6-ketoprostaglandin-f1-alpha and Edema

To examine whether dalteparin, a low molecular weight heparin, prevents hepatic damage by inhibiting leukocyte activation, we analyzed its effect on ischemia/reperfusion (I/R) injury of rat liver in which activated leukocytes play a critical role.. Prospective, randomized, controlled study.. Research laboratory at a university medical center.. Male Wistar rats weighing 220-280 g.. Hepatic damage was evaluated by changes in serum transaminase concentrations after I/R. Coagulation abnormalities were evaluated by changes in serum concentrations of fragment E of fibrin and fibrinogen degradation products after I/R. Hepatic tissue blood flow was measured by laser-Doppler flow meter. Hepatic edema was evaluated by determination of the change in the wet/dry tissue weight ratio. Rats were intravenously injected with dalteparin or unfractionated heparin (300 units/kg) and subcutaneously injected with DX9056a, a selective inhibitor of activated factor X (3 mg/kg). To determine whether dalteparin inhibits leukocyte activation, we examined the effect of dalteparin on hepatic concentrations of interleukin-12, tumor necrosis factor-alpha, and hepatic myeloperoxidase activity after I/R in vivo. In addition, we examined increases in tumor necrosis factor-alpha production in rat monocytes and in intracellular calcium concentrations in neutrophils in vitro. We also examined the effect of dalteparin on endothelial production of prostacyclin using isolated rat hepatic sinusoidal cells in vitro.. Intravenous administration of dalteparin inhibited increases in serum levels of both transaminases and serum concentrations of fragment E of fibrin and fibrinogen degradation products in animals subjected to hepatic I/R. Hepatic tissue blood flow after reperfusion was increased by dalteparin. Dalteparin inhibited hepatic edema, increases in hepatic tissue levels of interleukin-12 and tumor necrosis factor-alpha, and accumulation of neutrophils in animals subjected to hepatic I/R. Neither DX9065a nor unfractionated heparin showed any therapeutic effects, despite potent inhibition of increases in serum levels of fragment E of fibrin and fibrinogen degradation products. Neither monocytic tumor necrosis factor-alpha production nor neutrophil activation was inhibited by dalteparin in vitro. Dalteparin enhanced the hepatic I/R-induced increases in hepatic tissue levels of 6-keto-prostaglandin (PG) F1alpha, a stable metabolite of prostacyclin, which is capable of inhibiting monocytic tumor necrosis factor-alpha production. Pretreatment with indomethacin completely reversed both of the therapeutic effects of dalteparin, whereas pretreatment with NS-398, a selective inhibitor of cyclooxygenase-2, did not. Dalteparin did not directly increase the endothelial production of prostacyclin in vitro.. Dalteparin might reduce I/R-induced liver injury in rats by attenuating inflammatory responses. These therapeutic effects might be independent of its anticoagulant activity but dependent on its capacity to enhance endothelial production of prostacyclin via cyclooxygenase-1 activation. Furthermore, the mechanism or mechanisms by which dalteparin promotes the endothelial production of prostacyclin in vivo might involve unknown factors other than endothelial cells.

Topics: 6-Ketoprostaglandin F1 alpha; Animals; Anticoagulants; Calcium; Cyclooxygenase 2 Inhibitors; Dalteparin; Edema; Endothelium; Epoprostenol; Fibrin Fibrinogen Degradation Products; Heparin; In Vitro Techniques; Indomethacin; Inflammation; Interleukin-12; Leukocytes; Liver; Liver Diseases; Male; Monocytes; Naphthalenes; Nitrobenzenes; Peroxidase; Propionates; Prospective Studies; Random Allocation; Rats; Rats, Wistar; Reperfusion Injury; Sulfonamides; Transaminases; Tumor Necrosis Factor-alpha

