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PubMed1998

Relationship of endotoxin to tumor necrosis factor-alpha and interleukin-1 beta in children with otitis media with effusion.

Sixty-five middle ear effusions and paired sera from 41 children with chronic otitis media with effusion were assayed for endotoxin and for tumor necrosis factor alpha (TNF-alpha) and interleukin-1 beta (IL-1 beta) in order to establish whether a correlation exists between the concentrations of endotoxin and of these cytokines. Endotoxin concentration was determined by means of a chromogenic limulus amebocyte lysate assay, and the cytokine concentration by means of a quantitative enzyme-linked immunosorbent assay. Forty percent of the effusions had detectable levels of endotoxin, with a mean concentration of 2.9 +/- 7.8 endotoxin units per milligram of total protein. The mean concentration of TNF-alpha was 1.24 +/- 3.1 pg/mg total protein, and that of IL-1 beta was 18.79 pg/mg total protein. A strong, statistically significant correlation exists between the concentrations of endotoxin and TNF-alpha (r = .89) and IL-1 beta (r = .72). The data indicate that endotoxin may contribute to the pathogenesis of chronic otitis media with effusion by stimulating the sustained production of TNF-alpha and IL-1 beta in the middle ear.

Child↗
PubMedDate not supplied

Effects of chemically defined structured lipid emulsions on reticuloendothelial system function and morphology of liver and lung in a continuous low-dose endotoxin rat model.

BACKGROUND: This study was undertaken to determine the effect of chemically defined structured lipids on nonspecific host defense and on histologic patterns of liver and lungs compared with a physical mixture of long-chain triglycerides and medium-chain triglycerides in a continuous low-dose endotoxin rat model. METHODS: Forty male Sprague-Dawley rats, divided into four feeding groups (structured lipids, structured lipids+endotoxin, physical mixture, physical mixture+endotoxin), received total parenteral nutrition for 48 hours. During the first part of the study, 24 animals were given an injection of live Escherichia coli labeled with radioactive iron (59Fe) to investigate the function of the reticuloendothelial system. During the second part of the study, the liver and lungs of 16 animals were histologically examined using light and electron microscopy. RESULTS: Despite the similar values in the control groups, the animals receiving structured lipids+endotoxin sequestered a significantly greater percentage of bacteria in the liver and spleen (p < or = .01) and a significantly lesser percentage in the lung (p < or = .05) compared with the animals given physical mixture+endotoxin as part of their diet. Moreover, rats in the physical mixture+endotoxin group showed a microscopically evaluated higher fatty infiltration in the liver than did the structured lipids+endotoxin group. CONCLUSIONS: The results of this study indicate that chemically defined structured lipids reduce fatty infiltration of the liver compared with a physical mixture of the same compounds in an animal model of metabolic stress. They were accompanied by a better function of the reticuloendothelial system and a lesser bacterial sequestration in the lungs.

Animals↗
PubMed2000

Endotoxin in pooled pericardial blood contributes to the systemic inflammatory response during cardiac surgery.

Although endotoxin has been implicated as an important contributor to the systemic inflammatory response (SIR) during cardiopulmonary bypass (CPB), its source remains unclear. While gut translocation has traditionally been perceived as the primary source of endotoxemia, accumulation of endotoxin in pooled pericardial blood may represent an additional source of endotoxin that is continually reinfused into the CPB circuit. Eighteen patients undergoing primary coronary revascularization procedures were prospectively evaluated. Shed blood pooled in the pericardial space was returned to the CPB circuit through cardiotomy suction catheters at 45 min after placement of the aortic cross-clamp. Simultaneous samples of pooled pericardial and peripheral arterial blood were obtained and analyzed by a limulus amebocyte lysate assay for the determination of endotoxin concentration, and an enzyme-linked immunosorbent assay for tumor necrosis factor (TNF-alpha) levels. Significant elevations in endotoxin were demonstrated in pooled pericardial blood samples compared with arterial blood (3.5 +/- 0.5 vs 0.8 +/- 0.2 pg/ml; p < 0.05). TNF-alpha levels were below the limits of detection in both samples. These data implicate pooled pericardial blood as an important primary source of endotoxin that, when continually reinfused throughout CPB, may contribute to the overall SIR. Because endotoxemia has been identified as an important predictor of adverse outcomes following cardiac surgery, removal of endotoxin antigen in shed pericardial blood, prior to its reinfusion into the CPB circuit, may provide a directed means to improve perioperative outcome without compromising established blood conservation techniques.

