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[Slow excitation waves and mechanisms of polymorphic ventricular tachycardia in an experimental model: isolated walls of the right ventricle from rabbit and squirrel].

The mechanism of polymorphic disturbances of the heart rhythm is studied on an experimental model, isolated ventricular preparations of ground squirrel and rabbit. Polymorphic arrhythmias are identified from habitus of the isolated preparation pseudoECGs mathematically derived from electrograms registered simultaneously at 32 endocardial and 32 epicardial points. The same electrograms allow one to visualize the excitation wave propagation along each of the preparation surfaces. The comparison of excitation wave pictures and corresponding pseudoECGs enabled us to reveal the conditions necessary and sufficient for polymorphism in heart rhythm disturbances. Polymorphic arrhythmias are due to changes in wave pictures in the regions of retarded excitation propagation.

Animals↗

[Identification of an experimental model of partial portocaval shunt].

Portacaval shunt with interposition of 6 mm H-graft of PTFE is a real partial shunt. In this experimental study, the operation has been well tolerated and has been compared with 8 mm H-graft and direct "vein to vein" portacaval shunt. Intraoperative data show that 6 mm is the ideal diameter for a portacaval shunt to prompt an experimental model based on partial decompression of portal bed in animals in this size.

Animals↗

[Inflammatory demyelinating diseases if the peripheral nervous system: immunological concepts and experimental models].

Some inflammatory diseases of the peripheral nervous system, most prominently the Guillain-Barré syndrome, are currently regarded to be of autoimmune origin. Experimental models show clearly that the balance between cellular and humoral autoimmune reaction against peripheral myelin components significantly determines the appearance of the disease. Yet, important questions, such as target antigens of the antimyelin reaction are still unresolved.

Animals↗

Denatured muscle grafts for nerve repair in an experimental model of nerve damage in leprosy. 1. A functional and morphometric study.

The effectiveness of denatured autologous muscle grafts for nerve repair in an experimental model of leprosy was assessed. Nerve damage resembling that caused by Mycobacterium leprae in humans was induced by the injection of cobalt-irradiated M. leprae into the tibial nerve of guinea pigs. At the time of maximum functional loss, caused by the formation of a granuloma within the nerve, the area of damage was excised and a denatured autologous muscle graft was used to repair the nerve. Assessment of nerve regeneration through the graft was made using clinical, electrophysiological and microscopic morphometric analysis at intervals up to 20 weeks. The results were compared with regeneration after grafting of a normal nerve. Clinically, some motor and sensory recovery occurred in all of the graft recipients in the normal nerve by 8 weeks, and by 11 weeks in the recipients of grafts in the granulomatous nerve. Full sensory recovery occurred in all but one animal by 20 weeks. Motor function recovered to near normal levels at 14 weeks after repair of the normal nerve but, at 20 weeks, there was variation in motor recovery after repair of the granulomatous nerve. Electrophysiology showed increased conduction velocity of the nerve fibers at each time-point. The conduction velocity at 8 weeks after grafting of the normal nerve was similar to that at 12 weeks after grafting of the granulomatous nerve. Morphometry showed an increasing number of myelinated fibers repopulating the distal nerve up to 20 weeks. Myelin fiber numbers, at this time, were one third of normal after repair of the granulomatous nerve and two thirds after repair of the normal nerve.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

[Transcatheter ablation with high-frequency currents as a method for creating useful experimental models in the study of cardiac conduction and automatism].

PURPOSE: analyze the utility of transcatheter ablation with high-frequency currents to create different experimental models of altered cardiac automatism and conduction. METHOD: the results were obtained in six anesthetized dogs subjected to electrophysiological study after selectively applying transcatheter radiofrequency ablation to different zones of the specific cardiac conduction system. Ablation was carried out using conventional bipolar 7F catheter-electrodes. High-frequency currents (0.7 MHz) were emitted through the distal electrode, with variable intensity and duration according to the aim of the experiment. Anatomic (fluoroscopic) and electrophysiological criteria were used to position the electrode within the ablation zone. RESULTS: selective radiofrequency application to the atrioventricular junction zone affords complete A-V blocks with escape rhythms located in the A-V node or His-Purkinje system, together with different degrees of infra- and intra-hisian and intranodal blocks. The modification of intranodal refractoriness and conduction without interrupting atrial pulse transmission may manifest atypical patterns with truncated nodal conduction curves. The abolition of sinus function through ablation in the zone of the sulcus terminalis makes it possible to obtain supraventricular subsidiary rhythms. The obtaining of intranodal complete blocks with supra-Hisian escape rhythms demonstrates phenomena such as the modulation of subsidiary automatism by non-transmitted atrial pulses, analyzed by constructing phase-response curves. CONCLUSION: transcatheter ablation using high-frequency currents is useful in demonstrating phenomena related to intranodal and His-Purkinje conduction, subsidiary pacemaker automatism or the modulation of automatism and conduction via non-transmitted pulses.

