6-ketoprostaglandin-f1-alpha and Burns

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

This study aimed to investigate the endothelial function in a canine model of burn injury combined with seawater immersion. The model of burn injury was established. The dogs were randomly divided into four groups including dogs with burn injury (B group), or burn injury combined with seawater immersion (BI group), or only immersion in seawater (I group), or control animals with no injury or immersion (C group). The circulating endothelial cell (CEC) count and coagulation-fibrinolysis parameters were measured. The CEC count in B group increased at 4 h, 7 h, and 10 h after injury and then reduced, whereas it continuously increased to a greater extent in BI group (P < 0.05). The von Willebrand factor (vWF) activity, plasminogen activator inhibitor (PAI-1), and the ratio of thromboxane B2 (TXB2) to 6-keto-prostaglandin F1α (6-K-PGF1α ) in BI group had a marked increase after injury, and the tissue-type plasminogen activator (tPA) in the BI group decreased. Microscope observations revealed thrombus formation in lungs of the animals in BI group, but not in C, I, or B groups. Burn injury causes endothelial dysfunction, and seawater immersion lastingly aggravates this injury, leading to a higher risk of developing thrombosis.

Topics: 6-Ketoprostaglandin F1 alpha; Animals; Blood Coagulation; Blood Coagulation Disorders; Burns; Disease Models, Animal; Dogs; Endothelial Cells; Humans; Immersion; Lung; Plasminogen Activator Inhibitor 1; Seawater; Thromboxane B2; Tissue Plasminogen Activator; von Willebrand Factor

Previous studies have demonstrated potent inhibition of burn oedema and progressive ischaemia by local anaesthetics. Since eicosanoids have been suggested to play an important role in the pathophysiology of burns, we compared in the present ex vivo study the effects of topical lidocaine/prilocaine cream (EMLA, ASTRA, Sweden) and intravenous lidocaine with that of saline on eicosanoid formation by normal and burned rat skin.. A full-thickness burn trauma was induced in the abdominal skin. All the agents were given 5 min postburn until 2 h after the trauma. The experimental skin was subsequently removed and incubated in Krebs solution for 1 h. Eicosanoid concentrations in the solution were analysed by radioimmunoassay.. EMLA cream induced a significant inhibition of TXB2 (P<0.05) and 6-Keto-PGF1alpha (P<0.01) but not of PGE release from burned skin as compared to saline treatment. Intravenous lidocaine infusions did not significantly influence the release of any of the measured eicosanoids versus saline.. In conclusion, the lack of effect of intravenous lidocaine could relate to the severe burn trauma inducing rapid ischaemia which may have interfered with the delivery of the agent to the burned tissues or to insufficient concentrations achieved in the burn area. Topical treatment of burned skin with a local anaesthetic cream significantly reduced the release of TXB2 and 6-Keto-PGF1alpha, suggesting a possible mechanism of action in progressive burn ischaemia.

Topics: 6-Ketoprostaglandin F1 alpha; Administration, Topical; Anesthetics, Local; Animals; Burns; Eicosanoids; Infusions, Intravenous; Lidocaine; Lidocaine, Prilocaine Drug Combination; Male; Ointments; Prilocaine; Rats; Rats, Sprague-Dawley; Skin; Thromboxane B2

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

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

This study examines the hypothesis that acute thermal injury decreases renal and splanchnic vasodilator eicosanoids. Anesthetized rabbits were subjected to sham or a 25% total body surface area burn and fluid resuscitated. At 2, 4, 6, 12, and 24 h postburn the superior mesenteric and renal arteries were cannulated and perfused in vitro with their end organs with Krebs buffer (pH 7.4, 37 degrees C). Renal and splanchnic prostaglandins (PGs) 6-keto-PGF1 alpha (PGI2), and PGE2, and thromboxane B2 (TxB2) release were measured by EIA at 15 min of perfusion. The major eicosanoids released were PGI2 from the splanchnic bed and PGI2 and PGE2 from the kidney. Renal PGE2 and PGI2 and splanchnic PGI2 release were decreased by 50% or more 12 h postburn (p < 0.01) but were restored to sham burn levels 24 h postburn. Loss of these endogenous renal and splanchnic vasodilators 12 h postburn may contribute to ischemia of both vascular beds at this critical time period following acute burn injury.

