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Determinants of longitudinal changes in spirometric function among swine confinement operators and farmers.

To assess whether working in a swine confinement facility causes an excess or accelerated decline in lung function, we conducted a population-based study to evaluate the determinants of longitudinal changes in airflow in a population of swine confinement operators. Spirometric measures of lung function were compared between swine confinement operators (N = 168) and neighborhood farmer control subjects (N = 127). Study subjects were randomly selected from a cohort of swine confinement operators in eastern Iowa. The control farming population was matched by geographic location, age, and sex to the swine confinement operators. On average, the follow-up time was approximately 2 yr, with a range of follow-up between 56 and 1,900 d. Although swine confinement operators and neighborhood farmers had similar demographic characteristics (age, gender, racial background, smoking history, and atopy status), swine confinement operators tended to have less farming experience and were more extensively followed (more measures of lung function and longer periods of observation) than the neighborhood farmer control group. Swine confinement operators were also exposed to higher environmental dust concentrations and other irritants than the farmer control subjects. Interestingly, the cross-sectional data indicated that swine confinement operators tended to have slightly lower measures of airflow and greater workshift declines in forced expiratory volume in one second (FEV1), forced vital capacity (FVC), and mid-expiratory flow (FEF25-75) than the neighborhood farmer control group.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Effect of route of breathing on response to exposure in a swine confinement building.

Exposure of naive subjects to swine buildings results in acute nasal, lung, and peripheral blood inflammatory responses with an increase in nonallergic airway responsiveness. Because nasal passages filter large particles and soluble gases and because swine building exposure results in an acute inflammatory response at this level, we questioned what effect breathing through or avoiding this route would have on local and systemic inflammation. Nine normal young men 23 to 37 yr of age were exposed for 5 h to a swine building, once breathing normally and once with the mouth occluded (n = 8) (Protocol 1) or the nose occluded (n = 4) (Protocol 2); three subjects participated in both protocols. For each protocol each subject underwent a methacholine challenge for PC20 measurement, a nasal lavage, venous blood puncture, and a bronchoalveolor lavage (BAL) once before and once after each swine building exposure. Bronchial responsiveness as measured by PC20 decreased in most subjects after swine building exposure and was not influenced by the route of breathing. Nasal lavage neutrophils increased tenfold after each swine exposure, except when the nose was occluded where no alteration was observed. Total BAL cells significantly increased after each exposure to the swine building, this increase was not modified by the route of breathing. In Protocol 1, white blood cells increased from a baseline level of 7.0 to 10.5 x 10(9) cells/L after exposure with normal breathing and to 10.7 x 10(9) cells/L during nasal breathing exclusively. For Protocol 2, these respective values were: 5.6, 11.7 and 10.4 x 10(9)/L. Interleukins 6 and 8 levels in BAL, nasal washes, and serum were increased by swine building exposure, except in the nasal wash when the nose was occluded. In conclusion, the lung and blood responses to exposure in a swine confinement building are not modified by the route of breathing, suggesting that nasal inflammation and filtration are not important in the process and that small respirable particles and/or gases may be responsible for these responses.

Adult↗

Lymphocyte activation after exposure to swine dust: a role of humoral mediators and phagocytic cells.

Exposure to swine dust causes intense airway inflammation with multifold increase in inflammatory cells and secretion of pro-inflammatory cytokines. This in vitro study focuses on the swine-dust activation of lymphocytes in whole blood, in phagocyte-depleted whole blood and in peripheral blood mononuclear cells (PBMC), in order to investigate whether phagocytic cells and/or soluble mediators are involved in the activation of T-cells following exposure to organic dust from a swine confinement house. T-cell activation was analysed by flow cytometry with double staining for CD3 and the activation marker CD69. Swine dust (50 microg) incubated (24 h) with heparinized whole blood was shown to activate 27.6% of the T-cells, while swine dust incubated with whole blood depleted from phagocytic cells or PBMC only activated 4.5%, and 4.8% of the T-cells, respectively. Plasma separated from whole blood preincubated with swine dust for 24 h stimulated as much as 32.4% of PBMC T-cells and contained high levels of interleukin (IL)-12 (14 pg x mL) and interferon (IFN)-gamma (2284 pg x mL(-1)), while plasma from PBMC incubated with swine dust contained low levels of IL-12 (2 pg x mL(-1)) and IFN-gamma (196 pg x mL(-1)). This study demonstrates that activation of T-cells by organic dust from a swine confinement building seems to require phagocytic cells, most likely acting through the release of soluble mediators. Also, conditioned plasma from swine-dust exposed whole blood, which was capable of activating T-cells, contained high concentrations of interleukin-12 and interferon-y.

