[The efficiency of reamberinum in infusion therapy of acetonemic syndrome in children].

The current paper presents the results of monitoring of 69 patients with acute respiratory viral infection, acetonemic syndrome. It was shown the effectiveness of inclusion of Reamberinum into complex therapy as a means for reduction of with acetonemic syndrome and for detoxic effect.

[Impact of the combined application of elastic bandaging of the lower extremities and autohemotransfusion on biochemical indices of the blood and severity of endogenous intoxication in patients with concomitant cardiovascular insufficiency].

Venous congestion in abdominal inner organs in surgical diseases in patients with heart insufficiency may additionally impact biochemical indices of the blood and severity of endogenous intoxication (EI). Basing on the data obtained in the investigations, th was established, that the lower extremities bandaging promotes exit of the blood from depot, where it resides in a concentrated state in cellular and biochemical aspects. It promotes more effective accomplishment of hemodilution as well as reduction of the EI severity in taking of the autologous blood.

Acid-base and electrolyte status during early induced pregnancy toxaemia in goats.

Eleven Murciano-Granadina goats in late pregnancy were separated into two groups (1) control (n=6) and (2) fasting for 72 h to induce pregnancy toxaemia (n=5). Venous blood was taken daily to determine acid-base and electrolyte parameters. Significant decreases in blood pH, bicarbonate concentration and base excess, and a significant increase in anion gap were observed after 24h of fasting. These changes were significantly correlated with non-esterified fatty acid concentration. No significant changes were observed in pCO(2), and electrolyte or lactate concentrations. Clinical signs of pregnancy toxaemia in fasted goats appeared by 72h post-fasting. These signs and the changes in acid-base balance disappeared once feed was reintroduced. Blood pH, bicarbonate concentration, base excess and anion gap could be indicators of early pregnancy toxaemia in goats.

An outbreak of enterotoxaemia at livestock farm during subtropical summer.

Present investigations were carried out on 10 dead animals including eight in lambs, one in goat kid and one in calf during subtropical summer at a local farm. The weather was hot and humid with rain occurring during the period. The history suggests an association of weather and concentrate/lush green diet/fodder with occurrence of the disease. The most consistent clinical signs reported were no interest in feeding, herding in a corner with head down, diarrhea of low degree and temperature around 102 degrees F. At postmortem examination, the most consistent findings were swollen soft kidneys, hydropericardium, congested and edematous lungs, congested liver, myocardial hemorrhages and ballooning of intestines. The histopathological examination revealed the most striking changes in kidney of vacuolation in renal tubular epithelial cells and increased Bowman's space in the glomeruli. The histopathological examination of liver revealed congestion. Lungs revealed congestion and edema. The urine from urinary bladder collected showed high glucose. The deaths in these animals were probably due to enterotoxaemia type D.

Histomorphometric study of placental villi vascular volume in toxemia and diabetes.

The quantitative changes in the vascular tree in placentas from pregnancies complicated by diabetes mellitus and preeclampsia (PE) are not well defined. The purpose of this study was to quantify placental villi cross-sectional area of capillaries assessed by a computerized morphometry system in pregnancies complicated by PE (n = 23), well-controlled pregestational diabetes mellitus (PGDM; n = 10), and healthy controls (n = 13). Our aims were to test whether villous capillarization volume was changed in PE without intrauterine growth restriction or PGDM compared with the control group and to study these effects in 3 different areas of the placenta. Examination of placentas in women with PGDM and PE revealed limited pathological changes on light microscopic examination. However, the morphometric analysis revealed a more than 5-fold decrease of villous vascular volume in PGDM compared with controls (P = .003) and a 1.6-fold decrease in the PE group that did not reach statistical significance. These findings show quantitative changes in the villous vascular tree in PGDM that are not detectable by conventional light microscopy and suggest that morphometric analysis of the capillary tree may have diagnostic importance in this entity. The findings differ significantly from those previously reported in pregestational diabetes and do not differ significantly from those reported in PE without intrauterine growth restriction.

