Healthy Hamsters Research Articles

Pulmonary Surfactant as a Vehicle for Intratracheal Delivery of Technetium Sulfur Colloid and Pentamidine in Hamster Lungs

Tracheal instillation of pentamidine in a surfactant vehicle may be an effective direct method of antibiotic delivery to the lungs. In 10 healthy hamsters, we compared the pulmonary distribution of 99mTc sulfur colloid (TcSC) mixed with pentamidine, using as a vehicle either surfactant (n = 5) or saline (n = 5). Each animal was instilled with 0.25 ml/kg of suspension containing 0.0018 mCi TcSC and pentamidine mixed with either surfactant or saline. After 4 h of spontaneous respiration, the lungs were excised, inflated to TLC, dried, and sliced into 3-mm cross sections from apex to base. Autoradiographs were examined to evaluate 99mTc distribution. The surfactant group had detectable radioactivity in 93% of all slices compared with 72% in the saline group (p = 0.02). Six slices per animal (43% of total) and their corresponding autoradiographs were analyzed for distribution of radioactivity. Lung slice area was determined by planimetry, and autoradiograph area was determined by video densitometry. We calculated the fraction of each lung slice with detectable radioactivity. The surfactant group had 41% of the lung slice areas exposed compared with 21% in the saline group (p = 0.02). The coefficient of variation of radioactive intensities within each slice was used as an index of spatial uniformity. There was a trend towards more uniform distribution in the surfactant group, with a narrower range of variation of intensities (1.51 to 2.56) than the saline group (1.95 to 6.47). We conclude that a surfactant vehicle significantly increases airspace deposition of TcSC and pentamidine instilled intratracheally in normal hamster lungs, and may improve uniformity of spread.

Ca2+]i transients in the cardiomyopathic hamster heart.

Intracellular [Ca2+] transients were studied in isolated hearts of healthy and cardiomyopathic hamsters in late failure perfused with glucose or pyruvate. Hearts of healthy hamsters developed similar pressures when perfused with either glucose or pyruvate, and [Ca2+]i transients were comparable in amplitude when perfused with either substrate. On the other hand, hearts of cardiomyopathic hamsters in late failure developed normal pressure when perfused with pyruvate but developed depressed pressure (50%) when perfused with glucose. The amplitude of [Ca2+]i transients fell severely and was associated with a high diastolic [Ca2+]i in cardiomyopathic hamster hearts when the perfusate was switched from pyruvate to glucose. The high phosphomonoester sugars as evidenced by 31P nuclear magnetic resonance studies and the depressed oxygen consumption in the cardiomyopathic hamster hearts perfused with glucose reflect an inhibition in glycolysis and a subsequent decrease in mitochondrial activity. Without an adequate delivery of substrate to the mitochondria in the cardiomyopathic hamster, the myocardium is no longer capable of maintaining its [Ca2+]i homeostasis.

Changes of Heart Muscle Cells in the Dystrophic Hamster (BIO 14.6)

Comparative studies were made morphologically and biochemically on the hearts of an inbred strain of Syrian hamster (BIO 14.6) having a hereditary idiopathic cardiomyopathy, and of unrelated healthy hamster (BIO RB) . Ultrastructural and freeze-etch studies disclosed possible differences in the membrane structure between the diseased and healthy hamsters. The SDS-polyacrylamide gel electrophoresis (SDS-PAGE) of cardiac membranous fractions from diseased hamsters in the later stage of cardiomyopathy showed the quantitative difference at least in two of the composing proteins in comparison with healthy hamsters. The uptake of cholesterol by red blood cells in healthy hamsters was faster than that of cardiomyopathic hamsters. These results suggested the presence of abnormality in the membrane of heart cells of cardiomyopathic hamsters.The partially purified myocardial Ca2+ activated neutral protease (CANP) from healthy hamsters showed two main bands of approximately 78 and 74 kilodalton and several faint bands on SDS-PAGE. The enzyme was significantly activated by Ca2+ at pH 6.8 to 7.4. Myocardial myosin B from healthy hamsters demonstrated the gradual, progressive degradation of its main component during the incubation with CANP in the presence of Ca2+, and SDS-PAGE showed a similar pattern to that of myocardial myosin B from cardiomyopathic hamsters. The specific activity of the CANP showed no difference between the two groups. In contrast, the inhibitory effect of CANP inhibitor on CANP was lower in the fraction from diseased hamsters than that of healthy ones. The result of reduced Ca2+ uptake by microsomal vesicles of heart cells from diseased hamsters in comparison with that of healthy ones suggested an augmentation of intracellular Ca2+ concentration in heart cells of diseased hamsters.These two situations, membrane abnormality and CANP activity in association with CANP inhibitor, probably play a critical role for the genesis of cardiomyolysis in cardiomyopathic hamsters.