Topics: 6-Ketoprostaglandin F1 alpha; Acute Disease; Animals; Burns; Dinoprostone; Epoprostenol; Kidney; Kinetics; Male; Prostaglandins; Rabbits; Splanchnic Circulation; Thromboxane B2

This study examines the hypothesis that acute thermal injury decreases renal and splanchnic blood flow which correlates with altered endogenous vasodilator eicosanoid release. Anesthetized male Wistar rats were subjected to sham or a non-resuscitated 30% total body surface area burn. At 1, 2, 4, 8, and 24 h post-burn mean arterial pressure as well as superior mesenteric and renal artery in vivo blood flow were measured. The superior mesenteric and renal arteries were cannulated and perfused in vitro with their end organs with Krebs buffer (pH 7.4, 37 degrees C). Renal and splanchnic 6-keto-PGF1 alpha (PGI2), PGE2, and thromboxane B2 (TXB2) release were measured by EIA at 15 min of perfusion. Renal and superior mesenteric artery blood flow decreased by 40% or more at 1 and 2 h post-burn despite mean arterial pressure remaining unchanged. The major eicosanoids released were PGI2 from the splanchnic bed and PGI2 and PGE2 from the kidney. Splanchnic PGI2 and TXB2 release and renal TXB2 increased 2-3 fold at 1 h post-burn but returned to the sham level at 2 h post-burn. By 24 h post-burn the vasodilator eicosanoids were increased in both the splanchnic and renal vascular beds. These data show that decreased renal and splanchnic blood flow was associated with increased endogenous release of the potent vasoconstrictor TXB2. By 2 h post-burn, renal and splanchnic blood flow began returning toward the sham level as endogenous release of TXB2 from both organs fell to sham levels. These data suggest that increased endogenous release of TXB2 may contribute to the short-term decrease in renal and splanchnic blood flow in the immediate post-burn period and thus may contribute to ischemia of both vascular beds.

Topics: 6-Ketoprostaglandin F1 alpha; Animals; Burns; Dinoprostone; Eicosanoids; Epoprostenol; Kinetics; Male; Rats; Rats, Wistar; Renal Circulation; Splanchnic Circulation; Thromboxane B2

Topics: 6-Ketoprostaglandin F1 alpha; Adolescent; Adult; Burns; Cardiomyopathies; Creatine Kinase; Female; Hemodynamics; Humans; Male; Middle Aged; Thromboxane B2; Ventricular Function

To define the pathogenesis of hemodynamical and hemorrheological changes as well as multiple organ failure (MOF) during early postburn stage, we determined the levels of thromboxane A2(TXA2) and prostacyclin (PGI2) and some other related variables in 57 patients, of which 14 were complicated by MOF. The results showed that TXA2/PGI2 ratio increased markedly within 3 days postburn, and its dynamic change paralleled well with changes of hemodynamical and hemorrheological parameters as well as myocardial enzyme spectrum. Both plasma and visceral levels of TXA2/PGI2 ratio were significantly higher in MOF than those in non-MOF cases. The altered TXA2/PGI2 ratio coincided with the clinical course of MOF patients. These findings suggested that TXA2/PGI2 imbalance may be one of the important factors of early postburn damage.

Topics: 6-Ketoprostaglandin F1 alpha; Burns; Female; Humans; Male; Multiple Organ Failure; Thromboxane B2

This study examined the hypothesis that burn injury inhibits the release of splanchnic PGI2, a potent endogenous vasodilator of the splanchnic vascular bed. Male Hartley Guinea Pigs (350 grams) were anesthetized, shaved and subjected to a full thickness scald burn comprising 45% of the total body surface area (or sham burn). The animals were treated with intravenous or topical lazaroid, a 21-aminosteroid U75412E. After recovery for 24 hours, the animals were anesthetized, and the superior mesenteric artery was cannulated and removed with its intact intestine (SV + SI). The SV + SI was perfused in vitro with oxygenated Krebs buffer. The venous effluent was assayed for 6-keto-PGF1 alpha, PGE2 and thromboxane B2 by enzyme immunoassay. Acute burn injury decreased SV + SI release of 6-keto-PGF1 alpha by 57% but did not alter release of PGE2 or thromboxane B2. Treatment of the animals with topical lazaroid and not intravenous lazaroid restored SV+SI 6-keto-PGF1 alpha release to control levels. These data showed that topical lazaroid therapy maintained endogenous splanchnic PGI2 release following acute burn injury. Maintaining endogenous splanchnic PGI2 release by topical lazaroid treatment may be one strategy to avoid splanchnic ischemia following acute thermal injury.