Animals↗

[Experimental models of insulin resistance and obesity: lessons learned].

For better understanding the role of each element involved in the physiopathology of obesity and insulin resistance, researchers can use experimental models, which may in controlled manner evaluate the participation of each element on the obesity and insulin resistance and provide information for better understanding the physiopathology and treatment of obesity and insulin resistance. Experimental obesity and insulin resistance can be due to a deficient response to leptin, secondary to hypoleptinemia and/or mutations on leptin receptor, by modifications on insulin receptor, deletion or diminished insulin signal transduction, enhancement of the effects of orexigen peptides and/or diminution of anorexigen peptides actions on hypothalamus, as well as secondary to arterial hypertension, as in the spontaneously hypertension. Obesity and insulin resistance can also be induced by glucocorticoid excess, frutose enriched and cafeteria diet and due to hypothalamus lesions induced by neonatal administration of monossodium glutamate.

Adipose Tissue↗

[Axonal reaction precedes demyelination in experimental models of multiple sclerosis].

Taking into consideration that myelin phospholipids may be partially synthesized in neuronal bodies, while neurilemma readily reacts with antibodies against gangliosides by changing the properties of membrane ionic channels, the attempt was made to test the proposed assumption of the early axonal reaction in demyelinating processes in experimental models of multiple sclerosis. The models of chronic allergic encephalomyelitis in Lewis rats injected with homogenate of highly purified myelin or total brain gangliosides were used. First signs of demyelination (the destruction of intermediate dense lines) were demonstrated in the inner layers of myelin close to axon and were shown to develop synchronously with the aggregation of filamentous-tubular material in the neuroplasm. These changes are associated with significant shift of the ratio of myelin sheath thickness to axonal diameter (from 1:7-1:3 to 2:1-3:1). This swelling of myelin seems to be caused by neuroplasmic proteins aggregation, that must be accompanied by the drop in oncotic pressure and the separation of loosely-bound water fraction that may be assimilated by myelin. At light microscopic level the increase of myelin thickness is clearly observed that is in exact correspondence with the decrease in axonal diameter. The process starts with the exfoliation and swelling of the nodes of Ranvier and the incisures of myelin, which fuse after elongation, that corresponds to the total disintegration of myelin with the preservation of continuity of axon which appears to be harshly shrunken.

Animals↗

An experimental model of hemolysis-induced acute pancreatitis.

The literature indicates that acute pancreatitis is a complication of massive hemolysis with a prevalence of about 20%. We describe an experimental model of hemolysis-induced acute pancreatitis. Hemolytic anemia was induced in rats by a single ip injection of 60 mg/kg of 20 mg/ml acetylphenylhydrazine (APH) in 20% (v/v) ethanol on the first experimental day (day 0). One hundred and fifty Wistar albino rats weighing 180-200 g were divided into three groups of 50 animals each: groups 1, 2 and 3 were injected ip with APH, 20% ethanol, and physiological saline, respectively. Ten rats from each group were sacrificed on study days 1, 2, 3, 4 and 5. Serum amylase, lipase levels and pancreatic tissue tumor necrosis factor-alpha (TNF-alpha) and platelet-activating factor (PAF) contents were determined and a histological examination of the pancreas was performed. No hemolysis or pancreatitis was observed in any of the rats in groups 2 and 3. In group 1, massive hemolysis was observed in 35 (70%) of 50 rats, moderate hemolysis in seven (14%), and no hemolysis in eight (16%). Thirty-three of 35 (94.2%) rats with massive hemolysis had hyperamylasemia, and 29 of these rats (82.8%) had histologically proven pancreatitis. The most severe pancreatitis occurred on day 3, as demonstrated by histology. Tissue TNF-alpha and PAF levels were statistically higher in group 1 than in groups 2 and 3. Acute massive hemolysis induced acute pancreatitis, as indicated by histology, in almost 80% of cases. Hemolysis may induce acute pancreatitis by triggering the release of proinflammatory and immunoregulatory cytokines.

Acute Disease↗

Effect of immunosuppression and amphotericin B on Aspergillus antigenemia in an experimental model.

