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Biomedical subjects

W N Tapp

Publications and source records attributed to W N Tapp.

At least 37 records · Page 2Linked to original sources
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

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.

Alprazolam↗
PubMed1989

Alprazolam but not diazepam protects hamsters with heart disease from the medical consequences of stress.

We have previously shown that subjecting cardiomyopathic hamsters in the lesion-developing period of their heart disease to cold-immobilization stress had lethal consequences which could be blocked by alprazolam treatment. This experiment replicated that finding and also examined the efficacy of diazepam in this paradigm. In contrast to alprazolam, diazepam did not prevent the cardiomyopathic subjects from succumbing to the stressor. Thus, the effect of alprazolam in reducing stress-induced mortality did not reflect a generic benzodiazepine action.

Alprazolam↗
PubMed1989

Learned fear: a cause of arrhythmia onset in the presence of digitalis.

In earlier studies we have shown that guinea pigs exposed to signal-shock pairs develop digitalis toxicity earlier than control pigs on a test day when shocks are not delivered. Presenting subjects with signal-shock pairs is known to produce learned changes in autonomic tone thought to reflect fear. However, we were unable to find evidence of such changes in that model. A recent report extended our work on psychosomatic digitalis toxicity to the rabbit. Although that animal has been extensively used in studies of visceral learning, that study did not provide sufficient data to rigorously conclude that visceral learning had taken place. In this report, we show that rabbits which have learned that a signal accurately predicts the occurrence of shock develop digitalis-toxic arrhythmias more often during the signal and significantly earlier than other rabbits given prior exposure to equal numbers of signals and shocks, never explicitly paired. The use of this latter control group indicates that rabbits exposed to signal-shock pairs have learned to associate the signal with its consequences; independent evidence of learning exists in the fact that these rabbits showed a signal-locked bradycardia on their training day. However, bradycardia did not appear to be the mechanism for the early elicitation of digitalis toxicity on the test day when ouabain was infused during probes with the signal alone. These data may have clinical significance in their indication that factors in the external milieu can precipitate digitalis-toxic arrhythmias in individuals that would otherwise have no evidence of digitalis toxicity.

Animals↗
PubMed1989

Assessment of autonomic regulation of heart rate variability by the method of complex demodulation.

Complex demodulation was used to examine the effect of both divisions of the autonomic nervous system (sympathetic and parasympathetic) on heart rate. Data were analyzed from dogs during classical conditioning procedures which caused different changes in the autonomic regulation of heart rate. Two significant peaks in the heart rate variability spectrum were examined by this technique. The amplitude of the peak at the respiration frequency showed parasympathetic changes, while the amplitude of the low frequency peak (0-0.124 Hz) showed both sympathetic and parasympathetic effects. Complex demodulation results at these frequencies clearly showed the activities of both branches of the autonomic nervous system in regulating heart rate. During the CS+ period, when trained dogs were presented with a tone predicting a subsequent shock, the observed tachycardia was due to decreased parasympathetic activity and a transient increase in sympathetic activity. During the CS- period where a different tone predicts no shock, parasympathetic and sympathetic activities were unchanged from the baseline condition. The use of complex demodulation enables us to examine autonomic contributions to heart rate regulation in conditioning and a variety of other physiological and environmental conditions where autonomic input can be expected to change rapidly.

Animals↗
PubMed1989

Circadian rhythms and patterns of performance before and after simulated jet lag.

We have developed a rhesus monkey model that enables us to investigate physiological rhythms and circadian effects on performance in an integrated framework. Monkeys worked for 8 h/day on a two-component task (a vigilance trial followed by a discrimination trial) for their daily food aliquot. Concurrently, we recorded activity and temperature rhythms around the clock. To test the model, we studied rhythms and performance during entrainment to a 24-h light cycle and after a 6-h phase advance. Results from this animal model displayed many of the essential characteristics seen in similar human experiments. During stable entrainment, temperature rhythms reached their maximum amplitude in late afternoon, with activity rhythms reaching their maximum amplitude several hours earlier. Performance exhibited consistent task-dependent variations over the course of daily sessions. Speed of discrimination performance was fastest at the beginning of the session, and speed of vigilance performance was fastest several hours later. After a 6-h phase advance, monkeys exhibited transient internal desynchrony with activity resynchronizing faster than temperature. Both vigilance and discrimination were impaired after the phase shift, with vigilance exhibiting larger-magnitude and longer-lasting impairments than discrimination. A second drop in performance was seen 10-14 days after the phase shift. These data replicate and extend earlier work in humans and show that this model can be used in the study of chronobiological questions that would be too expensive or too impractical to do with humans.

