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[Göttingen miniature swine as a model for diet-induced atherosclerosis].

Twenty-four Göttingen Miniature Swine/csk, in order to evaluate their potential usefulness as a model for experimental atherosclerosis studies, were fed diets of three types, a high-fat plus high cholesterol diet, a high-fat diet, and a commercial diet. Each group consisted of 4 males and 4 females. Swine fed the experimental diet were investigated by gross, microscopic and serum biochemical examination on the 1st, 3rd, 6th and 9th month after start of experimentation. Lesions of atherosclerosis were observed in the high-fat plus high-cholesterol diet group. After a month on the experimental diet, intimal thickening was detected in the abdominal aorta just above the origin of internal iliac artery, left coronary artery and ascending aorta by microscopic examination. Thereafter, on the 9th month after the start, there was more extensive and severe atherosclerosis. These lesions were classified into two types by the difference in the histologic architecture of arterial wall. One was fatty streaks that were in thoracic aorta belonging to the elastic type and the other was fibrous plaques that were in abdominal aorta and iliac artery and so on, belong to the transitional or muscular type. High-fat plus high-cholesterol diet feeding led to elevated serum cholesterol and beta-lipoprotein levels, and had an effect on several kinds of metabolism. All of the swine fed high-fat or commercial diet had little gross, microscopic lesions and had no change in serum cholesterol and beta-lipoprotein levels. Hypercholesterolemia and hyper-beta-lipoproteinemia had a close relation to the development and acceleration of atherosclerosis. It was possible to show that the diet induced atherosclerosis was similar in quality to that observed in humans, and that the Göttingen miniature swine was a suitable animal for the study of atherosclerosis.

Animals↗

Miniaturized detection technology in molecular diagnostics.

Miniaturization of genetic tests represents the convergence of molecular biology and engineering and is leading to a new class of small analyzers and test systems for genetic testing with improved analytical characteristics. Miniaturization initially focused on devices that contained micrometer-sized features designed for a particular analytical purpose (e.g., filters for cell isolation and chips for capillary electrophoresis). Now, the focus is shifting to analytical applications based on nano-sized objects such as nanotubes, nanochannels, nanoparticles, nanopores and nanocapacitors. These nanofabricated objects provide new tools for sequencing of nucleic acids and rapid, multiplexed, nucleic acid detection.

Animals↗

Sexual dimorphism involving steroidal pheromones and their binding protein in the submaxillary salivary gland of the Göttingen miniature pig.

Submaxillary glands of mature Göttingen miniature pigs were examined for the presence of a sexual dimorphism. Gland weights, serous cell hypertrophy and total protein in the glands were much greater in male than female pigs. High concentrations of the pheromonal 16-androstene steroids were present in the glands of males and exceeded 2 mmol/g in some animals; this was primarily due to 5 alpha-androst-16-en-3 alpha-ol. The high concentration of 16-androstene steroids in boar glands was correlated with the presence of large amounts of binding protein for these steroids in the glands; smaller amounts of the binding protein were detected in female glands. These findings are similar to those found in domestic pigs, but the degree of sexual dimorphism assessed from these findings is more extreme in the miniature pig.

Androgen-Binding Protein↗

Yucatan miniature swine as a model for the study of human diabetes mellitus.

Two lines of Yucatan miniature swine have been developed by genetic selection for decreased and increased glucose clearance during an i.v. glucose tolerance test. The decreased glucose clearance is due to low peripheral insulin levels usually from a decrease in insulin secretion. In two pigs the decreased peripheral insulin resulted from increased hepatic uptake of insulin. During gestation and lactation, an increased insulin resistance and a diabetic-like state occurs in some animals. When fed a low fiber diet that contains 40% of calories from saturated fat (a typical American diet), Yucatan swine become more glucose intolerant. Seven to ten animals on the diet from the glucose intolerant line showed a glucose tolerance curve that would have been classified as diabetic if they were humans utilizing both intravenous and oral glucose tolerance tests. Miniature swine from this line are available to interested researchers.

Animals↗

Failure of genetically selected miniature swine to model NIDDM.