A modified enzyme-linked immunosorbent assay (ELISA) for crude carbohydrate antigen was used to evaluate the kinetics of aspergillus antigenemia and to determine the effect of therapy on circulating antigen levels in an experimental model. The ELISA was rapid, simple to perform, and able to detect less than 10 ng of antigen/mL of serum. The model was also used to evaluate the effect of temporary and persistent immunosuppression on experimental disease. Antigen levels rose progressively in untreated control rabbits; all 15 animals had significant antigenemia. Treated animals had markedly reduced antigen levels, but nine of 13 rabbits had detectable antigen after 72 h of therapy, a result that correlated with persistent disease. Therapy begun 24 h after challenge in temporarily immunosuppressed animals was more likely to sterilize tissues than was therapy begun 48 h after challenge. Therapy in persistently immunosuppressed rabbits was less effective and may require improved antifungal regimens to be successful.

Amphotericin B↗

Photoinduction of micronuclei by 4,4',6-trimethylangelicin and 8-methoxypsoralen in different experimental models.

The frequencies of micronuclei induced by treatment with 4,4',6-trimethylangelicin (TMA) and 8-methoxypsoralen (8-MOP) have been compared in the following experimental models: (1) peripheral normochromatic erythrocytes (NCE) during 10 days after single p.o. administration of TMA or 8-MOP in male and female mice; (2) peripheral NCE during photocarcinogenesis by TMA or 8-MOP topically administered to female mice; (3) primary cultures of human skin fibroblasts treated with TMA or 8-MOP. The frequency of micronuclei in peripheral NCE of mice (both sexes) was significantly enhanced after p.o. administration of TMA or 8-MOP. This latter was more active than TMA in inducing chromosomal damage. No increased frequencies of micronuclei in peripheral NCE were detected in mice subjected to TMA or 8-MOP photocarcinogenic treatment, even when malignancies developed. In human fibroblast cultures, at equimolar concentrations, the induction of lethal effects by TMA in the presence of 365-nm radiation was higher than that exerted by 8-MOP. At equal survival, however, TMA showed practically the same activity as 8-MOP in the induction of micronuclei. Our findings provide evidence of genotoxicity by TMA administered p.o. without irradiation and give further information about photogenotoxicity of these substances.

Animals↗

An experimental model of generalized seizures for the measurement of local cerebral glucose utilization in the immature rat. I. Behavioral characterization and determination of lumped constant.

An experimental model of status epilepticus has been developed in the immature rat by administration of pentylenetetrazol (PTZ) using repetitive, timed intraperitoneal injections of subconvulsive doses. The pattern of behavioral signs has been well characterized in each age group, i.e. 10 (P10), 14 (P14), 17 (P17) and 21 postnatal days (P21). In this model, the dose of convulsant could be adjusted as a function of interindividual sensitivity and status epilepticus lated for quite a long duration to allow the measurement of local cerebral metabolic rates for glucose (LCMRglc) by means of the [14C]2-deoxyglucose method [J. Neurochem., 28 (1977) 897-916]. To estimate LCMRglc during status epilepticus, the lumped constant (LC) was re-calculated in controls and PTZ-treated rats. The control LC was 0.54 at P10 and 0.50-0.51 at the three older ages studied (P14, P17 and P21). During status epilepticus, it increased to 0.64 in P10 rats and decreased to 0.42 and 0.40, respectively, in P17 and P21 animals. At P14, LC was not affected by seizures. The measurements of brain lactate levels showed a large 4.5-10-fold increase in PTZ-treated rats as compared to controls at all ages. The results of the present study show that the immature brain responds to sustained seizure activity in a specific way according to its postnatal age. Moreover, our results underscore the necessity of re-calculation of LC to the quantification of LCMRglc in such pathological states, particularly in immature animals.

Aging↗

Experimental modelling of drug membrane permeability by capillary electrophoresis using liposomes, micelles and microemulsions.

Capillary electrophoresis (CE) was evaluated as an in-vitro format for experimental modelling of membrane permeability using only nanogram quantities of drug compounds. The rationale for the CE technique emanates from emulation of a lipid-like pseudo-stationary phase that governs separations mainly as a result of differences in molecular size, lipophilicity, hydrogen bonding and charge, all of which also have a strong influence on in-vivo drug absorption. By means of micellar, microemulsion and liposome electrolytes, the migration behaviour was studied at 37 degrees C for 22 model drug compounds. The generated CE retention factor data were then compared with membrane permeability reference data. Both simple log D and more common Caco-2 cell parameters were evaluated. In addition, permeation through intestinal segments of rat ileum and rat colon was included. An improved correlation was obtained in the order: micellar < microemulsion < liposome systems. Although the correlation for the best liposome CE system was only R(2)=0.77, the evaluation results for all emphasized the strength and flexibility of CE for assessing specific drug-membrane interaction through tailor-made lipophilic media.

