6-ketoprostaglandin-f1-alpha and Hypotension

This study aimed to reveal the appropriate timing for the intravenous administration of flurbiprofen axetil for preventing mesenteric traction syndrome (MTS), caused by prostacyclin release.. In this prospective, randomized, clinical study, forty-five patients who were undergoing elective surgery for colorectal cancer via laparotomy were enrolled. Patients were randomly divided into 3 groups: a preoperative group (n = 16) receiving flurbiprofen axetil directly before surgery; a post-MTS group (n = 14) receiving following MTS onset; and a control group (n = 15) who were not administered flurbiprofen axetil. 6-keto-PGF1α, a stable metabolite of prostacyclin, levels were measured and mean blood pressures were recorded.. In the preoperative group, 6-keto-PGF1α levels did not increase, blood pressure levels did not decrease, and no facial flushing was observed. In both the post-MTS and control groups, 6-keto-PGF1α levels increased markedly after mesenteric traction and blood pressure decreased significantly. The post-MTS group exhibited a faster decreasing trend in 6-keto-PGF1α levels and quick restore of the mean blood pressure, and the use of vasopressors and phenylephrine were lower than that in the control group.. Even therapeutic administration of flurbiprofen axetil after the onset of MTS has also effects on MTS by suppressing prostacyclin production.. Clinical trial number: UMIN000009111 . (Registered 14 October 2012).

Topics: 6-Ketoprostaglandin F1 alpha; Aged; Anti-Inflammatory Agents, Non-Steroidal; Blood Pressure; Colorectal Neoplasms; Epoprostenol; Female; Flurbiprofen; Flushing; Hemodynamics; Humans; Hypotension; Infusions, Intravenous; Intraoperative Complications; Laparotomy; Male; Middle Aged; Prospective Studies; Syndrome; Tachycardia

Mesenteric traction syndrome (MTS) is caused by PGI(2) release during abdominal procedures and is often observed during abdominal surgery. We have demonstrated that MTS occurs more frequently in cases using remifentanil than in those that are not. The aim of this study was to assess the prophylactic benefit of flurbiprofen axetil on MTS in patients undergoing abdominal surgery using remifentanil.. Thirty ASA physical status I and II patients were enrolled. They were scheduled to undergo abdominal surgery under general anesthesia with remifentanil and were randomly assigned to receive flurbiprofen axetil (group F) or saline (group C) preoperatively (n = 15 each). MTS was defined according to our simplified diagnostic criteria. Arterial blood pressure and heart rate were recorded, and the plasma 6-keto-PGF(1α) (a stable metabolite of PGI(2)) concentration was measured just before skin incision and at 20 and 60 min after skin incision (T(0), T(20), T(60)) to confirm the diagnosis of MTS.. Twelve of 15 (80%) patients developed MTS in group C, whereas only 1 of 15 (6.7%) patients in group F developed MTS. At T(20), the group C patients showed significantly lower arterial blood pressure (P < 0.05) and a faster heart rate (P < 0.01) than those in group F. The mean plasma 6-keto-PGF(1α) concentration was significantly elevated in group C at T(20) (P < 0.01), whereas the plasma 6-keto-PGF(1α) level remained low throughout the observation period in group F.. We found that preoperative administration of flurbiprofen axetil reduced the incidence of MTS during abdominal surgery with remifentanil analgesia.

Topics: 6-Ketoprostaglandin F1 alpha; Abdomen; Aged; Anesthesia, General; Anesthetics, Intravenous; Anti-Inflammatory Agents, Non-Steroidal; Double-Blind Method; Epoprostenol; Female; Flurbiprofen; Humans; Hypnotics and Sedatives; Hypotension; Infusions, Intravenous; Laparotomy; Male; Midazolam; Middle Aged; Piperidines; Postoperative Complications; Preanesthetic Medication; Prospective Studies; Remifentanil; Splanchnic Circulation

The use of remifentanil is often associated with the observation of mesenteric traction syndrome (MTS) soon after manipulation of the intestine during abdominal surgery. MTS symptoms include facial flushing, hypotension, and tachycardia. In the study reported here, we prospectively investigated the effects of remifentanil on the incidence of MTS in abdominal surgery.. One hundred patients scheduled for abdominal surgery were randomly assigned to two groups. In one group (n = 50), fentanyl alone was used as intravenous analgesic (control, group C); in the second group (n = 50), both fentanyl and remifentanil were used (remifentanil group, group R). In all patients, anesthesia was induced with propofol and rocuronium and then maintained with sevoflurane inhalation. Remifentanil was continuously infused for patients in group R as an analgesic. Plasma concentration of 6-keto-PGF(1α) was measured before surgery and 20 min after the skin incision was made in six patients of group R and seven patients of group C.. MTS occurred in 20 cases in group R (40.0%), but in only five cases in group C (10.0%). In both groups, the incidence of MTS was higher in laparotomy than in laparoscopic surgery. The plasma concentration of 6-keto-PGF(1α) was low in both groups before surgery and was elevated 20 min after skin incision in both groups in patients in whom MTS appeared.. The results of this study suggest that the use of remifentanil in laparotomy facilitates MTS.

