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Query: UMLS:C0019270 (hernia)
 15,856 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Pulmonary hypertension is a major source of morbidity and mortality in infants born with congenital diaphragmatic hernia (CDH). Increased pulmonary vascular resistance leads to right-to-left shunting, which is evident as decreases in the PaO2 measured in postductal arterial blood. Thromboxane A2 (TXA2), a vasoconstrictor, and prostacyclin (prostaglandin I2, PGI2), a vasodilator, have been studied as possible mediators of pulmonary hypertension in certain conditions of the newborn, including congenital diaphragmatic hernia (CDH). The goal of our study was to determine the association of TXA2 and PGI2 levels with hypoxemia in infants born with CDH. Eleven newborn infants with severe respiratory insufficiency (birth weight 2.0-4.1 kg; gestational age 32-42 weeks) were studied 0-5 days after surgical repair of CDH. Umbilical artery samples were collected for arterial blood gas determinations and radioimmunoassay of thromboxane B2 (TXB2) and 6-keto prostaglandin F1 alpha (6-keto-PGF1 alpha), stable metabolites of TXA2 and PGI2, respectively. Postductal arterial hypoxemia (reflected by a low a-A ratio, the ratio of oxygen tension in arterial blood to that in the alveolus) was associated with increases in TXB2 (r = -0.71, P = 0.004) and 6-keto-PGF1 (r = -0.65, P = 0.017). The a-A ratio also correlated inversely with TXB2/6-keto-PGF1 alpha (r = -0.50, P = 0.01), suggesting an increased influence of the vasoconstrictor TXA2.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Relation between arterial hypoxemia and plasma eicosanoids in neonates with congenital diaphragmatic hernia. 149 96

We studied the vasoactive profile of a term infant with congenital diaphragmatic hernia and intractable pulmonary hypertension who was refractory to conventional medical management despite an early stable period. Plasma prostanoid vasoconstrictor thromboxane A2 (TxB2) levels were elevated prior to ECMO at 150pg/mL, rose to 310pg/mL with the first hour of bypass and remained elevated until 72 hours by which time they fell to less than 50pg/mL. This coincided with the decreased extracorporeal circulatory support needed to maintain systemic arterial pO2 between 70 to 90 torr. Pulmonary vasodilator prostacyclin (6-keto-PGF1 alpha) was minimally elevated prior to bypass a 50pg/mL and became undetectable. Catecholamine levels were markedly elevated prior to ECMO at 4,000pg/mL with no demonstrable pulmonary extraction of norepinephrine. Though catecholamine levels remained nonspecifically elevated, pulmonary metabolism of norepinephrine improved with bypass time to 48% at 96 hours and coincided with the overall improvement of the infant's respiratory function. These data suggest pulmonary hypertension associated with congenital diaphragmatic hernia is at least partially precipitated by alterations in prostanoid homeostasis as selective activation of thromboxane synthetase pathways rather than nonspecific activation of the entire archidonate cascade. While ECMO per se may have no lasting effect on prostanoid homeostasis, ECMO can allow a period of cardiopulmonary rest during which more physiologic prostanoid levels are established. Although activation of the sympatho-adrenal axis may contribute to pulmonary hypertension, the role of catecholamines in this infant is not clear. Return of the lungs ability to clear norepinephrine may be an additional marker of biologic lung recovery.
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PMID:Extracorporeal membrane oxygenation and congenital diaphragmatic hernia: modification of the pulmonary vasoactive profile. 384 61

After repair of a Bochdalek diaphragmatic hernia, shunting of blood away from the lungs produced progressive hypoxaemia in a neonate. Changes in plasma concentrations of the vasoconstrictor prostanoid thromboxane were associated with changes in pulmonary vascular resistance in this infant. Plasma concentrations of the vasodilator prostanoid prostacyclin were also monitored during acute changes in pulmonary vascular resistance. Tolazoline administration was followed by reductions in pulmonary vascular resistance and in plasma thromboxane and prostacyclin values. Further studies indicated that tolazoline inhibits platelet thromboxane synthesis and vascular prostacyclin synthesis. These data suggest that thromboxane plays a part in the increased pulmonary vascular resistance that occurs after repair of congenital diaphragmatic hernia and that tolazoline may reverse pulmonary hypertension by a mechanism additional to its known action as an alpha adrenergic blocking agent and its effect on histamine release.
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PMID:Congenital diaphragmatic hernia: association between pulmonary vascular resistance and plasma thromboxane concentrations. 654 58

