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Cardioprotective effects of amlodipine on ischemia and reperfusion in two experimental models.

The cardioprotective effect of amlodipine, a long-acting dihydropyridine derivative, was studied in 2 experimental models of ischemia and reperfusion. Isolated and blood-perfused feline hearts were made globally ischemic for 60 minutes and then reperfused for 60 minutes. Alterations of left ventricular developed pressure and compliance were monitored in both amlodipine-treated hearts and saline-treated control animals. Changes in perfusion pressure indicated that amlodipine significantly reduced myocardial oxygen consumption and coronary vascular resistance. Furthermore, a progressive increase in resting left ventricular diastolic pressure indicated that amlodipine, administered before the onset of global ischemia, attenuated the development of ischemic contracture. Return of contractile function 60 minutes after reperfusion and maintenance of tissue concentrations of electrolytes were significantly better in the amlodipine-treated group than in the control animals. In intact canine hearts, regional myocardial ischemia was induced for 90 minutes, followed by 6 hours of reperfusion. Although the hemodynamic variables and the size of the region of risk did not differ significantly between treated animals and control animals, the infarct size was significantly smaller in the amlodipine-treated group than in the control animals, and a gradual reduction in coronary blood flow was observed in the control group that was prevented in the amlodipine group. A comparison of these findings with those observed with oxygen radical scavengers also is discussed. A detailed report of these studies was published in The American Journal of Cardiology (1989;64:101I-116I). This review is included here to maintain continuity of the symposium for the convenience of the reader.

Amlodipine↗

Dissolution of pancreatic stones by oral trimethadione in a dog experimental model.

Experiments were conducted to develop a dissolution therapy for human pancreatic calculi in a dog experimental model of pancreatic calculi surgically prepared. On plain x-ray films of the abdomen, pancreatic calculi appeared in 19 of 39 dogs within 12 mo after operation. The antiepileptic agent trimethadione was given orally to 13 dogs at a dose of 1.0-1.5 g daily. Pancreatic calculi disappeared in 13 of 15 observations. The scanning electron microscopy, the elemental analysis, and the powder x-ray diffractometry of pancreatic calculi in this model revealed that the calculi closely resembled human pancreatic calculi, consisting mainly of a calcite of calcium carbonate. There was no histologic finding suggesting drug toxicity in the liver, the kidney, and the blood. Pancreatic calculi in 6 control dogs without the treatment neither disappeared nor diminished spontaneously. The oral treatment with trimethadione may have potential for dissolving human pancreatic calculi.

Administration, Oral↗

Human gamete fusion test: an experimental model for assessing the fusion potential of sperm from nonfertilizing normospermic patients.

OBJECTIVE: To develop an experimental model for assessing the ability of sperm to bind and subsequently fuse with the oolema and to use this test for evaluating the fusion potential of nonfertilizing human sperm. DESIGN: Aged human oocytes (n = 108) were denuded of their zonae and loaded with DNA-specific bisbenzamidazole fluorochrome. Sibling oocytes were inseminated by semen samples from either normospermic patients (study group; n = 12) who have repeatedly failed to achieve fertilization in vitro or patients demonstrating high fertilization rates (control; n = 12). Gamete fusion was ascertained by fluorescent microscopy and validated by scanning electron microscopy. Test results were analyzed in relation to current partial zona dissection treatment outcome. SETTING: Infertility and IVF Unit of an academic tertiary referral medical center and university-based basic research laboratory. RESULTS: In samples achieving fertilization by partial zona dissection (7/12; 9% to 23% fertilization rate), the mean numbers of fused spermatozoa were similar to those of the control (2.1 compared with 2.6) and significantly higher than in the partial zona dissection-failed fertilization subgroup. In six of seven cases in which partial zona dissection yielded embryos, fluorescent spermatozoa were detected on the oolema, whereas in all but one partial zona dissection-failed cases gamete fusion was not observed. CONCLUSIONS: The suggested human gamete fusion test may help focus on specific sperm dysfunction in nonfertilizing patients. It correlates well with the outcome of partial zona dissection-assisted IVF trials and may provide useful information before this treatment is attempted.

Cellular Senescence↗

The chicken retina as an experimental model for investigation of central nervous lesions.