To assess the effect of subeschar tissue fluid (STF) on the function and structure of endothelial cell in vitro.. Human umbilical vein endothelial cells (HUVEC) were incubated with STF obtained from patients in the early postburn stage. Then the morphological changes in EC were observed, and activity of EC and contents of LDH, 6-keto-PGF1 alpha in media were determined.. The activity of LDH and the content of 6-keto-PGF1 alpha were increased gradually after HUVEC incubated with STF, and were higher than that measured after HUVEC incubated with healthy volunteer's sera. Furthermore, activity of HUVEC decreased and they became deformed, showing shrinkage of the cell body with enlargement of intercellular space. In addition, small vacuoles appeared in cytoplasm with karyopyoknosis after 24 h.. STF can damage endothelial cell and might play an important role in the pathophysiological process of burn injury.

Topics: 6-Ketoprostaglandin F1 alpha; Adolescent; Adult; Body Fluids; Burns; Cells, Cultured; Child; Child, Preschool; Edema; Endothelium, Vascular; Female; Humans; L-Lactate Dehydrogenase; Male; Middle Aged; Umbilical Veins

Several reports have shown peritumoral edema accompanying primary bone tumors demonstrated by magnetic resonance imaging (MRI). However, the mechanism of this inflammatory reaction is still unclear. The authors postulated that the reaction was caused by some chemical mediators including prostanoids, because several investigators have observed that some types of bone tumors synthesize prostanoids. Therefore, the authors compared MRI findings and tumor prostaglandin (PG) levels.. The subjects were 29 patients with primary bone tumor or tumor-like conditions: chondroblastoma (n = 5); chondrosarcoma, including rare variants (n = 8); giant cell tumor (n = 6); osteochondroma (n = 5); osteoblastoma (n = 2); Ewing's sarcoma (n = 2); and eosinophilic granuloma (n = 1). T1- and T2-weighted spin echo images were obtained in all but one patient before surgery. The tumor concentration of prostaglandin E2, 6-keto-PGF1 alpha, and thromboxane B2 were measured by radioimmunoassay.. MRI distinctly showed bone marrow edema in 9 and soft tissue edema in 12 of the 28 patients examined. These findings were significantly correlated with the PG levels. Moreover, the PG levels were correlated with the histologic classifications (P < 0.001). In particular, the chondroblastomas showed prominent concentrations of PGs compared with other cartilaginous tumors or giant cell tumors.. Although peritumoral edema accompanying benign and malignant bone tumors is not necessarily related to one single pathophysiologic mechanism, these results suggest that PG production was an important cause of the inflammatory reaction that was revealed by MRI. Recognition of this phenomenon is advantageous not only for strict diagnostic purposes but also for understanding the characteristic features of individual primary bone tumors.

Topics: 6-Ketoprostaglandin F1 alpha; Bone Neoplasms; Chondroblastoma; Dinoprostone; Edema; Eosinophilic Granuloma; Humans; Magnetic Resonance Imaging; Neoplasm Proteins; Osteoblastoma; Osteosarcoma; Thromboxane B2