Adult↗
PubMed2004

A new method for removing endotoxin from plasma using hemocompatible affinity chromatography technology, applicable for extracorporeal treatment of septic patients.

The pathogenesis of sepsis begins with the proliferation of micro-organisms at a site of infection, followed by invasion of the bloodstream and other organs. Gram-negative bacteria account for a large part of sepsis cases. The structural component of Gram-negative bacteria, endotoxin or lipopolysaccharide (LPS), induces the synthesis and release of endogenous mediators of sepsis. A growing number of investigations of the molecular mechanisms occurring in sepsis, point to endotoxin as a central mediator leading to multi-organ failure and death. In numerous clinical trials, attempts to target molecules downstream of endotoxin have been made, but have not been associated with improved survival. We describe an affinity-based system for the selective removal of endotoxin from plasma. The small-scale device, a 1.5 ml cartridge, contains beads that bind endotoxin with high specificity and efficiency. In addition, evidence is presented that this device does not affect plasma hemostasis, nor does it activate the complement system. Taken together, these results represent a proof of principle for endotoxin removal from plasma, which may be of clinical value to treat sepsis by extracorporeal circulation of the blood through a scaled-up version of this endotoxin-removing device.

Blood Coagulation Tests↗
PubMed2005

Detoxifying endotoxin: time, place and person.

Animals that cannot sense endotoxin may die if they are infected by Gram-negative bacteria. Animals that sense endotoxin and respond too vigorously may also die, victims of their own inflammatory reactions. The outcome of Gram-negative bacterial infection is thus determined not only by an individual's ability to sense endotoxin and respond to its presence, but also by numerous phenomena that inactivate endotoxin and/or prevent harmful reactions to it. Endotoxin sensing requires the MD-2/TLR4 recognition complex and occurs principally in local tissues and the liver. This review highlights the known detoxification mechanisms, which include: (i) proteins that facilitate LPS sequestration by plasma lipoproteins, prevent interactions between the bioactive lipid A moiety and MD-2/TLR4, or promote cellular uptake via non-signaling pathway(s); (ii) enzymes that deacylate or dephosphorylate lipid A; (iii) mechanisms that remove LPS and Gram-negative bacteria from the bloodstream; and (iv) neuroendocrine adaptations that modulate LPS-induced mediator production or neutralize pro-inflammatory molecules in the circulation. In general, the mechanisms for sensing and detoxifying endotoxin seem to be compartmentalized (local versus systemic), dynamic, and variable between individuals. They may have evolved to confine infection and inflammation to extravascular sites of infection while preventing harmful systemic reactions. Integration of endotoxin sensing and detoxification is essential for successful host defense.

Animals↗
PubMed2001

Influence of in-vivo endotoxin liberation on anti-anaerobic antimicrobial efficacy.