Adult↗

Alterations in bronchoalveolar lavage fluid but not in lung function and bronchial responsiveness in swine confinement workers.

Testing of lung function and bronchial reactivity, bronchoalveolar lavage (BAL), and a skin prick test with a standard panel and six "swine" extracts obtained from swine and swine environment were performed in 20 randomly selected nonsmoking swine confinement workers. In addition, blood samples for detection of antibodies by the diffusion in gel-enzyme-linked immunosorbent assay (DIG-ELISA) technique and precipitating antibodies were drawn. Air samples for measurement of dust and endotoxin levels were collected. All the farmers regarded themselves as healthy. The results were compared with reference groups consisting of urban nonsmoking subjects who had not been exposed to pig farming environment. The pig farmers had normal lung function and the bronchial reactivity was not different from the reference group. In the BAL fluid of the farmers, the concentration of total cells and granulocytes was increased while the concentrations of lymphocytes and macrophages were normal. The BAL fluid concentrations of albumin, fibronectin, and hyaluronan were elevated in the farmers. Skin prick tests with swine extracts were negative in all farmers. Antibodies (assessed by DIG-ELISA) against swine dander, swine dust, and pig feed were increased and precipitating antibodies against swine dander were found in 14, against pig food in five, and against swine confinement dust in three of the 20 pig farmers. The concentration of airborne total dust was 7.4 mg/cu mm and the endotoxin concentration was 37 (22 to 60) ng/cu mm during tending the pigs and increased, during feeding, to 13.8 mg/cu mm and 315 (194 to 716) ng/cu mm, respectively. There was no correlation between exposure and lung function or lavage findings. In conclusion, randomly selected pig farmers had signs of airway inflammatory reaction and activation of the immune system without alteration in lung function and bronchial reactivity.

Adult↗

Enhanced monocyte progenitor cell proliferation in bone marrow of hyperlipemic swine.

This study demonstrated for the first time that bone marrow is a target of enhanced in vivo monocytopoiesis in hyperlipemia. A significantly greater number of bone marrow cells (BMC) were recovered per femur in swine fed a hyperlipemic (HL) diet compared with swine fed a normal (N) diet. In addition, a significantly elevated number of monocytic precursors proliferated in HL-swine compared with N-swine BMC cultures grown in standardized media in the absence of an exogenous source of colony stimulating factor (CSF). HL-swine sera stimulated a significant enhancement in the number of proliferating monocytic precursor cells, regardless of whether or not the BMC were from HL- or N-swine. In addition, HL-swine compared with N-swine BMC demonstrated an enhanced intrinsic capacity to form monocytic colonies in culture, irrespective of the source of swine sera used to stimulate growth.

Animals↗

Isolation and characterization of gamma delta T lymphocyte cell lines from Sinclair swine peripheral blood.

