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PubMed2005

Morphological characteristics of submandibular glands of miniature pig.

BACKGROUND: Miniature pig (minipig) is increasingly used as a large animal model for a variety of biomedical studies. Little information is available in the literature on anatomy, histology and sialograghy of the submandibular gland of the minipig. The purpose of this study was to characterize the morphology of a miniature pig's (minipig) submandibular gland as a large animal model for further biomedical studies. METHODS: Five minipigs were subjected to sialographic, anatomic, histologic, histochemical and ultrastructural evaluations for submandibular glands. RESULTS: Sialograms showed a long, horizontal main excretory duct and a pear-shaped gland located inferoposterior to the angle of the mandible. The submandibular glands lied superficial to the suprahyoid, and infrahyoid muscle groups, and were covered by the inferior portion of the parotid gland. The submandibular glands were characterized by a mixed parenchyma of mucous and serous secretory acini. Alcian blue (AB) staining and periodic acid-Schiff (PAS) reactions demonstrated that minipig submandibular glands synthesized and secreted acid mucous substances by serous cells and polysaccharide, and neutral mucous substances, by mucous cells. CONCLUSION: The submandibular gland of the minipig is considered a useful large salivary gland animal model for biomedical studies.

Animals↗
PubMed2005

A description of a prototype miniature extracorporeal membrane oxygenation circuit using current technologies in a sheep model.

In the United States, standardization of neonatal extracorporeal membrane oxygenation (ECMO) circuit was achieved during the 1980s. Since that time, the consoles and components of the ECMO circuit have remained fundamentally unchanged (bladder, rollerpump, silicone membrane oxygenator). Extracorporeal technology, however, has witnessed many significant advancements in components during the past two decades. These new technologies have characteristics that may improve outcomes when applied in the ECMO arena. Understanding how these technologies perform in long-term applications is necessary. Therefore, the purpose of this project is to evaluate the performance of a miniature ECMO circuit consisting of current generation technologies in an animal model. An ECMO circuit (prime volume 145 mL) was designed that included a hollow fiber oxygenator and a remote mounted centrifugal pump. All circuit tubing and components were surface coated. Three sheep (approx 13 kg) were placed on ECMO using standard neck cannulation techniques and maintained according to clinical protocols. Technical implementation, oxygenator function, and hematological parameters were accessed. Duration of ECMO was 20, 48, and 58 hours. There was no evidence of oxygenator failure, as measured by pressure drop and oxygen transfer, in any of the procedures. No plasma leak was observed in any oxygenators. Platelet count trended downward after 24 hours. Visual inspection after ECMO showed very little evidence of gross thrombosis. This ECMO circuit design departs dramatically from the typical North American systems. The use of this console and components facilitated a 70% reduction in priming volume over a traditional ECMO circuit. Further investigations should be conducted to determine if circuit miniaturization can reduce the morbidity associated with blood product consumption and the bloods contact with the artificial surfaces of the ECMO circuitry.

Animals↗
PubMed2005

[Autologus bone marrow-derived mesenchymal stem cells intracoronary delivery after acute myocardial infarction in miniature pig].

OBJECTIVE: To evaluate the possibility that using intracoronary delivery of autologus bone marrow-derived mesenchymal stem cells (MSCs) to improve the cardiac function after acute myocardial infarction (AMI) in miniature pig. METHODS: MSCs were cultured in Dulbecco's modified Eagle's medium-F12 (DMEM/F12) medium. AMI model was made by blocking the blood stream of the first diagonal branch in miniature pig, and released the branch after 90 minutes. After 10-14 days, (4-6) x 10(7) culture-expanded autologus 4', 6-diamidino-2-phenylindole (DAPI)-labelled MSCs were transplanted into each host heart's AMI area through intracoronary way. Ultrasonic cardiography (UCG) was performed to observe the left ventricular function at 3 months after transplantation. The cellular transplanted hearts were harvested and investigated by immunohistochemical analysis. RESULTS: Left ventricular function of the MSCs group was improved significantly 3 months later compared with the control group [(54.65 +/- 3.39) vs (43.98 +/- 4.21)%, (P < 0.01)]. Exogenous MSCs survived and site-differentiated into cardiomyocytes in infracted hearts. CONCLUSION: MSCs can play a benificial role to repair damaged heart. Heart function can be improved after MSCs transplantation in porcine myocardial infarction model.

Animals↗
PubMed2006

Establishment of submandibular gland allotransplantation model in miniature swine.

