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Experimental model of heterotopic cardiac transplantation for evaluation of graft viability and function.

An experimental model of heterotopic intrathoracic cardiac transplantation making possible an evaluation of graft viability and function has been studied. The technique requires only two anastomoses in the normothermic state without cardiopulmonary bypass. In this model, the ascending aorta of the recipient animal may be occluded completely, enabling an increasing preload on the graft. In case of adequate myocardial preservation of the cardiac graft, the aorta may be completely occluded and the recipient systemic circulation can be sustained by the graft. However, in case of inadequate graft myocardial function, or in case of size mismatch, the recipient heart alone contributes to the circulation. This technique appears quite useful because of its simplicity, the elimination of the need for extracorporeal circulation while allowing a functional evaluation following cardiac graft preservation.

Animals↗

[Experimental model of primary cultured metastatic melanoma by fine needle aspiration].

PURPOSE: Establish an experimental model of metastatic melanoma primary culture cells from fine-needle aspiration biopsies (FNAB). METHODS: Two metastatic melanoma primary culture cells from (FNAB) have been developed from patients who had been submitted to excision of metastatic lesions and they were identified by immunohistochemical analyses using S-100 and MB-45 melanoma markers. RESULTS: The culture diagnostic was confirmed by immunohistochemical. The technique of FNAB offers the advantage of providing a sequential analysis of the same tumor nodules throughout treatment, and is a minimally invasive procedure with almost no associated morbidity. CONCLUSION: The establishment of metastatic melanoma primary culture from FNAB samples showed a viable technique.

Animals↗

An experimental model of ischemia in rabbit hindlimb.

This study was performed to establish an experimental model of ischemia for the investigation of new treatment modality of limb-threatening ischemia. We produced ischemia in the hindlimbs of 8 New Zealand white rabbits. Under general anesthesia, the left femoral artery was exposed, freed, and excised from distal external iliac artery to proximal popliteal and saphenous arteries. And then both hindlimbs were serially examined to assess the ischemia according to the time table until postoperative 6 weeks. We assessed clinical observation, blood pressure, radioisotopic perfusion scan, and angiography. Clinical ischemic changes of the operated feet were observed in 63%. The blood pressure of left calves was measurable on postoperative day 3 (p<0.05, vs preoperative day 2) and then gradually increased to reach a plateau in postoperative week 6. Radioisotopic arterial perfusion showed similar profiles as in blood pressure. Angiography of ischemic hindlimbs demonstrated a few collateral vessels arising from the internal iliac artery with the reconstitution of the posterior tibial artery in postoperative week 2. In postoperative week 6, collaterals remained the same in number. However, these became dilated and tortuous and showed reconstitution in distal hindleg. In conclusion, this is a reproducible, measurable, and economical animal model of hind limb ischemia.

Angiography↗

Experimental models of small closed systems with spatially separated unicellular organism-based components.

Experimental models of small biotic cycles of different degree of closure and complexity with spatially separated components based on unicellular organisms have been studied. Gas closure of components looped into "autotroph-heterotroph" (chlorella-yeast) system doubled the lifetime of the system (as opposed to individually cultivated components). Higher complexity of the heterotroph component consisting of two yeast species also increased the lifetime of the system through more complete utilization of the substrate by competing yeast species. The lifetime of gas and substrate closed "producer-consumer" trophic chain (chlorella-paramecia) increased to 7 months. In 60 days the components' numbers reached their steady state followed by more than 40 cycles of the medium. The role of a predator organism (protozoan) in nitrogen cycling was demonstrated; reproduction of protozoa correlated directly with their emission of nitrogen in the ammonia form that is most optimum for growth of chlorella.

Animals↗

[Characteristics of the anxiolytic action of benzodiazepine and GABA derivatives on experimentally modelled anxiety states].

The anxiolytic effect of seduxen was revealed in rats in experimentally modelled anxiety states formed by aversive actions of various biological importance. Phenibut and baclofen were found to display no anxiolytic properties on the anxiety model during a conflict situation. The revealed differences of the anxiolytic effect of derivatives of benzodiazepine and GABA indicate diverse spectra of their psychotropic activity.

