Passive Rabbit Research Articles

Development and validation of a computational finite element model of the rabbit upper airway: simulations of mandibular advancement and tracheal displacement.

The mechanisms leading to upper airway (UA) collapse during sleep are complex and poorly understood. We previously developed an anesthetized rabbit model for studying UA physiology. On the basis of this body of physiological data, we aimed to develop and validate a two-dimensional (2D) computational finite element model (FEM) of the passive rabbit UA and peripharyngeal tissues. Model geometry was reconstructed from a midsagittal computed tomographic image of a representative New Zealand White rabbit, which included major soft (tongue, soft palate, constrictor muscles), cartilaginous (epiglottis, thyroid cartilage), and bony pharyngeal tissues (mandible, hard palate, hyoid bone). Other UA muscles were modeled as linear elastic connections. Initial boundary and contact definitions were defined from anatomy and material properties derived from the literature. Model parameters were optimized to physiological data sets associated with mandibular advancement (MA) and caudal tracheal displacement (TD), including hyoid displacement, which featured with both applied loads. The model was then validated against independent data sets involving combined MA and TD. Model outputs included UA lumen geometry, peripharyngeal tissue displacement, and stress and strain distributions. Simulated MA and TD resulted in UA enlargement and nonuniform increases in tissue displacement, and stress and strain. Model predictions closely agreed with experimental data for individually applied MA, TD, and their combination. We have developed and validated an FEM of the rabbit UA that predicts UA geometry and peripharyngeal tissue mechanical changes associated with interventions known to improve UA patency. The model has the potential to advance our understanding of UA physiology and peripharyngeal tissue mechanics.

Features of Conditioned Reflex Fear in Active and Passive Rabbits

The individual typological features of conditioned reflex fear were studied in groups of active and passive rabbits selected on the basis of analysis of their behavior in the open field and dark-light boxes by developing a classical conditioned reflex using a combination of a light (4 sec) and electrocutaneous stimulation of the hindpaws (10 Hz, 0.5 sec). Changes in respiratory and heart rates in the animals in response to stimulus combinations during training were analyzed. Conditioned defensive responses to light (freezing) were associated with reductions in respiratory and heart rates occurring in response to the light, i.e., before electrocutaneous stimulation. Active rabbits contrasted with passive rabbits in showing greater motor reactions, higher heart rates, delayed onset of conditioned reflex respiratory slowing to a later stage of training, and the absence of persistent bradycardia. Thus, judging from the these few autonomic measures, active animals experienced lower levels of fear than passive animals. The active and passive behavioral strategies persisted after training.

Effects of Administration of an Agonist and an Antagonist of GABAA Receptors into the Amygdala in Rabbits on the Respiratory and Cardiac Components of Conditioned Reflex Fear

The role of the GABAergic system of the amygdala in the autonomic and behavioral manifestations of conditioned reflex fear was studied in groups of “active” and “passive” rabbits selected on the basis of testing in an open field and a dark-light chamber. The animals were trained to a conditioned reflex by combining light (4 sec) and electrocutaneous stimulation of the hindlimbs (1 sec, 10 Hz). The extent of conditioned reflex fear was assessed in terms of changes in heart rate and respiratory movements in response to the conditioned and unconditioned stimuli as compared with rates prior to training. After training, a GABA receptor agonist (muscimol, 0.1 μg/1 μl) or antagonist bicuculline metabromide, 0.5 μg/1 μl) was applied locally into the right or left basal nucleus of the amygdala via a cannula. Administration of muscimol into the amygdala induced more extensive autonomic changes in passive rabbits than in active, eliminating the reduction in the rate of respiratory movements in response to the conditioned stimulus typical of freezing, as well as weakening or altering responses to electrocutaneous stimulation, as judged by heart and respiratory rates. Activation of the left amygdala with bicuculline increased the probability of active motor reactions in active rabbits, while activation of the right amygdala, conversely, increased the probability of freezing. These results provide evidence of the nonequivalence of the GABAergic system of the amygdala in animals with active and passive behavioral strategies.

A smoothed finite element method for analysis of anisotropic large deformation of passive rabbit ventricles in diastole.