Topics: 6-Ketoprostaglandin F1 alpha; Abdomen; Aged; Anesthesia Recovery Period; Anesthesia, General; Anesthetics, Intravenous; Flushing; Hemodynamics; Humans; Hypotension; Intraoperative Complications; Laparotomy; Mesentery; Middle Aged; Piperidines; Prospective Studies; Remifentanil; Splanchnic Circulation; Syndrome; Tachycardia

Our study aimed to determine the role of cyclooxygenase-2 in the release of prostaglandin-(PG)-I2 following mesenteric traction during abdominal surgery. In a prospective double-blind, randomized, placebo-controlled study, 40 patients electively scheduled for non-laparoscopic abdominal surgery, were pretreated with the cyclooxygenase-2 inhibitor parecoxib (n=20) or placebo (n=20). Heart rate, arterial blood pressure, oxygenation ratio and plasma concentrations of the stable PGI2-metabolite 6-keto-PGF1alpha were compared between groups before injection of parecoxib (-40 min), immediately before mesenteric traction (0 min), and 5, 10, and 30 min thereafter. In addition, plasma concentrations of valdecoxib, the active metabolite of the prodrug parecoxib, were determined. Plasma concentrations of 6-keto-PGF1alpha and heart rate increased in both groups after mesenteric traction. There were no significant differences between groups at individual times in heart rate, arterial blood pressure and plasma concentrations of 6-keto-PGF1alpha. Oxygenation ratio decreased after 10 and 30 min following mesenteric traction in the parecoxib group with a significant difference between treatment groups at 10 and 30 min. Plasma concentrations of valdecoxib revealed therapeutic values. Our data indicate that PGI2 release following mesenteric traction is mediated by cyclooxygenase-1.

Topics: 6-Ketoprostaglandin F1 alpha; Abdomen; Blood Pressure; Cyclooxygenase 1; Cyclooxygenase 2 Inhibitors; Double-Blind Method; Epoprostenol; Female; Flushing; Heart Rate; Humans; Hypotension; Intraoperative Complications; Isoxazoles; Laparoscopy; Male; Middle Aged; Oxygen; Prospective Studies; Sulfonamides; Surgical Procedures, Operative; Tachycardia; Time Factors; Treatment Outcome

Topics: 6-Ketoprostaglandin F1 alpha; Animals; Arterial Pressure; Cyclooxygenase 2; Epoprostenol; Gene Expression Regulation, Enzymologic; Heart Rate; Hypotension; I-kappa B Proteins; Inflammation; Lipopolysaccharides; Male; Nitric Oxide; Nitric Oxide Synthase Type II; Peroxidase; Peroxynitrous Acid; Rats; Rats, Wistar; Ribosomal Protein S6; Signal Transduction; TOR Serine-Threonine Kinases; Transcription Factor RelA; Tumor Necrosis Factor-alpha; Tyrosine

We attempted to determine whether activation of the sensory neuron contributes to reduction of endotoxin-induced hypotension by inhibiting tumor necrosis factor (TNF)-alpha production via calcitonin gene-related peptide (CGRP) release in rats.. Prospective, randomized, controlled study.. Research laboratory at a university medical center.. Wistar rats weighing 220-280 g.. Mean arterial blood pressure was measured in rats administered endotoxin intravenously. Animals were pretreated with capsazepine (a vanilloid receptor antagonist), CGRP(8-37) (a CGRP receptor antagonist), and indomethacin before endotoxin administration. Levels of CGRP, 6-keto-prostaglandin F1alpha, TNF-alpha, and cytokine-induced neutrophil chemoattractant (CINC) were measured by enzyme immunoassay methods. The concentration of NO2/NO3 was measured using the Griess reagent. Tissue levels of messenger RNA of the inducible form of nitric oxide synthase (iNOS) and TNF-alpha were determined by reverse transcription polymerase chain reaction.. Both lung levels of CGRP and plasma levels of 6-keto-prostaglandin F1alpha were increased after intravenous administration of endotoxin (5 mg/kg), peaking at 90 mins after endotoxin administration. Increases in plasma levels of 6-keto-prostaglandin F1alpha at 90 mins after endotoxin administration (766 +/- 134 pg/mL) were inhibited by pretreatment with capsazepine (373 +/- 44 pg/mL, p < .05), CGRP(8-37) (406 +/- 64 pg/mL, p < .05), and indomethacin (154 +/- 40 pg/mL, p < .05). Although none of the pretreatments affected a series of endotoxin-induced responses, including increases in lung tissue levels of TNF-alpha, CINC, and iNOS and the resultant hypotension in animals given 5 mg/kg endotoxin, such pretreatments enhanced these pathologic responses in animals given a smaller dose of endotoxin (1 mg/kg) to the same extent as those induced by 5 mg/kg of endotoxin, suggesting that shock responses induced by 5 mg/kg endotoxin are maximum responses and activation of sensory neurons in endotoxin-treated rats is essentially a reparative response.. Activation of sensory neurons might contribute to reduction of endotoxin-induced hypotension by releasing CGRP, which is capable of promoting endothelial production of prostacyclin.