[Disorders of the ventilation-diffusion correlations and of the gas-transport function of the blood in the acute period of burn trauma in children]. / Narushenie ventiliatsionno-diffuzionnykh vzaimootnoshenii i gazotransportnoi funktsii krovi v ostryi period ozhogovoi travmy u detei.

External respiration and blood gas composition were examined in 187 children aged 1 to 14 years during the acute period of burn disease (burn shock and toxemia). The patients were divided into three groups with different area of thermal injury to the skin. Group 1 were children with burns of up to 10% of body surface area. The ventilation parameters in this group were changed just negligibly, and the diffusion capacity of the lungs and gas composition of arterial blood were within the normal range of values both during shock and toxemia. In patients with burns involving 11 to 20% of body surface the ventilation parameters were changed appreciably and did not compensate for each other, as was observed in group 1. The diffusion capacity of the lungs and blood gas composition values were moderately decreased. During toxemia the minute-consumption of oxygen was decreased and alveolar oxygen tension remained unchanged. As a result of this, the diffusion capacity of the lungs and blood gas parameters continued to decrease. The most dynamic changes were observed in children with burns involving 21 to 45% of body surface. The ventilation-diffusion disorders and blood gas composition were altered, particularly so during toxemia; the changes consisted in a decrease of the minute ventilation volume and oxygen tension in arterial blood and a moderate increase of alveolar oxygen tension, which led to further decrease of the diffusion capacity of the lungs. In parallel with the disorders in the above parameters, x-ray changes in the lungs were observed, which were characterized by a vascular-interstitial pattern in group 2 and infiltrative changes in group 3. In children with burn wounds of 35 to 45% of body surface these changes presented as the developing lung edema.

Endogenous intoxication syndrome when acute process in abdominal cavity.

In the time of simultaneous study of the components of blood of sick patient and animals with acute processes in abdominal cavity it was revealed that in short periods there is increase in value indeces of endogenous intoxication syndrome. The independent index is offered for studying the endotoxicosis of whole blood. It is recommended to use for general and particular characteristics of dynamics during the pathological process.

Experimental human endotoxemia increases cardiac regularity: results from a prospective, randomized, crossover trial.

OBJECTIVE: To determine whether human endotoxemia is associated with a loss of the physiologic beat-to-beat variability of heart rate. DESIGN: Prospective, randomized, crossover, single-blind study. SETTING: Clinical research center in a federal, nonuniversity hospital. SUBJECTS: Healthy volunteers. INTERVENTIONS: Intravenous administration of reference (Escherichia coli) endotoxin or saline placebo, with or without previous administration of oral ibuprofen. MEASUREMENTS AND MAIN RESULTS: Electrocardiograms were continuously recorded and digitized using series of 1000 beat epochs of R-R intervals over 8 hrs. Analyses included measures in the time domain (standard deviation), frequency domain (power spectra), and a measure of regularity (approximate entropy). Endotoxin administration was associated with loss of variability by all measures. This loss of variability remained significant even with administration of ibuprofen, which blocked the development of fever and endotoxin-related symptoms. CONCLUSIONS: Infusion of endotoxin into human volunteers causes loss of heart rate variability, as measured by standard deviation and power spectra, as well as an increase in heart rate regularity, as measured by approximate entropy. Changes in approximate entropy occurred earlier than changes in other heart rate variability measures and may be a useful means of detecting early sepsis. This reduction in regularity is consistent with a model in which the pathogenesis of multiple organ system dysfunction syndrome involves the physiologic uncoupling of vital organ systems.

High plasma levels of von Willebrand factor as a marker of endothelial perturbation in cirrhosis: relationship to endotoxemia.

