Pulmonary hypertension after postlavage lung injury in rabbits: possible role of polymorphonuclear leukocytes

1991 ◽  
Vol 71 (5) ◽  
pp. 1990-1995 ◽  
Author(s):  
R. Burger ◽  
A. C. Bryan
Keyword(s):  
Pulmonary Hypertension ◽  
Gas Exchange ◽  
Lung Injury ◽  
Arterial Pressure ◽  
Airway Pressure ◽  
Pulmonary Arterial Pressure ◽  
Lung Lavage ◽  
High Frequency Ventilation ◽  
Mean Airway Pressure ◽  
Pulmonary Arterial

Previous studies showed that repeated lung lavage leads to a severe lung injury with very poor gas exchange, a substantial protein leak into the alveoli with hyaline membrane formation, pulmonary hypertension, and migration of granulocytes (PMN) into the alveolar spaces. Depletion of PMN leads to a better gas exchange and a markedly decreased protein leak with only scanty hyaline membranes. In this study we show that there is sustained pulmonary hypertension after the lung lavage, but in PMN-depleted rabbits there is no postlavage increase in pulmonary arterial pressure. Changing the shunt fraction by manipulating mean airway pressure still leads to a hypoxic vasoconstriction with increase of pulmonary arterial pressure. Thus, after lung lavage, pulmonary reactivity to hypoxia is still preserved. Comparisons between high-frequency ventilation and conventional mechanical ventilation at the same mean airway pressures showed that equal mean airway pressure in these two very different modes of ventilation do not translate into the same mean functional lung volumes.

Thromboxane does not mediate pulmonary hypertension in phorbol ester-induced acute lung injury in dogs

1990 ◽  
Vol 69 (1) ◽  
pp. 345-352 ◽  
Author(s):  
A. H. Stephenson ◽  
R. S. Sprague ◽  
T. E. Dahms ◽  
A. J. Lonigro
Keyword(s):  
Pulmonary Hypertension ◽  
Acute Lung Injury ◽  
Lung Injury ◽  
Arterial Pressure ◽  
Pulmonary Arterial Pressure ◽  
Pressor Response ◽  
H2 Receptor Antagonist ◽  
Arterial Blood ◽  
Pulmonary Arterial ◽  
The Relationship

Thromboxane (Tx) has been suggested to mediate the pulmonary hypertension of phorbol myristate acetate- (PMA) induced acute lung injury. To test this hypothesis, the relationship between Tx and pulmonary arterial pressure was evaluated in a model of acute lung injury induced with PMA in pentobarbital sodium-anesthetized male mongrel dogs. Sixty minutes after administration of PMA (20 micrograms/kg iv, n = 10), TxB2 increased 10-fold from control in both systemic and pulmonary arterial blood and 8-fold in bronchoalveolar lavage (BAL) fluid. Concomitantly, pulmonary arterial pressure (Ppa) increased from 14.5 +/- 1.0 to 36.2 +/- 3.5 mmHg, and pulmonary vascular resistance (PVR) increased from 5.1 +/- 0.4 to 25.9 +/- 2.9 mmHg.l-1.min. Inhibition of Tx synthase with OKY-046 (10 mg/kg iv, n = 6) prevented the PMA-induced increase in Tx concentrations in blood and BAL fluid but did not prevent or attenuate the increase in Ppa. OKY-046 pretreatment did, however, attenuate but not prevent the increase in PVR 60 min after PMA administration. Pretreatment with the TxA2/prostaglandin H2 receptor antagonist ONO-3708 (10 micrograms.kg-1.min-1 iv, n = 7) prevented the pressor response to bolus injections of 1-10 micrograms U-46619, a Tx receptor agonist, but did not prevent or attenuate the PMA-induced increase in Ppa. ONO-3708 also attenuated but did not prevent the increase in PVR. These results suggest that Tx does not mediate the PMA-induced pulmonary hypertension but may augment the increases in PVR in this model of acute lung injury.