1. Modulation of prostaglandin biosynthesis in vivo by either exogenous or endogenous nitric oxide (NO) has been studied in the rat using arachidonic acid (AA)-induced paw oedema and measuring both the foot volume and the amount of 6-keto-prostaglandin F1 alpha (6-keto-PGF1 alpha), the stable metabolite of prostacyclin (PGI2), in the oedematous fluid recovered from inflamed paws. 2. Paw injections of 150 or 300 nmol of AA were virtually inactive whereas 600 nmol produced a moderate oedema which was greatly reduced by the NO synthase inhibitor L-NG-nitro arginine methyl ester (L-NAME, 100 nmol/paw) and the NO scavenger haemoglobin (Hb, 30 mumol/paw), but unaffected by the inhibitor of the soluble guanylate cyclase, methylene blue (Mb, 3 mumol/paw) and L-arginine (15 mumol/paw). 3. The NO-donors (10 mumol/paw) 3-morpholino-sydnonimine-hydrochloride (SIN-1), S-nitroso-N-acetyl-D, L-penicillamine (SNAP) and sodium nitroprusside (SNP) significantly potentiated the paw oedema induced by AA (300 nmol/paw). 4. SIN-1 (2.5, 5 and 10 mumol/paw) produced a significant dose-dependent increase of the oedema induced by AA which was correlated with increased amounts of 6-keto-PGF1 alpha in the fluid recovered from inflamed paws. 5. Both oedema and prostaglandin biosynthesis induced by the combination AA+SIN-1 were greatly suppressed by either Hb (30 mumol/paw) or indomethacin (3 mumol/paw or 5 mg kg-1 s.c.) but unaffected by Mb (3 mumol/paw). 6. In LPS-treated rats (6 mg kg-1, i.p.) doses of AA inactive in normal animals produced a remarkable oedema which was reduced by L-NAME or Hb, unaffected by Mb and increased by L-arginine.7. These results demonstrate that NO increases prostaglandin biosynthesis in vivo through a guanosine 3': 5'-cyclic monophosphate (cyclic GMP)-independent mechanism and suggest that the interaction between NO synthase and cyclo-oxygenase (COX) pathways may represent an important mechanism for the modulation of the inflammatory response.

Topics: 6-Ketoprostaglandin F1 alpha; Amino Acid Oxidoreductases; Animals; Arachidonic Acid; Arginine; Capillary Permeability; Edema; Epoprostenol; Lipopolysaccharides; Male; Methylene Blue; Molsidomine; NG-Nitroarginine Methyl Ester; Nitric Oxide; Nitric Oxide Synthase; Prostaglandin-Endoperoxide Synthases; Prostaglandins; Rats; Rats, Wistar; Vasodilator Agents

1. The effect of purified crotapotin, a non-toxic non-enzymatic chaperon protein normally complexed to a phospholipase A2 (PLA2) in South America rattlesnake venom, was studied in the acute inflammatory response induced by carrageenin (1 mg/paw), compound 48/80 (3 micrograms/paw) and 5-hydroxytryptamine (5-HT) (3 micrograms/paw) in the rat hind-paw. The effects of crotapotin on platelet aggregation, mast cell degranulation and eicosanoid release from guinea-pig isolated lung were also investigated. 2. Subplantar co-injection of crotapotin (1 and 10 micrograms/paw) with carrageenin or injection of crotapotin (10 micrograms/paw) into the contralateral paw significantly inhibited the carrageenin-induced oedema. This inhibition was also observed when crotapotin (10-30 micrograms/paw) was administered either intraperitoneally or orally. Subplantar injection of heated crotapotin (15 min at 60 degrees C) failed to inhibit carrageenin-induced oedema. Subplantar injection of crotapotin (10 micrograms/paw) also significantly inhibited the rat paw oedema induced by compound 48/80, but it did not affect 5-HT-induced oedema. 3. In adrenalectomized animals, subplantar injection of crotapotin markedly inhibited the oedema induced by carrageenin. The inhibitory effect of crotapotin was also observed in rats depleted of histamine and 5-HT stores. 4. Crotapotin (30 micrograms/paw) had no effect on either the histamine release induced by compound 48/80 in vitro or on the platelet aggregation induced by both arachidonic acid (1 nM) and platelet activating factor (1 microM) in human platelet-rich plasma. The platelet aggregation and thromboxane B2 (TXB2) release induced by thrombin (100 mu ml-1) in washed human platelets were also not affected by crotapotin. In addition, crotapotin (10 microg/paw) did not affect the release of 6-oxo-prostaglandin Fla, and TXB2 induced by ovalbumin in sensitized guinea-pig isolated lungs.5. Our results indicate that the anti-inflammatory activity of crotapotin is not due to endogenous corticosteroid release or inhibition of cyclo-oxygenase activity. It is possible that crotapotin may interact with extracellular PLA2 generated during the inflammatory process thereby reducing its hydrolytic activity.