The aim of this study was to evaluate whether there is endothelial dysfunction in patients with cirrhosis and to detect the mechanism that may account for it. We measured plasma levels of von Willebrand factor (vWF), a marker of endothelial perturbation, and endotoxin, which releases vWF from endothelial cells in vitro, in 32 patients (18 men, 14 women, aged 39-70 years) with cirrhosis classified as mild (class A, n = 10), moderate (class B, n = 16), or severe (class C, n = 6) according to Child-Pugh's classification. vWF antigen (P < .0001) and endotoxemia (P < .0001) progressively increased from A to class C; but the increase of vWF antigen was not strictly related to liver failure, as shown by the lack of correlation between vWF and several indexes of liver protein synthesis. Analysis of the vWF subunit showed no sign of proteolytic fragmentation of the molecule. Multimeric analysis indicated intact vWF multimeric structure. In all patients, there was a strong correlation between vWF antigen and endotoxemia (rho = .92; P = .0001). In 20 selected patients, vWF antigen and endotoxemia were measured before and after 7 days of standard therapy (n = 10) or standard therapy plus nonabsorbable antibiotics. There was a significant decrease of vWF antigen (P < .02) concomitantly with the decrease of endotoxemia (P < .006) in patients taking nonabsorbable antibiotics. Human umbilical vein endothelial cells incubated in vitro with 125 to 500 pg/mL endotoxin released vWF antigen into the medium dose dependently. These results demonstrate that there is endothelial perturbation in cirrhosis and that endotoxemia may play a key role in its occurrence.

Evaluation of plasma alpha-2-macroglobulin and interactions with tumour necrosis factor-alpha in horses with endotoxemic signs.

The electrophoretic position and behavior of the native and activated forms of equine plasma alpha-2-macroglobulin (alpha 2M) were characterized and compared to human alpha 2M by nondenaturing polyacrylamide-gel electrophoresis (PAGE). Plasma alpha 2M was also compared between 6 normal horses and 6 horses with clinical signs of colic and endotoxemia due to volvulus or enteritis. Native and activated forms of alpha 2M were quantified by PAGE and densitometry. Binding of radio-labeled recombinant human tumour necrosis factor-alpha (125I-rhTNF-alpha) to native and activated forms of equine alpha 2M was also evaluated by autoradiography and densitometry of PAGE. Equine plasma alpha 2M migrated as a single band at a position equivalent to native human alpha 2M. Methylamine-reacted equine plasma samples resulted in faster migration of alpha 2M in a similar position to activated human alpha 2M. However, in methylamine-reacted equine plasma, an intermediate alpha 2M band was consistently present between the bands corresponding to native and activated alpha 2M. Amounts of plasma alpha 2M were similar in normal and endotoxemic horses, and remained in the electrophoretically slow or unreacted native form. The vast majority of 125I-rHuTNF-alpha did not bind to alpha 2M or other equine plasma proteins. 125I-rHuTNF-alpha bound weakly to both native and fast methylamine-reacted equine forms of alpha 2M, although binding was better to the activated form. This study indicates that: (1) equine plasma alpha 2M behaves similarly to human alpha 2M on PAGE, (2) plasma alpha 2M of horses can be activated to electrophoretically fast forms, but it is neither activated nor depleted during endotoxemia, and (3) the binding interactions between equine alpha 2M and TNF-alpha are too low to implicate equine alpha 2M as a regulator of TNF-alpha during endotoxemia in horses.

Lidocaine attenuates the hypotensive and inflammatory responses to endotoxemia in rabbits.

OBJECTIVE: To assess the effects of lidocaine on the hemodynamic and inflammatory responses to Escherichia coli endotoxemia in rabbits. DESIGN: Prospective, randomized, controlled experimental study. SETTING: University laboratory. SUBJECTS: Twenty-seven female Japanese rabbits, anesthetized with urethane and ventilated mechanically. INTERVENTIONS: Animals were randomly assigned to one of three groups: a) endotoxemic control group (n = 9), receiving intravenous Escherichia coli endotoxin (0.5 mg/kg bolus) via the mesenteric vein; b) laparotomy control group (n = 9), treated identically to the endotoxemic control group, except for substitution of 0.9% saline for endotoxin; and c) lidocaine-treated group (n = 9), treated identically to the endotoxemic controls and additionally, intravenous lidocaine (3 mg/kg bolus, followed by infusion at 2 mg/kg/hr) was administered immediately after endotoxin MEASUREMENTS AND MAIN RESULTS: We compared hemodynamics, blood gases, and microscopic findings of lung tissue obtained at necropsy in each group. Laparotomy alone had a minimal effect on the parameters and findings. Endotoxin injection decreased mean systolic arterial pressure from 135 +/- 6 (SD) to 95 +/- 25 mm Hg (p < .05) and increased the mean base deficit from -1.2 +/- 1.8 to -14.4 +/- 4.2 mmol/L (p < .05), and caused the infiltration of neutrophils into the lungs. Lidocaine administration abolished the hypotension and attenuated the increase the base deficit to -9.5 +/- 2.1 mmol/L (p < .05) and the cellular infiltration in comparison with endotoxemic controls. CONCLUSIONS: Lidocaine attenuated the hemodynamic and inflammatory responses to endotoxemia in rabbits. Findings suggest that lidocaine administration may prevent the development of hypotension and metabolic acidosis during endotoxemia.