The smoothed FEM (S-FEM) is firstly extended to explore the behavior of 3D anisotropic large deformation of rabbit ventricles during the passive filling process in diastole. Because of the incompressibility of myocardium, a special method called selective face-based/node-based S-FEM using four-node tetrahedral elements (FS/NS-FEM-TET4) is adopted in order to avoid volumetric locking. To validate the proposed algorithms of FS/NS-FEM-TET4, the 3D Lame problem is implemented. The performance contest results show that our FS/NS-FEM-TET4 is accurate, volumetric locking-free and insensitive to mesh distortion than standard linear FEM because of absence of isoparametric mapping. Actually, the efficiency of FS/NS-FEM-TET4 is comparable with higher-order FEM, such as 10-node tetrahedral elements. The proposed method for Holzapfel myocardium hyperelastic strain energy is also validated by simple shear tests through the comparison outcomes reported in available references. Finally, the FS/NS-FEM-TET4 is applied in the example of the passive filling of MRI-based rabbit ventricles with fiber architecture derived from rule-based algorithm to demonstrate its efficiency. Hence, we conclude that FS/NS-FEM-TET4 is a promising alternative other than FEM in passive cardiac mechanics.

Effects of Intra-Amygdalar Administration of GABAA Receptor Agonists and Antagonists on the Behavior of Active and Passive Rabbits in Emotionally Negative Situations

The effects of local administration of an agonist (muscimol hydrobromide, 0.1 μg in 1 μl) and antagonist (bicuculline methiodide, 0.05, 0.1, 0.5 μg in 1 μl) of GABAA receptors on the behavior of active and passive rabbits were studied in an open field test, dark–light box, and on exposure to emotionally significant stimuli. Treatment effects differed in animals with active and passive behavioral strategies: active rabbits were more sensitive to bicuculline, while passive animals were more sensitive to muscimol. In active animals, bicuculline had anxiolytic actions in the open field and dark–light box and motor-activating influences in response to emotionally significant stimuli. Muscimol had anxiolytic effects in passive rabbits and sedative actions in animals of both groups. Differences in the efficacies of right- and left-sided dosage sites were seen: more effective changes in behavior were produced when bicuculline was given into the left amygdala, while muscimol was more effective when given in the right amygdala. The anxiolytic effect appeared when bicuculline was given into the left amygdala in active rabbits and when muscimol was given into the right amygdala in passive animals. These results provide evidence of the existence of individual-typological and interhemisphere differences in the functioning of the GABAergic system of the amygdala.

Network Activity of “Interneurons” and Large Cells in the Amygdala in Active and Passive Rabbits

Cross-correlation histogram studies demonstrated differences in the interactions of presumptive small “interneurons” and large principal cells in the central and basal nuclei of the amygdala in rabbits in emotionally negative situations. “Interneurons” displayed greater network activity than principal cells. “Interneurons” more frequently had input and output excitatory and inhibitory connections with neighboring neurons, and the latencies of their connections with other cells were shorter, than in the case of principal cells. Interactions between “interneurons” and principal cells in emotionally negative situations differed in animals with active and passive behavioral strategies. In passive rabbits, there were more inhibitory connections with “interneurons” from any other cells than in active animals, while passive animals showed fewer excitatory and inhibitory connections from “interneurons” to principal cells.

Effects of intra-amygdala injection of GABA(A)-receptor agonist and antagonist on respiratory and cardiac components of conditioned fear in rabbits

The role of GABAergic system of amygdala in vegetative and behavioral manifestations of conditioned fear was studied in groups of active and passive rabbits, selected upon testing in open field and light-dark chamber. During training, the light (4 s) was paired with electrodermal stimulation of hind limbs(1 s, 10 Hz). Conditioned fear was judged by heartbeats and respiratory rates before and in the process of conditioned and unconditioned stimuli presentation. Solutions of GABA(A)-receptor agonist (muscimol, 0.1 μg/μL) or antagonist (bicuculline methbromide, 0.5 μg/μL) were applied to the right or left basal nucleus of amygdala after conditioning. Muscimol injection evoked more powerful vegetative changes in passive rabbits than in the active ones; respiratory deceleration during freezing in response to conditioned stimuli was eliminated and the reaction to electrodermal stimulation was reduced or altered. Activation of the left amygdala by bicuculline resulted in the increased probability of active locomotor reactions in active rabbits, activation of the right amygdale, on the contrary, increased probability of freezing. The results evidence the non-equivalence of amygdalar GABAergic system in active and passive animals.

