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Query: UMLS:C0042373 (vascular disease)
 17,070 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Rapidly accumulating evidence suggests that a proportion of patients with acquired immunodeficiency syndrome (AIDS) develop hypertensive pulmonary vascular disease reminiscent of primary pulmonary hypertension. As an initial step to explore the link between AIDS and hypertensive pulmonary vascular disease, the present study determined whether pulmonary hypertension is present in a well-characterized murine model of retrovirus-induced immunodeficiency. In agreement with previous reports, mice infected with the LP-BM5 murine leukemia virus developed polyclonal B and T cell activation followed by progressive and severe B and T cell immunodeficiency. At 12 wk postinfection, when persistent immunodeficiency was established, mice were anesthetized, and right ventricular systolic pressure was determined in open-chest, mechanically ventilated animals. Mean right ventricular systolic pressure was 14.7 +/- 1.3 mm Hg in control animals and was increased significantly to 22.5 +/- 3.2 mm Hg in virus-infected mice. Right ventricular hypertrophy was also present in infected mice as evidenced by a 27% increase in the ratio of right to left ventricular weights; there were no group-dependent differences in the left ventricular to total-body weight ratio. Morphometric evaluation indicated that medial thickness in muscularized pulmonary arteries, expressed as a percentage of the external diameter, was 9.6 +/- 0.4% in control lungs and increased to 14.4 +/- 0.5% in lungs from infected animals. Qualitative histopathologic analysis suggested increased perivascular collagen deposition in lungs from infected animals relative to control animals. Unlike AIDS patients with pulmonary hypertension, infected mice did not exhibit plexiform lesions or intimal fibrosis of the pulmonary arteries.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Pulmonary hypertension in a murine model of the acquired immunodeficiency syndrome. 802 49

A histopathologic study was carried out on pulmonary vessels of lung tissues from 5 children with primary pulmonary hypertension (PPH), in whom diagnosis was made on the basis of cardiac catheterization. Histological sections of lung were obtained in 4 patients by open lung biopsy and in one patient by closed needle necropsy soon after death. In all cases the vascular diseases were classified as grade 6 of the Heath-Edwards. Morphologic studies of small pulmonary arteries revealed medial hypertrophy (41.0%), intimal cellular proliferation (2.5%), intimal fibroelastic proliferation (36.9%) and medial destructive changes (19.6%) such as dilatation lesions, plexiform lesions, arteritis, or fibrinoid necrosis. Index of pulmonary vascular disease (IPVD) was 1.6 to 3.4 (mean 2.5). The advancement of these pulmonary changes sufficiently explains the extremely poor prognosis of children with PPH.
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PMID:Histopathologic findings of lung vessels in five children with primary pulmonary hypertension. 803 24

In 1% of the patients with cor pulmonale the cause of the high pulmonary artery pressure remains unclear. The underlying severe and mostly progressive pulmonary vascular disease with unknown aetiology is defined as primary pulmonary hypertension (PPH) with three different pathomorphological subtypes, plexogenic pulmonary arteriopathy (PPA), thrombotic pulmonary arteriopathy (TPA) and pulmonary venoocclusive disease (PVOD). The endemic occurrence of PPH after the ingestion of anorexigenic drugs (aminorex fumarate) and toxic rapeseed oil lead to the hypothesis that PPH is a pulmonary vascular reaction to exogenous toxic agents on the base of a genetic disposition. The initial response could be an endothelial cell dysfunction leading to pathological proliferation of vascular smooth muscle cells, vasospasm and local disturbances of haemostasis. The derived therapeutic concepts with vasodilators (high dose calcium channel-blocking therapy, prostacyclin) and with anticoagulant drugs show some encouraging results. The lung and heart-lung transplantation have become real therapeutic options for the patients with PPH considering the mostly still very unfavourable prognosis of PPH.
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PMID:[Primary pulmonary hypertension]. 829 Dec 74