BACKGROUND: Autologous transplantation of the submandibular gland (SMG) into the temporal fossa with microvascular anastomosis has been successfully applied in severe xerophthalmia patients as a permanent tear substitute. However, severe xerophthalmia can be accompanied by salivary gland dysfunction, making such autotransplantation unsuitable. Therefore, SMG allotransplantation might be a solution. The aim of this study was to assess the technical feasibility of submandibular gland allotransplantation. METHODS: Twelve miniature swine were randomized to serve as donors or recipients. One SMG was transplanted between a donor and a recipient. The donor SMG was revascularized by microvascular anastomosis of its vascular pedicle to the recipient lingual artery and external jugular vein. The secretory duct was implanted into the vestibule of the mouth through a subcutaneous tunnel. No immunosuppressive agent was administered. The results were assessed by visual inspection of the secretion, and histopathological examination of the transplanted SMG. RESULTS: Technically, all surgical procedures were successful. Clear secretion flowed out of the duct as soon as blood supply of the transplanted submandibular gland was reestablished. The secretion of the gland lasted for 5 days. As expected, an acute rejection reaction occurred after surgery because no immunosuppressive agents were used. Secretion from the transplanted SMG ceased within 5 days. CONCLUSIONS: A model of SMG allotransplantation can be established in miniature swine. The technique of submandibular gland allotransplantation is feasible.

Animals↗
PubMed1991

Ethanol-induced changes in hepatic free radical defense mechanisms and fatty-acid composition in the miniature pig.

In the miniature pig, ethanol consumption has been reported to induce alterations in hepatic antioxidant defense capacity, which could result in increased risk of peroxidative damage. However, ethanol may also induce changes in membrane fatty acid composition, which could reduce the risk of peroxidative damage. This study examined lipid peroxidation, antioxidant defense and fatty acid composition in livers from miniature pigs fed ethanol in diets containing 12% of their calories as fat for 20 mo. After 12 and 20 mo of feeding, ethanol-fed pigs had higher hepatic manganese-superoxide dismutase activity, lower hepatic copper concentrations and low hepatic copper-zinc-superoxide dismutase and glutathione peroxidase activities compared with controls. Lipid peroxidation as assessed by thiobarbituric acid reacting substance assay was lower in liver homogenate and mitochondrial and microsomal fractions from ethanol-fed pigs than in controls. The percentage contribution of highly unsaturated fatty acids to total fatty acids in liver homogenates (after 12 mo of feeding) and microsome fractions (after 20 mo of feeding) was lower in the ethanol-fed pigs than in the controls, resulting in a lower peroxidizability index. Ethanol-fed pigs had minimal or no hepatic damage as assessed by histological methods. We suggest that the relative resistance of microsomes to lipid peroxidation is due to the lower peroxidizability index in the ethanol-fed pigs and may account in part for the absence of significant histopathological findings after 20 mo of ethanol feeding.

Animals↗
PubMed1990

Heritable ventricular septal defect in Yucatan miniature swine.

A heritable ventricular septal defect (VSD) was found in a strain of Yucatan miniature swine. The defect was determined to be a high membranous VSD analogous in anatomic location to the most common from of VSD in humans. Eighteen animals were studied clinically, hemodynamically and at necropsy to characterize the defect. Three mature animals developed pulmonary hypertension. Three animals were found to have a patent foramen ovale (PFO) in addition to the VSD. VSD is heritable probably due to polygenic factors. VSD in Yucatan miniature swine may be a suitable model of the human disease syndrome.

Animals↗
PubMed1990

[Miniaturized extracorporeal circulation for infants].

By using the smallest commercially available oxygenator and our own modification of an apparatus for extracorporeal circulation we achieved minimal filling. By placing the apparatus close to the operating table the set can be miniaturized and the length of the tubes can be maximally reduced, while a satisfactory overview is ensured. The authors compared a group of 10 children operated by using this miniature apparatus with a control group of 20 children where the standard set up was used. The filling of the apparatus incl. added solutions was significantly smaller in the group with the mini-apparatus--on average 420 ml, as compared with the control group (671 ml). Despite the substantially larger amount of transfused blood in the control group with the greater volume (500 ml/patient), the resulting packed cell volume was the same in both groups. The other common postoperative parameters did not differ significantly in the two groups. The minimal filling of the apparatus for extracorporeal circulation in the described set up makes possible in the majority of children and infants with an elevated packed cell volume perfusion without the use of donor blood which is consistent with contemporary trends.

