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Adrenocortical function in deoxycorticosterone acetate (DOCA)-hypertensive Yucatan miniature swine.

Adrenocortical function was assessed in six normal and six chronic (greater than 12 weeks), DOCA-hypertensive Yucatan miniature swine; mean arterial pressures were 115.3 +/- 11.7 and 163.6 +/- 27.2 mm Hg, respectively (mean +/- SEM). Adrenocortical function was evaluated in vivo by measuring changes in plasma cortisol and aldosterone in response to exogenous ACTH (0.25 mg, iv), and in vitro by measuring the responses of collagenase-isolated adrenocortical cells to ACTH and angiotensin II. Corticoids were measured by specific radioimmunoassay. Basal plasma cortisol values of conscious DOCA-hypertensive swine were approximately 53% of the values of normotensive swine (P less than 0.05). However, ACTH induced a 419% increase in plasma cortisol values in DOCA-hypertensive swine compared to a 261% increase in the normotensive swine (P less than 0.05). These differences between the two groups were not altered by anesthesia. There were no significant differences in ACTH-induced changes in plasma aldosterone between the normotensive and DOCA-hypertensive swine. Experiments in vitro showed that the corticoid secretory responses of adrenocortical cells from DOCA-hypertensive animals were 6 times more sensitive to ACTH and 3.2 times more sensitive to angiotensin II than those of cells from normotensive swine. Thus, despite the possibility of adrenocortical insufficiency due to suppressed plasma renin activity and the negative feedback of DOCA on the hypothalamic-hypophyseal-adrenal axis, adrenocortical function of DOCA-hypertensive swine was hyperresponsive to trophic hormones. Results from this study suggest that the DOCA-hypertensive swine may be a valuable model in elucidating the relationship between hypertension and adrenocortical function and in investigating nonclassical control of the adrenal cortex, that is, control exerted during the hypertensive state that exists apart from or in addition to that exerted by ACTH and angiotensin II.

8-Bromo Cyclic Adenosine Monophosphate↗

Clinical and epidemiological implications of swine hepatitis E virus infection.

In nonendemic areas, most patients with acute hepatitis E were infected through traveling to endemic areas. However, some patients did not have a history of foreign travel before infection. Furthermore, high seroprevalence rates of antibody to hepatitis E virus (anti-HEV) were found in the general adult population in some countries without any recorded outbreak of hepatitis E. The significance of anti-HEV assay in these subjects remains obscure. To study if swine might be a source of HEV infection, HEV was tested in sera of 235 pigs in Taiwan, and from 5 patients with acute HEV infection who either denied or did not provide any foreign travel history. Three (1.3%) pigs had detectable swine HEV RNA. The swine and human HEV strains from Taiwan formed a monophyletic group, distinct from three previously reported groups: the United States human and swine HEV strains, the Mexico strain, and the largest group composed of the Asian and the African strains. The identity of nucleotide sequences was 84-95% between swine and human HEV strains in Taiwan, and 72-79% between Taiwan strains and those from different areas. The predicted amino acid sequence of a Taiwan swine HEV strain within the peptide 3-2 used in commercial anti-HEV assay showed a high identity (91-94%) with those of other human and swine HEV strains. Swine may be a reservoir of HEV and subclinical swine HEV infection may occur. Cross-reactivity of current anti-HEV assay may account for the high prevalence rate of anti-HEV in the general population in nonendemic areas.

Adult↗

Malignant hyperthermia susceptibility: cardiac histomorphometry of dogs and young and market-weight swine.

The defect causing malignant hyperthermia has been proposed to involve cardiac as well as skeletal muscle. We tested the hypothesis that histomorphometric parameters for ventricular wall from malignant hyperthermia-susceptible swine and dogs were abnormal. Hearts were obtained from: mature dogs, age- and weight-matched young swine (89 +/- 15 days, 30 +/- 3 kg); and market-weight swine (102 +/- 10 kg). Using light microscopy, estimates were made for muscle nuclear dimensions and the volume-fraction of nuclei, sarcoplasm, blood vessels, and interstitial space. Cardiac maturation in both MH and normal swine was accompanied by decreased myocyte volume-fraction due to decreased nuclear volume-fraction and increased interstitial space volume-fraction. Sarcoplasm and vasculature volume-fraction were unchanged after maturation. Nuclear volume-fraction was slightly greater (p less than 0.05) in the right ventricle than the left for malignant hyperthermia and normal swine. Myocyte nuclear dimensions were generally similar among animals. Dogs and the oldest group of swine were not significantly different. Myocytes of all swine contained multiple nuclei, closely spaced in rows of 2 to 12. In contrast, most myocytes of mature dogs apparently contained one or two nuclei. Histomorphometric values were not significantly different between normal and malignant hyperthermia young swine and dogs. However, within the market-weight swine, volume-fraction for malignant hyperthermia myocytes and myocyte nuclei was decreased and interstitial space was increased compared to normal.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Serological, pathological and cultural evaluations of swine infected experimentally with Mycoplasma flocculare.

