Biomedical subjects

B H Natelson

Publications and source records attributed to B H Natelson.

At least 91 records · Page 5Linked to original sources

PubMed1993

Persistent plasma cholesterol elevations are produced by one or three stressor exposures in rats fed a normal laboratory diet.

Typically, stress-related elevations in rat plasma cholesterol (CHOL) require preexposure to diets high in fats or cholesterol and lengthy stressor protocols. We report on two studies in which we measured plasma CHOL 22-h poststressor in rats fed Purina Laboratory Rodent Chow and exposed to 3 (3-day) or 1 (1-day) daily stressor sessions [40, 2 mA tailshocks]. In the first study, both the 3-day and 1-day groups exhibited moderately elevated morning plasma CHOL 22-h poststressor compared to nonshocked controls. Along with the groups in the first study, a second study included a restricted food control, rats transferred to the stressor environment, and rats simply transferred to an adjacent room. Neither restricted feeding nor the room transfers had an effect on morning plasma CHOL. However, the 3-day and 1-day groups again exhibited moderately elevated CHOL. Previous reports did not find elevated plasma CHOL in rats given a single stressor exposure when sampled at the end of the stressor session. Thus, the persistently elevated morning CHOL exhibited by the 1-day group may develop over time. The relatively slow development of plasma CHOL elevations may be related to the time course of stressor-induced thyroid suppression.

Animals↗

PubMed1993

Effect of life in a constant light environment on the course of hypertension in Dahl rats.

An important goal for biobehavioral scientists is to evaluate treatments that might extend life in the presence and absence of disease. The prototypic example of such a treatment is food restriction. Importantly, we have shown that exposure to a life-long environment of constant light extends life in hamsters with severe, life-threatening heart disease. The purpose of this experiment was to determine whether constant light would also extend the life of rats with an inherited form of hypertension. Constant light neither delayed the progression of hypertension nor extended life in this model. These data suggest that constant light may have a more limited use as an experimental therapeutic modality to extend life as compared to food restriction.

Adrenal Glands↗

PubMed1993

Constant light extends life in hamsters with heart disease.

Our previous work has shown that constant light can prolong the life of hamsters with heart disease. Although we have seen this result several times, constant light was not protective in our most recent experiment. We undertook this study because we had changed some conditions. As in previous experiments, we found that life in constant light extended life for cardiomyopathic hamsters as compared with others living in a 12:12-hr light:dark environment. A second factor affecting survival was the number of hamsters in a group. Hamsters housed in groups of five lived longer than those housed in groups of two under the same lighting conditions. Data from one experiment suggested that a short photoperiod (6:18 light:dark) was also protective. Although these experiments indicate that the protective effects of different light:dark schedules are not simple ones, they are important because their use may prove to be a helpful adjunct in the treatment of congestive heart failure.

Animals↗

PubMed1993

Brain-heart interactions. The neurocardiology of arrhythmia and sudden cardiac death.

Neuroanatomic connections between the brain and the heart provide links that allow cardiac arrhythmias to occur in response to brain activation. Recognition and analysis of such links in the pathogenesis of malignant cardiac arrhythmia are emphasized in this review. Neurocardiac links have been shown to produce arrhythmia both experimentally and clinically; specific examples, including stroke, epilepsy, and environmental stress are presented. We hypothesize that the individual with a diseased heart has a greater likelihood of experiencing cardiac arrhythmia and sudden cardiac death when the neurocardiac axis is activated. Reviewing possible mechanisms of brain-related arrhythmias, we suggest that the nervous system directs the events leading to cardiac damage by raising catecholamine levels and potentially inducing arrhythmia.

Animals↗

PubMed1993

Sudden death. A neurocardiologic phenomenon.

During the last two decades compelling evidence has been provided for the existence of a tight relation between brain activation of unbalanced autonomic function and arrhythmias ending in SCD. Insular and infralimbic cortex exert direct and indirect effects on hypothalamus and other brain stem nuclei in modulating cardiac sympathetic-parasympathetic interactions. Specifically, sympathetic hyperactivity favors the onset of life-threatening cardiac arrhythmias, whereas vagal activation usually exerts relatively protective and antifibrillatory effects. Epileptic activation of cortical brain sites can turn this system on and probably is responsible partially for the increased incidence of unexpected death in this patient population. The role of environmental stress in arrhythmogenesis and SCD is of great importance in the outcome of heart disease.

