Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0018799 (heart disease)
 34,133 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

In vitro studies showed that PGF2a constricted the ductus arteriosus of newborn animals, whereas PGEs produced dilatation. The finding that constriction could also be produced by c-GMP and dilatation by c-AMP raised the possibility that the PGs might produce their effects by altering the relative proportions of cyclic nucleotides in the ductus wall. Results of experiments with inhibitors of PG synthesis and with drugs which are known to interfere with the degradation of c-GMP and c-AMP accorded with this hypothesis. Angiographic studies in neonatal piglets showed that PGEs and PGAs were potent dilators of the ductus. Prostaglandin action was confirmed in infants with congenital heart disease who were dependent on ductus patency for survival. In those patients, PGs proved to be an extremely useful tool. Experimental studies are in progress in the hope of finding a PGE analog, active by the oral route, which may be suitable for the long-term treatment of patients.
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PMID:Effect of prostaglandins and some methyl derivatives on the ductus arteriosus. 20 22

We have shown that E-type prostaglandins are potent relaxant of the lamb ductus arteriosus at low, but not high, oxygen tensions, and that their effect is possibly controlled by the rate of endogenous PG synthesis. These findings, together with the demonstration of the contractile effect of PG synthesis blockers on the hypoxic ductus in vitro and in vivo and of the relaxant effect of GSH in vitro, strongly suggest that E-type prostaglandins are responsible for maintaining ductus patency during fetal life. The endoperoxide intermediates may act in concert with PGEs. While our findings argue against the idea that PGF2alpha mediates the oxygen-induced constriction, they suggest that suppression of PGE activity in a high oxygen environment might be important to the initiation of ductus closure at birth. An extension of this concept is that continued patency of the ductus after birth results from either the excessive formation of PGEs or from the persistence of a "fetal-like" response of ductal muscle to endogenous or bloodborne PGEs, or both. The present scheme of PGE action is amenable to practical applications. Our work and that of Elliott et al. (15) prove that PGEs can be used to reopen a constricted ductus in children with cyanotic congenital heart disease, thus improving their change of survival during subsequent corrective surgery. Conversely, treatment with blockers of PG synthesis is envisaged as an alternative to surgery for closing a persistent ductus.
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PMID:Prostaglandins: a possible regulator of muscle tone in the ductus arteriosus. 99 35

Prostaglandin E ( 1 ) (PGE ( 1 ) ) is a naturally occurring paracrine hormone that is used pharmacologically for treatment of peripheral occlusive arterial disease and to maintain ductus-arteriosus patency in neonates with congenital heart disease until the primary condition is operable. PGE ( 1 ) treatment also has been associated with reduction in pulmonary arterial pressure and increase in cardiac output in patients with left ventricular failure. In contrast, in isolated cases, patients with heart failure reportedly have developed pulmonary edema while receiving PGE ( 1 ). Therefore, to better define the effect of PGE ( 1 ) in heart failure, this double-blind study investigated the effect of PGE ( 1 ) on extravascular lung water in intensive-care patients with severe heart failure (New York Heart Association [NYHA] classes III and IV) and slightly above-normal extravascular lung water. Intravenous infusion of 60 microg PGE ( 1 ) (Prostavasin; Schwarz Pharma, Monheim, Germany) over a period of 2 hours caused no significant change in lung water relative to the baseline values (9.8 +/- 4.3 mL/kg before the infusion, 9.3 +/- 3.2 mL/kg after 1 hour, and 9.4 +/- 3.5 mL/kg after 2 hours) or to values observed in placebo-treated patients (6.5 +/- 3.3 mL/kg before the infusion, 7.1 +/- 2.7 mL/kg after 1 hour, and 7.0 +/- 3.2 mL/kg after 2 hours). Thus, administration of PGE ( 1 ) is unlikely to cause or worsen pulmonary edema in patients with severe heart failure (NYHA classes III and IV).
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PMID:Effect of prostaglandin E1 on extravascular lung water in patients with severe heart failure. 1042 35

