scholarly journals Lung eicosanoids in perinatal rats with congenital diaphragmatic hernia

1997 ◽  
Vol 6 (1) ◽  
pp. 39-45 ◽  
Author(s):  
H. Ijsselstijn ◽  
F. J. Zijlstra ◽  
J. P. M. Van Dijk ◽  
J. C. De Jongste ◽  
D. Tibboel

Abnormal levels of pulmonary eicosanoids have been reported in infants with persistent pulmonary hypertension (PPH) and congenital diaphragmatic hernia (CDH). We hypothesized that a dysbalance of vasoconstrictive and vasodilatory eicosanoids is involved in PPH in CDH patients. The levels of several eicosanoids in lung homogenates and in bronchoalveolar lavage fluid of controls and rats with CDH were measured after caesarean section or spontaneous birth. In controls the concentration of the stable metabolite of prostacyclin (6-keto-PGF1α), thromboxane A2(TxB2), prostaglandin E2(PGE2), and leukotriene B4(LTB4) decreased after spontaneous birth. CDH pups showed respiratory insufficiency directly after birth. Their lungs had higher levels of 6- keto-PGF1α, reflecting the pulmonary vasodilator prostacyclin (PGI2), than those of controls. We conclude that in CDH abnormal lung eicosanoid levels are present perinatally. The elevated levels of 6-keto-PGF1αin CDH may reflect a compensation mechanism for increased vascular resistance.

1997 ◽  
Vol 6 (3) ◽  
pp. 217-224 ◽  
Author(s):  
H. Ijsselstijn ◽  
F. J. Zijlstra ◽  
J. C. De Jongste ◽  
D. Tibboel

Vasoactive prostanoids may be involved in persistent pulmonary hypertension (PPH) in infants with a congenital diaphragmatic hernia (CDH). We hypothesized that increased levels of prostanoids in bronchoalveolar lavage (BAL) fluid would predict clinical outcome. We measured the concentrations of 6-keto-prostaglandin F1α(6-keto-PGF1α), thromboxane B2(TxB2), protein, albumin, total cell count, and elastase-α1-proteinase-inhibitor complex in BAL fluid of 18 CDH patients and of 13 control subjects without PPH. We found different concentrations of prostanoids in BAL fluid of CDH patients with PPH: infants with a poor prognosis had either high levels of both 6-keto-PGF1αand TxB2compared to controls, or high levels of 6-keto-PGF1αonly. TxB2levels showed a large variability in all CDH patients irrespective of outcome. We conclude that prostanoid levels in BAL fluid do not predict clinical outcome in CDH patients.


2019 ◽  
Vol 9 (4) ◽  
pp. 204589401988195
Author(s):  
Ioanna Nikitopoulou ◽  
Nikolaos Manitsopoulos ◽  
Anastasia Kotanidou ◽  
Xia Tian ◽  
Aleksandar Petrovic ◽  
...  

Pulmonary fibrosis is a progressive disease characterized by disruption of lung architecture and deregulation of the pulmonary function. Prostacyclin, a metabolite of arachidonic acid, is a potential disease mediator since it exerts anti-inflammatory and anti-fibrotic actions. We investigated the effect of treprostinil, a prostacyclin analogue, in bleomycin-induced experimental pulmonary fibrosis. Bleomycin sulfate or saline was administrated intratracheally to mice ( n = 9–10/group) at day 0. Orotracheal aspiration of treprostinil or vehicle was administered daily and started 24 h prior to bleomycin challenge. Evaluation of lung pathology was performed in tissue samples and bronchoalveolar lavage fluid collected 7, 14 and 21 days after bleomycin exposure. Lung injury was achieved due to bleomycin exposure at all time points as indicated by impaired lung mechanics, pathologic lung architecture (from day 14), and cellular and protein accumulation in the alveolar space accompanied by a minor decrease in lung tissue VE-cadherin at day 14. Treprostinil preserved lung mechanics, and reduced lung inflammation, fibrosis, and vascular remodeling (day 21); reduced cellularity and protein content of bronchoalveolar lavage fluid were additionally observed with no significant effect on VE-cadherin expression. Bleomycin-induced collagen deposition was attenuated by treprostinil from day 14, while treprostinil involvement in regulating inflammatory processes appears mediated by NF-κB signaling. Overall, prophylactic administration of treprostinil, a stable prostacyclin analogue, maintained lung function, and prevented bleomycin-induced lung injury, and fibrosis, as well as vascular remodeling, a hallmark of pulmonary hypertension. This suggests potential therapeutic efficacy of treprostinil in pulmonary fibrosis and possibly in pulmonary hypertension related to chronic lung diseases.