Animals↗

PubMed1992

A chronic stress state in rats: effects of repeated stress on basal corticosterone and behavior.

The chronic stress state has previously been defined as persistent visceral arousal coupled with behavioral abnormalities. To determine the number of stressor exposures necessary to induce a chronic stress state, male rats were given 2 hours of inescapable shock on 10, 7, 4, or 3 consecutive days. The 3-day stress group had the most pervasive changes in the variables measured: persistently elevated basal plasma corticosterone (CORT), continued weight loss in the post-stressor period, and abnormal behavior. More exposures to the stress regimen did not produce higher CORT levels or greater behavioral changes. Acutely stressed rats, exposed to 1 day of inescapable shock, had persistent CORT elevations without the other changes seen in the 3-day stress group. The data suggest that 3 days of our stress regimen are sufficient to produce a state of chronic stress and that some signs of this state begin to appear as early as the first exposure to our inescapable stress regimen.

Adrenal Cortex↗

PubMed1992

Effect of stress and food restriction on blood pressure and lifespan of Dahl salt-sensitive rats.

OBJECTIVE: To evaluate the long-term consequences of stress in rats with genetic hypertension. DESIGN: Rapp-Dahl salt-sensitive rats, maintained on a low-salt diet, were stressed periodically over 8 weeks during which time their blood pressures were measured. In experiment 1 both stressed and unstressed control rats were given ad libitum access to food. Because of significant differences in body weights, in experiment 2 the unstressed controls were pair-fed to maintain their food intake at a level similar to that of the stressed rats. METHODS: Rats were subjected to 2-h sessions of supine immobilization stress 5 days a week every other week for 8 weeks. Blood pressures were measured during non-stress weeks, at least 4 days after the last exposure to the stressor and at monthly intervals thereafter. Survival curves were also established. RESULTS: In experiment 1 stressed rats developed hypertension at a slower rate than controls and lived significantly longer, but also weighted significantly less than controls, presumably because of diminished food intake. In experiment 2, in which food intake was controlled, body weights were similar in the two groups of rats, and hypertension developed at the same rate in both groups. Survival curves were not significantly different. Food restriction extended life compared with free feeding. CONCLUSIONS: Stress need not have long-term, deleterious health consequences in rats with genetically inherited hypertension, whereas caloric restriction is protective.

Animals↗

PubMed1991

Alcohol-induced brain changes in dogs.

We studied the neuropathologic effects of chronic alcohol ingestion on the brains of healthy, well-nourished, male mongrel dogs. Five experimental dogs were provided 36% of their calories as ethyl alcohol for 1 year. Following killing, their brains were weighed, photographed, sectioned, and processed for computerized morphometric determinations of ventricular size, cortical thickness, and neocortical neuron and glial cell populations. Compared with a similarly handled control group, the alcoholic dog brains showed lateral ventricular enlargement, cortical thinning in the temporal lobe only, and fewer glial cells in the temporal and frontal cortices. There were no statistically significant differences between the alcoholic and control groups in brain weight, frontal or parietal cortical thickness, or neocortical neuron populations. These results imply a disproportionate vulnerability of white matter to the damaging effects of alcohol with consequent lateral ventricular enlargement, and some regional variation in neocortical susceptibility to alcohol-induced cortical thinning and glial cell loss. In general, such changes are consistent with those described in neuroradiologic imaging studies of human alcoholics.

Alcoholism↗

PubMed1990

Effect of different light-dark schedules on survival from heart failure.

Our earlier work showed that life in constant light prolonged life for hamsters with an inherited cardiomyopathy when compared to littermates spending their lives in 24 hour days (lights on 12 hr each day). This study was designed to begin evaluating the mechanism for this effect. 4-5.5 month old cardiomyopathic hamsters (CMHs) were placed on one of 5 different light-dark (LD) schedules for the remainder of their lives: (1) LD 12:12 (moderate total light exposure, short photoperiodic effect, 24 hr daylength); (2) LD 12:13 (same total light as LD 12:12, long photoperiodic effect, non-24 hr daylength); (3) LD 6:30 (less total light than LD 12:12, long photoperiodic effect, non-24 hr daylength); (4) LD 18:6 (more total light than LD 12:12, long photoperiodic effect, 24 hr daylength); (5) constant light (high total light exposure, long photoperiodic effect, non-24 hr daylength). CMHs living on the first two non-24 hr schedules lived longer than LD 12:12 controls. This study therefore suggests that manipulating the biological clock can have positive therapeutic consequences. However, in contrast to our earlier studies, hamsters living in constant light were not protected--perhaps because the hamsters began the treatment later in their lives or because their inherited disease was less severe than had been the case in hamsters used in previous studies. Defining the conditions that diminish or enhance the photobiological effect is an important challenge for future research.