Animals↗

Inflammatory reaction and collagen accumulation in an experimental model of open wounds in the rat. A comparison between gauze and Debrisan treatment.

Debrisan treatment was compared with the use of gauze in an experimental model of open wounds in the rat. The amounts of exudate absorbed by the gauze and by Debrisan were measured daily during the post-wounding period and the myeloperoxidase (MPO) activity in the exudate was determined. Blood flow, water content and accumulation of the collagen amino acid hydroxyproline in the granulation tissue were measured on days 3, 5, 7 and 10 post-wounding. The amount of exudate absorbed both by gauze and by Debrisan reached a peak on post-wounding days 4-5 and was greater in Debrisan-treated wounds. MPO activity in the Debrisan-absorbed exudate, on the other hand, was lower throughout the study period than in the exudate absorbed by gauze. Granulation tissue blood flow and water content reached maximum values on day 7 post-wounding, irrespective of treatment. Blood flows were 39% and 40% lower in the Debrisan-treated wounds on post-wound days 3 and 7, respectively, than in the gauze-treated wounds, whereas the water contents of the former wounds were 23% and 15% lower on days 3 and 10, respectively. The hydroxyproline content of the granulation tissue increased continuously from day 3 to day 10 and was similar in the two wounds. These results suggest that Debrisan is more effective than gauze for absorbing wound exudate, when applied on an openly secreting wound. In addition, the inflammatory reaction taking place in Debrisan-treated wounds seems to be less severe than in wounds treated with gauze.

Animals↗

Experimental modeling of anxiety and depression.

Anxiety and depression have dramatic impact on human and animal behaviors. We take an interdisciplinary approach and review the existing experimental models of anxiety and depression in order to promote further understanding of neurobiological aspects of anxiety and depression.

Animals↗

[Cellular mechanisms of pulmonary vasoconstriction in an experimental model of protamine reversal of heparin].

The neutralisation of heparin by protamine can cause life-threatening pulmonary hypertension. We studied this reaction in animal experimental models (sheep and rat) to determine the cellular mechanisms of the pulmonary vasoconstriction. The heparin-protamine reaction (H-P) with pulmonary hypertension (peak of mean pulmonary artery pressure = 57.3 +/- 2.2 mmHg), decreased cardiac output (-20%), leukopenia (-30%) and plasma release of high concentrations of thromboxane B2 (6.03 +/- 0.03 ng/ml) was constantly observed in sheep. The reaction was identical in sheep with induced thrombocytopenia by administration of antiplatelet antibodies. On the other hand, the neutralisation of heparin by protamine in rats did not cause thromboxane release or pulmonary vasoconstriction although the leukopenia was identical to that observed in sheep. Therefore, the platelets and white blood cells did not seem to cause the pulmonary vasoconstriction induced by the H-P complexes. The inter-species difference observed suggests that pulmonary intravascular macrophages may be responsible for the liberation of eicosanoids and acute pulmonary vasoconstriction occurring during the neutralisation of heparin by protamine.

Animals↗

[Chromosome aberrations in F1 (NZBxNZW) mice--an experimental model of systemic lupus erythematosus].

Spontaneous and mitomycin-C-induced chromosomal aberration level was studied in bone marrow cells of mice F1 (NZBXNZW), an experimental model of systemic lupus erythematosus and in C57BL/6J mice. The chromosome instability level is found to correspond to the degree of the autoimmune process: F1 (NZBXNZW) mice with the highest titer of autoantibodies to DNA has higher chromosomal mutability.

Animals↗

[Laparoscopic transplantectomy of renal graft. Experimental model].

Renal transplant nephrectomy carries a high morbidity and mortality. Conceptually, graft removal by laparoscopy is a logical less invasive alternative. We have developed an experimental model for renal autotransplantation in the pig, with laparoscopic graft removal eight weeks following autotransplantation. Although the clinical indication for laparoscopic nephrectomy of a failed graft will provoke controversy, a nonfunctioning renal graft with intolerance and no rupture or infection late post-transplantation theoretically could be the indication for this procedure.

Animals↗

Clinical chemotherapy: its correlation with experimental models.

The inputs into clinical trials are many and the possibilities for study are nearly infinite. The only way rational choices and priorities can be established is through the use of experimental models. Clinicians and experimentalists must develop a continuous dialogue so as to mutually develop their questions of importance for study.

Animals↗