6-ketoprostaglandin-f1-alpha and Shock

This study has shown that multiple organ failure (MOF) is one of the major causes of death in patients with severe burns. Both the plasma and visceral levels of TXB2 and the TXB2/6-keto-PGF1 alpha ratio were significantly increased. The changed plasma levels of TXB2 and the TXB2/6-keto-PGF1 alpha ratio paralleled the deterioration of the general condition in MOF patients. The circulatory platelet aggregation ratios (CPAR) in the MOF patients initially declined then dropped profoundly at 5-7 days postburn, indicating more microaggregate formation. CPK, LDH and GOT had increased markedly by 1 day, were elevated further at 2-3 days, and remained at supranormal levels for the first 7 days postburn. Degeneration, destruction, oedema, haemorrhage and thrombosis were observed in tissues from patients who died due to heart, lung, renal and hepatic failure. Clinically, 13 of the 16 MOF cases developed organ failure and 11 died between 3 and 7 days postburn. These findings confirmed that the increases of TXA2 and the TXA2/PGI2 ratio in plasma and visceral tissues can be an important factor in the genesis and development of postburn MOF.

Topics: 6-Ketoprostaglandin F1 alpha; Adolescent; Adult; Body Surface Area; Burns; Female; Humans; Male; Middle Aged; Multiple Organ Failure; Prospective Studies; Shock; Thromboxane A2

We showed previously that the administration of interleukin (IL)-1beta induces circulatory shock and impairs the oxygen consumption (VO2)/oxygen delivery (DO2) relation by increasing the slope of the supply-independent line in rabbits. We tested the effect of ibuprofen, a specific inhibitor of the development of shock in this model, on the VO2/DO2 abnormality. Eighteen rabbits were divided randomly into three groups (n = 6 each) and intravenously given 10 microg/kg of IL-1beta alone or 10 microg/kg of IL-1beta followed by 10 mg/kg of ibuprofen or saline (control). All rabbits were subjected to stepwise cardiac tamponade by inflation of a handmade balloon placed into the pericardial sac to reduce DO2. The VO2/DO2 relation was then analyzed by the dual line method. The IL-1beta group had a significantly lower mean arterial pressure than that of the other groups before cardiac tamponade, and this reduction in mean arterial pressure was suppressed completely by treatment with ibuprofen. The cardiac index did not differ between groups. The slope of the supply-independent line was increased significantly by administration of IL-1beta, and this increase was attenuated significantly by treatment with ibuprofen (IL-1beta only: y = 0.14x + 6.1, ibuprofen: y = 0.06x + 8.5, control: y = 0.01x + 9.0). We conclude that ibuprofen reversed the IL-1beta-induced shock by restoring the systemic vascular resistance to normal and thereby normalized the VO2/DO2 relation in the supply-independent range of DO2.

Topics: 6-Ketoprostaglandin F1 alpha; Animals; Anti-Inflammatory Agents, Non-Steroidal; Blood Gas Analysis; Cardiac Output; Cardiac Tamponade; Cytokines; Epoprostenol; Hemodynamics; Humans; Hypoxia; Ibuprofen; Interleukin-1; Oxygen; Oxygen Consumption; Pressure; Rabbits; Shock; Time Factors

These serial clinical and experimental studies were designed to clarify the pathogenesis of postburn MODS. Both animal and clinical studies were performed. In animal experiments, 46 male cross-bred dogs were cannulated with Swan-Ganz catheters and 39 of them were inflicted with 50% TBSA third degree burns (7 were used as controls). The burned dogs were randomly divided into 4 groups: immediate infusion, delayed infusion, delayed fast infusion and delayed fast infusion combined with ginsenosides. All dogs were kept under constant barbiturate sedation during the whole study period. Hemodynamics, visceral MDA, mitochondrial respiratory control rate (RCR) and ADP/O ratio, ATP, succinic dehydrogenase (SDH), organ water content as well as light and electron microscopy of visceral tissues were determined. In the clinical study, 61 patients with extensive deep burns were chosen, of which 16 sustained MODS. Plasma TXB2/6-keto-PGF1alpha ratio, TNF, SOD, MDA, circulatory platelet aggregate ratio (CPAR), PGE2, interleukin-1, total organ water content and pathological observations of visceral tissues from patients who died of MODS were carried out. Results demonstrated that ischemic-reperfusion damage due to severe shock, sepsis and inhalation injury are three main causes of postburn death. All inflammatory mediators increased markedly in both animals and patients who sustained organ damage or MODS. SDH, RCR, ADP/O and ATP decreased significantly. These findings suggested that ischemic damage and systemic inflammatory response syndrome (SIRS) initiated by mediators or cytokines might be important in the pathogenesis of postburn MODS.

