Effect of Gram-Negative Endotoxin on Pulmonary Circulation

1958 ◽  
Vol 192 (2) ◽  
pp. 335-344 ◽  
Author(s):  
Hiroshi Kuida ◽  
Lerner B. Hinshaw ◽  
Robert P. Gilbert ◽  
Maurice B. Visscher
Keyword(s):  
Pulmonary Artery ◽  
Vascular Response ◽  
Weight Changes ◽  
Hemodynamic Changes ◽  
Lung Weight ◽  
Pulmonary Hemodynamics ◽  
Pump System ◽  
Absolute Increase ◽  
Consistent Increase ◽  
Pulmonary Arterial

Effects of endotoxin on the pulmonary hemodynamics of dogs and cats have been studied in intact animals, open chest animals with and without control of cardiac output by an extracorporeal venous reservoir—pump system, and in isolated perfused continuously weighed lungs. Pulmonary artery pressure increased without a rise in left atrial pressure in all preparations following the injection of endotoxin. Pulmonary artery wedge and small pulmonary vein pressures uniformly increased. Total pulmonary vascular, pulmonary arterial and pulmonary venous resistances were calculated in five perfused lungs. The absolute increase in pulmonary venous resistance was greater than in the arterial resistance in four of the five studies and was relatively greater in every instance. There was a consistent increase in lung weight associated with these hemodynamic changes. Analysis of the determinants of lung weight changes has provided evidence to support the conclusion that the pulmonary vascular response to endotoxin administration is characterized predominantly by constriction of pulmonary venules and/or small veins.

Pulmonary microvascular response to LTB4: effects of perfusate composition

1988 ◽  
Vol 64 (5) ◽  
pp. 1989-1996 ◽  
Author(s):  
T. C. Noonan ◽  
W. M. Selig ◽  
K. E. Burhop ◽  
C. A. Burgess ◽  
A. B. Malik
Keyword(s):  
Pulmonary Edema ◽  
Protein Concentration ◽  
Autologous Blood ◽  
Endothelial Permeability ◽  
Leukotriene B4 ◽  
Albumin Concentration ◽  
Weight Changes ◽  
Lung Weight ◽  
Pulmonary Hemodynamics ◽  
Pulmonary Arterial

We examined the effects of leukotriene B4 (LTB4) on pulmonary hemodynamics and vascular permeability using isolated perfused guinea pig lungs and cultured monolayers of pulmonary arterial endothelial cells. In lungs perfused with Ringer solution, containing 0.5 g/100 ml albumin (R-alb), LTB4 (4 micrograms) transiently increased pulmonary arterial pressure (Ppa) and capillary pressure (Pcap). Pulmonary edema developed within 70 min after LTB4 injection despite a normal Pcap. The LTB4 metabolite, 20-COOH-LTB4 (4 micrograms), did not induce hemodynamic and lung weight changes. In lungs perfused with autologous blood hematocrit = 12 +/- 1%; protein concentration = 1.5 +/- 0.2 g/100 ml), the increases in Ppa and Pcap were greater, and both pressures remained elevated. The lung weight did not increase in blood-perfused lungs. In lungs perfused with R-alb (1.5 g/100 ml albumin) to match the blood perfusate protein concentration, LTB4 induced similar hemodynamic changes as R-alb (0.5 g/100 ml) perfusate, but the additional albumin prevented the pulmonary edema. LTB4 (10(-11)-10(-6) M) with or without the addition of neutrophils to the monolayer did not increase endothelial 125I-albumin permeability. Therefore LTB4 induces pulmonary edema when the perfusate contains a low albumin concentration, but increasing the albumin concentration or adding blood cells prevents the edema. The edema is not due to increased endothelial permeability to protein and is independent of hemodynamic alterations. Protection at higher protein-concentration may be the result of LTB4 binding to albumin.

scholarly journals Serotonin contributes to high pulmonary vascular tone in a sheep model of persistent pulmonary hypertension of the newborn

