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Abstract Purpose: To investigate the safety and clinical, hemodynamic and tissue improvement ability in mini pigs undergoing cell and gene therapy for the treatment of acute myocardial infarction. Methods: Thirty-two mini pigs Br1 lineage, 12 months old, undergoing induction of acute myocardial infarction by occlusion of the diagonal branch of the paraconal coronary. They were divided into 4 groups: one control group and 3 treatment groups (cell therapy and gene cell therapy). Echocardiography reviews were performed on three occasions and histopathological analysis was performed after 4 weeks. Analysis of variance (ANOVA), Tukey and Wilcoxon tests, were performed. Results: Association of vascular endothelial growth factor (VEGF) with angiopoietin1 (Ang1) presented satisfactory results in the improvement of ventricular function following ischemic cardiomyopathy in mini pigs when compared to the results of the other treated groups. Conclusion: The therapy with VEGF and the combination of VEGF with Ang1, promoted recovered function of the myocardium, characterized by reduced akinetic area and induction of neovascularization.
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Animals , Genetic Therapy/methods , Ventricular Function/physiology , Angiopoietin-1/therapeutic use , Vascular Endothelial Growth Factor A/therapeutic use , Cell- and Tissue-Based Therapy/methods , Myocardial Infarction/therapy , Swine , Swine, Miniature , Wound Healing , Echocardiography , Reproducibility of Results , Treatment Outcome , Neovascularization, Physiologic , Disease Models, Animal , Hemodynamics/physiology , Myocardial Infarction/physiopathology , Myocardial Infarction/pathology , NecrosisABSTRACT
Objective To study the effect of applying a new intravenous resuscitation solution to electrolyte imbalance in miniature pigs after seawater immersion injury.Methods A total of 20 Guizhou Ⅲ type miniature pigs aged 4 months were randomly divided to A and B groups,10 in each.The seawater immersion injury model was used to soak sea water for 3 hours.The changes of electrolytes in miniature pigs before and after soaking wererecorded.A group with intravenous infusion of 0.9％ sodium chloride solution,and B group with new type ofrecovery liquid intravenous rehydration.Electrolyte changes after infusion were recorded and analyzed.Data ofnormal distribution measurement data were expressed as ((x) ± s).The data of electrolyte before and after immersionwere analyzed by paired t test.After soaking,the relative data of electrolyte after sub-group rehydration wereanalyzed by independent sample t test.Results After seawater immersion,pH value were dropped from 7.39 ±0.06and 7.39 ±0.04 to 7.32 ±0.05 and 7.33 ±0.05,serum K + concentration elevated from (3.93 ±0.38) mmol/Land (3.93±0.42) mmol/L to (4.35 ±0.33) mmol/L and (4.37 ±0.14) mmol/L.Clconcentration increased from (93.38 ± 4.29) mmol/L and (92.88 ± 3.79) mmol/L to (102.80 ± 4.29) mmol/Land (103.50±2.46) mmol/L.Na+ concentration in serum were dropped from (140.64 ± 4.99) mmol/L and(140.69 ±4.72) mmol/L to (136.80 ±4.32) mmol/L and (136.90 ±3.03) mmol/L.After normal saline andnew type of recovery liquid rehydration respectively,group B with new recovery liquid,pH increased from 7.33 ±0.05 to 7.38 ±0.04 (P ＜0.05),serum concentration of K+ and Cl-concentration were dropped from (4.37 ±0.14) mmol/L and (103.50 ±2.46) mmol/L to (3.87 ±0.25) mmol/L and (94.15 ±4.23) mmol/L (P =0.005,P =0.007).The concentration of serum Na + back up from (136.90 ± 3.03) mmol/L to (139.30 ±3.06) mmol/L (P =0.038).A group of saline infusion after the various indicators did not change significantly.Conclusion The new intravenous resuscitation solution of miniature pigs electrolyte imbalance correction effect issignificant,that the resuscitation solution has some clinical value for seawater immersion iniurv.
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Objective To study the feasibility of Bama miniature pig model establishment of type 2 diabetes mellitus (T2DM) by high-fat and high-sugar diet combined with streptozotocin (STZ), and observe the changes in protein kinase B (PKB) and phosphorylation expressions in skeletal muscle, liver, and pancreatic tissues of the miniature pig model. Methods A total of 10 healthy male Bama miniature pigs were randomly divided into two groups:control group (n=5, fed normal diet) and diabetic model group (n=5, fed high-fat and high-sugar diet combined with STZ to establish T2DM Bama miniature pig model). The fasting plasma glucose (FPG) and fasting insulin (FINS) levels were measured, and insulin resistance (HOMA-IR) was calculated in two groups. The PKB and phosphorylation expressions in skeletal muscle, liver and pancreatic tissues were measured using Western blot assay. Results (1) After 10 months of high-fat and high-sugar diet, the body weight, FPG, FINS and HOMA-IR were significantly higher in model group than those of control group (P<0.01). (2) After STZ treatment, compared with control group, there was a further increased level of FPG and a significantly decreased level of FINS in model group (P<0.01). (3) Compared with control group, the PKB and phosphorylation expression levels in skeletal muscle, liver and pancreas were significantly lower in model group (P<0.05). Conclusion The high-fat and high-sugar diet combined with STZ can successfully establish the T2DM miniature pig model. The PKB and phosphorylation expression levels in skeletal muscle, liver, and pancreatic tissues are decreased in model pigs.
