Multiple-organ dysfunction in the surgical patient: pathophysiology, prevention, and treatment.
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Humans↗
Biomedical subjects
R Demling
Publications and source records attributed to R Demling.
Relationship between liver oxidant stress and antioxidant activity after zymosan peritonitis in the rat.
OBJECTIVE: To determine the effect of a severe nonbacterial-dependent peritonitis on the degree and time course of liver oxidant stress and antioxidant activity. DESIGN: Prospective, randomized, controlled study. SETTING: Animal laboratory. SUBJECTS: Thirty-eight male Sprague-Dawley rats were injected with zymosan 0.75 mg/g body weight, mixed in mineral oil, and fluid resuscitated. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Oxygen consumption (VO2), base deficit, and blood gases were determined. Liver tissue oxidized and reduced glutathione, malondialdehyde catalase, xanthine oxidase, and xanthine dehydrogenase were measured and data were compared with both a pair-fed and an ad libitum fed group over a 24-hr period. We noted a 30% mortality rate with animals dying between 20 and 24 hrs. Peak decrease in VO2 occurred at 12 hrs, corresponding with a metabolic acidosis. Marked liver oxidant stress was seen at 4 hrs with oxidized glutathione increased from a control value of 0.2 +/- 0.1 to 1.1 +/- 0.2 mg/g of tissue, while reduced glutathione decreased from a control value of 1.8 +/- 0.1 to 0.3 +/- 0.1 mg/g. By 24 hrs, oxidized glutathione activity was no longer increased, but reduced glutathione concentrations were still markedly decreased. Tissue catalase was also significantly decreased at the 24-hr period. Liver malondialdehyde was increased at 24 hrs when the peak decrease in antioxidants was evident. Liver xanthine oxidase activity increased significantly from 15 +/- 3 to 45 +/- 8 mumol uric acid/min/g by 4 hrs and remained increased, with the initial increase predating evidence of impaired perfusion. Pair-fed animals demonstrated no changes in oxidant or antioxidant activity. CONCLUSIONS: We conclude that a marked increase in liver oxidant stress and decrease in antioxidant activity occurs in the first several hours after the onset of nonbacterial peritonitis. An early increase in liver xanthine oxidase activity may be a source of the oxidants. Decreased liver antioxidant activity persists well after the oxidant stress resolves.
Acidosis, Lactic↗
Relationship of burn-induced lung lipid peroxidation on the degree of injury after smoke inhalation and a body burn.
OBJECTIVE: We compared the effect of a modest smoke inhalation injury, a burn injury alone, and a smoke inhalation injury plus a body burn, on the degree of lung oxidant-induced lipid peroxidation and lung injury. DESIGN: Prospective animal study with concurrent controls. SETTING: An animal laboratory. SUBJECTS: Forty-four adult yearling female sheep (weight range 45 to 50 kg). INTERVENTIONS: Forty-four sheep were prepared with lung and prefemoral (soft tissue) lymph fistulas. Twelve breaths of cooled smoke with tidal volume of 10 mL/kg body weight were given to 24 sheep, producing a peak blood carboxyhemoglobin of 25% to 30%. Twelve sheep also received a 15% total body surface third-degree burn. Sheep were killed at 4 or 24 hrs. MEASUREMENTS AND MAIN RESULTS: Circulating lipid peroxidation was monitored as conjugated dienes and tracheobronchial mucosal and lung parenchyma as malondialdehyde. Antioxidant defenses were monitored by catalase activity. Lung physiologic and histologic changes were compared. We noted intense airways inflammation in both smoke inhalation groups and lung parenchymal inflammation in all groups. Lung lymph flow was modestly increased (two-fold) in the smoke inhalation groups. Alveolar water content was not significantly increased after any injury. PaO2 was decreased at 24 hrs after the smoke insult alone. Parenchymal malondialdehyde content did not increase with the smoke insult alone, but did increase from a control value of 110 +/- 20 to 270 +/- 24 nmol/g tissue by 4 hrs in the combined burn and smoke injury group, while catalase activity decreased. Airway mucosal malondialdehyde did not increase in any group. CONCLUSIONS: We conclude that alveolar capillary permeability is not increased early after a moderate smoke injury or smoke injury with burn. Lipid peroxidation is not increased in large airway or lung parenchyma with early after-smoke exposure. The addition of a burn significantly increases lung parenchymal lipid peroxidation, but the oxidant changes do not correspond with the degree of early lung dysfunction.
Animals↗
The effect of acute nonbacterial dependent peritonitis on lung and liver oxidant stress and antioxidant activity.