Interactions among the Effects of Aging, Chronic Disease, and Stress on Adrenocortical Function in Syrian Hamsters*

This study examined the effects of aging and chronic congestive heart failure on plasma corticosterone and cortisol levels in hamsters. It also assessed the effects of aging and heart failure on glucocorticoid responses to acute and chronic stress. Aging in healthy hamsters increased plasma cortisol levels, decreased corticosterone levels, and did not change total glucocorticoid levels. A similar pattern occurred as cardiomyopathic (CM) hamsters aged, until they developed severe heart failure. Plasma cortisol levels fell in CM hamsters with severe heart failure, and corticosterone levels remained low, so total glucocorticoid levels fell. Adrenocortical function similarly declined in very old healthy hamsters near the ends of their lives. Adrenocortical responses to acute and chronic stress were diminished in old healthy hamsters, and heart failure in CM hamsters also reduced the glucocorticoid responses to chronic stress. However, heart failure greatly enhanced the cortisol and total glucocorticoid responses to acute stress, but not that of corticosterone. These data suggest a number of conclusions. First, aging clearly changes the the ratio of corticosterone to cortisol in hamster plasma without changing total glucocorticoid levels and blunts adrenocortical responses to acute and chronic stress. Second, ill health, in the form of severe heart failure in CM hamsters and very old age in health hamsters, decreases adrenocortical function. At the same time, heart failure greatly enhances cortisol responses to acute stress. These results indicate that aging and chronic disease in hamsters have many similar effects on adrenocortical function, but that disease alone sensitizes them to the effects of acute stress.

Isolation of a Campylobacter-like organism from healthy Syrian hamsters (Mesocricetus auratus).

A Campylobacter-like organism was isolated from the ilea of normal hamsters. The organism was isolated from an ileal homogenate which was passed through a filter (0.65-micron pore size) and cultured on blood-agar plates in a microaerophilic atmosphere at 37 degrees C. Pinpoint translucent colonies were first observed after 120 h of incubation. The isolated organism measured 2.0 to 3.5 microns in length (excluding flagella) by 0.17 to 0.25 micron in width and typically had a single terminal sheathed flagellum. The organism was oxidase, catalase, and urease positive, reduced nitrates, and was susceptible to nalidixic acid (30-micrograms disk) and resistant to cephalothin (30-micrograms disk). Unlike Campylobacter pylori subsp. mustelae, this organism did not hydrolyze indoxylacetate. Immunofluorescence studies with a Campylobacter species-specific monoclonal antibody (8322-2E6) revealed the presence of numerous positively stained organisms within the crypt epithelial cells of the hamsters from which this organism was isolated. The role of this organism in the pathogenesis of proliferative ileitis in hamsters is uncertain, as is the taxonomic relationship of this organism to other members of the genus Campylobacter.

Campylobacter cinaedi is normal intestinal flora in hamsters.

During the course of studies to reproduce proliferative enteritis in hamsters, Campylobacter cinaedi was recovered from the feces of the majority of healthy hamsters obtained from two commercial sources. The organisms were cultured by using filtration, a nonselective medium, and a microaerophilic atmosphere containing hydrogen. Isolation was hindered by the fastidious nature of C. cinaedi and by the presence of other Campylobacter species in the hamster intestine. All hamster C. cinaedi isolates were phenotypically similar to C. cinaedi ATCC 35683. Comparison of whole-cell protein profiles of one hamster isolate with a reference strain of C. cinaedi by sodium dodecyl sulfate-polyacrylamide gel electrophoresis and immunoblotting with C. cinaedi-specific rabbit antiserum supported the phenotypic identification of these isolates. Hamsters may be an animal reservoir for human C. cinaedi infections.

Conjunctival epithelial cells infected with Chlamydia trachomatis express HLA-DR antigens.