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Objective To develop miniature pig model of coronary microembolization (CME) by easy and cost-effi-cient technique. Methods A total of 11 miniature pigs were divided into control group (n=5) and CME group (n=6). Femo-ral artery was punctured using 21 gauge needle that is normally used for transradial procedures. Microspheres were injected into the left anterior descending artery of the CME group by 5 F coronary radiography catheter and 1.8 F coronary micro-guide catheter. Serum concentrations of brain natriuretic peptide (BNP) and cardiac troponin I (cTnI) were evaluated just be-fore CME and 6 hours after CME. Apical myocardial pathological lesions were evaluated by optical microscope 6 hours after CME. Results All miniature pigs in control group survived, but one died in the CME group. 5 F coronary radiography cathe-ter and 1.8 F coronary micro-guide catheter reached designated location successfully. Before CME, serum BNP (ng/L:143.00 ± 13.51 vs 134.00 ± 15.57) and cTnI (μg/L:0.39 ± 0.09 vs 0.38 ± 0.10) showed no significant differences between these two groups (t values are 0.976 and 0.294 respectively,both P>0.05). By contrast, serum BNP (561.00 ± 80.65) and cTnI (2.75±0.58) were much higher in CME group than those (BNP 139.00±13.87;cTnI 0.54±0.14 ) in control group after CME (t values are 11.530 and 8.337 respectively,both P＜0.001). In CME group, microspheres, micro-infarction and inflammatory cell infiltration were seen under an optical microscope which are absent in control group. Conclusion Using new surgical consumables can successfully develop miniature pig model with CME. And the technique is simple, cost-efficient, practical so it is worth promoting.
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INTRODUCTION: Radiotherapy (RT) of head and neck neoplasms often damages the salivary glands. AIM: To examine the pattern of morphologic changes resulting from RT of the head and neck region in minipig parotid glands in a clinical and experimental research setting. METHODS: Twelve 18-month-old male Brazilian minipigs weighing 30-40 kg were selected. Eight minipigs were assigned to the experimental group (group 1) and 4 to the control group (group 2). The RT was performed under general anesthesia at Erasto Gaertner Hospital, Curitiba, Brazil, using an á/â ratio of 2.5. The minipigs from group 1 underwent 3 sessions of irradiation with Cobalt 60 of the head and neck, bilaterally, with 3 exposures of 8 Gy each at 7-day intervals for a total dose of 24 Gy. The animals were sacrificed 12 weeks post-RT. RESULTS: The irradiated parotid glands displayed reductions in the size and number of acini as well as loss of secretory granules. The presence of fibrosis and loss of parenchyma relative to non-irradiated glands were observed, with an average reduction in volume of 54%. CONCLUSIONS: Our results demonstrate that this model for parotid gland damage resulting from an RT regimen appears to be useful for preclinical large animal studies of RT-induced damage and testing novel potential treatment options. Although recent advances in radiation therapy, such as intensity-modulated radiation therapy, have reduced the dose and limited the field of radiation, considerable salivary gland injury still occurs and can greatly impact the patient's quality of life after cancer treatment.
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Animals , Salivary Glands/radiation effects , Head and Neck Neoplasms/radiotherapy , Brazil , Swine, Miniature , XerostomiaABSTRACT
Objectives To track bone marrow stem cells (BMSCs) labeled by enhanced green fluorescent protein (EGFP) and superparamagnetic iron oxide ( SPIO ) -poly-L-lysine (PLL) compound by MRI in vitro for autotransplantation into pancreas of type 1 diabetes miniature pigs. Methods The BMSCs were isolated by density gradient centrifugation and attachment culture from type 1 diabetes minipigs' bone marrow. Expressional intensity of EGFP in BMSCs transfected lentivirus-EGFP with a multiplicity of infection Different magnetic resonance scanning protocols were carried out on various density BMSCs labeled by different concentration of SPIO in various time-point in vitro. Results When SPIO concentration was 25mg/L (count in Fe3 + ), the positive Fe3+ -labeling rate of BMSCs was 93. 1%. Most of SPIO particles in BMSCs' cytoplasm were observed in secondary lysosomes, but they were not detected in important organelle as cell nucleus. Comparing with gelatin the MRI of BMSCs labeled with SPIO in the condition with 1 ×104/ml cells density and 25 mg/L Fe3+ concentration in vitro, the signal intensity changes (△SI) after BMSCs labeled with SPIO 3 weeks and 6 weeks in TSE T1WI, TSE T2WI and FLASH T2 * WI sequences were 12%, 41%, 63% and 7%, 28%, 46% respectively (P ＜ 0.01 and P ＜ 0.05, respectively).Conclusions The data showed that the porcine BMSCs labeled with SPIO and EGFP could be traced successfully in vitro by MRI in the suitable sequences.
