Biomedical subjects

C Lalonde

Publications and source records attributed to C Lalonde.

At least 37 records · Page 2Linked to original sources

PubMed1992

Oxidants and the pathophysiology of burn and smoke inhalation injury.

A skin burn is a common traumatic injury that results in both local tissue damage and a systemic mediator-induced response. There is evidence of both local and systemic oxidant changes manifested by lipid peroxidation in animal burn models and also in burned man. Both increased xanthine oxidase and neutrophil activation appear to be the oxidant sources. Animal studies have also demonstrated decreased burn edema, and also decreased distant organ dysfunction with the use of antioxidants, suggesting a cause-and-effect relationship, which needs to be tested in man. Smoke inhalation injury, a chemical injury to the airways caused by incomplete products of combustion, is frequently seen in conjunction with a body burn. Lipid peroxidation, both in lung and in distant organs, is also seen with this injury. The combined body burn and smoke inhalation injury lead to a marked increase in mortality rate and also an increase in the degree of generalized oxidant release and lipid peroxidation. Although data in man are limited, the available information, along with that from animal research on burns and smoke inhalation, indicates oxidants may well play a key role, and antioxidants may be of clinical therapeutic use.

Burns↗

PubMed1992

Relationship between hepatic blood flow and tissue lipid peroxidation in the early postburn period.

OBJECTIVES: To determine the effect of a body burn on effective or nutrient liver blood flow and the relationship between blood flow and oxidant-induced lipid peroxidation. DESIGN: Anesthetized sheep were given a 40% of total body surface, third-degree burn, after which animals were fluid resuscitated to return ventricular filling pressures and cardiac output to baseline values. Animals, for the 6-hr study period, were resuscitated with lactated Ringer's solution alone or lactated Ringer's solution plus 1500 mL of 5% hydroxyethyl starch or lactated Ringer's solution plus hydroxyethyl starch on which was complexed the iron chelator deferoxamine to prevent oxidant release. Effective liver blood flow was measured using the galactose infusion technique. Liver tissue lipid peroxidation was monitored using malondialdehyde content. RESULTS: We found that effective liver blood flow was decreased by 50% in the 4- to 5-hr postburn period, even when animals were resuscitated to baseline cardiac output values with lactated Ringer's solution. Tissue malondialdehyde content increased in the group treated with lactated Ringer's solution from a control value of 110 +/- 7 to 202 +/- 59 nmol/g of tissue. Resuscitation with hydroxyethyl starch restored postburn effective liver blood flow to control values, but malondialdehyde content was still increased two-fold. Resuscitation with hydroxyethyl starch and deferoxamine resulted in an increase in effective liver blood flow postburn to a value 80% above controls. In addition, lipid peroxidation was prevented. CONCLUSIONS: Effective liver blood flow is markedly decreased after burn injury, even with apparently adequate volume resuscitation, when using lactated Ringer's solution. Liver lipid peroxidation persists even when effective liver blood flow is maintained, indicating that the oxidant process is not solely related to blood flow. Infusion of the antioxidant deferoxamine during resuscitation not only prevents the lipid peroxidation, most likely by a nonblood-flow-related process, but also results in an increase in blood flow above normal rates, suggesting that postburn liver oxygen needs exceed normal values.

Animals↗

PubMed1992

Lung oxidant changes after zymosan peritonitis: relationship between physiologic and biochemical changes.