Fourteen caesarean-derived, colostrum-deprived pigs and seven conventional swine were exposed to low passage, cloned, field isolates of Mycoplasma flocculare. Sera were collected at varying intervals postexposure (PE) and tested against M. flocculare and M. hyopneumoniae antigens in a semi-automated ELISA. Swine were killed six to 17 weeks PE and their lungs examined grossly for lesions and culturally for mycoplasmas. Pure cultures of M. flocculare were recovered from the lungs of 11 of 14 swine killed six to 12 weeks PE. Mycoplasmas were not isolated from the swine killed 15 to 17 weeks PE. Only one pig had gross lesions of pneumonia. Immunoassays revealed that swine were slow to seroconvert and titers (expressed in terms of optical density) were low. Three of 21 swine had antibodies to M. flocculare five weeks PE, five of 17 had seroconverted at seven to eight weeks and all surviving swine had antibodies to M. flocculare 76 days PE and beyond. Net optical density of positive sera was in the range of 0.201 to 0.412 (an optical density of 0.2 regarded as the breakpoint between negative and positive reactions in our ELISA). All of the sera were ELISA-negative when tested against M. hyopneumoniae antigen. This is regarded as a very significant finding. There has been concern that field sera might contain antibodies to M. flocculare and that such antibodies could render serodiagnostic tests for mycoplasmal pneumonia of swine nonspecific. Results of the present study suggest that swine infected with M. flocculare do not develop sufficient levels of antibodies to interfere with enzyme immunoassays for M. hyopneumoniae.

Animals↗

Probable elimination of swine dysentery after feeding ronidazole, carbadox or lincomycin and verification by feeding sodium arsanilate.

Swine dysentery did not recur during a nine week period after withdrawal of medication in swine fed ronidazole at a level of 60 parts per million of feed for ten weeks or fed either carbadox at 55 ppm or lincomycin at 110 ppm of feed for six weeks. During this period swine dysentery was neither transmitted to accompanying sentinels after the withdrawal of the above medication or was Treponema hyodysenteriae isolated and cultured or observed in stained smears from rectal swabs and feces or from colonic scrapings at necropsy. Beginning three weeks after the withdrawal of medication, all swine were fed sodium arsanilate at a concentration of 220 ppm of feed for three weeks in an attempt to excite the carrier of swine dysentery into developing a swine dysentery diarrhea. A swine dysentery diarrhea did recur during the feeding of sodium arsanilate in swine previously fed ronidazole at a level of 60 ppm of feed for only six weeks. It was concluded: that swine dysentery was probably eliminated with the feeding of ronidazole for the longer duration and with the feeding of carbadox and lincomycin and that sodium arsanilate was of value in identifying the carrier state.

Animals↗

Clinical and pathological observations on the experimental passage of swine dysentery.

The length of incubation for 36 eight and 12 week old swine in eight experimental passages averaged 11 days and ranged from five to 24 days. The duration of diarrhea for 24 of these swine averaged 6.4 days and ranged from two to 19 days. The consistent macroscopic lesion was a colitis and, subsequently, a typhlitis. In the swine euthanized on the first day of diarrhea, the colitis was most intense in the coils near the apex of the colon and, frequently, these swine had a hyperemia of the fundus of the stomach. The amount of visible blood in the colon varied. Organisms identified microscopically and ultrastructurally as spirochetes were observed commonly in the feces and the mucosal glands of the colon of swine with a diarrhea, but not in the adjacent mesenteric lymph nodes. These spirochetes which were the most numerous on the first day of diarrhea, could not be isolated and propagated in vitro. Swine which recovered naturally or were medicated at the height of a diarrhea, developed a resistance to swine dysentery. Colon from infected swine remained infectious when stored at -77 degrees C for nine months but not when stored at -16 degrees C. Feces from infected swine were not infectious after lyophilization and storage at -12 degrees C.