Topics: 6-Ketoprostaglandin F1 alpha; Administration, Oral; Animals; Arachidonic Acid; Carrageenan; Cell Degranulation; Crotoxin; Disease Models, Animal; Edema; Guinea Pigs; Histamine Release; Humans; Injections, Intraperitoneal; Male; Mast Cells; p-Methoxy-N-methylphenethylamine; Phospholipases A; Phospholipases A2; Platelet Activating Factor; Platelet Aggregation; Rats; Rats, Wistar; Serotonin; Thromboxane B2

Many nonsteroidal antiinflammatory drugs have the ability to cause gastrointestinal damage in both animals and man. The aim of the present study was to compare nabumetone, a nonacidic drug, with etodolac on rat gastric mucosal damage and prostanoid synthesis, while concurrently measuring prostanoid production during edema formation in a carrageenan model of paw inflammation. The results showed that both drugs inhibited paw exudate prostaglandin E2 and edema significantly, but they did not inhibit gastric prostanoid production 4 hr after dosing. Gastric damage, however, was observed with etodolac. Additional time-course studies showed that over a 4-hr period, etodolac, unlike nabumetone, markedly inhibited gastric mucosal prostaglandin E2 production, which was associated with gastric erosion formation. Further studies demonstrated that nabumetone did not induce gastrointestinal damage or blood loss when administered to rats in a high antiinflammatory oral dose. In contrast, etodolac produced marked gastrointestinal damage and bleeding, which was evident for up to 48 hr after the dose. It is suggested that nabumetone's favorable gastrointestinal irritancy profile may relate, in part, to its nonacidic nature and to its differential effects on prostanoid production.

Topics: 6-Ketoprostaglandin F1 alpha; Animals; Anti-Inflammatory Agents, Non-Steroidal; Butanones; Cecum; Depression, Chemical; Dinoprostone; Edema; Etodolac; Gastric Mucosa; Gastrointestinal Hemorrhage; Haptoglobins; Hemoglobins; Intestinal Mucosa; Male; Nabumetone; Rats; Rats, Wistar

The anti-inflammatory effects of Ph CL28A, a potentiator of prostacyclin output and inhibitor of leukotriene (LT) synthesis, were assessed in two models of acute inflammation. In paw oedema induced by carrageenan in rats, Ph CL28A (10-100 mg/kg), given i.p. at the same time as the carrageenan, inhibited oedema for up to 4 h. When indomethacin or Ph CL28A was given locally into the paw with carrageenan, indomethacin inhibited oedema formation but Ph CL28A potentiated the oedema for up to 4 h. As Ph CL28A does not inhibit cyclo-oxygenase, its anti-inflammatory effects in this model may reflect its ability to increase prostacyclin output. In pleurisy induced by carrageenan in rats, there were increases in leukocytes, LTB4, thromboxane B2 (TxB2) and 6-oxo-prostaglandin F1 alpha (6-oxo-PGF1 alpha) in the pleural fluid over 3 h. In this model, Ph CL28A (30 mg/kg) given i.p. decreased leukocyte numbers and LTB4 but did not affect TxB2 or 6-oxo-PGF1 alpha. Indomethacin decreased both prostanoids but did not affect leukocyte accumulation. The beneficial effects of Ph CL28A in two different models of acute inflammation suggests that it may have potential as an anti-inflammatory agent.