Topics: 6-Ketoprostaglandin F1 alpha; Animals; Burns; Dinoprostone; Epoprostenol; Guinea Pigs; In Vitro Techniques; Kinetics; Male; Mesenteric Arteries; Perfusion; Splanchnic Circulation; Steroids; Thromboxane B2

A prospective study was carried out on 57 patients with total burned surface area (TBSA) over 30%. It was found that myocardial damage occurred early postburn, which was one of the major causes of cardiac dysfunction and failure. The postburn respiratory failure (RF) might be classified into three patterns. The etiology of each pattern varied. The imbalance between thromboxane and prostacyclin in plasma and visceral tissues played important roles in the genesis and development of postburn MOF as well as the causes of pathophysiological alterations in the main factors (including inhalation injury, severe shock and systemic infection) which contributed to occurrence of visceral damage and MOF.

Topics: 6-Ketoprostaglandin F1 alpha; Adolescent; Adult; Burns; Burns, Inhalation; Child; Female; Humans; Male; Multiple Organ Failure; Prospective Studies; Shock, Traumatic; Thromboxane B2

Topics: 6-Ketoprostaglandin F1 alpha; Adolescent; Adult; Burns; Dinoprost; Female; Humans; Male; Middle Aged; Multiple Organ Failure; Thromboxane B2

51 burned patients with TBSA over 30% were studied prospectively. MOF developed in 17 of them. Postburn MOF occurred mainly in those with TBSA over 70%. Mortality of MOF was directly proportional to the number of organs involved. The incidence of pulmonary failure was the highest, and the highest mortality was attributed to renal failure. MOF occurring in the early stage was more related to burn shock, and those occurring in the late stage was predisposed mainly by infection. Oxygen free radicals play an important role in the genesis and development of postburn MOF. In this study, it was revealed that antiperoxidation ability declined, active oxygen was increased, and lipid peroxidation became excessive after the burn injury. It was also found that oxygen free radical-mediated effects produced more serious damages in patients with MOF than those without, and also more in those died than the survivors. The hypoxanthine-xanthine oxidase system was a significant source of oxygen radicals after the burn injury. There were also significant changes in plasma TXA2 and PGI2 levels postburn. The marked increase in TXA2/PGI2 ratio indicated imbalance between TXA2 and PGI2, which was correlated well with burn size and closely related to the development of postburn MOF. The excessive production of TXA2 might trigger or accelerate the formation of microaggregates and thromboxane, subsequently leading to visceral damages and failure.

Topics: 6-Ketoprostaglandin F1 alpha; Adult; Burns; Female; Humans; Male; Malondialdehyde; Multiple Organ Failure; Shock, Traumatic; Superoxide Dismutase; Thromboxane B2; Xanthine Oxidase

We determined the time course of the oxidant-induced systemic lipid peroxidation seen after burn injury. Twelve sheep were given a 15% of total body surface third-degree burn and monitored for 3 or 5 days. Circulating lipid peroxides were monitored by both malondialdehyde (MDA) and conjugated dienes (CD). Lung and liver tissue MDA was also measured and compared to controls. A significant but transient increase in circulating MDA and CD was noted several hours after burn. Venous plasma levels increased again 3-5 days postburn with onset of wound inflammation. Oxygen consumption, VO2, also increased by 35 +/- 12% at this time. Lung MDA, which increased to 64 +/- 5 from a control of 45 +/- 4 nMol/gm, at 12 hours after burn was still increased 3 days after injury. Marked lung inflammation was present early after injury and persisted for the 5-day study period. Liver MDA also increased from control value of 110 +/- 20 to 252 +/- 25 at 12 hours and remained increased over the 5-day period. Serum alkaline phosphatase was also increased. Burn biopsies revealed no infection to explain the ongoing lipid peroxidation process, i.e., bacterial content was less than 10(5) organisms/gram burn tissue. We conclude that an initial system lipid peroxidation occurs immediately after burn injury, and that this process continues well into the post-resuscitation period, corresponding in time with increased VO2, lung inflammation, and evidence of liver dysfunction. The ongoing oxidant changes with the presence of a burn may explain the accentuated organ dysfunction seen with an additional septic insult in burned patients.

Topics: 6-Ketoprostaglandin F1 alpha; Animals; Burns; Inflammation; Lipid Peroxidation; Liver; Lung; Malondialdehyde; Oxygen Consumption; Pneumonia; Sheep; Thromboxane B2; Time Factors

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

We conducted studies to determine the effects of parenteral therapy with indomethacin, ibuprofen, and piroxicam on key immunologic and hematologic alterations induced by thermal injury. Drugs (10-20 mg/kg) or placebo were administered intramuscularly to thermally injured guinea pigs at 3 h postburn and then daily for nine days postburn. All three drugs inhibited production of 6-keto prostaglandin F1 alpha and thromboxane B2 in wound fluid and concomitantly restored the bactericidal activity of polymorphonuclear leukocytes (PMNLs) against Pseudomonas aeruginosa to normal. Indomethacin also increased the proliferative response of splenic lymphocytes to concanavalin A; however, ibuprofen and piroxicam had no effect on this response. None of the drugs affected the extent of systemic complement consumption, thrombocytopenia, leukocytosis, or leukopenia in the injured animals. These results suggest that the PMNL bactericidal defect induced by thermal injury is preventable or reversible and that the mechanisms responsible for this defect are inhibitable by nonsteroidal anti-inflammatory drugs.