Topics: 6-Ketoprostaglandin F1 alpha; Adenosine Diphosphate; Adenosine Triphosphate; Adult; Animals; Body Water; Burns; Central Nervous System Agents; Dinoprostone; Dogs; Female; Fluid Therapy; Ginsenosides; Hemodynamics; Humans; Hypnotics and Sedatives; Interleukin-1; Male; Malondialdehyde; Mitochondria; Multiple Organ Failure; Oxygen Consumption; Panax; Plants, Medicinal; Platelet Aggregation; Random Allocation; Reperfusion Injury; Saponins; Sepsis; Shock; Succinate Dehydrogenase; Superoxide Dismutase; Syndrome; Systemic Inflammatory Response Syndrome; Thromboxane B2; Tumor Necrosis Factor-alpha

Splanchnic artery occlusion shock was induced in male anaesthetized rats by clamping the splanchnic artery for 45 min. The arteries were then released and survival rate, mean survival time, mean arterial blood pressure, plasma levels of thromboxane B2 and 6-keto-PGF1 alpha, macrophage phagocytosis activity and plasma levels of myocardial depressant factor were evaluated. In addition, the neutrophilic infiltrate was quantified in the ileum and lung using a myeloperoxidase (MPO) assay. Sham splanchnic-artery-occlusion-shocked rats were used as controls. Splanchnic-artery-occlusion-shocked rats died within 93 +/- 7 min, while all sham-shocked animals survived more than 3 h. Splanchnic artery occlusion shock caused changes in mean arterial blood pressure, significantly increased the plasma levels of thromboxane B2 (7.5 +/- 1.3 ng/ml; p < 0.001 vs. sham), 6-keto-PGF1 alpha (8.9 +/- 1.7 ng/ml; p < 0.001 vs. sham) and myocardial depressant factor (114 +/- 11 U/ml), and reduced macrophage phagocytosis. Furthermore, MPO activity was significantly elevated (0.12 +/- 0.03 x 10(-3) and 1.8 +/- 0.5 x 10(-3) U/g protein in the ileum and lung, respectively) 70 min after starting reperfusion. Administration of BAY u3405, a novel thromboxane A2 receptor antagonist (30 mg/kg i.v., 30 min before occlusion), significantly increased survival time (187 +/- 3.7 min) and survival rate, improved mean arterial blood pressure, reduced the plasma levels of myocardial depressant factor (54 +/- 3 U/ml), partially restored macrophage phagocytosis and lowered MPO activity in both the ileum and the lung. Our data are consistent with an involvement of thromboxane A2 in splanchnic artery occlusion shock and suggest that BAY u3405 might be of benefit in low-flow states such as circulatory shock.

Topics: 6-Ketoprostaglandin F1 alpha; Animals; Arterial Occlusive Diseases; Blood Pressure; Carbazoles; Macrophages; Male; Myocardial Depressant Factor; Peroxidase; Phagocytosis; Rats; Rats, Sprague-Dawley; Receptors, Thromboxane; Shock; Splanchnic Circulation; Sulfonamides; Survival Rate; Thromboxane A2; Thromboxane B2

