Intravenous Administration Of Prostaglandin E1 Research Articles

POS-025 EVALUATION OF PROSTAGLANDIN E1 INFUSION EFFECTS ON URINARY CALCIUM EXCRETION IN NEONATE WITH CONGENITAL HEART DISEASE

Congenital heart disease, related to the patent ductus arteriosus is one of the most important life-threating condition in human life. Administration of prostaglandin E1 to keep open the ductus arteriosus and fetal survival before corrective surgery is necessary. Despite the life-giving role of prostaglandin E1, numerous and dangerous side effects are considered; including the theories discussed, is effect of prostaglandin E1 on creation of hypercalciuria. This study is aimed to assess the effect of intravenous administration of prostaglandin E1 on calcium excretion in the urine of newborns with congenital heart disease.

Prostaglandins in migraine

This review presents recent findings on the role of prostaglandins in migraine pathophysiology. Experimental studies have shown that prostaglandins are distributed in the trigeminal-vascular system and its receptors are localized in the trigeminal ganglion and the trigeminal nucleus caudalis. Prostaglandins were found in smooth muscles of cranial arteries, and functional studies in vivo showed that prostaglandins induced dilatation of cranial vessels. Human studies showed that intravenous infusion of vasodilating prostaglandins such as prostaglandin E₂ (PGE₂), prostaglandin I₂ (PGI₂) and prostaglandin D₂ (PGD₂) induced headache and dilatation of intra-cranial and extra-cranial arteries in healthy volunteers. In contrast, infusion of non-dilating prostaglandin F₂α (PGF₂α) caused no headache or any vascular responses in cranial arteries. PGE₂ and PGI₂ triggered migraine-like attacks in migraine patients without aura, accompanied by dilatation of the intra-cerebral and extra-cerebral arteries. A novel EP4 receptor antagonist could not prevent PGE₂-induced headache in healthy volunteers. Recent in-vitro/in-vivo data demonstrated presence and action of prostaglandins within the trigeminal pain pathways. Migraine induction after intravenous administration of PGE₂ and PGI₂ suggests a specific blockade of their receptors, EP and IP respectively, as a new potential drug target for the acute treatment of migraine.

Induction of Labour by Intravenous Administration of Prostaglandin E2 with or without Prior Amniotomy.

Induction of Labour by Intravenous Administration of Prostaglandin E2 with or without Prior Amniotomy.

Effect of i.v. prostaglandin E2 on the secretion of pituitary hormones in healthy men.

The intravenous administration of prostaglandin E2 (PGE2) has been proposed as a diagnostic tool in the differentiation of hypothalamic and pituitary forms of growth hormone deficiency. We have therefore studied the effect of PGE2 (200 micrograms i.v.) on serum concentrations of GH, LH, FSH, PRL, TSH, and cortisol in six healthy, male subjects. Side-effects, reported as highly unpleasant, occurred within two minutes after i.v. PGE2 in each individual. The individual response in serum concentrations of GH and LH following PGE2 was variable. Thus, a stimulatory effect was seen in some, but not in all individuals. Concentrations of FSH, PRL, and TSH did not change after PGE2-challenge, but a transient rise in serum cortisol was observed (p less than 0.01). The release of GH and LH upon i.v. PGE2 may be part of a systemic reaction or be due to a direct action of PGE2 on the anterior pituitary. The inhomogeneity of the obtained results and the unpleasant side-effects of i.v. PGE2 disqualify its use for the evaluation of pituitary GH-releasing capacity.

Haemodynamic effects of intra-arterial and intravenous administration of prostaglandin E1 in patients with peripheral arterial disease.

The purpose of this study was to compare the haemodynamic effects of intra-arterial and intravenous prostaglandin E1 (PGE1) both injected and infused into ischaemic legs. Continuous intra-arterial infusion of PGE1 induced a significantly greater increase in skin temperature and blood flow than did intravenous drip infusion. Furthermore, intra-arterial infusion caused no steal phenomenon in the toe as indicated by skin temperature. On the other hand, toe skin temperature decreased during intravenous drip in 33 per cent of the legs tested. Continuous intravenous infusion also produced a significantly greater increase in toe skin temperature than did brief intravenous drip. In three of ten ulcers healed by continuous intra-arterial infusion, no definitive effect was obtained from continuous intravenous infusion even when it was repeated up to three times before continuous intra-arterial infusion. Intra-arterial injection of PGE1 caused no significant increase in toe skin temperature.

