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R H Demling

Publications and source records attributed to R H Demling.

At least 91 records · Page 5Linked to original sources
PubMed1986

The pulmonary and systemic response to recurrent endotoxemia in the adult sheep.

The pulmonary and systemic hemodynamic effects of recurrent endotoxemia were studied in the adult sheep with lung lymph fistulas. Six sheep were given 1 mu/kg Escherichia coli endotoxin every 12 hours for 5 days, after which animals were monitored for another 3 days. The pulmonary response to the first three injections was characterized by an initial severe pulmonary hypertension, hypoxia, and a two- to threefold increase in lymph flow, QL. Lymph and plasma thromboxane A2 (TxB2) and prostacyclin (6-keto-PGF1 alpha) levels increased from baseline values of nearly 200 pg/ml to values exceeding 2000 pg/ml. The systemic response to initial doses was characterized by an increase in systemic vascular resistance, a decrease in cardiac index, and a transient 20% increase in oxygen consumption. With later endotoxin doses, the pulmonary response was markedly attenuated, with only modest changes in pulmonary artery pressure, lymph flow, and arterial oxygen tension noted. TxB2 increases were less than 800 pg/ml, and 6-keto-PGF1 alpha levels remained unchanged. However, we noted the progressive onset of a hyperdynamic state characterized by a sustained increase in cardiac index and body temperature, and a 50% increase in oxygen consumption, whereas systemic vascular resistance decreased by 45%. Three days after endotoxin injections were discontinued, the hyperdynamic state (including leukocytosis) was still present, whereas pulmonary variables returned to baseline levels. We conclude that a hyperdynamic state can be produced by repeated doses of endotoxin that will present even after the endotoxin insult is discontinued, which is a characteristic of the multisystem organ failure syndrome.

6-Ketoprostaglandin F1 alpha↗
PubMed1986

Endotoxin-induced prostanoid production by the burn wound can cause distant lung dysfunction.

We injected Escherichia coli endotoxin, 2 micrograms/kg, beneath the eschar of sheep with 25% total body surface full-thickness burns to determine whether burn tissue in the presence of endotoxin releases prostanoids, particularly thromboxane A2, (TxA2), and if increased local TxA2 production can lead to distant lung dysfunction. We compared this response to the lung injury produced by the same dose given intravenously. We noted a marked increase in burn tissue TxA2 production after subeschar endotoxin as reflected in significant increases in burn lymph and pulmonary artery TxB2 levels. Pulmonary artery pressure increased from 22 to 38 mm Hg and PaO2 decreased from 89 to 71 torr while lung lymph flow (QL) increased only modestly with no evidence of increased lung permeability. The TxA2 production and the lung response were prevented by the subeschar injection of ibuprofen, 12.5 mg/kg. Circulating endotoxin was noted in only one of five sheep. After intravenous (endotoxin), a significant increase in lung TxA2 production was noted and a characteristic two-phase lung injury was seen with an initial phase basically identical to that seen with the subeschar injection followed by an increase in lung protein permeability. Burn tissue endotoxin can stimulate local TxA2 production leading to distant lung dysfunction without the need for circulating endotoxin. The source of the TxA2 is the burn, while with endotoxemia the source is the lung.

Animals↗
PubMed1985

Burns.

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Anti-Bacterial Agents↗
PubMed1985

Pulmonary dysfunction secondary to soft-tissue endotoxin.