Our purpose was to determine the effect of non-bacteria-dependent systemic inflammation on the degree and time course of lung oxidant activity and antioxidant defenses, comparing these changes with lung, physiologic, and histologic alterations. Adult male rats were given intraperitoneal zymosan (0.7 mg/g body weight) and were fluid resuscitated. Oxidant changes were measured as lung tissue oxidized glutathione (GSSG) and malondialdehyde (MDA) content, antioxidant defenses as tissue reduced glutathione (GSH), and catalase. Animals were killed at 4, 12, and 24 h, and at 5, 10, and 30 days. Lung data were compared with that found in liver. We noted a 45% mortality in the first 18 to 36 h with all remaining animals surviving. In the first 24 h, we noted a doubling of lung MDA and an 80% conversion of tissue GSH to GSSG compared with less than 5% in control animals, indicating a severe oxidant stress. These findings corresponded with marked increase in lung neutrophils. Arterial pressure (PaO2) was significantly decreased from a control of 95 +/- 4 mm Hg to 80 +/- 5 mm Hg and 75 +/- 4 mm Hg at Days 5 and 10, respectively, but returned toward control by 30 days. Lung GSSG and MDA remained significantly increased for the 30-day period, whereas amounts of the antioxidants, catalase, and GSH returned to control after 24 h. The ongoing oxidant stress corresponded with marked mononuclear cell infiltration and interstitial thickening, which persisted over the 30-day period even after peritonitis had completely resolved.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1992

Burn edema is accentuated by a moderate smoke inhalation injury in sheep.

We determined the lung and systemic response of a moderate smoke inhalation injury combined with a 15% total body surface third-degree burn compared with a burn alone and inhalation alone. Adult sheep were prepared with chronic lung and bilateral prefemoral soft tissue lymph fistula. The burn was confined to one side. Physiologic parameters, lymph flow (QL), and lymph/plasma protein ratio were monitored. Oxidant changes were measured as lipid peroxidation by circulating and lymph-conjugated dienes and lung tissue malondialdehyde. Animals were resuscitated with lactated Ringer's solution during the 24-hour study period to restore and maintain vascular filling pressures and cardiac index. We found net 24-hour fluid balance for burn-inhalation injuries to be 4.1 +/- 1.2 L compared with burn alone of 2.9 +/- 0.9 L and inhalation alone of 2.4 +/- 0.5 L, a significant difference. Protein-rich burn tissue QL increased by fivefold to sixfold with burn alone compared with more than tenfold with burn-inhalation injury. A twofold increase in both lung and nonburn soft tissue QL was also seen in the combined injury not seen with burn alone. Arterial blood gases decreased only at 12 hours. Plasma conjugated dienes were increased in all groups, whereas burn lymph values were increased only in combined insult. In addition, lung malondialdehyde content at 24 hours was 155 +/- 11 nmol/gm with burn-inhalation injury compared with 62 +/- 8 nmol/L for burn alone, 55 +/- 9 nmol/L in inhalation alone, and 45 +/- 4 nmol/L for controls. However, no alveolar flooding was noted in any group. We conclude that a modest smoke inhalation (carboxyhemoglobin of 25%) added to a 15% total body surface burn markedly increases the degree of burn edema, as well as nonburn soft tissue and lung QL, compared with burn alone, indicating increased plasma to interstitial fluid transport in these tissues as well. Increased burn tissue lipid peroxidation products corresponded with the increased burn fluid losses. The increased lung lipid peroxidation also indicates further lung oxidant activity as well.

Animals↗

PubMed1991

Effect of dobutamine on oxygen consumption and fluid and protein losses after endotoxemia.