Animals↗

Immune response of swine vaccinated with a group E Streptococcus whole-culture bacterin.

Swine (n = 10) were given a concentrated whole-culture adsorbate bacterin made from group E Streptococcus (GES). Two doses of bacterin were given subcutaneously 3 weeks apart. Control swine (n = 10) were given a blank preparation made from sterile culture medium. Swine were challenge exposed 3 weeks after the 2nd injection of bacterin by being penned continuously for 8 weeks with carrier swine infected with GES. A significant (P less than or equal to 0.009) immune response to vaccination with the bacterin was observed. Vaccinated swine, but not control swine, developed antibodies to an antiphagocytic factor (as detected with bactericidal and long-chain tests) before challenge exposure. Vaccinated swine also developed 51.2% (20 vs 41) fewer abscesses after challenge exposure than did control swine. Control swine developed a greater serologic response to challenge exposure, indicating a more extensive infection with GES.

Abscess↗

Campylobacter hyointestinalis (new species) isolated from swine with lesions of proliferative ileitis.

Intestines from 48 swine with enteric disease were examined by bacteriologic cultural technique for the presence of various Campylobacter species. Histopathologic techniques were used to determine whether the submitted specimens had lesions of either swine proliferative ileitis or other enteric diseases. Three species of Campylobacter were identified as Campylobacter jejuni/coli, Campylobacter sputorum ss mucosalis, and Campylobacter hyointestinalis (proposed new species) on the basis of biochemical characteristics and response to various inhibitory substances. The C hyointestinalis was isolated from 18 of 27 (67%) swine with proliferative ileitis and from only 1 of 21 (5%) swine with other enteric diseases. The C sputorum ss mucosalis was obtained from 16 of 27 (59%) swine with proliferative ileitis and from 2 of 21 (10%) swine with other enteric disease. The C jejuni/coli was isolated from 2 of 27 (7%) swine with proliferative ileitis and from 8 of 21 (38%) swine with other enteric disease. The new organism, C hyointestinalis, was catalase-positive, hydrogen sulfide positive in triple sugar iron agar, glycine tolerant, intolerant to 3.0% sodium chloride, able to grow at 25 C, sensitive to cephalothin, and resistant to nalidixic acid. On the basis of these characteristics, C hyointestinalis was differentiated from other campylobacters isolated from swine and from other sources.

Animals↗

Use of a DNA-based test for the mutation associated with porcine stress syndrome (malignant hyperthermia) in 10,000 breeding swine.

To test the hypothesis that the mutation associated with porcine stress syndrome (PSS; malignant hyperthermia) was present in a large proportion of North American and English swine, a simple and rapid laboratory protocol was used for cost-effective, large-scale diagnosis of susceptibility to PSS. This PSS test was applied to 10,245 breeding swine of various breeds from 129 farms in the United States, Canada, and England. Approximately 1 of 5 swine was a heterozygous carrier of the PSS mutation, with approximately 1% being homozygotes. Prevalence of the PSS mutation was 97% for 58 Pietrain, 35% for 1,962 Landrace, 15% for 718 Duroc, 19% for 720 Large White, 14% for 496 Hampshire, 19% for 1,727 Yorkshire, and 16% for 3,446 crossbred swine. The PPS gene frequencies for these breeds were 0.72, 0.19, 0.08, 0.10, 0.07, 0.10, and 0.09, respectively. In addition to these breeds, we have identified the PSS mutation in Poland China and Berkshire breeds. These gene frequencies were 30 to 75% lower in Canadian swine than in US swine, with the exception of Yorkshires, for which the gene frequency was threefold higher in Canadian swine. English swine were similarly, or more so, affected than were US swine. Accuracy was estimated at > 99%. Cost to perform the test was < $20/animal. Depending on the perceived net balance of deleterious and beneficial effects of the mutation, the PSS test could be used to eradicate the PSS mutation from herds, or for controlled expression of the mutation.

Animals↗

Antigenic and genetic analysis of a recently isolated H1N1 swine influenza virus.

