Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0042373 (vascular disease)
 17,070 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A more widespread application of combined heart-lung transplantation (HLT) for the treatment of pulmonary vascular disease has been limited by the lack of a simple and inexpensive method for preserving donor organs for transplantation from distant hospitals. Of the 12 HLT patients treated at Papworth Hospital, the last 7 involved distant procurement of donor organs. For this, a single flush hypothermic system was used, with a Ringer's solution containing albumin, mannitol, prostacyclin, and heparin. This was preceded by a prostacyclin infusion into the donor's pulmonary artery. A retrospective comparison has been made of the post-operative pulmonary function between the HLT patients with distant procurement, those with near procurement of organs, and a group of patients who underwent coronary artery bypass graft (CABG) over the same time span. The mean ischemic time for distant-procurement patients was 110 (+/- 10) min, compared with 50 (+/- 0.5) min for near procurement. During the initial 18 hr postoperatively, the alveolar-arterial oxygen gradients (A-aDO2) for both groups of HLT patients and the CABG patients were closely comparable. Two near-procurement patients died: 1 from tracheal dehiscence, and 1 from cytomegalovirus (CMV). One distant-procurement patient died of CMV. All the others recovered fully and are alive and well at home. No patient developed a classical reimplantation response, and pulmonary function in the distant-procurement group compared closely with the CABG patients. These observations suggest that a simple single flush preservation system can effectively extend the pulmonary ischemic time so facilitating distant organ procurement.
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PMID:Distant procurement of organs for clinical heart-lung transplantation using a single flush technique. 312 Mar 79

Plasma factors influencing PGI2-like activity in 19 patients with diabetes mellitus /Dm/ and 17 controls were studied through a comparison with the signs of retinal and glomerular angiopathy. The plasma PGI2 supporting activity /PSA/ was lower in 15 Dm cases than in the controls. Inhibitory activity against PGI2 production was detected in 6 patients. In the cases of more serious retinopathy associated with glomerulopathy, a significantly lower level of PSA was observed than in patients with mild retinopathy without glomerular diseases. The plasma concentrations of total and LDL-cholesterol were significantly higher, while the level of HDL-cholesterol was lower than in the controls. There was a positive correlation between PSA and HDL-cholesterol values and a negative correlation between PSA and LDL-cholesterol levels, which relates to an inhibitory effect of LDL and a protective role of HDL in PGI2 synthesis.
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PMID:Plasma factors influencing prostacyclin-like activity in patients with diabetic microangiopathy. 328 94

We have investigated the effects of a low-dose aspirin regimen (120 mg orally, then 20 mg twice daily) on the in vivo synthesis of prostacyclin, thromboxane and prostaglandin E in man by measurement of their urinary metabolites (PGI2-M, TxB2-M, PGE-M) using gas chromatography-mass spectrometry. A comparison was made between the selectivity of low-dose aspirin for thromboxane vs prostacyclin synthesis in patients with atherosclerosis, age-matched controls without vascular disease, and young healthy volunteers. After one week of treatment, aspirin reduced TxB2-M synthesis to a similar extent in the three groups (mean declines of 86, 84 and 78% respectively), while there was an unexpected difference in effect on PGI2-M, with only a 27% fall in the young volunteers but 53% and 54% declines in the patients with vascular disease and their age-matched controls. Serum TxB2 was reduced greater than 98% in all groups while PGE-M excretion was unchanged. These results indicate that bioselectivity for inhibition of Tx synthesis by aspirin is more difficult to achieve in older subjects than in the young volunteers previously studied and that very low, frequent dosing, or a sustained-release preparation of aspirin would be needed to achieve bioselectivity for Tx inhibition in patients with vascular disease.
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PMID:Effects of low-dose aspirin on endogenous eicosanoid formation in normal and atherosclerotic men. 329 63