Ten young adult miniature swine from a line reported to be genetically selected for glucose intolerance and eight normal controls were obtained from Colorado State University. They were consecutively exposed to 4 mo of a high-fiber, low-fat standard swine diet; 4 mo of a high-sucrose, high-fat, low-fiber diabetogenic diet; and 4 mo of excess diabetogenic diet for obesification. Results of oral glucose tolerance and intravenous insulin tolerance tests conducted at the end of each regimen were compared. Hyperglycemia was not observed in any animals after any manipulation. Insulin sensitivity was also not influenced by diet. We conclude that F7 low-K miniature swine from this colony fail to model human non-insulin-dependent diabetes.

Animals↗

The effect of swine leukocyte antigen haplotype on birth and weaning weights in miniature pigs and the role of statistical analysis in this estimation.

Miniature pigs of seven swine leukocyte antigen (SLA) genotypes were examined for birth and weaning weights to determine the influence of major histocompatibility (MHC) and background genes on these traits. Effects of different statistical analyses on the magnitude of these associations also were examined. Data on 154 piglets from 32 litters were analyzed by least squares using a linear model that included effects of SLA, litter, and sex of piglet. In these miniature pigs, SLA genotype had little influence on birth and weaning weight; litter, which includes effects of background genes, had a significant effect on both birth weight (P less than or equal to .0001) and weaning (P less than or equal to .005) weight. When litter effects were not accounted for, SLA haplotype appeared to influence both birth (P less than or equal to .001) and weaning (P less than or equal to .10) weights. Use of simple group means, as opposed to least squares means, for comparisons of genotypes yielded misleading results. Simple means indicated that piglets with the aa genotype were heavier (P less than or equal to .01) at birth than those with the cd genotype; in contrast, least squares means showed that cd piglets were slightly heavier at birth (P less than or equal to .10). Heterosis was not observed for birth or weaning weights among piglets of various genotypes, nor did one vs two copies of any haplotype influence these traits.

Analysis of Variance↗

Pituitary-ovarian relationships during the estrous cycle and the influence of parity in an inbred strain of miniature swine.

Pituitary-ovarian function was analyzed in a strain of miniature swine previously shown to produce a low ovulation rate resulting in the formation of only 8.6 corpora lutea (CL)/animal. Five multiparous (M) and four nulliparous (N) miniature pigs with a mean inbreeding coefficient of .39 were monitored for estrous behavior through four consecutive estrous cycles. Daily blood samples were collected from 5 d before to 5 d after the onset of the second, third and fourth estrus and at 48-h intervals during the remainder of the second and third estrous cycle. Laparoscopy was used to examine the ovaries 1 and 5 d after onset of the third estrus and 2 d after the beginning of the fourth estrus. For the entire group, temporal fluctuations among serum estradiol-17 beta, luteinizing hormone (LH) and progesterone concentrations and sexual behavior were similar to previously published data in standard swine breeds. Although the mean lengths of the estrous cycle were not different (P greater than .05) between parity subgroups (M, 23 +/- 1.3 vs N, 22 +/- .7 d), multiparous pigs were in estrus longer (P less than .05) than nulliparous females (M, 3.7 +/- .2 vs N, 2.2 +/- .4 d). Parity subgroups were similar with respect to the mean number of follicles forming CL (M, 8.8 +/- .7 vs N, 9.2 +/- .2). Although an average of 6.2 +/- 2.1 CL had formed by 24-h after onset of estrus in the nulliparous subgroup, no CL were detected in the multiparous subgroup at this time.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

The effect of scatter laser photocoagulation on intravitreal levels of growth factors in the miniature pig.