The ability of cefoxitin, clindamycin, imipenem, meropenem, metronidazole and piperacillin-tazobactam to cause gram-negative anaerobic bacteria to release endotoxin and the influence of such liberated endotoxin on antibiotic efficacy were investigated in in-vivo experiments in animal models. Experimental infections in various animal models (mice, hamster and infant rats) with cultures of wild and reference strains of Bacteroides fragilis group and Fusobacterium spp. were carried out by injecting these animals with different inocula (10(6), 10(7) and 10(8) cfu/ml) of the bacterial suspension, Appropriate doses of the test antibiotics were then injected and the plasma lipopolysaccharide (endotoxin) release measured by the Limulus Amoebocyte Lysate (LAL) Assay. Evidence of worsening of the outcome of the infections post-therapy was assessed, including histopathological changes in the internal organs. Infection with generalized septicemia was established with F. nucleatum in the mice and hamster models while with the B. fragilis group, infections only led to intra-abdominal abscess formation. Plasma endotoxin release was higher in animals infected with F. nucleatum than B. fragilis and was unrelated to the bacterial inoculum. Imipenem, meropenem and cefoxitin, in that order, induced the highest levels of endotoxin activities in the animal model, particularly following F. nucleatum infection. Histological examination of the internal organs of various animals showed variation in the pattern of histopathological changes; grades 3-4 inflammatory changes in the liver were observed in the Fusobacterium-infected animals that were treated with the carbapenems and cefoxitin. Therapy with the other antibiotics did not exacerbate anaerobic sepsis. In this study, bacteremia did not lead to massive endotoxin release and antibiotic therapy appeared not to have negatively influenced the outcome of most of the gram-negative anaerobic infections, except for infections caused by Fusobacterium spp. However, it is conceivable that if the gastrointestinal tract is the source of the endotoxin in patients with systemic inflammatory response syndrome, then the obligate anaerobes like Bacteroides and Fusobacterium species, which are members of the gut flora, may play a major role in the unfavorable outcome of antibiotic therapy in some of these infections.

Animals↗
PubMed2006

Pyometra in bitches induces elevated plasma endotoxin and prostaglandin F2alpha metabolite levels.

Endotoxemia in bitches with pyometra can cause severe systemic effects directly or via the release of inflammatory mediators. Plasma endotoxin concentrations were measured in ten bitches suffering from pyometra with moderately to severely deteriorated general condition, and in nine bitches admitted to surgery for non-infectious reasons. Endotoxin samples were taken on five occasions before, during and after surgery. In addition, urine and uterine bacteriology was performed and hematological, blood biochemical parameters, prostaglandin F2alpha metabolite 15-ketodihydro-PGF2alpha (PG-metabolite), progesterone and oestradiol (E2-17beta) levels were analysed. The results confirm significantly increased plasma levels of endotoxin in bitches with pyometra and support previous reports of endotoxin involvement in the pathogenesis of the disease. Plasma concentrations of PG-metabolite were elevated in pyometra bitches and provide a good indicator of endotoxin release since the concentrations were significantly correlated to the endotoxin levels and many other hematological and chemistry parameters. The gamma-globulin serum protein electrophoresis fraction and analysis of PG-metabolite can be valuable in the diagnosis of endotoxin involvement if a reliable, rapid and cost-effective test for PG-metabolite analysis becomes readily available in the future. Treatment inhibiting prostaglandin biosynthesis and related compounds could be beneficial for bitches suffering from pyometra.

Animals↗
PubMed1987

Oxygen toxicity in neonatal rats: the effect of endotoxin treatment on survival during and post-O2 exposure.

Neonatal rats were treated with low doses of bacterial lipopolysaccharide (endotoxin) to test for a protective effect of endotoxin against O2 toxicity and the severe inhibition of normal lung development which occurs during prolonged exposure to hyperoxia. The rationale for the prophylactic use of endotoxin included its marked protective effect against pulmonary O2 toxicity in adult rats and its lung growth-promoting effect in experimental pulmonary stress models. Neonatal rats (4-5 days old) survived a 14-day exposure to greater than 95% O2 equally well whether treated with saline (39/51 = 76%) or with endotoxin (41/51 = 80%). However, during the following 24 h of gradual weaning to room air breathing, there was a marked difference in survival between the endotoxin group (32/41 = 78%) and the saline pups (14/39 = 36%) (p less than 0.001). Both groups showed inhibition of lung development (alveolarization) during O2 exposure, but endotoxin treatment compared to saline was associated with increased specific lung volume (5.33 versus 4.50 ml/100 g) (air control = 4.08), smaller mean airspace diameter (mean linear intercept = 49.0 versus 55.8 microns) (air control = 43.3), increased specific internal surface area (4393 versus 3232 cm2/100 g) (air control = 3753), and greater preservation of alveolar wall capillary patency (24.83 versus 18.52% "capillary density") (air control = 27.70%). We conclude that endotoxin treatment resulted in significant protection against O2 toxicity in neonatal rats which was manifested during readaptation to room air breathing. The protective effect was likely due to a combination of reduced inhibition of lung growth and development and reduced hyperoxic damage to the respiratory membrane of the lung.