The carbon dioxide laser is frequently used for the treatment of Human Papilloma Virus infections and intraepithelial neoplasia of the lower genital tract. There has been mounting concern about possible health hazards from inhaling the CO₂ laser plume or from contact with particles of tissue or liquid produced during vaporization procedures. Five healthy young-adult female Syrian hamsters were housed in individual cages. Hamsters were selected because they were readily available, easy to maintain, lacked appreciable indigenous viral flora or infections, and were susceptible to oncogenic viruses. A special cage was constructed which allowed the hamsters to be bathed in a high concentration of lazer smoke which they were forced to inhale. Ninety-three patients underwent laser therapy for intraepithelial neoplasia or condylomata acuminata. The hamsters were exposed to laser fumes once every 11 days. At the end of the study, all animals were autopsied and samples of grossly abnormal tissue were obtained. When no gross abnormal findings were present the cheek pouches and entire respiratory tracts were removed. One animal developed an angiosarcoma. None of the hamsters had light microscopic changes of Human Papilloma Virus infection. None of the viral DNA probes used hybridized to nuclear DNA in the epithelial cells. Electron microscopy did not detect any viral inclusions. The present study did not show histopathologic changes in the exposed hamster respiratory tracts suggesting carcinogenesis, Human Papilloma Virus infection or any other acute process. The development of angiosarcoma in one animal may be viewed with concern, but is most likely incidental.

Alprazolam reduces stress-induced mortality in cardiomyopathic hamsters.

These experiments examined the role of several variables involved in the production of serious, stress-induced disease. Experiments 1 and 2 indicated that stress may not be medically dangerous except in animals with a predisposition or vulnerability to disease. Repeated exposure to cold-immobilization produced no detectable ill effects in healthy hamsters, but it was lethal for cardiomyopathic hamsters (CMHs). Experiment 3 showed that stressor intensity was also critical to the outcome of stress. CMHs succumbed when they were stressed in the supine position, but not when they were immobilized in the less stressful prone position. In Experiment 4, we attempted to reduce the stressfulness of cold-immobilization with the anxiolytic alprazolam. Alprazolam effectively blocked stress-induced mortality. In addition, we found that poststress body temperature was a crude predictor of an animal's ability to cope with stress. Alprazolam prevented CMHs from developing stress-induced hypothermia.

Heart protein kinase C activity increases during progression of disease in the cardiomyopathic hamster

Protein kinase C activity in the particulate fraction of the heart increases two-fold during mid-stage of disease in the cardiomyopathic hamster. No change in the corresponding enzyme activity occurs with aging in healthy control hamsters. In the solubilized particulate fraction of hearts from both myopathic and control animals, Ca++/phospholipid-dependent endogenous phosphorylation of proteins of Mr 26, 31, 45, 53, 69, 98, 105 and 126 kDa are observed. All of these proteins are more highly phosphorylated in the protein kinase C-enriched preparation from the myopathic heart compared to the control. No significant differences between myopathic and control hamsters are observed in the activities of protein kinase C or phosphoinositide-specific phospholipase C from heart cytosol.

Aging, stress, and chronic disease interact to suppress plasma testosterone in Syrian hamsters.

The effects of old age, chronic disease, and stress on testicular function were examined in Syrian hamsters living on a 12-hr photoperiod. Plasma testosterone concentrations and testes weights were maintained in healthy hamsters 16-19 months of age, but chronic stress decreased plasma testosterone in these old hamsters and not in younger ones (8-11 months of age). Chronic disease in the form of congestive heart failure (CHF) in cardiomyopathic hamsters also decreased plasma testosterone and testes weights, although it is not clear what aspects of this disease affected testicular function. There was an interaction between disease and stress, in that chronic stress produced lower plasma testosterone and testes weights in hamsters with heart failure than in age-matched stressed, healthy hamsters. It appears that younger hamsters can maintain reproductive function during stress, but older ones may not be able to do so. Congestive heart failure in hamsters clearly impairs normal reproductive function by itself; it also makes them more susceptible to stress, so that combining stress and disease results in almost complete suppression of plasma testosterone levels.

Utilization of monoclonal antibodies to evaluate the involvement of Campylobacter jejuni in proliferative ileitis in Syrian hamsters (Mesocricetis auratus).

The role of Campylobacter jejuni in the pathogenesis of proliferative ileitis in Syrian hamsters was evaluated with monoclonal antibodies of different specificities. Monoclonal antibodies were produced with two different specificities: one for all members of the genus Campylobacter tested (antibody 8322-2E6) and one for C. jejuni and Campylobacter coli (antibodies 841-2A11, 841-4C6, and 841-5B1). Heal sections from healthy hamsters, from hamsters with naturally occurring proliferative ileitis, and from hamsters with experimentally induced proliferative ileitis were examined by using fluorescein isothiocyanate-labeled, Campylobacter sp.-specific 8322-2E6 and tetramethylrhodamine isothiocyanate-labeled C. jejuni-C. coli-specific 841-2A11 for direct dual-labeling immunofluorescence. Organisms which stained with the C. jejuni-C. coli-specific monoclonal antibody were observed in the ileal lumens and along the distal tips of the villi of hamsters with either experimentally induced or naturally occurring proliferative ileitis. In contrast, organisms identified by the Campylobacter sp.-specific monoclonal antibody were present deep within the villus lumens and crypts and intracellularly within the apical portions of the epithelial cells. No organisms stained with the C. jejuni-C. coli-specific monoclonal antibody were observed in ileal sections from control hamsters; an occasional intracellular organism stained with the Campylobacter sp.-specific monoclonal antibody was observed in 2 of 10 control hamsters. Thus, at least two immunologically distinct patterns were identified in ileal sections from hamsters with proliferative ileitis. On the basis of these results, we conclude that the organism seen intracellularly in ileal sections from hamsters with proliferative ileitis is a member of the genus Campylobacter but that it probably is not C. jejuni or C. coli.