2013 ◽  
Vol 304 (12) ◽  
pp. L894-L901 ◽  
Author(s):  
Cassidy Delaney ◽  
Jason Gien ◽  
Gates Roe ◽  
Nicole Isenberg ◽  
Jenai Kailey ◽  
...  
Keyword(s):  
Pulmonary Hypertension ◽  
Pulmonary Artery ◽  
Tryptophan Hydroxylase ◽  
Late Gestation ◽  
Persistent Pulmonary Hypertension ◽  
Sheep Model ◽  
Pulmonary Hemodynamics ◽  
Fetal Sheep ◽  
Pulmonary Arterial

Although past studies demonstrate that altered serotonin (5-HT) signaling is present in adults with idiopathic pulmonary arterial hypertension, whether serotonin contributes to the pathogenesis of persistent pulmonary hypertension of the newborn (PPHN) is unknown. We hypothesized that 5-HT contributes to increased pulmonary vascular resistance (PVR) in a sheep model of PPHN and that selective 5-HT reuptake inhibitor (SSRI) treatment increases PVR in this model. We studied the hemodynamic effects of 5-HT, ketanserin (5-HT2A receptor antagonist), and sertraline, an SSRI, on pulmonary hemodynamics of the late gestation fetal sheep with PPHN caused by prolonged constriction of the ductus arteriosis. Brief intrapulmonary infusions of 5-HT increased PVR from 1.0 ± 0.07 (baseline) to 1.4 ± 0.22 mmHg/ml per minute of treatment ( P < 0.05). Ketanserin decreased PVR from 1.1 ± 0.15 (baseline) to 0.82 ± 0.09 mmHg/ml per minute of treatment ( P < 0.05). Sertraline increased PVR from 1.1 ± 0.17 (baseline) to 1.4 ± 0.17 mmHg/ml per minute of treatment ( P = 0.01). In addition, we studied 5-HT production and activity in vitro in experimental PPHN. Compared with controls, pulmonary artery endothelial cells from fetal sheep with PPHN exhibited increased expression of tryptophan hydroxylase 1 and 5-HT production by twofold and 56%, respectively. Compared with controls, 5-HT2A R expression was increased in lung homogenates and pulmonary artery smooth muscle cell lysates by 35% and 32%, respectively. We concluded that increased 5-HT contributes to high PVR in experimental PPHN through activation of the 5-HT2A receptor and that SSRI infusion further increases PVR in this model.

Effect of edema and hemodynamic changes on extravascular thermal volume of the lung

1984 ◽  
Vol 56 (4) ◽  
pp. 878-890 ◽  
Author(s):  
B. A. Gray ◽  
R. C. Beckett ◽  
R. C. Allison ◽  
D. R. McCaffree ◽  
R. M. Smith ◽  
...  
Keyword(s):  
Pulmonary Edema ◽  
Mean Transit Time ◽  
Hemodynamic Changes ◽  
Pulmonary Hemodynamics ◽  
Indocyanine Green Dye ◽  
Pulmonary Arterial ◽  
The Mean ◽  
The Difference ◽  
Acute Changes ◽  
Thermal Dilution

The extravascular thermal volume of the lung (ETV) has been measured in dogs as the difference between mean transit time (t) volumes for heat and indocyanine green dye across the pulmonary circulation, calculated as the product of thermal dilution cardiac output (CO) and the difference in t for aortic indicator-dilution curves generated by right and left atrial injections. ETV measurements were compared with the extravascular lung mass (ELM): in 21 normal dogs, ETV/ELM = 1.11 +/- 0.14 (SD); in 17 dogs with hydrostatic pulmonary edema (up to 21 g/kg), ETV/ELM = 0.90 +/- 0.11; and in 27 dogs with alloxan pulmonary edema (up to 51 g/kg); ETV/ELM = 0.93 +/- 0.13. For all 65 dogs the mean ETVELM was 0.98 +/- 0.15, and the liner regression was ETV (ml/kg) = 0.90 ELM (g/kg) + 0.86 +/- 2.25 (SEE; r = 0.96). Calculations based on measurements of lung specific heat predict that ETV/ELM should equal 0.984. With acute changes in pulmonary hemodynamics, ETV was reduced by reductions in pulmonary arterial pressure (Ppa) sufficient to produce zone 1 conditions at the top of the lung. However, ETV was not affected by increases in CO (mean = 50%) produced by nitroprusside or by increases in Ppa and pulmonary blood volume (mean = 27%) produced by partial mitral valve obstruction. Distortion of the thermal dilution curve due to position of the arterial thermistor appears to be the greatest source of variability and overestimation. Simultaneous measurements from pairs of thermistors differed by 14% (range 0.4–50%).