Animals↗
PubMed1994

Escherichia coli endotoxin depresses left ventricular contractility in neonatal lambs.

We evaluated the effects of Escherichia coli endotoxin on the peripheral vascular hemodynamics and myocardial function of the newborn lamb to understand how gram-negative endotoxemia can lead to cardiovascular collapse in newborn infants. Fifteen lambs, 0-3 d old, were acutely instrumented with a micromanometer-tipped catheter and two pairs of ultrasonic crystals to measure left ventricular (LV) pressure and LV anterior-posterior and septal-free wall dimensions, a fluid-filled catheter for monitoring aortic pressure, and an electromagnetic flow probe to measure systemic blood flow. Cardiovascular performance was evaluated by measuring or deriving the following variables: mean arterial blood pressure (MABP), LV pressure, heart rate, stroke volume, systemic vascular resistance, LV dp/dt, end-diastolic area, arterial elastance, and end-systolic elastance (the slope of the end-systolic pressure-area relationship) as an index of contractility independent of loading conditions and heart rate. Once instrumented, nine lambs received endotoxin, 0.5 mg/kg i.v., and six animals, serving as controls, received a saline infusion. Of the endotoxin-treated lambs, five survived the duration of the study (120 min from the beginning of the endotoxin infusion), and four died by 90 min from the beginning of the endotoxin infusion. No significant changes in any of the cardiovascular variables occurred in the control group. A significant decrease in MABP was seen in all endotoxin-treated animals by 45 min after the beginning of the endotoxin infusion. MABP decreased by 52% from baseline in the survivors and 38% in the nonsurvivors. In the survivors, the MABP stabilized with saline boluses, whereas in the nonsurvivors MABP continued to decrease until death.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed2002

Does cortisol mediate endotoxin-induced inhibition of pulsatile luteinizing hormone and gonadotropin-releasing hormone secretion?

Bacterial endotoxin (lipopolysaccharide), a commonly used model of immune/inflammatory stress, inhibits reproductive neuroendocrine activity and concurrently induces a profound stimulation of the hypothalamo-pituitary-adrenal axis. We employed two approaches to test the hypothesis that enhanced secretion of cortisol mediates endotoxin-induced suppression of pulsatile GnRH and LH secretion in the ovariectomized ewe. First, we mimicked the endotoxin-induced increase in circulating cortisol by delivering the glucocorticoid in the absence of the endotoxin challenge. Within 1-2 h, experimentally produced increments in circulating cortisol suppressed pulsatile LH secretion in a dose-dependent fashion. Second, we blocked the endotoxin-induced stimulation of cortisol secretion using the drug metyrapone, which inhibits the 11-beta hydroxylase enzyme necessary for cortisol biosynthesis. In the absence of a marked stimulation of cortisol secretion, endotoxin still profoundly inhibited pulsatile GnRH and LH secretion. We conclude that, although enhanced cortisol secretion may contribute to endotoxin-induced suppression of reproductive neuroendocrine activity, the marked stimulation of the glucocorticoid is not necessary for this response. Our findings are consistent with the hypothesis that immune/inflammatory stress inhibits reproductive neuroendocrine activity via more than one inhibitory pathway, one involving enhanced secretion of cortisol and the other(s) being independent of this glucocorticoid.

Animals↗
PubMed2003

Leptin modulates inflammatory cytokine and neuroendocrine responses to endotoxin in the primate.