Our purpose was to determine whether peripheral soft tissues produce and release prostanoids in response to local sepsis, and whether this mediator release can produce pulmonary dysfunction. Escherichia coli endotoxin (2 micrograms/kg in 100 mL of saline) was injected below the hide of the flank in seven unanesthetized sheep. In three additional sheep, ibuprofen (12.5 mg/kg of body weight) was injected with the endotoxin. Thromboxane B2 and 6-keto-PGF1 alpha (prostacyclin) levels were measured in tissue lymph draining the flank, lung lymph, pulmonary artery (Ppa), and aortic plasma. One hour after endotoxin administration, mean PaO2 decreased from 90 to 74 mm Hg and Ppa increased from 22 to 35 mm Hg. Lung lymph flow (QL) increased only 50% with QL being protein poor. No increase in lung or peripheral soft-tissue vascular permeability was noted. Tissue lymph (TxB2) increased from 220 +/- 114 to greater than 10,000 pg/mL with levels in Ppa plasma increasing from 300 +/- 128 to 595 +/- 124 pg/mL and aortic plasma from 270 +/- 141 to 410 +/- 104 pg/mL. Lung lymph TxB2 paralleled aortic values. Peak levels of 6-keto-PGF1 alpha in systemic lymph exceeded 2,000 pg/mL while levels in lung lymph remained relatively constant. The pulmonary injury and the increase in TxB2 was prevented by ibuprofen. We conclude that the response of soft tissue to local endotoxin is to release thromboxane in quantities sufficient to raise plasma levels and to produce hypoxia and pulmonary hypertension. The lung dysfunction is not produced by an increase in lung water or vascular permeability.

6-Ketoprostaglandin F1 alpha↗
PubMed1985

Chemotactic activity of plasma and lung lymph in sheep with endotoxemia: effect of hydroxyl radical scavengers.

The formation and release of circulating chemoattractants has been considered to be responsible for the initial pulmonary leukostasis and subsequent pulmonary vascular injury seen with endotoxemia. Oxygen radicals released from granulocytes can produce these factors. Our purpose was (1) to determine whether chemotaxins are released with endotoxemia and whether the lung is the source of these factors and (2) if there is a cause and effect relationship between the release of chemoattractants and the lung injury. Lung lymph flow, QL, lymph protein clearance, and vascular pressures were used to monitor lung vascular integrity. Escherichia coli endotoxin was infused into 12 sheep. Six sheep were pretreated with dimethyl thiourea (DMTU), a scavenger of hydroxide ion radicals. Chemotactic activity (CA) of plasma and lung lymph was determined during baseline, the pulmonary hypertensive phase, and the permeability phase of the lung injury. It was found that endotoxemia was associated with generation of a granulocyte chemotactic factor in plasma but not in lung lymph. The peak increase in plasma CA occurred after the early pulmonary leukostasis. Pretreatment with DMTU eliminated the increased CA but had no effect on the initial leukopenia or the lung injury. It was concluded that (1) the lung is not the major source of increased CA after endotoxin and (2) increased plasma CA occurs but does not appear to be causative of the initial pulmonary leukostasis or the granulocyte-induced lung injury.

Animals↗
PubMed1985

Effect of a body burn on the lung response to endotoxin.

Our purpose was, in general, to determine the effect of a body burn on the pulmonary response to endotoxemia and, specifically, to determine whether increased thromboxane (TxA2) production by the burn wound was responsible for the accentuated lung injury. Thirty-two unanesthetized sheep with lung and soft tissue lymph fistulae were studied. Twelve sheep were given a sublethal dose of intravenous E. coli endotoxin (2 micrograms/kg). A characteristic two-phase injury was noted as evidenced by early pulmonary hypertension and hypoxia and later increased lung permeability. TxA2 was significantly increased in lung lymph as well as aortic plasma relative to venous plasma, indicating the lung to be the source. Twelve of 12 sheep survived. Five of 13 sheep died from endotoxemia when given 3-5 days after a 25% total body surface (TBS) burn and five of seven died with endotoxin (2 micrograms/kg) and a 50% burn. Physiologic parameters were at preburn levels before endotoxin. Animals died both during the early phase from hypoxia and the later phase due, in large part, to increasing pulmonary dysfunction. Absolute levels of TxA2 were not increased in the postburn animals, nor was there a clear release of TxA2 from burn tissue to explain the accentuated response. Prostacyclin levels were, however, less elevated in postburn animals in response to endotoxin, thereby altering the TxA2/PGI2 ratio in favor of TxA2. However, a cause and effect relationship between the increased lung injury and TxA2 remains undetermined. Lymph flow or lymph protein content was not altered in burn tissue in response to endotoxin.