Topics: 6-Ketoprostaglandin F1 alpha; Animals; Blood Pressure; Calcitonin Gene-Related Peptide; Capsaicin; Cyclooxygenase Inhibitors; Disease Models, Animal; Dose-Response Relationship, Drug; Endotoxins; Hypotension; Iloprost; Indomethacin; Interleukin-16; Lung; Neurons, Afferent; Nitric Oxide Synthase; Prospective Studies; Rats; Rats, Wistar; Reference Values; Tumor Necrosis Factor-alpha; Vasodilator Agents

Impairment in cardiovascular functions sometimes manifested in astronauts during standing postflight, may be related to the diminished autonomic function and/or excessive production of endothelium-dependent relaxing factors. In the present study, using the 30 degrees head-down tilt (HDT) model, we compared the cardiovascular and biochemical effects of 7 days of suspension and a subsequent 6-h post-suspension period between suspended and non-suspended conscious female Sprague-Dawley rats. Mean arterial pressure (MAP) and heart rate were measured prior to suspension (basal), daily thereafter, and every 2h post-suspension. Following 7 days of suspension, MAP was not different from their basal values, however, upon release from suspension, MAP was significantly reduced compared to the non-suspended rats. Nitric oxide levels were elevated while thromboxane A(2) levels declined significantly in both plasma and tissue samples following post-suspension. The levels of prostacyclin following post-suspension remained unaltered in plasma and aortic rings but was significantly elevated in carotid arterial rings. Therefore, the post-suspension reduction in mean arterial pressure is due mostly to overproduction of nitric oxide and to a lesser extent prostacyclin.

Topics: 6-Ketoprostaglandin F1 alpha; Animals; Aorta, Thoracic; Blood Pressure; Carotid Arteries; Epoprostenol; Female; Heart Rate; Humans; Hypotension; In Vitro Techniques; Nitric Oxide; Prostaglandins; Rats; Rats, Sprague-Dawley; Space Simulation; Thromboxane A2; Thromboxane B2; Weightlessness; Weightlessness Simulation

Renal function in the fetus is important for maintenance of fetal fluid and electrolyte balance. This study was performed to test the role of prostaglandins and their interaction with arterial baroreceptors and chemoreceptors in the control of renal cortical blood flow during hypotension produced by vena caval obstruction in late-gestation fetal sheep. We studied 18 time-dated, chronically catheterized, fetal sheep (124-136 days gestation). Fetuses were either studied intact (n = 11) or sinoaortic denervated (n = 7), and each fetus was studied twice, with and without pretreatment with indomethacin (0.2 mg kg(-1), i.v.). Each fetus was subjected to hypotension caused by vena caval obstruction for 10 min. Before hypotension, renal cortical blood flow was higher in the vehicle-treated sinoaortic denervated fetuses than in vehicle-treated intact fetuses. The increased renal cortical blood flow observed in the sinoaortic denervated fetuses was counteracted by indomethacin, so that the difference between sinoaortic denervated and intact fetuses was eliminated after indomethacin treatment. Hypotension decreased renal blood flow equally in all groups. Plasma renin activity was increased in response to hypotension in the intact fetuses, but not in the sinoaortic denervated fetuses. Indomethacin treatment, by itself, did not alter plasma renin activity. It is concluded that both arterial baroreceptors and prostanoids influence renal blood flow. Further, renin secretion is influenced by arterial baroreceptors and chemoreceptors and there is no apparent modulatory effect of prostanoids on the baroreflex control of renin secretion.

Topics: 6-Ketoprostaglandin F1 alpha; Animals; Anti-Inflammatory Agents, Non-Steroidal; Catheterization; Denervation; Dinoprostone; Fetal Blood; Gestational Age; Hypotension; Indomethacin; Kidney Cortex; Kinetics; Pressoreceptors; Prostaglandins; Renin; Sheep; Sinus of Valsalva; Thromboxane A2; Venae Cavae