Eighteen patients with moderate to severe pulmonary hypertension were studied, nine with intracardiac shunts and nine without. The effects of an incremental infusion of epoprostenol (prostacyclin) (0.5-8 ng/kg per minute) or sublingual nifedipine (20-30 mg) were compared with the response to three months' treatment with oral nifedipine. Both epoprostenol and sublingual nifedipine caused a fall in pulmonary vascular resistance and pressure and a rise in cardiac output. Patients with intracardiac shunts had higher systemic blood flows than those without shunts. Exercise in the shunt group was accompanied by systemic desaturation and hyperventilation. Analysis of individual results showed that the size of the response was inversely related to the severity of the pulmonary vascular disease. A good long term response to nifedipine seemed to be as readily predicted by the resting control values for haemodynamic variables as by values after short term treatment. A favourable response was likely if the pretreatment mean pulmonary artery pressure was less than 50 mm Hg, the ratio of total pulmonary to systemic resistance was less than 0.7, or the ratio of mean pulmonary artery pressure to systemic artery pressure was less than 0.6. Short term vasodilator protocols may do harm. If such studies are carried out, an adequate dose range must be tried before the long term efficacy of an individual drug can be forecast.
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PMID:Prediction of favourable responses to long term vasodilator treatment of pulmonary hypertension by short term administration of epoprostenol (prostacyclin) or nifedipine. 329 41

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

Although low-dose soluble aspirin can be recommended as a useful anti-thrombotic drug regimen in patients with vascular disease, enteric-coated preparations have a theoretical advantage for aspirin preparations which are to be ingested daily for many years. We have demonstrated that a 50 mg enteric-coated aspirin formulation (Astrix) which has an absorption rate much lower than soluble aspirin, is sufficient to inhibit platelet thromboxane synthesis while causing no major decrease in vascular prostacyclin synthesis.
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PMID:Effect of 50 mg enteric-coated aspirin (Astrix) on thromboxane and prostacyclin synthesis. 332 48

Marine lipids containing omega-3 fatty acids (chiefly, eicosapentanoic acid [EPA] and docosahexanoic acid [DHA]) may inhibit the development of atherosclerotic vascular disease, but the mechanisms responsible for this putative beneficial effect are unknown. We investigated the effects of EPA and DHA in a canine model of accelerated vein graft arteriosclerosis during a 3-month period. Twenty-five dogs were divided into three dietary groups: group I (control), group II (2.5% cholesterol), and group III (2.5% cholesterol plus 2 gm EPA/day [as MaxEPA]). The effects of EPA on vein graft intimal thickening, platelet and vascular prostaglandin metabolism, lipid and lipoprotein receptor metabolism, and hematologic parameters were assessed. Cholesterol feeding caused a significant 54% increase in graft intimal thickness compared with control animals (124.9 +/- 50.4 vs 81.2 +/- 32.4 micron; p = 0.013), which was prevented by supplementation with EPA in group III (56.9 +/- 30.0 micron; p = 0.001 vs group II). Intimal thickness in group III was not significantly different from that of control. EPA supplementation was also associated with a 38% decline in serum thromboxane levels from 457.0 +/- 129.3 pg/0.1 ml in group II to 283.5 +/- 96.9 pg/0.1 ml in group III (p = 0.007). The alterations in lipoprotein metabolism associated with cholesterol feeding were not affected by EPA: in both groups II and III, serum cholesterol and high-density lipoproteins and liver cholesterol content were elevated and hepatic low-density lipoproteins (LDL) receptor content was reduced. There were no differences between the three groups in terms of vein graft or native vessel prostacyclin production, hematocrit, platelet count, or coagulation parameters. In this canine model, dietary supplementation with marine omega-3 fatty acids reduced the extent and magnitude of accelerated vein graft intimal thickening induced by hypercholesterolemia; moreover, this beneficial effect was associated with lower serum thromboxane production and appeared to be independent of alterations in lipoprotein metabolism or LDL receptor density.
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PMID:Inhibition of vein graft intimal thickening by eicosapentanoic acid: reduced thromboxane production without change in lipoprotein levels or low-density lipoprotein receptor density. 333 17