Animals↗

[Iron overload of the liver and protein synthesis. Progress made through experimental models].

To understand the disturbances in protein synthesis observed during idiopathic hemochromatosis, various experimental models may be used. The aim of this research was to review the principal models employed and to demonstrate the value of hepatic tissue culture techniques in each. This method has already made it possible to explain several mechanisms involving the control of proteins in iron metabolism such as transferrin and ferritin. Tissue culture techniques of human hepatocytes should make it possible to elucidate the nature of the basic metabolic disorder in this disease responsible for the iron overload in the near future.

Animals↗

[Experimental model for the study of the vascular system of the bronchial artery].

An experimental model was worked out for the isolated study of the vasculal system of the bronchial artery. The model allowed to study 1) the role of bronchiar circulation in the pathomechanism of the shock lung; 2) the effect of charges in fusion of the isolated circulation of the microstructure of the lungs; 3) the effect of changes in pH, CO2 level and O2 tension on the greater and lesser circulation, on ventilation, CO2 loss, and O2 uptake were studied.

Animals↗

Experimental model of focal sclerosis. I. Relationship to protein excretion in aminonucleoside nephrosis.

An experimental model of focal sclerosis (FS) following chronic administration of aminonucleoside (AMNS) is described in rats with pathologic features similar to those observed in human steroid-resistant idiopathic nephrotic syndrome. Six groups of rats were given intraperitoneal injections of either 0.9% normal saline or aminonucleoside (13 mg. per 100 gm. of body weight); four groups underwent a right nephrectomy on day 22; a second series of injections of saline or aminonucleoside were then administered to all six groups: group I (five animals), saline-saline; group II (10 animals), AMNS-AMNS; group III (10 animals), AMNS-nephrectomy-AMNS; group IV (five animals), AMNS-nephrectomy-saline; group V (five animals), saline-nephrectomy-AMNS; group VI (five animals), saline-nephrectomy-saline. A relationship between the percentage of glomeruli with focal sclerosis and the total amount of protein excreted during the course of the experiment was observed (r=0.80). An apparent threshold level of protein excretion essential for the development of FS was also noted in that all rats excreting greater than 2.2 integral units developed FS whereas those excreting less than this amount did not. The highest incidence of FS was seen in rats that had received AMNS after unilateral nephrectomy: 62% of glomeruli with FS in group III and 26% in group V; whereas no FS was seen in groups I and VI or in rats evaluated 7 to 23 days after a single injection of AMNS. These studies indicate a quantitative relationship between the breakdown in the permeability barrier to protein and the ultimate development of FS. The prior demonstration of epithelial cell alteration in acute AMNS disease and the morphologic changes presented in this and the subsequent paper (Velosa JA, Glasser RJ, Nevins TE, Michael AF: Lab Invest 36:527, 1977) support the concept that irreversible epithelial cell injury may be the primary event in the development of FS.

Animals↗

[Experimental model for the study of molybdenosis in the primary copper deficiency in rats].

An experimental model in rats was evaluated to differentiate the effects between Copper deficiency and Molybdenosis. Sixty weaning rats (30 male and 30 female) received a diet with 70% complete powder milk (1 ppm Cu) and 30% maize meal (0.8-1.5 ppm Cu). Three experimental groups received the following mineral supplementation: copper deficiency (40 ppm Fe), molybdenosis (40 ppm Fe + 40 ppm Cu + 500 ppm Mo) and control (40 ppm Fe + 40 ppm Cu). The animals were weighed each 14 days. At 70 days of treatment were sacrificed. Blood and liver were sampled for analyzing hematocrit, ceruloplasmin activity and Cu and Mo liver concentration. Copper deficiency group had less serum ceruloplasmin activity. Cu and Mo liver concentration were higher in the animals with molybdenosis. We concluded that when Cu levels are higher than minimum requirement, feeding with high Mo, do not affect ceruloplasmin activity. In addition, high Mo liver concentration allows us to elucidate effects "per se" of molybdenosis.

Animals↗

Suncus murinus as a new experimental model for motion sickness.

