Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0016382 (flushing)
 6,387 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Although patients with COPD often have elevated pulmonary artery pressures (PAP) and pulmonary vascular resistance (PVR), it is uncertain whether treatment of this pulmonary hypertension is beneficial. We evaluated the extent of pulmonary hypertension in 16 patients with severe COPD complicated by acute respiratory failure and pulmonary hypertension. We assessed the hypothesis that the vasodilator prostacyclin (PGI2) would reduce PVR and improve systemic O2 transport. Patients with a COPD exacerbation requiring mechanical ventilation, and mean PAP greater than 30 mm Hg, were randomized to receive PGI2 or placebo, in addition to conventional therapy. Randomization to PGI2 or placebo therapy occurred 1 to 12 h after intubation, while the patient was mechanically ventilated. An optimal PGI2 dose (2 to 12 ng/kg/min, IV) was established in an initial dose-ranging study and then this dose was infused continuously for 48 h. PGI2 initially reduced PVR, but this effect dissipated within 24 h, indicating the development of tachyphylaxis. Tolerance to the adverse effects of PGI2 (tachycardia, hypotension, flushing, and headache) also developed over time. PGI2 treatment was associated with a significant fall in PaO2 but no increase in systemic oxygen transport. PGI2 proved to be a nonselective vasodilator that caused mild hypoxemia. Despite acute respiratory failure, pulmonary hypertension is mild in patients with severe COPD receiving mechanical ventilation and IV PGI2 is not beneficial in such patients.
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PMID:A placebo-controlled trial of prostacyclin in acute respiratory failure in COPD. 861 59

Prostacyclin (PGI2) is a bioactive substance produced by vascular endothelial cells, which exerts powerful vasodilative and anti-platelet actions. Patients with pulmonary hypertension have an imbalance between vasodilative PGI2 and vasoconstrictive thromboxane B2 (TXB2). Treatment with vasodilative agents is essential for such patients. Continuous intravenous infusion of PGI2 is an effective treatment of primary pulmonary hypertension in terms of exercise capacity and survival rate. We tested a new stable PGI2 analogue, beraprost sodium (Procyclin, Dornar) suitable for oral administration, in patients with primary and secondary pulmonary hypertension. A short-term study of cardiac catheterization in four patients with primary pulmonary hypertension showed a 15 +/- 12% reduction in mean pulmonary artery pressure in three of the four patients, and a 24 +/- 22% decrease in pulmonary vascular resistance in all four patients. Cardiac index increased by 27 +/- 14% in three of the four patients. Among three patients with secondary pulmonary hypertension, there was a 7% reduction in pulmonary artery pressure in one patient, and a 24 +/- 14% decrease in pulmonary vascular resistance in all three patients. In a long-term study (23 +/- 11 months), NYHA functional class improved from 3.0 +/- 0.7 to 2.4 +/- 0.5 in two of the five patients with primary pulmonary hypertension. Although the radiographic cardiothoracic ratio was not significantly improved, cardiac index increased by 78 +/- 60% in four of the five patients. Only two patients, one with primary and one with secondary pulmonary hypertension, died during the long-term follow-up period. Plasma TXB2/6-keto prostaglandin F1 alpha ratio decreased from 8.1 +/- 8.7 to 1.5 +/- 0.4. The optimal dose remains uncertain, but the initial dosage of 40-60 micrograms/day given in three to four doses for adult patients is considered to be acceptable. Side effects such as flushing face, headache, vomiting, and nausea were mild and resolved when the dose was reduced. Oral PGI2, beraprost, appears to be an effective and possibly adequate substitute for intravenous vasodilators in pulmonary hypertension for both short- and long-term management.
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PMID:[Short- and long-term effects of the new oral prostacyclin analogue, beraprost sodium, in patients with severe pulmonary hypertension]. 864 6

