Pulmonary vascular reactivity and hemodynamic changes in elastase-induced emphysema in hamsters

1992 ◽  
Vol 73 (4) ◽  
pp. 1474-1480 ◽  
Author(s):  
C. M. Tseng ◽  
S. Qian ◽  
W. Mitzner
Keyword(s):  
Angiotensin Ii ◽  
Arterial Pressure ◽  
Right Ventricular ◽  
Pulmonary Vascular Resistance ◽  
Vascular Resistance ◽  
Ventricular Hypertrophy ◽  
Vascular Reactivity ◽  
Pulmonary Arterial Pressure ◽  
Pressor Responses ◽  
Pulmonary Arterial

Changes in pulmonary hemodynamics and vascular reactivity in emphysematous hamsters were studied in an isolated lung preparation perfused at constant flow with blood and 3% dextran. Hamsters were treated with intratracheal porcine pancreatic elastase at 70 days of age, and experimental studies were conducted at 1, 3, and 8 mo after treatment. Baseline pulmonary arterial pressure in elastase-treated lungs was increased compared with saline-treated control lungs 1 mo after treatment, but this increase did not progress at 3 and 8 mo. Increases in pulmonary arterial pressure in elastase-treated lungs were temporally correlated with the morphological development of emphysema and right ventricular hypertrophy; both of these were evident at 1 mo after treatment and showed little change thereafter. Pressor responses to hypoxia and angiotensin II were not different between elastase-treated and control lungs at 1 and 3 mo. At 8 mo, however, pressor responses in emphysematous lungs to 0% O2 (but not to angiotensin II) were significantly increased. This was the result of a lack of the normal age-related fall in the hypoxic pressor response. Our results suggest that the right ventricular hypertrophy found in these emphysematous animals results from a chronically increased pulmonary vascular resistance. Furthermore, increases in pulmonary vascular resistance in the early development of emphysema are likely a result of the loss of vascular beds and supporting connective tissue.

Pregnancy blunts pulmonary vascular reactivity in dogs

1980 ◽  
Vol 239 (3) ◽  
pp. H297-H301 ◽  
Author(s):  
L. G. Moore ◽  
J. T. Reeves
Keyword(s):  
Arterial Pressure ◽  
Pulmonary Vascular Resistance ◽  
Vascular Resistance ◽  
Pulmonary Circulation ◽  
Vascular Reactivity ◽  
Pulmonary Arterial Pressure ◽  
Acute Hypoxia ◽  
Limited Data ◽  
Mean Pulmonary Arterial Pressure ◽  
Pulmonary Arterial

Pregnancy decreases systemic vascular reactivity but comparatively little is known about the effects of pregnancy on the pulmonary circulation. Pulmonary vascular resistance (PVR) during acute hypoxia was lower (P < 0.01) in eight intact anesthetized pregnant dogs compared to the same animals postpartum. Mean pulmonary arterial pressure (Ppa) and PVR during infusion of prostaglandin (PG) F2 alpha were also reduced during pregnancy. Nonpregnant female dogs (n = 5) treated with estrogen (0.001 mg x kg-1 x da-1) for 2 wk had decreased Ppa (P < 0.01) during acute hypoxia compared to control measurements, but PVR was unchanged during hypoxia and PGF2 alpha infusion. Treatment with progesterone in four dogs had no effect on pulmonary vascular reactivity to hypoxia or PGF2 alpha. Inhibition of circulating PG with meclofenamate in four dogs during pregnancy did not appear to restore pulmonary vascular reactivity. Blunted pulmonary vascular reactivity is suggested by the limited data available for women, but is not seen in pregnant cows. We conclude that pregnancy decreases pulmonary as well as systemic vascular reactivity in the dog, but the mechanism is unclear.