Animals↗

PubMed1990

Effects of repeated stress on T cell numbers and function in rats.

Although stress has been reported to affect various functions of the immune system, the mechanism that mediate these effects remain unclear. Thus we examined the effects that 1, 7, and 14 days of stress could have on various aspects of immune and endocrine function in rats. Rats subjected to repeated stress (7 and 14 days) showed significant decreases in the total number of mononuclear cells, particularly suppressor/cytotoxic (CD8) T cells, in the spleen and blood. The mitogenic responses of T cells to phytohemagglutinin (PHA) and concanavalin-A (Con A) were also significantly diminished at these times, as well as after acute (1 day) stress in the case of PHA stimulation. The mechanisms of this impaired T cell mitogenesis were explored by assessing the effects of stress on T cell interleukin 2 (IL-2) production and T cell responsiveness to IL-2. T cells from repeatedly stressed rat showed a decreased production of IL-2 in response to PHA, although their proliferative response to exogenous IL-2 was normal. Repeated stress also decreased body weight and spleen weight, increased adrenal weight, and decreased plasma levels of triiodothyronine and testosterone. These results suggest that lower levels of IL-2 production during stress could be one reason for the decreased mitogen responsiveness of T cells, often seen with stress. This is important because defective IL-2 production could also lead to significant impairment of immunoregulatory T cell generation and thus a predisposition to malignancy or autoimmune disease that some have associated with stress.

Animals↗

PubMed1990

Effect of stressor intensity on habituation and sensitization of glucocorticoid responses in rats.

This experiment was designed to study the effect of stressor intensity on habituation/sensitization of the adrenocortical stress response in rats. Rats were given 18 shocks in 3-hr daily sessions for 8 days, and a single shock probe before the sessions was used to determine how adrenocortical responsiveness changed with repeated exposure to the stress sessions. When lower intensity shock was given, the changes in plasma corticosterone response to shock probes followed a U-shaped curve--with a response that first habituated to no-shock control levels but later returned to the same magnitude as seen on the 1st probe day. Plasma corticosterone responses in rats given higher intensity shock never habituated and instead demonstrated an increased response indicative of sensitization; a temporal delay of 1 week occurred before sensitization developed. Responsiveness to exogenous adrenocorticotropin 24 hr after the last stress session was monotonically related to the intensity of the stressor presented during the experimental sessions. These data are consistent with the rule from the habituation literature that stimulus intensity is inversely related to the magnitude of habituation. Thus the data extend the dual process theory of Groves and Thompson (1970) to an endocrine respondent. The data also suggest that an explanation as to discrepancies in the literature concerning adrenocortical response to repeated presentation of stressors may relate to differences in the stressor parameters used.

Adrenocorticotropic Hormone↗

PubMed1990

Phase-shifting the light-dark cycle resets the food-entrainable circadian pacemaker.

This experiment examined coupling between two circadian pacemakers, one entrained by light and the other by food. Rats were housed in running wheels: one-half on restricted feeding from 0900 to 1100 h whereas the others were free fed. After timed-fed rats developed bursts of running before 0900 h, all rats were given free access to food. A month later, the light-dark (LD) cycles for one-half the rats in each group were delayed by 6 h. After entrainment to the new LD cycles, all rats were probed with 96-h periods of food deprivation. During these probes, unshifted timed-fed rats ran more than their free-fed controls at 0600-1200 h, but delayed timed-fed rats ran more than their controls at 1200-1500 h, i.e., 6 h later than unshifted rats. Next, the unshifted rats were subjected to a 6-h advance in their LD cycle. One month later, all rats were again probed with food deprivation. Delayed timed-fed rats continued to run more at 1200-1500 h than their free-fed controls, but timed-fed and free-fed phase-advanced rats showed similar activity patterns after the phase advance. However, when activity patterns before these probes were subtracted, timed-fed advanced rats showed greater "responses" to food deprivation at 0001-0300 h than their free-fed controls, i.e., 6 h earlier than before the phase advance. Thus LD shifts delayed and advanced the running that was previously associated with food availability and reset the food-entrainable circadian pacemaker.