Extracorporeal Circulation↗
PubMed1988

Bone marrow transplantation in miniature swine. II. Effect of selective genetic differences on marrow engraftment and recipient survival.

In order to study the effect of defined genetic differences on bone marrow transplantation in miniature swine, five different combinations of major histocompatibility complex (MHC)-matched and mismatched bone marrow transplants were performed. Eight of nine fully MHC-mismatched allogeneic bone marrow transplants failed to reconstitute, and one animal reconstituted briefly but then died quickly thereafter. Five of six class I-matched/class II-mismatched (g----c) bone marrow transplants engrafted, showed a skin rash typical of graft-versus-host (GVH) reaction, and died 3 weeks after the marrow transplantation. None of five class II-matched/class I-mismatched (g----d) transplants engrafted. Parental marrow transplants into F1 hosts engrafted and caused GVH skin rash, with survivals from 1 to 9 months (n = 5). Serologic typing of the F1 recipients of parental marrow showed only donor-type peripheral blood lymphocytes (PBL), suggesting complete marrow replacement. Conversely, F1 into parental marrow transplants showed no engraftment (n = 6). These results indicate that resistance to MHC-mismatched allogeneic bone marrow engraftment in swine represents a host response recognizing donor class I MHC differences. This response appears to interfere with engraftment of donor bone marrow cells despite host preparation with 900-1100 rads total-body irradiation. In the absence of donor MHC class I differences, engraftment was seen despite the existence of multiple non-MHC differences, and even in the presence of class II differences. Such engraftment also led to GVH, varying in intensity according to the strength of genetic disparity (i.e., worst in parent----F1 combination). These results suggest that miniature swine should provide an effective model for study of both GVH elimination (in the parent----F1 combination) and problems of engraftment (in the F1----parent combination), the two most important obstacles to clinical allogeneic transplantation.

Animals↗
PubMed1987

[Functional morphology of the maxillo-mandibular apparatus in the mini-Lewe minipig. 1. Miniature swine in oro-anatomically-oriented research].

This bulletin marks the beginning of a cycle dealing with the structure, function, innervation and quantitative analysis of jaw muscles as well as postnatal cranial growth and dentition in the miniature pig MINI-LEWE. The aims, the importance of the miniature pig MINI-LEWE for medical research, the material and the methods are explained.

Animals↗
PubMed1988

[Gnotobiotic delivery and raising of piglets of the Göttinger miniature swine breed].

Germfree delivery and maintenance of two litters of Göttingen miniature pigs as well as equipment for operation, isolation and rearing are described. For a successful utilization of Göttingen miniature pigs following points have to be considered: 1. Hysterotomy has to take place on 113th day of gestation. For that reason it is absolutely necessary to know the exact date of mating and medical steps against spontaneous farrowing have to be taken. 2. In addition to extradural anaesthesia a light general anaesthesia is required to avoid sow losses in consequence of excitement and following circulatory collapse. 3. In the rearing isolator there have to be installations which allow an individual feeding of the piglets without fixation. In their first days of life newborn piglets should be handled as little as possible.

Animals↗
PubMed1985

Non-invasive blood pressure measurement in Yucatan miniature swine using tail cuff sphygmomanometry.

A relatively new non-invasive method using a photo-electric flow sensor in non-heated animals, was evaluated for its accuracy in measuring systolic blood pressure (SBP), diastolic blood pressure (DBP) and mean arterial pressure (MAP) in 40-90 Kg normotensive and hypertensive Yucatan miniature swine. Directly measured SBP, DBP and electronically averaged MAP were recorded from chronic arterial catheters simultaneously with indirect pressures, cuff pressure and tail blood flow under various conditions. In all of the tests tail cuff SBP estimation averaged within 5% of directly measured SBP. The correlation of the two methods was significant (r = .95, P less than 0.01). Over a 60 to 202 mmHg range of blood pressure induced pharmacologically or due to DOCA hypertension, the tail cuff SBP was within 4-10% of directly measured SBP. The tail cuff method was also used to determine DBP and MAP. DBP determined from the tail cuff record was found consistently to underestimate the direct measured DBP by approximately 17%. The two methods were correlated (r = .87 P less than 0.01). The measured tail cuff MAP generally underestimated the direct MAP by approximately 5%. The correlation of directly measured MAP and tail cuff methods was significant (r = .72, P less than 0.01). These results indicated that this system may be used to accurately assess blood pressure in miniature swine.