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ObjectiveTo study the mechanism of myocardial dielectric property changes in radio frequency during hypothermic preservation and explore myocardial viability evaluative method. Methods Hybrid young pigs (20-30 kg) were used in the experiment. Heart arrest was induced with GIK solution. According to preservative temperature, the animals were divided into three groups: group A (4 ℃),group B (15 ℃) and group C (25 C). The heart was preserved in saline for 12,6 and 4 h respectively. Myocardial dielectric properties and ATP content were tested every 5 and 30 min during hypothermic preservation respectively. The relationship between tanoδm and ATP content was analyzed. ResultsTanδm of three groups was decreased significantly at the beginning, most slightly in group A and most obviously in group C. There was no significant difference in Tanδm between group B and group C with group A at 1 h,but there was obvious difference at 2,3 and 4 h (P＜0. 05,P＜0. 05,P＜0. 01 ). There was correlation between tanδm and ATP in the three groups. ConclusionTanδm in three groups is dropped with preservation time and temperature, and tanδm had a correlation with ATP content. Detection of myocardial dielectric property in radio frequency is a kind of quick, accurate and noninvasive method.
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Objective To assess multi-detector CT (MDCT), MR and single photon emission computed tomography (SPECT) in detection of chronic myocardial ischemia in Chinese mini-swine models. Methods Six male pigs received MDCT scan firstly. Then Ameroid narrow ring was placed in the left descending branch and MDCT, MR were performed at the same day. On the 2nd, 27th day, SPECT was given. Coronary angiography (CAG) was given on the 28th day, and then MDCT and MRI. The animals were killed after allexaminations. The pathological examination was given at last. Results Two pigs died during the rearing and another 4 had results. Pathology showed 3 had subendocardium infarction and 1 had no infarction. CAG showed infarction in 3 pigs with stenosis more than 50%. Areas of reduced perfusion in arterial phase MSCT, first-pass MRI and SPECT were consistent to findings of TTC staining. MDCT detected that ESV on the 28th day was higher than that of preoperative and postoperative day (P0.05). CT value of left ventricular anterior wall on preoperative, postoperative day and the 28th day were statistically different (F=10.274, P=0.011). Conclusion Arterial phase of MDCT, first-pass perfusion of MRI and SPECT all show reducing perfusion in left ventricular anterior wall corresponded to myocardial infarction with TTC staining. CT value of myocardial ischemia decreases after myocardial ischemia.
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Objective To investigate the effects of lipoprotein lipase activator, NO-1886, on the mRNA and protein expression of glycogen synthase kinase-3β (GSK-3β) in the kidney of diet-induced diabetic minipigs. Methods Fifteen Guangxi Bama minipigs were randomized into three groups: C group (n=5, with the normal control diet), DM group (n=5, with the high-fat and high-sucrose diet), and NO-1886 group (n=5, with the high-fat and high-sucrose diet supplemented with 1.0% NO-1886). Plasma glucose, insulin, tfiglyceride (TG), oral glucose tolerant test, creatinine and blood urea nitrogen were measured monthly. Urinary samples in the morning were used for determination of microalbumin at month 0, 2, 4 and 5. The mRNA and protein expression of GSK-3β were measured by real time PCR, Western blot and immunohistochemistry in the kidneys obtained at the end of month 5. Results Compared with the C group, levels of plasma glucose, insulin, triglyceride and mieroalbuminuria were significantly increased in the DM group. The mRNA and protein expression of GSK-3β were increased in the kidneys of diabetic pigs (mRNA 0.0272±0.0052, protein 1.1600±0.0463, P<0.01) as compared with those of normal pigs (mRNA 0.0125±0.0045, protein 0.1385±0.0664). Compared with the DM group, the concentrations of plasma glucose, insulin, triglyceride and mieroalbuminuria obviously decreased in the NO-1886 group. The mRNA and protein expression of GSK-3β were decreased in the kidneys of the NO-1886 group (mRNA 0.0162±0.0019, protein 0.8429±0.0408, P<0.05) as compared with that of the DM group. Conclusion NO-1886 can improve disorders of glucose and TG metabolism and insulin resistance, and down-regulate the expression of GSK-3β in the kidneys, and protect renal function and morphologie damage in diet-induced diabetic minipigs.
