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)

Eight patients with severe bronchopulmonary dysplasia underwent cardiac catheterisation. Seven had a pulmonary vascular resistance greater than 3 mm Hg.l-1 min.m2 (mean 8.9, range 2.2-13.8). All had raised intrapulmonary shunts (mean 25.6%, range 5.4-50%, normal less than 5%). Two had a high alveolar dead space, and two had unsuspected congenital heart disease. Epoprostenol (prostacyclin), but not 100% oxygen, caused a significant fall in pulmonary vascular resistance. Death was associated with a high pulmonary vascular resistance and a high shunt. Morphometric studies in three cases showed normal numbers of airways, but increased thickness of bronchial muscle. The numbers of alveoli were reduced and the walls thickened. There was increased medial thickness in small pulmonary arteries with distal extension of muscle. In the oldest child some vessels were obliterated by fibrosis. We speculate that measurements of pulmonary vascular resistance and shunt may have prognostic value; that a trial of pulmonary vasodilators other than oxygen might be worthwhile in patients with poor prognosis; and that abnormalities of the pulmonary circulation contribute to the difficulties of managing patients with bronchopulmonary dysplasia.
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PMID:Changes in pulmonary circulation in severe bronchopulmonary dysplasia. 227 Sep 48

Hypoxic vasoconstriction has been the subject of many studies, but little is known about the interaction of hypercapnia and the pulmonary circulation. We performed two haemodynamic studies on each of three patients with pulmonary vascular disease secondary to congenital heart disease. On the first occasion ventilation was inadequate due to technical problems, and the patients were therefore hypercapnic (arterial pCO2 greater than 5.3 kPa). On the second occasion, they were normocapnic. Pulmonary vascular resistance was measured on each occasion while the patients were breathing 100% oxygen (alveolar hyperoxia) and while epoprostenol (prostacyclin) was infused at doses of 5-20 ng/kg/min. Pulmonary vascular resistance was elevated in the presence of hypercapnia and, despite oxygen and epoprostenol, could not be reduced to the levels observed in the normocapnic study. We conclude that hypercapnia causes significant vasoconstriction in infants; and that epoprostenol is a relatively ineffective pulmonary vasodilator in infants who are hypercapnic due to inadequate ventilation. Where possible, respiratory acidosis should be corrected before using oxygen or epoprostenol as a pulmonary vasodilator.
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PMID:Interactions between alveolar hypercapnia and epoprostenol on the pulmonary circulation: clinical and pharmacological implications. 213 21

Patients with diabetes mellitus have an increased susceptibility to heart disease. The exact mechanism for this phenomenon is unclear. Abnormalities in prostaglandin (PG) production have been suggested as a possible cause. In this connection, we examined the PG synthetic capacity of cardiac microsomes from spontaneously diabetic rats. Cardiac microsomes from diabetic and control rats produced varying amounts of 6-keto-PGF1 alpha (stable degradation product of PGI2), PGE2, PGD2, PGF2 alpha, and TXB2 (stable breakdown product of TXA2). In both instances the production of 6-keto-PGF1 alpha predominated, however, microsomes from diabetic rats showed markedly greater conversion of arachidonic acid to all the PG products, especially 6-keto-PGF1 alpha. When PGF2 alpha metabolism was detected between diabetic and control heart preparations. These results show an enhanced cyclooxygenase activity in diabetic rat hearts without any change in prostaglandin dehydrogenase activity. Such a change may promote some of the cardiac alterations seen in diabetic mellitus.
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PMID:Altered myocardial prostaglandin synthesis in spontaneously diabetic rats. 251 48