Animals↗
PubMed1985

Relationship of increased lung serotonin levels to endotoxin-induced pulmonary hypertension in sheep. Effect of a serotonin antagonist.

A persistent pulmonary artery hypertension, increased airways resistance, increased vascular permeability to protein, and hypoxia are characteristic of sepsis-induced ARDS in humans and are present in the late phase injury response seen in sheep after endotoxin. Our purpose was to determine the role of serotonin, 5-HT, in the steady-state pulmonary hypertension and decreased arterial oxygen tension seen beginning approximately 3 h after Escherichia coli endotoxin injury (2 micrograms/kg) in the adult sheep. Plasma 5-HT levels remained constant, whereas lung lymph values increased from a baseline of 60 +/- 40 to 180 +/- 70 and 270 +/- 90 ng/ml at 1-h and at 3- to 5-h periods, respectively, after endotoxin. Platelet count decreased significantly only at the 3-h time period. Ketanserin, a 5-HT antagonist, was infused (0.15 mg/kg/h) in 7 sheep during endotoxin injury. The degree of early pulmonary hypertension and hypoxia was not affected by ketanserin. Mean values for pulmonary artery pressure and arterial oxygen tension were 40 +/- 8 mmHg and 70 +/- 8 torr for endotoxin alone and 38 +/- 7 mmHg and 72 +/- 7 torr for the ketanserin group. Steady-state, protein-rich pulmonary perfusion was also not altered, being increased 3-fold in both groups. Pulmonary hypertension and hypoxia were significantly attenuated, however, at the 3- to 5-h period with ketanserin, compared with endotoxin alone, the pulmonary artery pressure decreasing from 29 +/- 5 to 22 +/- 4 mmHg and the PaO2 increasing from 75 +/- 4 to 83 +/- 5 torr.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1985

Early lung dysfunction after major burns: role of edema and vasoactive mediators.

We determined the effect of a body burn on pulmonary function. Full-thickness burns varying in size from 25 to 70% of total body surface (TBS), were produced in sheep. Resuscitation was performed with lactated Ringer's. We noted an increase in lung transvascular fluid flux as measured by lymph flow, Q1, during the resuscitation period, varying from one- to threefold over baseline with the degree of increase directly proportional to the burn size. The increase in QL could be totally explained by the degree of hypoproteinemia which was also proportional to burn size. Transient pulmonary hypertension 20 +/- 4 to 26 +/- 5 mm Hg and a decrease in PaO2 from 90 +/- 5 to 83 +/- 6 torr occurred in the 50 and 70% burns as well as a significant decrease in lung compliance. These alterations were not due to pulmonary edema as there was no increase in measured lung water. Also, the increase in QL could be prevented by using a combination of Dextran and protein for resuscitation but this had no effect on the hypertension or hypoxia. Burn lymph and venous plasma thromboxane levels were increased during this period of lung dysfunction. Ibuprofen 12.5 mg/kg preburn and 12.5 mg/kg every 2 hours postburn decreased the degree of dysfunction suggesting a cause and effect relationship.

Animals↗
PubMed1985

Burns. Fluid and electrolyte management.

Fluid resuscitation of the burn victim has evolved into a sophisticated science based on sound physiologic principles. This article presents these new developments in the context of the physiology of burn injury.

Blood Transfusion↗
PubMed1985

Effect of hydroxyl radical scavenging on endotoxin-induced lung injury.

The release of oxygen radicals, in particular the hydroxyl radical, from sequestered neutrophils produces acute lung injury after a number of insults. Our purpose was to determine whether hydroxyl radical, OH., is responsible for the lung injury from endotoxin characterized by (1) pulmonary leukostasis, (2) increased thromboxane production leading to pulmonary hypertension and hypoxia, and (3) increased protein permeability. This hypothesis was tested by infusion of a selective OH. scavenger, dimethyl thiourea (0.75 gm/kg), into unanesthetized sheep before endotoxin and comparison of the response to that seen with endotoxin alone. Pulmonary vascular integrity was measured by the use of lung lymph flow, QL, and lymph protein transport. Thromboxane A2 was measured as TxB2 and prostacyclin as 6-keto-PGF1 alpha. We found no difference in the degree of leukopenia and hypoxia after endotoxin or the levels of TxB2, 6-keto-PGF1 alpha, and pulmonary hypertension with dimethyl thiourea, compared with endotoxin alone. The permeability injury was also identical, with a twofold to threefold increase in protein-rich lymph seen in both groups. It appears that OH. does not play a major causative role in either phase of endotoxin lung injury.

