Validation of an automated determination of pulmonary resistance by electrical subtraction.

An analog computer to determine dynamic pulmonary compliance (C) and pulmonary resistance (R) on a breath-by-breath basis was tested in guinea pigs and dogs. C was determined by dividing volume by transpulmonary pressure at instants of zero flow. R was determined by the method of electrical subtraction at predetermined flows. In both species the computer outputs and the results of direct analysis were in close agreement. In guinea pigs, the device reliably followed the rapid three- to fourfold changes in C and R resulting from histamine infusion. In unanesthetized dogs, the dispersion and mean values of C and R were similar by the two methods.     

Assessing recruitment of lung diffusing capacity in exercising guinea pigs with a rebreathing technique.

Noninvasive techniques for assessing cardiopulmonary function in small animals are limited. We previously developed a rebreathing technique for measuring lung volume, pulmonary blood flow, diffusing capacity for carbon monoxide (Dl(CO)) and its components, membrane diffusing capacity (Dm(CO)) and pulmonary capillary blood volume (Vc), and septal volume, in conscious nonsedated guinea pigs at rest. Now we have extended this technique to study guinea pigs during voluntary treadmill exercise with a sealed respiratory mask attached to a body vest and a test gas mixture containing 0.5% SF(6) or Ne, 0.3% CO, and 0.8% C(2)H(2) in 40% or 98% O(2). From rest to exercise, O(2) uptake increased from 12.7 to 25.5 ml x min(-1) x kg(-1) while pulmonary blood flow increased from 123 to 239 ml/kg. The measured Dl(CO), Dm(CO), and Vc increased linearly with respect to pulmonary blood flow as expected from alveolar microvascular recruitment; body mass-specific relationships were consistent with those in healthy human subjects and dogs studied with a similar technique. The results show that 1) cardiopulmonary interactions from rest to exercise can be measured noninvasively in guinea pigs, 2) guinea pigs exhibit patterns of exercise response and alveolar microvascular recruitment similar to those of larger species, and 3) the rebreathing technique is widely applicable to human ( approximately 70 kg), dog (20-30 kg), and guinea pig (1-1.5 kg). In theory, this technique can be extended to even smaller animals provided that species-specific technical hurdles can be overcome.     

Comparison of tracheal mucous transport in rats, guinea pigs, rabbits, and dogs

Tracheal mucous transport was measured using similar techniques in several species. One- to 10-microliter quantities of 99mTc-macroaggregated albumin (99mTc-MAA) were instilled via oral intubation in the distal trachea of rats, rabbits, and dogs. Tracheostomies were used for the instillation in guinea pigs. All animals were anesthetized with halothane for the instillation and allowed to recover immediately in restrainers. Clearance of the 99mTc-MAA in rats and guinea pigs was measured by a slit-collimated NaI scanner. In rabbits and dogs a series of gamma-camera scintiphotos were taken. Clearance was faster and more efficient in dogs than in the other species. No significant differences existed among the rats, rabbits, and guinea pigs in the percentages of the originally deposited material remaining at the instillation site after 1 h (P greater than 0.2). Mean values and standard deviations were 83 +/- 23%, 81 +/- 22% and 70 +/- 20% for rats, guinea pigs, and rabbits, respectively. However, in the dogs a mean of 14 +/- 12% remained at the original site of deposition after only 25 min indicating much more rapid clearance. Mean leading-edge velocities were 9.8 +/- 2.1 (SD) for dogs, 3.2 +/- 1.1 for rabbits, 2.7 +/- 1.4 for guinea pigs, and 1.9 +/- 0.7 mm/min for rats. Clearance patterns qualitatively among the species. In dogs the material moved as a few discrete boluses, whereas in the other species the activity spread toward the larynx. The relatively slow mucous transport of rats, rabbits, and guinea pigs could have important implications in inhalation toxicological studies.     

Respiratory mechanics and maximal expiratory flow in the anesthetized mouse.

