thromboxane-b2 and Burns

Thromboxane (TXA2) and prostacyclin (PGI2) levels, circulatory platelet aggregate ratios (CPAR), CPK, LDH, GOT, platelet counts, blood viscosity, cortisol and urine epinephrine contents were determined in 42 burned patients who were divided into two groups: Group I control (n = 34) and Group II (n = 8) treated with TXA2 synthesis inhibitor, anisodamine. It was found that in controls, both TXA2 and the TXA2/PGI2 ratio increased significantly. There was no marked difference in PGI2 levels between the two groups. Platelet counts and CPAR decreased, while blood viscosity, CPK, LDH, GOT, cortisol and epinephrine in the controls were all significantly higher than those found in Group II patients. All these findings suggested that the changes of TXA2 and the TXA2/PGI2 ratios played an important role in the haemodynamics and haemorrheology in burn shock. The TXA2 synthesis inhibitor, anisodamine, showed beneficial effects by restoring the haemodynamic and rheological disturbances towards normal by virtue of their ability to induce vascular constriction, platelet aggregation, cellular destruction, destabilization of membranes and release of chemical mediators (including enzymes). Furthermore, at 1-3 days postburn, the levels of CPK, LDH and GOT in controls were higher than those measured at 12 h postburn, but this phenomenon was not marked in the treated group, suggesting that after resuscitation, reperfusion damage had occurred and TXA2 might be responsible for the damage. It is assumed that anisodamine could protect tissues from reperfusion damage. The findings also suggested that anisodamine could quicken the restoration of neuroendocrine disturbance initiated by shock (stress).

Topics: Adolescent; Adult; Aspartate Aminotransferases; Burns; Creatine Kinase; Epinephrine; Female; Humans; Hydrocortisone; Infusions, Intravenous; L-Lactate Dehydrogenase; Male; Middle Aged; Shock; Solanaceous Alkaloids; Thromboxane A2; Thromboxane B2; Vasodilator Agents

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

Most studies investigating the pathophysiological processes taking place inside an experimental burn wound use in vitro techniques, which only allow for fragmented measurements of the actual and complex processes occurring inside a burn wound in vivo. In the present study, which used a recently developed in vivo technique in the rat, a full-thickness burn was induced and resulted in the formation of a subcutaneous gelatinous edema with distinct borders to the surrounding connective tissue and free communication with the systemic circulation allowing it to be easily separated for further analysis. In the present study, we investigated the effects of topical local anaesthetics (EMLA) on the inflammatory cascade of a burn wound in vivo. Results showed significantly higher myeloperoxidase (MPO) levels in EMLA-treated burned animals (P<0.01) versus placebo-treated burned controls. EMLA treatment induced a significant inhibition of the synthesis of leukotrien B(4) (LTB(4)) (P<0.001), prostaglandin E(1) (PGE(1)) (P<0.001), prostaglandin E(2) (PGE(2)) (P<0.001) and thromboxane B(2) (TXB(2)) (P<0.001) versus control, while free radical formation did not differ significantly between EMLA-treated and control animals. In conclusion, topical local anaesthetics significantly inhibit the release of several mediators known to take important part in the pathophysiological events ensuing a burn injury, such as activation of pain mechanisms (PGE), oedema formation (LTB), and postburn ischemia (TXB). The increased numbers of leukocytes (MPO) in the burn wound induced by topical local anaesthetic treatment could suggest increased influx and/or increased viability of leukocytes postburn.

