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Biomedical subjects

R H Demling

Publications and source records attributed to R H Demling.

At least 73 records · Page 4Linked to original sources
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

Fluid replacement in burned patients.

The selection of the fluid replacement for the burned patients is based on a sound understanding of the pathophysiology of the burn injury as well as a similar understanding of the properties of the various fluids available. The appropriate matching of these properties with the specific goals and necessary monitoring techniques for each patient will result in success. Those caring for the burned patient must remain both flexible and knowledgeable in order to optimize results.

Burns↗
PubMed1987

Smoke inhalation injury.

Smoke inhalation injury is responsible for more deaths after fire than actual body burns. Many of the effects of heat and chemical burns to the airways are delayed and may not be clinically evident at first. Chest films are often not helpful, and direct laryngoscopic or bronchofibroscopic examination or a ventilation-perfusion scan may be necessary to verify the diagnosis. Treatment depends on the components involved, with chemically induced airway injury being the most complex to manage. Death rates remain high when inhalation injury is combined with severe body burns.

Bronchodilator Agents↗
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

Abnormalities of antibody production after thermal injury. An association with reduced interleukin 2 production.

Antibody (Ab) production was studied in 25 burned patients who were immunized with 0.5 mg of tetanus toxoid adsorbed. Anti-tetanus toxoid (TT) Ab was measured by hemagglutination, radial immunodiffusion, and an enzyme-linked immunosorbent assay, and the results for the patients were compared with those for five similarly immunized healthy controls. As measured by hemagglutination, 12 (63%) of 19 patients had lower Ab responses than all five controls (P less than .05 by chi 2), and the median Ab response during the period of maximum response was significantly less than that in controls (8 vs 15.5 log2 maximum dilution; P = .014). After the initial response, serum Ab levels were not maintained in patients, in contrast to controls. This pattern was demonstrated by all three assays; enzyme-linked immunosorbent assay demonstrated that IgG anti-TT Ab was the major class of Ab produced. In nine patients interleukin 2 production by T lymphocytes was measured simultaneously; it was significantly depressed throughout the study except during the period from 36 to 45 days. The Ab response was also impaired in this patient group. Since maintained antibody production in response to TT is known to be T-cell dependent, these results suggest that inadequate interleukin 2 production leading to reduced T-cell help may be responsible for the lack of a persistent Ab response in these burned patients.

Adolescent↗
PubMed1986

Mechanisms of immunosuppression associated with severe nonthermal traumatic injuries in man: production of interleukin 1 and 2.

Depression of cell-mediated immunity in patients following severe traumatic injury has been well documented in vitro and in vivo. However, the exact mechanism of this defect is still controversial. In this study, we have investigated the ability of injured patients' peripheral blood mononuclear cells (PBMC) to produce two important immunoregulatory molecules, interleukin 1 (IL 1) and interleukin 2 (IL 2). Eighteen traumatic injury patients were studied during the course of their hospital stay and their results compared with a group of 18 normal age- and sex-matched controls. The results showed the following. (1) Production of IL 2 by normal PBMC in response to optimal doses of mitogen may vary with sex as well as age. (2) Adherent mononuclear cells from trauma patients produced at least as much IL 1 as normals. (3) IL 2 production, however, was markedly suppressed (normals, 1.6 +/- 0.2 U; traumatic injury, 0.6 +/- 0.1 U; P = 0.001) and persisted for as long as 50 days postinjury. OKT4+ cells were not significantly decreased at any time, nor were OKT8+ suppressor/cytotoxic cells increased at any time. Decreased IL 2 production in patients treated with steroids or those who were septic was not different from that in those patients who were not treated with steroids or were not septic. These results suggest that the cause of the defect in IL 2 production in traumatic injury patients is not related to a lack of the IL 1 signal, producer T cells, or Ia+ monocytes or to increased suppressor T cells.(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenal Cortex Hormones↗
PubMed1986

The pathophysiology of free-fall injury.

The spectrum of injuries created by a free fall are governed by distinct physical properties, of which the height of the fall and the nature of the impacted surface are the most important factors. Other determinants include the victim's age and weight and the position at landing. Orthopedic injuries frequently are encountered in falls from two stories and less, and are largely determined by the position at landing. Visceral trauma, produced by deceleration forces, frequently involves the liver, spleen, lung, heart and aorta, and must be suspected in falls from three stories and more regardless of the landing position. Mortality from a six-story fall onto a hard surface such as concrete is almost 100% for adults, although considerably less for children. Falls onto softer surfaces, including water, are better tolerated. By appreciating the physical principles that dictate the type and degree of injury, one may correctly diagnose and manage free-fall injuries.

Accidents↗
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

Endotoxemia causes increased lung tissue lipid peroxidation in unanesthetized sheep.

