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Biomedical subjects

A Revhaug

Publications and source records attributed to A Revhaug.

At least 73 records · Page 4Linked to original sources
PubMed1989

Clearance of vasoactive intestinal polypeptide (VIP) in the porcine pulmonary circulation.

The clearance of vasoactive intestinal polypeptide (VIP) in the lung was determined in pigs. To measure the first pass uptake, a bolus of VIP (0.9 pmol.kg-1 and 9 pmol.kg-1) with an inert intravascular marker, indocyanine green (ICG), was injected into the right atrium. The percent uptake of VIP after the higher bolus, as estimated by comparing the levels of VIP and ICG in the pulmonary artery and the aorta, was 36 +/- 6% during control infusion and 36 +/- 13% during continuous infusion of VIP (3 pmol.kg-1.min-1). The VIP concentrations in the pulmonary artery and the aorta were not different under baseline conditions, but during continuous VIP infusion the levels of plasma VIP in the pulmonary artery were higher than those in the aorta (24.3 +/- 1.6 pmol.l-1 and 20.4 +/- 1.3 pmol.l-1, resp. P less than 0.0001). These results indicate that the lung is not a source of plasma VIP, but the pulmonary circulation is a substantial contributor to the removal of VIP from plasma.

Animals↗
PubMed1989

The effects of tumor necrosis factor and their selective inhibition by ibuprofen.

High doses of tumor necrosis factor (TNF) cause hypotension, metabolic acidosis and, death. At Brigham and Women's Hospital, the effects of a sublethal, 6-hour infusion of TNF (0.57 X 10(5) Units/kg body weight) in twelve anesthetized dogs were studied. The dose caused falls in mean arterial pressure from 153 mmHg to 96 mmHg, pulmonary artery pressure (-4.5 mmHg), central venous pressure (-2.5 mmHg) and pulmonary capillary wedge pressures (-5.25 mmHg). Associated with these responses were a fourfold increase in urine volume (22.4 ml/kg/6 hours as compared to 5.2 ml/kg/6 hours in controls), significant pyrexia (from 38.1 C to 39.5 C, rectal), tachycardia (from 125 to 175 beats/minute), and hypermetabolism. In addition, leukopenia and increased circulating stress hormone concentrations were observed. Blood glucose concentrations fell from 4.68 mM/1 to 3.97 mM/1 (84-71 mg/dl) within 3 hours of TNF infusion, whereas lactate and pyruvate concentrations increased. These alterations occurred in the absence of severe hypotension or acidosis and were similar to changes observed after endotoxin administration or gram-negative septicemia. Pretreatment of the animals with the cyclooxygenase inhibitor ibuprofen abolished most of the hemodynamic changes and attenuated other responses. These findings support the hypothesis that TNF is an important mediator of septic responses and that some of the effects of TNF are mediated via cyclooxygenase pathways.

Adrenocorticotropic Hormone↗
PubMed1989

Depression of plasma endotoxin levels during gram-negative septicemia subsequent to moderate trauma.

The influence of a moderate, standardized trauma on bacterial and endotoxin kinetics in post-traumatic Escherichia coli septicemia was studied in a porcine model. Septicemia was induced by intravenous infusion of live E. coli (2.5 x 10(9) cfu/kg, rough:K5:H6) into 14 piglets. Seven of these animals had been exposed to moderate trauma 48 hours previously. Following the E. coli infusion, cardiovascular signs of severe septicemia appeared in all the piglets, associated with gradual increase in the blood bacterial count and the plasma levels of endotoxin. This increase was significantly less pronounced in the animals with prior moderate trauma than in the nontraumatized animals. Thus no depression of the host defense system was demonstrable 2 days after moderate trauma.

Animals↗
PubMed1989

PMN activity and endotoxin kinetics in peritonitis induced after moderate trauma.

The effect of moderate trauma on bacterial and endotoxin kinetics during post-traumatic Escherichia coli peritonitis was studied in a controlled animal model. Peritonitis was induced in 14 piglets by intra-abdominal infusion of 2.5 x 10(9) cfu live E. coli (rough:K5:H6). The animals were studied in pairs. One of each pair was exposed to trauma consisting of forceful femoral marrow nailings 48 hours before induction of peritonitis and the other was a non-traumatized peritonitic control. The abdominal bacterial counts fell rapidly in all animals after a one-hour delay during which there was rapid spread of bacteria to the blood. After 4 hours blood cultures were regularly sterile. Circulating endotoxin showed slow but steady increase in the controls, but in the traumatized animals levels rose rapidly, in association with insignificantly higher levels of polymorphonuclear leukocyte chemiluminescence. The study indicated that trauma induces changes in endotoxin kinetics and polymorphonuclear leukocyte function during post-traumatic peritonitis.