Reperfusion is a critical phase of organ preservation. The purpose of this study was to develop a solution specifically for postischemic kidney reperfusion. Unilateral left normothermic kidney ischemia was induced for 60 minutes in two groups of micropigs. In group 1 (control pigs, n = 6) the kidney was reperfused immediately with pure blood at systemic pressure by unclamping the renal artery. In group 2 (test animals, n = 6) the kidney was initially reperfused with an intracellular flush solution enriched with solution BT01 composed of cytoprotectors (natriuretic factor, PGI2), free radical chelating agents (allopurinol, mannitol), and substrates for the mitochondrial respiratory chain (aspartate, glutamate). This solution was mixed immediately before use with blood in a ration of 1:4 parts and injected into the left renal artery with a perfuser at a constant pressure of 60 mm Hg. After 20 minutes, the kidney was reperfused with systemic blood for 100 minutes. Glomerular filtration rate (GFR) was determined by measuring inulin clearance. Kidney blood flow was measured throughout the experiment. After 120 minutes of reperfusion, the kidneys were removed for histologic examination. In the control pigs (group 1) 50% of the animals were anuric. The ratio between GFR measured in the left kidney at the end of perfusion and at equilibrium in the remaining animals was 0.16 +/- 0.01. In test animals (group 2) all animals recovered diuresis. The ratio between GFR measured in the left kidney at the end of perfusion and equilibrium was 0.51 +/- 0.12 (p < 0.001, group 2 vs. group 1). In group 2 postperfusion kidney blood flow was higher than in group 1 (63.0 ml/min vs. 27.4 ml/min; p < 0.05) because of a decrease in renal vascular resistance. Light microscopic examination of kidneys form animals in group 1 revealed tubular necrosis that extended to the parenchyma, with exposure of tubular interstitium. In group 2 only degenerative lesions with edema of tubular cells and disappearance of brush borders were observed. Our findings indicate that flushing the kidneys with BT01 solution mixed with blood improves postischemic kidney function by reducing reperfusion damage.
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PMID:Improvement of postischemic kidney function by reperfusion with a specifically developed solution (BT01). 868 15

Twelve patients with systemic sclerosis were treated with intravenous infusions of the prostacyclin-stable analogue iloprost 0.5-2.0 ng/kg/min for 6 h from 8 to 13 days. Imminent gangrene was stopped in 2 patients and followed by healing. In 4 of 6 patients iloprost led to complete healing of ischaemic ulcers and in the remaining 2 patients to partial healing. One patient with severe Raynaud's phenomenon discontinued the study after 3 days due to severe headache. The 2 remaining patients with Raynaud's phenomenon as an indication improved, while no improvement was recorded in a patient with vasculitis of the lower leg. Side-effects such as headache, nausea and flushing were the reason that only 5 patients reached the maximum infusion rate. No statistical differences were recorded in digital bloodflow before and after the study or in plasma endothelin in the 9 patients investigated. Three of the 6 patients with healing ulcers, however, showed a pronounced decrease in plasma endothelin. Iloprost appears useful as a treatment of imminent gangrene and ischaemic ulcers in systemic sclerosis. This reparatory capacity could also be of a more general importance in therapy of this disease.
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PMID:Treatment of ischaemic digital ulcers and prevention of gangrene with intravenous iloprost in systemic sclerosis. 880 Mar 8

The antiaggregation and hemodynamic effects of the new prostacyclin analogue beraprost sodium were investigated in a randomized, placebo-controlled, double-blind clinical trial of Latin-square design. Twelve healthy Caucasian males randomly received 8-day oral treatments of 20, 40, and 60 micrograms of beraprost sodium and a placebo. One-week washout periods followed each treatment. Pharmacokinetic and pharmacodynamic measurements were performed on days 1 and 8 for each period of treatment. All three doses of beraprost sodium significantly inhibited platelet aggregation on day 8 (compared with placebo) during the 1st h after drug intake. Incubation of the 60-micrograms beraprost sodium samples with ADP (2, 5, and 10 microM) and collagen (1.25 micrograms/mL) decreased platelet aggregation by 10, 19, 16, and 6 +/- 4% (mean +/- SE), respectively, compared with placebo. No significant hemodynamic effects on blood pressure, heart rate, and digital pulse were observed. The 60-micrograms dose of beraprost sodium did significantly decrease the IRZ index (which may reflect the left ventricular pre-ejection period) on days 1 and 8. Some subjects experienced headache and facial flushing, effects that were dose dependent and reversible. Beraprost sodium at 20- to 60-micrograms doses exerts platelet antiaggregation (day 8 of therapy) and slight hemodynamic (days 1 and 8 of treatment) effects in Caucasian males. Beraprost sodium hemodynamic effects and potential benefits in patients with cardiovascular disease should be explored further.
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PMID:Platelet-aggregation inhibition and hemodynamic effects of beraprost sodium, a new oral prostacyclin derivative: a study in healthy male subjects. 896 Mar 77