Air embolism-induced lung injury in isolated rat lungs

1992 ◽  
Vol 72 (4) ◽  
pp. 1235-1242 ◽  
Author(s):  
D. Wang ◽  
M. H. Li ◽  
K. Hsu ◽  
C. Y. Shen ◽  
H. I. Chen ◽  
...  
Keyword(s):  
Weight Gain ◽  
Lung Injury ◽  
Arterial Pressure ◽  
Pulmonary Arterial Pressure ◽  
Air Embolism ◽  
Lavage Fluid ◽  
Lung Lavage ◽  
Lung Model ◽  
Lung Weight ◽  
Pulmonary Arterial

Pulmonary air embolism causes physical obstruction of microvasculature and leads to permeability changes, release of mediators, and injury to lung tissue. In this study we employed an isolated perfused rat lung model to investigate the primary and secondary effects produced by infusion of air into the pulmonary artery. Infusion of various doses of air (0.10–0.25 ml) over a 1-min period produced a dose-dependent increase in pulmonary arterial pressure and lung weight gain. In contrast, when a constant air dose was administered over various periods of time (0.25 ml over 0.5–8.0 min), the pulmonary arterial pressure rose to the same extent regardless of the infusion rate, whereas the lung weight gain increased proportionately with the rate of infusion. Total vascular resistance rose from 1.41 +/- 0.04 to 5.04 +/- 0.09 mmHg.ml-1.min in rats given 0.25 ml air over 1 min (n = 14, P less than 0.001), with greater than or equal to 90% of this increase occurring in the arterial segments. Both thromboxane B2 and endothelin concentrations also increased in the perfusate, suggesting their involvement in this increased resistance. Furthermore the pulmonary filtration coefficient increased from 0.21 +/- 0.05 to 1.28 +/- 0.26 g.min-1.cmH2O–1.100 g (n = 8, P less than 0.001), and the protein concentration in lung lavage fluid also rose, indicating lung injury. Leukocyte counts in the perfusate were unaffected by embolization, but chemiluminescent activity was increased, indicating a possible role for activated leukocytes in lung injury induced by air emboli.(ABSTRACT TRUNCATED AT 250 WORDS)

Pulmonary hypertension due to monocrotaline pyrrole is reduced by moderate thrombocytopenia

1988 ◽  
Vol 255 (5) ◽  
pp. H1165-H1172 ◽  
Author(s):  
P. E. Ganey ◽  
K. H. Sprugel ◽  
S. M. White ◽  
J. G. Wagner ◽  
R. A. Roth
Keyword(s):  
Pulmonary Hypertension ◽  
Lung Injury ◽  
Arterial Pressure ◽  
Pulmonary Arterial Pressure ◽  
Lavage Fluid ◽  
Lung Weight ◽  
Lactate Dehydrogenase Activity ◽  
Pulmonary Arterial ◽  
Series Of Experiments ◽  
Monocrotaline Pyrrole

To elucidate further the role of the platelet in the development of monocrotaline pyrrole (MCTP)-induced lung injury and pulmonary hypertension, MCTP-treated rats were made thrombocytopenic by cotreatment with an anti-rat platelet serum (PAS). Lung injury was assessed from increases in lung weight, lavage fluid protein concentration, and lactate dehydrogenase activity and from accumulation in lung tissue of 125I-labeled albumin. These indexes of injury were not different in MCTP-treated rats with normal or reduced platelet numbers at day 4,8, or 14. In MCTP-treated rats not receiving the PAS, pulmonary arterial pressure was elevated by day 8. However, pulmonary arterial pressure was the same as controls at both day 8 and day 14 in MCTP-treated rats made moderately thrombocytopenic by cotreatment with PAS. More marked reduction of platelet number abolished the protective effect of thrombocytopenia against pulmonary hypertension. In a separate series of experiments, treatment with antibodies to platelet-derived growth factor (PDGF), a potential mediator in the response to MCTP-induced injury, did not protect rats from the cardiopulmonary effects of MCTP. These data indicate that moderate reduction of the number of circulating platelets prevents MCTP-induced pulmonary hypertension but not MCTP-induced lung injury, suggesting that the platelet is involved in the pulmonary hypertensive response to MCTP-induced lung injury by unknown mechanisms.