Cardiopulmonary bypass in children with congenital heart disease is associated with significant morbidity manifested by increased complement degradation products, heightened pulmonary vascular activity, and coagulopathy. In adults with cardiac disease, the prostaglandins (eicosanoids) have been shown to contribute to the pathophysiologic response to extracorporeal circulation. This study assessed the effect of cardiopulmonary bypass in infants and children on two potent eicosanoids: thromboxane, a vasoconstrictor and platelet aggregating agent, and prostacyclin, a vasodilator and platelet disaggregating agent. The biochemical profiles of thromboxane and prostacyclin were evaluated in temporal relationship to selected parameters of platelet loss and pulmonary vascular hemodynamics during and after cardiopulmonary bypass. Twenty-one children, aged 3 days to 9 years, with congenital heart defects who were undergoing repair with cardiopulmonary bypass were studied. Nine pediatric patients undergoing palliative heart operations with no cardiopulmonary bypass served as the control group. In the group having cardiopulmonary bypass, the thromboxane concentration significantly increased during bypass (195 +/- 10 to 910 +/- 240 pg/ml, +/- standard error of the mean, p less than 0.005), whereas the control group demonstrated no significant change in thromboxane concentration. The highest thromboxane values were seen in the youngest patients (p less than 0.002). There was no significant correlation between thromboxane changes with alterations in pulmonary vascular resistance, platelet loss, duration of cardiopulmonary bypass or aortic cross-clamping. Prostacyclin levels rose significantly in both the bypass group (100 +/- 20 to 570 +/- 80 pg/ml, p less than 0.01) and in the control group (109 +/- 44 to 589 +/- 222 pg/ml, p less than 0.01), which apparently is due to surgical manipulation of vascular endothelium. These data show that eicosanoid production is significantly altered in children during cardiopulmonary bypass. Although thromboxane, a potent vasoconstrictor, is produced in significant amounts during and after cardiopulmonary bypass, our data show that thromboxane does not directly mediate changes in pulmonary artery hypertension and is not quantitatively related to platelet loss during pediatric cardiovascular operations.
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PMID:Effects of cardiopulmonary bypass on eicosanoid metabolism during pediatric cardiovascular surgery. 328 61

We have shown that PGI2 is a powerful but not selective pulmonary vasodilator, and we believe that there is a role for PGI2 in pulmonary vascular disease secondary to congenital heart disease, but much work remains to be done, including comparisons of PGI2 with other vasodilators. The role of PGI2 in altering the cellular and chemical events producing pulmonary vascular disease secondary to congenital heart disease, and any role in long-term treatment, is largely unexplored.
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PMID:Modification of pulmonary hypertension secondary to congenital heart disease by prostacyclin therapy. 330 74

Dietary fats play a critical role in atherogenesis and thrombosis. Both the amount of fat consumed and its composition affect various events associated with coronary artery disease. Dietary unsaturated fatty acids appear to reduce the incidence of these events, in particular polyunsaturated fatty acids (PUFAs), which exert markedly different effects on risk factors related to heart disease. The omega-3 (n-3) PUFAs, at high levels of dietary intake, significantly reduce hyperlipidemia and the production of the prothrombotic substance thromboxane, and they enhance the production of the platelet-antiaggregatory substance prostacyclin. Data from clinical trials indicate a significant reduction of levels of very low density lipoprotein (VLDL). The n-3 PUFAs also depress hepatic fatty acid and triglyceride synthesis and VLDL secretion. The n-3 PUFAs of fish oils displace arachidonic acid from tissue phospholipids and concomitantly increase n-3 PUFA levels, which inhibit thromboxane synthesis. Most significantly, in human subjects the antiaggregatory prostacyclin PGI3 is also synthesized and the net effect is enhanced antiaggregatory/antiadhesive activity. In addition, the chemotactic platelet adhesion-promoting substance leukotriene B4 is suppressed. These composite effects reduce atherogenesis and thrombosis. Fish oil n-3 PUFAs may also reduce blood pressure and blood viscosity. Through the combined vasodilatory effects via prostacyclin (PGI2 and PGI3), fish oils may improve peripheral circulation and thereby facilitate VLDL removal. The n-3 PUFAs of fish oils, by altering membrane fluidity in a specific manner, alter the activities of membrane-bound enzymes and may change receptor activity, specificity and signal transduction. Overall, these data indicate a beneficial role for n-3 PUFAs as part of a dietary approach to minimizing coronary artery disease.
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PMID:Effects of polyunsaturated fatty acids on factors related to cardiovascular disease. 331 46