Method of Continuous Monitoring the Passive Rabbit Iris Deformation based on Stereo Vision

Quantification of the relation between passive iris deformation and pressure differences between the anterior and posterior chamber is necessary to diagnose primary angle closure glaucoma. We devised the animal experiment to simulate the total pupil-blocking. We accomplished the experiments using isolated rabbit irises without destroying orbicular structure. 2D image of the iris was screened when the pressure difference was changed. We computed 3D coordinates of rabbit iris based on stereo vision. The 3D data was used for plotting the curves to indicate the relation between passive iris deformation and pressure differences. Experimental results prove that the height of passive deformation of the iris was 0.6mm when pressure difference was 600Pa. The passive iris deformation plays an important effect in primary angle closure glaucoma.

Interaction of Neurons in the Basal and Central Nuclei of the Amygdala in Rabbits with Active and Passive Behavioral Strategies in Emotionally Negative Situations

Cross-correlation histograms were used to study the interaction between neurons in the central and basal nuclei of the amygdala in groups of passive and active rabbits in emotionally negative situations. The animals’ behavior was tested in an open field, a dark-light box, and on exposure to emotionally significant stimuli. Rabbits of the different groups retained a particular behavioral strategy in different tests. Intergroup differences were seen in the interaction of close-lying amygdalar neurons. Passive animals showed more excitatory and fewer inhibitory interneuronal connections with latent periods from 50 to 150 msec than active animals; interactions between neurons were rarer at the delta1 and theta2 frequencies. Asymmetry in interhemisphere interactions of neurons with right-sided dominance was seen in passive animals but was absent in active animals. These data provide evidence that the amygdala is involved in selecting the passive or active behavioral strategy, passive animals showing higher levels of activation of the amygdala than active rabbits.

Interhemisphere Asymmetry of the Hippocampus and Neocortex as a Correlate of the Active and Passive Behavioral Strategies in Emotionally Negative Situations

Cross-correlation histograms were used to study the interhemisphere interactions of cells in bilateral leads from the parietal and sensorimotor areas of the neocortex and hippocampal field CA1 in groups of rabbits with active and passive behavioral strategies in an open field test. Passive rabbits showed asymmetry in the bilateral interaction: with right-sided dominance in the neocortex and left-sided dominance in the hippocampus. Active animals, conversely, showed left-hemisphere dominance in the neocortex, with no asymmetry in the hippocampus. Brain lateralization was apparent as motor asymmetry in relation to preference for right or left turns in the open field: passive rabbits showed a relative preference for left turns and active animals for right turns. In all animals, systemic administration of the GABAB receptor agonist phenibut, which decreases behavioral reactivity to emotionally significant stimuli, eliminated the interhemisphere asymmetry seen in normal conditions in emotionally negative situations. These results provide evidence that interhemisphere asymmetry at the levels of the neocortex and hippocampus is linked with the individual-typological characteristics of the animals and reflects readiness for the most typical types of behavioral responding in active and passive animals.

Interaction of Hippocampal and Neocortical Neurons in Emotionally Negative Situations in Active and Passive Rabbits

Cross-correlation histograms were used to compare the interaction of close-lying cells in the hippocampus (field CA1) and the parietal-temporal areas of the neocortex in active and passive rabbits during exposure to emotionally significant stimuli. Interaction of hippocampal neurons depended on the type of the behavioral response to the stimulus. The greatest changes from baseline were seen in active rabbits in orientational-investigative and active defensive reactions, while the greatest changes in passive animals were in freezing. In all states, cases of common inputs to hippocampal neurons were found more frequently in passive rabbits and excitatory links between neurons with short delays (up to 40 msec) were more frequent in active rabbits. Interaction of neocortical neurons, in contrast with hippocampal neurons, was less dependent on the type of behavioral response to the stimulus and the animal's behavioral strategy. These results provide evidence of individual-typological features in information processing in hippocampal field CA1 in active and passive animals in emotionally negative situations.

Differences in the Spike Activity of Hippocampus and Neocortex Neurons in Active and Passive Rabbits in Emotionally Negative Situations

Autocorrelation histograms were used to compare the spike activity of neurons in the hippocampus (field CA1) and parietal-temporal areas of the neocortex in groups of active and passive rabbits during exposure to emotionally significant stimuli. The mean spike frequencies of single hippocampal neurons were greater in active rabbits than in passive rabbits, and also showed more frequent discharge grouping and periodicity, and frequencies in the theta-1 range (6.9-19.0 Hz) were more often seen in discharge periodicity (in baseline conditions and during active motor reactions to stimuli), while theta-2 frequencies (4.0-6.0 Hz), conversely, were less common (on freezing). Hippocampal neuron spike activity during exposure to stimuli showed more marked changes in active rabbits than in passive rabbits. Intergroup differences in neuron spike activity were smaller in the neocortex than in the hippocampus. These results lead to the conclusion that individual-typological differences in the behavior of animals in emotionally negative situations are reflected in neuron activity in hippocampal field CA1 and the parietal-temporal areas of the neocortex. It is suggested that active and passive rabbits have different levels of activation of the septohippocampal system and functional differences in the afferent inputs to hippocampal field CA1.

