RESUMO
We used pregnant sheep and their fetuses as well as newborn lambs (with and without severe respiratory distress due to prematurity) to study the differences in plasma clearance rate, production rate, and circulating concentrations of immunoreactive PGE2. Fetal PGE2 concentrations were significantly higher than simultaneous maternal concentrations. After delivery by cesarean section, all newborn animals were paralyzed and mechanically ventilated. The PGE2 concentrations fell in those lambs that required only minimal ventilatory support (FIO2 < 0.25) and were similar to maternal concentrations by two to three hours. Newborn lambs that developed severe respiratory distress (FIO2 < 0.55) continued to have concentrations that were even greater than fetal concentrations. The elevated PGE2 concentrations in severely distressed lambs were due not only to a decreased plasma clearance rate but also to an increased production rate of PGE2. Since PGE2 appears to maintain the patency of the ductus arteriosus in the fetus and preterm neonate, we examined the patency of the ductus arteriosus in 3-hour-old newborn lambs by radioactive microsphere injections. The ductus was more widely patent in lambs with higher concentrations of PGE2. The increased circulating concentrations of PGE2 in newborn lambs with severe respiratory distress may contribute to the pathogenesis of patent ductus arteriosus by exerting an additional vasodilatory effect on the vessel.
Assuntos
Permeabilidade do Canal Arterial/sangue , Sangue Fetal/análise , Prostaglandinas E/análise , Animais , Animais Recém-Nascidos/sangue , Permeabilidade do Canal Arterial/complicações , Feminino , Humanos , Recém-Nascido , Gravidez , Diagnóstico Pré-Natal , Síndrome do Desconforto Respiratório do Recém-Nascido/sangue , Síndrome do Desconforto Respiratório do Recém-Nascido/complicações , OvinosRESUMO
Endogenous prostaglandins inhibit the ability of the ductus arteriosus to contract in response to oxygen. We studied the effects of endogenous prostaglandins and indomethacin (an inhibitor of endogenous prostaglandin production) on isometric contraction of isolated rings of lamb ductus arteriosus from animals of different gestational ages (98 to 103 days and 136 to 147 days; term is 150 days). Rings from animals at about 100 days' gestation have a significantly larger indomethacin-induced contraction than rings from animals near term. The lamb ductus arteriosus forms two prostaglandins that relax the vessel: postaglandin E2 and prostacyclin. PGI2 was three orders of magnitude less potent than PGE2. Rings from the younger animals were significantly more sensitive to the relaxing action of PGE2 and PGI2 than were rings from animals near term. This increased sensitivity of immature animals to endogenous prostaglandins is consistent with the more potent effect of indomethacin on rings from immature animals. These observations are also consistent with the findings that preterm infants have an increased incidence of patent ductus arteriosus and that indomethacin can constrict the ductus arteriosus in preterm infants.
Assuntos
Canal Arterial/efeitos dos fármacos , Indometacina/farmacologia , Animais , Epoprostenol/farmacologia , Idade Gestacional , Humanos , Recém-Nascido , Recém-Nascido Prematuro , Contração Muscular/efeitos dos fármacos , Músculo Liso Vascular/efeitos dos fármacos , Oxigênio/farmacologia , Prostaglandinas E/farmacologia , OvinosRESUMO
Chronic pulmonary arterial hypertension was produced in six fetal lambs. In four (126 to 139 days' gestation) unilateral fetal renal artery constriction caused systemic arterial mean blood pressure elevations. In another fetus, constriction of the umbilical artery caused a systemic mean blood pressure elevation; in the sixth, partial occlusion of the ductus arteriosus caused isolated pulmonary arterial hypertension. The right lung of each fetus was perfused with fixative at the in vivo mean arterial pressure and the amount of smooth muscle in the fifth generation (resistance) vessels analyzed using the medial width/external diameter ratio. There was a significant increase in the medial width/external diameter ratio in the six experimental animals as compared to that in six normal fetuses. In separate fetuses the increased ratios were due to a decreased external diameter, increased smooth muscle, or both these factors. The total number of resistance vessels was counted in the right lung of each fetus and no significant difference from normal was observed. We postulate that either fetal systemic hypertension or constriction of the ductus arteriosus causes fetal pulmonary hypertension in utero and that this produces increased smooth muscle development in pulmonary arterial resistance vessels; this may be a pathogenic mechanism for the syndrome of persistent pulmonary hypertension of the newborn infant.
Assuntos
Doenças Fetais/complicações , Hipertensão Pulmonar/etiologia , Hipertensão/complicações , Doenças do Recém-Nascido , Pulmão/irrigação sanguínea , Músculo Liso , Animais , Sangue , Dióxido de Carbono/sangue , Constrição Patológica , Feminino , Humanos , Concentração de Íons de Hidrogênio , Recém-Nascido , Modelos Biológicos , Oxigênio/sangue , Gravidez , Artéria Pulmonar/fisiopatologia , Obstrução da Artéria Renal/complicações , Ovinos , Artérias Umbilicais , Resistência VascularAssuntos
Permeabilidade do Canal Arterial/tratamento farmacológico , Indometacina/uso terapêutico , Doenças do Prematuro/tratamento farmacológico , Relação Dose-Resposta a Droga , Permeabilidade do Canal Arterial/cirurgia , Humanos , Indometacina/efeitos adversos , Recém-Nascido , Nefropatias/induzido quimicamente , Ligadura , Prostaglandinas E/antagonistas & inibidoresRESUMO
Persistent pulmonary hypertension of the newborn infant can be difficult to distinguish from other cardiopulmonary causes of cyanosis during the newborn period. Infants with PPHN have cyanosis, tachypnea, acidemia, normal pulmonary parenchymal markings on the chest radiography, and anatomically normal hearts. We have identified and treated 11 infants and have noted several signs and symptoms not previously emphasized. These are cineangiocardiographic evidence of atrioventricular valve insufficiency in association with systolic murmurs and slow ventricular emptying, apnea, hypocalcemia, only a small rise in abdominal aortic blood oxygen tension during breathing of 100% oxygen, and no response to continuous positive airway pressure. Right-to-left shunting through the patent ductus arteriosus was documented in nine infants: in all six of those in whom simultaneous temporal and abdominal aortic blood oxygen tension measurements were made; in three by means of cardiac catheterization. Ten infants survived after variable courses and treatments which makes it difficult to ascribe improvement to any one therapy. The distinct increase in blood oxygen tension with tolazoline HCl and curare in some instances is discussed.