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

The cutaneous vasodilation produced by ethanol is exaggerated when acetaldehyde levels are increased after aldehyde dehydrogenase inhibition, producing a flushing reaction, the mechanism of which is unknown. The authors investigated whether ethanol and its metabolites affect the vascular release of prostacyclin, a potent vasodilator, and whether such an effect might be modified by chronic alcohol consumption. Aortic rings from rats fed Chow ad libitum or pair-fed liquid diets containing either ethanol (36% of energy) or isocaloric carbohydrate for 4 to 5 weeks were incubated in Krebs-Ringer bicarbonate supplemented with saturating amounts of arachidonate (10-20 microM) in the presence of ethanol (10-100 mM), acetaldehyde (10-100 microM) or acetate (1.25-5 mM). Prostacyclin was measured by the radioimmunoassay of 6-keto-prostaglandin F1 alpha. Acetaldehyde produced a concentration-dependent stimulation of prostacyclin production both in alcohol-fed and control rats, whereas acetate did not. This effect was associated with increased conversion of arachidonate (either exogenous or released with A23187) and of prostaglandin endoperoxide H2 to prostacyclin. Ethanol did not affect prostacyclin release in control rats, but, in aortas from alcohol-fed animals, 50 mM ethanol did stimulate prostacyclin formation. These effects may contribute to the cardiovascular responses associated with high blood acetaldehyde levels in flushers and with high ethanol levels in alcoholics. In conclusion, acetaldehyde is a potent stimulant of vascular prostacyclin production. This effect is due, at least in part, to enhanced activity of prostacyclin synthase. Ethanol acquires such a stimulatory effect on prostacyclin formation after chronic alcohol consumption.
 ...
PMID:Acute and chronic effects of ethanol and its metabolites on vascular production of prostacyclin in rats. 310 Jul 72

Although the retroperitoneal aortic approach (RP) is advocated to reduce myocardial ischemia and cardiac-related death, inadequate physiologic data exist to support this contention. As the aorta is exposed via the transabdominal approach (TA) we noted some patients have manifested reduced systemic vascular resistance (SVR) associated with tachycardia, reduced blood pressure, and facial flushing. To determine whether RP offered physiologic advantages over TA we compared cardiac dynamics and blood levels of 6-keto-prostaglandin F1 alpha (6-keto-PGF1 alpha), the stable metabolite of prostacyclin, during exposure of the aorta in 52 patients (33 with TA and 19 with RP), comparable in age, cardiac history, medications, and body surface area. Serial measurements of mean arterial pressure, heart rate, wedge pressure, pulmonary artery pressure, cardiac index, and 6-keto-PGF1 alpha were obtained. Results revealed decreased mean arterial pressure and systemic vascular resistance, increased cardiac index and heart rate, and facial flush occurring 10 minutes after the bowel was explored in TA. This was not observed in RP. These hemodynamic alterations correlated in time and magnitude with a fourteen fold increase in 6-keto-PGF1 alpha. These changes in cardiac indexes can produce increased myocardial oxygen consumption with the risk for myocardial ischemia, particularly in patients with coronary artery disease. The absence of this response to bowel exploration in RP may account for some of the observed advantages in "high-risk" aortic reconstruction.
 ...
PMID:Hemodynamics and prostacyclin release in the early phases of aortic surgery: comparison of transabdominal and retroperitoneal approaches. 333 67

