Pharmacological modification of pulmonary vascular injury: possible role of cAMP

1987 ◽  
Vol 62 (1) ◽  
pp. 47-54 ◽  
Author(s):  
I. S. Farrukh ◽  
G. H. Gurtner ◽  
J. R. Michael
Keyword(s):  
Pulmonary Hypertension ◽  
Vascular Permeability ◽  
Prostaglandin E1 ◽  
Lipid Hydroperoxide ◽  
Lipid Peroxide ◽  
Pharmacological Therapy ◽  
Common Mechanism ◽  
Lung Weight ◽  
Tert Butyl Hydroperoxide ◽  
Camp Analogue

Experiments were designed to test the hypothesis that drugs which increase adenosine 3′,5′-cyclic monophosphate (cAMP) in the lung would prevent the pulmonary hypertension and the increase in vascular permeability caused by the infusion of the oxidant lipid peroxide, tert-butyl hydroperoxide (t-bu-OOH), in isolated rabbit lungs perfused with Krebs-Henseleit buffer. Pretreatment with indomethacin or verapamil was also studied, since these drugs block the increase in pulmonary arterial pressure caused by t-bu-OOH. Indomethacin or verapamil prevented the pulmonary hypertension but did not prevent the increase in permeability caused by t-bu-OOH. Consequently, indomethacin or verapamil treatment partially reduced the gain in lung weight caused by t-bu-OOH. In contrast, pretreatment with isoproterenol, prostaglandin E1, or a cAMP analogue not only prevented the pulmonary hypertension but also inhibited the increase in vascular permeability caused by t-bu-OOH. Consequently, these drugs completely blocked the gain in lung weight caused by t-bu-OOH. Posttreatment with aminophylline or the cAMP analogue also significantly reduced the gain in lung weight caused by t-bu-OOH. These results indicate that pharmacological therapy can reduce the pulmonary hypertension and the increase in vascular permeability caused by the infusion of a lipid hydroperoxide. Since isoproterenol, aminophylline, prostaglandin E1, and a cAMP analogue all had similar effects, the results suggest that the likely common mechanism for their protective effect is an increase in cAMP.

scholarly journals Characterization of a Cohort of Patients with Chronic Thromboembolic Pulmonary Hypertension from Northeastern Colombia (REHINO Study)

2021 ◽  
Vol 1 (2) ◽  
pp. 105-113
Author(s):  
Javier Enrique Fajardo-Rivero ◽  
Melissa Mogollón ◽  
Diego Fernando García-Bohórquez ◽  
Andrés Villabona-Rueda ◽  
Tania Mendoza-Herrera ◽  
...  
Keyword(s):  
Pulmonary Hypertension ◽  
Thrombotic Event ◽  
Chronic Thromboembolic Pulmonary Hypertension ◽  
Pharmacological Therapy ◽  
Functional Class ◽  
World Health ◽  
Class Iii ◽  
European Respiratory Society ◽  
Cross Sectional ◽  
Number Of Patients

Chronic thromboembolic disease (CTEPH) is one of the causes for developing pulmonary hypertension (PH). PH is characterized by an increase in pulmonary vascular pressure and resistance, ultimately leading to chronic overload. This study describes the clinical, functional, and hemodynamic characteristics as well as the established treatment strategy for a cohort of patients diagnosed with CTEPH in Bucaramanga, Colombia. In Colombia, PH is considered as an orphan disease with limited epidemiological data. We aim to provide useful information in order to help guide future clinical decisions for PH treatment and prevention. We conducted a cross-sectional study, obtaining clinical data from patients under follow-up, over 18 years of age, with hemodynamic confirmation of CTEPH in two pulmonary outpatient centers in Bucaramanga, Colombia between 2012 and 2018. 35 patients with diagnosis of CTEPH were included. Mean age was 52.3 ± 17.9 years. The mean time between the onset of symptoms to diagnosis was 14 months. 71% had a previous thrombotic event and 69% had functional class III and IV according to the world health organization (WHO) criteria. Most of the patients were classified as at high risk of mortality according to the European Society of Cardiology (ESC) and the European Respiratory Society (ERS/ESC) criteria and 60% were referred to undergo thromboendarterectomy. Most of the patients were under monotherapy treatment with Bosentan, the most prescribed medication in both monotherapy and dual therapy. This study identified a high number of patients in advanced stages of CETPH due to late diagnosis, related to health care limitations. This resulted in worse prognosis and quality of life. In addition, low adherence to non-pharmacological interventions was evidenced in patients who were not candidates for thromboendarterectomy despite the onset of pharmacological therapy.