The normal functional state of the vasculature and the events leading to the development of significant arterial disease involve the interaction of important vasoactive substances, which play important modulating or initiating roles in the development of hypertension and arteriosclerosis. Three endothelins have now been identified, of which ET-1 is the best characterized. ET-1 is produced by epithelial, mesangial, neuronal and glial, and liver cells, and is the most potent vasoconstrictor yet found. Each endothelin is derived from a different gene on separate chromosomes, and each binds to at least 2 types of receptor. The plasma half-life of ET-1 is about 7 min, and this provides a rapid mechanism for adjusting vascular resistance or blood pressure. The actions of endothelin are mediated through several pathways of postreceptor signaling, including activation of the mitogen-activated protein kinase cascade, which give rise to its growth-stimulating properties. Secretion of ET-1 from cultured endothelial cells is stimulated by a wide range of substances, and is inhibited by some prostaglandins. Endothelin in turn stimulates secretion of nitric oxide, arginine vasopressin and atrial natriuretic peptide, and participates in the hormonal control of salt and water balance. Hypoxia and ischemia augment ET-1 secretion, as does insulin, and this could play a role in the accelerated vascular disease of diabetes. ET-1 also causes bronchoconstriction and has been implicated in the development of acute asthma, primary pulmonary hypertension and pulmonary fibrosis. Its role in hypertension is still debatable, though most of the manifestations of congestive heart failure can theoretically be explained by the actions of ET-1. Endothelin also has extensive renovascular and parenchymal effects in the kidney. It is hoped that a fuller understanding of the role of endothelins in normal or pathologic vasculature will lead to effective therapy based on antagonism or augmentation of specific functions.
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PMID:Endothelins as cardiovascular peptides. 873 84

Pulmonary vascular disease with or without associated congenital heart disease is the indication for lung transplantation in 30% of all children requiring this procedure. Although many of these children will have primary pulmonary hypertension, a substantial number are children whose pulmonary vascular disease is either associated with a congenital heart lesion or secondary to it. Heart-lung transplantation has been performed in these children in the past, but because of the scarcity of availability of donor heart-lung blocks, lung transplantation with repair of associated congenital cardiac lesions has of necessity been performed more frequently. As one might expect, the operative and postoperative management of these patients is a good deal more complex than pulmonary transplantation for primary lung diseases. The early mortality is correspondingly higher as well, although survival beyond that time is quite similar to that of lung transplantation for other diseases. Factors that increase the early mortality include previous thoracic procedures and the complexity of the underlying cardiac diagnosis. Although the overall experience with this complex group of patients is small, the results seem similar to the prior experience with heart-lung transplantation. Thus, we remain optimistic that this will continue to be a viable form of therapy for children with pulmonary vascular disease associated with congenital heart lesions. The quality of life of the surviving patients is excellent and limited only by those factors impacting upon lung transplantation in general, such as rejection, infection, and the development of bronchiolitis obliterans.
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PMID:Lung transplantation in children with pulmonary hypertension and congenital heart disease. 884 21

To present an overview of the surgical issues in lung transplantation, including the historical context and the rationale for choosing a particular procedure for a specific patient, we reviewed and summarized the current medical literature and our personal experience. Several surgical options are available, including single lung transplantation; double lung transplantation; heart-lung transplantation; bilateral, sequential single lung transplantation; and (recently) single lobe transplantation. Although single lung transplantation is preferred for maximal use of the available organs, bilateral lung transplantation is necessary for septic lung diseases and may be appropriate for pulmonary hypertension and bullous emphysema. Heart-lung transplantation is performed for Eisenmenger's syndrome and for primary pulmonary hypertension with severe right ventricular failure. General factors for consideration in assessment of compatibility of the donor and potential recipient include ABO blood group, height (the donor should be within +/- 20% of the recipient's height), and length of the lungs (determined on an anteroposterior chest roentgenogram). Graft preservation and minimal duration of ischemia are important. Complications associated with airway healing are related to ischemia of the donor bronchus. We have addressed the issue of donor bronchial ischemia by direct revascularization of the donor bronchial arteries with use of the recipient's internal thoracic artery. Currently, lung transplantation offers a realistic therapeutic option to patients with end-stage pulmonary parenchymal or vascular disease.
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PMID:Surgical issues in lung transplantation: options, donor selection, graft preservation, and airway healing. 900 92