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Prostaglandin E1 (PgE1) may have a role in ameliorating hepatic ischaemia–reperfusion injury (IRI). Metabolism occurs after intravenous administration of PgE1 and limits its efficacy. This study has investigated the cytoprotective effect of PgE1 administered intraportally. Since leucocyte–endothelial cell adhesion has been strongly implicated in IRI, we also studied intracellular adhesion molcule-1 (ICAM-1) and vascular adhesion molecule-1 (VCAM-1) expression to assess if PgE1 acted through this pathway. Under general anaesthesia hepatic ischaemia was induced in 20 canine livers by 60 min of in situ inflow occlusion with continuous intraportal infusion of PgE1 0.02 µg kg−1 per min lactated Ringers solution (n = 10) or equal volumes of lactated Ringers solution (controls, n = 10). The infusion started 15 min before ischaemia and continued during the ischaemic phase and 30 min after reperfusion. Hepatic venous blood and liver biopsies were taken at baseline, 60-min ischaemia and 30-min reperfusion. The blood samples were assessed for liver enzymes, TNF-α, IL-1β, serum ICAM-1 (sICAM-1) and VCAM-1 (sVCAM-1), while the liver biopsies were assessed histologically for IRI and immunohistochemically for ICAM-1 and VCAM-1 expression. PgE1 treatment significantly reduced the rise in AST, ALT, TNF-α, sICAM-1 and sVCAM-1 following ischaemia and reperfusion (P < 0.05). It reduced hepatocyte necrosis and sinusoidal congestion. However, it did not reduce IL-1β. These changes were associated with significant down-regulation of ICAM-1 and VCAM-1 (P < 0.05). Intraportal PgE1 infusion ameliorates IRI, inhibits ICAM-1 and VCAM-1 expression and TNF-α secretion. One of the mechanisms of cytoprotection may be through ICAM-1 and VCAM-1 inhibition.

Multiple Occlusive Retinal Arteritis in Both Eyes of a Patient with Rheumatoid Arthritis

Purpose: To report multiple occlusive retinal arteritis as a complication of rheumatoid arthritis. Case: A 67-year-old woman developed superotemporal branch retinal artery occlusion in both eyes, together with arterial sheathing and large cotton wool patches around the optic disc, in the course of rheumatoid arthritis with moderate activity. Observations: Fluorescein angiography disclosed delayed filling of the superotemporal retinal artery in the right eye and no filling of the superotemporal artery in the left eye. In addition, segmental absence of filling was found in peripheral branches of the other major retinal arteries in both eyes. After hyperbaric oxygen therapy and intravenous administration of prostaglandin E1 and urokinase for 2 weeks, there was improvement in her vision. Conclusion: Multiple occlusive retinal arteritis in rheumatoid arthritis can manifest as retinal artery occlusion. Rheumatoid arthritis should be included in the differential diagnosis of bilateral retinal artery occlusion.

Liposomal prostaglandin E1 enhances optic nerve head blood flow in cats.

We investigated the effects of intravenous administration of prostaglandin E1 (PGE1) and lipo-prostaglandin E1 (lipo-PGE1), on optic nerve head blood flow (ONHBF) using ten anesthetized cats. Changes in relative ONHBF were noninvasively and continuously measured with fundus camera-based laser Doppler flowmetry. The blood pressure (BP) decreased significantly by 6 +/- 5 (mean +/- SD)% and 8 +/- 4%, respectively, after PGE1 (30, 100 ng/kg/min) administration, but at either of these concentrations there were no significant changes in ONHBF. On the other hand, with lipo-PGE1 (10 ng/kg/min), the BP remained unchanged, but ONHBF increased significantly by 61 +/- 49%. A larger dose of lipo-PGE1 (30 ng/kg/min) had opposite effects because the BP decreased significantly by 14 +/- 4% after administration, and the ONHBF remained unchanged (i.e., 67 +/- 102%). In all cases, there were no changes in IOP. With 10 ng lipo-PGE1, the large increase in ONHBF can be accounted for by vasodilation since perfusion pressure was unchanged. The inability of 30 ng lipo-PGE1 to affect ONHBF could be ascribed to the decrease in BP resulting in decreased ocular circulation. These results suggest that, in humans, lipo-PGE1 may also increase ONHBF provided that it is used at doses that do not produce large decreases in BP.

Prostaglandin E1 improves hepatic encephalopathy produced by ischaemia-reperfusion liver injury in rats.

