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)

Normal subjects received infusions of epoprostenol (prostacyclin, PGI2) at doses of 2, 4, 6, and 8 ng/kg/min on each of two occasions after pretreatment with dipyridamole (400 mg/day for 3 days) or placebo. Baseline headache and bleeding time were increased and preejection period (PEP) shortened after dipyridamole. The baseline heart rate was increased on dipyridamole by an amount that correlated to the blood dipyridamole level. PGI2 infusion increased heart rate, systolic blood pressure (BP), pulse pressure, left ventricular ejection time index, and degree of flushing and severity of headache, and reduced diastolic BP, PEP, and T wave height. There was no apparent interaction between PGI2 and dipyridamole on these variables. PGI2 inhibited adenosine diphosphate-induced platelet aggregation and increased bleeding time. We conclude that, despite the synergism between dipyridamole and PGI2 that might be predicted and has been demonstrated in some animal experiments, no such interaction is apparent in normal humans after standard doses.
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PMID:Effects of intravenous epoprostenol on platelets and the cardiovascular system are not potentiated by dipyridamole. 633 4

When epoprostenol (prostacyclin, PGI2) is given by infusion to man, cardiac output is increased, and it appears that the gastrointestinal tract may receive a disproportionate share of this. We have used the clearance of indocyanine green dye to estimate liver blood flow in 8 healthy subjects. During an infusion of PGI2 at a dose of 5 ng/kg/min, apparent liver blood flow increased from 925 +/- 220 ml/min (Mean +/- s.d) to 1320 +/- 453 ml/min, an average increase of 41.1%. Significant changes in heart rate, headache, facial flushing, systolic blood pressure, and pulse pressure were noticed. We suggest that endogenous epoprostenol (PGI2) may be of importance in the physiological regulation of liver blood flow in man. As this dose of epoprostenol could be tolerated readily, epoprostenol therapy could prove a therapeutic advance in some liver disorders, particularly liver transplantation, and possibly in the therapy of certain drug overdoses.
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PMID:Epoprostenol (prostacyclin,PGI2) increases apparent liver blood flow in man. 634 2

Epoprostenol (prostacyclin, PGI2) was given intravenously to seven healthy volunteers in a dose of 4 ng kg-1 min-1 over a 30 min period. Diastolic blood pressure fell but there was no change in cardiac output. The mean PGI2 concentration at the end of the infusion was 0.43 ng/ml (1.1 nM) and a significant inhibition of ADP-induced platelet aggregation occurred. Although obvious facial flushing occurred in all subjects and some subjects complained of headache, cerebral blood flow tended to fall. The results do not support the hypothesis that PGI2 acts as a physiological vasodilator involved in the homeostasis of normal cerebral blood flow.
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PMID:The effect of intravenous epoprostenol (prostacyclin, PGI2) on cerebral blood flow and cardiac output in man. 636 96

Therapy to decrease the load in congestive heart failure is now classified as acute and chronic vasodilator therapy. In this symposium, we presented prostacyclin (PG I2) as an acute and prazosin as a chronic vasodilator. Their hemodynamic and clinical effectiveness were evaluated and their effect on the sympathetic nervous system was also studied. We studied the effect of intravenous prostacyclin infusion in doses of 22 +/- 11 ng/kg/min in nine patients with severe congestive heart failure refractory to digitalis and diuretic drugs. After prostacyclin infusion, mean pulmonary capillary wedge pressure decreased from 21.0 +/- 7.9 to 15.0 +/- 6.6 mmHg (p less than 0.001), mean arterial pressure from 98.9 +/- 12.8 to 76.2 +/- 7.0 mmHg (p less than 0.001), systemic vascular resistance from 2,574 +/- 384 to 1,368 +/- 283 dynes X sec X cm-5 (p less than 0.001), pulmonary vascular resistance from 1,008 +/- 451 to 443 +/- 135 dynes X sec X cm-5 (p less than 0.001) and pulmonary arteriolar resistance from 330 +/- 111 to 189 +/- 73 dynes X sec X cm-5 (p less than 0.001). The cardiac index increased from 2.0 +/- 0.37 to 3.2 +/- 0.59 l/min/m2 (p less than 0.001), and the stroke index from 27.6 +/- 8.69 to 42.0 +/- 0.62 ml/m2 (p less than 0.001). Moreover, prostacyclin therapy counteracted the sensation of coldness of the limbs and face, and patients felt warmth and mild flushing of the face. The effect of prazosin on the exercise duration time until dyspnea was evaluated by the treadmill test.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Effect of prostacyclin and prazosin in the treatment of congestive heart failure; with special reference to the sympathetic nervous system. 637 Dec 82