In acute hypoxemic respiratory failure of term and near-term neonates, extra- and intrapulmonary right-to-left shunting contribute to refractory hypoxemia. Inhaled nitric oxide (NO) decreases pulmonary arterial pressure and improves ventilation-perfusion mismatch in a variety of animal models and selected human patients. We report on 10 consecutive term and near-term newborns with severe acute hypoxemic respiratory failure due to diaphragmatic hernia, meconium aspiration syndrome, group B streptococcus sepsis, pneumonia or acute respiratory distress syndrome, who received increasing doses of inhaled NO (up to 80 ppm) to improve the arterial partial pressure of oxygen (PaO2). The response to NO and the optimum NO concentration which improved PaO2 varied considerably between patients. Improvement of PaO2 was absent or poor (less than 10 mm Hg) in the 4 newborns with meconium aspiration syndrome and in 1 patient with congenital diaphragmatic hernia, while in the other 5 patients inhaled NO increased the mean (+/- SE) PaO2 from 41 +/- 6 to 57 +/- 9 mm Hg (P < 0.05). Optimum NO concentrations determined by dose-response measurements performed during the first 8 hr of NO inhalation were 8-16 ppm except for 2 newborns with congenital diaphragmatic hernia who required 32 ppm to effectively increase PaO2. Four of the 5 patients in whom the PaO2 rose by more than 10 mm Hg received inhaled NO for extended periods of time (5 to 23 days) with no signs of tachyphylaxis. The optimum NO concentration dropped to less than 3 ppm after prolonged mechanical ventilation or when intravenous prostacyclin was given concomitantly.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Dose-response to inhaled nitric oxide in acute hypoxemic respiratory failure of newborn infants: a preliminary report. 756 4

The addition of 10-20 parts per million nitric oxide to the inspired gas was successful in controlling near fatal pulmonary hypertension after surgical repair of a congenital diaphragmatic hernia in a neonate. A preceding prostacyclin infusion was unable to prevent the failure of pulmonary perfusion. No side effect of nitric oxide therapy was observed, and ventilatory support could be substantially reduced as a result of the treatment. On the basis of the striking and lifesaving effects of nitric oxide therapy demonstrated in this child, we believe that nitric oxide treatment will prove to be a major contribution to the management of postoperative pulmonary hypertensive crises.
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PMID:Near fatal pulmonary hypertension after surgical repair of congenital diaphragmatic hernia. Successful use of inhaled nitric oxide. 821 57

Survival of congenital diaphragmatic hernia patients depends on the gravity of pulmonary hypoplasia and persistent pulmonary hypertension (PPH). Many vasoactive drugs have been used in the treatment of PPH, but often they also lower peripheral resistance, leading to a significant drop in arterial blood pressure. The incidence of PPH in 52 high-risk diaphragmatic hernia patients and the results of treatment with tolazoline and prostacyclin were evaluated in a study lasting 52 months and involving 52 patients. High-risk patients require ventilatory support within 6 hours after birth. Study parameters were alveolar-arterial oxygenation difference (AaDO2), oxygenation index (OI), and mean arterial blood pressure (MABP), measured at set times before and after administration of tolazoline or prostacyclin. Twenty-one patients had documented episodes of PPH (46%), and 18 of them died. Tolazoline did not lower AaDO2 and OI values, but MABP dropped significantly. Prostacyclin caused a significant decrease of AaDO2 and OI values without an effect on MABP. We concluded: (1) PPH presented in 46% of our patients, associated with a high mortality rate; (2) tolazoline is not an effective dilator of the pulmonary vascular bed and lowers MABP; and (3) prostacyclin is an effective pulmonary vasodilator as reflected by ventilation parameters without systemic side effects; it does not affect overall outcome but can used as a "bridge" to extracorporeal membrane oxygenation.
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PMID:Persistent pulmonary hypertension in high-risk congenital diaphragmatic hernia patients: incidence and vasodilator therapy. 830 59