To investigate the action of prostaglandin E1 on hepatic encephalopathy. Prospective, randomised, controlled animal study. University animal laboratory. Male Wistar rats. After passive avoidance learning, acute liver failure was induced by occlusion of the left portal vein and the hepatic artery for 90 min. Then memory retention was evaluated 48 h later. The effects of prostaglandin E1 on memory retention were examined in animals treated with the agent systemically (intravenous injections with prostaglandin E1 twice before and after surgery, 20 microg/kg each time) and animals treated with the agent topically (intracerebroventricular injection with prostaglandin E1, 0.1 microg/h for 48 h beginning at liver ischaemia). Marked damage was found on plasma analysis in animals subjected to liver ischaemia, and the memory retention was also impaired. Intravenous administration of prostaglandin E1 improved both the liver injury and memory retention. However, intracerebroventricular administration of prostaglandin E1 alleviated neither. These findings show that prostaglandin E1 contributes to the amelioration of hepatic encephalopathy by improving liver function.

Prenatal diagnosis of a highly undifferentiated brain tumour—a case report and review of the literature

Intracranial tumours, often presenting with progressive hydrocephalus, are rare congenital diseases accounting for 0·5–1·5 per cent of all cases of brain tumours diagnosed during childhood. The differential diagnosis includes vascular malformations, infarctions, and haemorrhages. Sonographic signs suggestive of glioblastoma, teratoma, and astrocytoma do not establish the histological diagnosis, however. We report a case of an undifferentiated fetal glioma detected at 29 weeks' gestation. The diagnosis of an undifferentiated brain tumour was suspected by sonography because of the lack of normal brain structures in conjunction with a diffuse echogenic central lesion and an external hydrocephalus. Because of the very poor prognosis, we induced labour by intravaginal and intravenous administration of prostaglandin E2 and achieved the vaginal delivery of a stillborn child whose head circumference corresponded to 38 weeks of pregnancy. Histological and immunochemical features of this undifferentiated congenital glioma (glioblastoma) are presented. © 1997 John Wiley & Sons, Ltd.

Prenatal diagnosis of a highly undifferentiated brain tumour—a case report and review of the literature

Intracranial tumours, often presenting with progressive hydrocephalus, are rare congenital diseases accounting for 0.5-1.5 per cent of all cases of brain tumours diagnosed during childhood. The differential diagnosis includes vascular malformations, infarctions, and haemorrhages. Sonographic signs suggestive of glioblastoma, teratoma, and astrocytoma do not establish the histological diagnosis, however. We report a case of an undifferentiated fetal glioma detected at 29 weeks' gestation. The diagnosis of an undifferentiated brain tumour was suspected by sonography because of the lack of normal brain structures in conjunction with a diffuse echogenic central lesion and an external hydrocephalus. Because of the very poor prognosis, we induced labour by intravaginal and intravenous administration of prostaglandin E2 and achieved the vaginal delivery of a stillborn child whose head circumference corresponded to 38 weeks of pregnancy. Histological and immunochemical features of this undifferentiated congenital glioma (glioblastoma) are presented.

Effect of prostaglandin E1 on ammonia concentration in blood of patients with hepatic resection

Plasma concentrations of ammonia were examined following prostaglandin E1 (PGE1) administration in 16 patients who received hepatectomy for hepatocellular carcinoma. PGE1 at 0.01-0.04 microgram/kg/min was administered for approximately 24 hr during the perioperative periods. The ammonia concentration was reduced a day after the operation following intravenous administration of PGE1 in cirrhotic patients compared to noncirrhotic patients with or without PGE1 injection. Serum liver function scores, glutamic pyruvic transaminase, and total bilirubin concentrations were decreased after PGE1 administration. A similar ammonia response due to PGE1 was obtained after operation in cirrhotic patient when PGE1 0.5 microgram/kg was administered intravenously for 30 min. These results suggest that PGE1 administration is useful in reducing the enhanced ammonia concentration associated with hepatic resection, and it is particularly effective in the case of liver cirrhosis.

The effect of intraportal PGE1 on warm ischemic liver damage.

To determine the most effective route of administering prostaglandin E1 (PGE1) to inhibit warm ischemic liver damage, 90-min warm ischemia was established in a canine model. The dogs were divided into three groups according to the treatment given. Thus, group A (n = 10) was the control group which received no treatment, group B (n = 7) was administered PGE1 intravenously, and group C (n = 7) was administered PGE1 intraportally. PGE1 was continuously administered before and after the ischemia at a rate of 0.02 microgram/kg/min. The branched-chain amino acid to aromatic amino acid ratio in the hepatic vein, and the arterial ketone body ratio of acetoacetic acid to beta-hydroxybutyric acid, were examined to observe the metabolism of each amino acid and the oxidation-reduction ability of hepatocytes. Both ratios were maintained only in the group C dogs, three of which survived for over 3 days, whereas in groups A and B, all the dogs died within 24 h. The results of this study imply that the intraportal administration of PGE1 was more effective against warm ischemic liver damage than the intravenous administration of PGE1.