1. Endotoxaemia is associated with the expression of the inducible isoform of cyclo-oxygenase, cyclo-oxygenase-2 (COX-2), and an overproduction of arachidonic acid (AA) metabolites. The role of the AA metabolites generated by COX-2 in the circulatory failure and multiple organ dysfunction caused by endotoxin is unclear. Dexamethasone prevents the expression of COX-2 and exerts beneficial effects in animal models of shock. 2. Here we compare the effects of two inhibitors of COX-2 activity, namely NS-398 (5 mg kg(-1), i.p., n=7) and SC-58635 (3 mg kg(-1), i.p., n=9) with those of dexamethasone (3 mg kg(-1), i.p., n=9) on the circulatory failure and organ dysfunction caused by lipopolysaccharide (LPS, E. coli, 6 mg kg(-1), i.v., n=11) in the rat. 3. Endotoxaemia for 6 h caused hypotension, acute renal dysfunction, hepatocellular injury, pancreatic injury and an increase in the plasma levels of 6-keto-PGF1alpha (indicator of the induction of COX-2) and nitrite/nitrate (indicator of the induction of iNOS). 4. Pretreatment of rats with dexamethasone attenuated the hypotension, the renal dysfunction, the hepatocellular and pancreatic injury and the induction of COX-2 and iNOS caused by LPS. In contrast, inhibition of COX-2 activity with SC-58635 or NS-398 neither attenuated the circulatory failure nor the multiple organ failure caused by endotoxin. 5. Thus, the prevention of the circulatory failure and the multiple organ injury/dysfunction caused by dexamethasone in the rat is not due to inhibition of the activity of COX-2. Our results suggest that an enhanced formation of eicosanoids by COX-2 does not contribute to the development of organ injury and/or dysfunction in rats with endotoxaemia.

Topics: 6-Ketoprostaglandin F1 alpha; Animals; Celecoxib; Cyclooxygenase 2; Cyclooxygenase 2 Inhibitors; Cyclooxygenase Inhibitors; Dexamethasone; Endotoxemia; Endotoxins; Hypotension; Isoenzymes; Male; Multiple Organ Failure; Nitrates; Nitrites; Nitrobenzenes; Prostaglandin-Endoperoxide Synthases; Pyrazoles; Rats; Sulfonamides

This study was designed to examine haemodynamic and haematologic effects of the crown-of-thorns starfish venom (Acanthaster planci venom: APV) in dogs. Severe systemic hypotension, thrombocytopenia and leukopenia were induced by APV (1.0 mg protein/kg i.v.), followed by gradual return to the baseline level within 60 min. Hypotension was presumably caused by two factors: an early decrease in systemic vascular resistance and the large reduction in cardiac output due to reduced ventricular filling. Indomethacin, a cyclooxygenase inhibitor, remarkably suppressed systemic hypotension induced by APV. The peak reduction in systemic pressure was associated with concomitant rise of plasma 6-keto-PGF1 alpha, a major stable metabolite of prostacyclin. Thus, the hypotensive effect of APV may be caused primarily by prostacyclin and/or some vasodilating prostaglandins. In contrast, thrombocytopenia and leukopenia were not affected by cyclooxygenase inhibitor, 5-lipoxygenase inhibitor or platelet activating factor (PAF) receptor antagonist. When APV was administered repeatedly, tachyphylaxis was developed in haemodynamic effects, but not in haematologic effects. These findings suggest that APV-induced hypotensive effects may occur mainly through endogenous production of vasodilating prostaglandins including prostacyclin, although APV-induced thrombocytopenia and leukopenia may be caused by other mechanism(s) unrelated to arachidonate metabolites and/or PAF.

Topics: 6-Ketoprostaglandin F1 alpha; Animals; Blood Cells; Blood Pressure; Cardiac Output; Cyclooxygenase Inhibitors; Dogs; Dose-Response Relationship, Drug; Female; Hemodynamics; Hypotension; Indomethacin; Injections, Intravenous; Leukopenia; Lipoxygenase Inhibitors; Male; Platelet Activating Factor; Starfish; Tachyphylaxis; Thrombocytopenia; Vascular Resistance; Venoms

Piglet brains generate superoxide during postischemic reperfusion, and topical application of activated oxygen species alters pial arteriolar responses. We investigated effects of pretreatment with scavengers of superoxide and H2O2 on ischemia-induced alterations of pial arteriolar responses in anesthetized newborn pigs. Four groups were studied: 1) time control, 2) untreated ischemia, 3) ischemia pretreated topically and systemically (conjugated to polyethylene glycol) with superoxide dismutase (SOD) and catalase, and 4) ischemia pretreated with Tiron. Pretreatment with SOD conjugated to polyethylene glycol alone during postischemic reperfusion effectively removed superoxide from its site of generation during postischemic reperfusion, but topical SOD was used also an insurance. Piglets were studied before and after 20 min of total cerebral ischemia caused by maintaining intracranial pressure above mean arterial pressure. As reported previously, before ischemia, hypercapnia and isoproterenol dilated pial arteries and arterioles and hypercapnia but not isoproterenol increased cortical periarachnoid cerebrospinal fluid 6-keto-prostaglandin F1 alpha, measured as an index of cerebral cortical prostacyclin synthesis. After cerebral ischemia, pial arterioles did not dilate in response to hypercapnia and 6-keto-prostaglandin F1 alpha did not increase, but dilation to isoproterenol was unchanged. The present study found that treatment with SOD/catalase or Tiron did not prevent loss of vasodilation to hypercapnia or the loss of hypercapnia-induced cerebral 6-keto-prostaglandin F1 alpha synthesis after cerebral ischemia. The postischemic loss of cerebral vasodilation to hypercapnia does not appear to involve superoxide or a subsequent reduced form of oxygen.