Sinclair miniature swine represent a breed of miniature swine which display a significant incidence of inheritable melanoma which undergo a developmentally regulated spontaneous regression. In an attempt to characterize the host cellular immune response to the melanoma, lymphocyte cell lines have been generated from peripheral blood and designated as peripheral blood lymphocyte cell lines (PBLCLs). The cell lines were expanded in vitro without the addition of exogenous mediators, cloned by limiting dilution, and characterized by flow microfluorimetry, Western, and Northern blot analysis. The cell lines were shown to be CD2-, CD4-, CD8-, and slg-, a phenotype consistent with a null cell population described in swine. The null cell population in swine has been reported to consist of a subpopulation of cells which express the gamma delta T cell receptor (TCR) heterodimer, swine gamma delta T lymphocytes. The PBLCLs were further analyzed by flow microfluorimetry and observed to express the IL-2R, swine MHC Class II antigens, and the endothelial lymphocyte adhesion marker (CD44), which can function as a homing receptor for the skin. In addition, the PBLCLs were observed to express the antigen which is recognized by mAb 86D, an antibody that has been reported to recognize an external epitope on a subset of gamma delta TCR bearing swine T lymphocytes. Western blot analysis of Triton X-114 phase fractions of a PBLCL revealed a protein recognized by the W6 antibody, an antibody which recognizes a conserved region of the C delta chain. Furthermore, Southern and Northern blot analysis indicated that the PBLCL have rearranged the TCR gamma chain gene and express mRNA from the TCR gamma and delta chain genes prior to and following treatment with ionomycin or Concanavalin A. Therefore, the data indicates that the PBLCLs represent swine gamma delta T lymphocyte cell lines which should enable us to enhance our understanding of the role of gamma delta T lymphocytes in the porcine immune system.

Animals↗

Contribution of KATP+ channels to coronary vasomotor tone regulation is enhanced in exercising swine with a recent myocardial infarction.

Previous studies demonstrated a decreased flow reserve in the hypertrophied myocardium early after myocardial infarction (MI). Previously, we reported that exacerbation of hemodynamic abnormalities and neurohumoral activation during exercise caused slight impairment of myocardial O(2) supply in swine with a recent MI. We hypothesized that increased metabolic coronary vasodilation [via ATP-sensitive K(+) (K(ATP)(+)) channels and adenosine] may have partially compensated for the increased extravascular compressive forces and increased vasoconstrictor neurohormones, thereby preventing a more severe impairment of myocardial O(2) balance. Chronically instrumented swine were exercised on a treadmill up to 85% of maximum heart rate. Under resting conditions, adenosine receptor blockade [8-phenyltheophylline (8-PT), 5 mg/kg i.v.] and K(ATP)(+) channel blockade (glibenclamide, 3 mg/kg i.v.) produced similar decreases in myocardial O(2) supply in normal and MI swine. However, while glibenclamide's effect waned in normal swine during exercise (P < 0.05), it was maintained in MI swine. 8-PT's effect was maintained during exercise and was not different between normal and MI swine. Finally, in normal swine combined treatment with 8-PT and glibenclamide produced a vasoconstrictor response that equaled the sum of the responses to blockade of the individual pathways. In contrast, in MI swine the vasoconstrictor response to 8-PT and glibenclamide was similar to that produced by glibenclamide alone. In conclusion, despite significant hemodynamic abnormalities in swine with a recent MI, myocardial O(2) supply and O(2) consumption in remodeled myocardium are still closely matched during exercise. This close matching is supported by increased K(ATP)(+) channel-mediated coronary vasodilation. Although the net vasodilator influence of adenosine was unchanged in remodeled myocardium, it became exclusively dependent on K(ATP)(+) channel opening.

Adenosine↗

Swine hepatitis E virus: cross-species infection and risk in xenotransplantation.

Swine hepatitis E Virus (swine HEV), a ubiquitous agent recently discovered in pigs, is antigenically and genetically closely related to the human HEV. Swine HEV infection in pigs generally occurs at about 2-3 months of age, and about 80%-100% of the pigs in commercial farms in the USA were infected. Swine HEV infections have now been recognized in pigs in many other countries of the world. Interspecies transmission has been documented, as swine HEV infects non-human primates and some strains of human HEV infect pigs. Recent seroepidemiological studies showed that swine veterinarians and other pig handlers are at higher risk of HEV infection compared to normal blood donors. In addition, novel strains of human HEV recovered from hepatitis patients in the USA, Japan and Taiwan are genetically more closely related to strains of swine HEV from respective countries than to other strains of human HEV. The ubiquitous nature of the virus in pigs and the demonstrated ability of cross-species infection raise a potential concern for swine HEV infection in xenotransplantation with pig organs. This chapter discusses the recent advances in HEV research with emphases on potential zoonosis and xenozoonosis.