Topics: 6-Ketoprostaglandin F1 alpha; Animals; Anti-Inflammatory Agents, Non-Steroidal; Azo Compounds; Blood Pressure; Carrageenan; Edema; Epoprostenol; Hydroxyprostaglandin Dehydrogenases; Indomethacin; Leukotriene B4; Male; Pleurisy; Radioimmunoassay; Rats; Rats, Wistar; Thromboxane B2

Interleukin-2 (IL-2) produces toxicity characterized by generalized edema within 24 hours. This study tests whether the rate of IL-2 administration modulates the onset of edema and examines thromboxane (Tx) and neutrophils as possible mediators of this event. Recombinant human IL-2, 10(5) U (n = 7), 10(6) U (n = 9), or vehicle (n = 8) were given to anesthetized rats intravenously during a period of 1 hour. At 6 hours edema, as measured by increase in wet to dry weight (w/d) ratio, was present in the heart, liver, and kidney, with 10(5) U IL-2 and in the lung, heart, liver and kidney, with 10(6) U IL-2, relative to values with vehicle-infused controls (all p less than 0.05). With a 1-hour infusion of 10(6) U IL-2, there was an increase in plasma thromboxane (Tx)B2 level to 1290 +/- 245 pg/mL, higher than 481 +/- 93 pg/mL in control rats (p less than 0.05); lung polymorphonuclear leukocyte (PMN) sequestration of 53 +/- 7 PMN/10 higher-power fields (HPF) relative to 23 +/- 2 PMN/10 HPF in controls (p less than 0.05); and increased bronchoalveolar lavage (BAL) fluid protein concentration of 1970 +/- 210 micrograms/mL relative to 460 micrograms/mL in controls (p less than 0.05). When 10(6) U IL-2 was given as a 1-minute intravenous bolus (n = 9), edema was not demonstrated, plasma TxB2 levels were similar to controls, there was no leukosequestration, and BAL protein levels were normal. These data indicate that a constant infusion but not the rapid bolus administration of IL-2 produces in rats multiple-system organ edema, increased plasma TxB2, sequestration of PMNs, and microvascular permeability. These findings may explain the early toxicity seen in patients given high-dose IL-2 in cancer treatment.

Topics: 6-Ketoprostaglandin F1 alpha; Animals; Bronchoalveolar Lavage Fluid; Edema; Heart Diseases; Infusions, Intravenous; Injections, Intravenous; Interleukin-2; Kidney Diseases; Liver Diseases; Male; Neutrophils; Pulmonary Edema; Rats; Rats, Inbred Strains; Recombinant Proteins; Thromboxane A2; Thromboxane B2

Thromboxane A2 production is increased early after burn. We studied the effect of inhibiting thromboxane synthetase, using dazmegrel, on postburn hemodynamic stability and edema formation, the latter monitored by burn tissue lymph flow. Dazmegrel (3.4 mg/kg) was given to six anesthetized sheep, and a 40% of total-body-surface third-degree burn was produced. Lactated Ringer's solution was infused at a rate to restore filling pressures during a 12-hour study period. Data were compared to burn alone (n = 8), anesthesia alone (n = 6), and dazmegrel alone (n = 5) groups. The latter two groups showed no physiologic changes. Dazmegrel pretreatment prevented increased thromboxane A2, measured as thromboxane B2, but resulted in a significant increase in plasma prostacyclin, measured as 6-keto-PGF1 alpha. In addition, a marked vasodilatation and decrease in systemic vascular resistance were noted, as well as a 30% increase in fluid requirements and an increase in lymph flow compared with burn alone. The increase in prostacyclin more than likely accentuated the burn-induced permeability change. Of interest was that oxygen consumption was better maintained with dazmegrel postburn, even with the relative hypovolemia, indicating that postburn vasoconstriction impairs adequate O2 delivery to tissues and that thromboxane synthetase inhibition attenuates this process.