Pregnancy-induced pulmonary hypertension in cows susceptible to high mountain disease

1979 ◽  
Vol 46 (1) ◽  
pp. 184-188 ◽  
Author(s):  
L. G. Moore ◽  
J. T. Reeves ◽  
D. H. Will ◽  
R. F. Grover
Keyword(s):  
Arterial Pressure ◽  
Pulmonary Vascular Resistance ◽  
Vascular Resistance ◽  
Vascular Reactivity ◽  
Pulmonary Arterial Pressure ◽  
Pressor Response ◽  
Acute Hypoxia ◽  
High Mountain ◽  
Mean Pulmonary Arterial Pressure ◽  
Pulmonary Arterial

Observations in several species suggest that pulmonary vascular reactivity may be reduced during pregnancy. We tested this hypothesis in two groups of unanesthetized cows, one “susceptible” and one “resistant” to high mountain or brisket disease. At the altitude of residence (1,524 m), mean pulmonary arterial pressure was elevated during pregnancy by 18% and total pulmonary vascular resistance by 32% in susceptible but not in resistant cows. During acute exposure to simulated altitudes of 2,120--4,550 m, pulmonary arterial pressure was increased by 16% and total pulmonary resistance by 28% during pregnancy in susceptible cows. The pulmonary pressor response to a 5 microgram/kg bolus of prostaglandin FIalpha was not different during pregnancy in either group. Resistant cows hyperventilated while pregnant, raising arterial partial pressure of oxygen (PaO2) by 6 Torr both at 1,524 m and, on the average, by 7 Torr at altitudes of 2,120--4,550 m. Susceptible cows increased their PaO2 less than did the resistant cows during pregnancy. The results indicated that pregnancy was associated with a greater rise in pulmonary arterial pressure and total pulmonary vascular resistance during acute hypoxia and failed to elicit as great a ventilatory response in susceptible than in resistant cows.

Effects of Hemoglobin on Pulmonary Arterial Pressure and Pulmonary Vascular Resistance in Patients with Chronic Emphysema

Respiration ◽  
2000 ◽  
Vol 67 (5) ◽  
pp. 502-506 ◽  
Author(s):  
Akira Nakamura ◽  
Norio Kasamatsu ◽  
Ikko Hashizume ◽  
Takushi Shirai ◽  
Suguru Hanzawa ◽  
...  
Keyword(s):  
Arterial Pressure ◽  
Pulmonary Vascular Resistance ◽  
Vascular Resistance ◽  
Pulmonary Arterial Pressure ◽  
Pulmonary Arterial

Low exercise pulmonary resistance is not dependent on vasodilator prostaglandins

1983 ◽  
Vol 55 (2) ◽  
pp. 558-561 ◽  
Author(s):  
J. Lindenfeld ◽  
J. T. Reeves ◽  
L. D. Horwitz
Keyword(s):  
Cardiac Output ◽  
Arterial Pressure ◽  
Pulmonary Vascular Resistance ◽  
Vascular Resistance ◽  
Pulmonary Arterial Pressure ◽  
Cyclooxygenase Inhibitors ◽  
Pulmonary Resistance ◽  
Before And After ◽  
Pulmonary Arterial

In resting conscious dogs, administration of cyclooxygenase inhibitors results in modest increases in pulmonary arterial pressure and pulmonary vascular resistance, suggesting that vasodilator prostaglandins play a role in maintaining the low vascular resistance in the pulmonary bed. To assess the role of these vasodilator prostaglandins on pulmonary vascular resistance during exercise, we studied seven mongrel dogs at rest and during exercise before and after intravenous meclofenamate (5 mg/kg). Following meclofenamate, pulmonary vascular resistance rose both at rest (250 24 vs. 300 +/- 27 dyn . s . cm-5, P less than 0.01) and with exercise (190 +/- 9 vs. 210 +/- 12 dyn . s . cm-5, P less than 0.05). Systemic vascular resistance rose slightly following meclofenamate both at rest and during exercise. There were no changes in cardiac output. The effects of cyclooxygenase inhibition, although significant, were less during exercise than at rest. This suggests that the normal fall in pulmonary vascular resistance during exercise depends largely on factors other than vasodilator prostaglandins.

Pulmonary vascular reactivity is blunted in pregnant rats

1982 ◽  
Vol 53 (3) ◽  
pp. 703-707 ◽  
Author(s):  
K. I. Fuchs ◽  
L. G. Moore ◽  
S. Rounds
Keyword(s):  
Angiotensin Ii ◽  
Vascular Reactivity ◽  
Pulmonary Arterial Pressure ◽  
Pressor Response ◽  
Female Rats ◽  
Pregnant Rats ◽  
Constant Flow Rate ◽  
Pressor Responses ◽  
Pulmonary Arterial ◽  
In Pregnancy