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Objective To evaluate the efficacy and safty of bioabsorbable polylactic acid sirolimus eluting-stents(BPSES) in inhibiting neointimal hyperplasia in porcine coronary model.Methods Bare metal stents(BMS)(n=18),mere bioabsorbable polylactic acid polymer coated stents(BPOS)(n=18) and BPSES(n=18) were implanted in left anterior descending(n=18),left circumflex coronary(n=18) and right coronary artery(n=18) of 18 swines in random.Coronary angiography was performed 28 days and 90 days after the stenting procedure and histomorphologic analysis was done in a certain number of animals after 7 days(n=4),18 days(n=6) and 90 days(n=6),respectively.Results The 28-day(n=6) and 90-day(n=6) outcome by quantitative coronary angiography(QCA) showed significant reduction in luminal loss(LL) in BPSES(28-day-LL: 0.54?0.45 mm vs 1.11?0.45mm,P=0.048;90-day-LL:0.42?0.34 mm vs 0.96?0.41 mm,P=0.024)compared with BMS.With similar injury scores,histomorphologic analysis on day 28 showed there was a significant reduction in neointimal tissue proliferation with BPSES compared with BMS control(average neointimal area: 0.90?0.40 mm2 vs 1.88?0.71 mm2,P=0.015).High magnification histomorphologic examination revealed similar inflammation score and endothelialization score between BPSES and BMS.Conclusion Bioabsorbable polymeric sirolimus-eluting stents showed reduction in neointimal hyperplasia with good biocompatibility in porcine coronary model.
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Objective To evaluate the formation of coronary collateral circulation with intracoronary Doppler ultrasound in pigs after acute occlusion and the influence of nitroglycerin and phentolamine on it.Methods The blood flow spectrun was detected in 14 pigs using intracoronary Doppler ultrasound before and after acute occlusion of the left circumflex artery (LCX) and its response to nitroglycerin and phentolamine.The average peak velocity (APV) and the diastolic systolic velocity ratio (DSVR) were recorded. Results The APV of the LCX decreased significantly at 10 min after acute occlusion (0.97?1.05 vs 25.78?4.36 cm/s,P0.05). Conclusion Intracoronary Doppler ultrasound can be used to evaluate coronary collateral circulation. The formation collateral circulation was insufficient after acute occlusion of coronary artery in pigs and nitroglycerin or phentolamine can improve the blood flow.
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Objective To investigate the cell dynamic changes of conventional intermittent tissue expansion (CITE) and continuous pressure controlled tissue expansion (CPTE). Methods Domestic pigs were chosen for CITE and CPTE models. Immunohistochemical technique was used to detect proliferative cells, DNA fragments in situ labeling for apoptotic cells, and H E stain for total fibroblast counting. Results Proliferative index of basal cell increased during expansion. The peak value of 78.5% reached at the ninth day in the CITE group versus 84.2 % at fourth day in the CPTE group. Proliferation index in both groups decreased after expansion. Fibroblast proliferation, apoptosis and total fibroblast density increased slowly in both groups during and after expansion. At the sixth day, total fibroblast densities in CITE group (38.1 cells/H) and in CPTE group (40.9 cells/H) were significantly increased, compared with 34.93 cells/H in the normal skin. There were obvious proliferation and apoptosis phenomena in epidermal cells and skin adnexa. Conclusion Tissue expansion has both effects of proliferation and apoptosis on cell dynamics. Continuous tissue expansion can induce tissues growing much effectively.
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Objective To evaluate the efficacy and safty of Polymer-free sirolimus eluting-stents(PFSES) in preventing restenosis in porcine coronary model.Methods Bare metal stents(BMS)(n=13),polymer-free bare metal stents(PFBMS)(n=13),polymeric sirolimus-eluting stents(PSES)(n=13) and PFSES(n=13) were implanted in left anterior descending coronary arteries(n=26) and left circumflex coronary(n=26) of 27 swines randomly.Coronary angiography was performed 28 days and 90 days after the procedure.Twelve animals were sacrificed for histomorphologic analysis after 90 days.Results The 28-day(n=24) and 90-day(n=12) outcome by quantitative coronary angiography(QCA) showed significant reduction in luminal loss(LL) in PFSES(LL:0.69?0.49 mm vs 1.27?0.36 mm,P=0.041;0.77?0.44 mm vs 1.33?0.29 mm,P