OBJECTIVE: To determine the effect of a dobutamine infusion on the relationship between oxygen consumption (VO2) and oxygen delivery (DO2) after endotoxin administration, as well as the rate of fluid and protein loss from permeability-injured tissue. METHODS: Unanesthetized adult sheep with lung and soft-tissue lymph fistulas were given 5 micrograms/kg Escherichia coli endotoxin alone, or E. coli endotoxin plus a continuous infusion of dobutamine (10 to 15 micrograms/kg.min) beginning at 3 hrs. Lymph flow reflected the vascular permeability and surface area perfused. Data were compared with dobutamine alone and with controls. Filling pressures were maintained at baseline. RESULTS: Dobutamine alone produced a 75% increase in DO2, a transient 10 +/- 4% increase in VO2, but no increase in lung or soft-tissue lymph flow. Beginning at 3 hrs after endotoxin alone, a significant increase in protein-rich lung and soft-tissue lymph flow was noted, but only a transient 14 +/- 5% increase in VO2. Plasma proteins were slightly decreased. With the addition of dobutamine at 3 hrs postendotoxin, DO2 increased by greater than 50% for the 3-hr infusion period, while VO2 increased for a 30-min period by 25 +/- 8%, which was not different than endotoxin alone. Lung and soft-tissue lymph flow did not increase further, but plasma proteins did decrease significantly compared with controls and with endotoxin alone. CONCLUSION: Increasing DO2 with dobutamine postendotoxin does not increase the surface area perfused or the edema process, at least in lung and soft tissue. Therefore, no microvessels in these tissues are reopened with dobutamine when normal filling pressures are present. Dobutamine administration does not increase VO2 more than the increase seen with endotoxin alone.

Animals↗

PubMed1990

Systemic lipid peroxidation and inflammation induced by thermal injury persists into the post-resuscitation period.

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.

6-Ketoprostaglandin F1 alpha↗

PubMed1989

Effect of increasing oxygen delivery postburn on oxygen consumption and oxidant-induced lipid peroxidation in the adult sheep.

We studied the relationship between oxygen delivery (DO2) and oxygen consumption (VO2) in the early post-burn period. Unanesthetized sheep with a 15% total body surface (TBS) third-degree burn were resuscitated back to baseline VO2 and vascular pressures. DO2 was adjusted further by infusion and removal of whole blood. The response was compared to the same maneuver in nonburned sheep. We found that increasing DO2 after burns resulted in a 32% increase in VO2, while the same maneuver in controls produced no change in VO2. We then determined whether the increase in VO2, caused by volume loading, resulted in a further increase in postburn oxidant release and lipid peroxidation measured as conjugated dienes. Plasma conjugated dienes increased significantly and equally by 30% in burns maintained at baseline VO2 vs. the increased VO2. Therefore, the increased oxygen used is not simply resulting in further oxidant damage. VO2 was maintained equally in both burned animals and controls with a decrease in DO2 by increased oxygen extraction from Hgb. We conclude that standard burn resuscitation does not restore adequate DO2 for oxygen demands. The 30% increase in VO2 achieved by increasing DO2 does not lead to a further release of oxidants from burn tissue and is therefore potentially beneficial for cell function.

Animals↗

PubMed1988

Endotoxin causes hydrogen peroxide-induced lung lipid peroxidation and prostanoid production.

We studied the role of hydrogen peroxide release on endotoxin-induced lung injury in unanesthetized sheep with chronic lung lymph fistulas. We also further defined the relationship between endotoxin injury, lipid peroxidation, and prostaglandin production. Sheep were given endotoxin alone (1 microgram/kg) or pretreated with catalase (32,500 U/kg) or ibuprofen (12.5 mg/kg). Endotoxin alone resulted in an early prostanoid release, lipid peroxidation measured as circulating conjugated dienes both one and four hours after the administration of endotoxin, pulmonary hypertension, hypoxia, and increased protein permeability. Permeability was monitored by lymph flow and lymph protein content. Catalase pretreatment significantly attenuated all of these aspects of the endotoxin response. Ibuprofen prevented the early lung changes and blocked prostanoid release but did not attenuate the increased permeability. In addition, cyclo-oxygenase inhibition had a dual effect on lipid peroxidation, increasing initial conjugated diene levels while suppressing the later release. The initial effect was clearly related to cyclo-oxygenase blockade. The early conjugated diene release appears to be related to arachidonic acid metabolism and does not correspond to the degree of increased permeability. We conclude that H2O2 plays a major role in lung injury after endotoxin.

Animals↗

PubMed1988

Endotoxemia produces an increase in arterial but not venous lipid peroxides in sheep.