Acclimatization↗
PubMed1988

An assessment of prolactin's value as an index of stress.

On an every other day basis, chronically catheterized male rats were subjected to a 30 sec grid shock in either an ascending (0.0, 0.25, 1.0, 4.0 mA) or descending order. A third group was repeatedly subjected to 1.0 mA shock over the same time frame. In 85% of the shock trials, plasma prolactin increased from baseline levels, thus indicating that prolactin is a relatively reliable index of stress. However prolactin did not change in a step-wise fashion with stressor intensity for a significant number of rats. Data from the group given repeated exposure to the 1 mA stressor showed no evidence of habituation--a process which might have explained the findings. This study indicates that prolactin levels do not sensitively track stressor intensity for individual rats.

Animals↗
PubMed1988

Effect of stressor intensity on habituation of the adrenocortical stress response.

Although it is known that the number of presentations of a stressor can influence the adrenocortical stress response, relatively little information exists on how stressor intensity affects this process. To evaluate this, we repeatedly presented rats with stressors of 3 different intensities and sampled blood for corticosterone. The first major finding was that the rat's initial adrenocortical responsiveness regardless of the stressor employed was a critical variable. Rats that showed a small corticosterone response showed no evidence of habituation or of differences due to stressor intensity. Rats that showed an initial robust response all showed partial habituation of their corticosterone response over time but the patterns varied with stressor intensity. Handled and prone restrained rats showed the same pattern but rats subjected to the more intense stressor of supine restraint showed delay in habituation and tonically elevated responses. These data indicate that individual differences in reactivity to stressors as well as stressor intensity can influence the pattern of the stress response over the course of repeated administration of the stressor.

Adrenal Cortex↗
PubMed1988

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.

Aging↗
PubMed1988

Consequences of stress: a multiplicative function of health status.

We hypothesized that an individual's state of health affects its response to stress. To test this, we used the natural history of inherited heart disease in hamsters as a sliding scale of organ vulnerability on which we superimposed a constant set of stressors. When the animal was stressed at an early point in its disease, heart failure did not develop. Later, after cardiac compensatory changes had developed, stress precipitated overt heart failure. Finally, stress administered when the animal was in overt heart failure further amplified the medical consequences of stress, and some animals succumbed.

Animals↗
PubMed1988

Verapamil sensitizes cardiomyopathic hamsters to the effects of stress.

The major working hypothesis for the genesis of cardiac lesions in young cardiomyopathic hamsters is microvascular spasm--a process which is prevented with verapamil. Our work has shown that stress is often lethal to these animals. The purpose of this experiment was to see if verapamil blocked the effects of stress. Instead, we learned that the drug sensitized the animals to the effects of stress.

Animals↗
PubMed1987

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 measured gonadal and seminal vesicle mass and plasma testosterone at 1 year of age in CM hamsters raised in the 2 light conditions and 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.

Age Factors↗
PubMed1987

Adrenal hormonal indices of stress in laboratory rats.

When individual rats were exposed to different intensities of a stressor, foot shock, plasma catecholamines were found to be sensitive and reliable indices of the stress. Plasma corticosterone did not perform as well. Similarly, levels of both plasma epinephrine and norepinephrine correlated highly significantly with a behavioral measure of the degree of stress--namely, the amount of movement about the cage seen during the 30 sec shock period. Importantly, this behavioral measure was as sensitive and reliable an index of stress as the catecholamines. However, use of either the catecholamines or this behavioral measure as a clinically useful measure of the level of stress was limited by the fact that their responses to the stressor were extremely short-lived. Nonetheless, because the catecholamines reliably and sensitively track the intensity of a stressor, they appear to be a good visceral measure of stress, perhaps the best currently available. But the behavioral concomitants of stress are quickly and easily quantifiable and present a wide range to study, starting with alerting, through a progression of more aroused motor activity, and ending with fight-flight. Because the behavioral concomitants of stress have not been as intensively studied as the endocrine ones, we believe that future efforts to find a clinically useful index of stress will be rewarded by a refocussing of attention away from the visceral respondent to the overt behavioral one.

Animals↗