fluorescent intensity of each color in each 2-cm3 lung piece was determined and regional perfusion was calculated from the weight-normalized fluorescence. Both hypoxia and exercise shifted PBF away from the ventral cranial lung regions toward the dorsal caudal regions of the lung, but hypoxia caused a greater dorsal caudal shift in PBF at rest than did near-maximal exercise in normoxia. The variance in PBF due to hypoxia, exercise, and vascular structure was 16 ± 4.2, 4.0 ± 4.4, and 59.4 ± 11.4%, respectively, and the interaction between hypoxia and exercise represented 12 ± 6.5%. This observation implies that there is already a maximal shift with in PBF with hypoxia in the dorsal-caudal regions in pigs that cannot be exceeded with the addition of exercise. However, exercise greatly increases the pulmonary arterial pressures and therefore the risk of capillary rupture in high flow regions.

Regional pulmonary blood flow during 96 hours of hypoxia in conscious sheep

1986 ◽  
Vol 61 (6) ◽  
pp. 2136-2143 ◽  
Author(s):  
D. C. Curran-Everett ◽  
K. McAndrews ◽  
J. A. Krasney
Keyword(s):  
Blood Flow ◽  
Arterial Pressure ◽  
Pulmonary Blood Flow ◽  
Pulmonary Arterial Pressure ◽  
Pressor Response ◽  
Superior Vena ◽  
Acute Hypoxia ◽  
Vena Cava ◽  
Normobaric Hypoxia ◽  
Pulmonary Arterial

The effects of acute hypoxia on regional pulmonary perfusion have been studied previously in anesthetized, artificially ventilated sheep (J. Appl. Physiol. 56: 338–342, 1984). That study indicated that a rise in pulmonary arterial pressure was associated with a shift of pulmonary blood flow toward dorsal (nondependent) areas of the lung. This study examined the relationship between the pulmonary arterial pressor response and regional pulmonary blood flow in five conscious, standing ewes during 96 h of normobaric hypoxia. The sheep were made hypoxic by N2 dilution in an environmental chamber [arterial O2 tension (PaO2) = 37–42 Torr, arterial CO2 tension (PaCO2) = 25–30 Torr]. Regional pulmonary blood flow was calculated by injecting 15-micron radiolabeled microspheres into the superior vena cava during normoxia and at 24-h intervals of hypoxia. Pulmonary arterial pressure increased from 12 Torr during normoxia to 19–22 Torr throughout hypoxia (alpha less than 0.049). Pulmonary blood flow, expressed as %QCO or ml X min-1 X g-1, did not shift among dorsal and ventral regions during hypoxia (alpha greater than 0.25); nor were there interlobar shifts of blood flow (alpha greater than 0.10). These data suggest that conscious, standing sheep do not demonstrate a shift in pulmonary blood flow during 96 h of normobaric hypoxia even though pulmonary arterial pressure rises 7–10 Torr. We question whether global hypoxic pulmonary vasoconstriction is, by itself, beneficial to the sheep.

Pulmonary fluid balance following pulmocutaneous baroreceptor denervation in the toad

1986 ◽  
Vol 61 (1) ◽  
pp. 331-337 ◽  
Author(s):  
A. W. Smits ◽  
N. H. West ◽  
W. W. Burggren
Keyword(s):  
Blood Flow ◽  
Pulmonary Blood Flow ◽  
Venous Pressure ◽  
Driving Pressure ◽  
Pulmonary Hemodynamics ◽  
Pulmonary Capillaries ◽  
Neural Input ◽  
Order Of Magnitude ◽  
Capillary Resistance ◽  
Recurrent Laryngeal Nerves

Pulmonary hemodynamics and net transcapillary fluid flux (NTFF) were measured in conscious toads before and following bilateral denervation of the recurrent laryngeal nerves (rLN), which contain afferents from baroreceptors located in the pulmocutaneous arteries. Denervation caused an acute doubling of the arterial-venous pressure gradient across the lung and a threefold increase in pulmonary blood flow. Calculated pulmonary vascular resistance fell and remained below control values through the period of experimentation. NTFF increased by an order of magnitude (0.74–7.77 ml X kg-1 X min-1), as filtration increased in response to the hemodynamic changes caused by rLN denervation. There was a better correlation between NTFF and pulmonary blood flow than between NTFF and pulmonary driving pressure. Our results support the view that tonic neural input from pulmocutaneous baroreceptors protects the anuran lung from edema by restraining pulmonary driving pressure and blood flow and perhaps by reflexly maintaining vascular tone in the extrinsic pulmonary artery, therefore tending to increase the pre-to-postpulmonary capillary resistance ratio and biasing the Starling relationship in the pulmonary capillaries against filtration.

