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Biomedical subjects

R H Demling

Publications and source records attributed to R H Demling.

At least 19 recordsLinked to original sources
PubMed1992

The Surgical Infection Society's policy on human immunodeficiency virus and hepatitis B and C infection. The Ad Hoc Committee on Acquired Immunodeficiency Syndrome and Hepatitis.

The Ad Hoc Committee on Acquired Immunodeficiency Syndrome and Hepatitis of The Surgical Infection Society has outlined its policy regarding three deadly blood-borne viral infections. The risk of transmission of these microbes, the role of preoperative testing, the problem of the human immunodeficiency virus-infected surgeon, and conduct in the operating room are discussed.

General Surgery↗
PubMed1992

Oxygen consumption early postburn becomes oxygen delivery dependent with the addition of smoke inhalation injury.

We determined the relationship between oxygen delivery, DO2, and oxygen consumption, VO2, in sheep after a moderate smoke inhalation injury and 15% TBSA third-degree burn compared with burn alone and controls. Comparison was made beginning three hours after injury when carboxyhemoglobin levels were back to baseline values. We decreased DO2 between three and eight hours by 25% by either removing blood (controls) or decreasing the resuscitation fluid infusion rate. Lung oxidant, measured as tissue malondialdehyde (MDA) levels, and histologic changes were also assessed. Animals were killed at 24 hours. We found that in controls and animals with a burn alone, a 25% decrease in DO2 was compensated for by an increase in O2 extraction, maintaining VO2 constant. Correlation of DO2 to VO2 was r2 = 0.3, indicating independence of VO2 from DO2. With the combined injury, VO2 decreased in proportion to DO2, since O2 extraction did not increase. The correlation of DO2 to VO2 was r2 = 0.9, indicating delivery-dependent consumption, a pathologic process most likely caused by increased inflammatory mediators from the combined injury. Lung lipid peroxidation was markedly increased in the combined injury, 148 +/- 18 nmol MDA/gram of tissue compared with burn alone, 64 +/- 5 nmol/g, or controls, 45 +/- 4 nmol/g. However, no decrease in arterial O2 tension or increase in lung water was noted, i.e., the sheep did not have ARDS, which is known to impair O2 extraction. We conclude that a pathologic O2 delivery-dependent consumption develops with the combination of burn and inhalation injury, increasing the potential for tissue hypoxemia. This change corresponds with increased lung tissue oxidant change.

Animals↗
PubMed1992

Effect of dobutamine infusion on endotoxin-induced lipid peroxidation in awake sheep.

beta-agonists are known to not only increase oxygen delivery, but also attenuate the inflammatory response. We studied the effect of infusing the beta-agonist, dobutamine, on the oxidant-induced lung and liver tissue lipid peroxidation seen after endotoxemia. Twelve unanesthetized adult sheep with lung and soft tissue (prefemoral) lymph fistulae were given 5 micrograms/kg of Escherichia coli endotoxin intravenously. In six sheep, dobutamine 10 to 15 micrograms/kg/min was infused beginning 3 hours after endotoxin to increase oxygen delivery by 75% above baseline. Animals were killed at 6 hours, and lung and liver lipid peroxidation, measured as malondialdehyde, was obtained. Data were compared to six control sheep. Endotoxin alone produced increased lung and soft tissue vascular permeability as evidenced by a twofold increase in protein-rich lymph flow. Lung and liver malondialdehyde increased to 116 +/- 40 nmol/gm and 202 +/- 64 nmol/gm, respectively, compared to control values of 42 +/- 7 nmol/gm and 110 +/- 20 nmol/gm, respectively. Dobutamine infusion after endotoxin increased oxygen delivery by 75%, although changes in total oxygen consumption were not different from those seen with endotoxin alone. Lung and soft tissue lymph flow did not change with dobutamine. However, lung malondialdehyde was 41 +/- 17 nmol/gm, not different from controls. Liver malondialdehyde remained elevated at 164 +/- 26 nmol/gm. We conclude that dobutamine infusion prevents further oxidant-induced lung tissue lipid peroxidation but does not reverse the increased permeability already present. Liver lipid peroxidation was not decreased, suggesting the liver oxidant process may not be caused by the same mechanism as the lung lipid peroxidation.

Animals↗
PubMed1991

Effect of sequential early burn wound excision and closure on postburn oxygen consumption.