Leptin, which plays a crucial role in regulating energy balance, can also modulate the inflammatory response. Although leptin-deficient rodents are more sensitive to the toxic effects of bacterial endotoxin, it is unknown if leptin can modulate inflammatory cytokine or neuroendocrine responses to inflammation in a primate model. We have therefore studied the effects of leptin on plasma cytokine and hypothalamic-pituitary-adrenal responses to endotoxin (5 microg iv) in nine ovariectomized rhesus monkeys. Human leptin (50 microg/h) or saline was infused iv for 16 h before and 4 h after endotoxin injection; mean plasma leptin increased from 3.6 +/- 1.0 ng/ml to 18 +/- 1.7 ng/ml (P < 0.001). Leptin infusion had no effect on baseline plasma cytokine and hormone levels before endotoxin injection. As expected, endotoxin stimulated TNF-alpha, IL-6, IL-1 receptor antagonist (IL-1ra), ACTH, and cortisol in the saline-infused animals (P < 0.001). There was a significant attenuation of the IL-6 (P < 0.005) and cortisol (P < 0.001) responses (repeated measures ANOVA) to endotoxin in the leptin-infused animals. There was a significant reduction (by paired analysis) in the responses of the leptin compared with saline-treated animals: 47% for TNF-alpha, 48% for IL-6, 30% for IL1ra, 42% for ACTH, and 22% for cortisol (P < 0.05). We conclude that an increase in circulating leptin, within the physiological range of our monkey colony, can blunt the inflammatory cytokine and hypothalamic-pituitary-adrenal responses to an inflammatory challenge. These results, coupled with our recent finding that endotoxin stimulates leptin release in the monkey, demonstrate that leptin can be both released in response to inflammatory cytokines and act to attenuate the responses to these cytokines.

Animals↗
PubMed1993

Human recombinant interleukin-1 receptor antagonist prevents adrenocorticotropin, but not interleukin-6 responses to bacterial endotoxin in rats.

The present study was designed to analyze the role of endogenous interleukin-1 (IL-1) in the ACTH, corticosterone (CORT), and IL-6 responses of rats to bacterial endotoxin. Recombinant rat IL-1 beta (rIL-1 beta) when given ip resulted in dose-dependent increases in plasma ACTH, CORT, and IL-6 concentrations. Plasma ACTH and CORT responses could be induced by low rIL-1 beta doses that did not elevate plasma IL-6 levels. The half-maximally effective dose of rIL-1 beta was less than 0.6 microgram/kg for the ACTH and CORT responses and higher than 2.5 micrograms/kg for the IL-6 response. Time-course studies indicated that plasma ACTH and CORT concentrations were already elevated 30 min after the injection of rIL-1 beta (2.5 micrograms/kg, ip), with peak values after 1-2 h, followed by a subsequent decline. In contrast, plasma IL-6 concentrations became elevated 2 h after the injection of rIL-1 beta. In another set of experiments, the administration of endotoxin resulted in a dose-dependent elevation of the plasma ACTH, CORT, and IL-6 concentrations. The dose-response characteristics for ACTH, CORT, and IL-6 were different. The half-maximally effective dose for the ACTH and CORT, and IL-6 responses were approximately 2.5 micrograms/kg and more than 10 micrograms/kg, respectively. Time courses of plasma ACTH, CORT, and IL-6 responses to endotoxin (2.5 micrograms/kg, ip) were similar, with peak values measured after 2 h. When given alone, the human IL-1 receptor antagonist (IL-1RA; 1 or 2.5 mg/kg, ip) did not affect resting plasma ACTH and CORT concentrations and reduced plasma IL-6 concentrations in one experiment. At a dose of 1 mg/kg, IL-1RA inhibited ACTH and IL-6 responses to rIL-1 beta (2.5 micrograms/kg, ip) by 75% and 90%, respectively. Administration of IL-1RA (2.5 mg/kg, ip) 30 min after endotoxin (2.5 micrograms/kg, ip) completely prevented the ACTH response and partially inhibited the CORT response, but did not affect the IL-6 response measured 2.5 h after endotoxin administration. We conclude that 1) IL-1 receptors are involved in the ACTH and IL-6 responses to rat IL-1 beta; 2) the ACTH response, but not the IL-6 response, to a low dose dose of endotoxin in rats requires IL-1 receptor activation by endogenous produced IL-1; and 3) circulating IL-6 is not a prime mediator involved in ACTH and CORT responses to low doses of rIL-1 beta and endotoxin.