Pressure-dependent increase in lung vascular permeability to water but not protein

1992 ◽  
Vol 72 (1) ◽  
pp. 211-218 ◽  
Author(s):  
I. C. Ehrhart ◽  
W. F. Hofman
Keyword(s):  
Vascular Permeability ◽  
Plasma Proteins ◽  
Autologous Blood ◽  
Relative Increase ◽  
Solvent Drag ◽  
Lung Weight ◽  
Fluid Filtration ◽  
Lung Lobe ◽  
Highly Correlated ◽  
Lung Vascular Permeability

Simultaneous measures of vascular permeability to fluid (capillary filtration coefficient, Kf) and to plasma proteins (solvent drag reflection coefficient, sigma) were obtained over venous pressures (Pv) from 14 to 105 Torr in the isolated ventilated canine lung lobe (n = 70) pump perfused with autologous blood. The sigma was obtained from the relative increase in the concentration of plasma proteins vs. erythrocytes during fluid filtration. Kf's were obtained from two gravimetric methods as well as from change in hematocrit. All Kf's increased (P less than 0.05) as Pv was increased. However, sigma averaged 0.59 +/- 0.01 (range 0.54–0.67) and was unchanged (P greater than 0.05) by elevation of Pv over 20–105 Torr. In 44 lobes where all three Kf measures were obtained, gravimetric measures of Kf did not differ (P greater than 0.05) and were highly correlated with Kf obtained from hematocrit change, Vf Kf (P less than 0.001). However, both weight-based Kf's exceeded Vf Kf (P less than 0.05), suggesting that fluid filtration was overestimated by rate of lung weight gain or underestimated by hematocrit change. Increased permeability to water but not to protein over Pv from 20 to 105 Torr indicates that permeability to both can change independently and is counter to the theory that elevated vascular pressure “stretches” vascular pores.

Fructose 1,6-diphosphate augments paraquat injury in isolated dog lungs

1991 ◽  
Vol 71 (5) ◽  
pp. 1830-1835 ◽  
Author(s):  
T. Shibamoto ◽  
J. C. Parker
Keyword(s):  
Free Radicals ◽  
Vascular Permeability ◽  
Cyclic Oxidation ◽  
Oxygen Free Radicals ◽  
Weight Ratio ◽  
Reduction Reaction ◽  
Microvascular Permeability ◽  
Lung Weight ◽  
Activated Neutrophils ◽  
Pretreated Group

Paraquat (PQ; 1,1'-dimethyl-4,4′-bipyridylium dichloride), a widely used herbicide, causes pulmonary edema by a cyclic oxidation and reduction reaction with oxygen molecules with the production of oxygen free radicals. Because fructose 1,6-diphosphate (FDP) has recently been shown to inhibit the generation of oxygen free radicals by activated neutrophils, we determined the effects of FDP on PQ-induced increase in microvascular permeability in isolated blood-perfused dog lungs. Vascular permeability was assessed using the capillary filtration coefficient (Kf,c) and isogravimetric capillary pressure (Pc,i). There was no change in these variables over 5 h in the control lungs treated with saline (n = 5). A significant increase in Kf,c and a decrease in Pc,i, both of which indicated increased vascular permeability, were observed at 5 h of perfusion with 4 x 10(-3) M PQ (n = 5). Unexpectedly, an increase in microvascular permeability occurred within 4 h after administration of PQ in the lungs that were pretreated with FDP (2.7–14.2 mM, n = 6). Moreover the increases of Kf,c in the FDP-pretreated lungs were significantly greater than those in the lungs treated with PQ alone. Also, the final-to-initial lung weight ratio of the FDP-pretreated group was greater than those of the other groups. Thus the FDP dose used in the present study accentuated rather than prevented the PQ lung injury.