Epoprostenol (prostacyclin) is a potent inhibitor of platelet aggregation and causes relaxation of vascular smooth muscle. These effects may be beneficial in patients with acute myocardial infarction. The effect of epoprostenol infusion in patients with acute myocardial infarction was evaluated in a randomised double blind study of 45 patients with evidence of myocardial infarction of less than 16 hours' duration. The patients were given a 72 hour infusion of epoprostenol (23) or placebo (22). The maximum dose was 5 ng/kg/min. The mean time to treatment was 8.3 hours (range 3.8-15.9 hours). The mean dose was 4.9 ng/kg/min. The patients were followed until day 30. No significant differences were found between the groups in mortality, development of congestive heart failure, cardiogenic shock, arrhythmias, recurrent chest pain, reinfarction, peak creatine kinase concentration, or the time taken to attain peak creatine kinase concentration. No significant difference in baseline ejection fraction was noted between groups, and no significant change in ejection fraction occurred within each group or between groups. The only significant side effect was the development of facial flushing in the epoprostenol group. In this pilot study epoprostenol was well tolerated by patients with acute myocardial infarction. No benefit from epoprostenol could be demonstrated at the dose range used when the drug was administered within 16 hours of the onset of symptoms.
 ...
PMID:Epoprostenol sodium (prostacyclin) infusion in acute myocardial infarction. 353 63

The therapeutic efficacy of prostacyclin in nonhemorrhagic cerebral infarction was assessed in a placebo-controlled double-blind trial. A total of 80 patients with stroke onset within 24 hours were randomized into placebo (37 patients) and prostacyclin (43 patients) groups. Demographic data and risk factors were comparable. Patients in the prostacyclin group received a continuous i.v. infusion of prostacyclin at an average rate of 8.5 ng/kg/min for an average of 64 hours. The placebo group received vehicle only in a similar fashion. During treatment hemodynamic changes were more prominent in the patients receiving prostacyclin and included reduction of systolic and diastolic blood pressure and increase in pulse rate. In contrast there was only a slight (but significant) reduction of diastolic blood pressure in the placebo group. Neurologic deficit scores were determined on admission, at Day 3, and at Weeks 1, 2, and 4. Mean neurologic deficit scores upon entry were comparable in the placebo and prostacyclin groups, and a significant improvement in the score for neurologic deficit was noted in both. The placebo group tended to fare better throughout the study, with a significant difference in neurologic deficit score favoring the placebo group at Week 2 (p = 0.0048). Two patients in the placebo and one in the prostacyclin group died. The only difference in adverse reactions was flushing (6 patients in prostacyclin vs. 0 in placebo group, p less than 0.05). The results of this study suggest a lack of therapeutic efficacy of prostacyclin in a defined population of patients with nonhemorrhagic cerebral infarction.
 ...
PMID:Intravenous prostacyclin in acute nonhemorrhagic stroke: a placebo-controlled double-blind trial. 355 Dec 12

The involvement of dermal prostanoids in menopausal flushing was studied in 8 women suffering from climacteric hot flushes and in 10 asymptomatic control subjects by inducing suction blisters on abdominal skin and assaying blister fluids for 6-keto-PGF1 alpha, a metabolite of the vasodilative prostacyclin (PGI2), thromboxane B2 (TxB2), a metabolite of the vasoconstrictive thromboxane A2 (TxA2), and 13,14-dihydro-15-keto-PGF2 alpha (M-PGF2 alpha), a metabolite of prostaglandin F2A (PGF2A). No marked differences were observed in the levels of these prostanoids in the two study groups. The women experiencing flushes then received conjugated oestrogens for 3 mth to abolish vascular instabilities. This decreased the blister fluid concentration of M-PGF2 alpha from 1720 +/- 476 pg/ml (mean +/- SE) to 1490 +/- pg/ml (P less than 0.05), but had no effect on the dermal levels of 6-keto-PGF1 alpha or TxB2. It was concluded that although certain dermal prostanoids may be affected by oestrogen treatment they are not of primary significance as regards menopausal flushing.
 ...
PMID:Dermal prostacyclin, thromboxane A2 and prostaglandin F2 alpha in climacteric women: effect of oestrogen replacement therapy. 375 16

