thromboxane-a2 and Respiratory-Distress-Syndrome--Newborn

Prostacyclin (PGI(2)) and thromboxane A(2) (TxA(2)) may take part in lung pathology; high concentrations of PGI(2) may protect newborn rabbits against hyperoxic lung injury, and TxA(2) may participate in the development of bronchopulmonary dysplasia (BPD).. To examine in small preterm infants, the relationship between pulmonary PGI(2) and TxA(2) and respiratory distress during the early postnatal period.. The stable metabolite of prostacyclin, 6-keto-prostaglandinF(1 alpha), and that of thromboxane A(2), thromboxane B(2), were quantified by radioimmunoassays in 284 samples of tracheal aspirates from 48 infants (GA: 27.4+/-2.1 week, BW 959+/-334 g) during the first 12 postnatal days.. Mean concentration of 6-keto-prostaglandinF(1 alpha) was 414+/-31 pg/ml (mean+/-S.E.M.), and of thromboxane B(2) was 418+/-37 pg/ml. Correlations existed between 6-keto-prostaglandinF(1 alpha) and gestational age, birth weight, and the initial arterial-alveolar oxygenation ratio. Negative correlations existed between 6-keto-prostaglandinF(1 alpha) and both mean inspiratory oxygen and duration of mechanical ventilation. Indomethacin treatment was associated with lower pulmonary 6-keto-prostaglandinF(1 alpha), but not with lower TxB(2). Thromboxane B(2) correlated positively with gestational age, birth weight, and initial arterial-alveolar oxygenation ratio, and inversely with duration of mechanical ventilation.. In preterm infants, higher pulmonary 6-keto-prostaglandinF(1 alpha) was associated with less severe respiratory distress and with maturity, whereas thromboxane B(2) was associated more strongly with maturity than with respiratory distress.

Topics: 6-Ketoprostaglandin F1 alpha; Epoprostenol; Gestational Age; Humans; Infant, Newborn; Infant, Premature; Intubation, Intratracheal; Lung; Radioimmunoassay; Respiratory Distress Syndrome, Newborn; Thromboxane A2; Thromboxane B2; Trachea

Intravenous administration of some liposomal drugs can trigger immediate hypersensitivity reactions that include symptoms of cardiopulmonary distress. The mechanism underlying the cardiovascular changes has not been clarified.. Anesthetized pigs (n=18) were injected intravenously with 5-mg boluses of large multilamellar liposomes, and the ensuing hemodynamic, hematologic, and laboratory changes were recorded. The significant (P<0.01) alterations included 79+/-9% (mean+/-SEM) rise in pulmonary arterial pressure, 30+/-7% decline in cardiac output, 11+/-2% increase in heart rate, 236+/-54% increase in pulmonary vascular resistance, 71+/-27% increase in systemic vascular resistance, and up to a 100-fold increase in plasma thromboxane B2. These changes peaked between 1 and 5 minutes after injection, subsided within 10 to 20 minutes, were lipid dose-dependent (ED50=4. 5+/-1.4 mg), and were quantitatively reproducible in the same animal several times over 7 hours. The liposome-induced rises of pulmonary arterial pressure showed close quantitative and temporal correlation with elevations of plasma thromboxane B2 and were inhibited by an anti-C5a monoclonal antibody (GS1), by sCR1, or by indomethacin. Liposomes caused C5a production in pig serum in vitro through classic pathway activation and bound IgG and IgM natural antibodies. Zymosan- and hemoglobin-containing liposomes and empty liposomes caused essentially identical pulmonary changes.. The intense, nontachyphylactic, highly reproducible, complement-mediated pulmonary hypertensive effect of minute amounts of intravenous liposomes in pigs represents a unique, unexplored phenomenon in circulation physiology. The model provides highly sensitive detection and study of cardiopulmonary side effects of liposomal drugs and many other pharmaceutical products due to "complement activation-related pseudoallergy" (CARPA).

Topics: Animals; Complement Activation; Complement C5a; Complement System Proteins; Female; Hemodynamics; Hemoglobins; Humans; Hypersensitivity; Indomethacin; Infant, Newborn; Liposomes; Pulmonary Circulation; Receptors, Complement 3d; Respiratory Distress Syndrome, Newborn; Swine; Thromboxane A2

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.

Topics: 6-Ketoprostaglandin F1 alpha; Epinephrine; Extracorporeal Circulation; Hernia, Diaphragmatic; Hernias, Diaphragmatic, Congenital; Humans; Hypertension, Pulmonary; Infant, Newborn; Lung; Male; Norepinephrine; Oxygenators, Membrane; Pulmonary Circulation; Respiratory Distress Syndrome, Newborn; Thromboxane A2