Mesenteric traction syndrome (MTS) consists of decreased systemic vascular resistance, increased cardiac output, facial flushing and palmar erythema. Local production of PGI2 is thought to be the cause. We experienced a rare case of MTS that occurred during coronary artery bypass graft surgery (CABG). A 64-year-old man was scheduled for CABG for the treatment of angina pectoris. Hemodynamic variables were stable until 50 minutes after surgical incision. Blood pressure fell down suddenly from 110/50 to 70/40 mmHg, accompanied by obvious facial flushing and palmar erythema, when the surgeons were preparing the right gastroepiploic artery. Hemodynamic changes and cutaneous hyperemia returned to the baseline level in about 40 minutes. After this episode, the operation was performed uneventfully. The time sequence between the onset of the surgical procedure and the hemodynamic and cutaneous findings strongly suggest the release of PGI2 and MTS. In patients undergoing CABG with the gastroepiploic artery graft, pretreatment with NSAID might avoid sudden circulatory changes of MTS.
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PMID:[Mesenteric traction syndrome during coronary artery bypass graft surgery]. 907 Nov 11

Recently much interests have focused on the imbalance between the release of thromboxane A2 (TXA2) and prostaglandin I2 (PGI2), which may contribute to the development of pulmonary vascular injury. TXB2 has potents of platelet aggregation and vasoconstriction, while PGI2 has against in its activities. We investigated the effect of new PGI2 analogue (ONO-1301), which is a novel prostacyclin mimetic with inhibitory activity against thromboxane synthetase, on the early graft function in canine left single lung allotransplantation model. 19 donor dogs were divided into three groups. Seven dogs were comprised control group and received heparin administration (400 Unit/kg) before pulmonary arterial flushing with 50 ml/kg of 4 degrees C low potassium dextran glucose (LPDG) solution. Each six dogs were comprised I2-10 and I2-50 groups respectively, with receiving a 10-minute infusion of ONO-1301 (10 micrograms/kg/min) before flushing. The pulmonary cold preservation was performed with LPDG solution at 4 degrees C for 18 hours. After left single lung transplantation, in control group, saline solution was administered to the recipient for 10 minutes encompassing the reperfusion process (starting from 5 minutes prior to reperfusion). In I2-10 group, the ONO-1301 (10 micrograms/kg/min) was administered in the same manner. In I2-50 group, the ONO-1301 was administered from the same timing as I2-10 group, but for 50 minutes. The recipient dogs were observed for 6 hours after ligation of the right pulmonary artery and bronchus. We measured the transplanted lung function, including arterial blood gas and pulmonary hemodynamics, and plasma 6-keto-PGF1 alpha, TXB2 and lipid peroxide levels of left atrial blood. Pulmonary histological investigation was performed after preservation and sacrifice the recipient dog. All recipient dogs were survived for observation period. I2 groups provided significantly better gas exchange and pulmonary hemodynamics than control group. The 6-keto-PGF alpha levels in control group peaked after an early rise in TXB2 levels, and reached maximum at one hour after contra-lateral ligations. These prostanoid release levels rose again at 6 hours. While in I2 groups, the levels of them were significantly lower compared with control group. Histological examination of the transplanted lung after assessment, revealed disruption of alveoli forced by pulmonary edema in control group. In contrast, there was minimal fluid extravasation without alveolar disruption in both I2-10 and I2-50 groups. There were no significant differences between I2-10 and I2-50 groups. Although it dose not protect the implanted lung completely from developing edema, the ONO-1301 administration (10 micrograms/kg/min) to the donor and the recipient resulted in prevention of TXA2 and PGI2 release and improvement of the respiratory function and pulmonary hemodynamics after reperfusion. We conclude that it seems beneficial to administer the ONO-1301 to the donor and the recipient in order to regulate the prostanoid release and maintain the early graft function.
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PMID:[Beneficial effect of a stable PGI2 analogue (ONO-1301) on prostanoid release after reperfusion in canine left single lung allotransplantation model]. 945 4