Severe VA/Q mismatch in perfused lungs evoked by sequential challenge with endotoxin and E. coli hemolysin

1994 ◽  
Vol 76 (3) ◽  
pp. 1020-1030 ◽  
Author(s):  
D. Walmrath ◽  
J. Pilch ◽  
M. Scharmann ◽  
F. Grimminger ◽  
W. Seeger
Keyword(s):  
Pulmonary Hypertension ◽  
Gas Exchange ◽  
Arterial Pressure ◽  
Pulmonary Arterial Pressure ◽  
Low Doses ◽  
Edema Formation ◽  
Shunt Flow ◽  
E Coli ◽  
Vasoconstrictor Response ◽  
Pulmonary Arterial

Escherichia coli hemolysin (ECH), an important pathogenicity factor in extraintestinal E. coli infections, provokes pulmonary hypertension and microvascular leakage in buffer-perfused rabbit lungs. We investigated gas exchange abnormalities in response to low doses of ECH, lipopolysaccharides (LPS), and sequential and combined application of these bacterial agents by using the multiple inert gas elimination technique. In control lungs and after admixture of 100 ng/ml of LPS, unimodal narrow distribution of perfusion and ventilation to midrange ventilation-perfusion (VA/Q) areas was noted. ECH [0.08 hemolytic units (HU)/ml] caused a moderate increase in pulmonary arterial pressure (< 10 mmHg), progressive lung edema formation (approximately 10 g within 20 min), and a broadening of perfusate and gas flow dispersion. Application of 0.08 HU/ml of ECH in lungs “primed” with 100 ng/ml of LPS in a preceding 125-min perfusion period provoked a large increase in pulmonary arterial pressure (> 50 mmHg within 5 min), rapid edema formation (approximately 10 g within 10 min), and severe VA/Q mismatch with predominance of shunt flow. Vasoconstrictor response and VA/Q mismatch, but not edema formation, were largely inhibited by pretreatment of lungs with acetylsalicylic acid or the thromboxane receptor antagonist BM-13.505. In addition, “rescue” application of BM-13.505 rapidly reversed pressure rise and shunt flow due to sequential LPS and/or ECH stimulation, whereas edema formation was not affected. We conclude that the marked pulmonary hypertension in response to low doses of ECH in LPS-primed lungs is paralleled by severe gas exchange abnormalities with predominance of shunt flow. Both the vasoconstrictor response and the development of shunt are closely related to toxin-induced thromboxane generation.

Hyperbaric oxygen toxicity: role of thromboxane

1992 ◽  
Vol 72 (2) ◽  
pp. 416-422 ◽  
Author(s):  
J. M. Jacobson ◽  
J. R. Michael ◽  
R. A. Meyers ◽  
M. B. Bradley ◽  
A. M. Sciuto ◽  
...  
Keyword(s):  
Pulmonary Hypertension ◽  
Lung Injury ◽  
Arterial Pressure ◽  
Pulmonary Arterial Pressure ◽  
Combined Therapy ◽  
Combined Treatment ◽  
Lavage Fluid ◽  
Thromboxane B2 ◽  
Lung Weight ◽  
Pulmonary Arterial