OBJECTIVE: To determine the effect of early excision and closure of burns on postburn hypermetabolism, measured as oxygen consumption (VO2). METHODS: Twelve patients with deep burns of 30% to 50% of total body surface underwent sequential excisions and wound coverage, beginning 1 to 3 days after burn. The majority of the deep burn was removed by day 7, but with the addition of a donor site area of 20% to 25% of total body surface. RESULTS: No decrease in VO2 was noted in relation to the percent removal of burn tissue. In addition, a transient further increase in VO2 was noted early after excision, especially with surgical procedures performed after 5 days. This response could not be attributed to wound manipulation-induced bacteremias. CONCLUSION: We conclude that early surgical excision and closure of burns in excess of 30% to 50% of total body surface do not decrease postburn hypermetabolism in proportion to the area closed. It is possible that remaining open wounds in the form of donor sites and nonexcised burn are sufficient to perpetuate the hypermetabolic process, once established.

Adult↗
PubMed1991

Relationship between the lung and systemic response to endotoxin: comparison of physiologic change and the degree of lipid peroxidation.

The lung and systemic response to Escherichia coli endotoxin either 2 or 5 micrograms/kg was measured in 16 sheep with chronic lung and soft tissue lymph fistulae. Oxidant-induced lung and liver lipid peroxidation was measured as tissue malondialdehyde (MDA). Conjugated dienes were also monitored. Both doses produced a comparable pulmonary hypertension and hypoxia as well as a comparable increase in protein-rich lymph flow, QL. However, lung MDA was significantly greater with the 5 micrograms/kg than with the 2 micrograms/kg dose, both being more than twofold greater than controls. The systemic physiologic responses between the two doses were quite different. The 5 microgram/kg dose resulted in a significant increase in oxygen delivery (DO2), oxygen consumption (VO2), and decrease in arterial O2 extraction in the 3-5 hr postendotoxin period compared with the 2 microgram/kg dose. A twofold increase in protein-rich soft tissue QL was also seen after the 5 micrograms/kg dose, whereas QL was not changed after 2 micrograms/kg. Liver MDA was only increased by 30% over controls with both doses. We conclude that the relationship between oxidant change and physiologic response varies considerably between lung and systemic tissues after endotoxemia with the degree of lung lipid peroxidation corresponding with the degree of impairment in systemic tissue O2 extraction and the onset of delivery-dependent O2 consumption.

Animals↗
PubMed1991

Topical flurbiprofen decreases burn wound-induced hypermetabolism and systemic lipid peroxidation.

We studied the effect of the topical application of the nonsteroidal anti-inflammatory agent, flurbiprofen, on postburn hypermetabolism and systemic lipid peroxidation. Twelve sheep with a 15% total body surface third-degree burn were monitored over a 4-day postburn period. In six sheep, a single application of a 5% flurbiprofen cream was placed on the burn wound on day 3. Data were compared to both burned and nonburned controls (n = 6). All animals were killed on day 4. Oxygen consumption was increased at day 3 by 28% +/- 10% over the preburn value in all animals. Flurbiprofen significantly attenuated the increase in oxygen consumption, returning the value essentially to baseline by 12 hours after application. Lung and liver peroxidation, as measured by malondialdehyde, was significantly increased in the burned, nontreated sheep at day 4 from a control value of 45 +/- 9 and 110 +/- 12 to 60 +/- 6 and 310 +/- 71 nmol/gm tissue, respectively. In flurbiprofen-treated animals, values were 42 +/- 8 and 160 +/- 18 nmol/gm at day 4, significantly attenuated from burn alone. Protein-rich burn lymph flow remained fourfold increased in both groups, indicating a persistent increase in burn tissue vascular permeability, not modified by flurbiprofen. Burn wound biopsies revealed bacterial contents of less than 10(4) organisms/gram tissue in all animals. We conclude that topical flurbiprofen significantly decreases burn wound-induced systemic hypermetabolism and oxidant-induced lipid peroxidation seen at 3 days after burn injury, but does not attenuate the remaining local burn-wound vascular permeability.

Administration, Cutaneous↗
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↗
PubMed1990

Effect of endotoxin and a burn injury on lung and liver lipid peroxidation and catalase activity.

Both endotoxin and a burn alone produce oxidant-induced tissue lipid peroxidation. The endotoxin response is due in large part to hydrogen peroxide. The combination of endotoxin after a burn results in an increased liver, but not lung, oxidant injury. Our purpose was to determine whether the burn oxidant injury inactivated endogenous liver tissue catalase, thereby amplifying a subsequent H2O2 insult. Twenty-six adult sheep were studied. Twelve sheep had a 15% TBS burn. Tissue catalase activity, measured in lung and liver 3 days postburn, was significantly decreased from a control of 3.58 +/- 1.8 and 193 +/- 63, respectively, to 1.72 +/- 0.63 and 148 +/- 33 k(sec-1)/0.5 gram tissue. The addition of endotoxin 3 days postburn resulted in an increase in liver malondialdehyde, MDA, a measure of lipid peroxidation, from a control of 110 +/- 80 to 450 +/- 54 nmol/gram tissue. This value was significantly greater than the 210 +/- 80 nmol/gram tissue seen after endotoxin alone. Lung tissue MDA with burn and endotoxin was 65 +/- 8 compared to 42 +/- 7 for control and 80 +/- 6 nmol/gram for endotoxin alone. We conclude that a decrease in liver catalase activity occurs after a burn. The decrease corresponds to an accentuated oxidant-induced lipid peroxidation after an added endotoxin insult where H2O2 is known to be an etiologic agent. The catalase activity also decreases in postburn lung, but accentuated lung damage was not seen, indicating a variable tissue response from the burn-induced decrease in antioxidant activity.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1990

Current concepts on the adult respiratory distress syndrome.