Patency of the ductus arteriosus (DA) is maintained during gestation by locally produced and circulating prostaglandins (PGE's). As gestation proceeds, the ductus becomes less sensitive to dilating prostaglandins and more sensitive to constricting factors such as PGE's synthetase inhibitors. This case report describes a fetus at term (38 weeks) with signs of severe right ventricular failure due to constriction of DA. Maternal history documented 5 day assumption of a non-steroid antiinflammatory agent to relieve skeletal-muscle pain. Careful echocardiogram ruled out a structural heart disease, such as coarctation of the aorta. A gradient of 41 mmHg across the ductus was recorded. A cesarean section delivery was immediately undertaken. The 3.5 kg newborn delivered appeared to be in good health, with Apgar score of 8/9 at 1 and 5'. There were no signs of congestive heart failure and mild respiratory distress. An echocardiogram showed a dilated, well contractile right ventricle, with a pressure of 50 mmHg. DA was already closed. The fetal echocardiogram was the most relevant investigation in the decision-making process of this case treatment. Any different evaluation of this fetal heart, delaying the delivery would have very seriously compromised the survival of the fetus. Fetal echocardiography is the most important diagnostic tool in the evaluation of the fetal heart; non steroid antiinflammatory drugs to mother at term should be avoided or given with close echocardiographic assessment of DA patency.
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PMID:[Timely detection of premature closure of the ductus arteriosus in a full-term fetus. Important role of fetal echocardiography]. 1043 30

Prostaglandins (PGs) have complex and multiple effects on bone metabolism. Although the osteogenic effect of PGE in humans was initially found in an infant with a congenital heart disease, there have been few reports on the effect of PGE in human in vivo. The aim of this study was to investigate the effect of PGE1 on human bone metabolism, using biochemical bone markers. A total of 18 subjects were treated with PGE1 in lipid microspheres. Six subjects were given 10 microg of lipo-PGE, intravenously daily for 14 days, and twelve subjects were given the same dose twice a week for 7 weeks. Before and after the administration of PGE1, blood and a spot urine was obtained in the morning. Bone formation markers (alkaline phosphatase, osteocalcin, procollagen I carboxy-terminal peptide) did not change. In the subjects with daily administration for 2 weeks, type I collagen pyridinolines crosslinked C-telopeptide (ICTP) increased significantly. In the subjects treated twice a week, free deoxypyridinoline (Dpd) increased significantly. When all subjects were analyzed, bone resorption markers (ICTP and Dpd) increased, but not significantly (p=0.055 for ICTP, p=0.055 for Dpd). Therefore, PGE1 at the dosage used in this study did not increase bone formation but increased bone resorption in humans.
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PMID:The effect of prostaglandin E1 on human bone metabolism: evaluation by biochemical markers for bone turnover. 1071 28

Cyclooxygenase-2 (COX-2)-catalyzed synthesis of prostaglandin E(2) (PGE(2)) plays a key role in inflammation and its associated diseases, such as cancer and vascular heart disease. Here we report that gamma-tocopherol (gammaT) reduced PGE(2) synthesis in both lipopolysaccharide (LPS)-stimulated RAW264.7 macrophages and IL-1beta-treated A549 human epithelial cells with an apparent IC(50) of 7.5 and 4 microM, respectively. The major metabolite of dietary gammaT, 2,7,8-trimethyl-2-(beta-carboxyethyl)-6-hydroxychroman (gamma-CEHC), also exhibited an inhibitory effect, with an IC(50) of approximately 30 microM in these cells. In contrast, alpha-tocopherol at 50 microM slightly reduced (25%) PGE(2) formation in macrophages, but had no effect in epithelial cells. The inhibitory effects of gammaT and gamma-CEHC stemmed from their inhibition of COX-2 activity, rather than affecting protein expression or substrate availability, and appeared to be independent of antioxidant activity. gamma-CEHC also inhibited PGE(2) synthesis when exposed for 1 h to COX-2-preinduced cells followed by the addition of arachidonic acid (AA), whereas under similar conditions, gammaT required an 8- to 24-h incubation period to cause the inhibition. The inhibitory potency of gammaT and gamma-CEHC was diminished by an increase in AA concentration, suggesting that they might compete with AA at the active site of COX-2. We also observed a moderate reduction of nitrite accumulation and suppression of inducible nitric oxide synthase expression by gammaT in lipopolysaccharide-treated macrophages. These findings indicate that gammaT and its major metabolite possess anti-inflammatory activity and that gammaT at physiological concentrations may be important in human disease prevention.
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PMID:gamma-tocopherol and its major metabolite, in contrast to alpha-tocopherol, inhibit cyclooxygenase activity in macrophages and epithelial cells. 1100 41

We conducted a retrospective study of neonatal leukocytosis induced by prostaglandin E(1). Among 45 neonates with congenital heart disease, leukocyte counts increased during PGE(1) infusion. We conclude that PGE(1) infusion is a predictable cause of leukocytosis in newborns with congenital heart disease.
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PMID:Leukocytosis caused by prostaglandin E1 in neonates. 1117 27