Levels of immunoreactive 6-oxo-prostaglandin F1 alpha (6-oxo-PGF1 alpha) and thromboxane B2 (TXB2) were measured in peripheral venous plasma in a group of volunteers and non-insulin dependent diabetic patients (NIDDS). Levels of these eicosanoids were close to the limit of sensitivity of the radioimmunoassays and consequently data are reported as maximal values. Basal plasma levels of 6-oxo-PGF1 alpha did not exceed 5 pg/ml in either group and maximal levels of immunoreactive TXB2 were 125 +/- 14 and 128 +/- 8 pg/ml for volunteers and NIDDS respectively. Attempts to elicit peripheral vascular prostacyclin biosynthesis in volunteers by using forearm ischaemia produced no increase in plasma 6-oxo-PGF1 alpha levels. Measurement of the combined plasma levels of 6-oxo-PGF1 alpha, 13,14-dihydro-6-oxo-PGF1 alpha, 13,14-dihydro-6,15-dioxo-PGF1 alpha and 6-oxo-PGE1 indicated that these were also low (less than 5 pg/ml) and that failure to demonstrate increased 6-oxo-PGF1 alpha levels was unlikely to have arisen from metabolism of prostacyclin to one or more of these metabolites. Measurement of 6-oxo-PGF1 alpha and TXB2 in peripheral venous plasma before and during chloropropamide alcohol flushing (CPAF) did not provide evidence for a role for these eicosanoids in the etiology of this phenomenon. These findings point to the need for a reappraisal of studies that have described altered plasma levels of 6-oxo-PGF1 alpha and TXB2 in CPAF and other pathophysiological conditions in man.
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PMID:Prostacyclin and thromboxane in non-insulin dependent diabetes: the chlorpropamide alcohol flush reaction revisited. 654 28

Following an open pilot study, BW 245C , a hydantoin prostaglandin analogue, was given by mouth in an aqueous solution to six healthy volunteers. The subjects received BW 245C 50 and 150 micrograms and placebo on separate occasions according to a double blind randomised design. Heart rate, blood pressure and, using visual analogue scales, facial flushing, abdominal discomfort and headache, were measured before dosing, at 15 minute intervals after dosing for 2 hours and at 30 minute intervals for a further 2 hours. Platelet aggregation responses to ADP and to collagen were measured before dosing and at 15 minutes, 45 minutes, 2 hours and 4 hours after dosing. Cutaneous bleeding time was measured before and 45 minutes after dosing. 150 micrograms BW 245C produced significant (p less than 0.05) facial flushing over the period from 15 to 120 minutes after dosing. Heart rate increased slightly but significantly (p less than 0.05) in response to both doses of 245C only at 75 minutes after dosing. Systolic and diastolic blood pressures were unchanged by either dose of BW 245C . Platelet aggregation responses to ADP were significantly (p less than 0.05) inhibited only at 120 minutes after 150 micrograms BW 245C . Aggregation responses to collagen were significantly (p less than 0.05) inhibited 45 and 120 minutes after 150 micrograms BW 245C and also at 120 minutes after 50 micrograms BW 245C . Bleeding time was unchanged in response to either dose of BW 245C . There was no change in headache or abdominal discomfort scores following either dose of BW 245C . Nausea was reported after 7 out of 12 administrations of BW245C but not after placebo. Nasal congestion was experienced by two subjects receiving 150 micrograms BW 245C and muscle tension and stiffness, especially of the jaw muscles, was also reported following administration of BW 245C but not of placebo. BW 245C is active when given by mouth and has similar pharmacodynamic effects to prostacyclin in man.
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PMID:Effects of single oral dose administration of a hydantoin prostaglandin analogue BW 245C in man. 672 64