Gonadal function during prolongation of life produced by constant light in hamsters with heart failure

In a prior experiment, we showed that living in constant light prolonged the lives of cardiomyopathic (CM) hamsters dying of heart failure. One possible explanation for this therapeutic effect related to the physiological effects of living in short and long days. The control hamsters for our constant light experiment lived in light/dark 12:12, a short day regimen which produces inhibitory effects on the gonadal function of healthy hamsters. To see whether the CM hamster responded to short days like healthy hamsters, we (a) measured gonadal and seminal vesicle mass and plasma testosterone at 1 year of age in CM hamsters raised in the 2 light conditions and (b) assessed testicular size repeatedly over the lives in a second group of hamsters raised in the 2 light conditions. As in healthy hamsters, we found gonadal function in CM hamsters to be greatly inhibited by LD 12:12. Importantly, we replicated our finding that living in constant light prolongs the life of CM hamsters in heart failure. We also found that the stress and trauma inherent in our repeatedly using surgery to assess testicular size acted as an additional risk factor controlling the lifespan of these animals. Our findings suggest that a photoperiodic effect of day length should be considered as one possible explanation of the mechanism of prolongation of life produced in hamsters with heart failure by constant light.

Increases responsiveness to stimulation of α- but not β-adrenoceptors in the hereditary cardiomyopathy of the Syrian hamster. Intact adenosine- and cholinoceptor-mediated isoprenaline antagonistic effect

The effects of phenylephrine (in the presence of propranolol) or isoprenaline and of adenosine or carbachol (alone and in the presence of isoprenaline) were studied on the force of contraction in electrically driven papillary muscles isolated from the hearts of cardiomyopathic (strain BIO 8262) and age-matched, healthy Syrian hamsters. All experiments were performed in the so-called prenecrotic stage of the disorder within the first 30 days of life. Phenylephrine exerted a positive inotropic effect in all preparations from the cardiomyopathic hamsters. In contrast, in thirteen preparations from healthy Syrian hamsters, phenylephrine increased force of contraction in only four preparations. The positive inotropic effect of isoprenaline was similar in both cardiomyopathic and healthy Syrian hamsters. Adenosine and carbachol apparently reduced the isoprenaline-induced increase in force of contraction in both cardiomyopathic and healthy Syrian hamsters. We conclude that an increased responsiveness to α-adrenergic stimulation occurs in the hearts of cardiomyopathic Syrian hamsters and may be related to the myocardial injury occuring in this syndrome. An increased responsiveness to β-adrenoceptor stimulation or an impaired adenosine-mediated or cholinoceptor-mediated feedback inhibition is unlikely to play a role in the aetiology of this syndrome.

Use of motor performance tests to differentiate aging effects from disease effects

The present study has demonstrated that behavioral testing can provide non-invasive methods for monitoring the time-courses of aging and disease processes. Performance on two of our tests changed linearly with increasing age in both cardiomyopathic and healthy hamsters, but these changes occured at an earlier age in the CM hamsters than in healthy control hamters. In addition, healthy hamsters showed age-related changes in performance on some tests, while sick CM hamsters did not show parallel changes. These results indicate that disease can modify the rate of change in some markers of aging, and thus they suggest that disease might be able to modify the aging process. However, such a preliminary hypothesis requires much further work. Performance on another behavioral test was shown to be stable throughout much of the lifespan of healthy hamsters, and yet disease in CM hamsters was clearly able to affect it. Thus it was possible to find some tests which discriminated between aging and disease effects, but only because the time-course of the disease we were studying was well defined. Most importantly, these results have suggested a way of thinking about the problem of disease in aging studies that may be more fruitful than others previously used. Examining the changes over time in both healthy subjects (putatively disease-free) and those with disease should allow one to determine which age-related changes are dependent on the presence of organic disease and to separate these from the changes which might inevitably occur solely from increasing age.

Verapamil preserves adenine nucleotide pool in cardiomyopathic Syrian hamster.