Animals↗
PubMed1988

Detection of circulating tumor necrosis factor after endotoxin administration.

Cytokines, products of stimulated macrophages, are thought to mediate many host responses to bacterial infection, but increased circulating cytokine concentrations have not been detected consistently in infected patients. We measured plasma concentrations of circulating tumor necrosis factor alpha (cachectin), interleukin-1 beta, and gamma interferon, together with physiologic and hormonal responses, in 13 healthy men after intravenous administration of Escherichia coli endotoxin (4 ng per kilogram of body weight) and during a control period of saline administration. Eight additional subjects received ibuprofen before receiving endotoxin or saline. Plasma levels of tumor necrosis factor were generally less than 35 pg per milliliter throughout the control period, but increased 90 to 180 minutes after endotoxin administration to mean peak concentrations of 240 +/- 70 pg per milliliter, as compared with 35 +/- 5 pg per milliliter after saline administration. Host responses were temporally associated with the increase in circulating tumor necrosis factor at 90 minutes, and the extent of symptoms, changes in white-cell count, and production of ACTH were temporally related to the peak concentration of tumor necrosis factor. Ibuprofen pretreatment did not prevent the rise in circulating tumor necrosis factor (mean peak plasma level, 170 +/- 70 pg per milliliter) but greatly attenuated the symptoms and other responses after endotoxin administration. Concentrations of circulating interleukin-1 beta and gamma interferon did not change after endotoxin administration. We conclude that the response to endotoxin is associated with a brief pulse of circulating tumor necrosis factor and that the resultant responses are effected through the cyclooxygenase pathway.

Adrenocorticotropic Hormone↗
PubMed1988

Inhibition of cyclo-oxygenase attenuates the metabolic response to endotoxin in humans.

Acute infection initiates fever, acute-phase changes, and catabolic responses in the host, resulting in weight loss, hypermetabolism, and accelerated proteolysis. To test the hypothesis that cyclo-oxygenase inhibition might attenuate these responses, we administered Escherichia coli endotoxin intravenously to seven normal volunteers and to seven additional subjects pretreated with a cyclo-oxygenase inhibitor (ibuprofen). Control studies were also performed following administration of saline and ibuprofen alone. Vital signs, metabolic rate, and concentrations of pituitary and stress hormones, as well as those of other substrates, were serially measured. Endotoxin administration produced a response similar to an acute illness, with flulike symptoms, fever, tachycardia, increased metabolic rate, and stimulation of stress hormone release. These changes were markedly attenuated by cyclo-oxygenase inhibition. The leukocytosis, hypoferremia, and elevation of the C-reactive protein level induced by endotoxin were unaffected by cyclo-oxygenase inhibition. These data indicate that activation of the cyclooxygenase pathway is necessary to produce many of the metabolic changes observed during critical illness.

Adult↗
PubMed1988

A single dose of endotoxin increases intestinal permeability in healthy humans.

To investigate the effects of endotoxin on gut barrier function, we performed paired studies of intestinal permeability in healthy humans (N = 12) receiving intravenous Escherichia coli endotoxin (4 ng/kg) or 0.9% saline solution. Two nonmetabolizable sugars, lactulose and mannitol, which are standard permeability markers, were administered orally, 30 minutes before and 120 minutes after the test injection. The 12-hour urinary excretion of these substances after endotoxin/saline solution administration was used to quantitate intestinal permeability. After endotoxin administration systemic absorption and excretion of lactulose increased almost two-fold (mean +/- SEM, 263 +/- 36 mumol per 12 hours vs 145 +/- 19 mumol per 12 hours during saline studies). Similar but less marked alterations in mannitol absorption and excretion occurred after endotoxin injection (5.7 +/- 0.3 mmol per 12 hours vs 4.9 +/- 0.3 mmol per 12 hours). When individual 12-hour lactulose excretion after endotoxin administration was related to the magnitude of systemic responses, a significant relationship occurred between lactulose excretion and elaboration of norepinephrine and between lactulose excretion and minimum white blood cell count. These data suggest that a brief exposure to circulating endotoxin increases the permeability of the normal gut. These observations are consistent with the hypothesis that during critical illness, prolonged or repeated exposure to systemic endotoxins or associated cytokines may significantly compromise the integrity of the gastrointestinal mucosal barrier.

Administration, Oral↗
PubMed1988

Epidemiology of NSAID-induced gastrointestinal problems and the role of cimetidine in their prevention.