The aim of this study was to establish an experimental model to investigate neuronal lesions. The retina is an easy accessible model system to study central nervous system (CNS) disorders or neuronal effective drugs. It consists of only a few characteristic layers and is easy to prepare as an intact piece of tissue. In the retina the typical cell swelling of a developing lesion is accompanied by a very strong intrinsic optical signal (IOS) which is simultaneous with the electrical signal and is based on changes in light scattering. The IOS can be easily observed during the whole experiment and can be recorded with non-invasive optical methods for further quantification of damage. In the developed model, the lesions are elicited electrically with a tungsten microelectrode (0.1 M[omega]). The degree of damage depends on the magnitude of the stimulus. The parameters for the quantification of damage are the area and the brightness of the affected tissue. The growth of the lesions can be influenced with drugs added to the perfusion system. In the present study we tested, glycerol, mannitol and ketamine which are known to be neuroprotective in other animal models.

Animals↗

Otomicroscopic and histologic findings of induced myringosclerosis in rats: a critical study of an experimental model.

UNLABELLED: Myringosclerosis is characterized by hyaline changes of the lamina propria of the tympanic membrane. Experimental studies have used otomicroscopy or histology to evaluate myringosclerosis in animals, but they do not correlate precisely these two methods. AIM: The present study evaluates the accuracy of otomicroscopy in the diagnosis of myringosclerosis in rats. STUDY DESIGN: Experimental. MATERIAL AND METHOD: Myringosclerosis was induced by transtympanic inoculation of Streptococcus pneumoniae in 25 Wistar rats, which were examined weekly through otomicroscopy and sacrificed after eight weeks for histologic study of their tympanic membranes. RESULTS: From the comparison of the otomicroscopic data in relation to the histologic findings, we could observe sensibility of 80% and specificity of 75% for the otomicroscopy. CONCLUSION: Considering the results in this study, otomicroscopy did not represent a good method to evaluate myringosclerosis in this experimental model.

Animals↗

Experimental model for repetitive ischemic attacks in the gerbil: the cumulative effect of repeated ischemic insults.

An experimental model for repeated ischemic attacks, which allows easy induction of cerebral ischemia of any desired duration and frequency, has been developed in the gerbil. With this procedure, a pronounced cumulative effect on development of edema and tissue injury was observed using 3 separate, 5-min bilateral occlusions of the common carotid arteries spaced at various time intervals. This effect was most evident when the occlusions were carried out at 1-h intervals, i.e., during the period of marked postischemic hypoperfusion. Such animals, killed after 24 h of recirculation, showed significantly more severe edema and brain tissue injury in the areas exposed to ischemia than was observed in animals killed 24 h after single 5- or 15-min occlusions. The changes of regional CBF, assayed with a [3H]nicotine method, indicated a relatively rapid onset of hypoperfusion of similar degree after each release of arterial occlusion. The hypoperfusion recovered significantly within 6 h of recirculation following either single or multiple occlusions, and no residual hypoperfusion was observed in animals which, when killed at 24 h, showed severe edema and brain tissue injury. This model should prove useful in elucidating the pathophysiological mechanisms operative in repetitive cerebral ischemia.

Animals↗

New developments in experimental models of inflammatory bowel disease.

PURPOSE OF REVIEW: To consider new data and directions coming from experimental models of inflammatory bowel diseases. RECENT FINDINGS: Advances are discussed in the areas of microbial-host interactions in the intestine, the role of cytokines like IL-23, chemokines like IP-10, and various costimulatory molecules in disease pathogenesis. Multiple regulatory cells have been identified as well as the mechanisms they use to inhibit pathogenic responses to the microbiota in the intestine. New data is available on how the intestine heals after inflammatory insults. SUMMARY: These data are providing fundamental insights into the pathogenesis of IBD and thus are forming the basis of new therapeutic approaches, many of which will be translated to the clinic in the near future.

Journal Article↗

Experimental model for studies of continuous peritoneal'dialysis in uremic rabbits.

In this paper we describe an experimental model designed for studies of continuous ambulatory peritoneal dialysis (CAPD) in uremic rabbits. We preferred the study of uremic animals because it is not known whether peritoneal membrane differs between normal and uremic animals. Animals made uremic after bilateral nephrectomy could not survive on dialysis. Instead, partial nephrectomy of one kidney and partial (5/6) destruction of the cortex of the remaining kidney by electrocauterization provided a simple and reproducible model. CAPD resulted in adequate control of uremia but the animals showed significant decreases in total plasma proteins and weight. This model is suitable for studies of the metabolic complications of CAPD.