Animals↗

Transmission of Salmonella typhimurium to swine.

These studies were designed to determine the rate of transmission and the colonization pattern of Salmonella typhimurium in swine. Two experiments were conducted. In experiment 1, swine challenged per os with either S. typhimurium strain 798T + or strain 798N + were exposed to heterologous feces. Following exposure to heterologous strains, heterologous Salmonella were recovered from the feces of infected swine within 3 days and from the tonsil and ileum at necropsy. Bacterial populations in swine initially challenged with Salmonella remained constant. In experiment 2, Salmonella-free swine were commingled with a population of pigs that were shedding 2.69 log10 CFU Salmonella/gram feces. Salmonella was recovered from pooled fecal samples from the commingled swine on day 2 post-exposure to the infected group. Low numbers of Salmonella were detected in the ileocolic lymph node, ileum, cecum or spleen of all commingled swine throughout the necropsy period. These data provide a means for evaluating transmission of Salmonella to a population of swine which may be used to study the mechanisms involved in transmission and maintenance of the disease.

Animals↗

Localization of swine hepatitis E virus in liver and extrahepatic tissues from naturally infected pigs by in situ hybridization.

BACKGROUND/AIMS: The objective of this study was to detect and localize the swine hepatitis E virus (HEV) in the liver and extrahepatic tissues from 20 pigs naturally infected with swine HEV. METHODS: cDNA probe 289 base pairs for swine HEV were generated by reverse transcription-polymerase chain reaction. In situ hybridization with a nonradioactive digoxigenin-labeled cDNA probe was used for the detection of swine HEV in formalin-fixed, paraffin-embedded tissues. RESULTS: When liver tissues from the pigs naturally infected with swine HEV were hybridized with the nonradioactive digoxigenin-labeled cDNA probe, a strong signal was seen in hepatocytes and bile duct. Positive hybridization signals were also detected in small and large intestine, lymph node, tonsil, spleen, and kidney. CONCLUSIONS: Swine HEV was detected primarily in the hepatocytes. Swine HEV may also replicate in tissues other than the liver. In situ hybridization described in the present study has greatly facilitated the application of in situ hybridization procedures to the clinical setting, thus allowing for the diagnosis of swine HEV infection while preserving the morphology of the tissue.

Animals↗

Acute toxicity pilot evaluation of proliferol in rats and swine.

Proliferol is an investigational new drug containing lidocaine hydrochloride 0.25%, dextrose 12.5%, glycerin 12.5%, and phenol 1.0% in aqueous solution. Despite extensive previous experience with similar drug solutions administered in humans by intraligamentous injection for chronic musculoskeletal conditions for over 50 years, animal toxicity data are unavailable. A pilot study was conducted to assess acute toxic effects prior to undertaking further assessment of this drug. Test animals were four Sprague-Dawley rats and four Yucatan mini-swine. Rats received injections into lumbar paraspinal muscles, whereas swine received injections into lumbosacral ligaments in an attempt to mirror the method of administration in humans. Two doses were studied equivalent to 1x and 5x the typical human dose. Outcomes measured at 24 h and 14 days included clinical observations, clinical chemistry, hematology, urinalysis, local tolerance, and major organ histopathology. In rats and swine, results from clinical chemistry, hematology, and urinalysis were indicative of acute local inflammation. At the high dose, marked (rats) and moderate (swine) short-term above-normal levels in certain liver enzymes were noted. In rats and swine, local tolerance results were indicative of acute local inflammatory changes in the skin, subcutis, and muscle around the injection sites. In rats and swine, major organ histopathology results did not reveal lesions attributable to the drug and clinical observations were within normal limits. In swine, fibroplasia was noted in deeper muscle tissues after 14 days. Injections of Proliferol in lumbar paraspinal muscles in rats and lumbosacral ligaments in swine elicited a modest acute local inflammatory response with no other indications of local or systemic toxicity.

Animals↗

Are swine workers in the United States at increased risk of infection with zoonotic influenza virus?

