Disease relevance of epoprostenol

• Recently, aerosolized iloprost, a stable prostacyclin analogue, has been introduced as an alternative therapy for severe pulmonary hypertension [1].
• Prostacyclin infusion in hypertension: acute hemodynamic and hormonal effects [2].
• We adjusted the rate of infusion into the dialyzer to prevent prostacyclin-induced hypotension [3].
• Prostacyclin infusion in patients with acute myocardial infarction (preliminary report) [4].
• We performed a randomized study of the effect of the long-term daily administration of 60 mg of aspirin (n = 17) or placebo (n = 16) on platelet thromboxane A2 and vascular prostacyclin in women at risk for pregnancy-induced hypertension [5].

Psychiatry related information on epoprostenol

• BACKGROUND & AIMS: Prostacyclin and nitric oxide have been involved in the hyperkinetic syndrome in portal hypertension [6].
• Four patients in the epoprostenol group and five in the conventional therapy group died (P value not significant) [7].
• Thus, part of the mechanism by which hyperlipidemia, diabetes mellitus, smoking, hypertension, sex hormones, age, heredity, emotional stress and diet contribute to the development and progression of atherosclerosis may be through an imbalance between thromboxane A2 and prostaglandin I2 [8].
• Ethanol acquires such a stimulatory effect on prostacyclin formation after chronic alcohol consumption [9].
• CONCLUSION: Physical activity may stimulate vasoactive prostacyclin and thromboxane excretion during pregnancy [10].

High impact information on epoprostenol

• Long-term treatment of primary pulmonary hypertension with aerosolized iloprost, a prostacyclin analogue [1].
• Seven of the eight patients who had minimal pulmonary vasodilation in response to adenosine (mean reduction in resistance units, <20 percent) still had a significant reduction in pulmonary vascular resistance when treated with epoprostenol (mean, 39+/-14 percent; P=0.002) [11].
• Reduction in pulmonary vascular resistance with long-term epoprostenol (prostacyclin) therapy in primary pulmonary hypertension [11].
• Epoprostenol therapy was initiated and the rate of infusion was increased by an average of 2.4 ng per kilogram of body weight per minute each month [11].
• Continuous intraarterial measurement of oxygenation during aerosolized prostacyclin administration in severe respiratory failure [12].

Chemical compound and disease context of epoprostenol

• We successfully used an infusion of prostacyclin, which has an in vitro half-life of three to five minutes, as the sole anticoagulant in 10 patients on long-term hemodialysis and in one patient undergoing dialysis for acute renal failure (this patient bled severely on three occasions when heparin was used) [3].
• A low-dose infusion of calcium or norepinephrine (known stimulants of prostacyclin) increased renal prostacyclin release in normal subjects and controls with renal insufficiency [13].
• Prostacyclin, a potent, naturally occurring prostaglandin exerts a variety of cardiovascular and cellular actions of potential value in acute myocardial ischemia [14].
• Some of the agents that are thought to be released during hypoxia, which may trigger this cascade, are adenosine (A2 activation), eicosanoids (PGE2, PGI2, and 6-keto PGE1), oxygen-free radicals (superoxide and H2O2), and catecholamines with beta-2 adrenergic receptor agonist properties [15].
• CONCLUSIONS: Our results show that reduced PGI2 production, but not increased TxA2 production, occurs many months before clinical onset of preeclampsia [16].

Biological context of epoprostenol

• These findings indicate that a low dose of aspirin (40 to 80 mg) can largely inhibit platelet aggregation and thromboxane synthesis but has much less effect on prostacyclin production in arterial and venous endothelium [17].
• The effects of vasodilation with prostacyclin on oxygen delivery and uptake in critically ill patients [18].
• To evaluate the functional importance of the altered prostacyclin production, we studied the responses of renal blood flow and blood pressure to the calcium infusion [13].
• Increased prostacyclin biosynthesis in patients with severe atherosclerosis and platelet activation [19].
• Hemodynamic variables, gas exchange, and ventilation-perfusion distributions were measured by means of multiple inert-gas-elimination techniques during nitric oxide inhalation; the results were compared with those obtained during intravenous infusion of prostacyclin [20].

Anatomical context of epoprostenol

• Thrombin also stimulates PGI2 production in endothelial cells [21].
• Prostacyclin production may be low in healthy persons because there is almost no stimulus for its production but enhanced in patients with severe atherosclerosis as a consequence of platelet interactions with endothelium or other vascular insults [19].
• Characterization of prostacyclin synthesis in cultured human arterial smooth muscle cells, venous endothelial cells and skin fibroblasts [22].
• Infusion of prostacyclin reduced pulmonary-artery pressure but increased intrapulmonary shunting and reduced the PaO2/FiO2 and systemic arterial pressure [20].
• Prostacyclin is a potent vasodilator and platelet inhibitor produced by vascular endothelium [19].

Associations of epoprostenol with other chemical compounds

• To address this hypothesis, we measured the plasma and urinary metabolites of thromboxane, presumably of platelet origin, and of prostacyclin, derived from endothelial cells, in addition to more conventional indexes of platelet function [23].
• Venous and arterial smooth muscle cells and skin fibroblasts synthesized PGI2 from exogenous arachidonic acid, but they did not synthesize a significant amount of PGI2 when treated with histamine [21].
• We then measured prostacyclin (PGI2) synthesis with a radioimmunoassay for its stable metabolite, 6-keto-prostaglandin F1 alpha [24].
• Hemodialysis using prostacyclin instead of heparin as the sole antithrombotic agent [3].
• Regulation of histamine-mediated prostacyclin synthesis in cultured human vascular endothelial cells [21].

Gene context of epoprostenol

• Endothelin-1 and the ETB receptor agonist, sarafotoxin-S6C, increased synthesis of PGI2 and PGE2, leading to elevation of cAMP [25].
• Platelet microparticles can also induce expression of COX-2 and prostacyclin (PGI2) production, but not expression of COX-1, in human endothelial cells [26].
• The clinical information is biologically plausible, as it is compatible with evidence that inhibition of COX-2-derived PGI2 removes a protective constraint on thrombogenesis, hypertension, and atherogenesis in vivo [27].
• The cyclooxygenase (COX) product, prostacyclin (PGI(2)), inhibits platelet activation and vascular smooth-muscle cell migration and proliferation [28].
• PGI2 and PCA were elicited by "22K factor" and by human recombinant IL 1 beta and alpha but not by murine recombinant IL 1 alpha [29].

Analytical, diagnostic and therapeutic context of epoprostenol

• Prostacyclin was infused intravenously for 10 minutes before dialysis and into the arterial line of the dialyzer during dialysis [3].
• Prostacyclin produced an increase in oxygen delivery (median value before vs. during infusion, 375 vs. 492 ml of oxygen per minute per square meter of body-surface area, P less than 0.001) that was similar in the 14 patients who survived and the 13 who died [18].
• The inhibitory effect of prostacyclin may limit the extent of platelet-fibrinogen interaction in vivo and in extracorporeal circulation [30].
• Epoprostenol now the focus of numerous clinical trials [31].
• To investigate whether or not PGI2 affects vascular capacity, we infused PGI2 intraarterially at both 10 and 25 micrograms/min into 15 dogs on total cardiopulmonary bypass [32].

References