It is difficult to ascertain the incidence of gastrointestinal side-effects associated with intake of non-steroidal anti-inflammatory drugs (NSAIDs). In retrospective studies, some NSAIDs have been reported to be associated with a higher incidence of gastrointestinal side-effects than others. However, this has not been verified either in a prospective case-review study or in a large double-blind study. Serious side-effects, such as bleeding, perforation and heart failure, occur in approximately 1% of patients using NSAIDs. One-third of all patients receiving NSAIDs will have gastrointestinal complaints. Since at least 10% of patients terminate treatment with NSAIDs as a result of side-effects, even reduction of those that are not life-threatening would be of great benefit. H2-receptor antagonists have proved effective in ulcer treatment, and their use as prophylaxis against the side-effects of NSAIDs is being widely studied. In a recent study, 63 patients who had experienced serious upper gastrointestinal side-effects were given cimetidine while continuing their NSAID therapy. All but 4 of the 47 who had gastric or duodenal ulcer on first admission were healed at 8 weeks, and none of the remaining 16 with diffuse bleeding gastritis experienced further clinical episodes of bleeding or ulcer-related dyspepsia.

Anti-Inflammatory Agents, Non-Steroidal↗
PubMed1988

Effects of endotoxin on the pancreatic ultrastructure.

Intravenous administration of Escherichia coli endotoxin caused a state of shock with increased serum cationic trypsin-like immunoreactivity (CTLI) in a porcine model. The pancreatic acinar cells revealed focal changes, including intracellular oedema, appearance of membrane-bound vacuoles and breaks in the plasma membrane. In the micro circulatory vessels, there was swelling of endothelial cells. Similar changes have been observed in hemorrhagic and cardiogenic shock. This study demonstrates severe ultrastructural changes in the pancreas during E. coli endotoxin shock.

Acute Disease↗
PubMed1988

Phagocytic cell activity in pre-eclampsia.

To compare the immune response in normal and pathological pregnancy, some functions of phagocytic cells were studied in 8 women with pre-eclampsia and 7 healthy women matched for age and parity. Free oxygen radical activity determined by chemiluminescence (CL) of polymorphonuclear leukocytes (PMN) and monocytes (MN) during phagocytosis of preopsonized zymosan, and cell migration measured by tube migration of PMN were studied together during and after pregnancy. CL of MN decreased or remained unchanged during normal pregnancy, but a marked increase was observed in pre-eclampsia. CL of PMN increased, too, in the pre-eclamptic patients, but the difference was not significant. Tube migration was enhanced during pregnancy compared with baseline values, but the values were significantly lower in the pre-eclamptic group. Immuno-globulins (Ig G, Ig M and Ig A) were studied in both groups. A decline in Ig G level from baseline to the 3rd trimester was observed in patients. The complement fractions C3 and C4 were not altered during pregnancy in any group. The study indicates a difference in behavior of phagocytic cells in normal vs. pre-eclamptic pregnancy.

Adult↗
PubMed1988

Tumor necrosis factor and endotoxin induce similar metabolic responses in human beings.

After injury, infection, or major operations a number of predictable metabolic responses occur. It has been proposed that the cytokine tumor necrosis factor (TNF)/cachectin is a primary mediator of these host responses. To test this hypothesis, we studied 16 tumor-bearing humans with normal renal and hepatic function, who received 24-hour continuous intravenous infusions of escalating doses of recombinant TNF (4 to 636/micrograms/m2/24 h). Serial measurements were made of vital signs and plasma concentrations of TNF, interleukin-1, adrenocorticotropic hormone, cortisol, iron, glucose, and C-reactive protein. Low doses of TNF had minimal metabolic effects, but infusions of greater than or equal to 545 micrograms/m2/24 hr (n = 8) resulted in fever, pituitary, and stress hormone release and acute phase changes. These alterations were compared with the changes that occurred in healthy humans (n = 13) receiving intravenous bolus injections of Escherichia coli endotoxin (4 ng/kg). TNF infusion in doses greater than or equal to 545 micrograms/m2/24 hr produced peak plasma TNF concentrations and metabolic responses that were similar to those after endotoxin injection. Interleukin-1 concentrations remained basal after TNF or endotoxin administration. TNF may represent the primary afferent signal that initiates many of the metabolic responses associated with sepsis and endotoxemia.

Acute-Phase Proteins↗
PubMed1988

Increased plasma levels of endotoxin and corresponding changes in circulatory performance in a porcine sepsis model: the effect of antibiotic administration.