Hemagglutinins (HA) of H1N1 swine influenza viruses isolated in the United States have remained antigenically and genetically conserved for many years. In contrast to such conservation, the HA of A/Swine/Nebraska/1/92 (Sw/Neb) could readily be distinguished from those of contemporary porcine viruses. Twenty-eight amino acid mutations differentiated the HA of Sw/Neb and A/Swine/Indiana/1726/88, the most recent H1N1 swine influenza virus for which HA sequence data were available. Among these differences were mutations at potential asparagine-linked glycosylation sites and charge changes at many residues. The Sw/Neb virus also could be differentiated from other swine influenza viruses in hemagglutination-inhibition assays with monoclonal antibodies to recent H1 swine HA. Nonetheless, overall sequence analysis of the HA and the nucleoprotein genes of Sw/Neb indicated that this virus was more closely related genetically to classic H1N1 swine influenza viruses than to H1N1 avian or human viruses. Infection of swine with Sw/Neb under experimental conditions induced clinical signs and lesions typical of swine influenza. However, affected swine in the field had high, persistent fevers, but relatively mild signs of respiratory tract disease. This study indicated that an antigenically and genetically novel variant of swine influenza virus was detected in the United States.

Amino Acid Sequence↗

Preliminary evaluation of antimicrobial agents for treatment of Leptospira interrogans serovar pomona infection in hamsters and swine.

OBJECTIVE: To evaluate antimicrobial agents for treatment of models of acute and persistent leptospirosis caused by Leptospira interrogans serovar pomona. DESIGN: Randomized trials comparing dosages and regimens of various antimicrobial agents for treatment of acute and persistent leptospirosis. ANIMALS: 245 Golden hamsters to model acute leptospirosis and 121 mixed-breed swine to model persistent leptospirosis. PROCEDURE: Hamsters and swine were inoculated with L interrogans serovar pomona. Antimicrobial agents were given to hamsters for 3 or 5 days after inoculation, with necropsy at 14 days after inoculation. Swine were treated for 1, 3, or 5 days beginning at 3 weeks after inoculation, and were necropsied 7 to 10 days after completion of antimicrobial agent treatment. Hamster tissue and swine tissue and urine specimens were examined by culture, fluorescent antibody testing, and histologic examination for presence of leptospires. RESULTS: All untreated control hamsters became infected and manifested clinical signs and lesions of acute leptospirosis. Leptospires were not detected in hamsters treated with dihydrostreptomycin/penicillin G (25 mg/kg of body weight). Administration of ampicillin at all dosages reduced the number of hamsters infected, as confirmed at necropsy; the other agents tested required dosages greater than label recommendations to reduce the number infected. All untreated control swine became infected and shed leptospires in urine through the time of necropsy. Leptospires were not detected in kidneys or urine of swine treated with dihydrostreptomycin/penicillin G (25 mg/kg) for 1, 3, or 5 days, or in swine treated with oxytetracycline (40 mg/kg for 3 or 5 days), tylosin (44 mg/kg for 5 days), or erythromycin (25 mg/kg for 5 days). Treatment with ceftiofur and ampicillin was not effective in elimination of L interrogans serovar pomona in swine. CONCLUSIONS: Dihydrostreptomycin/penicillin G is effective for treatment of acute and persistent leptospirosis. Differences between the effectiveness of antimicrobial agents in the acute and persistent model of leptospirosis emphasize the importance of using the appropriate model for treatment evaluation. Antimicrobial agents evaluated for treatment of persistent leptospirosis in swine required the use of dosages above those recommended by the manufacturer. CLINICAL RELEVANCE: Use of antimicrobial agents at extra-label dosages for treatment of persistent leptospirosis may cause residue problems in food animals; however, these regimens may be useful for treatment of breeding stock or animals destined for import/export.

Animals↗

Japanese encephalitis DNA vaccine candidates expressing premembrane and envelope genes induce virus-specific memory B cells and long-lasting antibodies in swine.