Seven patients with acute preeclampsia and six with superimposed preeclampsia were infused intravenously with incremental doses of prostacyclin (up to 8 ng/min/kg during 80 minutes). Prostacyclin infusion was accompanied by significant decreases in maternal blood pressure and consistent rises in maternal plasma or urinary 6-keto-prostaglandin F1 alpha, but it caused no changes in maternal or fetal pulse rate or uterine contractility. Moreover, prostacyclin did not change the placental and umbilical blood flow, which were measured before and at the end of infusion. All women experienced facial flushing and two complained of headache during infusion. There was no difference in prostacyclin effects between women with acute or superimposed preeclampsia. These results may be taken as evidence that intravenous prostacyclin is not a specific therapy to increase placental or umbilical blood flow in preeclampsia.
 ...
PMID:Failure of exogenous prostacyclin to change placental and fetal blood flow in preeclampsia. 388 81

Although the exposure of human subjects to prostacyclin (PGI2) infusion has been broad, no systematic approaches have been made in order to investigate the dose-related side effects in patients with angina pectoris and coronary artery disease (CAD). We studied 25 patients with typical chest pain and overt CAD. All patients underwent a cycloergometer stress testing (25 W increments at 2-min intervals). PGI2 was infused in scalar doses up to 10 ng/kg/min. During the infusion 25 patients (100%) had facial flushing, 7 (28%) moderate headache and one (4%) had nausea. In addition, 4 patients experienced the typical chest pain and had significant (greater than or equal to 0.1 mV) ST segment depression at 8.10 ng/kg/min infusion rates. These patients had lower tolerance to exercise (6.7 +/- 1.7 vs. 8.8 +/- 1.9 min; p less than 0.05) and coronary artery lesions more severe than those observed in patients without drug-induced angina pectoris. Our data therefore indicate that PGI2 at therapeutic doses may induce myocardial ischemia in patients with angina pectoris, low tolerance to exercise and severe CAD. In patients with mild to moderate degree of CAD, PGI2 was found to be well tolerated. These findings suggest that patients with angina pectoris and low tolerance to exercise should be excluded from clinical studies directed at elucidating the effectiveness of PGI2 in cardiovascular disorders.
 ...
PMID:Side effects of prostacyclin in patients with angina pectoris and coronary artery disease. 390 57

The effects of 9 beta-methyl carbacyclin, a chemically stable analogue of epoprostenol (prostacyclin, PGI2) were studied, in comparison with epoprostenol, both in vitro and in vivo in man. In vitro 9 beta-methyl carbacyclin and epoprostenol inhibited platelet aggregation induced by ADP, collagen, the endoperoxide analogue U46619 and arachidonic acid. The potency of 9 beta-methyl carbacyclin relative to epoprostenol was comparable in ADP and collagen-aggregated platelet rich plasma (PRP), 9 beta-methyl carbacyclin being 0.01 times as active as epoprostenol. The anti-aggregatory potencies of the two compounds were comparable in PRP and whole blood. The phosphodiesterase inhibitor isobutyl methyl xanthine enhanced the anti-aggregatory activity of both compounds in vitro. 9 beta-methyl carbacyclin and epoprostenol elevated platelet cyclic AMP, 9 beta-methyl carbacyclin being 0.04 times as active as epoprostenol. In a placebo controlled trial both drugs produces significant headache and facial flushing when compared with placebo. Nasal stuffiness, abdominal discomfort and nausea were reported on all three treatments. Both drugs caused significant and comparable increase in heart rate and decrease in pre-ejection (PEP) and PEP/left ventricular ejection time (LVET) ratio compared with placebo. Systolic and diastolic blood pressure, LVET and QS2 index were unchanged. Platelet aggregation responses to ADP were significantly inhibited by all three doses of both drugs compared with placebo. Bleeding time was significantly longer during epoprostenol infusion than either placebo or 9 beta-methyl carbacyclin infusion. Neither drug had significant effect, compared with placebo, on kaolin activated clotting time in PPP, PRP or in PRP in the presence of heparin, prothrombin time, partial thromboplastin time, thrombin clotting time, fibrinogen, fibrinogen degradation products or euglobulin clot lysis time. The pharmacodynamic effects and duration of action of 9 beta-methyl carbacyclin and of epoprostenol are similar; 9 beta-methyl carbacyclin is approximately 100 times less potent than epoprostenol in man.
 ...
PMID:A chemically stable analogue, 9 beta-methyl carbacyclin, with similar effects to epoprostenol (prostacyclin, PGI2) in man. 608 4