Topics: 6-Ketoprostaglandin F1 alpha; Animals; Anti-Inflammatory Agents, Non-Steroidal; Blood Bactericidal Activity; Blood Cell Count; Burns; Complement System Proteins; Concanavalin A; Cyclooxygenase Inhibitors; Disease Models, Animal; Guinea Pigs; Ibuprofen; Indomethacin; Kinetics; Lymphocyte Activation; Neutrophils; Phagocytosis; Piroxicam; Pseudomonas aeruginosa; Spleen; 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

Pulmonary dysfunction is a well-recognized complication of burn wound excision. It remains unclear whether this is caused by bacteria or inflammatory mediators released during excision of the wound. We produced a 15% full-thickness burn in 18 sheep, and between days 5 and 7 completely excised the wound under general anesthesia. Pulmonary parameters of static and dynamic lung compliance (CSTAT and CDYN), PaO2/FiO2, and pulmonary artery pressure (Ppa) were measured, as well as burn lymph, venous and aortic thromboxane B2 (TxB2), chemotactic index (chemotaxis/chemikinesis), and oxygen radical activity reflected in the level of lipid peroxidation in lung tissue. We noted a transient increase in burn lymph and venous TxB2 during excision, increasing from a preburn value of 200 and 220 +/- 50 pg/ml to 950 +/- 210 and 980 +/- 280 pg/ml, respectively. In 13 of 18 sheep, chemotactic activity and lung tissue lipid peroxidation, measured as malondialdehyde (MDA) content, were not increased. In this group only a very transient decrease in CDYN, PaO2/FiO2, and a 3 mm Hg increase in mean Ppa was seen with excision, with these parameters returning rapidly to baseline. Five of the 13 sheep had wound biopsy specimens that were greater than 10(6) organisms/gm tissue. In the remaining five sheep, plasma chemotactic index was also significantly increased with excision, as was lung MDA content, while decreases in CDYN, CSTAT, and PaO2/FiO2 and an increase in Ppa were more protracted. Three of these five sheep had wound biopsy specimens greater than 10(6) organisms/gm. We conclude that a release of thromboxane occurs during excision, which corresponds in time to transient lung dysfunction. If there is also a release of chemotactic factors, a more protracted pulmonary response occurs with evidence of O2 radical-induced lung changes.

Topics: 6-Ketoprostaglandin F1 alpha; Anesthesia; Animals; Burns; Chemotactic Factors; Disease Models, Animal; Lung; Lung Compliance; Lymph; Malondialdehyde; Oxygen; Prostaglandins; Pulmonary Wedge Pressure; Sheep; Thromboxane B2; Vascular Resistance

A full-thickness burn wound in adult sheep releases prostanoids when they are injected locally with E. coli endotoxin, 2 micrograms/kg, resulting in an increase in pulmonary artery pressure (Ppa) from 20 +/- 3 to 34 +/- 5 mm Hg, and a decrease in mean arterial oxygen tension (PaO2) from 88 +/- 6 to 70 +/- 5 torr; this corresponds to an increase in venous plasma TxB2 content from a baseline of 220 +/- 79 pg/ml to 440 +/- 90 pg/ml. Burn prostanoid production, measured in lymph, increased ten- to fifteen-fold for both thromboxane A2, measured as TxB2, and prostacyclin, 6-keto-PGF1 alpha. The intravenous administration of ibuprofen, 12.5 mg/kg, eliminated both the increase in Ppa and decrease in PaO2 as well as the increase in burn lymph prostanoids. However, plasma prostanoids were also decreased below baseline, a potentially deleterious effect. A topical ibuprofen cream, 5% ibuprofen in a water-soluble ester, was applied to the burn hide every 6 hrs x 4 after which endotoxin was again injected below the hide. The pulmonary dysfunction was prevented as was the increase in plasma TxB2 with the value remaining at baseline. Burn lymph levels were only increased three- to five fold. Ibuprofen levels in burn lymph were maintained at 1-2 mcg/ml. The addition of the cream to the burn, however, did increase the wound bacterial content to 10(5)-10(7) bacteria/gram of tissue compared to 10(2)-10(3) for the dry, untreated burn, probably due to softening of the burn. Topically applied ibuprofen, therefore, can decrease burn wound prostanoid production from local endotoxin, preventing lung dysfunction.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: 6-Ketoprostaglandin F1 alpha; Administration, Topical; Animals; Blood Pressure; Burns; Endotoxins; Escherichia coli; Ibuprofen; Infusions, Parenteral; Lymph; Ointments; Oxygen; Skin Absorption; Thromboxane B2; Thromboxanes