2021 ◽  
pp. 51-60
Author(s):  
А.G. Babintseva ◽  
◽  
Yu.D. Godovanets ◽  
Yu.Yu. Khodzinska ◽  
N.O. Popeliuk ◽  
...  

Congenital diaphragmatic hernia (CDH) is a defect of diaphragm development which is characterized by herniation of the abdominal content into the chest resulting in pulmonary hypoplasia and pulmonary hypertension of various degrees. Mortality and sickness rates among survived children with this pathology remain high all over the world. Prenatal diagnostics of high quality will help to find neonates with severe CDH and promote mobilization of human and material resources for optimal management at the tertiary level of giving medical aid. Attention of specialists in prenatal ultrasound diagnostics should be drawn to the necessity of measuring observed/expected lung(to(head ratio and location of the liver in fetus. Optimal treatment of neonates during preoperative period is focused on mild ventilation, avoidance of oxygen toxicity, baro/volutrauma of a hypoplastic lung and cardiac support. Administration of pulmonary vasodilator therapy including inhaled nitric oxide and extracorporal membrane oxygenation is pathogenetically substantiated for patients with pulmonary hypertension, and surgical correction should be delayed till stabilization of patient's condition. Echocardiography is a critically important diagnostic method. It enables to determine severity of pulmonary hypertension and myocardial functional disorders, to find targeted systemic methods of treatment that improve hemodynamic function or decrease pulmonary vascular resistance. Considering an insufficient level of evidence of the existing international recommendations, large(scale multi(center randomized studies on investigation of the best methods to prevent, diagnose and treat neonates with CDH are essential. No conflict of interest was declared by the authors. Key words: congenital diaphragmatic hernia; neonate; lung-to-head ratio; pulmonary hypertension; extracorporal membrane oxygenation.


1991 ◽  
Vol 19 (4_part_1) ◽  
pp. 406-411 ◽  
Author(s):  
Hillel S. Koren ◽  
Robert B. Devlin ◽  
Susanne Becker ◽  
Raphael Perez ◽  
William F. Mcdonnell

Acute exposure of humans to 0.4 ppm ozone results in reversible respiratory function decrements, and cellular and biochemical changes leading to the production of substances which can mediate inflammation and acute lung injury. While pulmonary function decrements occur almost immediately after ozone exposure, it is not known how quickly the cellular and biochemical changes indicative of inflammation occur in humans. Changes in neutrophils and PGE2 have been observed in humans as early as 3 hr (28) and as late as 18 hr post exposure (19). The purpose of this study was to determine whether inflammatory changes occur relatively rapidly (within 1 hr) following exposure to ozone, or if the cascade of events which are initiated by ozone and lead to inflammation, take some time to develop. We exposed 10 healthy volunteers twice: once to filtered air and once to 0.4 ppm ozone. Each exposure lasted for 2 hr at an exercise level of 60 L/min, and bronchoalveolar lavage was performed 1 hr following exposure. The data from this study were compared to those from a previous study in which 10 subjects were exposed to O3 under identical conditions except that bronchoalveolar lavage was performed 18 hr following exposure. The results of the present study demonstrate that O3 is capable of inducing rapid cellular and biochemical changes in the lung. These changes were detectable as early as 1 hr following a 2 hr exposure of humans to ozone. The profiles of these changes were different at 1 hr and 18 hr following ozone exposures. Bronchoalveolar lavage fluid had levels of neutrophils, IL-6, and prostaglandin E2 that were higher at 1 hr than at 18 hr post exposure. On the other hand, the levels of fibronectin and plasminogen activator were found to be higher at 18 hr than at 1 hr after ozone exposure. A temporal association appeared to exist between changes occurring in the biochemical markers and alterations in lung function. Further studies may be useful in determining if a causal relationship exists between these parameters.


1997 ◽  
Vol 27 (4) ◽  
pp. 396-405 ◽  
Author(s):  
L. M. TERAN ◽  
M. G. CAMPOS ◽  
B. T. BEGISHVILLI ◽  
J.-M. SCHRODER ◽  
R. DJUKANOVIC ◽  
...  

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