Mechanisms of pulmonary edema induced by a diacylglycerol second messenger

1990 ◽  
Vol 258 (1) ◽  
pp. H85-H91 ◽  
Author(s):  
A. Johnson ◽  
D. C. Hocking ◽  
T. J. Ferro
Keyword(s):  
Pulmonary Edema ◽  
Capillary Pressure ◽  
Vascular Permeability ◽  
Second Messenger ◽  
Base Line ◽  
Lung Weight ◽  
Pulmonary Response ◽  
Group Response ◽  
Isolated Lung ◽  
Pkc Activation

We investigated the effect of dioctanoylglycerol (DOG), a second messenger of protein kinase C (PKC) activation, in the absence and presence of neutrophils in isolated perfused guinea pig lung. DOG was given after a base-line isogravimetric steady-state period. Pulmonary capillary pressure (Ppc) and change in lung weight (delta W) were monitored at 15, 30, and 60 min. Capillary filtration coefficient (Kf,c, an index of vascular permeability) was measured during base-line period and at 30 min. DOG increased the Ppc and delta W at 30 and 60 min, and the Kfc at 30 min. Monooctanoylglycerol, a monoacylglycerol that does not activate PKC, had no effect on Ppc, Kf,c, and delta W. Pretreatment with two different PKC inhibitors, 1-(5-isoquinolinylsulfonyl)-2-methyl piperazine or staurosporin, prevented the pulmonary response to DOG. With neutrophils present, DOG caused greater increases in delta W and the (wet-dry)-to-dry wt ratio compared with DOG group. Response to DOG+ neutrophils was due to oxygen radical production because it was prevented by pretreatment with catalase and because DOG increased superoxide release from neutrophils. PKC activation using DOG in the isolated lung results in pulmonary edema mediated by increases in capillary pressure and vascular permeability. Lung weight-gain response to DOG is greater in the presence of neutrophils. Response to DOG+ neutrophils is mediated by oxygen radicals.

Efficacy of vasodilator therapy in canine model of acute pulmonary hypertension

1988 ◽  
Vol 255 (5) ◽  
pp. H1232-H1239 ◽  
Author(s):  
H. J. Priebe
Keyword(s):  
Pulmonary Hypertension ◽  
Gas Exchange ◽  
Pulmonary Artery ◽  
Prostaglandin E1 ◽  
Canine Model ◽  
Lung Compliance ◽  
Myocardial Segment ◽  
Vasodilator Therapy ◽  
Artery Flow ◽  
Subsequent Administration

This study was performed to determine 1) the effects of acute pulmonary embolization (induced by injection of autologous muscle) on right ventricular (RV) performance, coronary hemodynamics, and gas exchange; and 2) the efficacy of subsequent administration of nitroglycerin, prostaglandin E1, and hydralazine with regard to improvement in RV function and gas exchange in eight open-chest dogs. After embolization, pulmonary artery (PA) pressure and vascular resistance (PVR) increased three- to fivefold without changes in RV end-diastolic dimensions (ultrasonic dimension technique) or pressure. However, systolic dimensions increased, and stroke volume (SV) fell. Gas exchange, lung compliance, and pH worsened. Subsequent administration of nitroglycerin (5 micrograms.kg-1.min-1) and prostaglandin E1 (0.2 micrograms.kg-1.min-1) caused further decreases in SV and pH. In contrast, hydralazine (mean 0.15 mg/kg) improved myocardial segment shortening, SV, PVR, pulmonary artery flow, and gas exchange. Coronary blood flow increased by 110%. Thus in this canine model of combined pulmonary hypertension and respiratory insufficiency, nitroglycerin and prostaglandin E1 exerted no beneficial cardiopulmonary effects. In contrast, hydralazine improved regional and global RV performance and gas exchange.