Maintaining patency of the ductus arteriosus pending surgical intervention can be critical to the survival of the neonate with ductal dependent congenital heart disease. Spontaneously delayed ductal closure has been observed clinically and experimentally in newborns with critical pulmonic stenosis. Infants with ductal dependent congenital heart lesions were therefore studied to ascertain whether there was an endogenous increase in dilator prostaglandins prolonging ductal patency. Six neonates with cyanotic lesions (group 1) and six with left ventricular obstructive lesions (group 2) were studied. Circulating PGE2 was not increased in either group. The levels of plasma 6 keto PGF1 alpha, a stable hydrolysis product of prostacyclin, were found to be elevated, but only in the cyanotic group (3143 +/- 1844 vs 404 +/- 250 pg/ml; p less than 0.05; normal less than 500 pg/ml). As expected, PaO2's were also different (36 +/- 15 vs 72 +/- 34 mmHg; p less than 0.05). It is speculated, therefore, that increased synthesis and/or release of prostacyclin, possibly mediated by the hypoxia of the cyanotic ductal dependent lesion, contributes to persistent patency of the ductus arteriosus.
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PMID:Endogenous dilator prostaglandins in congenital heart disease. 332 70

We have obtained dose-response curves for the effects of prostacyclin on the pulmonary and systemic circulations in 20 children (median age 3 years) with pulmonary hypertension complicating congenital heart disease. Results were obtained with the children breathing both air and 100% oxygen. Under both sets of conditions, remote respiratory mass spectrometry was used to measure oxygen consumption and hence cardiac output by the direct Fick principle. When the subjects breathed air, prostacyclin caused a dose-dependent fall in pulmonary vascular resistance (measured in mm Hg . liter-1 . min . m2) (11.12 to 8.07, standard error of difference [SED] = 0.5, p less than .01). The level of the pulmonary vascular resistance when the subjects breathed air during the infusion of 20 ng/kg/min prostacyclin was not significantly different from that found when they breathed 100% oxygen and did not receive the drug (8.67 vs 8.93, SED = 0.55, p = NS). When infused while the subjects breathed 100% oxygen, prostacyclin caused additional dose-dependent pulmonary vasodilation (pulmonary vascular resistance 8.93 to 7.23, SED = 0.3, p less than .01). Unlike 100% oxygen, prostacyclin was not selective, and caused tachycardia and systemic hypotension at the higher doses. These results suggest that in children with congenital heart disease 100% oxygen does not maximally vasodilate the pulmonary circulation, and further pulmonary vasodilatation can be obtained with a blood-borne agent.
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PMID:Does prostacyclin enhance the selective pulmonary vasodilator effect of oxygen in children with congenital heart disease? 351 81

The role of prostaglandins (PGs) in cardiac pathophysiology has been reviewed with special emphasis on clinically applied aspects. Several PGs are synthesized and released by the heart and coronary vessels. Their synthesis is altered by various factors such as physical manipulation of tissue, pharmacological treatments and pathological conditions such as myocardial over-reactivity and ischemia. The involvement of PGs in cardiac dysfunction remains controversial, although it has been proposed that various PGs such as PGI2 or PGB2 may play a role in disaggregating platelets, inhibiting thrombus progression and coronary vasodilatation. The balance between thromboxane A2 (TXA2), a proaggregatory agent released from platelets and PGI2 may have a role in the genesis and management of angina and myocardial infarction. The use of non-steroidal anti-inflammatory agents in these conditions remains controversial; their possible beneficial effects are believed to be due to inhibition of TXA2 synthesis whereas their failure to be effective may be a consequence of concomitant inhibition of PGI2 production. Modulation of endogenous PG synthesis and administration of exogenous PGs or their analogues appear to be two therapeutic approaches in the management of certain cardiac diseases. Accordingly, there is a great need for synthesizing stable and potent PG analogues as well as specific inhibitors of PG synthesis in addition to studying their pharmacology and therapeutics. In this review we have emphasized the involvement of PGs in the pathogenesis of some forms of cardiac disease and have highlighted some therapeutic implications of these substances for the treatment of heart disease.
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PMID:Prostaglandins and heart disease. 385 Jul 65

We have obtained dose-response curves for the effects of prostacyclin on the pulmonary and systemic circulations of 10 patients with pulmonary hypertension secondary to congenital heart disease. With the subjects breathing air, prostacyclin caused statistically significant, pulmonary and systemic vasodilation. When the patients breathed 100% oxygen, pulmonary blood flow rose and pulmonary vascular resistance fell with no significant change in pulmonary artery pressure. Prostacyclin had a small additional vasodilator effect, but this did not reach statistical significance. Prostacyclin may be of some use in the assessment of the reversibility of an elevated pulmonary vascular resistance when surgery for the underlying congenital heart defect is being contemplated.
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PMID:The use of oxygen and prostacyclin as pulmonary vasodilators in congenital heart disease. 390 74


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