The pulmonary and systemic response to a full-thickness burn (15% of total body surface area) was determined in 15 adult sheep. Also compared was the effect of wound bacterial content and prostanoid release on this response. Burn wound thromboxane A2, measured as TxB2, and prostacyclin, measured as 6-keto-PGF1 alpha, were measured in burn wound lymph. Animals were monitored for 7 days. On the final day, a full-thickness biopsy specimen of burn tissue was obtained for quantitative bacteriology. Wounds with 10(4) or less organisms per gram of burn tissue were considered colonized, whereas those with 10(5) or more organisms per gram of burn tissue indicated wound infection. Seven sheep had 10(4) or less bacteria and the remaining eight sheep had 10(6) or greater bacteria. We noted a significant mean increase in cardiac index from a baseline of 5 to 6.2 L/min/m2, a decrease in systemic vascular resistance from 16 to 12 mm Hg/L/min, and a mean increase in oxygen consumption from a baseline of 135 to 165 ml/min/m2 during the 7-day study period. There were no differences in these responses between the colonized and the infected wounds. Pulmonary artery pressure increased from a mean baseline of 19 to 24 mm Hg and arterial oxygen tension (PaO2) decreased from a baseline of 90 to 80 mm Hg in the infected wound group, with values remaining at baseline in the colonized wound group. These changes corresponded with an increase in lymph and plasma TxB2 from a baseline of 200 to 210 pg/ml to 1000 +/- 250 and 600 +/- 190 pg/ml, respectively. Values in the animals with colonized wounds were not significantly increased.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: 6-Ketoprostaglandin F1 alpha; Animals; Burns; Escherichia coli Infections; Extracellular Space; Hemodynamics; Lung; Lymph; Pseudomonas Infections; Sheep; Thromboxane B2; Time Factors; Wound Infection

Levels of both thromboxane B2 and 6-keto-prostaglandin-F1a, the stable metabolites of thromboxane A2 and prostacyclin, respectively, were quantitated in plasma samples from burn patients at various times postinjury. Our results indicate that, although thromboxane B2 levels were elevated throughout the burn course, quite large increases occurred both in the acute stage (less than three days postinjury) and during septic episodes. The results of our study demonstrate that, at the same time thromboxane B2 levels were elevated, 6-keto-prostaglandin-F1a levels were unchanged and remained at control levels. Increased production of thromboxane B2 without a concomitant increase in 6-keto-prostaglandin-F1a in the plasma of burn patients gives support to the hypothesis that elevated thromboxane A2 production contributes to post-thermal injury systemic responses, both in the acute phase as well as during sepsis.

Topics: 6-Ketoprostaglandin F1 alpha; Adolescent; Adult; Aged; Arachidonic Acid; Arachidonic Acids; Burns; Child; Child, Preschool; Female; Humans; Male; Middle Aged; Thromboxane B2; Thromboxanes; Time Factors; Wound Infection

Differences in the vascular response to burn and freeze injuries were investigated as a model for defining the mechanism and cause of vascular occlusion in rats after dermal burns. Concentrations of thromboxane and prostacyclin in wound fluid were elevated in both types of trauma. However, inhibition of prostaglandin synthesis by indomethacin failed to promote vascular patency in burn-injured animals. However, the systemic administration of ibuprofen and imidazole led to increased vascular patency. Ibuprofen promoted vascular patency even when given six hours after burn trauma. These studies indicate that ibuprofen and imidazole promote vascular patency by fostering fibrinolysis rather than by inhibiting prostaglandin synthesis and release.

Topics: 6-Ketoprostaglandin F1 alpha; Animals; Blood Vessels; Body Fluids; Burns; Fibrinolysis; Freezing; Ibuprofen; Imidazoles; Indomethacin; Prostaglandin Antagonists; Rats; Rats, Inbred Strains; Skin; Thromboxane B2; Time Factors; Wound Healing

Topics: 6-Ketoprostaglandin F1 alpha; Animals; Burns; Fistula; Hemodynamics; Lung Diseases; Lymphatic Diseases; Lymphatic System; Prostaglandins; Sheep; Thromboxane A2; Thromboxane B2; Thromboxanes