Characteristics of motion sickness and effects of possible prophylactic drugs were studied using Suncus murinus (house musk shrew) for its potential use as an experimental model in motion sickness. Mild reciprocal shaking (amplitude: 10-40 mm; frequency: 0.5-3.0 Hz) induced vomiting in most of Suncus murinus within 2 min. Adaptation was observed when the motion stimulus was repeated with an interval of 2 to 3 days. During the repetitive motion training, both the ratio of sensitive animals and the number of vomiting episodes decreased, and the time from the start of shaking to the first vomiting was extended. Subcutaneous injection of scopolamine (100 mg/kg), chlorpromazine (8 mg/kg), promethazine (50 mg/kg), diphenhydramine (20 mg/kg), chlorphenylamine (20 mg/kg) and methamphetamine (2 mg/kg) decreased the emetic effect of motion sickness, but pyrilamine (20 mg/kg), meclizine (20 mg/kg) and dimenhydrinate (32 mg/kg) were not effective or very weak. These results indicate that the Suncus murinus is sensitive to the motion stimulus and antiemetic drugs are effective as prophylaxis. The Suncus murinus is useful as a new experimental animal model for motion sickness.

Acceleration↗

Protein turnover states of tumour cells and host tissues in an experimental model.

To investigate the progress of tissue protein metabolic perturbations in animals developing cancer cachexia, we analyzed an experimental model system based on a highly-deviated, transplantable ascites hepatoma of the rat (Yoshida AH-130). After inoculation, at first this tumour grew rapidly at an exponential rate, then it entered a stationary state until animal death (in about 15 days). Cessation of protein accumulation (growth) was achieved by tumour cells thanks to a combined reduction of synthesis and enhancement of protein degradation (slow-turnover protein pool); the latter was apparently operated through activation of the acidic vacuolar (lysosomal) mechanism. The body weight, net of tumour, early and progressively declined in transplanted rats. Their liver initially showed a moderate enlargement, mostly accounted for by a reduction in the protein breakdown rate; then the liver eventually atrophied, in spite of an enhanced synthetic rate, because of an even greater increase of the degradative rate. By contrast, gastrocnemius muscles started loosing weight and protein since the early phases of tumour growth; their atrophy was associated with elevation of the apparent protein degradative rate, with no change in the apparent synthetic rate. Therefore, tumour growth somehow elicited perturbations in the host tissues examined, which apparently mostly affected the catabolic side of protein turnover.

Animals↗

[Lesions produced by radiofrequency ablation of the cavotricuspid isthmus in an experimental model].

INTRODUCTION AND OBJECTIVES: Experimental studies have shown that deeper and wider lesions (up to 10 mm long or deep) can be safely created using an 8 mm or irrigated tip catheter for ablation to treat atrial flutter. However, potential damage to the tricuspid valve or inferior cava vein has not been systematically evaluated. PATIENTS AND METHOD: The cavotricuspid isthmus was ablated in 26 pigs (body weight 26-52 kg), with a total of 187 radiofrequency pulses. Standard 4 mm, 8 mm and irrigated tip catheters were used at random. For each ablation, energy, impedance and temperature were recorded continuously. RESULTS: The lesions were larger with irrigated tip and 8-mm catheters than with standard ones. In 7 animals (1 with an irrigated tip, 4 with an 8-mm, and 2 with a standard tip) the tricuspid valve was damaged. The tricuspid valve was severely damaged in 3 pigs and lesions were moderate in 4. In animals with tricuspid valve lesions, maximal energy was higher (59 +/- 27 vs. 51 +/- 24 W; p=0,03) and higher temperatures were reached (63 +/- 4 vs. 55 +/- 11 degrees C; p<0.001). Low energy pulses measured before ablation were also more intense in animals in which damage was produced (0.55 +/- 0.24 vs. 0.35 +/- 0.29; p=0.001), indicating greater contact pressure. CONCLUSIONS: The tricuspid valve may be severely damaged during the ablation of the cavotricuspid isthmus for atrial flutter: damage was seen most often with high energy pulses and with 8-mm catheters, but can also occur with usual energy levels and standard catheters. To minimize damage this technique should not be used from the inside of the right ventricle just above the tricuspid valve.