Endothelins are ubiquitously produced 21-amino-acid peptides that were discovered as an endothelial product and may play important roles in cardiovescular physiology and pathophysiology. The main endothelin produced by the endothelium is endothelin-1. The vasoconstrictor role of endothelins may participate in blood pressure elevation and vascular hypertrophy in salt-dependent models of hypertension (deoxycorticosterone acetate-salt hypertensive rats, spontaneously hypertensive rats treated with deoxycorticosterone, acetate and salt, and Dehl salt-sensitive rats), and in stroke-prone spontaneously hypertensive rats. In humans, endothelins may play important roles in moderate to severe essential hypertension, and in the hypertension of African-Americans. Endothelins may be involved in cardiac hypertrophy, and there is increasing evidence of their participation in heart failure, in which acute endothelin antagonism in humans exerts beneficial effects. Endothelin expression is enhanced in smooth muscle cells migrating into the intima of arteries in atherosclerosis, suggesting a role in atherogenesis. Endothelin may participate as a vasoconstrictor in coronary artery disease, and as a contributor to intimal proliferation in restenosis after coronary angioplasty. In patients with myocardial infarction, cardiac production of endothelin is increased, particularly in those with cardiogenic shock. There is a potential for participation of endothelins in vasospasm accompanying stroke or subarachnoid hemorrhage: in the latter, endothelin antagonism has shown beneficial effects in experimental models. In neonatal and in primary pulmonary hypertension, endothelin expression is enhanced, and in experimental models endothelin antagonism resulted in favorable responses. Systemic sclerosis is another, peripheral, form of vascular disease in which endothelin may play a role and in which endothelin antagonism may be an interesting therapeutic alternative. The pathophysiologic role of endothelins is becoming increasingly apparent in cardiovascular disease, generating interesting potential therapeutic targets for the use of endothelin antagonists or endothelin-converting enzyme inhibitors.
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PMID:Clinical significance of endothelin in cardiovascular disease. 926 47

In this article, we describe pulmonary hypertension in two men (31 and 43 years of age) with human immunodeficiency virus (HIV) infection who were examined at Mayo Clinic Rochester. Among 88 reported cases (including the two current ones) of HIV- or acquired immunodeficiency syndrome (AIDS)-associated pulmonary hypertension, 61% were male; the age range was 2 to 56 years (mean, 32). Dyspnea was the usual initial symptom. Of the 74 patients in whom pulmonary artery pressure was recorded or calculated by echocardiography, systolic pressures ranged from 49 to 118 mm Hg (mean, 68). Of the 33 cases in which lung tissue was evaluated microscopically, 28 (85%) were of the plexogenic variant of pulmonary arterial hypertension. Of the other five cases examined histologically, three consisted of thrombotic pulmonary arteriopathy (one was due to recurrent thromboembolism, and the other two were due to in situ thrombosis), and two were of pulmonary venoocclusive disease. No correlation existed between either CD4 counts or a history of pulmonary infections and the development of pulmonary hypertension. In 15 of the 88 patients (17%), confounding factors for hypertensive pulmonary vascular disease were present, including coexisting liver disease in 13 and coagulation abnormalities in 2. In 83% of the patients, the development of pulmonary hypertension seems to have been related primarily to the chronic HIV infection. Pulmonary hypertension was more rapidly progressive in patients with HIV or AIDS than in those with primary pulmonary hypertension; the reported time intervals between onset of symptoms and diagnosis were 6 months and 30 months, respectively. The 1-year survival rate for patients with HIV and pulmonary hypertension was 51%, based on the follow-up data compiled from the 63 patients in whom it was described; this compares with a 1-year survival rate of 68% for patients with primary pulmonary hypertension. Death was considered a direct consequence of pulmonary hypertension in 29 (76%) of the 38 fatal cases.
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PMID:Human immunodeficiency virus infection and pulmonary hypertension: two new cases and a review of 86 reported cases. 944 76