Our purpose was to determine the effect of an endotoxin-induced lung injury on circulating lipid peroxides. We measured both malondialdehyde (MDA) and conjugated dienes (as optical density at 233 nm) in aortic and venous plasma and lung lymph in 10 unanesthetized sheep given 1 microgram/kg of Escherichia coli endotoxin. Total lipids and prostanoids 6-ketoprostaglandin F1 alpha and thromboxane B2 were also measured. Six control sheep were also studied. Animals were monitored for a 12-h period and then killed, and lung tissue MDA was determined. A two-phase endotoxin response was noted with an initial pulmonary hypertension followed by a steady-state increase in protein-rich lung lymph flow (QL) between a 3- and 6-h period. Aortic plasma MDA was significantly increased from a base line of 4.8 +/- 1.4 to 8.9 +/- 1.6 and 7.5 +/- 1.3 nmol/ml at 1 and 4 h post-endotoxin. Aortic plasma conjugated dienes increased in all 10 sheep post-endotoxin. Venous levels of both MDA and conjugated dienes were not significantly increased. Lung QL increased two- to three-fold. Lung lymph MDA increased significantly at 1 h post-endotoxin. Lymph conjugated dienes decreased. Plasma and lymph lipid peroxide levels returned to base line by 12 h in most animals. However, tissue MDA remained significantly increased in all sheep from base line of 45 +/- 9 to 85 +/- 14 nmol/g tissue. We conclude that both MDA and conjugated dienes are transiently released into aortic plasma during endotoxin-induced oxidant lung injury.(ABSTRACT TRUNCATED AT 250 WORDS)

6-Ketoprostaglandin F1 alpha↗

PubMed1988

Catalase prevents prostanoid release and lung lipid peroxidation after endotoxemia in sheep.

We determined the effect of H2O2 on both the physiological and biochemical lung changes seen in the adult sheep after endotoxin. Fourteen unanesthetized adult sheep with chronic lung lymph fistula were given Escherichia coli endotoxin (1 microgram/kg) over 30 min. Seven sheep were given catalase (32,500 U/kg body wt) as an intravenous bolus 30 min before endotoxin. Four sheep were given catalase alone. Oxidant lung changes were measured using arterial plasma conjugated dienes and lung tissue malondialdehyde (MDA) content, both reflecting the lipid peroxidation process. Animals were killed 5 h after endotoxin. We found that endotoxin alone caused an early increase in pulmonary arterial pressure lung lymph flow (QL), plasma thromboxane B2, 6-keto-prostaglandin F1 alpha, and plasma conjugated dienes. A decrease in cardiac output and arterial PO2 was also seen. A three- to four-fold increase in protein-rich QL was noted at 3-4 h as well as a continued increase in arterial conjugated dienes. Lung MDA and water content were also significantly increased from base line. Catalase pretreatment significantly attenuated both the physiological changes and the prostanoid and conjugated diene release. Lung MDA and water content also remained at base line. We conclude that H2O2 plays a major role in endotoxin-induced lung injury as well as the resulting lipid peroxidation process.

Animals↗

PubMed1988

Effect of partial burn excision and closure on postburn oxygen consumption.

We studied the effect of partial excision and wound closure on the postburn hypermetabolic state. A 25% of total body surface burn was produced in seven sheep. Oxygen consumption (VO2) was significantly increased to 215 +/- 44 ml/min/M2 by day 3 compared with baseline of 125 +/- 21 ml/min/M2. The calculated increase was the result of the increased cardiac index as the average oxygen (AvO2) difference remained relatively constant. Body temperature was not significantly increased. Plasma and burn lymph thromboxane B2 were significantly increased. On day 7, 60% of the burn was completely excised to fascia and covered with a full-thickness graft from a donor animal. The VO2 decreased to below preburn levels during the period of anesthesia but returned completely to the preexcision hypermetabolic state by 2 hours after anesthesia and remained at this level for the remaining 2-day postexcision period. Quantitative cultures of burn hide at day 7 postburn and of the remaining 10% of total body surface burn at 2 days after excision revealed values less than 10(5) bacteria/gram eschar. No positive blood cultures were evident. We conclude that postburn hypermetabolism, once developed, may be perpetuated by a burn of lesser size. Partial excision, therefore, does not appear to significantly decrease the hypermetabolic state if a substantial inflammatory wound remains. Infection is not necessary to perpetuate the increased VO2.