The shock- and trauma-induced process known as ARDS remains a major cause of mortality and morbidity. The time course of the clinical disease has changed dramatically as support systems have improved. In addition, it is becoming increasingly clear that ARDS is part of an inflammation-induced systemic disease state which can evolve to multi-system organ failure. It is MSOF which is now the leading cause of death in the post-trauma patient in the ICU. ARDS from shock and trauma must now be studied not solely as a primary pulmonary process but as a critical component of a generalized inflammatory reaction to distant tissue trauma.

Humans↗
PubMed1990

Effect of a body burn on endotoxin-induced lipid peroxidation: comparison with physiologic and histologic changes.

We determined the effect of a 15% total body surface (TBS), full-thickness burn on the physiologic, histologic, and oxidant-induced lipid peroxidation changes produced by endotoxin. The endotoxin-burn response was compared with that of endotoxin alone. Twenty-two adult sheep with chronic lung and flank lymph fistulas were studied. In 11 sheep a burn was produced under anesthesia and 3 days later they were given 2 micrograms/kg of endotoxin. Data were also compared with those of control sheep and those that were given burns alone. Circulating conjugated dienes increased with endotoxin alone but remained at baseline with endotoxin and burn injury. The lung lymph flow response was increased significantly in the endotoxin-burn group (sixfold) compared with that of endotoxin alone (fourfold). Histologic quantitation of lung neutrophil count was comparable in both groups 6 hours after injury, although mononuclear cells were much more evident in lungs in the endotoxin-burn group. Lipid peroxidation measured by malondialdehyde was significantly increased in the endotoxin group compared with the endotoxin-burn group, despite the greater increase in lymph flow and lung water in the burned group. Oxygen consumption (VO2) remained constant after endotoxin alone compared with baseline. However, VO2 increased twofold immediately after endotoxin in the endotoxin-burn group. This marked increase was followed by a significant decrease in VO2 from baseline. Flank soft-tissue nonburned increased lung lymph flow twofold to threefold with endotoxin and burn, indicating increased soft-tissue permeability, whereas it remained unchanged with endotoxin alone. Liver malondialdehyde increased from a control of 110 +/- 20 to 210 +/- 80 mmol/gm tissue with endotoxin alone and to 450 +/- 54 nmol/gm tissue with endotoxin and burn. We can conclude that burn injury accentuates both the pulmonary and systemic physiologic response to endotoxin, possibly as a result of mediators released from mononuclear cells already activated in the presence of the burn. The increased lung physiologic response does not appear to be caused by greater oxidant-induced lipid peroxidation, as was seen in the liver with the combined injury.

Animals↗
PubMed1990

Changes in catalase activity in lung and liver after endotoxemia in sheep.

Endotoxemia in the sheep produces oxidant-induced cardiopulmonary dysfunction and lung and liver lipid peroxidation, which can be prevented with exogenous catalase, indicating a role for hydrogen peroxide. We determined whether endotoxin-induced oxidant release altered endogenous catalase activity to help explain the lipid peroxidation. Unanesthetized sheep were given 2 micrograms/kg Escherichia coli endotoxin and killed at 5 hr or 24 hr. Lung and liver lipid peroxidation, measured as malondialdehyde, and catalase activity were determined after endotoxin and compared with controls. Lung tissue MDA increased by 100% at 5 hr and was still elevated by 50% at 24 hr, while catalase activity decreased by 50% at 5 hr and remained decreased, suggesting irreversible inactivation. Liver MDA was also doubled at both 5 and 24 hr, but catalase activity remained unchanged. We conclude that endotoxemia results in a significant inactivation of endogenous catalase activity in lung, but not in liver. The lung may be more prone to a subsequent H2O2 injury before restoration of catalase activity.

Animals↗
PubMed1990

Early postburn lipid peroxidation: effect of ibuprofen and allopurinol.