Animals↗

The Gunn rat: an experimental model for central deafness.

The Gunn rat which develops neonatal hyperbilirubinemia has been used as an experimental model to evaluate the effect of bilirubin on the auditory system. Electrocochleographic and morphological studies (including light microscopy, surface preparations and transmission electron microscopy) did not reveal any cochlear abnormality in homozygous Gunn rats. Brainstem auditory evoked potentials showed morphological and amplitude changes suggesting a functional damage in the brainstem auditory pathways. These results suggest that hearing loss, when observed in kernicterus, is primarily due to neuronal damage at the level of brainstem auditory nuclei.

Animals↗

[An experimental model of electrically-induced coronary thrombosis in the closed chest].

The authors report on an experimental model of coronary thrombosis, electrically induced in the closed thorax. By this technique they succeeded inducing coronary thrombosis with myocardial infarction in 13 cases out of 21. In three cases just disseminated myocardial necrosis was proved. All of the other animals showed vast myocardial infarctions. Coronarography, arterial pressures, typical shifts of serum enzymes, decrease of thrombocytes and fibrinogen and elevation of spontaneous fibrinolysis during the first hours proved to be valuable for the confirmation of successful inducing of thrombosis; in individual cases, however, these estimations yield no absolute certainty.

Animals↗

[Method for measuring dental roots by roentgenograms for making experimental models].

Two methods were used for measuring the true size of abutment teeth roots for making experimental models. One method was based on the use of intraoral contact roentgenograms made with a Russian 5D-2 x-ray diagnostic dental device and the other on the use of roentgenograms made with parallel beam bundles from a longer distance using an x-ray diagnostic dental device with a more potent x-ray tube, Evolution-300 (Italy) on a Kodak x-ray film (USA) Ultra-speed-58, 3.1[symbol: see text]4.1 cm. The results obtained by the latter method are more accurate, the difference from the true size being no more than 0.5 mm. However intraoral contact roentgenograms give the results close to the true size of abutment teeth roots, for example, for one of the mandibular premolars; however a correction coefficient should be used.

Dental Abutments↗

[Efficacy evaluation of cloxacillin and cloxacillin-gentamicin in an experimental model of methicillin-sensitive Staphylococcus aureus].

23 rabbits with Staphylococcus aureus methicillin-sensitive, SAMS, experimentally induced endocarditis (EIE) were studied to compare the efficacy of cloxacillin vs the association cloxacillin-gentamicin. Twelve animals made the control group and 11 the treated ones, 5 with cloxacillin-gentamicin and 6 with cloxacillin. The animals were treated 3 days, then, mortality, blood cultures at 48 and 72 hours and the title of the unit-forming colonies per gram of vegetation (UFC/g) were evaluated. The control group had a mortality of 100% in the first 72 hours, its blood cultures were positive at 48 and 72 hours and the UFC/g was 10,48 o 0.20. There was statistical significance between the control group and both treatment, in mortality, blood culture's positivity and the UFC/g of vegetation. This results confirm the similar efficacy of cloxacillin either alone or in combination in the treatment of SAMSIE and the effectiveness of the experimental model to evaluate antimicrobial treatments.

Animals↗

Development of a new experimental model for total exclusion of the right heart without the aid of cardiopulmonary bypass.

A new experimental model for the total exclusion of the right heart was successfully developed in mongrel dogs without the use of cardiopulmonary bypass. A Y-shaped conduit was constructed with tube grafts spirally stented on the exterior (10 mm in diameter), and each upper limb of the conduit was provided with a 30F cannula. The foot of the conduit was anastomosed with the main pulmonary artery in an end-to-side way with a side clamp. After a closed atrioseptostomy was performed with a special knife of our design, the upper limbs of the graft were connected to the superior and inferior venae cavae by a cannulation method. The operative procedure was completed by tightening the occluding snares around the venae cavae and ligating the root of the pulmonary artery and azygos vein. Thus, without any use of the right atrium, venous blood from the venae cavae was totally diverted to the pulmonary circulation via the conduit, and only the coronary venous return was shunted to the left atrium. Five consecutive dogs tolerated the operative procedure. No pressure gradients were observed between the pulmonary arteries and venae cavae. The circulation with this model was able to be sufficiently sustained with mean pulmonary arterial pressures of about 25 mm Hg, and no significant changes were shown in the left ventricular pump function from the preoperative state. However, the decrease in the mean pulmonary artery pressure to 20 mm Hg resulted in severe circulatory failure, and two of the five dogs succumbed to this condition. Our new model will be useful for studying the hemodynamic characteristics of the circulation after operations that result in total exclusion of the right heart.