Changes in endotoxin levels and cardiovascular performance during antibiotic therapy in septicemia were investigated in a porcine model. One group of animals (n = 9) received gentamicin 2 mg/kg intravenously infusion two hours after induction of sepsis with live E. coli bacteria. Another group (n = 7) served as non-treated septic controls. Plasma-levels of endotoxin increased significantly after antibiotic administration from 0.26 +/- 0.02 ng/ml before treatment (0 hrs), to 1.1 +/- 0.3 ng/ml after two hours (p less than 0.01) and 2.1 +/- 0.98 ng/ml four hours after treatment (p less than 0.01). In the control group no significant increase occurred in the observation period. No difference could be demonstrated between the groups with regard to the number of live bacteria in blood, either before or after treatment. When the data from all the animals were taken together for the first two hours following antibiotic administration a significant negative correlation (p less than 0.05) was demonstrated between changes in endotoxin levels and cardiac output. This correlation was significant for animals in which the levels of endotoxin increased above 0.5 ng/ml (p less than 0.05). The present study indicates that endotoxin is liberated after antibiotic administration during bacteremia, and that this increase correlates with cardiac performance.

Animals↗
PubMed1987

The role of the small intestine in ammonia production after gastric blood administration.

It is commonly believed that the digestion of intraluminal blood by colonic bacteria is the primary cause of increased ammonia production after upper gastrointestinal hemorrhage. To evaluate the role of the small intestine in ammonia production, blood, amino acids, or water (5 mL/kg) was administered as a meal or enema to awake dogs with chronic indwelling catheters. After blood meals, intestinal ammonia production increased rapidly to peak at 60 minutes and returned to basal levels. This response was mimicked by the gastric administration of ammoniagenic amino acids. No change in ammonia production occurred with water administration. In contrast, colonic blood administration resulted in a gradual rise in ammonia production, and peaked at 150 minutes. Amino acid enemas resulted in a similar but somewhat more rapid response. No change occurred with water enemas. After gut decontamination, ammonia production did not increase after blood enemas. However, the rapid increase in ammonia production persisted after blood meals. It is concluded that both the small bowel and colon participate in the augmented ammonia production that occurs after upper gastrointestinal hemorrhage. Gut decontamination reduces ammonia production by altering the colonic microflora, but is not specific therapy directed towards amino acid metabolism by the enterocytes of the small bowel and thus, does not alter the ammonia produced by the small intestine.

Amino Acids↗
PubMed1987

The effect of pregnancy on functions of inflammatory cells in healthy women and in patients with rheumatic disease.

Chemiluminescence (CL) after zymosan stimulated phagocytosis of polymorphonuclear granulocytes (PMN) and mononuclear cells (MNC), random migration of PMN and intra- and extracellular activities of nine lysosomal enzymes were assessed serially in 8 healthy women and 10 women with rheumatic disease during and after pregnancy. A gestational increase of lysosomal enzymes in serum and enhancement of PMN random migration was observed in all women. Significant differences between healthy and rheumatic women were found for CL of phagocytic cells. In healthy women, CL of PMN was slightly enhanced, while it remained unchanged in MNC during pregnancy. In patients, CL of PMN was markedly suppressed, while MNC CL increased during gestation. An inverse relationship between CL and intracellular enzyme activities was noted. Thus, the presence of an inflammatory state seemed to influence the gestational behavior of phagocytic cells.

Female↗
PubMed1987

A single dose of endotoxin activates neutrophils without activating complement.

Both complement (C) and neutrophils (PMN) are activated in critically ill patients. To evaluate the role of endotoxin in this response, we studied C activation products and PMN cell surface receptors in seven normal subjects before and after endotoxin (USRef 20 U/kg) or saline solution administered on separate occasions. By 4 hours, with endotoxin only, all subjects had myalgia, headache, an increase in body temperature and heart rate, and leukocytosis that returned to normal by 24 hours. At the same time, PMN cell surface receptors for the complement opsonin C3b increased, as measured by indirect immunofluorescence, rising to 251 +/- 44% of baseline by 4 hours (p less than 0.01) and remaining elevated at 24 hours (237 +/- 16%, p less than 0.01). PMN receptors for iC3b increased to 308 +/- 49% of baseline by 4 hours (p less than 0.02) and returned to normal by 24 hours. There was no change in plasma of C3a desArg, C4a desArg, and C5a desArg (4 hours: mean C3a: 153.4 +/- 11.5 ng/ml versus 176.2 +/- 16.2 ng/ml for saline solution, p = ns; C4a: 159.6 +/- 32 ng/ml versus 151.4 +/- 21 ng/ml, p = ns; C5a: undetectable). To confirm the lack of C activation, we examined PMN chemotaxis (CTX) to C5a for any impairment caused by prior in vivo exposure to C5a. CTX to C5a was unaffected (4 hours: 109% +/- 22% of normal versus 114% +/- 10% for saline solution, p = ns). PMN CTX to formyl-methionyl-leucine-phenylalanine and PMN phagocytosis and killing of S. aureus were also unaffected by endotoxin. Thus, a single dose of endotoxin produced a subjective febrile illness and precipitated sustained PMN activation as indicated by increased PMN cell surface complement receptor number in the absence of C activation.

Adult↗