Mice have been widely used in immunologic and other research to study the influence of different diseases on the lungs. However, the respiratory mechanical properties of the mouse are not clear. This study extended the methodology of measuring respiratory mechanics of anesthetized rats and guinea pigs and applied it to the mouse. First, we performed static pressure-volume and maximal expiratory flow-volume curves in 10 anesthetized paralyzed C57BL/6 mice. Second, in 10 mice, we measured dynamic respiratory compliance, forced expiratory volume in 0.1 s, and maximal expiratory flow before and after methacholine challenge. Averaged total lung capacity and functional residual capacity were 1.05 +/- 0.04 and 0.25 +/- 0.01 ml, respectively, in 20 mice weighing 22.2 +/- 0.4 g. The chest wall was very compliant. In terms of vital capacity (VC) per second, maximal expiratory flow values were 13.5, 8.0, and 2.8 VC/s at 75, 50, and 25% VC, respectively. Maximal flow-static pressure curves were relatively linear up to pressure equal to 9 cm H(2)O. In addition, methacholine challenge caused significant decreases in respiratory compliance, forced expiratory volume in 0.1 s, and maximal expiratory flow, indicating marked airway constriction. We conclude that respiratory mechanical parameters of mice (after normalization with body weight) are similar to those of guinea pigs and rats and that forced expiratory maneuver is a useful technique to detect airway constriction in this species.     

Pathogenesis of CAR bacillus in rabbits, guinea pigs, Syrian hamsters, and mice.

Cilia-associated respiratory (CAR) bacillus isolated from infected mice (designated, CBM) and propagated in embryonated chicken eggs was inoculated intranasally in rabbits (Oryctolagus cuniculus), guinea pigs (Cavia porcellus), hamsters (Mesocricetus auratus) and mice (Mus musculus). Gross and microscopic lesions, localization of CBM antigen in the respiratory tract, development of antibody, and ability to reisolate the CAR bacillus were studied in animals killed at 2-, 4-, or 8-week intervals postinoculation (PI). In rabbits, although no histopathological changes were observed in the respiratory tract, CBM antigen was detected on the ciliated epithelium of the respiratory tract, and serum CBM antibody was also detected 4 and 8 weeks PI. In guinea pigs, no histopathological changes were noted, CBM antigen was detected in the respiratory tract 2 and 4 weeks PI but not 8 weeks PI, and serum CBM antibody was detected 4 and 8 weeks PI. In hamsters, mononuclear cell proliferation in the submucosa of the bronchus and trachea was observed 8 weeks PI. CBM antigen was detected at first in the nasal cavity 2 weeks PI and in the lower respiratory tract 4 and 8 weeks PI and serum CBM antibody was detected 4 and 8 weeks PI. In mice, histopathological changes, CBM antigen and CBM antibody were observed. CBM was reisolated from the tracheal washouts of hamsters and mice 8 weeks PI but not from those of rabbits and guinea pigs. These results confirm and extend previous reports of experimentally-induced CAR bacillus infection in mice, guinea pigs, and rabbits. To this list of susceptible laboratory animals, we now add hamsters.(ABSTRACT TRUNCATED AT 250 WORDS)     

Susceptibility of experimental animals to reinfection with Clonorchis sinensis

The present study observed the resistance to reinfection with Clonorchis sinensis in various experimental animals including mice, guinea pigs, rabbits, and dogs, as well as rats and hamsters. The resistance rates to reinfection in rats, mice, hamsters, guinea pigs, rabbits, and dogs were 79.7%, 58.0%, -12.6%, 54.8%, 62.6%, and 6.0%, respectively. Worms recovered from reinfected rats and mice were immature, and significantly smaller than those from the primarily infected (P < 0.01), whereas those from other animals were fully matured to adults. These findings indicate that the protective response against reinfection with C. sinensis is prominent in rats and mice, and that they may be a good animal model to investigate the mechanism of resistance to reinfection with C. sinensis.     

Comparative respiratory system mechanics in rodents.