Our purpose was to determine whether lipid peroxidation of lung tissue, a reflection of O2 radical injury, occurs with endotoxin, and whether the degree of tissue change corresponds with the degree of increased protein permeability. Unanesthetized adult sheep with lung lymph fistulas were given Escherichia coli endotoxin at a dose of 2 micrograms/kg (n = 34). Tissue lipid peroxidation was measured using the thiobarbituric acid assay for malondialdehyde (MDA). The MDA content of lung tissue in nanomoles per gram increased from a control value of 48 +/- 8 to 98 +/- 18 at 5 h postendotoxin (2 micrograms/kg), whereas lung lymph protein transport (Cp), was increased 3- to 4-fold. The MDA content returned to base line with Cp by 24 h postendotoxin. Six sheep given endotoxin were pretreated with 12.5 mg/kg of ibuprofen, and six were infused with dimethylthiourea (DMTU) 0.75 g/kg. With ibuprofen, Cp was only increased 2.5- to 3-fold and MDA was increased to 69 +/- 15 nmol/g. With DMTU, the increase in Cp was comparable to that with endotoxin alone, as was the MDA of lung tissue with a value of 92 +/- 12 nmol/g. The correlation of tissue MDA with Cp in all animals was 0.83. We conclude that lipid peroxidation occurs in lung tissue after a moderately severe endotoxin injury with the degree of change corresponding to the degree of increased Cp.

Animals↗
PubMed1986

Lung dysfunction after thermal injury in relation to prostanoid and oxygen radical release.

We studied whether changes in lung function after burns (1- to 12-h period) were due to changes in lung water or airways resistance and the relationship of the changes to prostanoid and O2 radical activity (measured as lipid peroxidation). Twenty-five anesthetized mechanically ventilated adult sheep were given a 40% of body surface scald burn and resuscitated to restore and maintain base-line filling pressures. Dynamic lung compliance (Cdyn) decreased by 40% from 38 +/- 5 to 24 +/- 4 ml/cmH2O at 12 h. Venous thromboxane B2 transiently increased from 210 +/- 40 to 1,100 +/- 210 pg/ml, and the value in lung lymph increased from 180 +/- 80 to 520 +/- 80 pg/ml. Prostacyclin levels in lung lymph and plasma remained at base line. Protein-poor lung lymph flow increased two- to threefold, but postmortem lung analysis revealed no increase in lung water from the control of 3.5 +/- 0.3 g H2O/g dry wt. No increase in protein permeability was seen. However, the lipid peroxidation of lung tissue measured as malondialdehyde was significantly increased from the control value of 56 +/- 4 nmol/g lung to a value of 69 +/- 6. Ibuprofen pretreatment (12.5 mg/kg) markedly attenuated the decrease in Cdyn, with the value at 12 h being 90% of base line. Ibuprofen also decreased the amount of lung lipid peroxidation but did not decrease the lung lymph response. We conclude that the decrease in Cdyn seen early postburn is not due to increased lung water, but, rather, is due to a mediator-induced bronchoconstriction, attenuated by ibuprofen; the mediator being either thromboxane or a byproduct of O2 radicals as evidenced by increased lipid peroxide production in lung tissue.

Anesthesia↗
PubMed1986

Comparison of the postburn hyperdynamic state and changes in lung function (effect of wound bacterial content).

The pulmonary and systemic response to a full-thickness burn (15% of total body surface area) was determined in 15 adult sheep. Also compared was the effect of wound bacterial content and prostanoid release on this response. Burn wound thromboxane A2, measured as TxB2, and prostacyclin, measured as 6-keto-PGF1 alpha, were measured in burn wound lymph. Animals were monitored for 7 days. On the final day, a full-thickness biopsy specimen of burn tissue was obtained for quantitative bacteriology. Wounds with 10(4) or less organisms per gram of burn tissue were considered colonized, whereas those with 10(5) or more organisms per gram of burn tissue indicated wound infection. Seven sheep had 10(4) or less bacteria and the remaining eight sheep had 10(6) or greater bacteria. We noted a significant mean increase in cardiac index from a baseline of 5 to 6.2 L/min/m2, a decrease in systemic vascular resistance from 16 to 12 mm Hg/L/min, and a mean increase in oxygen consumption from a baseline of 135 to 165 ml/min/m2 during the 7-day study period. There were no differences in these responses between the colonized and the infected wounds. Pulmonary artery pressure increased from a mean baseline of 19 to 24 mm Hg and arterial oxygen tension (PaO2) decreased from a baseline of 90 to 80 mm Hg in the infected wound group, with values remaining at baseline in the colonized wound group. These changes corresponded with an increase in lymph and plasma TxB2 from a baseline of 200 to 210 pg/ml to 1000 +/- 250 and 600 +/- 190 pg/ml, respectively. Values in the animals with colonized wounds were not significantly increased.(ABSTRACT TRUNCATED AT 250 WORDS)

6-Ketoprostaglandin F1 alpha↗