Effect of prostaglandin E1 on arterial ketone body ratio in hepatectomy.

We evaluated the effect of prostaglandin E1 (PGE1) administration during hepatectomy on arterial ketone body ratio (AKBR), which is an indicator of liver function, and on other liver functions in the postoperative period. Eighteen patients were divided into two groups: Continuous intravenous administration of PGE1 (0.02 μg·kg-1·h-1) was started immediately before hepatic resection and ceased at the end of operation in nine patients (PGE1 group); the other nine did not receive PGE1 (control group). After hepatic resection, a significant increase in AKBR was observed in the PGE1 group. However, no change was observed in the control group. In the PGE1 group, total bilirubin and SGOT recovered more rapidly to the preoperative level than in the control group. These findings suggested that PGE1 might have a protective effect on the liver.

Determination of gastroduodenal alkaline responses using pH deflection in the rat.

We set up a new system for measuring the gastroduodenal HCO3- responses using pH deflection and the potential difference (PD) in the anesthetized rat. The stomach or the proximal duodenum was perfused at a flow rate of 0.7 ml/min with saline (pH 4.5), the pH of the perfusate and PD were continuously monitored, and HCO3- output was determined as acid-neutralizing capacity by back-titration of the perfusate to pH 4.5. In the case of the stomach, acid secretion was inhibited by omeprazole (60 mg/kg i.p.). Under these conditions, the pH, PD, and HCO3- output were 5.5 +/- 0.03, -3.8 +/- 0.4 mV, and 1.5 +/- 0.3 microEq/10 min in the duodenum and 5.4 +/- 0.04, -52.4 +/- 1.8 mV, and 1.2 +/- 0.3 microEq/10 min in the stomach, respectively. In addition, when various amounts of NaHCO3 were added into the system, a linear relationship was obtained between the area of pH deflection and the amount of added HCO3- (r = 0.999). Both pH and HCO3- output in these tissues were significantly increased by intravenous administration of prostaglandin E2, carbachol, and YM-14673 (a TRH analogue); the net HCO3- output in the duodenum was 8.7 +/- 1.3, 2.3 +/- 0.5, and 5.2 +/- 0.9 microEq, respectively. The values of net HCO3- output measured by back-titration coincided well with those obtained from the area of pH deflection caused by various agents. These results indicate that this system using pH deflection may be useful for quantitative determination of HCO3- response in the gastroduodenal mucosa.

Immediate improvement of diabetic mononeuropathy after intravenous administration of prostaglandin E1.

The effects of intravenously administered prostaglandin E1 (PGE1) on diabetic mononeuropathy was investigated in three patients with diabetic oculomotor palsy. PGE1 (1.0-1.5 micrograms/day) was intravenously administered every morning for 4 or 6 weeks. Diplopia, blepharoptosis and decreased range of ocular movement, which were observed on admission, immediately began to improve at 1-4 days after the beginning of the treatment. On the final day of the treatment, none of the above signs remained in the three cases. The present study suggests that improvement of intraneural microcirculation by PGE1 administration results in an immediate recovery from diabetic oculomotor nerve palsy.

EFFECTS OF PROSTAGLANDIN E1 ON tcPo2 AND tcPco2 IN PATIENTS WITH ARTERIOSCLEROSIS OBLITERANS

Transcutaneous oxygen tension (tcPo2) and transcutaneous carbon dioxide tension (tcPco2) of the lower extremities were investigated in 12 patients with arteriosclerosis obliterans throughout intravenous administration of Prostaglandin E1 (PGE1). Levels of ΔtcPo2 and ΔtcPco2 were measured serietely 20min. before to 20min. after PGE1 infusion. The patients were divided into two groups; one consisted of six patients with ankle pressure indexes (APIs) of more than 0.5 and the other six with APIs of less than 0.5. There was a statistically significant correlation between API and tcPo2, but no correlation between API and tcPco2. ΔTcPo2 levels in patients with APIs of less than 0.5 increased to 8.22±5.07 and 9.07±4.33 at 10 and 15 minutes after the end of PGE1 infusion, respectively. ΔTcPco2 levels in patients with APIs of less than 0.5 decreased to 0.85±0.05, 0.80±0.07 and 0.73±0.06 at 10, 15 and 20 minutes after the end of PGE1 infusion, respectively. The changes of ΔtcPo2 and ΔtcPco2 in patients with APIs of more than 0.5 were minimal. There were no statistically significant differences between ΔtcPo2 and ΔtcPco2 levels found above and below the femoral arterial occlusion, though ΔtcPo2 levels, after the end of the PGE1 infusion in the distal femoral arterial occlusion, were higher than those in the proximal femoral arterial occlusion. These results suggest that the intravenous PGE1 infusion is effective in patients with APIs of less than 0.5 and/or with distal femoral arterial occlusion.