Because of the wide utilization of rodents as animal models in respiratory research and the limited data on measurements of respiratory input impedance (Zrs) in small animals, we measured Zrs between 0.25 and 9.125 Hz at different levels (0-7 hPa) of positive end-expiratory pressure (PEEP) in mice, rats, guinea pigs, and rabbits using a computer-controlled small-animal ventilator (Schuessler TF and Bates JHT, IEEE Trans Biomed Eng 42: 860-866, 1995). Zrs was fitted with a model, including a Newtonian resistance (R) and inertance in series with a constant-phase tissue compartment characterized by tissue damping (Gti) and elastance (Hti) parameters. Inertance was negligible in all cases. R, Gti, and Hti were normalized to body weight, yielding normalized R, Gti, and Hti (NHti), respectively. Normalized R tended to decrease slightly with PEEP and increased with animal size. Normalized Gti had a minimal dependence on PEEP. NHti decreased with increasing PEEP, reaching a minimum at approximately 5 hPa in all species except mice. NHti was also higher in mice and rabbits compared with guinea pigs and rats at low PEEPs, which we conclude is probably due to a relatively smaller air space volume in mice and rabbits. Our data also suggest that smaller rodents have proportionately wider airways than do larger animals. We conclude that a detailed, comparative study of respiratory system mechanics shows some evidence of structural differences among the lungs of various species but that, in general, rodent lungs obey scaling laws similar to those described in other species.     

Nonrebreathing valve system for small animal respiratory measurements.

Flow resistence, frequency response, and backflow characteristics of a nonrebreathing valve system applicable to measuring small animal respiratory volumes are described. Unidirectional valves, molded from liquid resin, were fitted into a modified Y tube for direct use on an endotracheal tube or face mask. Valve size and dead space volume can be scaled to fit several small animal species. In this system, valve resistance was 2.0 and 5.6 mm of water for steady flow rates of 0.5 and 3.0 1/min, respectively.     

Resistance of Erythrocytes of Hibernating Mammals to Loss of Potassium during Hibernation and during Cold Storage

In two species of hibernators, hamsters and ground squirrels, erythrocytes were collected by heart puncture and the K content of the cells of hibernating individuals was compared with that of awake individuals. The K concentration of hamsters did not decline significantly during each bout of hibernation (maximum period of 5 days) but in long-term bouts in ground squirrels (i.e. more than 5 days) the K concentration of cells dropped significantly. When ground squirrels were allowed to rewarm the K content of cells rose toward normal values within a few hours. Erythrocytes of both hamsters and ground squirrels lose K more slowly than those of guinea pigs (nonhibernators) when stored in vitro for up to 10 days at 5°C. In ground squirrels the rate of loss of K during storage is the same as in vivo during hibernation, and stored cells taken from hibernating ground squirrels also lose K at the same rate. The rate of loss of K from guinea pig cells corresponded with that predicted from passive diffusion unopposed by transport. The actual rate of loss of K from ground squirrel cells was slower than such a predicted rate but corresponded with it when glucose was omitted from the storage medium or ouabain was added to it. Despite the slight loss of K that may occur in hibernation, therefore, the cells of hibernators are more cold adapted than those of a nonhibernating mammal, and this adaptation depends in part upon active transport.     

Morphometric analysis of the translocation of lumenal membrane between cytoplasm and cell surface of transitional epithelial cells during the expansion-contraction cycles of mammalian urinary bladder

The flow of membrane between the cytoplasm and the lumenal surface during the expansion-contraction cycle of urinary bladder was estimated by stereological examination of electron micrographs of urothelial cells from guinea pigs, gerbils, hamsters, rabbits, and rats. The quantitative data obtained allowed an approximation of the surface area, volume, and numbers of lumenal membranelike vesicles and infoldings per unit volume of cytoplasm. Depending upon the species, approximately 85 to approximately 94% of the membrane surface area translocated into and out of the cytoplasm was in the form of discoidal vesicles. The remainder was accounted for by infoldings of the lumenal plasma membrane. The density of vesicles involved in transfer of membrane was quite similar in all the species examined, except guinea pigs which yielded lower values. In contrast, the densities of the total cytoplasmic pools of discoidal vesicles potentially available for translocation varied greatly among the different species. In general, species of animals with a highly concentrated urine had a greater density of discoidal vesicles than species with a less concentrated urine. This correlation may indicate an authentic relationship between lumenal membranes and the tonicity of urine, such as increased membrane recycling or turnover with increasingly hypertonic urine; or it may signify the existence of some other, more obscure relationship.     

