Search PubMed⌕ Search

Biomedical subjects

R H Demling

Publications and source records attributed to R H Demling.

At least 55 records · Page 3Linked to original sources
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↗
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↗
PubMed1989

The lung inflammatory response to thermal injury: relationship between physiologic and histologic changes.

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.

Animals↗
PubMed1989

Effect of ibuprofen on the pulmonary and systemic response to repeated doses of endotoxin.

We infused 10 doses of Escherichia coli endotoxin, 1 microgram/kg, during a 5-day period, into eight unanesthetized sheep with lung and systemic lymph fistulas. The animals were then monitored for an additional 5 days. We noted an attenuation of the lung microvascular permeability changes with the later endotoxin doses. However, a 50% increase in cardiac index and oxygen consumption and a leukocytosis were seen beginning with the ninth endotoxin injection; these persisted throughout the 15-day postendotoxin period, as did an increase in pulmonary artery pressure. The hyperdynamic state was present when plasma prostanoids were only modestly increased, and there was no evidence of increased lung or systemic vascular permeability. Postmortem lung findings, 5 days after endotoxin administration, showed a marked interstitial inflammatory response, with infiltration of macrophages, neutrophils, and some lymphocytes and an increase in interstitial fibrous tissue. Six sheep were then given ibuprofen, 12.5 mg/kg, intravenously before the ninth and tenth doses and on the subsequent day. Ibuprofen significantly attenuated the hyperdynamic state and the pulmonary hypertension. In addition, the lung inflammation and fibrous tissue deposition was markedly attenuated. We conclude that a systemic hyperdynamic state develops that corresponds in time with lung inflammation but not with increased permeability. The lung and systemic changes may be blocked by ibuprofen. The ibuprofen effect may be due to a response other than prostanoid production.

Animals↗
PubMed1989

Inhibition of thromboxane synthetase accentuates hemodynamic instability and burn edema in the anesthetized sheep model.

Thromboxane A2 production is increased early after burn. We studied the effect of inhibiting thromboxane synthetase, using dazmegrel, on postburn hemodynamic stability and edema formation, the latter monitored by burn tissue lymph flow. Dazmegrel (3.4 mg/kg) was given to six anesthetized sheep, and a 40% of total-body-surface third-degree burn was produced. Lactated Ringer's solution was infused at a rate to restore filling pressures during a 12-hour study period. Data were compared to burn alone (n = 8), anesthesia alone (n = 6), and dazmegrel alone (n = 5) groups. The latter two groups showed no physiologic changes. Dazmegrel pretreatment prevented increased thromboxane A2, measured as thromboxane B2, but resulted in a significant increase in plasma prostacyclin, measured as 6-keto-PGF1 alpha. In addition, a marked vasodilatation and decrease in systemic vascular resistance were noted, as well as a 30% increase in fluid requirements and an increase in lymph flow compared with burn alone. The increase in prostacyclin more than likely accentuated the burn-induced permeability change. Of interest was that oxygen consumption was better maintained with dazmegrel postburn, even with the relative hypovolemia, indicating that postburn vasoconstriction impairs adequate O2 delivery to tissues and that thromboxane synthetase inhibition attenuates this process.

6-Ketoprostaglandin F1 alpha↗
PubMed1988

Increased intestinal permeability associated with infection in burn patients.

Thermal injury may be associated with disruption of normal gut barrier integrity. To test this hypothesis, we assessed intestinal permeability with the nonmetabolizable, poorly absorbed disaccharide lactulose, which is efficiently excluded by the normal intestinal mucosa. Permeability studies were performed in 15 burned patients (aged 18 to 67 years; mean burn size, 40%) and 11 healthy controls. Lactulose, 10 g, was administered enterally, together with 5 g of mannitol as a control, and urinary excretion rates were determined. Lactulose excretion and the lactulose/mannitol excretion ratio increased threefold (160 +/- 30 vs 57 +/- 7 mumol and 0.113 +/- 0.033 vs 0.035 +/- 0.005) in the infected patients (sepsis score, 10 +/- 2; burn size, 38% +/- 6%). In contrast, noninfected burn patients (sepsis score, 0) had permeability values similar to those of controls (66 +/- 10 mumol and 0.036 +/- 0.007). Permeability increased as the severity of infection increased. Infection in burn patients is associated with increased bowel permeability. The intestine may be a primary source of sepsis. Alternatively, the systemic response to infection may alter gut barrier function, which could facilitate translocation of bacteria and absorption of endotoxin.

Adolescent↗
PubMed1988

Incidence and morbidity of extubation failure in surgical intensive care patients.

The rate of extubation failure (reintubation rate) was determined for 700 consecutive extubations in surgical patients admitted to one of two ICUs. Patients were weaned in a standardized fashion and extubated using a standardized gas exchange and mechanics criteria. Of 400 extubations in the general surgical ICU, there were 22 reintubations in 20 patients. Average age was 65 yr, and the major reason for reintubation was need for positive-pressure ventilation. Morbidity (pulmonary edema and/or pneumonia) was 36%, and the inhospital mortality was 40% in this group. The major cause of death was progressive cardiopulmonary failure. There were 10 failures in eight patients, of 300 extubations in the Burn/Trauma unit, where the mean age was 44 yr. Five failures occurred in patients with smoke inhalation and burns, a 13% incidence in this population. The reason for reintubation was airway maintenance and pulmonary toilet. Four failures occurred in head injury patients, a 5% incidence with the major reason for reintubation being airway protection. Morbidity was 60% (new pulmonary infiltrates), while mortality rate was only 10% in this group. Only one failure was noted in a nonhead-injured trauma patient. In no group studied were any predictors of extubation failure detected. We conclude that the incidence, reasons for, and outcome of reintubations in surgical ICU patients varies dramatically depending on the underlying disease process. Overall failure rate was 4%.

Adult↗
PubMed1988

Restrictive pulmonary dysfunction caused by the grafted chest and abdominal burn.

We report on the effect of the excised and grafted chest and abdominal burn on lung function. Six consecutive patients with 3 degree burns to the entire chest and abdomen (72 +/- 10% total body surface area 3 degree burns) were studied. A severe restrictive lung dysfunction due to the noncompliant nature of the excised and grafted chest and abdominal wound was identified; this was most evident when inspiratory pressure (IP) was even modestly impaired with general anesthetics. Measured vital capacity (VC) was 12 to 14 ml/kg at 6 to 8 wk postburn, in the absence of any significant parenchymal injury. The measured VC was identical to the tidal volume (VT) used during the extended period of mechanical ventilatory support. Dynamic compliance (or characteristic) (Cdyn) decreased dramatically from 35 +/- 8 to 15 +/- 9 ml/cm H2O when the positive pressure VT was increased by as little as 100 ml above prior VT settings, indicating the noncompliant nature of the combined chest and abdominal excised and grafted burn. Major cardiopulmonary complications developed in the first two patients after onset of the restrictive process when general anesthesia was used for grafting procedures (n = 8) and the limits of chest wall excursion were unrecognized. Patients received only continuous positive airway pressure preoperatively. A modest but significant decrease in IP from -45 +/- 8 to -33 +/- 5 cm H2O and 30% decrease in spontaneous VT were noted in the early postoperative period. These changes, however, resulted in a dramatic decrease in pulmonary function leading to hypercarbia, PCO2 greater than 50 torr.(ABSTRACT TRUNCATED AT 250 WORDS)

Abdominal Injuries↗
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

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↗