Topics: 6-Ketoprostaglandin F1 alpha; Animals; Animals, Newborn; Brain Ischemia; Catalase; Cerebrovascular Circulation; Free Radical Scavengers; Hypercapnia; Hypotension; Isoproterenol; Superoxide Dismutase; Superoxides; Swine; Vasodilation

We observed previously that 20 min of global cerebral ischemia followed by 45 min of reperfusion selectively blocked cerebral vasodilation to hypercapnia and hypotension. This study determines the effects of pretreatment with transforming growth factor-beta (TGF-beta) on cerebrovascular responses after cerebral ischemia in piglets equipped with closed cranial windows. Hypercapnia-induced pial arteriolar dilation was blocked after cerebral ischemia (20 +/- 1 vs. 2 +/- 1% dilation before and after ischemia, respectively). Similarly, the increases in periarachnoid cortical cerebrospinal fluid 6-ketoprostaglandin F1 alpha (6-keto-PGF1 alpha) and prostaglandin E2 (PGE2) concentration in response to hypercapnia were blocked (2.5 +/- 0.2- vs. 0.2 +/- 0.4-fold and 2.1 +/- 0.1- vs. 0.3 +/- 0.4-fold increase in 6-keto-PGF1 alpha and PGE2, respectively). Treatment with topical TGF-beta (400 ng/ml) before and during ischemia-reperfusion attenuated the loss of hypercapnia-induced cerebrovascular dilation (20 +/- 1 vs. 14 +/- 1% dilation before and after ischemia, respectively) and the loss of associated changes in cerebrospinal fluid prostanoids (2.0 +/- 0.2- vs. 1.7 +/- 0.2-fold and 2.3 +/- 0.2- vs. 2.2 +/- 0.3-fold increase in 6-keto-PGF1 alpha and PGE2 before and after ischemia, respectively). The loss of cerebrovascular dilation in response to hemorrhagic hypotension after ischemia was similarly prevented by TGF-beta. Cerebrovascular dilation to topical isoproterenol was unchanged after ischemia. TGF-beta may preserve endothelial cell function. We conclude that topical TGF-beta can attenuate cerebromicrovascular compromise caused by ischemia-reperfusion in newborn pigs.

Topics: 6-Ketoprostaglandin F1 alpha; Animals; Animals, Newborn; Arterioles; Brain Ischemia; Cerebral Cortex; Cerebrovascular Circulation; Dinoprostone; Female; Hypercapnia; Hypotension; Isoproterenol; Male; Swine; Transforming Growth Factor beta; Vasodilation

In order to evaluate the role of prostacyclin in d-tubocurarine-induced hypotension in human, the authors examined the relationship of changes of arterial blood pressure and plasma 6-keto-PGF1 alpha level following iv administration of d-tubocurarine (dTc), with or without prior administration of aspirin and H1 antagonist. The bolus injection of dTc 0.6 mg/kg caused a significant decrease in mean arterial pressure (MAP) that was associated with a significant increase in plasma 6-keto-PGF1 alpha (P less than 0.05 in both). The maximum MAP decrease and plasma 6-keto-PGF1 alpha increase were noted at 2 min after dTc administration. Pretreatment with aspirin DL-lysine (25 mg/kg) or diphenhydramine (1 mg/kg) significantly attenuated the responses of MAP (P less than 0.05 in both) and plasma 6-keto-PGF1 alpha level (P less than 0.01 for aspirin group, P less than 0.05 for diphenhydramine group). There was a significant correlation between the changes in plasma 6-keto-PGF1 alpha and those in MAP (Kendall tau (tau) = -0.504, P less than 0.01). These findings suggest that a bolus injection of dTc induces a release of prostacyclin through H1 receptor, which is responsible for the dTc-induced transient decrease of blood pressure in humans.