Damaging action of dithizone on insulin-releasing cells

Alterative action of dithizone was investigated in the experiments on various species of animals (fish, frogs, pigeons, mice, guinea pigs, golden hamsters, rats, rabbits, cats and dogs). The data received support the previously advanced suggestion that unsaturated (electrophilic) zinc complex formation is the basic mechanism of the alterative chelant's action.     

Karyotypes of Pneumocystis carinii derived from several mammals

Pneumocystis carinii is the most important opportunistic pathogen of humans in the world. Pneumocystis carinii is experimentally detected in the lungs of rats, mice, rabbits, and monkeys, however, the organisms from different mammals are identical in microscopic morphology. The present study tried to find out more mammalian hosts of P. carinii and also to differentiate the organisms from different mammals by karyotyping. Rats, mice, hamsters, rabbits, cats, and dogs were successfully infected by P. carinii, but guinea pigs and pigs were not. Karyotype of P. carinii from rabbits showed similar size range of chromosomes with that of the prototype, but in different pattern. The patterns from cats and dogs were also different from that of rats. The present study confirms that cats and dogs are infected by P. carinii and at least total three karyotype strains of P. carinii are proven in Korea.     

The biochemistry of aromatic amines: The metabolism of 2-naphthylamine and 2-naphthylhydroxylamine derivatives

1. 2-Naphthylhydroxylamine and 2-nitrosonaphthalene were present in urine of dogs but not of guinea pigs, hamsters, rabbits or rats dosed with 2-naphthylamine. N-Acetyl-2-naphthylhydroxylamine and its O-sulphonic acid and O-glucosiduronic acid were not detected in the urine of any of these species. 2. Bile from rats dosed with 2-naphthylamine contained (2-naphthylamine N-glucosid)uronic acid and 6- and 5,6-substituted derivatives of 2-acetamidonaphthalene. 2-Amino-1-naphthyl and 2-acetamido-1-naphthyl derivatives, 2-naphthylhydroxylamine and its N-acetyl derivative or conjugates of these were not detected. Bile from a dog dosed with 2-naphthylamine contained no 2-amino-1-naphthyl derivatives. 3. 2-Naphthylhydroxylamine was metabolized by the dog, rat and guinea pig to the same products as those formed by these species from 2-naphthylamine. Rabbits formed mainly 2-amino-1-naphthyl derivatives; these are minor metabolites of 2-naphthylamine in this species. 4. (N-Acetyl-2-naphthylhydroxylamine O-glucosid)uronic acid was excreted in the urine and the bile of rats and in the urine of guinea pigs and rabbits dosed with N-acetyl-2-naphthylhydroxylamine. 5. After the administration of 2-acetamidonaphthalene, (N-acetyl-2-naphthylhydroxylamine O-glucosid)uronic acid was detected in the urine of dogs, but not in the urine of other species. The dog excreted an acid-labile cysteine derivative of 2-acetamidonaphthalene, but only traces of the corresponding mercapturic acid. 6. After dosing with N-acetyl-2-naphthylhydroxylamine-O-sulphonic acid, rats excreted derivatives of 2-amino-1-naphthol. 7. 2-Nitrosonaphthalene, N-acetyl-2-naphthylhydroxylamine, N-acetyl-2-naphthylhydroxylamine-O-sulphonic acid, 2-naphthylhydroxylamine-N-sulphonic acid, N-benzyloxycarbonyl-2-naphthylhydroxylamine and N-benzyloxycarbonyl-2-naphthylhydroxylamine-O-sulphonic acid were synthesized.     

Sensibilité comparée de divers animaux de laboratoire à l'infection par instillations nasales de la phase saprophytique d'Emmonsia crescens Emmons & Jellison, 1960: Fréquence et intensité du parasitisme,réactions histopathologiques

Comparative observations were made on the development of Emmonsia crescens in the lungs of laboratory rats and mice, golden hamsters and guinea pigs after a nasal instillation of a heavy suspension of the saprophytic phase of the fungus. 95% of 80 experimental rats were found to be parasited against 80% of 200 inoculated mice, while only 30% of 70 hamsters and all of 4 guinea pigs showed an infection. The lungs of the mice, rats and guinea pigs were frequently more heavily infected than those of the hamsters. In addition, the adiaspores obtained from the mice and rats had, on average, a diameter double those from the hamsters and their walls were thicker. Thus, the laboratory mice and rats were shown to be better hosts of E. crescens than were golden hamsters.     