Adrenocorticotropic Hormone↗
PubMed2004

[Metabolic aspects of endotoxin as a model of septic shock--approached from oxidative stress].

Despite the remarkable progress in intensive care medicine, sepsis and shock continue to be major clinical problems in intensive care units. Septic shock may be associated with a toxic state initiated by the stimulation of monocytes by bacterial toxins such as endotoxin, which is released into the bloodstream. This study describes the role of oxidative stress in endotoxin-induced metabolic disorders. We demonstrate that endotoxin injection results in lipid peroxide formation and membrane injury in experimental animals, causing decreased levels of free radical scavengers or quenchers. Interestingly, it was also suggested that tumor necrosis factor (TNF)-induced oxidative stress occurs as a result of bacterial or endotoxin translocation under conditions of reduced reticuloendothelial system function in various disease states. In addition, we suggest that intracellular Ca2+, Zn2+, or selenium levels may participate, at least in part, in the oxidative stress during endotoxemia. On the other hand, it is also suggested that the extent of endotoxin-induced nitric oxide (NO) formation may be due, at least in part, to a change in heme metabolic regulation during endotoxemia. However, in our experimental model, NO is not crucial for lipid peroxide formation during endotoxemia. Sho-saiko-to is one of the most frequently prescribed Kampo medicines and has primarily been used to treat chronic hepatitis. We report that Sho-saiko-to decreases the rh TNF-induced lethality in galactosamine-hypersensitized mice and protects mice against oxygen toxicity and Ca2+ overload in the cytoplasm or mitochondria during endotoxemia. We further suggest that Sho-saiko-to shows a suppressive effect on NO generation in macrophages stimulated with endotoxin and that it may be useful in improving endotoxin shock symptoms.

Animals↗
PubMed1994

[Specific assay for endotoxin using immobilized histidine. Application to serum sample].

The amount of endotoxin in the serum was measured by the new assay method of endotoxin using a filtercup, Limulus amebocyte lysate, and immobilized histidine which is a specific adsorbent for endotoxin. The maximum recovery of endotoxin in the rabbit serum was obtained using acetate buffer (pH 5.5, mu = 0.1) for the adsorption. Using this buffer, various kinds of endotoxin in water were adsorbed quantitatively on immobilized histidine, and the activity of the adsorbed endotoxin was well recovered. The value of the amount of endotoxin in the bovine serum measured by the new assay method, which includes heat treatment (70 degrees C, 10 min) after separation followed by washing, was closer to that calculated from pyrogenic activities in rabbits than that measured by the PCA-Toxicolor method.

Animals↗
PubMed1999

[The application of the endotoxin test for globulin and other blood products].

The application of the endotoxin test for globulin and other blood products were investigated by two different limulus amebocyte lysate (LAL) test methods, colorimetric and kinetic turbidimetric methods, using two endotoxin-specific reagents. By the dilution of the blood products in 40 times or more, spiked endotoxin in the products was recovered accurately showing neither inhibition nor enhancement. The definite difference was not shown between the results obtained by the two LAL test methods. According to the method of the endotoxin test described under General Tests of The Japanese Pharmacopeia (thirteenth edition), JPXIII, the maximum valid dilution (MVD) for these products will be calculated to be 40 or more, so it is capable to measure the endotoxin limit for each product. This study indicates that the endotoxin test is applicable to measure the endotoxin content in globulin and other blood products as an alternative method for the rabbit pyrogen test.