Swine are an important amplifier of Japanese encephalitis (JE) virus in the paradomestic environment. In this study, two JE DNA vaccine candidates were evaluated for immunogenicity in swine. Both vaccine plasmids encode a cassette consisting of the signal of premembrane (prM), prM, and envelope (E) coding regions of JE virus. One plasmid, designated pcJEME, is based on a commercial vector (pcDNA3), whereas the other plasmid, designated pNJEME, is based on a vector (pNGVL4a) designed to address some of the safety concerns of DNA vaccine use. No differences were detected in the immunogenicity of these two plasmids in mice or swine. Swine immunized with the DNA vaccines at a dose of 100 to 450 microgram at an interval of 3 weeks developed neutralizing and hemagglutination-inhibitory (HAI) antibody titers of 1:40 to 1:160 at 1 week after the second immunization. However, swine administered two doses of a commercial JE vaccine (formalin-inactivated virus preparation; JEVAX-A) developed low (1:10) or undetectable antibody responses after their boost. Interestingly, serum antibody titers elicited by DNA vaccines in swine were higher than those detected in mice. Eight days after boosting with viral antigen (JEVAX-A) to detect an anamnestic response, swine immunized two times with the DNA vaccine showed a >100-fold elevation in HAI titer, indicating a strong recall of antibody response. Swine maintained detectable levels of HAI antibody for at least 245 days after two immunizations with a DNA vaccine. These results indicate that these DNA vaccines are able to induce virus-specific memory B cells and long-lasting antibodies in swine, which were of higher levels than those obtained with a commercial formalin-inactivated JE vaccine.

Animals↗

The surface phenotype of swine blood and tissue eosinophil granulocytes.

Cell surface antigens of swine eosinophil granulocytes were studied with flow cytometry and immunohistochemistry. The monoclonal antibody 335-2, specific for swine differentiation antigen swC1a, originally described to be present on swine T and myeloid cells, is able to distinguish swine eosinophils (swC1a negative) from neutrophils (swC1a positive). This monoclonal antibody (mAb) was used in two-colour fluorescence measurements in combination with anti-swine -CD2, -CD4, -CD8, -MHC class II, -LFA-1 or -swC3 mAbs. All of the blood eosinophils proved to be positive for LFA-1 and swC3, a common marker of swine monocytes, granulocytes and macrophages. However, they do not react with antibodies recognizing swine CD2, CD4, CD8 or MHC class II cell surface molecules. The reactivity pattern of tissue eosinophils with these mAbs was determined on cryostat sections of different tissues of swine. Tissue eosinophils were negative for swC1a, CD2, CD8, while all of them reacted with swC3. In contrast with blood eosinophils, 10-30% of tissue eosinophils were demonstrated to be negative for LFA-1. In some cases, a few tissue eosinophils were found to be stained weakly by antibodies to swine CD4 or MHC class II antigens.

Animals↗

Swine models in the design of more effective medical countermeasures against organophosphorus poisoning.

Although the three most commonly used large mammal species in the safety assessment of drugs remain the dog, the macaque and the marmoset, swine, especially minipigs, have also been widely used over the years in many toxicological studies. Swine present a number of interesting biological and physiological characteristics. Similarities in skin properties with humans have led to extensive in vitro and in vivo studies. There is a specific interest in cardiovascular research, as well as in anaesthesiology and critical care medicine due to common features of swine and human physiology. Although knowledge of swine brain structure and functions remains incomplete, data does exist. The multiple blood sampling that is necessary in pharmacokinetic and toxicokinetic studies are possible, as well as multiparametric monitoring and interventions with equipment used in human clinical settings. Practicality (handling), scientific (stress reduction) and ethical (invasive monitoring) reasons have led research teams to incorporate anaesthesia into their paradigms which makes the analysis of data increasingly difficult. Although not substantiated by scientific data, the swine appears to have an intermediate position in the scale of public perception between non-human primates and animals commonly referred to as pets (i.e. dogs and cats) and rodents. The benefits of the swine model justify the use of these animals in the design of more effective medical countermeasures against known chemical warfare agents (nerve agents, vesicants and lung damaging agents). Exposure to organophosphorus (OP) pesticides represents a severe health issue in developing countries, while OP intoxication with the more lethal military nerve agents is not only of military concern but also a terrorist threat. Tailoring therapeutic regimens to the reality of OP poisoning is of the utmost importance when little experimental data and sparse human clinical data are available in the decision making process. We will present some of the advantages and disadvantages of the swine model in OP countermeasures elaborating on two examples. First, we will present the issues related to the use of anaesthesia during experimental OP poisoning and second we will show how results from experiments with swine can be integrated into a kinetic-based dynamic model to evaluate oxime efficacy. A better knowledge of OP poisoning in swine (comparative toxicokinetics, pharmacokinetics and biochemistry) is definitely necessary before accepting it as a first choice non-rodent model. However, there exists a large amount of data in the model on anaesthesia and different types of shock favouring their use for evaluation of complex situations such as the anaesthesia of OP poisoned patients and combined injuries.