Topics: 6-Ketoprostaglandin F1 alpha; Adult; Aspirin; Blood Pressure; Depression, Chemical; Diphenhydramine; Epoprostenol; Female; Heart Rate; Humans; Hypotension; Lysine; Male; Middle Aged; Stimulation, Chemical; Tubocurarine

Mesenteric traction syndrome consists of sudden tachycardia, hypotension, and cutaneous hyperemia, and frequently occurs during mesenteric traction in patients undergoing abdominal aortic aneurysm (AAA) reconstructive surgery. The etiology and clinical impact of this phenomenon are unknown, but the symptoms suggest a release of vasoactive materials from the mesenteric vascular bed. Thirty-one patients who underwent AAA surgery were studied. Mesenteric traction was accompanied by a decrease in systolic (p = 0.005) and diastolic (p less than 0.05) blood pressures, and in systemic vascular resistance (p less than 0.005), and was accompanied by an increase in heart rate (HR) (p less than 0.005), and cardiac output (p = 0.01). These hemodynamic changes coincided with an increase (p less than 0.001) in plasma concentrations of 6-keto-prostaglandin F1 (6-K-PGF1). No apparent change was found in prostaglandin E2, thromboxane B2, and histamine concentrations. The concentration of 6-K-PGF1 was correlated with diastolic blood pressure (r = -0.52, p less than 0.005) and HR (r = 0.65, p less than 0.001). Cutaneous hyperemia was observed in 58% of the patients. In an additional six patients, who had taken aspirin daily before AAA surgery, no significant changes were observed in the hemodynamic measurements or 6-K-PGF1 concentrations. These data suggest that mesenteric traction syndrome may be mediated at least in part by a selective release of prostacyclin.

Topics: 6-Ketoprostaglandin F1 alpha; Aged; Aged, 80 and over; Anesthesia, General; Aortic Aneurysm; Epoprostenol; Female; Flushing; Humans; Hypotension; Intraoperative Complications; Male; Mesenteric Arteries; Mesenteric Veins; Middle Aged; Syndrome; Tachycardia; Thromboxane B2

Effects of hypotensive hemorrhage on pial arteriolar diameter and cortical subarachnoid fluid prostanoid concentrations were investigated in newborn pigs. Chloralose-anesthetized piglets were equipped with closed cranial windows over the parietal cortex for observation of pial arterioles and collection of cerebrospinal fluid (CSF) passing over the cerebral surface (cortical subarachnoid CSF). Prostanoids in the CSF were determined by radioimmunoassay. Measurements of pial arterioles were made during normotension (63 +/- 4 mmHg) and hypotension (28 +/- 3 mmHg). Hypotension caused pial arteriolar diameters to increase from 162 +/- 22 to 193 +/- 22 microns. During normotension, the cortical subarachnoid prostanoid concentrations were (in ng/ml) prostaglandin E2 (PGE2) 2.6 +/- 0.7, 6-ketoprostaglandin F1 alpha (6-keto-PGF1 alpha) 1.7 +/- 0.4, thromboxane B2 (TXB2) 0.25 +/- 0.02. Hypotension caused 6-keto-PGF1 alpha to increase 245 +/- 104% and PGE2 to increase 132 +/- 38%. TXB2 increased slightly (37 +/- 21%). Topical application of PGE2 and prostacyclin caused marked dilation of pial arterioles. Treatment of hypotensive newborn pigs with indomethacin caused constriction of pial arterioles to diameters not significantly different from the normotensive diameters. These data are consistent with the hypothesis that the prostanoid system contributes to the maintenance of cerebral blood flow during hypotension in piglets.

Topics: 6-Ketoprostaglandin F1 alpha; Animals; Animals, Newborn; Arterioles; Cerebral Arteries; Cerebrovascular Circulation; Dinoprostone; Epoprostenol; Female; Hypotension; Indomethacin; Male; Prostaglandins; Prostaglandins E; Swine; Thromboxane B2; Vasodilation

The possibility that the prostanoid system contributes to the capability of the newborn piglet to maintain cerebral blood flow and cerebral metabolic rate during hypotension was investigated. The effect of hemorrhage on net (arterial-to-venous) cerebral prostacyclin production and the effects of indomethacin on cerebral hemodynamic response to hemorrhage and on the cerebral oxygen utilization following hemorrhage were determined in chronically instrumented, unanesthetized newborn pigs. Hemorrhage decreased arterial pressure about 35% but did not affect cerebral blood flow or cerebral O2 consumption. Hemorrhage was accompanied by an increase in net cerebral 6-keto-PGF1 alpha production from 4.0 +/- 1.1 to 15.3 +/- 4.9 ng/100g X min (mean +/- SEM). Indomethacin treatment of piglets following hemorrhage inhibited the net cerebral production of 6-keto-PGF1 alpha and caused a decrease in blood flow (approximately equal to 40%) to all brain regions within 20 minutes. The decrease in cerebral blood flow was the result of an increase in cerebral vascular resistance of 57 and 180%, 20 and 40 minutes post treatment, respectively. Cerebral O2 consumption was reduced from 2.5 +/- 0.3 ml/100 g X min to 1.5 +/- 0.3 ml/100 g X min 20 minutes following treatment of hemorrhaged piglets with indomethacin and to 1.1 +/- 0.3 ml/100 g X min 40 minutes after treatment. Six of 8 piglets for whom the data were recorded that were administered indomethacin following hemorrhage became comatose with cerebral O2 consumption of 0.4 +/- 0.1 ml O2/100 g X min by 40 minutes after treatment. These data are consistent with the hypothesis that the prostanoid system contributes to the maintenance of cerebral blood flow and cerebral metabolic rate during hypotension in the newborn.