Topics: Administration, Topical; Anesthetics, Local; Animals; Burns; Free Radicals; Inflammation; Leukotriene B4; Lidocaine; Lidocaine, Prilocaine Drug Combination; Male; Models, Animal; Peroxidase; Prilocaine; Prostaglandins E; Rats; Rats, Sprague-Dawley; Thromboxane B2

The effect of omega-3 fat emulsion on nitrogen retention and kinetics in relation to fatty acid profile were investigated in burned rats receiving total parenteral nutrition (TPN). A fat emulsion of a structured symmetrical triacylglycerol containing only eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) (2:1) was prepared. Sprague-Dawley rats were fed by fat-free chow for 2 wk. Then rats were fed exclusively with one of three types of TPN for 7 d. Animals in group C received fat-free TPN (n = 11). Group omega 6 received safflower oil fat emulsion, which accounted for 20% of total caloric intake (n = 11). Group omega 3 received fat emulsion containing only EPA and DHA (1% of total calories, n = 11), in addition to safflower oil emulsion (19% of total calories). On day 5, each rat was subjected to 20% full-thickness scald burns. Rats were sacrificed under ether anesthesia 48 h after burning. The rats in group C became deficient in omega-6 essential fatty acids. Cumulative nitrogen balance was decreased significantly in group omega 6. The rates of whole-body protein synthesis were increased significantly in both groups omega 6 and omega 3. In omega 6, however, the rates of whole-body protein breakdown were increased significantly. In conclusion, the rates of whole-body protein breakdown increased and nitrogen retention was aggravated significantly in animals administered the safflower oil emulsion. Significant increases of urinary excretion of total catecholamine were also observed. Prostaglandin E2 and thromboxane B2 concentrations were not significantly different among three groups. Supplementation with the new omega-3 fat emulsion, however, improved protein metabolism in burned rats receiving TPN.

Topics: Animals; Burns; Catecholamines; Dinoprostone; Energy Intake; Fat Emulsions, Intravenous; Fatty Acids; Fatty Acids, Omega-3; Fatty Acids, Omega-6; Fatty Acids, Unsaturated; Kinetics; Male; Nitrogen; Parenteral Nutrition, Total; Proteins; Rats; Rats, Sprague-Dawley; Thromboxane B2

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

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

D-myo-Inositol-1,2,6-triphosphate (IP3) has been shown to reduce edema and progressive ischemia following experimental skin burns. The mechanism(s) are not identified but could be related to antiinflammatory effects of the agent. In the present ex vivo study we compared the effects of IP3 with those of saline and indomethacin on eicosanoid formation by normal and burned rat skin. In burned skin IP 3 treatment reduced the release of thromboxane B2 (TXB2) (P < 0.01) and leukotriene B4 (LTB 4) (P < 0.05) but there was only a weak trend for less prostaglandin E (PGE) compared to burned control animals receiving saline. Indomethacin reduced the release of TXB2 (P < 0.01), and PGE (P < 0.001), but not LTB 4 from burned skin compared to skin from saline-treated burned animals. In non-burned skin IP 3 increased the release of PGE (P < 0.01) and LTB 4 (P < 0.01), but did not significantly influence TXB2 accumulation in the incubation fluid compared to the saline-treated group. Indomethacin reduced the release of TXB2 (P < 0.001) and PGE (P < 0.001), but increased LTB 4 (P < 0.001) in normal skin compared to the saline-treated group. In conclusion, IP 3 inhibited the release of TXB2 and LTB 4 from burned skin ex vivo, but increased PGE and LTB 4 release from normal skin. These results suggest that the mode of action of IP 3 differs from that of nonsteroidal antiinflammatory drugs. The effects of IP 3 on the arachidonic acid cascade also seem to differ in burned versus normal skin.

Topics: Animals; Anti-Inflammatory Agents, Non-Steroidal; Burns; Eicosanoids; Indomethacin; Inositol Phosphates; Leukotriene B4; Male; Prostaglandins E; Rats; Rats, Sprague-Dawley; Skin; Thromboxane B2

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

Since fatty acids influence prostaglandin synthesis, and since both fatty acids and prostaglandins modulate immune function, we investigated the hypothesis that manipulation of dietary fats would affect survival after infection in a murine burn model. Mice were fed for 2 to 3 weeks with diets containing different types and amounts of fat. They were then subjected to a 20% flame burn and infected with Pseudomonas aeruginosa. Survival in the group fed 40% of total calories as fish oil had significantly higher mortality than those fed safflower oil. This difference was not noted at lower fat levels. Similar groups of animals were sacrificed the day after injection. Splenic macrophage production of PGE2 was significantly lower in the fish-oil group, but production of LTB4 and TXB2 were not affected. In vitro tests of T- and B-cell function were not different amongst groups. We conclude that manipulation of dietary fats can alter outcome in this murine model of infection after thermal injury.