BACKGROUND: Pandemic influenza strains originate in nonhuman species. Pigs have an important role in interspecies transmission of the virus. We examined multiple swine-exposed human populations in the nation's number 1 swine-producing state for evidence of previous swine influenza virus infection. METHODS: We performed controlled, cross-sectional seroprevalence studies among 111 farmers, 97 meat processing workers, 65 veterinarians, and 79 control subjects using serum samples collected during the period of 2002-2004. Serum samples were tested using a hemagglutination inhibition assay against the following 6 influenza A virus isolates collected recently from pigs and humans: A/Swine/WI/238/97 (H1N1), A/Swine/WI/R33F/01 (H1N2), A/Swine/Minnesota/593/99 (H3N2), A/New Caledonia/20/99 (H1N1), A/Panama/2007/99 (H3N2), and A/Nanchang/933/95 (H3N2). RESULTS: Using multivariable proportional odds modeling, all 3 exposed study groups demonstrated markedly elevated titers against the H1N1 and H1N2 swine influenza virus isolates, compared with control subjects. Farmers had the strongest indication of exposure to swine H1N1 virus infection (odds ratio [OR], 35.3; 95% confidence interval [CI], 7.7-161.8), followed by veterinarians (OR, 17.8; 95% CI, 3.8-82.7), and meat processing workers (OR, 6.5; 95% CI, 1.4-29.5). Similarly, farmers had the highest odds for exposure to swine H1N2 virus (OR, 13.8; 95% CI, 5.4-35.4), followed by veterinarians (OR, 9.5; 95% CI, 3.6-24.6) and meat processing workers (OR, 2.7; 95% CI, 1.1-6.7). CONCLUSIONS: Occupational exposure to pigs greatly increases workers' risk of swine influenza virus infection. Swine workers should be included in pandemic surveillance and in antiviral and immunization strategies.

Adult↗

Detection of lymphoproliferative responses against pseudorabies virus immediate early protein (IE180) in swine immunized with a modified live virus vaccine.

The immediate early protein (IE180) of pseudorabies virus (PrV) was generated by cycloheximide (CHX) reversal procedures in PrV-infected swine skin cells. Using this IE180 preparation as antigen, specific proliferation was detected in mononuclear cells (PBMNCs) from swine vaccinated with a modified live virus (MLV) PrV vaccine. Two sets of data support this conclusion. (a) PBMNCs of c/cSLA inbred swine vaccinated with an MLV vaccine a year before the test exhibited significant responses against structural virion proteins and IE180. (b) Vaccination of PrV-negative swine with the same MLV vaccine induced a conversion from an unresponsive state against IE180 to one of specific antigen-driven responsiveness. The responses of vaccinated swine against IE180 were significantly higher than their preimmune responses (p < or = 0.003) or to the response of control swine (p < or = 0.045). Moreover, IE180 antigens obtained from lysates of CHX-reversed, PrV-infected cells by heparin/agarose affinity separation also stimulated specific proliferation of PBMNCs from MLV-vaccinated swine, as their proliferative responses were significantly higher than those of unvaccinated swine (p < or = 0.05). These data suggest that PrV IE180 contributes at least in part to the overall cellular response to PrV.

Animals↗

Bradycardic agent UL-FS 49 attenuates ischemic regional myocardial dysfunction and reduces infarct size in swine: comparison with the beta-blocker atenolol.