Topics: 6-Ketoprostaglandin F1 alpha; Animals; Blood Flow Velocity; Blood Volume; Burns; Cardiac Output; Disease Models, Animal; Edema; Hemodynamics; Imidazoles; Lymph; Oxygen Consumption; Sheep; Skin Diseases; Thromboxane-A Synthase; Vascular Resistance; Vasodilation

Edema formation and prostanoid production (prostaglandin E2 (PGE2), thromboxane B2 (TXB2), and 6-keto-prostaglandin F1 alpha (6-keto-PGF1 alpha) were studied in a model of neoplastic epidural cord compression (NSCC) in rats harboring a thoracolumbar tumor. Tumor-free and tumor-bearing animals were randomized for three treatments at 12-hour intervals with saline, dexamethasone (10 mg/kg i.p.), or indomethacin (10 mg/kg i.p.). Increase in water content was observed only in the compressed lumbar cord segments of paralyzed rats; the cervical and thoracic segments did not differ from controls. The rate of release of prostaglandins was evenly distributed along the spinal segments in tumor-free rats. In tumor-bearing rats, a consistent significant increase in PGE2 production was found in the compressed lumbar segment in the presence of neurological dysfunction: early (limp tail), P less than 0.05; paraplegia, P less than 0.001. A significantly elevated PGE2 synthesis preceded the increase in water content by 2 to 3 days. A 2-fold increase in TXB2 was detected in only one of three experiments, and synthesis of 6-keto-PGF1 alpha was elevated to 4 times the normal value (P less than 0.005) in two of three experiments. Dexamethasone failed to inhibit prostaglandin synthesis in the spinal cord of normal controls or paralyzed rats, whereas in nonneural tissues (liver, uterus) it reduced synthesis of the three metabolites by at least 50%, thus demonstrating a differential effect on central nervous system (CNS) vs. non-CNS tissues. Dexamethasone also failed to reduce the increased water content of the compressed segments.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: 6-Ketoprostaglandin F1 alpha; Animals; Body Water; Dexamethasone; Dinoprostone; Edema; Indomethacin; Prostaglandins; Prostaglandins E; Rats; Rats, Inbred F344; Spinal Cord; Spinal Cord Compression; Spinal Cord Neoplasms; Thromboxane B2

Eicosanoids are known mediators of inflammation, vascular permeability, and are involved in microcirculatory blood flow regulation. To study their potential involvement in the pathophysiology of CNS trauma we used a rabbit spinal cord trauma model. Rabbits were subjected to lumbar spinal cord trauma produced by a modification of the Allen weight-drop method. TXB2, 6-keto-PGF1 alpha, PGE2, and 5-hydroxyeicosatetraenoic acid (5-HETE) release from spinal cord slices incubated ex vivo were measured by radioimmunoassay at 5, 30 min, 24 hrs, and 2 wks after trauma. Five and 30 min after trauma the TXB2/6-keto-PGF1 alpha ratio was elevated and the release of 5-HETE at 5 min after trauma increased in the injured spinal cord whereas release of 6-keto-PGF1 alpha and PGE2 remained at base-line levels. In the thoracic spinal cord, TXB2 and 6-keto-PGF1 alpha release were increased at 30 min after trauma. Release of 5-HETE from the injured spinal cord was also elevated 24 hrs after trauma. Two wks after trauma, TXB2 and 6-keto-PGF1 alpha release were also elevated in the injured spinal cord. Measurements of tissue water content by microgravimetry indicated progressive edema in the injury site while histopathological evaluation indicated progressive damage and tissue destruction. The results of this study suggest that eicosanoids may be involved in the pathophysiology of spinal cord trauma through two potential mechanisms: 1) site specific increase in the TXB2/6-keto-PGF1 alpha ratio immediately following trauma which is due primarily to an increase in TXA2 synthesis; 2) the increase synthesis of 5-HETE which signals the activation of the 5-lipoxygenase pathway of arachidonate metabolism and production of mediators that are involved in inflammatory mechanisms and may affect local blood flow regulation and blood-spinal cord barrier integrity.