We measured lipid peroxidation of plasma, lung, and liver in anaesthetized sheep after third-degree burns involving 30% of total body surface. Animals were resuscitated to baseline filling pressures with lactated Ringer's solution and killed 10 hours after burn. Six sheep were pretreated with ibuprofen (12.5 mg/kg) and five with allopurinol (50 mg/kg). We used conjugated dienes and malondialdehyde as measures of lipid peroxidation. Circulating conjugated dienes increased from a baseline of 0.48 +/- 0.06 to 0.64 +/- 0.05 after burn, while protein-rich burn tissue lymph flow increased up to eightfold. We also noted a significant increase in lung tissue malondialdehyde from 45 +/- 4 to 60 +/- 6 nmol/gm and liver malondialdehyde from 110 +/- 20 to 271 +/- 34 nmol/gm along with increased tissue neutrophil sequestration. Ibuprofen attenuated lung-tissue malondialdehyde but had no effect on lung inflammation, circulating lipid peroxides or burn edema, indicating that ibuprofen most likely decreased O2 radical release in lung tissue by the already-sequestered neutrophils. Allopurinol, possibly via xanthine oxidase inhibition, markedly attenuated burn QL and circulating lipid peroxides and prevented all pulmonary lipid peroxidation and inflammation, indicating that release of oxidant from burn tissue was in part responsible for local burn edema, as well as distant inflammation and oxidant release, the latter most likely from complement activation. Neither antioxidant decreased lipid peroxidation in the liver; this indicates that its mechanism of production was different from that seen in burn tissue, in plasma, or in the lung. An ischemic event resulting from a selective decrease in splanchnic blood flow may be the cause of the liver changes.

Allopurinol↗
PubMed1990

Early burn excision attenuates the postburn lung and systemic response to endotoxin.

The lung and systemic physiologic response to endotoxin is markedly accentuated in the presence of a body burn. Our purpose was to determine whether early burn excision and closure would decrease this response. We compared the endotoxin (2 micrograms/kg)-induced response in 10 adult sheep with lung and soft-tissue lymph fistulas 3 days after a 15% total-body surface full-thickness burn that was excised immediately with that of sheep without burn excision and nonburned sheep. No infection was present in the burn wound. Early excision prevented the ongoing postburn lipid peroxidation and lung inflammation seen 3 days after burn before endotoxemia in animals with 15% total body surface burn wound not excised. Sheep that underwent excision demonstrated significantly less pulmonary hypertension and hypoxia after endotoxin than did either endotoxin-treated and intact burned sheep or endotoxin-treated nonburned sheep. Lung inflammatory changes as determined by neutrophil content of lung tissue and the increase in lung tissue malondialdehyde in the group that underwent burn excision after endotoxin were comparable to those seen with endotoxin alone, as was the lung lymph-flow response. Also, the systemic response was nearly identical to that seen with endotoxin alone with no increase in soft-tissue permeability as measured by lymph flow. Oxygen consumption (VO2) remained unchanged from baseline. In contrast, VO2 doubled in burn-intact animals initially after endotoxin, after which VO2 decreased to levels below baseline. An increase in soft-tissue vascular permeability was also noted. We can conclude that early burn excision and closure prevent the accentuated response to endotoxin that is seen when the burn wound is left intact, even if it is uninfected.

Animals↗
PubMed1990

Moderate smoke inhalation produces decreased oxygen delivery, increased oxygen demands, and systemic but not lung parenchymal lipid peroxidation.

We studied the first 24-hour lung and systemic physiologic response to a moderate smoke inhalation injury. In addition, we monitored oxidant-induced lipid peroxidation (LP), using malondialdehyde and conjugated dienes. Sixteen adult sheep with lung and soft tissue lymph fistulas were given 20 breaths of smoke while under anesthesia. Eight sheep were given a tidal volume of 5 ml/kg smoke, confining the inflammatory injury to airways only. Eight sheep were given 10 ml/kg smoke after which focal alveolar collapse and a carboxyhemoglobin level of 28% +/- 5% were noted in addition to airways injury. No significant lung or systemic physiologic changes were noted in the 5 ml/kg smoke exposure. However, plasma levels of malondialdehyde increased significantly, indicating that LP had occurred. With the 10 ml/kg smoke exposure, a 50% early decrease in oxygen consumption was noted. At 12 hours, oxygen consumption was then significantly increased by 30% over baseline. Fluid requirements to maintain filling pressures were also significantly increased, comparable to that seen after a 20% total body surface burn. A change in soft tissue permeability was noted with a twofold increase in systemic lymph, which could in part explain the fluid requirements. Lung lymph flow increased by only twofold, and lung water was not increased, whereas arterial partial oxygen pressure decreased from a baseline of 95 +/- 4 mm Hg to 60 +/- 5 mm Hg. Systemic LP was evident when both plasma malondialdehyde and conjugated dienes increased significantly. Liver tissue malondialdehyde at postmortem examination was double the normal level. However, lung parenchymal malondialdehyde was not increased.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