There is a decrease in total adenine nucleotides, cyclic AMP (cAMP), ATP/total ADP, and phosphocreatine (PCr)/creatine (Cr) both in situ and in the perfused heart in the heart failure stage of the cardiomyopathic Syrian hamster. There were decreases in developed pressure, dP/dt, and O2 consumption associated with the decrease in total adenine nucleotides and cAMP. Cardiomyopathic Syrian hamsters (180-240 days old) with congestive heart failure were given water with the calcium entry blocker, verapamil, as an additive 2 mo before death. In the cardiomyopathic group given verapamil the adenine nucleotides, cAMP, and high-energy phosphates were preserved and cardiac performance was not significantly different from that of the verapamil-treated healthy hamsters at the time of death. Pretreatment of cardiomyopathic animals with verapamil (6.6 mg verapamil/ml water consumed by drinking) resulted in significantly higher ATP/total ADP and PCr/Cr compared with nontreated cardiomyopathic hamsters. This is the first report demonstrating that a calcium entry blocker may improve cardiac performance and preserve total adenine nucleotides during the heart failure stage of the cardiomyopathic hamster.

Epidemiology of colitis induced by Clostridium difficile in hamsters: application of a bacteriophage and bacteriocin typing system.

The epidemiology of colitis induced by Clostridium difficile in hamsters was studied with a new bacteriophage and bacteriocin typing system. Fatal enterocolitis was induced by administration of N-formimidoyl thienamycin. Environmental cultures were obtained repeatedly throughout the experiments. Thirteen percent of 90 healthy hamsters were already colonized with C difficile on arrival from the supplier. Mortality from enterocolitis after antibiotic administration was 75% and was not diminished by use of a laminar-flow facility. The same uncommon bacteriocin type (83/1309/2329) of toxigenic C difficile that colonized hamsters on arrival was recovered from the cecal contents of all hamsters dying with enterocolitis and from most environmental isolates. Previously uncolonized , antibiotic-treated hamsters placed into cages where animals had died from enterocolitis also developed enterocolitis with the same bacteriocin type (83/1309/2329), an outcome suggesting acquisition of C difficile from the environment.

Stress-induced heart failure.

Stress produced heart failure in cardiomyopathic hamsters (CMHs) with subclinical heart disease. CMHs exhibited a variety of peripheral manifestations of heart failure including subcutaneous edema, fluid in the abdominal and thoracic cavities, and increased organ weight. In contrast, stress did not produce heart failure in healthy hamsters. These data indicate that the presence of covert heart disease can dramatically alter the pathogenic consequences of stress.

Adenosine 3’ ,5’-Cyclic Monophosphate and Guanosine 3’,5’-Cyclic Monophosphate Levels in Tumour, Plasma and Urine during the Growth of a Fibrosarcoma in Hamsters

Levels of cyclic AMP and cyclic GMP were measured in tumours, plasmas, and urines from groups of hamsters at different times after implantation of a fibrosarcoma (of kidney cell origin) and in kidney cortices, plasmas and urines from healthy hamsters. Initially, tumour cyclic AMP levels were significantly lower than those in kidney cortex but this difference disappeared during the growth of the tumour. Plasma and urine cyclic AMP levels were significantly depressed during all phases of tumour growth. In general, cyclic GMP levels were unaffected by the presence of a tumour except when hamsters carried a very high tumour load.

Spontaneous glomerular basement membrane changes in the golden Syrian hamster (Mesocricetus auratus): a light and electron microscope study.

Changes in apparently healthy hamsters, consistent with proteinuria, are reported, but no IgG deposits or amyloid in the glomeruli were detected. Further investigation is required into the significance and the aetiology of these, as yet, obscure alterations.

The cardiomyopathy of the Syrian hamster (strain BIO 8262)--hypertrophic or dystrophic?

Chemical as well as cytophotometric studies were carried out on myocardium of cardiomyopathic hamsters of strain BIO 8262 and of healthy control hamsters of strain CLAC. Our interest was to find out whether the cardiomyopathic hamsters suffer from hypertrophic cardiomyopathy or not. The heart muscle mass was only slightly increased in the older cardiomyopathic hamsters when compared with the controls. This increase was accompanied by an elevated content of total DNS, RNS and protein. Furthermore, the number of hyperdiploid heart muscle cells was slightly increased in the older diseased animals. However, all these changes were of minor degree. Thus, a distinct hypertrophying process in the myocardium of the cardiomyopathic hamsters can be excluded. On the other hand, the connective tissue components (polysaccharides and collagen) were distinctly increased in the hearts of older cardiomyopathic hamsters. This is in accordance with morphological investigations, in which replacement of necrotic myocardium by fibrosis could be detected.