Pulmonary arterial pressure is decreased in pregnant women despite increased cardiac output, suggesting that pulmonary vascular resistance is decreased in pregnancy. To determine if pulmonary vascular reactivity is decreased in pregnant rats, lungs isolated from pregnant rats were perfused with blood from other pregnant rats at constant flow rate, and pressor responses to airway hypoxia and to angiotensin II were measured. Compared with responses obtained in lungs from nonpregnant female rats, hypoxic and angiotensin II pressor responses were blunted in pregnancy. To separate possible effects of pregnancy on the lung from those of substance(s) circulating in the blood in pregnancy, we perfused lungs from nonpregnant rats with blood from pregnant rats. Both the hypoxic and angiotensin II pressor responses were blunted by blood from pregnant rats. The angiotensin II pressor response was blunted also in lungs from pregnant rats perfused with blood from nonpregnant rats. These results suggest that a circulating substance is responsible for blunting of pulmonary vascular reactivity in pregnancy and that changes in the lung induced by pregnancy also depress angiotensin II responses. It is unlikely that estrogen and progesterone were responsible for these effects, since lungs and blood obtained from animals treated with these hormones did not have blunted pulmonary vascular reactivity.

Evidence that hypoxic pulmonary vascular remodeling in rats is polyamine dependent

1987 ◽  
Vol 62 (4) ◽  
pp. 1562-1568 ◽  
Author(s):  
J. E. Atkinson ◽  
J. W. Olson ◽  
R. J. Altiere ◽  
M. N. Gillespie
Keyword(s):  
Arterial Pressure ◽  
Right Ventricular ◽  
Vascular Remodeling ◽  
Ventricular Hypertrophy ◽  
Chronic Hypoxia ◽  
Pulmonary Arterial Pressure ◽  
Right Ventricular Hypertrophy ◽  
Polyamine Biosynthesis ◽  
Pulmonary Vascular Remodeling ◽  
Pulmonary Arterial

This study tested the hypothesis that the polyamines, a family of low-molecular-weight organic cations with documented regulatory roles in cell growth and differentiation, are mediators of chronic hypoxia-induced pulmonary vascular remodeling. Relative to room air controls, chronically hypoxic animals (inspired O2 fraction = 0.1; 21 days) exhibited higher pulmonary arterial pressures (measured in room air), thicker medial layers in pulmonary arteries of 50–100 microns diam, increased hematocrits, and right ventricular hypertrophy. In addition, lung contents of the polyamines, putrescine, spermidine, and spermine were greater in hypoxic animals than in controls. alpha-Difluoromethylornithine (DFMO), an inhibitor of polyamine synthesis, attenuated the hypoxia-induced elevations in lung putrescine and spermidine content and blunted the increases in pulmonary arterial pressure and medial thickness. Neither the increased hematocrit nor right ventricular hypertrophy associated with chronic hypoxia were abrogated by DFMO. In addition, DFMO failed to influence vasoconstrictor responses provoked by acute hypoxic ventilation in isolated, buffer-perfused rat lungs. These observations suggest that depression of polyamine biosynthesis with DFMO blunts the sustained increase in pulmonary arterial pressure by attenuating hypoxia-induced medial thickening.

Chronic hypercapnia inhibits hypoxic pulmonary vascular remodeling

2000 ◽  
Vol 278 (2) ◽  
pp. H331-H338 ◽  
Author(s):  
Henry Ooi ◽  
Elaine Cadogan ◽  
Michèle Sweeney ◽  
Katherine Howell ◽  
R. G. O'Regan ◽  
...  
Keyword(s):  
Arterial Pressure ◽  
Right Ventricular ◽  
Vascular Remodeling ◽  
Ventricular Hypertrophy ◽  
Chronic Hypoxia ◽  
Pulmonary Arterial Pressure ◽  
Hypoxic Pulmonary Vasoconstriction ◽  
Right Ventricular Hypertrophy ◽  
Pulmonary Vascular Remodeling ◽  
Pulmonary Arterial