Topics: Animals; Burns; Dietary Fats, Unsaturated; Dinitrofluorobenzene; Dinoprostone; Fatty Acids, Unsaturated; Female; Hemolytic Plaque Technique; Leukotriene B4; Lymphocyte Activation; Lymphocyte Culture Test, Mixed; Mice; Mice, Inbred BALB C; Mice, Inbred C57BL; Pseudomonas Infections; Thromboxane B2

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

We studied the effect of a body burn on lung physiologic, biochemical, and histologic changes in a 2-day postburn period. A 15% of total-body-surface third-degree burn was produced in 24 adult sheep with lung and burn lymph fistulas. Eight sheep were killed at 12 hours and eight at 48 hours. At 12 hours we noted increased lung tissue lipid peroxidation, lung congestion, and neutrophil sequestration, in addition to a 30% decrease in lung compliance. Lung permeability and water content were not increased. Increased release of lipid peroxides and prostanoids were noted from burn tissue, as evidenced by increased plasma levels of malondialdehyde and conjugated dienes that remained elevated for about 8 hours and were decreased with wound removal. The lung inflammatory response was still present at 48 hours, the cells being primarily neutrophils. Nevertheless, the lipid peroxidation process, as measured by lung tissue malondialdehyde, had resolved. There was no evidence of burn tissue infection, measured by quantitative culture, to explain the persistent increase in lung inflammatory cells. Excision and closure of the burn wound at 3 hours postburn in eight sheep attenuated the lipid peroxidation and compliance changes but did not decrease the neutrophil sequestration. We conclude that burn injury results in a local wound oxidant release that leads to lipid peroxidation, both in wounds and in lung, as well as lung inflammation. The lipid peroxidation process may be attenuated by removal of the wound. The neutrophil sequestration is not altered, however, indicating this response occurs very early after injury, probably as a result of oxidant-initiated complement activation.

Topics: Animals; Blood Pressure; Blood Proteins; Burns; Carbon Dioxide; Cardiac Output; Epoprostenol; Hemodynamics; Inflammation; Lung; Lymph; Malondialdehyde; Oxygen; Partial Pressure; Reference Values; Sheep; Thromboxane B2

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

We determined the effect of a body burn on pulmonary function. Full-thickness burns varying in size from 25 to 70% of total body surface (TBS), were produced in sheep. Resuscitation was performed with lactated Ringer's. We noted an increase in lung transvascular fluid flux as measured by lymph flow, Q1, during the resuscitation period, varying from one- to threefold over baseline with the degree of increase directly proportional to the burn size. The increase in QL could be totally explained by the degree of hypoproteinemia which was also proportional to burn size. Transient pulmonary hypertension 20 +/- 4 to 26 +/- 5 mm Hg and a decrease in PaO2 from 90 +/- 5 to 83 +/- 6 torr occurred in the 50 and 70% burns as well as a significant decrease in lung compliance. These alterations were not due to pulmonary edema as there was no increase in measured lung water. Also, the increase in QL could be prevented by using a combination of Dextran and protein for resuscitation but this had no effect on the hypertension or hypoxia. Burn lymph and venous plasma thromboxane levels were increased during this period of lung dysfunction. Ibuprofen 12.5 mg/kg preburn and 12.5 mg/kg every 2 hours postburn decreased the degree of dysfunction suggesting a cause and effect relationship.