Topics: 6-Ketoprostaglandin F1 alpha; Animals; Culture Techniques; Dinoprostone; Edema; Hydroxyeicosatetraenoic Acids; Male; Prostaglandins E; Rabbits; Spinal Cord; Spinal Cord Injuries; Thromboxane B2

We determined the effect of topically applied ibuprofen on formation of second-degree burn edema and prostanoid production, a possible causative factor. Six adult sheep were given second-degree burns on both flanks with water at 80 degrees C while they were under general anesthesia. Lymph (QL), draining the flank areas, was used to monitor edema formation and prostanoid production. A 5% ibuprofen cream was applied at 2 and 5 hours after the burn and full-thickness biopsy specimens of burned hide were obtained at 8 hours for determination of water content. The QL increased sixfold in nontreated and 2.5 times in treated burn tissue. The lymph/plasma (L/P) protein ratio increased from 0.4 to 0.58 in both sides. Lymph TxB2 was increased from baseline of 200 pg/ml to 500 +/- 100 and 310 +/- 90 pg/ml in untreated and treated sides, respectively. Lymph 6-keto-PGF1 alpha increased from a baseline of 50 +/- 10 to 150 +/- 40 and 90 +/- 80 pg/ml in untreated and treated sides. The difference between PG content of lymph in treated and untreated sides was significant. Plasma prostanoids, except for a transient early rise, remained at preburn baseline. Lymph ibuprofen content on the treated side rose to 1.9 +/- 0.8 mcg/ml with no detectable plasma level. Water content of hide increased from a control value of 74 +/- 2% to 84 +/- 2% in untreated burn, while the value in the treated side was 76 +/- 4%, a significant difference between the two sides. We conclude that topically applied ibuprofen decreases both local edema and prostanoid production in burn tissue without altering systemic production.

Topics: 6-Ketoprostaglandin F1 alpha; Administration, Topical; Animals; Burns; Edema; Ibuprofen; Lymph; Prostaglandin Antagonists; Prostaglandins; Sheep; Thromboxane B2

An increased accumulation of tissue thromboxane A2 occurred shortly after spinal cord injury. Prostacyclin formation was not affected. The magnitude of the increase in thromboxane and the extent of post-traumatic vascular damage as determined by extravasation of 125I-labeled human serum albumin were both dependent on the degree of injury. These findings raise the possibility that activation of arachidonic acid metabolism with a preponderance in thromboxane formation may contribute to microvascular injury in experimental spinal cord contusion.

Topics: 6-Ketoprostaglandin F1 alpha; Animals; Blood Vessels; Edema; Epoprostenol; Rats; Rats, Inbred Strains; Spinal Cord; Spinal Cord Injuries; Thromboxane A2; Thromboxane B2

Topics: 6-Ketoprostaglandin F1 alpha; Animals; Blood Platelets; Edema; Lung; Male; Platelet Activating Factor; Pulmonary Circulation; Rats; Rats, Inbred Strains; SRS-A; Vasoconstriction

To examine the possibility that prostaglandin metabolism is pathophysiologically important in Raynaud's phenomenon, peripheral venous 6-keto prostaglandin F1 alpha (6-keto PGF1 alpha) and thromboxane B2 (TXB2) concentrations were measured in 45 patients with severe Raynaud's phenomenon. Patients with Raynaud's phenomenon had a significantly higher plasma concentration of 6-keto PGF1 alpha compared to controls (p less than .001), although their plasma TXB2 concentration was not statistically different from control patients. Subgroup analysis revealed that only patients with progressive systemic sclerosis (PSS) had an elevated plasma 6-keto PGF1 alpha concentration. To gauge the functional significance of the 6-keto PGF1 alpha elevations, seven patients with Raynaud's phenomenon were chronically administered indomethacin (50 mg P.O. b.i.d.); six of the seven patients noted no improvement in their Raynaud's phenomenon. Three of the patients developed pedal edema shortly after starting indomethacin. This study suggests that the increased plasma 6-keto PGF1 alpha concentration in Raynaud's phenomenon may be due to a compensatory release of prostacyclin and that the pathophysiologic defect does not involve the thromboxane mechanism.

Topics: 6-Ketoprostaglandin F1 alpha; Adult; Aged; Edema; Female; Humans; Indomethacin; Male; Middle Aged; Raynaud Disease; Thromboxane B2