Reaction of various experimental animals to exposure to acetylcholine or histamine, and morphological observations of bronchial smooth muscle

We investigated the sensitivity of the airway of various experimental animals to acetylcholine (ACh) and histamine (Hist). The experimental animals were exposed to 0.1% ACh or 0.05% Hist. Guinea pigs and rabbits exhibited an asthmatic reaction to both chemicals, but rabbits seemed to have a milder reaction than guinea pigs to both chemicals. Mice, rats and hamsters showed no reaction. We then performed a morphological study of the airways of 5 species in order to clarify the reason for their different reactivities to ACh and Hist. In the morphological study, abundant smooth muscle could be seen in the terminal bronchioles and respiratory bronchioles of guinea pigs and rabbits. In contrast, animals of other species had little smooth muscle in either site. Mice had no respiratory bronchioles. Consequently, we concluded that there is a high correlation between sensitivity to ACh and Hist and the extent of smooth muscle distribution around the airway.     

Uptake and retention of3H-estradiol by gonadotrophs and lactotrophs in the pituitary glands of the guinea pig,hamster and gerbil

Summary Nuclear uptake and retention of³H-estradiol by luteinizing hormone (LH) and prolactin (PRL) cells was examined in three species of rodents (guinea pigs, hamsters and gerbils) using the combined techniques of immunocyto-chemistry and autoradiography. Castrated animals were injected with³H-estradiol and decapitated 1.5 h later. The pituitary glands were processed for thaw-mount autoradiography followed by conventional immunocytochemical staining for LH and PRL.³H-estradiol accumulated in more than 80% of the anterior pituitary cells in the gerbils, while only 33 and 22% of the cells accumulated³H-estradiol in the hamsters and guinea pigs, respectively. A varying percentage of immunoreactive LH and PRL cells in all three species were found also to contain binding sites for estradiol. Some LH and PRL cells in hamsters and guinea pigs and only some in PRL cells of gerbils were found to be devoid of grains. Quantitative analysis revealed that the number of grains per nucleus differed considerably from cell to cell. LH cells of guinea pigs accumulated much larger amounts of³H-estradiol than did the PRL cells, while the LH cells in the hamsters and gerbils accumulated only slightly more³H-estradiol than the PRL cells.These results confirm the previous observations in rats and baboons that demonstrated tremendous species differences in percentage of cells in the anterior pituitary gland that accumulated³H-estradiol. Also, these data suggest that there are functionally heterogeneous cell types among the LH and PRL cells in hamsters, guinea pigs and gerbils as has been previously demonstrated in rats and baboons.     

Species differences in hepatic peroxisome proliferation, cell replication and transforming growth factor-beta1 gene expression in the rat, Syrian hamster and guinea pig

The objective of this study was to evaluate species differences in the hepatic effects of three potent rodent peroxisome proliferators, namely methylclofenapate (MCP), ciprofibrate (CIP) and Wy-14,643 (WY), particularly with respect to effects on replicative DNA synthesis and transforming growth factor-beta1 (TGF-beta1) gene expression. Male Sprague-Dawley rats, Syrian hamsters and Dunkin-Hartley guinea pigs were given daily oral doses of 0 (corn oil) and 75 mg/kg MCP for periods of 6 and 21 days. Syrian hamsters and guinea pigs were also treated with 25 mg/kg CIP and 25 mg/kg WY. Relative liver weights were significantly increased in peroxisome proliferator-treated rats and Syrian hamsters, but not in guinea pigs. Hepatic peroxisomal (palmitoyl-CoA oxidation) and microsomal (lauric acid 12-hydroxylase) fatty acid oxidising enzyme activities and CYP4A isoform mRNA levels were significantly increased in rats and Syrian hamsters, whereas only minor effects were observed in the guinea pig. Replicative DNA synthesis was studied by implanting 7-day osmotic pumps containing 5-bromo-2'-deoxyuridine during study days -1 to 6 and 14 to 21. Hepatocyte labelling index values were increased by MCP in the rat, but neither MCP, CIP nor WY produced any significant effect on replicative DNA synthesis in the Syrian hamster and guinea pig. MCP treatment increased TGF-beta1 and insulin-like growth factor II/mannose-6-phosphate (IGFII/Man6P) receptor gene expression in the rat. In the Syrian hamster, effects on TGF-beta1 and IGFII/Man6P receptor gene expression were also observed in some instances, whereas TGF-beta1 mRNA levels were essentially unchanged in the guinea pig. These results provide further evidence for marked species differences in response to rodent peroxisome proliferators. While peroxisome proliferators produce a wide spectrum of effects in rat liver, other species such as the Syrian hamster and guinea pig are less responsive and in the case of some endpoints (e.g., cell replication) may be refractory.     