Topics: Animals; Burns; Dextrans; Ibuprofen; Isotonic Solutions; Lung; Lung Compliance; Lymphatic System; Pulmonary Edema; Resuscitation; Ringer's Solution; Sheep; Thromboxane B2

Our purpose was, in general, to determine the effect of a body burn on the pulmonary response to endotoxemia and, specifically, to determine whether increased thromboxane (TxA2) production by the burn wound was responsible for the accentuated lung injury. Thirty-two unanesthetized sheep with lung and soft tissue lymph fistulae were studied. Twelve sheep were given a sublethal dose of intravenous E. coli endotoxin (2 micrograms/kg). A characteristic two-phase injury was noted as evidenced by early pulmonary hypertension and hypoxia and later increased lung permeability. TxA2 was significantly increased in lung lymph as well as aortic plasma relative to venous plasma, indicating the lung to be the source. Twelve of 12 sheep survived. Five of 13 sheep died from endotoxemia when given 3-5 days after a 25% total body surface (TBS) burn and five of seven died with endotoxin (2 micrograms/kg) and a 50% burn. Physiologic parameters were at preburn levels before endotoxin. Animals died both during the early phase from hypoxia and the later phase due, in large part, to increasing pulmonary dysfunction. Absolute levels of TxA2 were not increased in the postburn animals, nor was there a clear release of TxA2 from burn tissue to explain the accentuated response. Prostacyclin levels were, however, less elevated in postburn animals in response to endotoxin, thereby altering the TxA2/PGI2 ratio in favor of TxA2. However, a cause and effect relationship between the increased lung injury and TxA2 remains undetermined. Lymph flow or lymph protein content was not altered in burn tissue in response to endotoxin.

Topics: Animals; Burns; Endotoxins; Epoprostenol; Escherichia coli; Female; Hemodynamics; Hypertension, Pulmonary; Lung; Lymph; Oxygen; Partial Pressure; Sheep; Thromboxane A2; Thromboxane B2; Time Factors

The participation of prostaglandin E in the regulation of the immune response via suppressor cell activation, and the release of large quantities of these prostaglandins as a result of thermal injuries, are both (separately) well documented. In this report, we present evidence that prostaglandin E plays an important immunologic role following thermal injuries. The concentration of PGE in sera from patients with major burn injuries is generally high (1,000-3,000 pg/ml), and these same sera are often significantly suppressive to in vitro lymphocyte responsiveness. We have documented the ability of PGE (both that which is commercially synthesized, and that isolated in fractions obtained from burned patient sera by column chromatography) to suppress mixed lymphocyte cultures, and show that such suppression can be blocked by either delipidation of serum fractions, or by the addition of monospecific anti-PGE to the cultures. We also report evidence suggesting the existence of a serum protein with a molecular weight of approximately 5,000 daltons which appears to be necessary for the expression of the immunosuppressive properties of PGE contained in patient sera.

Topics: Adolescent; Adult; Blood Proteins; Burns; Chromatography, Gel; Female; Humans; Hydrocortisone; Immune Tolerance; Lymphocyte Culture Test, Mixed; Lymphocytes; Male; Middle Aged; Prostaglandins; Prostaglandins E; Radioimmunoassay; Thromboxane B2

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

We studied the effects of a burn injury on the response of the lung to endotoxin. Seventeen unanesthetized sheep with lung lymph fistulas were studied. Eight were given Escherichia coli endotoxin (1.5 micrograms/kg) alone and nine were given the same dose 72 hours after a 25% total body surface burn injury. At this time after burn, all physiologic parameters were at baseline levels. A characteristic two-phase lung injury was seen after administration of endotoxin with an initial hypertension phase, characterized by pulmonary artery hypertension, and a second or permeability phase, characterized by an increase in protein-rich lymph flow. all eight animals that underwent only endotoxin administration survived, whereas four of the nine burned animals died during the permeability phase in pulmonary edema. Major physiologic differences between the groups were noted during the permeability phase, including a more severe hypoxia, pulmonary hypertension, and increased postburn lymph flow. Major biochemical changes included significant increases in lymph thromboxane, thromboxane B2, and beta-glucuronidase activity in the burn group. We conclude that the lung is more sensitive to endotoxin after burn, probably as a result of an increased release of products of arachidonic acid metabolism and products of leukocyte activation caused by the body burn.