To evaluate the role of certain plasma biosubstances on the development of pulmonary hypertension and shock during severe hypoxia, hypercapnia and acidosis, plasma renin activity (PRA), angiotensin II (ATII), angiotensin converting enzyme (ACE), TXB2 and 6-Keto-PGF1 alpha (the stable metabolites of TXA2 and PGI2) were assayed in blood from pulmonary artery and aorta in seven pigs. Pulmonary arterial pressure (PAP) was monitored via Swan-Ganz catheter. During hypoxic and hypercapnic ventilation, PaO2 dropped to 4.7 kPa, PaCO2 rose to 21.1 kPa, pH dropped to 6.82, PAP increased from 2.43 +/- 0.06 to 4.46 +/- 0.45 kPa when acidotic shock developed (all P less than 0.05). Meanwhile ATII levels rose (all P less than 0.05). PRA significantly increased during acidotic shock as compared with normal ventilation (P less than 0.02). ACE dropped significantly (P less than 0.05), TXB2 and 6-keto-PGF1 alpha showed no significant change before and after hypoxic and hypercapnic ventilation.

Topics: 6-Ketoprostaglandin F1 alpha; Acidosis; Animals; Hypercapnia; Hypoxia; Male; Peptidyl-Dipeptidase A; Renin; Shock; Swine; Thromboxane B2

Splanchnic artery occlusion (SAO) shock was induced in anesthetized rats by clamping the celiac trunk and the superior mesenteric artery for 45 min. The arteries were then released and survival rate, mean survival time, mean arterial blood pressure (MAP), plasma levels of thromboxane B2 (TxB2) and 6-keto-PGF1 alpha, and the phagocytotic activity of peritoneal macrophages were evaluated. Shocked animals died within 89 +/- 10 min, while all sham-shocked rats survived greater than 3 h. SAO shock produced relevant changes in MAP, significantly increased plasma levels of TxB2 and 6-keto-PFG1 alpha, and decreased peritoneal macrophage phagocytotic activity. The administration of G 619, a dual thromboxane synthase inhibitor/thromboxane A2 receptor antagonist (50 mg/kg, 15 min before SAO shock) significantly increased survival time (190 +/- 13 min) and survival rate, reduced plasma levels of TxB2, and partially restored the impairment in peritoneal macrophage phagocytosis. Finally, the administration of G 619 had beneficial effects on changes in MAP-induced bay SAO shock. These data further confirm the involvement of TxA2 in SAO shock and suggest that G 619 may have positive effects in low-flow states.

Topics: 6-Ketoprostaglandin F1 alpha; Animals; Arterial Occlusive Diseases; Benzamides; Blood Pressure; Macrophages; Male; Phagocytosis; Picolines; Radioimmunoassay; Rats; Rats, Inbred Strains; Receptors, Prostaglandin; Receptors, Thromboxane; Shock; Splanchnic Circulation; Thromboxane B2; Thromboxane-A Synthase

The effects of platelet-activating factor (PAF) on prostanoid release during mesenteric ischemia-reperfusion-induced shock were investigated in anesthesized dogs 1) by measuring plasma levels of prostaglandin (PG)F2 alpha, 6-keto-PGF1 alpha and thromboxane (TX)B2 in the superior mesenteric vein during reperfusion following 2 hr occlusion of the superior mesenteric artery; 2) by monitoring the effects of BN 52021, a specific PAF receptor antagonist and indomethacin on hemodynamic parameters and prostanoid levels; and 3) by studying circulatory responses to PAF and PGF2 alpha injected into the superior mesenteric vein in the presence of BN 52021 or indomethacin. Restoration of the blood flow following 2 hr ischemia resulted in an immediate dramatic decrease in mean arterial blood pressure, with a concomitant increase in mean portal venous pressure, hematocrit values, and plasma prostanoid levels. Pretreatment of the animals either with BN 52021 (4 mg.kg-1) or indomethacin (2 mg.kg-1 plus 3 mg.kg-1hr-1) prevented the circulatory collapse and the increase in prostanoid levels during reperfusion. Administration of exogenous PAF (0.1 micrograms.kg-1) or PGF2 alpha (10 micrograms.kg-1) into the superior mesenteric vein evoked hypotension similar to that observed during reperfusion. Pretreatment of the animals with BN 52021 completely prevented the effects of PAF but failed to modify the responses to PGF2 alpha. Indomethacin at a dose that inhibited prostanoid formation was highly effective to attenuate the hypotensive response to exogenous PAF. These data suggest that prostanoid formation may be secondary to PAF release in circulatory collapse evoked by intestinal ischemia-reperfusion and give further support to the notion of the importance of PAF prostanoid interaction during ischemia-reperfusion-induced shock.