Exposing rabbits for 1 h to 100% O2 at 4 atm barometric pressure markedly increases the concentration of thromboxane B2 in alveolar lavage fluid [1,809 +/- 92 vs. 99 +/- 24 (SE) pg/ml, P less than 0.001], pulmonary arterial pressure (110 +/- 17 vs. 10 +/- 1 mmHg, P less than 0.001), lung weight gain (14.6 +/- 3.7 vs. 0.6 +/- 0.4 g/20 min, P less than 0.01), and transfer rates for aerosolized 99mTc-labeled diethylenetriamine pentaacetate (500 mol wt; 40 +/- 14 vs. 3 +/- 1 x 10(-3)/min, P less than 0.01) and fluorescein isothiocyanate-labeled dextran (7,000 mol wt; 10 +/- 3 vs. 1 +/- 1 x 10(-4)/min, P less than 0.01). Pretreatment with the antioxidant butylated hydroxyanisole (BHA) entirely prevents the pulmonary hypertension and lung injury. In addition, BHA blocks the increase in alveolar thromboxane B2 caused by hyperbaric O2 (10 and 45 pg/ml lavage fluid, n = 2). Combined therapy with polyethylene glycol- (PEG) conjugated superoxide dismutase (SOD) and PEG-catalase also completely eliminates the pulmonary hypertension, pulmonary edema, and increase in transfer rate for the aerosolized compounds. In contrast, combined treatment with unconjugated SOD and catalase does not reduce the pulmonary damage. Because of the striking increase in pulmonary arterial pressure to greater than 100 mmHg, we tested the hypothesis that thromboxane causes the hypertension and thus contributes to the lung injury. Indomethacin and UK 37,248–01 (4-[2-(1H-imidazol-1-yl)-ethoxy]benzoic acid hydrochloride, an inhibitor of thromboxane synthase, completely eliminate the pulmonary hypertension and edema.(ABSTRACT TRUNCATED AT 250 WORDS)

MO746CARDIAC REMODELING AND PULMONARY HYPERTENSION IN HEMODIALYSIS PATIENTS

2021 ◽  
Vol 36 (Supplement_1) ◽  
Author(s):  
Ekaterina Borodulina ◽  
Alexander M Shutov
Keyword(s):  
Pulmonary Hypertension ◽  
Left Ventricular Hypertrophy ◽  
Arterial Pressure ◽  
Ventricular Hypertrophy ◽  
Pulmonary Arterial Pressure ◽  
Hemodialysis Patients ◽  
Left Ventricular ◽  
Hemodialysis Treatment ◽  
Systolic Pulmonary Arterial Pressure ◽  
Pulmonary Arterial

Abstract Background and Aims An important predictor of cardiovascular mortality and morbidity in hemodialysis patients is left ventricular hypertrophy. Also, pulmonary hypertension is a risk factor for mortality and cardiovascular events in hemodialysis patients. The aim of this study was to investigate cardiac remodeling and the dynamics of pulmonary arterial pressure during a year-long hemodialysis treatment and to evaluate relationship between pulmonary arterial pressure and blood flow in arteriovenous fistula. Method Hemodialysis patients (n=88; 42 males, 46 females, mean age was 51.7±13.0 years) were studied. Echocardiography and Doppler echocardiography were performed in the beginning of hemodialysis treatment and after a year. Echocardiographic evaluation was carried out on the day after dialysis. Left ventricular mass index (LVMI) was calculated. Left ventricular ejection fraction (LVEF) was measured by the echocardiographic Simpson method. Arteriovenous fistula flow was determined by Doppler echocardiography. Pulmonary hypertension was diagnosed according to criteria of Guidelines for the diagnosis and treatment of pulmonary hypertension of the European Society of Cardiology. Results Pulmonary hypertension was diagnosed in 47 (53.4%) patients. Left ventricular hypertrophy was revealed in 71 (80.7%) patients. Only 2 (2.3%) patients had LVEF&lt;50%. At the beginning of hemodialysis correlation was detected between systolic pulmonary arterial pressure and LVMI (r=0.52; P&lt;0.001). Systolic pulmonary arterial pressure negatively correlated with left ventricular ejection fraction (r=-0.20; P=0.04). After a year of hemodialysis treatment LVMI decreased from 140.49±42.95 to 123.25±39.27 g/m2 (р=0.006) mainly due to a decrease in left ventricular end-diastolic dimension (from 50.23±6.48 to 45.13±5.24 mm, p=0.04) and systolic pulmonary arterial pressure decreased from 44.83±14.53 to 39.14±10.29 mmHg (р=0.002). Correlation wasn’t found between systolic pulmonary arterial pressure and arteriovenous fistula flow (r=0.17; p=0.4). Conclusion Pulmonary hypertension was diagnosed in half of patients at the beginning of hemodialysis treatment. Pulmonary hypertension in hemodialysis patients was associated with left ventricular hypertrophy, systolic left ventricular dysfunction. After a year-long hemodialysis treatment, a regress in left ventricular hypertrophy and a partial decrease in pulmonary arterial pressure were observed. There wasn’t correlation between arteriovenous fistula flow and systolic pulmonary arterial pressure.