Topics: Animals; Burns; Endotoxins; Escherichia coli Infections; Fistula; Glucuronidase; Hypertension, Pulmonary; Hypoxia; Lung Diseases; Lymph; Sheep; Thromboxane B2; Thromboxanes

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

Although edema is evident immediately after a burn, the diffusion of nutrient chemical constituents of the body is not impaired. Blister fluid, not unlike plasma or serum, contained all substances found in the body, including parenterally administered penicillin. The elevation of potassium and the cation to anion imbalance is primarily due to the Na/K cellular pump malfunction, and the destruction of the permeability of the cell membrane is most likely a direct result of complement and other cellular enzymes, which include the prostaglandins and thromboxanes. The elevated SGOT, CPK, and LDH indicated severe trauma to the cells in the immediate area of burn and possibly to the skeletal muscle. The presence of immunoglobulins indicated that high-molecular-weight proteins diffuse equally well during this edematous phase (IgM, 900,000; IgG, 190,000). Evidence of this nature strongly suggests that the integrity of the burn blister by maintained.

Topics: Biological Assay; Blister; Blood Proteins; Burns; Electrolytes; Enzymes; Exudates and Transudates; Humans; Immunodiffusion; Immunoelectrophoresis; Penicillins; Prostaglandins E; Thromboxane B2

Topics: Animals; Burns; Histocytochemistry; Humans; Immunoenzyme Techniques; Prostaglandins; Skin; Thromboxane B2; Thromboxanes

Leg lymph was collected from pentobarbital anaesthetized rabbits before and after scalding injury of the paw (75 degrees C for 20 s), and the contents of cyclic AMP (cAMP), prostaglandin E2 (PGE2) and PGF2 alpha and thromboxane B2 (TXB2) in lymph were determined. After injury lymph flow increased about four times. The maximal rate of flow was found between 30 and 60 min after scalding. The efflux of cAMP and immunoreactive iPGE2, iPGF2 alpha and iTXB2 also increased. The maximum values were detected at approximately 0-30, 30-60, 30-60 and 180-240 min, respectively, after the injury. The output of cAMP, iPGE2 and iPGF2 alpha and iTXB2 in lymph of the contralateral non-scalded paw remained low throughout the experiments. When rabbits were injected with indomethacin (2.5 mg/kg) or diclofenac sodium (2.5 mg/kg) immediately after the scalding injury, the efflux of cAMP, iPGE2 and iPGF2 alpha were low. Lymph flow was markedly reduced after treatment with diclofenac sodium; treatment with indomethacin did not significantly affect lymph flow. The results suggest a prostaglandin-dependent formation of cAMP following scalding injury which may be related to the initial responses to scalding.

Topics: Animals; Burns; Cyclic AMP; Diclofenac; Hindlimb; Indomethacin; Lymph; Prostaglandins E; Prostaglandins F; Rabbits; Thromboxane B2; Thromboxanes; Time Factors

The main urine metabolite of prostaglandin F2 alpha (5 alpha, 7 alpha-dihydroxy-11-ketotetranor-phostane-1, 16-dioic acid, PGF-metabolite) was determined by mass spectrometry (MS) and radioimmunoassay (RIA) in burned patients treated under routine conditions. The amount of the PGF-metabolite as determined by MS was 130 and 67 microgram/24 h (normal value 24 +/- 17 microgram/24 h) on days 3 and 5 respectively in one patient. In serial determinations using RIA the urine level of the PGF-metabolite was within normal values during the first days and rose to a broad peak 1-4 weeks after the injury. Thromboxane B2 (TXB2) was identified and quantitated in burn blister fluid. The amount of TXB2 was 1.7 ng/ml.

Topics: Adult; Burns; Humans; Male; Mass Spectrometry; Middle Aged; Prostaglandins F; Radioimmunoassay; Thromboxane B2; Thromboxanes; Time Factors