Anesthesia↗

PubMed1988

Early pulmonary and hemodynamic effects of a chest wall burn (effect of ibuprofen).

The cardiopulmonary effects of a third-degree scald burn involving the anterolateral chest wall was compared with a burn of equal size (30% of total body surface) to the flanks in anesthetized sheep with lung lymph fistulas. The chest-burn group was characterized by immediate decreases in cardiac output (6.5 to 3.0 L/min), central venous pressure (5 mm Hg to 0 mm Hg), pulmonary wedge pressure (10 mm Hg to 6 mm Hg), and urine output 1.5 ml/kg/hr to less than 0.5 ml/kg/hr. The temperature of pulmonary artery blood increased from 38 to 42 degrees C and plasma prostacyclin increased from 20 to 200 pg/ml. These changes were significantly different from those seen in the body sheep with burns. Initial fluid requirements necessary to restore filling pressures were 50% greater in the sheep with chest burns than in the sheep with body burns. An early decrease in static lung compliance was also seen after chest burn that was not the result of increased lung edema. A progressive decrease in compliance, urine output, and stroke output was also seen in the later postburn period (6 to 7 hours), which was significantly improved by a chest wall escharotomy. Postmortem analysis in the chest-burn group revealed a significantly increased malondialdehyde content, a reflection of increased oxygen radical-induced lipid peroxidation relative to the body burn. Pretreatment of the chest burn with ibuprofen, 12.5 mg/kg, prevented the initial vasodilator and lung compliance changes so that early cardiopulmonary status was identical to that seen with a body burn alone. Ibuprofen also decreased the lung tissue malondialdehyde content. We conclude that a burn involving the chest wall results in cardiopulmonary abnormalities, not seen after a body burn of a comparable size, which appear to be due to hyperthermia and an increased release of prostacyclin and O2 radicals.

Animals↗

PubMed1988

Tissue inflammation without bacteria produces increased oxygen consumption and distant organ lipid peroxidation.

An inflammatory focus was produced by implantation of gauze below the hide in the flanks of six sheep with flank lymph fistulas. Physiologic and metabolic parameters were monitored in the unanesthetized animals for 7 days, after which the gauze was removed and monitoring continued for another 5 days. Animals were then killed. Lung and liver tissue was inspected and analyzed for lipid peroxide content. Data were compared with those of six controls in which gauze was not implanted. We noted a transient significant increase (on day 1 only) in wound lymph, thromboxane B2, and 6-keto-PGF1 alpha from baseline values of 190 +/- 70 and 20 +/- 10 pg/ml to 1000 +/- 240 and 420 +/- 70 pg/ml, respectively. Plasma values were also significantly increased on day 1. Body temperature increased by 1 degree C and cardiac index increased by 30% during this period, whereas oxygen consumption, VO2, was not significantly increased. The VO2 and cardiac index increased by 50% over baseline, beginning on day 5, whereas systemic vascular resistance decreased. Body temperature was not increased. These changes corresponded with an increase in wound lymph monocyte count from 0% to 15% of total. The VO2 and cardiac index remained increased after gauze removal. No bacteria were found in the wound. Postmortem analysis revealed a marked monocyte-macrophage infiltration in both lung and liver. Lung water, represented as water content over dry weight, was normal. Lung and liver lipid peroxidation, measured by the by-product malondialdehyde content, increased 300% and 90% over control values, respectively. We conclude that a local, nonbacteria-induced wound inflammation increases VO2, with the increase not corresponding to increase in body temperature. Distant organ changes, namely, changes in lung and liver, were also evident 5 days after gauze removal.