Animals↗

An experimental model for the treatment of lethal bleeding injury to the juxtahepatic vena cava with stent graft.

BACKGROUND: Juxtahepatic vein injuries present a high mortality rate. Our objectives were to develop an experimental model of endovascular lethal injury of the juxtahepatic inferior vena cava (JHIVC) and to evaluate its hemodynamic alterations; to treat the lesion with volume replacement, and a stent graft (SG); and to follow the animals after treatment. METHODS: Twenty dogs were anesthetized and monitored [heart rate (HR), mean arterial pressure (MAP), vesical and peritoneal pressures], and submitted to a JHIVC endovascular injury. After volume replacement the dogs were divided into two groups: control (GI) and experimental (GII). GI was observed until death. GII was treated with SG and followed by Doppler ultrasound (DUS) and cavography for 4 (GIIA), and 8 weeks (GIIB), and then sacrificed and IVC and SG were analyzed. RESULTS: GI presented increased abdominal pressures, arterial hypotension, and death after 80 minutes. GII had a 100% survival rate till sacrifice, without clinical repercussions. At DUS and cavography all SG were patent, with monophasic pulsatile flow. On US, SG diameters after 2, 4, and 8 weeks did not show differences. On cavography IVC diameters presented no difference between groups GIIA and GIIB throughout the experiment. These data analyzed for the GII as a whole, showed statistically significant differences. Average lumen diameter reduction of SG was 27.43+/-20,00%. Pressure values in the IVC cranially, caudally to the SG, and inside the SG, did not show differences. In the IVC with the SG we observed a thicker neointima layer, and the injury in the media layer was covered with fibroconnective tissue. CONCLUSIONS: We developed an experimental dog model of endovascular lethal injury of the JHIVC with significant increase in abdominal pressures, and a mortality rate of 100%. The treatment of this lesion with SG resulted in a thickened neointima layer, and a 27% reduction in the JHIVC lumen diameter, without clinical repercussion, and with a 100% survival rate.

Analysis of Variance↗

[Experimental models of atherosclerosis. Contribution, limits and trends].

Experimental approaches to the problem of atherosclerosis involve animal or cellular models and procedures of lesional induction. Relevant animal models are rare. The rat, the mouse and the dog are free of "natural" atherosclerosis and only develop diffuse lipidosis after high cholesterol diet and thyroid block. They are more appropriate models of experimental arteriosclerosis and intimal proliferation induced by different procedures. The rabbit, also free of spontaneous atherosclerosis, is extremely sensitive to lipid-rich diets, but the lesions induced resemble more a xanthomatosis than an atherosclerosis. Immunological procedures in this model result in a generalised immune arteriosclerotic arteriopathy. The monkey and pig, which are phylogenetically close to man, develop spontaneous atherosclerosis exacerbated by lipid-rich diets or other procedures: hormones, psychosocial stress. The cost and problems of upkeep make these two models inaccessible to most laboratories. Although the hen, turkey and pigeon are grain-eating, they develop natural atherosclerosis, are sensitive to atherogenic diets, and provide satisfactory replacement models, especially for research into the viral and tumoral theories of atherogenesis. The pigeon is particularly suitable for studying cellular, biochemical and genetic aspects of atherosclerosis: these spontaneous plaques, similar to those in man, are ontogenetically and topographically predictable. The species include genetic types both sensitive and resistant to the disease. Moderately lipid-rich diets induce lesions even in very young pigeons. They also lend themselves well to the study of the antiatherosclerotic effects of pharmacological agents. Endothelial, smooth muscle and macrophage cell cultures are widely used to study the factors influencing cellular modulation and proliferation, lipid metabolism and movement of cholesterol, cellular biosynthesis and cell-cell and cell-matrix interactions.

Animals↗

Obesity and diabetes - a possible experimental model of maturity-onset-type diabetes.