1. Prostaglandins play a major role in maintaining ductal patency in utero. Ductal tone is regulated by both locally released and circulating vasodilatory prostaglandins. In infants with ductus arteriosus-dependent congenital heart disease, ductal patency is maintained by intravenous administration of prostaglandin (PG) E(1). Little information is available regarding the expression of prostaglandin receptors in man. 2. By means of RT-PCR and immunohistochemistry we studied the expression of the PGI(2) receptor (IP), the four different PGE(2) receptors (EP1, EP2, EP3 and EP4), and the receptors for thromboxane (Tx) A(2) (TP), PGD(2) (DP) and PGF(2alpha) (FP) in the ductus arteriosus of three newborn infants with ductus arteriosus-dependent congenital heart disease and intravenous infusion of PGE(1) and of one 8 month old child with a patent ductus arteriosus. 3. The EP3, EP4, FP, IP and TP receptor were markedly expressed at the mRNA and protein level, whereas the EP2 receptor was weakly expressed and the EP1 receptor was detected in two out of four tissue specimens only. The DP receptor was not detected in any of the samples. The most pronounced expression, which was located in the media of the ductus arteriosus, was observed for the EP4 and TP receptors followed by IP and FP receptor protein. 4. These data indicate that ductal patency during the infusion of PGE(1) in infants with ductus arteriosus-dependent congenital heart disease might be mediated by the EP4 and IP receptor. The data further suggest that a heterogeneous population of prostanoid receptors may contribute to the regulation of ductus arteriosus tone in humans.
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PMID:Expression of prostanoid receptors in human ductus arteriosus. 1259 19

Interrupted aortic arch (IAA) is an uncommon congenital anomaly representing approximately 1% of congenital heart disease. More than 97% of the cases also have associated cardiac anomalies complicating their treatment. Because the median age at death in untreated cases is 10 days, this condition usually occurs as a complicated neonatal surgical emergency. There are three types of IAA: Type A is interrupted distal to the left subclavian artery. Type B, which is the most common form, is interrupted between the left common carotid and the left subclavian arteries. Type C, which is the most uncommon type, is interrupted between the innominate and left common carotid arteries. Since the first patient with this congenital anomaly was treated at our institution in 1965, 39 patients have undergone surgical treatment. Two of these (4.6%) had no associated intracardiac lesions, and both survived bypass grafting without complications. There were 12 Type A (30%), 26 Type B (67%) and one Type C (3%). A variety of individualized techniques were used to repair the defects. The three basic techniques were (1) direct aortic to aortic anastomosis bridging the gap, (2) "turndown" or "turnup" of one of the arch vessels to the aorta across the gap, or (3) bypass of the interruption with graft material. Because aortic arch and associated cardiac anomalies represent a neonatal surgical emergency, our therapeutic plan consists of treatment for biventricular failure and PGE(1) infusion to maintain ductal patency, and surgical correction as soon as feasible.
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PMID:Interrupted aortic arch: brief review and summary of an eighteen-year experience. 1522 58

Pivotal role in atherogenesis is played by macrophages, which are early site for lipid accumulation and mediate the inflammatory and immune response in the intima. Epidemiological evidence indicates that natural antioxidants reduce the risk of heart disease, but, so far, supplementation studies have failed to confirm any protective effects of these compounds against cardiovascular disease. This study evaluated the effects of the natural antioxidant alpha-tocotrienol and of the newly designed compound, FeAOX-6, which combines antioxidant structural features of both tocopherols and carotenoids into a single molecule, on macrophage functions involved in foam cell formation. FeAOX-6 or alpha-tocotrienol induce a strong dose-dependent reduction of cholesterol and reduce cholesterol accumulation in human macrophages. The extent of the reduction found with alpha-tocotrienol was greater than that induced by FeAOX-6 and did not correlate with their respective antioxidant capacities. Treatment of HMDM with alpha-tocotrienol or FeAOX-6 enhanced also tumor necrosis factor-alpha secretion. These results are consistent with a reduction in scavenger receptor activity, but we found that antioxidant treatment did not affect cholesterol uptake from modified LDL. The effects on release on pro-inflammatory prostanoid precursors, PGE(2) and cytokine suggest a variety of metabolic responses that are both dependent on antioxidant compounds and macrophages activation status.
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PMID:Effects of new combinative antioxidant FeAOX-6 and alpha-tocotrienol on macrophage atherogenesis-related functions. 1733 2


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