The Source Of Thromboxane Formation Associated With Complement-Mediated Pulmonary Leukostasis In Sheep

1981 ◽  
Author(s):  
J W D McDonald ◽  
M Ali ◽  
J D Cooper ◽  
E R Townsend
Keyword(s):  
Pulmonary Artery ◽  
Blood Clotting ◽  
Ex Vivo ◽  
Lung Parenchyma ◽  
Mechanical Obstruction ◽  
Vascular Response ◽  
In Vivo Experiments ◽  
Pulmonary Arterial

The infusion of plasma containing Zymosan-activated complement (ZAC) into sheep produces leukopenia with pulmonary leukostasis and transient pulmonary arterial hypertension (PAH). Previous work has related PAH to elevations of plasma thromboxane B2 (TXB2) rather than to mechanical obstruction by sequestered leukocytes (WBC). We have investigated the source of the TXB2 formation in this model. Incubation of platelet-poor WBC preparations with arachi- donate resulted in negligible TXB2 formation. WBC-poor platelet preparations on the other hand formed significant amounts of TXB2 (approximately 6-18 ng/108 platelets). Incubation of whole sheep blood or plasma with ZAC failed to generate significant amounts of TXB2. Thus, WBC agglutination in vitro did not induce platelet TXB2 formation.Pretreatment of sheep with aspirin (ASA)(10 mg/kg IV) completely blocked TXB2 formation and PAH in response to infusion of plasma containing ZAC. The infusion of 10-50% nonnal platelets into sheep 4 hours after ASA pretreatment failed to restore TXB2 formation and pulmonary vascular response to subsequent challenge with ZAC. TXB2 formation during blood clotting ex vivo was restored by the platelet infusions. These experiments make it appear unlikely that platelets are the source of the TXB2. It is possible that the transfused platelets respond to thrombin but are unable to interact with sequestered leukocytes. Sheep lung and pulmonary artery were incubated in vitro with arachidonate. Lung formed 630 ng TXB2 and 39 ng 6-keto-PGF1α/g of wet tissue. Pulmonary artery formed 9 ng TXB2 and 180 ng 6-keto-PGF1α/g of wet tissue. The relative proportions of TXB2 and 6-keto-PGF1α formed by lung parenchyma but not pulmonary artery resemble the proportions observed in previous in vivo experiments with ZAC. It appears that lung tissue is the most likely source of TXB2 formation causing PAH in response to ZAC-mediated pulmonary leukostasis.

Lung inflation can cause pulmonary edema in zone I of in situ dog lungs

1980 ◽  
Vol 49 (5) ◽  
pp. 815-819 ◽  
Author(s):  
R. K. Albert ◽  
S. Lakshminarayan ◽  
W. Kirk ◽  
J. Butler
Keyword(s):  
Weight Gain ◽  
Venous Pressure ◽  
Lower Lobe ◽  
Alveolar Pressure ◽  
Weight Changes ◽  
Lung Water ◽  
Lung Weight ◽  
Lung Inflation ◽  
Pulmonary Arterial

We investigated whether increases in lung water can occur due to lung inflation in zone I when alveolar vessels are collapsed. Static left lower lobe alveolar pressure, pulmonary arterial pressure, and pulmonary venous pressure were controlled in living, anesthetized, open-chested dogs. The lobe was inflated with 6% CO2 in air and suspended from a strain gauge, which allowed continual weight recording. The lung was held in zone I conditions. Arterial and venous pressures were equal at either 1 or 5 cmH2O, relative to the base of the 10- to 14-cm-high lobes. Weight changes were measured for 5 min after 5-cmH2O increments of alveolar pressure from 0 or 5 to 30 cmH2O. Lung weight gain due to edema occurred with inflation to alveolar pressures above 10 cmH2O. Greater lung distension resulted in greater rates of weight gain. Weight loss occurred on deflation. The fluid may have leaked from distended extra-alveolar vessels. This mechanism could explain the increased lung water seen with mechanical ventilation and/or positive end-expiratory pressure breathing.