Basal and PGE2-stimulated duodenal bicarbonate secretion in the rat in vivo.

We studied basal and prostaglandin E2 (PGE2)-stimulated duodenal HCO3- transport in the rat in vivo both in the presence and absence of a concentration gradient for HCO3- from blood to lumen. Basal HCO3- transport was not reduced when the luminal solution was changed from one containing 0 mM HCO3- to one containing 22 mM HCO3- either at pH 9.0 or 7.5. Thus basal duodenal HCO3- transport in rats is independent of a blood-to-lumen HCO3- concentration gradient, which indicates an energy-dependent process with little passive flux of HCO3-. Luminal or intravenous administration of PGE2 significantly (P less than 0.01) increased HCO3- secretion into a HCO3(-)-free luminal solution but had no effect on HCO3- secretion into luminal solutions containing 22 mM HCO3-, either at pH 9.0 or 7.5. Therefore prostaglandins may act by increasing passive flux of HCO3- rather than by stimulating energy-dependent duodenal HCO3- transport.

Avoiding cesarean deliveries by intravenous prostaglandin E2 administration (PGE2)

The study reported here was prompted by the question whether caesarean deliveries which would otherwise be necessary can be avoided by intravenous infusion of prostaglandin E2 (PGE2). The authors consider intravenous administration of PGE2 during delivery to be indicated in cases which fail to respond to therapy after three local cervical maturation attempts and in standstills where oxytocin has no effect. Out of a total of 5835 women who gave birth at the Obstetrics Department of the Berlin-Neukölln Gynecological Clinic between 1980 and 1981, those who had been given intravenous infusions of PGE2 were identified and a check was made to establish whether this treatment offers any advantages. PGE2 infusion after unsuccessful intracervical application of PGE2 gel: Out of 1122 risk patients in whom cervical maturation prior to induction of birth appeared desirable, 43 (3.8%) still had a Bishop Score of less than or equal to 7 after three local applications of PGE2 gel. Attempts to achieve a vaginal delivery in spite of this, by means of PGE2 infusion, were successful in 60% of the cases. The mean rate of PGE2 infusion was 1.1 +/- 0.3 microgram/min. Four women were given oxytocin in addition, in an average dose of 9.3 +/- 1.1 mU/min. The average duration of labour was 10 hours 30 min. Complications in mother and child occurred no more frequently than in other risk births. PGE2 infusion in cases with standstill not responding to oxytocin treatment: In 82 parturients (1.4%) a standstill occurred during labour after initially normal dilation of the cervix, and could not be overcome by administration of oxytocin.(ABSTRACT TRUNCATED AT 250 WORDS)

In vivo bronchodilator activity of vasoactive intestinal peptide in the cat.

Vasoactive intestinal peptide (VIP) is an octacosapeptide that occurs widely in the animal kingdom, is distributed in many organs and tissues, and has a broad range of biologic actions. We evaluated the ability of VIP to produce bronchodilation in anesthetized, mechanically ventilated, atropinized, closed chest cats. Boluses of VIP injected intravenously (0.1 to 10 micrograms X kg-1) reversed in a dose-dependent manner the increase in lung resistance (RL) and the decrease in dynamic lung compliance (Cdyn) induced by an intravenously administered infusion of 5-hydroxytryptamine (5HT) (5 to 30 micrograms X kg-1 X min-1). Distribution of bronchodilator activity was assessed by using RL as an index of central airways caliber and dynamic elastance (Edyn; the inverse of Cdyn) as an index of tone in peripheral airways and lung parenchyma. Although all levels of the tracheobronchial tree responded to VIP, the predominant site of action appeared to be in central airways. A similar distribution and magnitude of relaxant effects were observed after the intravenous administration of prostaglandin E2 (PGE2) (0.1 to 10 micrograms X kg-1). Prostaglandin E2 also was effective in reversing 5HT-induced bronchoconstriction when given by ultrasonic nebulization, whereas VIP was not. Bronchodilation mediated by VIP persisted after pretreatment with indomethacin or propranolol. We conclude that VIP is a potent relaxant of feline airways smooth muscle in vivo and that this effect of the peptide occurs independent of prostaglandin production or beta adrenergic receptor activation.