Animals↗
PubMed1985

Mevinolin and cholestyramine inhibit the direct synthesis of low density lipoprotein apolipoprotein B in miniature pigs.

Previous studies established that following simultaneous injection of 125I-labeled homologous very low density lipoproteins (VLDL) and 131I-labeled homologous low density lipoproteins (LDL) into miniature pigs, a large proportion of LDL apolipoprotein B (apoB) was synthesized directly, independent of VLDL or intermediate density lipoprotein (IDL) apoB catabolism. The possibility that cholestyramine alone (a bile acid sequestrant) or in combination with mevinolin (a cholesterol synthesis inhibitor) could regulate the direct LDL apoB synthetic pathway was investigated. 125I-labeled VLDL and 131I-labeled LDL were injected into miniature pigs (n = 8) during a control period and following 18 days of cholestyramine treatment (1.0 g kg-1d-1) or following 18 days of treatment with cholestyramine and mevinolin (1.2 mg kg-1d-1). ApoB in each lipoprotein fraction was selectively precipitated using isopropanol in order to calculate specific activity. In control experiments, LDL apoB specific activity curves reached their peak values well before crossing the VLDL or IDL apoB curves. However, cholestyramine treatment resulted in LDL apoB curves reaching maximal values much closer to the point of intersection with the VLDL or IDL curves. Kinetic analyses demonstrated that cholestyramine reduced total LDL apoB flux by 33%, which was due entirely to inhibition of the LDL apoB direct synthesis pathway since VLDL-derived apoB was unaffected. In addition, the LDL apoB pool size was reduced by 30% and the fractional catabolic rate of LDL apoB was increased by 16% with cholestyramine treatment. The combination of mevinolin and cholestyramine resulted in an even more marked inhibition of the direct LDL apoB synthesis pathway (by 90%), and in two animals this pathway was completely abolished. This inhibition was selective as VLDL-derived LDL apoB synthesis was not significantly different. LDL apoB pool size was reduced by 60% due primarily to the reduced synthesis as well as a 40% greater fractional removal rate. These results are consistent with the idea that cholestyramine and mevinolin increase LDL catabolism by inducing hepatic apoB, E receptors. We have now shown that the direct synthesis of LDL apoB is selectively inhibited by these two drugs.

Animals↗
PubMed1977

Rapid miniaturized chromatographic quality-control procedures for Tc-99m radiopharmaceuticals.

Our laboratory has adopted a complete miniaturized charomatography system for Tc-99m radiopharmaceuticals in order to improve upon the commercial systems currently available. Three distinct, separate, chromatographic procedures are used to determine the labeling efficiencies of Tc-99m-labeled sulfur colloid, MAA, stannous chloride, phytate, DMSA, DTPA, pyrophosphate, diphosphonate, methylene diphosphonate, polyphosphate, and glucoheptonate. The chromatographic systems include Whatman 31 ET paper and acetone, Gelman ITLC-SG and 0.9% sodium chloride, and Gelman ITLC-SA and acetone. The chromatographic strips are miniaturized (1 X 6 cm), colored-coded, marked, and numbered. All the chromatographic quality-control procedures are simple, rapid, and can easily be incorporated into the routine quality-control program of any nuclear medicine facility.

Chromatography↗
PubMed1983

Influence of vitamin E and ICRF-187 on chronic doxorubicin cardiotoxicity in miniature swine.

Studies were made of the potential of vitamin E and ICRF-187 to protect against the cardiotoxicity resulting from chronic administration of doxorubicin. Miniature swine (19 to 40 kg) received six injections of doxorubicin (1.6 mg/kg) at 3-week intervals (total dose, 9.6 mg/kg), either alone or concurrently with vitamin E (5000 IU/day for 4 days and 1000 units/day for the next 17 days). In a second study, miniature swine received six injections of doxorubicin (2.4 mg/kg) at 3-week intervals (total dose 14.4 mg/kg), either alone or 30 minutes after 12.5 mg of ICRF-187/kg (intraperitoneally). All animals were sacrificed 3 weeks after the last injection. The frequency and extent of myocardial lesions (vacuolization and myofibrillar loss) were scored on a scale of 0 to 4+. Such lesions were noted in eight of nine pigs given 9.6 mg/kg of doxorubicin alone and in all pigs receiving doxorubicin and vitamin E; however, the severity of the lesions was decreased in the latter animals (average score 1.0, compared with 1.8 in those receiving doxorubicin alone). All swine receiving 14.4 mg/kg of doxorubicin alone developed myocardial lesions (average score, 2.7); these lesions were severe (3+) in four of the animals. In contrast, cardiac lesions were absent in two and minimal (average score, 0.7) in five of the seven animals given 14.4 mg/kg of doxorubicin in combination with ICRF-187.