Effect of chronic thromboembolism on the pulmonary artery pressure-flow relationship in dogs

1994 ◽  
Vol 76 (2) ◽  
pp. 875-881 ◽  
Author(s):  
M. A. Olman ◽  
R. Z. Gan ◽  
R. T. Yen ◽  
I. Villespin ◽  
R. Maxwell ◽  
...  
Keyword(s):  
Pulmonary Artery ◽  
Pulmonary Circulation ◽  
Flow Line ◽  
Pulmonary Arteries ◽  
Chronic Thromboembolic Pulmonary Hypertension ◽  
Elastic Tube ◽  
Pulmonary Hemodynamics ◽  
Thromboembolic Pulmonary Hypertension ◽  
Pulmonary Arterial

To understand the hemodynamic alterations associated with chronic thromboembolic pulmonary hypertension, the large pulmonary arteries of mongrel dogs were chronically obstructed with lysis-resistant thrombi. Pulmonary hemodynamics were experimentally measured and described by multipoint pulmonary arterial pressure (PAP) vs. flow plots. In nine anesthetized chronically embolized dogs, but not in six control dogs, the PAP-flow line shifted significantly upward in a parallel fashion by 4.2 +/- 0.7 mmHg. The postembolic pulmonary circulation was further characterized by predictions from a morphometric-based elastic tube and sheet flow model of the canine pulmonary circulation. After model validation with the preembolic PAP-flow data, the derived postembolic PAP matched the in vivo results to within 1 mmHg. A detailed analysis of the model-derived PAP drop revealed that the PAP-flow line shift can be accounted for by a novel fixed resistor in the largest obstructed pulmonary artery.

Effects of Histamine, 5 Hydroxytryptamine and Epinephrine on Pulmonary Hemodynamics With Particular Reference to Arterial and Venous Segment Resistances

1958 ◽  
Vol 194 (1) ◽  
pp. 165-170 ◽  
Author(s):  
Robert P. Gilbert ◽  
Lerner B. Hinshaw ◽  
Hiroshi Kuida ◽  
Maurice B. Visscher
Keyword(s):  
Pulmonary Artery ◽  
Pulmonary Vein ◽  
Pulmonary Veins ◽  
Lung Weight ◽  
Pulmonary Hemodynamics ◽  
Resistance Increase ◽  
Arterial Resistance ◽  
Venous Resistance ◽  
Venous Segment ◽  
Sizeable Increase

Studies were made of the effects of histamine and 5 hydroxytryptamine (5HT) on arterial and venous segmental resistances in the isolated perfused dog lung. The lung was perfused at constant flow while pressures were measured in the pulmonary artery (PA), left atrium (PV) and in either the pulmonary artery wedge position (PAw) or a small pulmonary vein (PVs). Arterial resistance changes were inferred from changes in the PA-PAw pressure drop, and venous resistance from the PAw-PV pressure gradient. Changes in lung weight were recorded continuously. It was found that histamine usually caused a greater increase of the venous resistance than of the arterial resistance, while 5HT usually increased the arterial resistance more than the venous resistance. When the predominant resistance increase was arterial the lung weight fell, but when there was a sizeable increase of the venous resistance the lung weight rose, presumably as a result of increased capillary blood content. The correlation coefficient between the change in lung weight and the change in venous resistance was + .791. Small pulmonary vein pressures rose after administration of epinephrine, norepinephrine, histamine and 5HT. This result gives further proof of constriction of pulmonary veins by these agents.