Parathyroid hormone-related protein is induced during lethal endotoxemia and contributes to endotoxin-induced mortality in rodents.

BACKGROUND: Parathyroid hormone-related protein (PTHrP) is a ubiquitous and highly conserved vasoactive peptide whose role and regulation in normal physiology remain an enigma. Recently, we demonstrated that low-dose endotoxin (LPS) induces intrasplenic, but not systemic, levels of PTHrP; and that tumor necrosis factor, a pro-inflammatory cytokine, is the major mediator of this effect. We have therefore hypothesized that, with higher, lethal doses of endotoxin, PTHrP could be induced in multiple tissues to such a degree that it could contribute to the lethality of septic shock. MATERIALS AND METHODS: Northern blot analysis was used to measure PTHrP mRNA levels in vital organs of rats after administration of a near lethal dose (5 mg/250 g) of LPS (or vehicle alone). Plasma levels of PTHrP were also measured by immunoradiometric assay. The ability of the immunoglobulin fraction of two different PTHrP(1-34) antisera to protect from LPS-induced lethality was also studied in mice using survival analysis. RESULTS: In response to a near-lethal dose of endotoxin, PTHrP mRNA levels increased acutely in every vital organ examined (spleen, lung, heart, kidney, and liver). Circulating levels of PTHrP also increased, peaking 2 hr after administration of high-dose endotoxin. Passive immunization of mice with anti-PTHrP(1-34) antibody 6 hr prior to administration of a lethal dose of LPS protected mice from endotoxin-induced death (p < 0.00005). CONCLUSIONS: These results suggest that PTHrP belongs to the cascade of pro-inflammatory cytokines induced during lethal endotoxemia that is responsible for the toxic effects of LPS.

The role of tumor necrosis factor and nitric oxide in the acute cardiovascular response to endotoxin.

OBJECTIVE: This study was designed to examine the differential effects of tumor necrosis factor (TNF) and nitric oxide on the acute cardiovascular changes that occur in response to endotoxemia. SUMMARY BACKGROUND DATA: Recent studies have suggested that some, if not all, of the cardiovascular effects of TNF are mediated through release of nitric oxide. However, the mechanisms through which TNF and nitric oxide induce hypotension and shock in vivo in response to systemic endotoxemia remain poorly characterized, despite current interest in the use of nitric oxide antagonists to ameliorate septic shock. METHODS: A reproducible model of endotoxemia was established in adult Sprague-Dawley rats. The acute cardiovascular changes that occur after bolus infusion of endotoxin was then determined in rats treated with either TNF antibody, N-methyl arginine, or both. RESULTS: Inhibition of either TNF or nitric oxide restores mean arterial blood pressure to normal after endotoxemia (p < 0.05). However, nitric oxide exerts its effects principally on the peripheral vasculature, whereas TNF appears to act on the myocardium. A combination of TNF antiserum pretreatment and N-methyl arginine administration is necessary to return mean arterial blood pressure to normal 60 minutes after endotoxin infusion. CONCLUSION: Tumor necrosis factor and nitric oxide mediate the acute cardiovascular effects of endotoxemia through distinct mechanisms. Nitric oxide is released as a result of both TNF-dependent and TNF-independent mechanisms, whereas the cardiovascular effects of TNF are only partially mediated through nitric oxide.

The effects of glibenclamide, a blocker of K+ ATP-sensitive potassium channels, on diaphragmatic fatigue during endotoxaemia in pigs.