The etiology and pathogenesis of the vascular lesions characterizing primary pulmonary hypertension (PPH), an often fatal pulmonary vascular disease, are largely unknown. Plexiform lesions composed of proliferating endothelial cells occur in between 20 and 80% of the cases of this irreversible pulmonary vascular disease. Recently, technology to assess monoclonality has allowed the distinction between cellular proliferation present in neoplasms from that in reactive nonneoplastic tissue. To determine whether the endothelial cell proliferation in plexiform lesions in PPH is monoclonal or polyclonal, we assessed the methylation pattern of the human androgen receptor gene by PCR (HUMARA) in proliferated endothelial cells in plexiform lesions from female PPH patients (n = 4) compared with secondary pulmonary hypertension (PH) patients (n = 4). In PPH, 17 of 22 lesions (77%) were monoclonal. However, in secondary PH, all 19 lesions examined were polyclonal. Smooth muscle cell hyperplasia in pulmonary vessels (n = 11) in PPH and secondary PH was polyclonal in all but one of the examined vessels. The monoclonal expansion of endothelial cells provides the first marker that allows the distinction between primary and secondary PH. Our data of a frequent monoclonal endothelial cell proliferation in PPH suggests that a somatic genetic alteration similar to that present in neoplastic processes may be responsible for the pathogenesis of PPH.
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PMID:Monoclonal endothelial cell proliferation is present in primary but not secondary pulmonary hypertension. 948 60

Abnormal biosynthesis of thromboxane and prostacyclin has been implicated in patients with primary pulmonary hypertension and secondary pulmonary hypertension associated with congenital heart disease, and could be involved in the pathogenesis of pulmonary vascular disease. The chronic effects of an oral prostacyclin analogue, beraprost sodium, on thromboxane and prostacyclin biosynthesis and on pulmonary circulation were investigated in 15 children with pulmonary hypertension. The plasma concentrations of thromboxane B2 and 6-keto-prostaglandin F1 alpha were measured, as was the urinary excretion of 11-dehydro-thromboxane B2 and 2,3-dinor-6-keto-prostaglandin F1 alpha, which are stable metabolites of thromboxane A2 and prostacyclin, respectively. In patients with pulmonary hypertension, the plasma concentration of thromboxane B2 and the ratio of thromboxane B2 to 6-keto-prostaglandin F1 alpha were greater than in healthy controls: 210 +/- 49 versus 28 +/- 4 pg/mL (P < 0.05) and 32.6 +/- 8.9 versus 5.7 +/- 1.8 (P < 0.01), respectively. After 3 months of administration of beraprost, the plasma concentration of thromboxane B2 and the ratio of thromboxane B2 to 6-keto-prostaglandin F1 alpha were reduced significantly: 210 +/- 49 to 98 +/- 26 pg/mL (P < 0.01) and 32.6 +/- 8.9 to 18.0 +/- 6.7 (P < 0.05), respectively. In contrast, the plasma concentrations of 6-keto-prostaglandin F1 alpha in patients were slightly but not significantly higher than in controls, and did not change significantly after administration of beraprost. The concentrations of 11-dehydro-thromboxane B2 and 2,3-dinor-6-keto-prostaglandin F1 alpha in urine correlated significantly with thromboxane B2 and 6-keto-prostaglandin F1 alpha, respectively, in plasma. Beraprost improved the imbalance of thromboxane and prostacyclin biosynthesis and has a potential efficacy for preventing the progressive development of pathological changes in pulmonary vasculature.
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PMID:Chronic effects of oral prostacyclin analogue on thromboxane A2 and prostacyclin metabolites in pulmonary hypertension. 958 94


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