BACKGROUND: The role of oxidant release and tissue antioxidant defenses on inflammation-induced organ injury is not clearly defined. METHODS: We determined the effect of acute zymosan peritonitis in rats on lung and liver tissue oxidant stress and antioxidant defenses during a 5-day period. Oxidant activity was measured as tissue malondialdehyde and oxidized glutathione (GSSG). Antioxidant activity was measured as tissue-reduced glutathione (GSH) and catalase activity. Rats were maintained hydrated with subcutaneous crystalloid. Animals were killed at 4, 12, and 24 hours and 5 days. RESULTS: Acute peritonitis was evident at 12 and 24 hours but was resolving at 5 days. Peritoneal fluid cultures were negative after 24 hours. A 50% mortality rate was noted between 20 and 30 hours, with no deaths after 30 hours. We noted a significant increase in lung GSSG and malondialdehyde at 4 hours that persisted for the 5 days, as did histologic evidence of a progressing severe lung inflammation. No increased conversion of lung xanthine dehydrogenase to xanthine oxidase was noted. Lung GSH and catalase activity were maintained at control despite negligible food intake. In contrast, liver GSSG was increased significantly only at the 4-hour period, corresponding with a transient conversion of xanthine dehydrogenase to xanthine oxidase from 10% to 31%. Tissue malondialdehyde did not increase despite the initial oxidant stress. However, tissue GSH and catalase values decreased by more than 50% after 24 hours and remained decreased at 5 days. CONCLUSIONS: We conclude that early lung and liver oxidant stress is initiated by acute peritonitis. Lung oxidant changes persist and lung dysfunction progresses, even though antioxidant activity is maintained and acute peritonitis is resolving. Liver lipid peroxidation did not develop despite oxidant release, probably because of a large antioxidant reserve. However, a severe and sustained decrease in liver antioxidants results, increasing the potential damage from a subsequent oxidant insult.
Animals↗
Pentoxifylline does not prevent endotoxin induced lung and liver lipid peroxidation in the adult sheep.
Our purpose was to determine the effect of pentoxifylline pretreatment on endotoxin-induced (5 microgram/kg) lung and systemic oxidant activity, measured as lipid peroxidation. We used the awake adult sheep with lung and soft tissue lymph fistulae to monitor microvascular changes as well as to monitor oxygen delivery and consumption. Oxidant activity was monitored using the level of plasma conjugated dienes, a measure of circulating lipid peroxides, and lung and liver malondialdehyde content, a measure of tissue lipid peroxidation. Sixteen sheep were given endotoxin, eight of which were pretreated with pentoxifylline (20 mg/kg bolus) followed by a 6 mg/kg/hr infusion. We found that the degree of early endotoxin-induced pulmonary hypertension and hypoxia and later increased pulmonary microvascular permeability was not attenuated with pentoxifylline. In addition, a comparable increase in circulating conjugated dienes, lung neutrophil sequestration, and a three-fold increase in lung malondialdehyde was seen in both groups. Soft tissue QL also increased to the same degree in both groups. Liver MDA increased from a control of 110 +/- 20 nM/g tissue to 165 +/- 32 nM/g with endotoxin alone and to 260 +/- 55 nM/g with pentoxifylline pretreatment, a significant increase over both control and endotoxin alone groups. Pentoxifylline, however, did improve hemodynamic stability, required significantly less fluid, and prevented the hyperdynamic state seen at 4-5 hr post endotoxin. We conclude that pentoxifylline attenuates the initial endotoxin-induced hemodynamic instability, and later hyperdynamic state. However, pentoxifylline pretreatment does not appear to prevent endotoxin-induced oxygen radical release in the unanesthetized sheep.
Animals↗
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↗
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↗
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↗
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↗
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↗
Fluid resuscitation with deferoxamine prevents systemic burn-induced oxidant injury.
We studied the effect of deferoxamine (DFO) infused after burns on hemodynamic stability as well as local and systemic inflammation and oxidant-induced lipid peroxidation. Eighteen anesthetized sheep were given a 40% of total body surface burn and fluid resuscitated to restore oxygen delivery (DO2) and filling pressures to baseline values. Animals were resuscitated with lactated Ringer's (LR) alone or LR plus 1,500 ml of a 5% hetastarch complexed with DFO (8 mg/ml). Animals were killed 6 hours postburn. The sheep resuscitated with LR and LR plus hetastarch demonstrated significant lung inflammation and significant increases in lung and liver malondialdehyde (MDA) from controls of 47 +/- 6 and 110 +/- 7 nMol/gm to 63 +/- 13 and 202 +/- 59 for LR and 67 +/- 4 and 211 +/- 9 for LR + hetastarch, respectively. The group resuscitated with hetastarch alone required 15% less fluid. VO2 returned to baseline values in both groups by 2 hours. Resuscitation with the 5% hetastarch-DFO decreased total fluids by 30% over LR and prevented the increase in lung and liver MDA. In addition, postburn VO2 increased by 25% above baseline values. Burn tissue edema, measured as protein-rich lymph flow, was significantly increased with the administration of DFO compared with the other groups. We conclude that DFO used for burn resuscitation prevents systemic lipid peroxidation and decreases the vascular leak in nonburn tissues while also increasing O2 utilization. Resuscitation with hetastarch-DFO may accentuate burn tissue edema, possibly by increased perfusion of burn tissue.