Persistent pulmonary hypertension of the newborn (PPHN) is a potentially life-threatening condition characterized by a failure of pulmonary vascular resistance to decrease adequately during the transition to extrauterine life. Inhaled nitric oxide, a vasodilator that acts selectively on the pulmonary circulation, has revolutionized the treatment of this condition. However, inhaled nitric oxide has not proven effective in all patients, particularly those with congenital diaphragmatic hernias or meconium aspiration syndrome. Furthermore, large clinical trials of inhaled nitric oxide have failed to demonstrate significant differences in mortality between nitric oxide-treated and control infants with PPHN. Other therapeutic approaches to PPHN have been limited by a relative lack of specificity for the pulmonary circulation, and have received much less attention. Pharmacologic approaches, including pulmonary surfactants, prostacyclin, endothelin antagonists, Ca(2+)-channel blockers, magnesium sulfate, and tolazoline, have exhibited varying degrees of efficacy in lowering pulmonary vascular pressures in humans and/or animals. A number of these agents are also effective when used in combination. For example, phosphodiesterase inhibitors have been reported to act synergistically with inhaled nitric oxide. Surfactants also appear to be useful in PPHN, particularly in patients with congenital diaphragmatic hernia, when used in combination with other therapies. Surfactant lavage and other novel therapies may also be effective in combination therapy of meconium aspiration syndrome. Further studies should be directed at defining the optimal therapies in specific clinical settings. Validation of multiple therapeutic modalities for PPHN, including inhaled nitric oxide, will allow for rational, combined vasodilator strategies that are specific for the underlying pathophysiology in each patient.
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PMID:Pharmacologic therapy of persistent pulmonary hypertension of the newborn. 1131 14

Persistent pulmonary hypertension (PPHN) and subsequent hypoxic respiratory failure is seen in association with numerous diseases and conditions in the neonate. This includes infections such as group B streptococcus, meconium aspiration syndrome, perinatal asphyxia, congenital diaphragmatic hernia, congenital heart disease, and as an idiopathic phenomenon. Conventional therapy of persistent pulmonary hypertension is discussed, as well as integrated with current treatment modalities such as surfactant replacement therapy and high frequency ventilation. The molecular action of nitric oxide including its relationship to neonatal cardiopulmonary transition at birth and the human neonatal clinical experience with term infants from 1992 to the present is explored. Also, the current use of inhaled nitric oxide in preterm infants is reviewed. Additionally, the follow-up of infants treated with inhaled nitric oxide is summarized, and novel therapies including inhaled prostacyclin and other pulmonary vasodilators such as sildenafil are introduced.
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PMID:Inhaled nitric oxide in the treatment of persistent pulmonary hypertension/ hypoxic respiratory failure in neonates: an update. 1585 81

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-PGF(1alpha)), thromboxane A(2) (TxB(2)), prostaglandin E(2) (PGE(2)), and leukotriene B(4) (LTB(4)) decreased after spontaneous birth. CDH pups showed respiratory insufficiency directly after birth. Their lungs had higher levels of 6- keto-PGF(1alpha), reflecting the pulmonary vasodilator prostacyclin (PGI(2)), than those of controls. We conclude that in CDH abnormal lung eicosanoid levels are present perinatally. The elevated levels of 6-keto-PGF(1alpha) in CDH may reflect a compensation mechanism for increased vascular resistance.
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PMID:Lung eicosanoids in perinatal rats with congenital diaphragmatic hernia. 1847 32

Persistent pulmonary hypertension of the newborn (PPHN) is a syndrome of failed circulatory adaptation at birth, seen in about 2/1000 live born infants. While it is mostly seen in term and near-term infants, it can be recognized in some premature infants with respiratory distress or bronchopulmonary dysplasia. Most commonly, PPHN is secondary to delayed or impaired relaxation of the pulmonary vasculature associated with diverse neonatal pulmonary pathologies, such as meconium aspiration syndrome, congenital diaphragmatic hernia, and respiratory distress syndrome. Gentle ventilation strategies, lung recruitment, inhaled nitric oxide, and surfactant therapy have improved outcome and reduced the need for extracorporeal membrane oxygenation (ECMO) in PPHN. Newer modalities of treatment discussed in this article include systemic and inhaled vasodilators like sildenafil, prostaglandin E1, prostacyclin, and endothelin antagonists. With prompt recognition/treatment and early referral to ECMO centers, the mortality rate for PPHN has significantly decreased. However, the risk of potential neurodevelopmental impairment warrants close follow-up after discharge for infants with PPHN.
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PMID:Update on PPHN: mechanisms and treatment. 2458 Jul 63


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