A comparison of intestinal permeability between humans and three common laboratory animals

Intestinal permeability of humans and three species of experimental animals was assessed by the oral administration of the three non-metabolizable sugars: lactulose, rhamnose and mannitol and collecting all the urine produced in a specified time. The total percentage recovery of the permeability markers was determined by high performance liquid chromatographic assays of urinary aliquots. The permeability of the human gut to mannitol was substantially greater than that of rats, guinea pigs, or hamsters (18-, 6- and 29-fold increases, respectively). The permeability to lactulose in humans was somewhat less than that found in guinea pigs (P less than 0.05), but three times greater than that found in rats or hamsters (P less than 0.001). Human rhamnose permeability was substantially greater than that of rats, guinea pigs or hamsters (6-, 2.5-, and 7-fold increases, respectively). The results suggest that the permeability of the human gut to probe molecules is considerably different from that of three common laboratory rodents, but is closest to that of guinea pigs. Possible species differences in the physiological factors which control permeability are discussed.     

Comparative metabolism of the cis and trans isomers of N-nitroso-2-6-dimethylmorpholine in rats,hamsters and guinea pigs

The in vivo metabolism of the cis and trans isomers of N-[3,5-³H] nitroso-2,6-dimethylmorpholine (NDMM) was studied in female Fischer rats, Syrian golden hamsters and guinea pigs by analysis of urinary metabolites using high pressure liquid chromatography (HPLC). Animals were treated by gavage with 12 mg/kg body wt. of NDMM, composed of both isomers and 12 μCi/kg body wt. of either of the separated radioactive isomers (cis or trans). Control animals received 12 mg, 12 μCi/kg body wt. NDMM with both isomers labeled in their natural proportion.There was a substantial increase in the excretion of a particular metabolite, 2-(2-hydroxyl-methyl)ethoxy propanoic acid, in the urine of rats, hamsters and guinea pigs 24 h after received the trans isomer (24, 22 and 13% of the total dose excreted, respectively). A minor metabolite was determined to be 2,6-dimethylmorpholine-3-one, another product of α-oxidation. The metabolite 1-amino-2-hydroxypropanol was identified, indicating that NDMM was metabolized by both α-and β-oxidation.In all three species, animals administered the cis isomer excreted larger amounts of N-nitroso(2-hydroxypropyl)(2-oxopropyl)amine (HPOP) and N-nitroso-bis(2-hydroxypropyl)amine (BHP) products of beta oxidation, than those treated with the trans isomer. Hamsters and guinea pigs treated with the more carcinogenic cis isomer in these species, also excreted twice as much of two other metabolites than was found in the urine of animals given the trans isomer.The trans isomer of NDMM appeared to be preferentially metabolized by α-oxidation and from earlier studies this metabolic pathway seemed to be important in carcinogenesis by NDMM in the rat. The cis isomer might be in a conformation more favorable for β-oxidation and this pathway may be of primary importance in carcinogenesis by NDMM in hamsters and guinea pigs.     

Lung function tests in small experimental animals by means of a signal processing system

For the analysis of the airflow velocity and oesophageal pressure signals of anaesthetized spontaneously breathing small animals (rats and guinea pigs), a signal processing program package was developed for a multiprocessor system (Electronic Measuring Gears Co., Budapest). 4-10 respiratory cycles were analysed in a signal series and the arithmetic mean value was used to increase the accuracy of the method. Since standardization of the respiratory parameters of small animals has not yet been specified, the normalization of volume values per 100 cm2 body surface is proposed.