6-Ketoprostaglandin F1 alpha↗
PubMed1985

Role of subcutaneous tissue endotoxin in the production of prostanoid-induced lung injury: comparison with intravenous endotoxin response.

Local injection of endotoxin into soft tissues of the flank results in hypoxia and pulmonary hypertension. Our purpose was to determine whether this was caused by tissue prostanoid production or production by the lung as is seen with endotoxemia. Twenty-six sheep were prepared with lung and flank tissue lymph fistulae. Thirteen sheep were given 2 micrograms/kg Escherichia coli endotoxin into the flank soft tissue, six of which were pretreated with ibuprofen, 12.5 mg/kg. Thirteen sheep were given intravenous endotoxin, 2 micrograms/kg, with six pretreated with ibuprofen. An early hypertensive phase was noted with both insults characterized by pulmonary hypertension, hypoxia, and increased lung lymph flow (QL). With subcutaneous tissue endotoxin, there was a significant increase in tissue lymph TxB2 and 6-keto-PGF1 alpha when compared to lung lymph and increased values in venous plasma compared to arterial plasma, indicating tissue to be the source. With intravenous endotoxin, lung lymph and aortic plasma levels were significantly higher than tissue lymph and venous plasma, respectively. The hypoxia, hypertension and increased prostanoids were prevented using ibuprofen. An increased lung permeability phase was noted with intravenous endotoxin but not with tissue endotoxin. As expected, this phase was not inhibited with ibuprofen and, therefore, not prostanoid-induced.

6-Ketoprostaglandin F1 alpha↗
PubMed1985

Burn injury.

The pathophysiologic changes demonstrated by a burn patient basically cover the entire spectrum of surgical critical care. Management of the particular disease state is based more on the principles of prevention rather than on the treatment of complications, as the latter are frequently fatal. Although extremely complex, most of the physiological, biochemical, metabolic and immunological changes leading to these complications are predictable with reasonable knowledge of the time course of burn injury and repair. The objective of this review was not to present a detailed treatment plan, but rather knowledge of the mechanism behind postburn pathology so as to allow one to predict and in turn prevent mortality and morbidity.

Burns↗
PubMed1984

Role of oxygen radicals in endotoxin-induced lung injury.

We tested the hypothesis that the increased permeability in the pulmonary microcirculation seen with endotoxin is caused by the release of oxygen radicals from activated neutrophils. We first compared the pulmonary injury in sheep caused by low-dose endotoxin with that produced by phorbol myristate acetate, an agent that selectively causes the release of oxygen radicals from neutrophils. We then determined the degree of lung tissue lipid peroxidation, a reflection of direct oxygen radical damage after endotoxin and phorbol myristate acetate. Both agents produced a nearly identical increase in protein permeability; however, peroxidation was only evident with phorbol myristate acetate. Higher doses of endotoxin did result in increased lung peroxidation as well as a more severe physiologic injury. We can conclude that oxygen radical release, most likely from neutrophils, occurs with endotoxin. However, the permeability injury may not be the direct result of increased lipid peroxidation, as increased permeability can be seen without measurable increases in this parameter.

Animals↗
PubMed1984

Release of amino-terminal procollagen peptides in paraquat-induced acute pulmonary fibrosis.