Animals↗
PubMedDate not supplied

Comparison of the offspring of three serial pregnancies during voluntary alcohol consumption in Sinclair (S-1) miniature swine.

The offspring of serial breedings of voluntary alcohol consuming Sinclair (S-1) miniature swine have been evaluated over the past three years. The first and second litters of 12 dams and the third litter of 6 dams were examined. All study animals had been consuming alcohol for at least 18 months prior to the first breeding. Alcohol consumption was continuous throughout the ninth study. Twelve non-alcohol-consuming sows were used as controls. The results of the study revealed a progressive decrease in mean litter size from controls of 6.66 in the control litters to 1.8 piglets per litter in the third litter born to alcohol-consuming dams. Perinatal deaths showed a progressive increase from 10% in the controls to 36.4% in the L3 litter. The birth weight showed a decline from a mean of 719 +/- 186 g in the control group to 467 +/- 122 g in the L3 litter. Abortions were not seen in control, first litter or second litter; however, there were 3 aborted fetuses in the third litter. Observation revealed no additional anomalies beyond the previous reports of anomalies seen in litters of alcohol-consuming S-1 miniature swine dams.

Alcohol Drinking↗
PubMed1984

Practical miniaturized membrane oxygenator for isolated organ perfusion.

Silastic membrane tubing oxygenators possess valuable atraumatic properties, but no satisfactory miniature system for isolated organ perfusion has been achieved. We describe the construction of a new type of miniaturized Silastic membrane tubing oxygenator, 1.5 m long, 1.5-mm diameter, 75-micron wall thickness, incorporated in a single self-supporting unit readily applicable to isolated organ perfusion because of its simplicity, durability, and small prime volume of less than 3 ml. In vitro experiments using out-dated human banked blood demonstrated that the unit can effectively oxygenate blood of hematocrit 35% at flow rates of at least 10 ml/minute and that higher flow rates may be used to oxygenate blood or perfusates of a lower hematocrit. The results were verified in three different practical experimental applications: isolated rat liver, rabbit heart, and rat free skin flap perfusion.

Animals↗
PubMed1983

A comfortable, minimum stress method of restraint for Yucatan miniature swine.

For comfortable, minimal-stress restraint of Yucatan miniature swine, a heavy cotton duck sling reinforced with nylon webbing and covered with vinyl was used. The sling was designed with four leg openings and one hole for access to the anterior vena cava. Custom padding was used to line the leg holes and minimize chafing. Five sling sizes were developed for the restraint of any size Yucatan miniature pig (3 to 75 kg) or other pigs up to 150 kg. A steel frame on wheels was designed with or without a boat winch crank mechanism to support the interchangeable slings. The pig restraint was accomplished by lifting or hoisting the animal, depending on animal size.

Animals↗
PubMed1983

Cerebral, coronary, and renal blood flows during hemorrhagic hypotension in anesthetized miniature swine.

The purpose of these studies was to measure cerebral, coronary, and renal blood flow in miniature swine during hemorrhagic hypotension. Blood flows (BF) were measured in 16 anesthetized, female, miniature swine (35-50 kg) with the radiolabeled microsphere technique using 15-microns spheres. The animals were exposed to a standard, stepwise hemorrhagic shock protocol which set mean aortic pressure at 65, 50, 35, and 20 mm Hg for 10-15 min at each stage. Heart rate and aortic and central venous pressures were measured throughout these studies. Arterial pCO2, pO2 pH, and Hct were measured at the time of BF measurements. BFs were measured under baseline conditions and during three of the four stages of hypotension in each animal. BF was measured in the following tissues: brain (13 samples), heart (120 samples), kidney (left and right), spleen, liver, muscle, and skin. Coronary BF was consistently decreased during hypotension. Endo/Epi flow ratios were also decreased; however, they remained greater than or equal to 1.0. Renal BF and BF to most other tissues showed graded decreases with hypotension. Cerebral BF did not change significantly at any level of hypotension. The maintenance of cerebral BF in swine at such low arterial pressures (22 mm Hg) may be related to the decrease in central venous pressure (-8 mm Hg), which results in a delta P of 30 mm Hg, and/or to the swine's carotid rete mirabile.

Animals↗