Des-amino-D-arginine vasopressin (DDAVP) stimulates the release of factor VIII and plasminogen activator from the vascular endothelium. An infusion of exogenous factor VIII given to haemophiliacs causes an increase in platelet activation. This activation does not occur after stimulating a rise in the patient's own factor VIII level caused by DDAVP infusion. We hypothesised therefore that DDAVP could also cause the endothelial release of prostacyclin (PGI2), a potent anti-platelet agent which would counteract the aggregating effect of factor VIII. To examine this possibility we studied the effect of DDAVP on prostacyclin release, as measured by its stable metabolite 6-oxo-PGF1 alpha, in vitro and in vivo. Rabbit aortic rings were incubated with different concentrations of DDAVP using saline as control. The supernatant was assayed for 6-oxo-PGF1 alpha by radioimmunoassay. All concentrations of DDAVP gave a significant release of 6-oxo-PGF1 alpha. Vasopressin was much less potent. When DDAVP was infused into haemophilic patients there was a significant increase in circulating 6-oxo-PGF1 alpha levels immediately after the infusion. The facial flushing observed as a side-effect of DDAVP could therefore be prostacyclin-mediated. We confirmed this by abolishing the DDAVP induced flushing seen in normal subjects by prior treatment with aspirin which inhibits PGI2 formation.
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PMID:DDAVP stimulates prostacyclin production. 680 93

Circulating basal levels of prostanoids were measured in non-insulin dependent diabetics (NIDDs) who showed chlorpropamide alcohol flushing (CPAF), with and without diabetic complications, and in non-diabetic controls. Prostanoids were also measured during CPAF in those diabetics in whom CPAF is or is not blocked by indomethacin and also in CPAF-negative patients. There was no significant difference in circulating prostanoids between diabetics with and without severe vascular disease. The level of prostaglandin F, however, was significantly higher in the diabetic than in the non-diabetic subjects (mean +/- SEM PGFM 521 +/- 23 v. 414 +/- 18 pmol/l respectively P less than 0.01). In the group in whom CPAF could be blocked by indomethacin there was a significant rise in thromboxane during CPAF when compared with basal values (mean +/- SEM 905 +/- 48 v. 688 +/- 46 pmol/l respectively P less than 0.01) which was abolished by prior administration of indomethacin. There was no significant rise in prostacyclin or PGF. The group in which CPAF could not be blocked by indomethacin and the CPAF negative group showed no rise in any of the prostanoids measured. These findings support the concept of at least two different groups of CPAF positive NIDDs, one in which prostanoids are involved in CPAF and one in which they are not. It is the group in which prostanoids are involved in CPAF who seem to be highly protected against vascular disease.
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PMID:Circulating prostanoid levels, both basal and during the chlorpropamide alcohol flush, in non-insulin dependent diabetes. 689 21

The cardiovascular actions of prostacyclin (PGI2) were investigated in a double-blind, randomised, balanced study. Six healthy volunteers received intravenous infusions of PGI2 in a range of doses up to 4 ng/kg per min, which is the lowest dose which consistently inhibits platelet aggregation. Measurements of systolic time intervals, peak normalised first derivative of the apexcardiogram, high-speed surface electrocardiogram and arterial blood pressure were made during each infusion. PGI2 caused dose-related decreases in diastolic blood pressure, preejection period and QS2 index, and an increase in heart rate. Systolic blood pressure, left ventricular ejection time index, the peak normalised first derivative of the apexcardiogram, and PR interval, QRS duration, QT index and T-wave amplitude were unchanged. Facial flushing was seen in all subjects at PGI2 4 ng/kg per min. These results suggest that PGI2 has an important arteriolar vasodilator action, but do not exclude a minor direct effect on contractility.
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PMID:Noninvasive assessment of the cardiovascular effects of prostacyclin (PGI2) in man. 700 63

Prostacyclin is a potent vasodilator and the most potent inhibitor of platelet aggregation yet discovered. A possible role for prostacyclin in the harvesting of kidneys in experimental canine transplantation has been investigated. Prostacyclin gives a 52.6% increase in renal blood flow prenephrectomy despite inducing a 23% drop in mean arterial blood pressure, without changing the rate of urine output. There is an associated drop in renal vascular resistance of 50.2% and an increase in renal blood volume of 25%. The value of heparin treatment before donor nephrectomy is confirmed as it improves the flow of flushing solution through the kidney after nephrectomy and improves red blood cell washout from the kidney. Prostacyclin and heparin together improve these parameters further. After a warm ischemic period of 45 min, autotransplanted kidneys in dogs pretreated with prostacyclin had normal renal function within 48 hr as judged by the serum creatinine whereas untreated dogs had permanent impairment of function.
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PMID:Experimental assessment of prostacyclin in the harvesting of kidneys for transplantation. 700 43


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