An in vivo porcine model of endotoxaemia was used to study the effects of glibenclamide, a K+ ATP-sensitive potassium channel blocker. Escherichia coli lipopolysaccharides (LPS, 70 micrograms/kg, i.v., as a bolus) were infused into anaesthetized, mechanically ventilated, indomethacin-treated pigs. After 120 min of endotoxaemia, glibenclamide was administered (10 mg/kg, i.v., over 5 min) to half the pigs. The strength at different frequencies of stimulation (10, 20, 30, 50 Hz, 20 V,) 1 s) and the endurance capacity (10 Hz, 20 V, 30 s) of the diaphragm were evaluated after 120 min of endotoxaemia and 5, 10, 20 and 30 min after drug infusion. Glibenclamide transiently increased the blood pressure without changing the decreased cardiac output and at the same time further impaired the diaphragmatic activity. The reduced ability of the diaphragm to generate force in response to different electrical stimulations was shown by a significant reduction in strength. The endurance index decreased 5 min after glibenclamide infusion, returning to the pre-glibenclamide values by 150 min. These results indicate that glibenclamide modifies the activity of vascular smooth muscle and of the diaphragm.

Effect of pentobarbital anesthesia on the pressor response to agonists in vivo in normal and endotoxemic rats.

Studies of cardiovascular physiology are frequently performed under barbiturate anesthesia even though the effect of barbiturates on the pressor response to catecholamines is controversial, and their effect on the response to other agonists is unknown. The effect of pentobarbital (PB) anesthesia on the pressor and heart rate (HR) dose responses to norepinephrine (NE), angiotensin II (AII), vasopressin (VP) and neuropeptide Y (NPY) was studied in vivo in normal and endotoxemic rats. Four groups of rats (5-6 rats/group) were studied for each agonist: 1) anesthetized/endotoxemic, 2) anesthetized/control, 3) conscious/endotoxemic, and 4) conscious/control. Anesthesia was maintained with 10 mg/kg of PB i.v. q 45 minutes. Endotoxemia was established by infusion of a non-hypotensive dose of E. coli lipopolysaccharide 0127:B8, (LPS, 10 micrograms/10 microliters/min) throughout the experiment. One hour after the LPS (or saline control) infusion was started, dose response curves of the pressor and HR responses to agonists were established. LPS infusion resulted in marked suppression of the pressor response to NE, AII, and VP in both conscious and anesthetized rats. LPS infusion suppressed the response to NPY in conscious, but not in anesthetized rats. LPS did not affect the baroreceptor reflex. In both normal and endotoxemic rats, PB anesthesia suppressed the pressor response and attenuated the baroreceptor reflex to AII and NPY, enhanced the pressor response without affecting the heart rate response to NE, and attenuated the baroreceptor reflex to VP. The pressor response to VP was suppressed by anesthesia in normal, but not in endotoxemic rats. PB anesthesia interferes with the cardiovascular effects of different agonists in a variable manner, depending on the agonist tested and the presence or absence of endotoxemia, indicating their different modes of action. These effects should be considered when planning in vivo experiments with these and other agonists.

Inhibition of nitric oxide synthesis aggravates reperfusion injury after hepatic ischemia and endotoxemia.

The potential role of nitric oxide (NO) was investigated in the pathophysiology of liver injury after priming with 20 min hepatic ischemia-reperfusion and administration of .5 mg/kg Salmonella enteritidis endotoxin. Liver injury during the early reperfusion phase of 4 h was characterized by severe vascular oxidant stress, lipid peroxidation (LPO), neutrophil infiltration, and a 33% reduction of the microvascular blood flow in the liver. Inhibition of NO synthesis with N omega-nitro-L-arginine methyl ester hydrochloride (L-NAME) aggravated liver injury by 90%, reduced LPO, and did not affect liver neutrophils but further impaired microvascular blood flow. Treatment with the NO-donor spermine-NONOate or L-arginine did not affect these parameters in postischemic animals, however, treatment did restore all values of L-NAME-treated animals back to disease control levels. These data suggest that endogenous NO formation is sufficient to limit ischemic liver injury during reperfusion but inhibition of NO synthesis will result in additional ischemic damage. NO may also be involved in scavenging of superoxide in the vasculature and in inducing LPO.