PURPOSE: To characterise changes in intravitreal growth factor profiles following retinal photocoagulation in the miniature pig. METHODS: Miniature pig eyes underwent scatter photocoagulation by either diode infrared or emerald green laser. Animals were sacrificed at various times (up to 42 days) post-laser. The eyes were than removed and vitreous samples analysed for basic fibroblast growth factor, insulin-like growth factor-I and epidermal growth factor by radioimmunoassay, transforming growth factor-beta 2 by ELISA and insulin-like growth factor binding proteins using Western ligand blotting. RESULTS: Vitreous transforming growth factor-beta 2 levels were decreased at 1 h post diode laser and at 4 and 7 days post emerald laser but returned to normal by 21 and 42 days respectively. Vitreous insulin-like growth factor-I levels increased at 4 and 7 days post diode and emerald laser respectively but returned to normal by 21 days. Insulin-like growth factor Western ligand blotting demonstrated that a 34 kDa insulin-like growth factor binding protein was predominant in the pig vitreous; the levels of this binding protein followed an identical trend to those observed for insulin-like growth factor-I. No changes in vitreous levels of either basic fibroblast growth factor or epidermal growth factor were observed following laser treatment. CONCLUSIONS: Our results demonstrate a significant shift in the balance of intravitreal growth factors following retinal laser photocoagulation. Such changes may be pertinent to the regression of preretinal new vessels after laser photocoagulation.

Animals↗

Warfarin sodium for anticoagulation of atherosclerotic miniature swine.

Warfarin sodium (Coumadin) has been used as an effective anticoagulating agent in human medicine for many years, although careful monitoring of its effects are necessary to avoid excessive anticoagulation. Previous experience with this drug for chronic anticoagulation therapy in miniature swine has been limited. The effect of warfarin sodium was studied by measuring prothrombin time in twelve 8-month-old Hanford miniature swine. The pigs had been fed a high-cholesterol diet and had undergone a prior coronary artery abrasion procedure for development of an atherosclerotic coronary disease model. Atherosclerosis was induced by feeding a high-cholesterol diet. Baseline prothrombin time ranged from 12.8 to 15.0 s (13.7 s mean). Prothrombin time was determined daily for the first 5 days of treatment and at least twice weekly thereafter until the animals were sacrificed. Animals received warfarin for 37-41 days. Prothrombin time could be increased 33-50% by once daily oral administration of warfarin 0.04-0.08 mg/kg. Oral administration of more than 0.08 mg/kg as a maintenance dose resulted in the death of two pigs. Most animals responded well to 0.08 mg/kg for the first 3 days of treatment followed by a maintenance dose of 0.06 mg/kg. Dosage was adjusted periodically when prothrombin times exceeded 50% above baseline. It is our experience that monitoring prothrombin time at least twice weekly and adjusting the maintenance dose can eliminate death losses due to warfarin intoxication.

Animals↗

Miniaturized heart-lung machine.

The miniaturized heart-lung machine consists of commercially available roller pumps, a flexible heat exchanger, a newly devised bubble oxygenator, and polyethylene cannulas and silicone tubes. The minimum and maximal priming volume of the entire system is 4.7 and 16.7 mL, respectively. The efficiency of the system is reflected in an heat transfer coefficient ranging from 0.96 to 0.31 at flow rates between 1 and 20 mL/min, a high value of oxygen uptake in the range of 0.061 mL O2/min mL blood-1, and low blood trauma with plasma hemoglobin concentrations of 47.5 +/- 5.0 mg/dL after 60 min of in vitro perfusion. The system is a simple, reliable, and efficient miniaturized heart-lung machine for use in small animals.

Animals↗

Hanford miniature swine model for extracorporeal membrane oxygenation.

Extracorporeal membrane oxygenation (ECMO) is now an accepted therapy for neonatal respiratory failure due to reversible lung disease. There is a continued need to train ECMO team members using animal models. Hanford miniature swine are an appropriate model for this purpose because of the availability and size as well as anatomic and physiologic similarities to humans. This article describes training ECMO team members in venoarterial and venovenous bypass utilizing Hanford miniature swine.

Animals↗

Effects of 6-hydroxydopamine in hypertensive adult miniature swine.

To validate a miniature swine model of sympathectomy, six swine that had chronic high blood pressures for unknown reasons and five DOCA hypertensive swine were treated with a single dose of the neurotoxin 6-hydroxydopamine (6-OHDA) (50 mg/kg i.v.). One week after 6-OHDA, conscious mean arterial pressure (MAP) had fallen by 47-49 mmHg and the pressor response to tyramine was attenuated in both groups. Norepinephrine content was significantly decreased in the kidneys (greater than 85%) and left ventricle (greater than 94%) in both 6-OHDA treated groups. These results indicate that 6-OHDA can be used to effectively sympathectomize adult swine. Chemical sympathectomy of swine with either unexplained high blood pressure or experimentally induced DOCA hypertension resulted in an equivalent fall in MAP in both of these populations. Further studies using 6-OHDA in miniature swine may help to elucidate the mechanisms involved in maintaining hypertension in this animal model.