Chronic hypercapnia is commonly found in patients with severe hypoxic lung disease and is associated with a greater elevation of pulmonary arterial pressure than that due to hypoxia alone. We hypothesized that hypercapnia worsens hypoxic pulmonary hypertension by augmenting pulmonary vascular remodeling and hypoxic pulmonary vasoconstriction (HPV). Rats were exposed to chronic hypoxia [inspiratory O2 fraction ([Formula: see text]) = 0.10], chronic hypercapnia (inspiratory CO2 fraction = 0.10), hypoxia-hypercapnia ([Formula: see text]= 0.10, inspiratory CO2 fraction = 0.10), or room air. After 1 and 3 wk of exposure, muscularization of resistance blood vessels and hypoxia-induced hematocrit elevation were significantly inhibited in hypoxia-hypercapnia compared with hypoxia alone ( P < 0.001, ANOVA). Right ventricular hypertrophy was reduced in hypoxia-hypercapnia compared with hypoxia at 3 wk ( P < 0.001, ANOVA). In isolated, ventilated, blood-perfused lungs, basal pulmonary arterial pressure after 1 wk of exposure to hypoxia (20.1 ± 1.8 mmHg) was significantly ( P < 0.01, ANOVA) elevated compared with control conditions (12.1 ± 0.1 mmHg) but was not altered in hypoxia-hypercapnia (13.5 ± 0.9 mmHg) or hypercapnia (11.8 ± 1.3 mmHg). HPV ([Formula: see text] = 0.03) was attenuated in hypoxia, hypoxia-hypercapnia, and hypercapnia compared with control ( P < 0.05, ANOVA). Addition of N ω-nitro-l-arginine methyl ester (10−4 M), which augmented HPV in control, hypoxia, and hypercapnia, significantly reduced HPV in hypoxia-hypercapnia. Chronic hypoxia caused impaired endothelium-dependent relaxation in isolated pulmonary arteries, but coexistent hypercapnia partially protected against this effect. These findings suggest that coexistent hypercapnia inhibits hypoxia-induced pulmonary vascular remodeling and right ventricular hypertrophy, reduces HPV, and protects against hypoxia-induced impairment of endothelial function.

Effects of ONO-5046, a specific neutrophil elastase inhibitor, on endotoxin-induced lung injury in sheep

1994 ◽  
Vol 77 (3) ◽  
pp. 1333-1340 ◽  
Author(s):  
K. Kubo ◽  
T. Kobayashi ◽  
T. Hayano ◽  
T. Koizumi ◽  
T. Honda ◽  
...  
Keyword(s):  
Lung Injury ◽  
Arterial Pressure ◽  
Pulmonary Vascular Resistance ◽  
Vascular Resistance ◽  
Neutrophil Elastase ◽  
Pulmonary Arterial Pressure ◽  
Pulmonary Vascular Permeability ◽  
Lung Dysfunction ◽  
Pulmonary Arterial ◽  
Lung Lymph

The purpose of the present study was to assess the role of polymorphonuclear leukocyte (neutrophil) elastase in endotoxin-induced acute lung injury in sheep with lung lymph fistula. We studied the effects of ONO-5046, a specific inhibitor of neutrophil elastase, on the lung dysfunction induced by the intravenous infusion of 1 microgram/kg of Escherichia coli endotoxin. Endotoxin alone produced a biphasic response as previously reported. Early (0.5–1 h) after endotoxin, pulmonary arterial pressure increased from 19.5 +/- 0.9 cmH2O at baseline to a peak of 46.8 +/- 2.4 cmH2O (P > 0.05). Pulmonary vascular resistance increased from 3.03 +/- 0.17 cmH2O.l–1.min at baseline to a peak of 9.77 +/- 0.70 cmH2O.l–1.min (P < 0.05). Circulating neutrophils decreased from 7,355 +/- 434/mm3 at baseline to a nadir of 1,762 +/- 32/mm3 (P < 0.05). Thromboxane B2 and 6-ketoprostaglandin F1 alpha concentrations in plasma and lung lymph were significantly increased. Late (3–5 h) after endotoxin, pulmonary arterial pressure and pulmonary vascular resistance returned to baseline levels, but lung lymph flow remained increased from 4.2 +/- 0.3 ml/0.5 h at baseline to 7.3 +/- 0.7 ml/0.5 h (P < 0.05), with a slight increase in lung lymph-to-plasma protein concentration ratio, suggesting increased pulmonary vascular permeability. The histopathological features of the lungs during the early period in sheep treated with endotoxin alone revealed a large increase in neutrophils per 100 alveoli and changes of pulmonary edema such as thickening of the interstitium of the lung and alveolar flooding.(ABSTRACT TRUNCATED AT 250 WORDS)

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