Topics: 6-Ketoprostaglandin F1 alpha; Animals; Dinoprost; Diterpenes; Dogs; Ginkgolides; Hemodynamics; Indomethacin; Lactones; Male; Mesenteric Arteries; Mesenteric Veins; Platelet Activating Factor; Prostaglandins; Reperfusion Injury; Shock; Thromboxane B2

Splanchnic artery occlusion shock was induced in anesthetized rats by clamping the splanchnic arteries for 45 min. The survival rate, plasma levels of thromboxane B2 (TxB2) and 6-keto-PGF1 alpha, serum and peritoneal levels of macrophage tumor necrosis factor (TNF alpha), the phagocytotic and killing activity of peritoneal macrophages and white blood cells count were evaluated. Shocked rats died within 2 h, while all sham-shocked rats survived more than 6 h. Plasma TxB2 and 6-keto-PGF1 alpha levels were increased in rats subjected to splanchnic artery occlusion shock compared to the levels in sham-shocked animals. Serum and peritoneal macrophage TNF alpha levels were undetectable in sham-shocked rats, whereas shocked rats exhibited increased levels of TNF alpha. Moreover, splanchnic artery occlusion shock reduced peritoneal macrophage phagocytotic and killing activity, and also produced severe leukopenia. A specific receptor antagonist of platelet activating factor (PAF), L-652, 731 (an i.v. bolus of 3.2 mg/kg 2 min after removal of the clamps followed, 5 min thereafter, by a continuous infusion of 0.16 mg/kg per min for 30 min) significantly increased the survival rate, lowered plasma TxB2 levels and reduced both serum and macrophage TNF alpha levels in shocked rats. In addition, L-652,731 completely restored macrophage phagocytosis, partially improved macrophage killing and significantly inhibited leukopenia. Finally, the administration of L-652,731 had beneficial effects on the cardiovascular changes induced by splanchnic artery occlusion shock. These findings are consistent with the involvement of PAF in splanchnic artery occlusion shock and indicate that PAF produces shock through direct and indirect (TxB2-mediated and TNF alpha-mediated) actions.

Topics: 6-Ketoprostaglandin F1 alpha; Animals; Arterial Occlusive Diseases; Blood Pressure; Furans; Leukocyte Count; Leukopenia; Macrophages; Male; Phagocytosis; Platelet Activating Factor; Radioimmunoassay; Rats; Rats, Inbred Strains; Shock; Splanchnic Circulation; Thromboxane B2; Tumor Necrosis Factor-alpha

The role of thromboxane and prostacyclin in circulatory shock of intestinal origin was investigated in anesthetized dogs by measuring their stable metabolites, thromboxane B2 (TXB2) and 6-keto-PGF1 alpha, respectively, in superior mesenteric vein (SMV), right ventricle (RV), and aorta during superior mesenteric artery occlusion-induced (SMAO) shock and by inhibiting prostanoid synthesis with indomethacin (IM). Release of the SMAO caused a dramatic decrease in mean arterial blood pressure and a significant increase in 6-keto-PGF1 alpha levels in SMV, RV, and aorta within 5 min. Thereafter, 6-keto-PGF1 alpha concentration decreased so that at 60-min postrelease it was not significantly different from the control values. TXB2 levels rose continuously during shock. IM significantly attenuated the magnitude of postocclusion hypotension and reduced both TXB2 and 6-keto-PGF1 alpha production.