Mediators and vascular effects in response to endotoxin.

Recent experimental findings indicate that endotoxin (i.e. lipopolysaccharide) interacts with specific membrane receptors localized to mononuclear phagocytic cells and neutrophils. Binding of endotoxin to these cells, together with endotoxin-induced activation of host vascular endothelium, initiates a series of signal transduction events that culminate in release of numerous biochemical mediators. The latter include cytokines, platelet-activating factor, thromboxane A2, prostaglandins, leukotrienes, nitric oxide, proteases, toxic O2 radicals, and vasoactive amines. These mediators orchestrate complex biological interactions and amplification signals that lead to cardiopulmonary dysfunction and multi-organ failure within 4-6 h of experimental infusion of endotoxin into animals. The pathophysiological changes include decreased cardiac output, systemic hypotension, decreased blood flow and O2 delivery to tissues, intense pulmonary vasoconstriction and hypertension, bronchoconstriction, increased permeability, pulmonary oedema, ventilation-to-perfusion inequalities, hypoxaemia, and haemoconcentration. Metabolic alterations include increased blood lactate and pyruvate, metabolic acidosis, hyperkalaemia and hypoglycaemia. Potential therapeutic modalities for treatment of endotoxaemia/septic shock include specific antagonists directed against lipopolysaccharide, cytokine, and platelet-activating factor receptors, monoclonal antibodies directed against cytokines and lipid A/core polysaccharides of endotoxin, antiproteases, and agents that block release of toxic O2 and arachidonic acid metabolites.

Release of EDRF and NO in ex vivo perfused aorta: inhibition by in vivo E. coli endotoxemia.

Previous studies have yielded contradictory results about interrelations between endotoxin and endothelium-derived relaxing factor (EDRF). We tested the hypothesis that in vivo endotoxemia inhibits basal and/or agonist-mediated release of EDRF and nitric oxide (NO). EDRF bioactivity, NO production, and NO synthase (NOS) activity were measured in aorta from guinea pigs following 16 h of Escherichia coli endotoxemia (4 mg/kg endotoxin i.p.). Endothelium-dependent relaxation of aortic rings was studied under standard isometric conditions. Endotoxemia resulted in an 89% reduction in basal EDRF bioactivity and a 62% reduction in basal NO production in perfused aorta. EDRF bioactivity and NO production in response to the receptor-dependent agonists acetylcholine and ADP were significantly reduced in perfused aorta from endotoxemic animals. In contrast, endotoxin did not significantly inhibit EDRF bioactivity and NO production by the receptor-independent agonist A-23187. Aortic rings from endotoxemic animals likewise showed decreased vasodilator responses to acetylcholine and ADP but not to A-23187. Inducible (Ca2+ independent) NOS activity was not significantly different in control and endotoxin-treated animals. These findings indicate that prolonged endotoxemia resulted in diminution of release of EDRF, consistent with the interpretation that endotoxemia decreases basal and agonist-stimulated EDRF bioactivity and NO production with loss of endothelium-dependent vasodilator reserves during gram-negative sepsis.

Endogenously opsonized particles divert prostanoid action from lethal to protective in models of experimental endotoxemia.

We report that, in rats, the lethal consequences of high-dose endotoxin challenge are exacerbated by the intravascular administration of prostaglandin E1 but attenuated by the intravascular administration of endocytosable particles. This protection is mediated by opsonins. Nonopsonizable particles were unable to provide protection unless first pseudoopsonized with antibody directed against the CR3 (CD11b/CD18) phagocyte receptor. We show that endogenously opsonized particles can act in concert with prostaglandin E1 (putatively by elevation of neutrophil intracellular cAMP and the resultant downregulation of CR3) to completely rescue animals from the lethal late-stage sequelae of experimental endotoxemia. These data illustrate that the interaction of particles with cellular receptors can transform the overall systemic response to prostaglandin E1 from pro- to antiinflammatory. This suggests a role for multiple receptor engagement events in defining the systemic prostaglandin response and offers a rationale for developing new therapeutic modalities in the treatment of sepsis and other inflammatory diseases.