Cardiopulmonary mechanics in anesthetized pigs and dogs

1960 ◽  
Vol 198 (2) ◽  
pp. 346-348 ◽  
Author(s):  
Ernst O. Attinger ◽  
John M. Cahill
Keyword(s):  
Pulmonary Artery ◽  
Pulmonary Artery Pressure ◽  
Flow Resistance ◽  
Human Lung ◽  
Pulmonary Vasculature ◽  
Lung Weight ◽  
Pulmonary Hemodynamics ◽  
Residual Capacity ◽  
Ventilatory Mechanics ◽  
Nembutal Anesthesia

Ventilatory mechanics and pulmonary hemodynamics were investigated in 39 mongrel dogs and 19 pigs under Nembutal anesthesia. It was found that the pig lung is much less compliant than the dog lung but resembles the human lung if the elastic properties are compared with respect to lung weight or functional residual capacity. The pulmonary artery pressure in the pig was found to be around 42 cm H2O. The flow resistance of the pulmonary vasculature of the pig is approximately 12 times as great as that of the human lung and 2–3 times greater than in the canine lung. The compliance of the pulmonary artery is correspondingly decreased. The pig appears to be a more suitable animal for the study of pulmonary vasomotion than dog or man.

scholarly journals Dynamics of the clinical functional and hemodynamic profile of patients with pulmonary arterial hypertension with initial monotherapy with endothelin receptor antagonists: bosentan vs. macitentan

Kardiologiia ◽  
2020 ◽  
Vol 60 (7) ◽  
pp. 28-35
Author(s):  
T. V. Martynyuk ◽  
A. M. Aleevskaya
Keyword(s):  
Pulmonary Arterial Hypertension ◽  
Treatment Group ◽  
Pulmonary Artery ◽  
Arterial Hypertension ◽  
Systolic Pressure ◽  
Pulmonary Artery Systolic Pressure ◽  
Eisenmenger Syndrome ◽  
Pulmonary Hemodynamics ◽  
Cardiothoracic Ratio ◽  
Pulmonary Arterial

Aim To compare results of 24-h treatments with bosentan and macitentan by the clinical functional status and indexes of pulmonary hemodynamics in patients with pulmonary arterial hypertension (PAH).Materials and methods Based on the Russian National Registry (NCT03707561), 44 patients older than 18 years with PAH (34 patients with idiopathic pulmonary hypertension (IPH) and 10 patients with Eisenmenger syndrome) were retrospectively included into this study. Based on the statistical method of pairwise comparison, two groups were formed and matched by age, gender, WHO functional class (FC), and 6-min walk distance (6MWD). 22 patients of group 1 (17 with IPH and 5 with Eisenmenger syndrome) were treated with macitentan 10 mg/day, and 22 patients of group 2 (17 with IPH and 5 with Eisenmenger syndrome) were treated with bosentan 250 mg/day. Clinical instrumental data (6MWD, Borg dyspnea score, chest X-ray, transthoracic echocardiography (EchoCG), and right heart catheterization (RHC)) were evaluated at baseline and after 24 weeks of therapy.Results By week 24 of the treatment, FC and 6MWD improved in both groups. The macitentan treatment was associated with a significant decrease in Borg score. Significant intergroup differences in EchoCG data were not observed. The bosentan treatment was associated with a decrease in right ventricular (RV) dimension and a tendency towards a decrease in calculated pulmonary artery systolic pressure (PASP). By week 24, the macitentan treatment as compared to the bosentan treatment, was associated with a decrease in cardiothoracic ratio (CTR). In both groups, RHC showed decreases in PASP, mean pulmonary artery pressure and pulmonary vascular resistance, and improvements in cardiac output (CO), cardiac index, and stroke volume (SV) values. By week 24, the increase in SV was greater in the macitentan treatment group than in the bosentan treatment group (р=0.05).Conclusion The 24-week treatment with bosentan or macitentan provided significant and comparable improvement of the functional profile in PAH patients with FC II (WHO) at baseline. The decrease in CTR was significantly more pronounced in the macitental treatment group compared to the bosentan treatment group. The 24-week bosentan treatment resulted in a decrease in RV anterior-posterior dimension, a tendency towards a decrease in PASP according to EchoCG data. Macitentan provided more pronounced dynamics of dyspnea than bosentan according to the results of 6MWD test and the increase in SV according to RHC data.

Sign in / Sign up

Export Citation Format

Share Document