Animals↗

The role of mineralization in experimental models of osteogenetic induction with decalcified bone matrix.

The role of mineralization was studied in an experimental model of osteoinduction consisting of the implant of decalcified bone matrix in the rat muscle. After vascular connective tissue invasion of the matrix, the first phenomena is the appearance of hydroxyapatite crystals in the area of chondroid metaplasia from where the deposit of calcium-phosphate is extended to the surrounding decalcified matrix. The recalcified areas act as a substratum for the neo-osteogenesis. The appearances observed reproduced those of enchondral ossification, where the first osteoblasts differentiated on the calcified cartilaginous matrix and began to supply new bone matrix. Non-decalcified bone matrix implants were surrounded by a connective tissue capsule with features identical to those of a foreign body reaction and with total absence of vascular invasion. The absence of induction in this type of implant may be related either to masking of the osteoinducing protein in the calcified matrix, or to the absence of cells with osteogenic differentiation potential due to the lack of cellular invasion of the implant.

Animals↗

Influence of NMR measuring sequences and gradient variation on signals from flowing systems. Magnetic resonance tomography on experimental models.

The influence of flow on MR tomography images and signal intensities has been studied using experimental model tubes and an aqueous NiCl2 solution having the same relaxation time as human blood. We applied the inversion recovery (IR) and the spin-echo (SE) sequence on a .15T MR tomography system. The influence of RF pulse distance (tau) in the IR and SE experiment as well as the influence of magnetic z-gradient strength on the flow images has been investigated. IR images revealed that signals from flowing systems recover more rapidly due to influx of non-inverted longitudinal magnetization into the scan slice. SE images in presence of flow are characterized by signal intensity loss with increasing time caused by the outflow and dephasing of transverse magnetization. With increasing strength of the z-gradient, the MR signals of flowing fluids decrease drastically. Thus for detection of flow, all the above mentioned parameters are of importance.

Blood↗

[The pathogenesis of hematoxylin bodies--observations on an experimental model in animals (author's transl)].

Paraquat induced lung damage in guinea pigs was used as experimental model producing respiratory distress syndrom. Lung specimens investigated in early stages after this injury showed hyaline membranes combined with hematoxylin bodies. The latter result from epithelial necrosis and local deficit of lysosomal enzymes with reduced cell degradation. Hematoxylin bodies consist of nuclear debris forming spherical bodies by their high surface tension. Their structure is the same as in human newborns where sometimes basophilic bodies are to be recognized in the beginning of pulmonary hyaline membranes.

Animals↗

[Evaluation of the efficacy of various hypotensive drugs in broad-breasted white turkeys as an experimental model of arterial hypertension with high catecholamine levels].

Male Broad Breasted White Turkeys (BBWT) represent an experimental model of arterial hypertension characterized by high levels of circulating and tissue catecholamines. We thought interesting to evaluate the efficacy of the long term treatment with different antihypertensive drugs. 59 male BBWT were studied, divided in five groups. The first group (13 animals) was treated with placebo; the second (14 animals) with oxprenolol 4 mg/Kg/q.d.; the third (10 animals) with labetalol 25 mg/Kg/q.d.; the fourth (11 animals) with verapamil 15 mg/Kg/ q.d.; the fifth (11 animals) with captopril 8 mg/Kg/ q.d. and furosemide 2,5 mg/Kg/q.d. All drugs were given p.o, from the 8th to the 33rd week of age. Weekly or every two weeks Blood Pressure (BP) and Heart Rate (HR) were measured by an indirect method. In all animals BP progressively increased and HR progressively decreased with age. Only the labetalol-treated animals showed a significant reduction of BP and HR through the study period as compared with the placebo-treated animals. These results confirm the preminent role played by the high levels of circulating catecholamines in determining and maintaining the arterial hypertension.

Animals↗