This study aimed to acquire a possible experimental model of obese non-insulin-dependent diabetes. Around 230 g Sprague-Dawley female rats were divided into 4 gp: (1) sham ventromedial hypothalamic (VMH) lesioned rats fed low-fat diet (control rats); (2) VMH lesioned rats fed low-fat diet; (3) sham VMH lesioned rats fed high-fat diet and (4) VMH lesioned rats fed high fat diet, and they were observed for 10 weeks (Exp. 1). This experiment was repeated using rats treated by small doses of streptozotocin (5 mg/kg) (Exp. 2). Body weight was measured weekly, blood glucose, every other week and serum insulin, at the end of the experiments. VMH obese rats fed low-fat diet showed normal levels of fasting blood glucose with hyperinsulinemia. VMH obese rats fed high-fat diet showed mildly elevated levels of fasting blood glucose (155 +/- 8 mg/dl as compared to 125 +/- 3 mg/dl of controls) with hyperinsulinemia (5.92 +/- 0.61 ng/ml). Streptozotocin treated VMH obese rats fed low-fat diet did not show increasing levels of fasting blood glucose, while streptozotocin treated VMH obese rats fed high-fat diet showed marked elevation of fasting blood glucose (229 +/- 23 mg/dl). The latter group of rats also had hyperinsulinemia (3.82 +/- 0.45 ng/ml compared to 1.36 +/- 0.14 ng/ml of controls), although concentrations of serum insulin were decreased by streptozotocin treatment compared to levels of VMH obese rats fed high-fat diet. These results demonstrated that VMH obese rats fed high-fat diet showed milk hyperglycemia with hyperinsulinemia. Following treatment of small doses of streptozotocin, VMH obese rats fed high fat diet showed marked hyperglycemia with hyperinsulinemia. The profile of these rats resembles that of maturity onset-type diabetes which accompanies with obesity and hyperinsulinemia.

Animals↗

[Posterior uveitis--clinical forms and experimental models].

The author presented contemporary views concerning etiology and clinical forms of endogenous posterior uveitis as well as the experimental models and histopathological studies of these diseases. The similarities between clinical and experimental forms of choroiditis are emphasized.

Animals↗

Glutathione S-transferase 8-8 is localized in smooth muscle cells of rat aorta and is induced in an experimental model of atherosclerosis.

Allylamine (AA) is an electrophilic amine with a long history of experimental usage because of its extremely potent and relatively specific cardiovascular toxicity; it has been utilized in a variety of experimental models attempting to mimic human atherosclerotic lesions, myocardial infarction, and vascular injury. Even though the exact mechanisms by which AA causes vascular lesions remain unresolved, recent studies on the acute effects of AA exposure in rats strongly suggest that deamination to the aldehyde acrolein, oxidative stress, and the resultant increase in lipid peroxidation, generation of .OH radicals, and acute depletion of glutathione (GSH) may be some of the causative factors in AA-induced vascular lesions. Since glutathione S-transferase 8-8 (GST8-8) of rat belongs to a distinct subgroup of GST isozymes involved in the detoxification of products of lipid peroxidation, we designed studies to examine the effects of AA exposure on this GST isoform in rat aorta using Western blotting and immunohistochemical techniques. The results of these studies demonstrate that GST8-8 is expressed in rat aorta and is dramatically induced upon AA exposure. By immunohistochemistry, GST8-8 was localized in the smooth muscle cells of the vascular media which is believed to be the site of metabolism of AA. A significant increase in gamma-glutamylcysteine synthetase activity and GST activity toward 4-hydroxynonenal and acrolein, which are preferred substrates of GST8-8, was seen as early as 3 days following AA treatment. Alterations in GSH and other GSH-related enzymes at 3 and 10 days support the concept that--upon AA exposure--aortic defense mechanisms respond early and induction of GSH biosynthesis and rat GST8-8 occur to alleviate the toxic effects of acrolein, a major, genotoxic product of AA metabolism. The presence of GST8-8 in the vasculature, which is constantly exposed to products of lipid peroxidation, and its induction by AA, suggest that GST8-8 plays a key role in protecting blood vessels against oxidative stress and hence, may be involved in the atherogenic process.

Allylamine↗