Animals↗

A new model of focal cerebral ischemia in the miniature pig.

OBJECT: The purpose of this set of studies is to design a minimally invasive, reproducible stroke model in the gyrencephalic brain. This paper provides information on both surgical technique and methods of quantification of ischemic damage to both gray and white matter in the miniature pig. METHODS: Sixteen male miniature pigs were randomly divided into three groups and underwent transcranial surgery involving a frontotemporal approach with orbital rim osteotomy for permanent middle cerebral artery occlusion (MCAO; five animals), permanent internal carotid artery occlusion (ICAO; six animals), and a sham operation (five animals). Histological mapping and magnetic resonance (MR) imaging were used to delineate the areas of ischemic damage. The volumes of infarction measured directly from MR images were 16.2 +/- 1.1, 1.5 +/- 0.5, and 0.0 +/- 0.0 cm3 (mean +/- standard deviation [SD], p < 0.001) in the MCAO, ICAO, and sham-operated groups, respectively. The areas of ischemia identified through histological analysis and MR imaging showed a good correlation (r2 = 0.86, p < 0.0001). Immunohistochemical staining with an amyloid precursor protein (APP) antibody was used to evaluate axonal damage and calculate a total APP score for axonal damage of 44.8 +/- 2.9 in the MCAO, 13.2 +/- 6.6 in the ICAO, and 0.0 +/- 0.0 (mean +/- SD, p < 0.002) in the sham-operated animals. CONCLUSIONS: This new model of focal cerebral ischemia induces a reproducible amount of ischemic damage in both gray and white matter, and has significant utility for studies of the pathophysiology of ischemia in the gyrencephalic brain and for assessment of the therapeutic efficacy of drugs prior to the initiation of human clinical trials.

Animals↗

Hypoxic moderation of renal hypertension in the miniature swine.

Eleven male Yucatan miniature swine were subjected to unilateral renal artery constriction (RAC) with an intact contralateral kidney. Five pigs remained at laboratory altitude of 1524 m and served as normoxic, hypertensive controls (NH) while the other six (HH) were subjected to a simulated altitude of 4267 m for 9 weeks to determine the effect of hypoxia on the development of renal hypertension. Systemic blood pressure was increased less in HH as compared with NH. Data from three sib-pairs represented in each treatment group suggested a diverse, apparently familial response to RAC. The hypertensive process, irrespective of treatment groups, included a diminution of free circulating serum thyroxin and an increase in serum sodium. Hypoxia moderates renal hypertension in the miniature pig primarily via a decrement in stroke volume and cardiac output.

Animals↗

Power spectral analysis of heart rate variability for assessment of diurnal variation of autonomic nervous activity in miniature swine.

BACKGROUND AND PURPOSES: The purpose of the study was to document diurnal variation of autonomic nervous functions by use of power spectral analysis of heart rate (HR) variability. METHODS: To clarify characteristics of power spectral analysis of HR variability, electrocardiogram (ECG), blood pressure (BP), and respiratory (Resp) waveform simultaneously were recorded. RESULTS: Two major spectral components were examined at low (LF)- and high (HF)-frequency bands for HR variability. Coherence between HR and Resp variabilities and HR and BP variabilities was maximal at approximately 0.14 and 0.03 Hz, respectively. On the basis of these data, two frequency bands of interest--LF (0.01 to 0.07 Hz) and HF (0.07 to 1.0 Hz)--were defined. Autonomic blockade studies indicated that the parasympathetic system mediated the HF and LF components, whereas the sympathetic system mediated only the LF component; HR had a diurnal pattern. The LF and HF bands in the dark phase tended to be higher than those in the light phase. The LF-to-HF ratio had a diurnal pattern similar to that of the HR. CONCLUSION: Parasympathetic nervous activity in miniature swine may be predominant in the dark phase. The characteristics of power spectra and diurnal variations of autonomic nervous functions are almost the same as those of humans. Therefore, miniature swine may be a useful animal model for future biobehavioral and pharmacotoxicologic studies.