Iloprost is a stable prostacyclin analogue with a pharmacokinetic profile allowing nebulised administration in patients with primary pulmonary hypertension (PPH). Inhaled iloprost is a potent acute pulmonary vasodilator with a duration of action of about 60 minutes. It may exert additional long-term benefit through antiproliferative and antithrombotic effects. Inhaled iloprost 2.5 or 5 microg six or nine times daily for 12 weeks (n = 101) significantly (p < 0.01) improved a combined clinical endpoint of a > or =10% increase in distance walked in 6 minutes and an improvement of > or =1 class in New York Heart Association functional class without clinical deterioration or death (16.8 versus 4.9% of placebo recipients, n = 102) in patients with severe PPH or selected forms of nonprimary pulmonary hypertension. Statistical analysis of the response for the PPH subgroup (20.8 versus 5.5% with placebo; n = 51 and 51) was not reported. Improvements from baseline in exercise capacity and haemodynamic/gas exchange variables have been reported in patients with PPH with continued use of inhaled iloprost. In addition, improvement in preinhalation vascular resistance occurred after 12 weeks of inhaled iloprost (p < 0.01 versus placebo) in a large randomised trial. Increased cough, headache, flushing and an influenza-like syndrome were the most common adverse events in the largest trial of patients receiving inhaled iloprost. Headache, flushing and jaw pain occurred significantly more frequently with inhaled iloprost than with placebo.
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PMID:Inhaled iloprost: in primary pulmonary hypertension. 1502 51

Pulmonary arterial hypertension (PAH) is a rare debilitating disease characterized by an increase in pulmonary vascular resistance and progressive right ventricular failure. PAH may be primary or associated with other conditions such as collagen vascular disease, portal hypertension, and HIV. Intravenous epoprostenol improves the survival, exercise tolerance, hemodynamics, and quality of life in patients with PAH and is believed to work through multiple pathways including vasodilation, opposition of smooth-muscle hypertrophy, and inhibition of platelet aggregation. Common dose-limiting side effects are flushing, jaw pain, arthralgias, myalgias, and headache, which are attributed to the vasodilatory effects of epoprostenol. In clinical practice, patients often develop persistent rash that is distinct from the flushing associated with epoprostenol. The specific findings both on physical examination and on dermatopathology have not, however, been well described. This report describes the cutaneous and dermatopathologic findings of 12 patients who developed persistent rash while receiving long-term prostacyclin for PAH.
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PMID:Cutaneous findings in patients with pulmonary arterial hypertension receiving long-term epoprostenol therapy. 1524 33

Although sildenafil, an oral phosphodiesterase type-5 inhibitor, may offer benefits in the pharmacological management of pulmonary hypertension (PH), safety and effectiveness have not been studied during coadministration with beraprost, an oral prostacyclin analogue. To address this issue, we administered oral beraprost (40 microg) on day 1 and beraprost (40 microg) plus sildenafil (25 mg) on days 2 to 6 patients with moderate to severe PH. Although sildenafil plus beraprost produced transient flushing in 2 of 6 patients, systemic hemodynamics and arterial and venous gas analyses were similar in comparisons between the 2 treatment groups. In contrast, sildenafil plus beraprost therapy resulted in a 2.2-fold greater reduction in mean pulmonary arterial pressure and a 1.6-fold greater reduction in pulmonary vascular resistance compared with beraprost alone, and reductions in these parameters persisted longer with combination therapy than with beraprost alone. Addition of oral sildenafil to beraprost appears to represent a safe and effective therapeutic option, at least in the acute phase, for patients with pulmonary hypertension.
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PMID:Addition of oral sildenafil to beraprost is a safe and effective therapeutic option for patients with pulmonary hypertension. 1577 14


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