Heart rate (HR) is a major factor determining the severity of myocardial ischemia, and HR reduction is an effective therapy for myocardial ischemia. We tested the effects of HR reduction induced by either UL-FS 49 or atenolol on regional myocardial blood flow, function, and infarct size (IS) in a porcine model of 90-min low-flow ischemia and 2-h reperfusion. In 24 Göttinger miniswine, the left anterior descending coronary artery (LAD) was cannulated and hypoperfused at constant inflow to reduce anterior systolic wall thickening (AWT, sonomicrometry) by approximately 85%. Eight swine served as a placebo group, and 8 other swine received UL-FS 49 (0.60 mg/kg intravenously, i.v.) after 10-min ischemia. In the remaining 8 swine, atenolol was infused after 10-min ischemia at a dosage [mean 1.75 +/- 1.20 (SD) mg/kg i.v.] to mimic the HR reduction observed with UL-FS 49. Systemic hemodynamics, subendocardial blood flow (ENDO, microspheres) and AWT were measured under control conditions, at 10 and 90 min of ischemia. In the swine receiving UL-FS 49 or atenolol, additional measurements were made 5 min after administration of the respective drug. After 2-h reperfusion, IS (percentage of area at risk) was determined with TTC-staining. Five minutes after administration of UL-FS 49, HR was decreased from 113 +/- 9 to 83 +/- 13 beats/min (p < 0.05) and remained unchanged when ischemia was prolonged to 90 min. In the swine receiving atenolol, HR was reduced from 117 +/- 14 to 93 +/- 7 beats/min (p < 0.05) 5 min after drug administration and decreased further to 87 +/- 10 beats/min when ischemia was prolonged to 90 min. After 10 min of ischemia, AWT in the placebo, UL-FS 49, and atenolol group was decreased to 7.0 +/- 5.5, 6.4 +/- 3.5, and 6.2 +/- 3.3% (all p < 0.05 vs. control), respectively. The reduction in ENDO was also comparable among the three groups. In the placebo group, AWT remained unchanged when ischemia was prolonged to 90 min (4.4 +/- 2.6%). In swine receiving atenolol, AWT tended to increase (13.6 +/- 10.5%), whereas in swine receiving UL-FS 49, AWT was significantly increased to 21.4 +/- 7.1% (p < 0.05 vs. 10-min ischemia and vs. the placebo and atenolol groups). IS was significantly reduced in swine receiving atenolol (3.9 +/- 3.5%) or UL-FS 49 (5.8 +/- 4.6%) as compared with the placebo-group (10.4 +/- 8.9%).(ABSTRACT TRUNCATED AT 400 WORDS)

Adenosine Triphosphate↗

Allosensitization does not increase the risk of xenoreactivity to alpha1,3-galactosyltransferase gene-knockout miniature swine in patients on transplantation waiting lists.

BACKGROUND: The recent availability of alpha1,3-galactosyltransferase knockout (GalT-KO) miniature swine has eliminated anti-Gal antibodies as the major barrier to xenotransplantation, potentially bringing this modality closer to clinical application. Highly-allosensitized patients, who have poor prospects of receiving a suitable cross-match negative human organ, might be the first patients to benefit from xenotransplantation of porcine organs. However, concerns exist regarding cross-reactivity of alloreactive anti-human leukocyte antigen (HLA) antibodies against xenogeneic swine leukocyte antigen (SLA) antigens. We have investigated this question using sera from such patients on GalT-KO target cells. METHODS: Using flow cytometry and complement-dependent cytotoxicity (CDC) assays, we have tested a panel of 88 human serum samples from patients awaiting cadaveric renal allotransplantation for reactivity against: 1) human; 2) standard miniature swine; and 3) GalT-KO peripheral blood lymphocytes (PBL) and cultured endothelial cells. RESULTS: Anti-swine IgM and IgG antibody binding, as well as CDC, were significantly attenuated on GalT-KO versus standard swine. No correlation was found between the degree of anti-human panel reactive antibodies (PRA) and xenoreactivity against either standard or GalT-KO miniature swine. Treatment of sera with dithiothreitol (DTT) showed that the majority of remaining lymphocytotoxicity against GalT-KO swine was mediated by preformed IgM antibodies. Patients with high alloreactivity but low anti-GalT-KO xenoreactivity were readily identified. CONCLUSIONS: Highly allosensitized patients awaiting renal transplants appear to be at no increased risk of xenosensitization over their non-sensitized cohorts, and could therefore be candidates for xenotransplantation using GalT-KO swine donors.

Animals↗

Large outbreak of swine influenza in southern Japan caused by reassortant (H1N2) influenza viruses: its epizootic background and characterization of the causative viruses.