Animals↗

Effects of recombinant staphylokinase on coronary thrombosis in Chinese experimental miniature swine.

AIM: To study the effects of recombinant staphylokinase (r-Sak) on coronary thrombosis, cardiac ischemia, and myocardial infarction in Chinese experimental miniature swine. METHODS: Endarterium was injuried and coronary thrombi were formed gradually through direct electrical stimulation on the coronary artery of Chinese experimental miniature swine. Effects of r-Sak in vitro were studied through coronary pathological section, microkinematography, multi media graphic analysis, epicardial electrogram mapping, myocardium histo chemical stain, serum creatine phosphokinase (CPK), and hemorheology. RESULTS: r-Sak showed a remarkable effect on coronary thrombus. Compared w ith the control group, the two dosage groups, r-Sak 0.45 mg/kg and 1.35 mg/kg, reduced the transverse section area of coronary thrombus (P<0.01), lessened the degree and range of cardiac ischemia (P<0.01), decreased the myocardial infarction area (P<0.01), the activity of CPK and blood viscosity (P<0.05), restrained platelet adhesion and aggregation, and reduced fibrinogen concentration (P<0.05). CONCLUSION: r-Sak could dissolve coronary thrombus obviously and lessen the pathologic reaction of myocardium.

Animals↗

[Therapeutic effect of qingyi decoction and tetrandrine in treating severe acute pancreatitis in miniature pigs and serum drug level determination].

OBJECTIVE: To investigate the therapeutic effect of Qingyi Decoction (QYD) and tetrandrine (Tet), used singly or combind, in treating miniature pigs with severe acute pancreatitis (SAP) and its mechanism. METHODS: Thirty-two Guizhou miniature pigs were made into SAP model by pancreatic duct retrograde injection of 5% sodium taurocholate. They were randomly divided into 4 groups: the control group, the QYD group, the Tet group and the combined treated group. The serum amylase activity and interleukin-1 and 6 (IL-1, IL-6) contents in serum from vena cava and portal vein were tested by biochemistry and radioimmunoassay (RIA). Serum emodin and plasma Tet levels were measured by high performance liquid chromatography (HPLC) 24, 48 and 72 hrs after treatment. And the pathological changes of pancreas, lung and liver were observed under microscope. RESULTS: The mortality of SAP pigs was reduced significantly and the inflammatory injury of the organs was ameliorated obviously in all treated groups, and the increased amylase activity and IL-1, IL-6 levels was attenuated. The therapeutic effect was much more obvious, and the plasma Tet level at different time points were much higher in the combined treated group than those in the other two groups treated by single drug (P < 0.01). CONCLUSION: Both QYD and Tet could treat effectively SAP through multiple pathways, combination of them reveals an elevation of serum drug concentration and shows a synergistic effect.

Alkaloids↗

Antibody avidity in swine lymphocyte antigen-defined miniature pigs.

Antibody avidity to hen egg white lysozyme (HEWL) was measured by thiocyanate ion elution enzyme-linked immunosorbent assay (ELISA) in swine lymphocyte antigen (SLA) defined miniature pigs. Serum antibody avidity was evaluated on day 14 and 30 after primary (day 0) and secondary (day 14) immunizations in eight to ten week old miniature pigs previously typed for swine lymphocyte antigen genotype. The effect of SLA genotype, litter, and gender on anti-HEWL antibody avidity was determined by least squares. Antibody avidity varied amongst individuals. Antibody avidity maturation was observed as a mean rise in antibody avidity from primary response (0.89 +/- 0.64) to secondary response (1.23 +/- 0.54) (p < 0.0005). Overall, SLA genotype did not significantly influence antibody avidity or avidity maturation, but pigs of dd genotype had greater avidity maturation between primary and secondary responses than other genotypes. Litter effects significantly affected antibody avidity and maturation.

Analysis of Variance↗