Activity Cycles↗

PubMed1990

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.

Adrenal Cortex↗

PubMed1990

The heart rate spectrum in simulated flight: reproducibility and effects of atropine.

The heart rate spectrum (HRS) was computed on eight pilots during simulated flight. Although respiratory-coupled heart rate variability (i.e., that produced by vagal inputs to the heart) varied three-fold across volunteers, each individual volunteer's data were very stable on three test days (median coefficient of variation = 5.4%). Atropine rapidly reduced heart rate variability at the respiratory frequency to the noise level (i.e., 74% decrease from predrug levels). Although there was no significant difference in the reduction induced by a 2 mg or 4 mg dose, there was a tendency for variability at this component of the spectrum to return to normal faster following 2 mg injection than after 4 mg injection. By the morning after injection at either dose, heart rate variability at the respiration component of the HRS was back to normal--indicating complete washout of the drug. This study revealed no technical limitation to using the HRS in real life situations outside of the laboratory and suggests that the test can be used to test the efficacy of other treatments or manipulations that reduce vagal tone to the heart.

Aerospace Medicine↗

PubMed1989

Effects of chronic alprazolam treatment on plasma concentrations of glucocorticoids, thyroid hormones, and testosterone in cardiomyopathic hamsters.

In the first of two experiments, young male cardiomyopathic hamsters were injected intraperitoneally twice a day for 29 days with 8 mg alprazolam/kg body weight or saline. Three hours after the same injections on day 30, they were sacrificed and plasma hormone levels were measured. Alprazolam increased cortisol, total glucocorticoid and triiodothyronine levels. It did not affect corticosterone, thyroxine or testosterone levels. The same protocol was used in a second experiment, except the controls received vehicle and a third group was treated with 48 mg diazepam/kg body weight. Alprazolam again increased cortisol and total glucocorticoid levels, but not those of corticosterone. On the other hand, diazepam increased both cortisol and corticosterone levels. These experiments suggest that chronic benzodiazepine treatment can affect adrenocortical function and perhaps some aspects of thyroid function.

Alprazolam↗

PubMed1989

Responses of nucleus ambiguus neurons to arterial pressure manipulations.

Nearly 69% of nucleus ambiguus neurons in the anesthetized, artificially respired dog responded to nonpharmacological manipulations of arterial pressure (AP). All were active at resting AP, most responded robustly to increased AP, and of these, about half showed activity modulated by the respiratory cycle. Other AP-sensitive neurons fired only during the inspiratory or expiratory phase of the pump-driven respiratory cycle, and were inhibited by increased AP and excited by decreased AP.

Action Potentials↗

PubMed1989

Adrenocortical and behavioral responses to repeated stressors: toward an animal model of chronic stress and stress-related mental illness.

Research in chronic stress has been hampered by the absence of an operational definition for that condition. To explore possible criteria for chronic stress, we repeatedly exposed rats to 2 hr of tail shock per day. After several days, we found elevated prestress corticosterone levels and abnormal behavior, including decreased food consumption, fear-like suppression of activity immediately before stress, greater hesitancy to drop from a suspended wire, and decreased exploratory behavior in a novel environment. A less intensely stressed group of rats also had elevated prestress corticosterone levels, but not the abnormal behaviors that persisted in shocked rats after the stress sessions were discontinued. We propose that abnormalities in both adrenocortical function and behavior are a better marker for chronic stress than abnormalities in either of these systems alone. The animal model we have described may be useful for studying factors that contribute to development of chronic stress or PTSD.

Adrenal Cortex↗

PubMed1989

A methodological improvement for experimental control and blood sampling in rats.

We have developed an apparatus and techniques that permit repeated, undisturbed blood sampling and concurrent assessment of activity in rats. The apparatus also allows experimental control of conditioning stimuli and contingencies without the need to transfer the rat to a separate chamber. In the experimental apparatus, body weights remain stable at approximately 90% of the original body weight. Plasma corticosterone and prolactin levels in the apparatus are comparable to levels obtained in undisturbed free-ranging rats and remain at basal levels for the 7 day duration of this experiment. Additionally, circadian activity rhythms in the apparatus are similar to those seen in free-ranging rats. This technique has potential applications for investigators who need to be able to control shock delivery, monitor activity, and sample blood without disturbing rats.

Animals↗