Animals↗

PubMed1987

Topical ibuprofen decreases early postburn edema.

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.

6-Ketoprostaglandin F1 alpha↗

PubMed1987

The effect of complete burn wound excision and closure on postburn oxygen consumption.

We determined the effect of complete excision and closure of the burn wound on the postburn increase in oxygen consumption. Twelve sheep were given a 15% of total body surface full-thickness burn and were monitored for 7 days. By the third day, a 50% increase in O2 consumption, VO2, was noted, as was a significant increase in cardiac index and decrease in mixed venous PO2, compared to baseline. The hypermetabolic process persisted for the 7-day pre-excision period. On the seventh postburn day all sheep were anesthetized for 2 hours with halothane and placed on positive pressure ventilation, and then one half of these sheep underwent excision and closure. During anesthesia, VO2 decreased to 76 +/- 15 ml/min/M2, a value significantly lower than even the preburn awake baseline of 122 +/- 14 ml/min/M2 and the 7-day postburn value of 180 +/- 18 ml/min/M2. Quantitative cultures, before excision, revealed the wounds to be noninfected (less than 10(5) organisms per gram). In six animals, the burns were totally excised to fascia and closed with full-thickness defatted hide from other sheep obtained at the same time under sterile conditions. In these animals, the VO2 returned to preburn baseline by 24 hours postexcision and remained there for the 3-day postexcision study period. In the other six burned sheep, the 15% full-thickness burns remained. The hypermetabolic state returned to the 7-day postburn level on return to the awake state and persisted for the remainder of the study. We conclude that complete excision and wound closure can reverse the postburn increase in O2 consumption.

Anesthesia↗

PubMed1987

The immediate effect of burn wound excision on pulmonary function in sheep: the role of prostanoids, oxygen radicals, and chemoattractants.

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.

6-Ketoprostaglandin F1 alpha↗

PubMed1986

Effect of anesthesia and positive pressure ventilation on early postburn hemodynamic instability.

Our purpose was to determine the effect of anesthesia and positive pressure ventilation, PPV, on early postburn (1-12 hr) cardiopulmonary changes. Adult sheep were given a 40% full-thickness TBS burn not involving chest wall. Halothane anesthesia and PPV alone decreased cardiac output by 20% but also decreased oxygen demands by 30% from the awake state. Systemic vascular resistance, SVR, was increased by 40% over the awake state in the first several hours postburn: cardiac output was decreased despite baseline filling pressures. Low molecular weight dextran, LMWD, prevented the increased SVR by decreasing resistance to flow. A continued decrease in cardiac output was evident during the next 6-12 hr postburn with anesthesia while awake sheep values returned to baseline. Fluid requirements to maintain filling pressures also increased by 30% over the awake state. Static lung compliance, CSTAT, decreased from a baseline of 43 +/- 5 to 32 +/- 4 ml/cm H2O with anesthesia and ventilation. This was due to nonburn chest wall edema: lung water was normal. The 7-cm H2O increase in inspiratory pressure necessary to maintain constant volume was the cause of the decreased cardiac output, because maintaining pressure constant resulted in no decrease in cardiac output. VO2 remained relatively constant due to increased O2 extraction. LMWD prevented the CSTAT changes and, in turn, the decreased output. We conclude that both the increase in SVR and decrease in CSTAT postburn resulted in a significant decrease in cardiac output with anesthesia not seen in the awake burn state. The decreased output was, however, in large part compensated for by decreased O2 demands and increased O2 extraction.

Anesthesia↗

PubMed1986

Topical ibuprofen decreases thromboxane release from the endotoxin-stimulated burn wound.

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)

6-Ketoprostaglandin F1 alpha↗