Colorimetry↗
PubMed1998

Nitric oxide production and energy state in the heart after endotoxin administration.

To evaluate nitric oxide (NO) production and the energy state of the heart after endotoxin administration, Wistar rats were injected i.p. with 10 mg/kg Escherichia coli lipopolysaccharide (endotoxin). Morphologic changes, plasma nitrite concentration, expression of inducible NO synthase (iNOS), and cardiac energy state, as reflected by several metabolites, were observed chronologically 0 (control), 4, 6 and 8 h after endotoxin administration. Electrocardiography (ECG) demonstrated arrhythmia after endotoxin administration. Biochemically, NO production increased in blood and iNOS increased in the heart. The amount of myocardial beta-ATP measured by 31P magnetic resonance spectroscopy (31P-MRS) increased transiently and then decreased. This transient increase might be a hyperdynamic response to endotoxin administration. At 4 and 6 h after endotoxin administration, pH measured by 31P-MRS was slightly decreased, but this decline was not statistically significant. On the other hand, the amount of lactate in heart samples increased in the 1H magnetic resonance spectra (1H-MRS). Ultrastructurally, in cardiovascular tissue, intracytoplasmic organelles were observed to be injured in blood vessels and cardiomyocytes associated with mast cell infiltration. These results suggest significant metabolic and morphologic abnormalities in the heart after endotoxin administration.

Animals↗
PubMed1995

Cell damage and liberation of nitric oxide synthase in rat heart induced by endotoxin administration.

To evaluate the relationship between cardiovascular injury and the pathological aspect of the liberation of the nitric oxide synthase in endotoxin shock, Wistar rats were injected intraperitoneally with 10 mg/kg E. coli endotoxin and the cardiovascular changes were observed chronologically by immunohistochemical and electron microscopic techniques at 2, 4, 8 and 12 h respectively after endotoxin administration. Light microscopically, irregular contraction of cardiomyocytes was observed in the early stage. After 8 h of endotoxin administration, occasional disintegration of the myocytes as well as lysis of myofibrils became prominent, and diminished stainings of myoglobin and actin were seen in these myocytes. Ultrastructurally, increased pinocytotic vesicles were observed in endothelial cells associated with widened intercellular spaces, and vacuolization of endothelial and medial cells of the vasculature. In cardiomyocytes, swelling of mitochondria and interstitial edema were noted at 12 h after endotoxin administration. Immunohistochemically, an increased permeability of albumin was noted in the myocytes and vasculature and nitric oxide synthase was localized on the cytomembrane of the endothelium of the coronary arteries in control rats. After endotoxin administration, the reaction products of nitric oxide synthase increased in the endothelial and medial cells, and cardiomyocytes. These results suggest that the increased activity of nitric oxide synthase is an important factor in the excessive production of nitric oxide and in promoting the pathologic changes in the cardiovascular system after endotoxin administration.

Animals↗
PubMed1993

Changes in reticuloendothelial function in dogs with endotoxin-induced shock.

A shock model was experimentally produced by intravenous injection of a lethal dose (3 mg/kg) of endotoxin under general anesthesia induced by pentobarbital sodium using 7 beagles. The effect of this endotoxic shock on the reticuloendothelial function was investigated. The blood endotoxin concentration peaked immediately after administration and decreased subsequently. However, the value still remained on an increased level (1,051 pg/ml) even at 360 min after endotoxin treatment. The lipid emulsion test as an index of reticuloendothelial phagocytotic activity and the arterial ketone body ratio as an index of the energy charge in the liver decreased after endotoxin treatment and failed to recover during the experiment. Fibronectin, one of opsonic proteins, tended to decrease after injection of the endotoxin and was significantly (p < 0.01) low at 180 and 360 min compared with the value before injection of the endotoxin. These results suggested the depression of the reticuloendothelial function during endotoxin-induced shock.

Animals↗