Pulmonary gas exchange in humans exercising at sea level and simulated altitude

1986 ◽  
Vol 61 (1) ◽  
pp. 260-270 ◽  
Author(s):  
P. D. Wagner ◽  
G. E. Gale ◽  
R. E. Moon ◽  
J. R. Torre-Bueno ◽  
B. W. Stolp ◽  
...  
Keyword(s):  
Gas Exchange ◽  
Arterial Pressure ◽  
Sea Level ◽  
Pulmonary Arterial Pressure ◽  
Minute Ventilation ◽  
Statistical Significance ◽  
Random Order ◽  
Normal Subjects ◽  
Simulated Altitude ◽  
Pulmonary Arterial

In a previous study of normal subjects exercising at sea level and simulated altitude, ventilation-perfusion (VA/Q) inequality and alveolar-end-capillary O2 diffusion limitation (DIFF) were found to increase on exercise at altitude, but at sea level the changes did not reach statistical significance. This paper reports additional measurements of VA/Q inequality and DIFF (at sea level and altitude) and also of pulmonary arterial pressure. This was to examine the hypothesis that VA/Q inequality is related to increased pulmonary arterial pressure. In a hypobaric chamber, eight normal subjects were exposed to barometric pressures of 752, 523, and 429 Torr (sea level, 10,000 ft, and 15,000 ft) in random order. At each altitude, inert and respiratory gas exchange and hemodynamic variables were studied at rest and during several levels of steady-state bicycle exercise. Multiple inert gas data from the previous and current studies were combined (after demonstrating no statistical difference between them) and showed increasing VA/Q inequality with sea level exercise (P = 0.02). Breathing 100% O2 did not reverse this increase. When O2 consumption exceeded about 2.7 1/min, evidence for DIFF at sea level was present (P = 0.01). VA/Q inequality and DIFF increased with exercise at altitude as found previously and was reversed by 100% O2 breathing. Indexes of VA/Q dispersion correlated well with mean pulmonary arterial pressure and also with minute ventilation. This study confirms the development of both VA/Q mismatch and DIFF in normal subjects during heavy exercise at sea level. However, the mechanism of increased VA/Q mismatch on exercise remains unclear due to the correlation with both ventilatory and circulatory variables and will require further study.

Lung injury in a surfactant-deficient lung is modified by indomethacin

1990 ◽  
Vol 69 (6) ◽  
pp. 2067-2071 ◽  
Author(s):  
R. Burger ◽  
D. Fung ◽  
A. C. Bryan
Keyword(s):  
Pulmonary Hypertension ◽  
Lung Injury ◽  
Thromboxane A2 ◽  
Neutrophil Infiltration ◽  
Lung Lavage ◽  
Thromboxane A2 Receptor ◽  
Beneficial Effects ◽  
Thromboxane Receptor ◽  
Pulmonary Arterial ◽  
Arterial Po2

Repetitive total lung lavage in adult rabbits leads to a reproducible severe surfactant-deficient lung injury. Hypoxemia requiring mechanical ventilation occurs, accompanied by a substantial pulmonary hypertension, a large intra-alveolar protein leak, peripheral neutropenia, and pathological features of marked neutrophil infiltration with extensive hyaline membrane formation. Pretreatment with indomethacin abolishes postlavage pulmonary hypertension, preserves a slightly better lung function with higher arterial PO2, and prevents the postlavage peripheral neutropenia found in untreated animals. Pretreatment with a thromboxane A2 receptor blocker (L 655,240, Merck Frosst, Canada) also completely attenuated pulmonary hypertension, providing evidence that thromboxane A2 mediates pulmonary arterial hypertension after lung lavage. However, specific thromboxane receptor blockade had no other long-lasting beneficial effects on the ongoing injury in this model.

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