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Biomedical subjects

B H Natelson

Publications and source records attributed to B H Natelson.

At least 109 records · Page 6Linked to original sources
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

Plasma corticosterone levels during repeated presentation of two intensities of restraint stress: chronic stress and habituation.

This study measured plasma corticosterone levels in male rats during repeated daily presentations of two intensities of restraint stress. The corticosterone response to a stress session was defined as the change from pre-stress levels to levels after 60 minutes of restraint. With the relatively intense stress imposed by four limb prone restraint, the corticosterone response partially habituated over seven days due to increasing basal corticosterone levels. However, even on day 7, there was still a large corticosterone response. With the milder stress of immobilization in a tube, the corticosterone response did not habituate at all over 21 days of repeated stress despite rising basal levels. Stress levels of corticosterone did not show significant change over days in either of the two restraint groups. Further, rising basal corticosterone levels suggest that repeated restraint produced a chronic stress state in these rats which may vary in some qualitative way with stressor intensity. Control rats placed in the same room as the stressed rats during the two stresses initially had increased corticosterone levels that matched the levels achieved in the stressed rats. The responses in control rats for the intense stress did not habituate completely in 7 days, whereas those in the control rats for the mild stress habituated completely within 3 days. These data suggest intraspecific communication of the intensity of stress.

Animals↗
PubMed1988

Summation of baroreflex and classically conditioned heart rate responses in dogs.

Following instrumentation with pneumatic cuffs around the inferior vena cava and the descending aorta, dogs were studied either following differential classical conditioning or in a control state. The cuffs functioned to raise and lower blood pressure for the construction of baroreflex curves for heart rate. Conditioned dogs received 8 trials each day with each CS+ (tone paired with flank shock) and CS- (a different tone without shock). Curves were constructed from cuff inflations timed to coincide with the maximum conditioned heart rate response. These curves were constructed from data acquired during infusion of saline, methyl atropine, or propranolol. Comparison of these curves revealed that the CS+ shifted the curves toward higher heart rates while the CS- curve was shifted toward lower heart rates without a change in gain. The amount of shift was comparable to that of the conditioned heart rate response. This suggested that the responses were independent and additive. Neither propranolol nor atropine eliminated this separation between the curves induced by the conditioning. These observations lead us to conclude that classically conditioned stress and baroreceptor stimulation exert independent control over heart rate that are mediated by both sympathetic and parasympathetic influences.

Animals↗
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↗
PubMed1987

Coronary vasospasm: a neuro-behavioral event?

Evidence exists for the presence of a neuro-anatomy that can produce cardiac vasospasm. Recent experimental and clinical data suggest that this neuro-anatomic mechanism can be activated by behavioral events in the psycho-social surround of the patient with coronary artery disease. I hypothesize that this mechanism can produce myocardial ischemia and can explain the variability in onset of clinical angina.

Behavior↗
PubMed1987

Recordings from arterial pressure-sensitive units in the awake dog.

Recordings were made from units in or near nucleus ambiguus (NA) in the awake, drug-free dog while arterial pressure (AP) was increased and decreased nonpharmacologically by inflating occlusion cuffs that had been placed around the descending aorta and inferior vena cava, respectively. Units were recorded differentially through floating fine-wire electrodes that extended from vertically movable cannulas in a chronically implanted microdrive. Fifty-three percent of units recorded in or near NA were excited by increased AP, but were unresponsive to decreased AP. The remaining units were unresponsive to increased or decreased AP. About 25% of AP-sensitive units had activity patterns related to the cardiac cycle. AP-sensitive, cardiac cycle related units located in NA displayed several of the properties previously demonstrated for antidromically identified preganglionic parasympathetic cardiac motoneurons involved in baroreflex control of heart rate and rhythm. Recording from such neurons in the awake, neurologically intact, drug-free dog permits the fullest and most natural expression of neuro-cardiologic interactions and will allow the investigation of behavioral influences on autonomic and cardiovascular function.

Action Potentials↗
PubMed1987

Differential effect of stimulation of nucleus ambiguus on atrial and ventricular rates.

Acute experiments were performed on open-chest male mongrel dogs that were anesthetized with thiopental sodium and respired. An average of 10 penetrations per side was used to explore the rostral-caudal organization of the nucleus ambiguus (NA) and the area ventrolateral to it. Atrial pacing was performed on some trials to clarify the occurrence of atrioventricular (AV) block. In addition, the vagi were sectioned in some animals to confirm the peripheral pathway of the observed effects. Finally, the twin-pulse technique was used to classify the neurons underlying the observed effects according to their refractory periods. Stimulation in the area of the NA and lateral to it produced bradycardia and bradyarrhythmias without altering blood pressure. Stimulation of either the left or right NA produced slowing of both atrial and ventricular rates. However, slowing of the atrial rate was greatest with right NA stimulation, whereas slowing of the ventricular rate was predominant with left-side stimulation. The presence of AV block was evident from dropped QRS complexes with and without pacing. Vagotomy demonstrated that these effects were conducted by ipsilateral but not contralateral nerves. Measurement of the refractory periods showed that the neurons underlying both atrial and ventricular slowing were characteristic of B-fibers.

Analysis of Variance↗