Topics: 6-Ketoprostaglandin F1 alpha; Animals; Animals, Newborn; Blood Gas Analysis; Brain; Cerebrovascular Circulation; Epoprostenol; Hemorrhage; Hypotension; Indomethacin; Oxygen Consumption; Swine

The effect of haemorrhagic hypotension on the levels of prostaglandin E2 (PGE2), thromboxane B2 (TXB2), and 6-keto prostaglandin F1 alpha (6-keto-PGF1 alpha) in cortical tissue of rats was studied. Lightly anesthetized rats were subjected to steady-state hypotension for 15 min, with a mean arterial blood pressure of 80, 60, and 40 mm Hg, and compared to a control group of normotensive rats. No significant change was found in the levels of PGE2 and TXB2. The level of 6-keto-PGF1 alpha increased from 7.8 +/- 0.9 to 14.1 +/- 1.9 pg/mg protein (p less than 0.02) at 80 mm Hg. Our findings suggest that prostacyclin, which is a potent vasodilator, might play a role in setting the lower limit of the autoregulation range.

Topics: 6-Ketoprostaglandin F1 alpha; Animals; Blood Gas Analysis; Brain; Dinoprostone; Epoprostenol; Hemorrhage; Homeostasis; Hypotension; Male; Prostaglandins E; Rats; Thromboxane B2

In order to assess the pathophysiological role of renal prostacyclin in genetic hypertension, the urinary excretion of its main stable metabolite, 6-ketoprostaglandin F1 alpha, was followed in 12 hypertensive, normotensive and low blood pressure female rats of the Lyon strains at the ages of 5, 9, 21, 32 and 45 weeks. The urinary excretion of 6-ketoprostaglandin F1 alpha, which progressively decreased in the three strains between 5 and 21 weeks of age, was found to be increased in 5- and 9-week-old hypertensive rats and it was reduced in 5-week-old low blood pressure rats, compared with age-matched normotensive controls. The urinary 6-ketoprostaglandin F1 alpha was found to be significantly related to the systolic blood pressure in 5- and 9-week-old rats of the three strains (r = 0.42; n = 71; P less than 0.001). These results exclude a primary role in the development of hypertension for a genetically determined defect in the renal biosynthesis of prostacyclin in the spontaneous hypertensive rat of the Lyon strain.

Topics: 6-Ketoprostaglandin F1 alpha; Age Factors; Animals; Epoprostenol; Female; Hypertension; Hypotension; Kidney; Rats; Rats, Inbred Strains

Intravenous endotoxin injection in rabbits led to complement activation, a biphasic hypotension and elevated arterial levels of prostacyclin and/or 6-oxo-prostaglandin F1 alpha. Primary hypotension and stimulation of prostacyclin biosynthesis were completely dependent on complement activation whereas the secondary changes of these parameters were partly complement dependent, as indicated by experiments with cobra venom factor pretreated rabbits. Prostacyclin, which was never detectable in arterial blood, contributed to the development of hypotension in rabbit endotoxic shock.

Topics: 6-Ketoprostaglandin F1 alpha; Animals; Blood Pressure; Complement Activation; Epoprostenol; Hypotension; Rabbits; Shock, Septic

Embolisation of blood clots produced an increased pulmonary artery pressure in vitro and systemic hypotension in vivo. In control anaesthetized animals, systemic blood pressure fell by 44.9 +/- 28.0 mm Hg following embolisation and 40% of the animals died within 5 minutes of embolisation. Plasma concentrations of thromboxane B2 (TXB222222 2) and 6-keto-prostaglandin F 1 alpha (6-keto-PGF 1 alpha) were increased by 0.54 +/- 0.13 ng/ml and 0.41 +/- 0.25 ng/ml, respectively. Pretreatment of animals with aspirin (ASA), 5 mg/kg or 250 mg/kg, reduced the hypotensive response and the TXB 2 and 6-keto-PGF 1 alpha release. Embolisation of isolated lungs perfused with blood-free medium induced an increase in pulmonary artery pressure of 32.7 +/- 21.0 mm Hg and significantly increased the content of TXB 2 and 6-keto-PGF 1 alpha in the perfusate. Pretreatment of lungs with indomethacin, 10 micrograms/ml, reduced the mean pulmonary pressure response to embolisation to 10.6 +/- 4.9 mm Hg and blocked the appearance of TXB 2 in the perfusate. Embolisation with an agarose clot induced only a 2.58 +/- 0.8 mm Hg increase in pressure and no detectable TXB 2 release. These results indicate that embolisation of lungs with a blood clot induces the release of TXB 2 and 6-keto-PGF 1 alpha. The release of these mediators, the hemodynamic responses and mortality were blocked by ASA pretreatment.