The pulmonary vasculature in a neonatal porcine model with increased pulmonary blood flow and pressure

2001 ◽  
Vol 11 (4) ◽  
pp. 420-430 ◽  
Author(s):  
Elisabeth V. Stenbøg ◽  
Daniel A. Steinbrüchel ◽  
Anne Bloch Thomsen ◽  
Ulrik Baandrup ◽  
Lene Heickendorff ◽  
...  
Keyword(s):  
Blood Flow ◽  
Pulmonary Artery ◽  
Vascular Disease ◽  
Pulmonary Blood Flow ◽  
Left Pulmonary Artery ◽  
Pulmonary Vasculature ◽  
Pulmonary Vascular Disease ◽  
Systolic Pulmonary Arterial Pressure ◽  
Pulmonary Arterial ◽  
Circulating Levels

Introduction: Hypertension and hyperperfusion of the pulmonary vascular bed in the setting of congenital cardiac malformations may lead to progressive pulmonary vascular disease. To improve the understanding of the basic mechanisms of this disease, there is a need for clinically relevant animal models which reflect the disease process. Material and Results: We randomly allocated 45 newborn pigs, at the age of 48 hrs, to groups in which there was either construction of a 3 mm central aorto-pulmonary shunt, undertaken in 9, or ligation of the left pulmonary artery, achieved in 13. Controls included sham operations in 13, or no operations in 10 pigs. Follow-up was continued for three months. The interventions were compatible with survival in most pigs. The shunts resulted in an acute 85% increase in systolic pulmonary arterial pressure, and a more than twofold increase in pulmonary blood flow. By three months of age, nearly all shunts had closed spontaneously, and haemodynamics were normal. Ligation of the left pulmonary artery resulted in a normal total pulmonary blood flow, despite only the right lung being perfused, and a 33% increase in systolic pulmonary arterial pressure. These haemodynamic changes were maintained throughout the period of study. In both groups, histomorphometry revealed markedly increased muscularity of the intra-acinar pulmonary arteries. Circulating levels of endothelin were normal in the shunted animals, and elevated in those with ligation of the left pulmonary artery. Conclusion: In neonatal porcine models of pulmonary vascular disease, created by construction of 3 mm central aorto-pulmonary shunts and ligation of one pulmonary artery, we observed histopathological changes of the pulmonary vasculature similar to early hypertensive pulmonary vascular disease in humans. Elevated circulating levels of endothelin were associated with abnormal haemodynamics rather than abnormal pathology. These findings could be valuable for future studies on the pathogenesis of hypertensive pulmonary vascular disease associated with congenital cardiac malformations.

Effect of furosemide on pulmonary blood flow distribution in resting and exercising horses

1999 ◽  
Vol 86 (6) ◽  
pp. 2034-2043 ◽  
Author(s):  
Howard H. Erickson ◽  
Susan L. Bernard ◽  
Robb W. Glenny ◽  
M. Roger Fedde ◽  
Nayak L. Polissar ◽  
...  
Keyword(s):  
Blood Flow ◽  
Pulmonary Blood Flow ◽  
Flow Distribution ◽  
Thoroughbred Horses ◽  
Dorsal Portion ◽  
Primary Finding ◽  
Pulmonary Arterial ◽  
Relationship Of ◽  
The Relationship ◽  
Rest And Exercise

We determined the spatial distribution of pulmonary blood flow (PBF) with 15-μm fluorescent-labeled microspheres during rest and exercise in five Thoroughbred horses before and 4 h after furosemide administration (0.5 mg/kg iv). The primary finding of this study was that PBF redistribution occurred from rest to exercise, both with and without furosemide. However, there was less blood flow to the dorsal portion of the lung during exercise postfurosemide compared with prefurosemide. Furosemide did alter the resting perfusion distribution by increasing the flow to the ventral regions of the lung; however, that increase in flow was abated with exercise. Other findings included 1) unchanged gas exchange and cardiac output during rest and exercise after vs. before furosemide, 2) a decrease in pulmonary arterial pressure after furosemide, 3) an increase in the slope of the relationship of PBF vs. vertical height up the lung during exercise, both with and without furosemide, and 4) a decrease in blood flow to the dorsal region of the lung at rest after furosemide. Pulmonary perfusion variability within the lung may be a function of the anatomy of the pulmonary vessels that results in a predominantly fixed spatial pattern of flow distribution.