Acute pulmonary fibrosis following intoxication with paraquat is characterized by increased collagen synthesis and deposition in the lungs. In the present study, a chronic lung lymph fistula preparation in sheep was used to investigate the changes in procollagen type III peptide level in the lung lymph in acute pulmonary distress associated with paraquat application. The procollagen type III peptide is supposed to be an indicator of the changing biosynthetic pattern of pulmonary collagen in lung fibrosis. All animals tested showed a progressive pulmonary distress following the application of paraquat characterized by increasing lymph flows and lymph protein flows which monitored the microvascular membrane damage. In parallel to these findings, procollagen peptide levels in the lymph fluid increased, even before manifest biochemically or histologically detectable pulmonary fibrosis occurred. The present results suggest that the release of procollagen type III peptides into lymph fluid is an early indicator of beginning fibrotic tissue disarrangement, even before completed pulmonary fibrosis can be detected by common tissue analysis.

Acute Disease↗
PubMed1984

Effect of nitroprusside administration and sudden withdrawal on pulmonary vascular tone and lung fluid balance.

We previously reported an increase in lung lymph flow rate (QL) on cessation of nitroprusside (NP) infusion after endotoxin lung injury. Utilizing sheep with chronic lung lymph fistulas and no lung injury, we studied pulmonary transvascular fluid filtration rate and protein flux (as measured via lung lymph flow and lymph protein content, respectively) during and after NP administration. The mean aortic pressure (Ao) and pulmonary arterial pressure (PAP) were significantly reduced by NP infusion. QL rose slightly during this reduction in pressure. Sudden withdrawal of NP infusion resulted in a significant rise in QL (as seen in our previous study) and a decrease in lymph to plasma protection ratio (L/P). There were only slight changes in PAP and mean pulmonary capillary wedge pressures (WP). We suggest that withdrawal of NP increases pulmonary microvascular pressure (Pmv).

Animals↗
PubMed1984

Effect of early burn excision and grafting on pulmonary function.

The effects of early burn excision and grafting on pulmonary function were measured. Blood gases, PaO2/FIO2, and dynamic lung compliance were measured before, during, and after 70 procedures in 37 patients with major body burns, 22 of whom also had significant superimposed impairment in lung function. Excisions were carried out 24 to 48 hours and again 5 to 7 days postburn, only in hemodynamically stable patients in whom ventilation could be safely maintained to, from, and in the operating room. We noted no instances of increased pulmonary dysfunction which were not rapidly reversible in the postoperative period. A modest transient decrease in lung compliance and oxygen exchange, as well as an increase in PaCO2, was seen which we attributed to a discontinuation of PEEP (positive end expiratory pressure) and underestimation of needed minute ventilation intraoperatively and during transport. This was in large part corrected in the latter part of the study period. Seven patients, mean age 67 years, were included in the series. All patients did well. We conclude that if proper precautions are made, early excision can be safely performed in patients with altered lung function.

Adolescent↗
PubMed1984

Depression of cellular immunity after multiple trauma in the absence of sepsis.

We have previously reported that severe burn injury was regularly accompanied by impaired lymphocyte responses to T cell mitogens, circulating suppressor lymphocytes, and serum factors suppressive of lymphocyte activation. However, in burned patients it was difficult to determine whether these manifestations of suppressed immunity were predictive of, or the result of, sepsis which was ubiquitous in this population. In an attempt to clarify this issue, we have studied 31 patients with multiple trauma (without burns) mean age, 31 years; average injury severity score, 22; range, 9-56; in whom sepsis was less common. Patients were tested for lymphocyte response to the T cell mitogens PHA and Con A, the percentage of circulating putative suppressor (OKT8) and helper (OKT4) T cells using monoclonal antibodies, circulating suppressor cell activity as revealed by functional assays, and serum suppression of lymphocyte activation. Patients were compared with ten normal volunteers (mean age, 32) studied simultaneously. Significant suppression (greater than 50% compared with controls) in lymphocyte responses to mitogens 1 to 5 days after injury was seen in 12 patients, was accompanied by a shift in the ratio of helper (OKT4) to suppressor (OKT8) T cells (patients, 0.96:1; normals, 1.82:1; p less than 0.01), and was followed by the appearance of significant (greater than 50%) serum suppressive activity in six of the 12 patients. Circulating suppressor cell activity as revealed by functional assays was also seen early after injury in three of 12 patients.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