1 Atenolol 0.2 mg/kg i.v., propranolol 0.2 mg/kg i.v. or placebo were given in a double-blind crossover study to six healthy male subjects, and the effects of a subsequent infusion of epoprostenol (prostacyclin, PGI2) 0-6 ng kg-1 min-1 monitored. 2 PGI2 caused a tachycardia, a fall in diastolic blood pressure, a rise in pulse pressure, reduction in pre-ejection period (PEP) and rise in left ventricular ejection time index (LVETI), headache and facial flushing at doses of PGI2 greater than 2 ng kg-1 min-1,, (P less than 0.05). 3 Beta-adrenoceptor blockade did not prevent the tachycardia in response to PGI2, and did not interact with any of the other dynamic effects of PGI2. 4 In vitro, PGI2 at 1 and 2 ng/ml inhibited platelet aggregation to ADP (P less than 0.01), although no significant effect on platelet aggregation was seen in the in vivo study. Atenolol and propranolol at a final concentration of 1 microgram/ml did not affect this in vitro study. Atenolol and propranolol at a final concentration of 1 microgram/ml did not affect in vitro effect of PGI2 on platelet aggregation. 5 Pretreatment with atropine 0.04 mg/kg i.v. in three subjects did not attenuate the tachycardia caused by PGI2 infusion, even though the baseline heart rate was increased. 6 Adverse effects to PGI2 infusion included sudden bradycardia, pallor and sweating, suggesting that the Bezold-Jarisch reflex seen in animals in response to PGI2 may also occur in humans. 7 Neither increased sympathetic drive nor vagal withdrawal are likely causes of the tachycardia following PGI2 infusion.
 ...
PMID:The cardiovascular and platelet effects of epoprostenol (prostacyclin, PGI2) are unaffected by beta-adrenoceptor blockade in man. 612 95

Prostacyclin (PGI2) therapy has been evaluated in many vascular diseases. However, it is unstable and a potent vasodilator, able to lower blood pressure. Although such effects may be desirable in some situations, they are unwanted in others. ZK36-374 (Schering AG) is a carbacyclin derivative with a similar action to PGI2; however, it is chemically stable and has less of a hypotensive action. We evaluated the effects of a 4-hour I.V. infusion of ZK36-374 at a maximum dose of 2ng/Kg/min. in ten normal volunteers. Prior to the infusion and at 2 and 4 hours, blood was sampled for estimation of platelet aggregation in both platelet rich plasma and whole blood. Beta-thromboglobulin, 6-keto-PGF1 alpha and TXB2 were measured by radioimmunoassay, as were other coagulation and rheological tests. The infusion was well tolerated with facial flushing, jaw trismus and some nausea at max dose. Blood pressure and pulse rate were not significantly altered. During infusion of ZK36-374, the rates of platelet aggregation to 2 microns ADP and 2 micrograms collagen in PRP were significantly decreased when compared to baseline, as was whole blood aggregation to 2 microns ADP and 0.5 microgram collagen. Beta TG also fell significantly, as did the levels of 6-keto-PGF1 alpha and TXB2. Fibrinolysis, blood viscosity, and red cell deformability were unchanged. ZK36-374 is an effective anti-platelet agent without major toxic or hypotensive effects.
 ...
PMID:The effects of intravenous ZK36-374, a stable prostacyclin analogue, on normal volunteers. 620 61


<< Previous 1 2 3 4 5 6 7 8 Next >>