Pulmonary vasodilator drugs decrease lung liquid production in fetal sheep

1995 ◽  
Vol 79 (4) ◽  
pp. 1212-1218 ◽  
Author(s):  
J. J. Cummings
Keyword(s):  
Blood Flow ◽  
Pulmonary Vascular Resistance ◽  
Vascular Resistance ◽  
Pulmonary Blood Flow ◽  
Fetal Lung ◽  
Prostaglandin D2 ◽  
Fetal Sheep ◽  
Pulmonary Vasodilator ◽  
Pulmonary Arterial ◽  
Lung Liquid

To examine a potential relationship between pulmonary vasodilatation and fetal lung liquid production, I measured lung liquid production in 20 fetal sheep at 130 +/- 4 days gestation while using several agents known to increase pulmonary blood flow. Thirty-two studies were done in which left pulmonary arterial flow (Qlpa) was measured by an ultrasonic Doppler flow probe and net lung luminal liquid production (Jv) was measured by plotting the change in lung luminal liquid concentration of radiolabeled albumin, an impermeant tracer that was mixed into the lung liquid at the start of each study. Qlpa and Jv were measured during a 1- to 2-h baseline period and then during a 1- to 2-h infusion period in which the fetuses received either an intravenous infusion of acetylcholine (n = 8), prostaglandin D2 (n = 10), or the leukotriene blocker FPL-55712 (n = 7). These vasodilators work by different mechanisms, each mechanism having been implicated in the decrease in pulmonary vascular resistance seen at birth. Control (saline) infusions (n = 7) caused no change in either Qlpa or Jv over 4 h. All vasodilator agents significantly increased pulmonary blood flow and decreased Jv. Pulmonary arterial pressure did not change significantly in either the control, acetylcholine, prostaglandin, or leukotriene-blocker studies, indicating that pulmonary vascular resistance decreased. Thus agents that increase pulmonary blood flow by mechanisms that occur at birth also decrease lung liquid production in fetal lambs.

Gene expression profile in flow-associated pulmonary arterial hypertension with neointimal lesions

2010 ◽  
Vol 298 (4) ◽  
pp. L483-L491 ◽  
Author(s):  
Mirjam E. van Albada ◽  
Beatrijs Bartelds ◽  
Hans Wijnberg ◽  
Saffloer Mohaupt ◽  
Michael G. Dickinson ◽  
...  
Keyword(s):  
Gene Expression ◽  
Blood Flow ◽  
Pulmonary Arterial Hypertension ◽  
Arterial Hypertension ◽  
Pulmonary Blood Flow ◽  
Molecular Mechanisms ◽  
Expression Profiles ◽  
Response To Therapy ◽  
High Morbidity ◽  
Pulmonary Arterial

Pulmonary arterial hypertension (PAH) is a pulmonary angioproliferative disease with high morbidity and mortality, characterized by a typical pattern of pulmonary vascular remodeling including neointimal lesions. In congenital heart disease, increased pulmonary blood flow has appeared to be a key mediator in the development of these characteristic lesions, but the molecular mechanisms underlying the pulmonary vascular lesions are largely unknown. We employed a rat model of flow-associated PAH, which induced specific pulmonary neointimal lesions. We identified gene expression profiles in rats specifically related to the addition of increased pulmonary blood flow to monocrotaline and the associated occurrence of neointimal lesions. Increased pulmonary blood flow induced the expression of the transcription factors activating transcription factor-3 (ATF3) and early growth response factor-1 (EGR-1), for which presence was confirmed in neointimal lesions. Monocrotaline alone induced increased numbers of activated mast cells and their products. We further identified molecular pathways that may be involved in treatment with the prostacyclin analog iloprost, a vasoactive compound with clinically beneficial effects in patients with PAH, which were similar to pathways described in samples from patient studies. These pathways, associated with the development of angioproliferative lesions as well as with the response to therapy in PAH, may provide new therapeutic targets.

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