Prostaglandin E1 in infants with congenital diaphragmatic hernia (CDH) and life-threatening pulmonary hypertension

2020 ◽  
Vol 55 (9) ◽  
pp. 1872-1878
Author(s):  
Kévin Le Duc ◽  
Sébastien Mur ◽  
Dyuti Sharma ◽  
Estelle Aubry ◽  
Morgan Recher ◽  
...  
Keyword(s):  
Pulmonary Hypertension ◽  
Congenital Diaphragmatic Hernia ◽  
Diaphragmatic Hernia ◽  
Prostaglandin E1 ◽  
Life Threatening

Use of Prostaglandin E1 to Treat Peri-Anaesthetic Pulmonary Hypertension Associated with Mitral Valve Disease

1993 ◽  
Vol 21 (3) ◽  
pp. 161-164 ◽  
Author(s):  
K Mikawa ◽  
N Maekawa ◽  
R Goto ◽  
H Yaku ◽  
K Nishina ◽  
...  
Keyword(s):  
Pulmonary Hypertension ◽  
Mitral Valve ◽  
Glyceryl Trinitrate ◽  
Mitral Valve Disease ◽  
Prostaglandin E1 ◽  
Valve Disease ◽  
Prostaglandin E ◽  
Severe Pulmonary Hypertension ◽  
Critical Problem ◽  
Ventricular Afterload

Severe pulmonary hypertension (PH) can be a critical problem during and after cardiac surgery, since it increases right ventricular afterload resulting in decreased cardiac output. A case of pulmonary hypertension associated with mitral valve disease and resistant to glyceryl trinitrate therapy during surgery is reported. The case was treated successfully with prostaglandin E1 (PGE1), indicating that PGE1 can be used peri-operatively in a patient with refractory PH resistant to glyceryl trinitrate treatment.

Abnormal lung growth and the development of pulmonary hypertension in the Fawn-Hooded rat

1999 ◽  
Vol 277 (4) ◽  
pp. L709-L718 ◽  
Author(s):  
Timothy D. le Cras ◽  
Dug-Ha Kim ◽  
Sarah Gebb ◽  
Neil E. Markham ◽  
John M. Shannon ◽  
...  
Keyword(s):  
Pulmonary Hypertension ◽  
Subsequent Development ◽  
Supplemental Oxygen ◽  
Secretory Protein ◽  
Clara Cell ◽  
Lung Hypoplasia ◽  
Lung Growth ◽  
Sprague Dawley ◽  
Lung Weight ◽  
Increased Risk

The Fawn-Hooded rat (FHR) strain develops accelerated and severe pulmonary hypertension when exposed to slight decreases in alveolar[Formula: see text]. We recently observed that adult FHR lungs showed a striking pattern of disrupted alveolarization and hypothesized that abnormalities in lung growth in the perinatal period predisposes the FHR to the subsequent development of pulmonary hypertension. We found a reduction in lung weight in the fetus and 1-day- and 1-wk-old FHR compared with a normal rat strain (Sprague-Dawley). Alveolarization was reduced in infant and adult FHR lungs. In situ hybridization showed similar patterns of expression of two epithelial markers, surfactant protein C and 10-kDa Clara cell secretory protein, suggesting that the FHR lung is not characterized by global delays in epithelial maturation. Barium-gelatin angiograms demonstrated reduced background arterial filling and density in adult FHR lungs. Perinatal treatment of FHR with supplemental oxygen increased alveolarization and reduced the subsequent development of right ventricular hypertrophy in adult FHR. We conclude that the FHR strain is characterized by lung hypoplasia with reduced alveolarization and increased risk for developing pulmonary hypertension. We speculate that altered oxygen sensing may cause impaired lung alveolar and vascular growth in the FHR.