Animals↗
Use of antioxidant therapy in shock and trauma.
Antioxidant therapy can be defined in the clinical setting as any process that prevents or decreases oxidant injury. A number of common clinical approaches to the shock and trauma patient can be considered as preventing oxidant damage. In fact, their beneficial effects may be related more to antioxidant activity than is currently recognized. In addition, there are a number of new drugs, many of them already clinically used for other indications, that have antioxidant and general inflammatory activity and are either undergoing or are about to undergo clinical testing. The era of antioxidant therapy has arrived.
Antioxidants↗
Pulmonary dysfunction after cerebral injury.
Pulmonary dysfunction is a common complication of severe head injury. The degree of initial hypoxemia which develops appears to correspond with the location and magnitude of the head injury. If unrecognized and not aggressively treated, the hypoxic insult will magnify the cerebral insult. A severe postinjury hypermetabolic state also develops and, if unrecognized and not managed aggressively with nutritional support, can also lead to severe catabolism, increased infection, and further lung dysfunction. Although supportive care is the major treatment at present, pharmacologic manipulation of the increased catecholamine activity, which is considered to be causative, may be effective in controlling both the impaired gas exchange and the hypermetabolic state. A knowledge of the various lung dysfunction states which occur in the head-injured patient population is required to optimize recovery and minimize complications.
Craniocerebral Trauma↗
Relationship between lung injury and lung lipid peroxidation caused by recurrent endotoxemia.
We compared the relationship between lung lipid peroxidation and the histologic and physiologic changes seen after repeated doses of low dose endotoxin in unanesthetized sheep. Thirty-two sheep with lung lymph fistula were given from 1 to 10 doses of 1 micrograms/kg Escherichia coli endotoxin, 12 h apart. Animals were killed 5 h after 1, 3, 5, or 9 doses of endotoxin or 3 to 5 days after the tenth dose of endotoxin. The lipid peroxidation process was monitored by circulating conjugated dienes and lung tissue malondialdehyde (MDA) content. We found that conjugated dienes and MDA were increased after one dose of endotoxin corresponding in time with the increased prostanoid production and increased permeability. Acute lung inflammation was also evident histologically. Lipid peroxidation was not increased, however, when 3 to 7 doses were given. The permeability change was also markedly attenuated whereas severe lung inflammation was still present on histologic examination. After 9 doses, we noted a fourfold increase in lung tissue MDA that corresponded histologically with a marked mononuclear cell infiltration. Physiologic changes included a sustained 50% increase in oxygen consumption. However, lung lymph flow was not increased, again, reflecting lung inflammation with no change in lung vascular permeability. The MDA remained increased 5 days after the last dose of endotoxin along with a marked lung mononuclear cell infiltration. The lung MDA content corresponded with the level of increase in VO2, but not with changes in pulmonary vascular permeability. Conjugated dienes were increased only after the first injection of endotoxin. The lung lipid peroxidation process does not appear to correspond to physiologic or histologic lung changes after recurrent exposures to endotoxin.
Animals↗
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↗
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↗
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↗
Entry of four cephalosporins into the ovine lung.
Following cannulation of the right external jugular vein and the efferent duct of the right caudal mediastinal lymph node (the caudal end of this node having been ligated to cut off the inflow of systemic lymph), sheep were each given one of four "cephalosporins" (cefazolin, moxalactam, cefoperazone, or ceftriaxone) as single doses injected iv over 30 min. All of the drugs appeared in the pulmonary lymph during iv infusion. Peak concentrations in the lymph were attained at 5 min postinfusion with cefazolin, cefoperazone, and ceftriaxone; the peak for moxalactam was attained at 30 min postinfusion. Cefazolin and cefoperazone penetrated better than did ceftriaxone, which penetrated better than did moxalactam. The concentrations of moxalactam, as compared with the other drugs, declined more gradually in both venous blood and pulmonary lymph. In view of the prompt entry and transit through the lungs and the high concentrations attained in the pulmonary lymph, these drugs should be effective in the treatment of pneumonias caused by susceptible bacteria.
Albumins↗