Behavior and measures of respiration in rabbits differing in terms of movement activity in an open field

Analysis of the behavior of 19 Chinchilla rabbits the first time they were placed in an open field allowed them to be divided into three groups differing in terms of investigative movement activity (passive rabbits accounted for 37%, active for 21%, and intermediate for 42%). On repeat placing in the open field, passive rabbits increased and active rabbits decreased their levels of activity. Correlations were found between the rabbits' behavior in the open field and the nature of their external respiration in the absence of movements in the comfort situation. Passive rabbits, as compared with intermediate and active animals, showed longer respiratory cycles, expirations, and breath holds in expiration. Animals with a predominance of right-hand turns in the open field showed shorter respiratory cycles and expirations than animals with a predominance of left-hand turns. These studies led to the conclusion that the characteristics of external respiration can serve as a predictive factor for the passive-defensive strategy of behavior in rabbits in emotionally negative situations.

Three-Dimensional Stress and Strain in Passive Rabbit Left Ventricle: A Model Study

To determine regional stress and strain distributions in rabbit ventricular myocardium, an anatomically detailed finite element model was used to solve the equations of stress equilibrium during passive filling of the left ventricle. Computations were conducted on a scalable parallel processing computer and performance was found to scale well with the number of processors used, so that stimulations previously requiring approximately 60 min were completed in just over 5 min. Epicardial strains from the model analysis showed good agreement (RMSE = 0.007332) with experimental measurements when material properties were chosen such that cross fiber strain was more heterogeneous than fiber strain, which is also consistent with experimental observations in other species.

The need to account for residual strains and composite nature of heart wall in mechanical analyses.

We studied 19 excised, passive rabbit left ventricular walls to delineate the forms of the strain-energy functions (W) for myocardium and epicardium, to quantify residual strains across the wall, and to investigate whether the mechanical behavior of the intact wall can be predicted by accounting for the above properties. The unloaded dimensions and the stress-strain responses to equibiaxial and uniaxial loadings were obtained first for the intact wall and then individually for the epicardium and myocardium. Results show that the previously proposed W for canine myocardium and epicardium are suitable. The unloaded intact wall has residual strains: the epicardium is stretched and the myocardium shrunk from their respective isolated, unloaded states. The predicted mechanical responses of the intact wall to biaxial loadings were inaccurate when the residual strains were not taken into account. Accounting for these, however, yielded reasonable predictions. Thus information on the unloaded reference state and properties of each portion is needed to accurately predict the behavior of the intact wall.

Passive tension and stiffness of vertebrate skeletal and insect flight muscles: the contribution of weak cross-bridges and elastic filaments

Tension and dynamic stiffness of passive rabbit psoas, rabbit semitendinosus, and waterbug indirect flight muscles were investigated to study the contribution of weak-binding cross-bridges and elastic filaments (titin and minititin) to the passive mechanical behavior of these muscles. Experimentally, a functional dissection of the relative contribution of actomyosin cross-bridges and titin and minititin was achieved by 1) comparing mechanically skinned muscle fibers before and after selective removal of actin filaments with a noncalcium-requiring gelsolin fragment (FX-45), and 2) studying passive tension and stiffness as a function of sarcomere length, ionic strength, temperature, and the inhibitory effect of a carboxyl-terminal fragment of smooth muscle caldesmon. Our data show that weak bridges exist in both rabbit skeletal muscle and insect flight muscle at physiological ionic strength and room temperature. In rabbit psoas fibers, weak bridge stiffness appears to vary with both thin-thick filament overlap and with the magnitude of passive tension. Plots of passive tension versus passive stiffness are multiphasic and strikingly similar for these three muscles of distinct sarcomere proportions and elastic proteins. The tension-stiffness plot appears to be a powerful tool in discerning changes in the mechanical behavior of the elastic filaments. The stress-strain and stiffness-strain curves of all three muscles can be merged into one, by normalizing strain rate and strain amplitude of the extensible segment of titin and minititin, further supporting the segmental extension model of resting tension development.