In the winter of 1989 and the spring of 1990, there were large outbreaks of respiratory disease in two swine herds in Nagasaki Prefecture, southern Japan. Serological surveillance indicated that the majority of swine possessed antibodies to swine influenza virus H1 haemagglutinin and neuraminidase of early H3N2 influenza virus strains. Eight viruses were isolated from swine that showed typical clinical symptoms of influenza. The haemagglutinin and neuraminidase of these isolates were closely related to those of swine H1N1 and early human H3N2 viruses, respectively. At least two types of haemagglutinin antigens, distinguished by two monoclonal antibodies, were involved in the outbreaks. Evolutionary analyses indicated that the haemagglutinin gene of the H1N2 reassortants was closely related to those of a recent swine lineage (A/sw/HK/1/74 and A/sw/Ehime/1/80 viruses). However, the neuraminidase genes of the H1N2 reassortants were similar to those of swine N2 viruses which in turn are related to early human H3N2 viruses. A comparison of partial nucleotide sequences revealed that the six other genes of A/sw/Nagasaki/1/89 were derived from those of swine H1N1 virus.

Animals↗

Lactate production by swine adipocytes: effects of age, nutritional status, glucose concentration, and insulin.

To develop an alternative model in which to study the relationship between adipose tissue lactate production, obesity, and non-insulin-dependent diabetes mellitus (NIDDM), we investigated lactate production by swine adipocytes. Subcutaneous adipocytes from fasted 3-wk-old, fasted 7-mo-old, and fed 7-mo-old Yucatan minIature swine were isolated and incubated with 0.2, 1, 5, 10, or 25 mM glucose +/- 1 mU/ml insulin. Total glucose metabolism (TGM) was estimated by product summation. Results showed that 1) TGM was threefold greater in cells from fasted 7-mo- vs. 3-wk-old swine (P < 0.05), 2) TGM was 2.7-fold greater in cells from fed 7-mo-old vs. fasted 7-mo-old swine (P < 0.05), 3) insulin failed to stimulate TGM in adipocytes from swine of either age and either nutritional status, and 4) lactate and pyruvate accounted for 34 and 30% of TGM, respectively, in adipocytes from swine of both ages. Similarities in glucose metabolism and lactate production in adipocytes from swine and obese NIDDM humans make the swine a potentially valuable model for studying lactate production associated with obesity and NIDDM.

Adipocytes↗

Pentobarbital versus medetomidine-ketamine-fentanyl anaesthesia: effects on haemodynamics and the incidence of ischaemia-induced ventricular fibrillation in swine.

The present study was performed to compare haemodynamic variables at baseline and the incidence of ventricular fibrillation during the early phase of ischaemia in swine during pentobarbital or medetomidine-ketamine-fentanyl anaesthesia. Twenty-two swine (mean +/- SD: 29+/- 3 kg) were anaesthetized with sodium pentobarbital (induction with 36 mg/kg intraperitoneally, and maintenance with 5-20 mg/kg/h intravenously [i.v.]) and 6 swine (27+/- 3 kg) were anaesthetized with ketamine and fentanyl (premedicated with medetomidine 0.1 mg/kg and ketamine 10 mg/kg intramuscularly, induction with ketamine 20 mg/kg and fentanyl 0.025 mg/kg i.v., and maintenance with ketamine 20 mg/kg/h and fentanyl 0.025 mg/kg/h i.v.). After a stabilization period of 30 min, the left anterior descending coronary artery (LAD) was occluded for 10 min. Haemodynamic data and occurrence of ventricular fibrillation were recorded. The ischaemic area was measured by fluorescing microspheres. Swine anaesthetized with medetomidine-ketamine-fentanyl had significantly lower heart rate, myocardial contractility, peak left ventricular pressure, arterial blood pressure, aortic blood flow, myocardial blood flow and cardiac index at baseline, than swine anaesthetized with pentobarbital. Whereas none of the swine anaesthetized with pentobarbital fibrillated during the LAD occlusion, ventricular fibrillation occurred in 83% of the animals anaesthetized with medetomidine-ketamine-fentanyl (P< 0.001). No significant difference was found in size of ischaemic area between the two groups. Thus, we show a depression in haemodynamic variables at baseline and a higher incidence of ventricular fibrillation during the early phase of ischaemia in swine anaesthetized with medetomidine-ketamine-fentanyl compared to swine anaesthetized with pentobarbital.

Anesthesia↗