Correlation of acute with chronic hypoxic pulmonary hypertension in cattle

1975 ◽  
Vol 38 (3) ◽  
pp. 495-498 ◽  
Author(s):  
D. H. Will ◽  
J. L. Hicks ◽  
C. S. Card ◽  
J. T. Reeves ◽  
A. F. Alexander
Keyword(s):  
Pulmonary Hypertension ◽  
Arterial Pressure ◽  
Pulmonary Arterial Pressure ◽  
Pressor Response ◽  
Acute Hypoxia ◽  
Common Mechanism ◽  
Mean Pulmonary Arterial Pressure ◽  
Pressor Responses ◽  
Pulmonary Arterial ◽  
Highly Correlated

We investigated acute and chronic hypoxic pulmonary pressor responses in two groups of calves, one bred to be susceptible, the other resistant to high-altitude pulmonary hypertension. Twelve 5-mo-old susceptible calves residing at 1,524 m increased their mean pulmonary arterial pressure from 26 +/- 2 (SE) to 55 +/- 4 mmHg during 2 h at a simulated altitude of 4,572 m. In 10 resistant calves pressure increased from 22 +/- 1 to 37 +/- 2 mmHg. Five calves were selected from each group for further study. When 9 mo old, the 5 susceptible calves again showed a greater pressor response to acute hypoxia (27 +/- 1 to 55 +/- 4 mmHg) than did 5 resistant calves (23 +/- 1 to 41 +/- 3 mmHg). When 12 mo old, the 5 susceptible calves also developed a greater increase in pulmonary arterial pressure (21 +/- 2 to 9 +/- 4 mmHg) during 18 days at 4,572 m than did the 5 resistant calves (21 +/- 1 to 64 +/- 4 mmHg). Acute and chronic hypoxic pulmonary pressor responses were highly correlated (r = 0.91; P less than 0.001) indicating that they were probably produced through a common mechanism.

Effects of transient pulmonary hypertension on pulmonary vascular permeability

1983 ◽  
Vol 55 (3) ◽  
pp. 983-989 ◽  
Author(s):  
F. L. Minnear ◽  
P. S. Barie ◽  
A. B. Malik
Keyword(s):  
Pulmonary Edema ◽  
Vascular Permeability ◽  
Left Atrial ◽  
Lymph Flow ◽  
Balloon Inflation ◽  
Lung Water ◽  
Lung Weight ◽  
Pulmonary Vascular Permeability ◽  
Airway Edema ◽  
Vascular Surface

The effects of a transient increase in pulmonary microvascular pressure (Pmv) on pulmonary fluid and protein exchange were studied in anesthetized sheep in which pulmonary lymph was collected. Pmv was increased to 30-40 mmHg for 15-30 min in 18 sheep by either an intra-aortic injection of norepinephrine (NE) or a rapid inflation of a left atrial balloon. NE injection produced sustained two- to threefold increases in pulmonary lymph flow and protein flux, whereas rapid balloon inflation transiently elevated lymph flow even though Pmv increased to similar levels with both methods. The sustained increases with NE were not due to an increase in vascular permeability but probably the result of a persistent increase in vascular surface area. In three additional animals, Pmv was increased to over 50 mmHg for 15-30 min. In these animals, lymph flow increased only by 49%, but airway edema fluid was present. The ratio of extravascular lung water to bloodless dry lung weight was 5.77 +/- 0.13 as compared with 4.30 +/- 0.11 in sheep subjected to Pmv less than 50 mmHg and to 4.08 +/- 0.19 for controls. These findings indicate that high pressure-induced pulmonary edema depends on a threshold Pmv around 50 mmHg. A combination of high capillary pressure and impaired lymphatic flow may be the bases for the development of neurogenic and catecholamine-induced pulmonary edema.

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