The fetal and maternal morbidity and mortality from the hypertensive disease states of pregnancy is a major problem. While much is known about the syndrome, the cause has been elusive. The ewe was chosen to test a hypothesis that depletion of magnesium may be involved. Twelve Finnish ewes were subjected to low magnesium diets with half given magnesium in the water. Tests included measurement of blood pressure in the waking state and by noninvasive technique. Magnesium levels were measured by atomic absorption spectrophotometry in the plasma and tissue of the ear tips. Findings included significant elevation of arterial blood pressure, reduction in fetal weight with pathologic confirmation of placental and renal lesions which were similar to those seen in the human condition. Significant lowering of both plasma and tissue of magnesium was noted. The hypothesis was supported and extended to include possible interaction with prostacyclin and thromboxane as intermediaries in a hypomagnesic coagulative angiopathy. This entity would also explain the association of migraine in the eclamptic and preeclamptic syndrome reported by previous authors. The success of parenteral magnesium in the treatment of these human conditions is therefore more than purely empiric.
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PMID:Pregnancy-induced hypertension and low birth weight in magnesium-deficient ewes. 352 57

The object of this study was to investigate clinical conditions in which increased production of prostacyclin (PGI2) has been reported. 6-Oxo-prostaglandin F1 alpha (6-oxo-PGF1 alpha) is the stable hydrolysis product of PGI2 and was measured in plasma from patients undergoing hepatic or cardiac surgery and in unoperated patients with vascular and hepatic disease, using gas chromatography/mass spectrometry. Blood obtained simultaneously from portal and peripheral veins, during emergency surgery for bleeding oesophageal varices in six patients with cirrhosis of the liver, contained very high concentrations of 6-oxo-PGF1 alpha (range 99-11,485 pg/ml of plasma). 6-Oxo-PGF1 alpha was higher in portal than in peripheral blood in five out of six patients. Six unoperated patients with cirrhosis and oesophageal varices which were not bleeding all had normal peripheral plasma concentrations of 6-oxo-PGF1 alpha less than 2 pg/ml (normal up to 5 pg/ml). Seventeen patients with severe vascular disease had normal basal plasma 6-oxo-PGF1 alpha concentrations (less than 2 pg/ml). Eighteen subjects with atheromatous coronary artery disease underwent aorta-coronary artery grafting, and plasma concentrations of 6-oxo-PGF1 alpha were markedly elevated during surgery (range 55-1207 pg/ml). We conclude that surgery stimulates PGI2 production substantially, and argue that the function of PGI2 may be to limit intravascular extension of thrombus from sites of haemostasis. Inappropriate PGI2 synthesis may contribute to the massive haemorrhage characteristic of oesophageal variceal bleeding.
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PMID:Prostacyclin in the circulation of patients with vascular disorders undergoing surgery. 353 59

To study prostaglandin (PG) metabolism in peripheral vascular beds, PGs and TxB2 released from perfused mesenteric tissues were measured in both normal and streptozotocin (STZ)-induced diabetic rats. The release of 6-keto-prostaglandin F1 alpha (6-keto-PGF1 alpha), thromboxane B2 (TxB2) and prostaglandin E2 (PGE2) was significantly increased in mesenteric vascular beds from diabetics in comparison with control rats. The 6-keto-PGF1 alpha/TxB2 ratio was decreased in diabetics. In order to clarify the mechanism of this imbalanced synthesis of eicosanoids, we infused buffer with 500 mg/dl glucose which was similar to the concentration of blood glucose in the diabetic rats. In response to this high glucose concentration, TxB2 released into the effluent from the mesenteric beds of normal animals was increased to the diabetic level. The release of the other PGs was not changed significantly. The 6-keto-PGF1 alpha/TxB2 ratio was decreased in control rats perfused with buffer containing 500 mg/dl glucose. We also investigated the effect of insulin (50 and 100 microU/ml) in the diabetic mesenteric vascular beds, but there were no changes in prostaglandin or TxB2 release. These data suggest that a high glucose level may have an important role in regulating TxA2 synthesis and in modulating the balance between PGI2 and TxA2 in diabetes. It is postulated that an increase in the micro-circulation of PGI2 may partially be protective against the progression of angiopathy.
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PMID:Increased release of prostaglandins from the mesenteric vascular bed of diabetic animals: the effects of glucose and insulin. 354 Sep 97


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