Topics: 6-Ketoprostaglandin F1 alpha; Anesthesia, General; Animals; Aspirin; Hypotension; Indomethacin; Lung; Male; Perfusion; Pressure; Pulmonary Artery; Pulmonary Embolism; Rabbits; Thromboxane B2; Thromboxanes

Administration of endotoxin (lipopolysaccharide W E. coli O111 B4, 0.5 mg/kg i.v.) induced about 20% activation of the complement system (measured as CH50 and C3), a biphasic hypotension, thrombocytopenia and a significant rise in blood levels of 6-oxo-PGF1 alpha. Complement depletion (CH50 and C3 less than 3%) with Cobra Venom Factor significantly reduced the initial fall in blood pressure and the rise in 6-oxo-PGF1 alpha, and abolished the second phase of hypotension and the thrombocytopenia, due to subsequent injection of endotoxin. It is concluded that activation of about 20% of the complement system by endotoxin is a prerequisite for the occurrence of thrombocytopenia and secondary hypotension, and that it is involved in the increase in blood levels of 6-oxo-PGF1 alpha. The results of histamine determinations in rabbit blood and plasma indicate that, besides products derived from prostaglandin endoperoxides, other vasoactive substances, possibly released during complement-mediated adherence aggregation of platelets, might contribute to the endotoxin-induced hypotension.

Topics: 6-Ketoprostaglandin F1 alpha; Animals; Complement System Proteins; Endotoxins; Female; Histamine; Hypotension; Male; Rabbits; Thrombocytopenia

Topics: 6-Ketoprostaglandin F1 alpha; Animals; Complement Activation; Endotoxins; Hypotension; Prostaglandins F; Rabbits; Thrombocytopenia

The mechanism of enhanced renal prostaglandin (PG) release in the in situ pump-perfused kidney was studied in anesthetized dogs. Pump perfusion caused a gradual decrease in mean arterial blood pressure (BP) from 163 to 128 mmHg over an 80-min period. The renal arteriovenous level of PGE and plasma renin activity (PRA) were increased by a mean of 1.36 ng/ml and 22 ng AI.ml-1.h-1, respectively. In a second group of dogs treated with captopril, pump perfusion did not alter PGE or BP, but increased PRA. When the animals were treated with indomethacin, the renal arteriovenous levels of PGE and 6-keto-PGF1 alpha were not changed but PRA increased during the 80 min of pump perfusion. In a fourth group of dogs that had undergone renal denervation and phentolamine treatment, changes in PGE and BP occurred during pump perfusion similar to the changes in the control group, and 6-keto-PGF1 alpha release by the kidney also increased. The results indicate that renal PG release during group perfusion is mainly due to the activation of the renin-angiotensin system and that the hypotension due to pump perfusion is PG mediated.

Topics: 6-Ketoprostaglandin F1 alpha; Animals; Blood Pressure; Captopril; Dogs; Epoprostenol; Female; Hypotension; Indomethacin; Kidney; Kinetics; Male; Prostaglandins; Prostaglandins E; Prostaglandins F; Renin

Topics: 6-Ketoprostaglandin F1 alpha; Animals; Blood Pressure; Carbon Dioxide; Female; Hypotension; Male; Oxygen; Prostaglandins F; Rabbits; Shock, Septic

Levels of 6-oxo-prostaglandin F1 alpha (6-oxo-PGF1 alpha), the non-enzymic degradation product of prostacyclin, were measured in arterial blood from anaesthetized rabbits, before and after intravenous (i.v.) administration of endotoxin (Lipopolysaccharine W E. coli 0111:B4, 5 mg/kg). 6-Oxo-PGF1 alpha was assessed by radioimmunoassay after extraction and separation by thin-layer chromatography. The basal concentration of 6-oxo-PGF1 alpha in blood was less than 100 mg/ml in 19 out of 20 rabbits. This indicates that the level of circulating prostacyclin is generally below 100 pg/ml. The administration of endotoxin induced a biphasic hypotension, and increased levels of 6-oxo-PGF1 alpha were found in all endotoxin-treated animals during the secondary hypotension after 60 and 120 min. Pretreatment with indomethacin (2.5 mg/kg) prevented the secondary fall in arterial blood pressure and significantly suppressed the rise in 6-oxo-PGF1 alpha. However, indomethacin failed to alter the endotoxin-induced thrombocytopenia and did not modify the endotoxin-induced platelet aggregation in vitro. It is concluded that prostacyclin contributed to the secondary hypotension which accompanied the i.v. administration of endotoxin. Thromboxane A2 seems not to be of primary importance in the endotoxin-platelet interaction.

Topics: 6-Ketoprostaglandin F1 alpha; Animals; Endotoxins; Epoprostenol; Heart Rate; Hypotension; Male; Platelet Aggregation; Prostaglandins F; Rabbits; Thrombocytopenia; Thromboxane A2