Animals↗

Hyperacute rejection is attenuated in GalT knockout swine lungs perfused ex vivo with human blood.

BACKGROUND: Hyperacute rejection (HAR) is one of the principal obstacles to successful xenotransplantation. Homozygous alpha-1,3-galactosyltransferase knockout (GalT-KO) miniature swine now offer the prospect of overcoming this barrier to xenotransplantation. In this study, the short-term function of GalT-KO swine lungs was evaluated in a well-established ex vivo model of swine-to-human lung xenotransplantation. METHODS: Lungs from homozygous GalT-KO swine (n = 3) and control lungs from pigs of the background strain used to create the GalT-KO pig line (n = 2) were perfused ex vivo with freshly collected heparinized human blood. Graft function was assessed by various physiologic measurements, serial histologic and immunohistochemical evaluation, and assays of complement and platelet activation. RESULTS: Xenoperfused control swine lungs exhibited HAR with graft survival times <5 minutes. In contrast, GalT-KO swine lungs retained their function for approximately 2 hours, on average. GalT-KO swine lungs showed decreased complement and platelet activation compared with controls. Nonetheless, activation of complement and coagulation cascades was not completely eliminated in the GalT-KO swine lungs. CONCLUSIONS: The survival of xenoperfused GalT-KO swine lungs was significantly prolonged, as compared with control lungs expressing Gal. This appears to have been due largely to substantially reduced complement activation. Nonetheless, the xenoperfused GalT-KO lungs still showed some evidence of complement fixation and intravascular coagulopathy by the time of graft demise.

Acute Disease↗

Overview of the Second International Workshop to define swine cluster of differentiation (CD) antigens.

The aim of the Second International Swine Cluster of Differentiation (CD) Workshop, supported by the Veterinary Immunology Committee (VIC) of the International Union of Immunological Societies (IUIS), was to standardize the assignment of monoclonal antibodies (mAb) reactive with porcine leukocyte differentiation antigens and to define new antibody clusters. At the summary meeting of the workshop in July, 1995, revisions in the existing nomenclature for Swine CD were approved, so that the rules are now in accord with those for human and ruminant CD. Swine CD numbers will now be given to clusters of mAb to swine orthologues of human CD molecules when homology is proven by (1) suitable tissue distribution and lymphoid cell subset expression, (2) appropriate molecular mass of the antigen recognized by the mAbs, and (3) reactivity of mAbs with the cloned swine gene products, or cross-reactivity of the mAb on the human gene products. In some cases, this reactivity would not be fully proven, mainly due to the lack of cloned gene products; for these CD antigens, the respective clusters will be assigned by the prefix 'w' which will lead to 'wCD' antigens. As a result of the Second International Swine CD Workshop the assignment of 16 mAb to existing CD groups (CD2a, CD4a, CD5a, wCD6, wCD8, CD14, CD18a, wCD21, wCD25) was confirmed, and 2 mAb to existing swine workshop clusters (SWC). More importantly, for the work on the porcine immune system, was the definition of 5 new swine CD antigens, namely CD3 (recognized by 6 new mAb and 3 epitopes), CD16 (1 new mAb), wCD29 (2 mAb), CD45RA (3 mAb) and CD45RC (1 new mAb). Finally, the demarcation of two new SWC molecules in swine, SWC8 (2 mAb) and SWC9 (2 mAb) was confirmed.

Animals↗

Challenge differentially affects cytokine production and metabolic status of growing and finishing swine.