Topics: 6-Ketoprostaglandin F1 alpha; Animals; Blood Pressure; Dogs; Epoprostenol; Indomethacin; Male; Mesenteric Arteries; Mesenteric Vascular Occlusion; Shock; Thromboxane A2; Thromboxane B2

Plasma thromboxane B2 (TXB2) and 6-keto-prostaglandin F1 alpha (6-keto-PGF1 alpha) were measured in 84 patients at risk of developing adult respiratory distress syndrome (ARDS) (44 patients following multiple trauma, 29 patients following abdominal surgery and 11 patients with acute pancreatitis). Forty-nine of these 84 patients developed an ARDS. High (greater than 140 pg/ml plasma) TXB2 values were found in 52/84 patients. The median values of TXB2 were: 360 pg/ml in multiple injured, 250 pg/ml in abdominal surgery and 410 pg/ml in acute pancreatitis patients. The median TXB2 value was 575 pg/ml in patients developing ARDS and 140 pg/ml in those without this complication: this difference was statistically significant (p less than 0.05). The median values of 6-keto-PGF1 alpha were 55 pg/ml in multiple injured, 25 pg/ml in abdominal surgery and 120 pg/ml in acute pancreatitis patients. The median 6-keto-PGF1 alpha value was 122 pg/ml in ARDS patients and 25 pg/ml in non-ARDS patients (statistically significant: p less than 0.05). High TXB2 and 6-keto-PGF1 alpha values were particularly related to sepsis in abdominal surgery patients (p less than 0.05) and in multiple injured patients (p less than 0.01). No relation could be established between abnormal TXB2 or 6-keto-PGF1 alpha values and death. High TXB2 values often persisted for several days and were observed particularly at the time ARDS diagnostic criteria were fulfilled.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: 6-Ketoprostaglandin F1 alpha; Abdomen; Adult; Critical Care; Female; Humans; Male; Middle Aged; Postoperative Complications; Prognosis; Respiratory Distress Syndrome; Sepsis; Shock; Thromboxane B2; Wounds and Injuries

Administration of dazoxiben (5 mg/kg, i.v.), which effectively suppressed plasma thromboxane concentrations, decreased the number of dogs that deteriorated into shock following a temporary (3-hr) splanchnic artery occlusion (SAO). Dazoxiben pretreatment also moderated the rise of plasma prostacyclin, but it augmented circulating prostaglandin E2 following the release of SAO. These alterations in arachidonic acid metabolism were accompanied by a moderation in the rise of plasma beta-glucuronidase activity, suggesting a moderation of tissue damage in the ischemic splanchnic region, and mitigation of the progressive hemodynamic deterioration caused by the SAO. The possible existence of causal relationships between the plasma eicosanoid concentrations, extent of damage in the ischemic splanchnic region, hemodynamic deterioration, and ultimate production of circulatory failure in dogs subjected to SAO are discussed.

Topics: 6-Ketoprostaglandin F1 alpha; Animals; Blood Pressure; Cardiac Output; Dogs; Female; Glucuronidase; Heart Rate; Imidazoles; Indomethacin; Ischemia; Kinetics; Male; Shock; Splanchnic Circulation; Thromboxane B2; Thromboxane-A Synthase; Vascular Resistance

Synthetic platelet-activating factor (PAF-acether) was shown to act as a shock inducer when a dose of 9 or 36 nmol . kg-1 was injected i.v. into dogs anesthetized with 30 mg . kg-1 i.v. sodium pentobarbitone. Nine nmol . kg-1 PAF-acether caused portal vein and pulmonary artery hypertension but only transiently; blood TXB2 and 6 keto PGF1 alpha levels rose; there was a lasting fall of 77% in systemic blood pressure, cardiac output fell by 86%, heart rate by 17%, plasma volume by 43%, and femoral artery blood flow by 66%, whereas the hematocrit rose by 33%. A dose of 36 nmol . kg-1 PAF-acether reduced coronary artery blood flow by 56%, diminished myocardial O2 consumption, raised O2 extraction and caused metabolic acidosis leading to death in 2 out of 7 animals. All these changes displayed the typical features of common acute circulatory collapse with distributive and hypovolemic etiologies, suggesting that PAF-acether might be an endogenous mediator in the early and late stages of shock.

Topics: 6-Ketoprostaglandin F1 alpha; Animals; Blood Pressure; Dogs; Electrocardiography; Endotoxins; Heart; Heart Rate; Myocardium; Oxygen Consumption; Platelet Activating Factor; Shock; Thromboxane B2