Growing (35 kg body weight) and finishing (85 kg body weight) swine challenged with endotoxin (Escherichia coli O55:B5) at a dose of either 2 or 20 microg/kg produced tumor necrosis factor (TNF)alpha in a dose-response relationship as measured by bioassay. Peak TNFalpha plasma levels were observed 1-2 hr post-challenge, returning to basal values 4 hr post-challenge. However, both an enzyme-linked immunosorbent assay specific for swine TNFalpha and total human TNFalpha demonstrated no dose-response relationship; peak plasma levels of immunoreactive TNFalpha were also observed 1-2 hr post-challenge. Maximal plasma interleukin-6 levels occurred 1-2 hr post-challenge and remained elevated through 8 hr post-challenge; there was no effect of lipopolysaccharide dose or metabolic status. Although the metabolic status of the animals also affected glucose levels, with growing animals exhibiting greater sensitivity compared with finishing animals, endotoxin-induced decreases in blood glucose levels were primarily dose-dependent. In contrast, changes in plasma urea nitrogen and free fatty acid (FFA) levels were strictly related to the metabolic status. Urea nitrogen levels were unchanged in growing swine, whereas they were increased in finishing swine and remained elevated 24 hr post-challenge. FFA levels in growing and finishing swine increased 3-6 hr post-challenge. FFA levels returned to basal values for finishing swine 24 hr post challenge, but in growing swine remained elevated 24 hr post-challenge. Plasma aspartate transaminase levels were increased through 24 hr post-challenge; animals given a dose of 20 microg/kg exhibited the greatest increase. Similarly, swine challenged with a dose of 20 microg/kg also exhibited the greatest increase in levels of conjugated bilirubin; there was no effect on unconjugated (free) bilirubin. These results demonstrate that endotoxin challenge of swine result in a pattern of changes that are dependent on both the dose of endotoxin used and the metabolic status of the animal examined.

Animals↗

Evaluation of a double-lumen multiorifice catheter for resuscitation of swine from lethal venous air embolism.

BACKGROUND: A double-lumen multiorifice catheter has been developed to potentially enhance accurate electrocardiographic central venous localization and resuscitation from a massive venous air embolism (VAE). This double-lumen multiorifice catheter was compared to a Bunegin-Albin multiorifice catheter for flow characteristics, air aspiration efficiency, and efficacy in resuscitating swine from a lethal VAE. METHODS: Flow characteristics of both catheters were determined by aspirating both agitated and unagitated citrated swine blood with a 50-ml syringe. Swine were anesthetized with halothane and positioned to approximate a modified sitting craniotomy position (45-degree elevation). By a random block method, 24 swine were assigned to either catheter (n = 12 each catheter) for the initial air aspiration. Catheters were positioned, using intravenous electrocardiography, with the distal aspiration orifice in the high right atrium. A 5-ml/kg air embolism was administered over 30 s into the sagittal sinus, and the swine were resuscitated by aspirating air through the multiorifice catheters and then positioning the swine horizontally. Surviving animals were allowed to recover for 60 min. The initial catheter was exchanged and repositioned in the high right atrium using intravenous electrocardiography. A 5-ml/kg air embolus was administered, and the swine were resuscitated as in the first challenge. Surviving swine recovered for 60 min, repositioned, and administered a third 5-ml/kg air embolism. On this final challenge, no attempt was made to resuscitate the animal by aspirating the multiorifice catheter. RESULTS: Flow characteristics of both catheters were similar in the unagitated blood (195.3 +/- 1.9 vs. 196.7 +/- 2.5 ml/min). The flow rate of agitated blood through the double-lumen multiorifice catheter was 14% greater than through the Bunegin-Albin catheter (136.3 +/- 6.8 vs. 117 +/- 5.9 ml/min, P = 0.001). Forty-three air embolism trials were conducted at 5 ml/kg. All nine trials at 5 ml/kg without air aspiration resulted in death. Five animals died during the embolism dose determination trials, and four died during the third embolism challenge. The use of a multiorifice catheter for aspiration after a VAE enhanced survival after a 5-ml/kg sagittal sinus air embolus (14/34 vs. 0/9, P = 0.02). Although the double-lumen multiorifice catheter was more efficient than the Bunegin-Albin catheter in percentage of air retrieved (37.7 +/- 12.0 vs. 29.7 +/- 10.1, P = 0.042). Aspiration of the VAE with the double-lumen multiorifice catheter successfully rescued 9 of the 15 trials, and aspiration using the Bunegin-Albin catheter resuscitated 5 of the 19 (P = 0.08). CONCLUSIONS: Multiorifice catheters are effective in resuscitating swine from a lethal VAE. The double-lumen multiorifice catheter evaluated aspirated a larger percentage of the VAE but was not statistically more effective than the Bunegin-Albin catheter in resuscitating the animals. Based on these findings of improved flow rate and efficiency in air aspiration, further investigation of this double-lumen multiorifice catheter is warranted.

Animals↗