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Biomedical subjects

S B Manuck

Publications and source records attributed to S B Manuck.

At least 91 records · Page 5Linked to original sources
PubMed1990

Lowering cholesterol concentrations and mortality: a quantitative review of primary prevention trials.

OBJECTIVE: To determine the effects of lowering cholesterol concentrations on total and cause specific mortality in randomised primary prevention trials. DESIGN: Qualitative (meta-analytic) evaluation of total mortality from coronary heart disease, cancer, and causes not related to illness in six primary prevention trials of cholesterol reduction (mean duration of treatment 4.8 years). PATIENTS: 24,847 Male participants; mean age 47.5 years. MAIN OUTCOME MEASURES: Total and cause specific mortalities. RESULTS: Follow up periods totalled 119,000 person years, during which 1147 deaths occurred. Mortality from coronary heart disease tended to be lower in men receiving interventions to reduce cholesterol concentrations compared with mortality in control subjects (p = 0.06), although total mortality was not affected by treatment. No consistent relation was found between reduction of cholesterol concentrations and mortality from cancer, but there was a significant increase in deaths not related to illness (deaths from accidents, suicide, or violence) in groups receiving treatment to lower cholesterol concentrations relative to controls (p = 0.004). When drug trials were analysed separately the treatment was found to reduce mortality from coronary heart disease significantly (p = 0.04). CONCLUSIONS: The association between reduction of cholesterol concentrations and deaths not related to illness warrants further investigation. Additionally, the failure of cholesterol lowering to affect overall survival justifies a more cautious appraisal of the probable benefits of reducing cholesterol concentrations in the general population.

Aged↗
PubMed1990

The effect of feedback-assisted reduction in heart rate reactivity on videogame performance.

In 67 male volunteers, we examined the reduction of cardiovascular responsivity to a psychomotor challenge (videogame) achieved by use of heart rate (HR) feedback and effects of these procedures on concomitant behavioral performance. Each subject participated in a pretraining assessment of his cardiovascular responses to the videogame, a training condition, and a posttraining assessment identical to the initial evaluation. During training, subjects were assigned to one of four conditions: (a) a habituation control group receiving no instructions to alter HR (HC); (b) an instructions-only control group receiving instructions to maintain a low or unchanged HR during videogame presentations (IC); (c) a feedback group receiving instructions to reduce HR using ongoing HR feedback (FB-); or (d) a feedback group receiving instructions to lower HR and given HR feedback plus a score contingency in which total game score was jointly determined by subjects' game performance and success at HR control (FB+). Subjects receiving feedback (FB+, FB-) exhibited greater reductions in HR response to the videogame in the posttraining assessment than control (HC, IC) subjects; FB+ subjects showed greater HR reductions than subjects in any other group. FB+ and FB- subjects showed a lower SBP at posttraining relative to the two control groups, but no reduction in task-induced blood pressure reactivity. There were no group differences in videogame performance, either before or following training.

Adolescent↗
PubMed1990

Oral contraceptive administration, interfemale relationships, and sexual behavior in Macaca fascicularis.

The effects of oral contraceptive administration on the social relationships of adult female cynomolgus monkeys (Macaca fascicularis) were examined. Ten females were administered ethinyl estradiol/ethynodiol diacetate (Demulen), 10 were administered ethinyl estradiol/norgestrel (Ovral), and 10 served as a control group. The monkeys lived in social groups of 5 females each, and patterns of social interaction and social status were recorded. Interfemale relationships were also observed when a vasectomized male was placed in each social group for 50 min, once/week. During the latter observations, preliminary data on the effects of oral contraceptive treatment on sexual interaction were also collected. In the absence of the male, interfemale agonistic interactions and time spent alone were influenced by social status but not by oral contraceptive treatment. Time spent in passive body contact, an affiliative state, was reduced by Ovral treatment. In the presence of the male, dominant females aggressively interfered with the sexual interactions of subordinates. This aggression resulted in the termination of a greater proportion of the sexual interactions of subordinates than dominants in the control group only, indicating suppression of this type of interaction by oral contraceptive treatment. Other effects included a decreased frequency of ejaculation with Ovral-treated females. These results suggest that oral contraceptives may suppress certain types of female agonistic behavior (e.g., in the context of mate competition) and some oral contraceptives may interfere with sexual activity. More broadly, these findings indicate that intrasexual competition for access to mates may occur in females as well as males.

Aggression↗
PubMed1990

Anabolic-androgenic steroids: effects on social behavior and baseline heart rate.

Examined the effects of anabolic-androgenic steroids (AS) on behavior, baseline heart rate (HR), and stress-induced HR responses. Twenty-four cynomolgus monkeys were assigned to four mixed social groups of both AS and sham control animals. For 2 months, AS-treated monkeys received biweekly injections of testosterone, and, on an identical schedule, the control animals were injected with a sham solution. Behavioral data revealed that AS disrupted the social milieu such that all dominant animals exhibited increases in dominant behavior and subordinates manifested increased submission. These changes returned to pretest levels 8 weeks following termination of the drug intervention. Affiliative behaviors decreased on the part of all animals as a function of AS and, with the exception of play behavior, failed to return to pretest levels after the 8-week period of recovery. AS created an increase in baseline HR, particularly among the dominant animals. Interestingly, the subordinate AS animals experienced a decrease in baseline HR response. AS had no apparent influence on stress-induced HR reactivity.

Agonistic Behavior↗
PubMed1990

Hemodynamic and endocrine effects of mental stress in untreated borderline hypertension.

Mental arithmetic and mirror tracing were compared in 40 untreated patients with borderline hypertension, tested in random sequence in standardized protocols. Both tasks significantly increased systolic and diastolic blood pressure, heart rate, cardiac index, plasma renin, and decreased peripheral resistance. Mental arithmetic also increased cholesterol, triglycerides and HDL; plasma catecholamines were not changed significantly. Lipid changes were correlated with blood pressure changes. These methods will be useful in exploring the relationships between hemodynamic reactivity to stress, and the presence and progression of atherosclerosis, as well as testing the effects of antihypertensive drugs on stress-induced changes that may influence atherosclerotic complications of hypertension.

Adult↗
PubMed1990

Absence of behavioral differences in young normotensive adults as a function of parental history of hypertension.

It has been previously demonstrated that mildly hypertensive subjects show deficits in their performance on various sensory-perceptual, cognitive, and psychomotor tests relative to matched normotensive control subjects, and that these behavioral deficits are reversible following treatment with antihypertensive medication. To examine whether these deficits are an outcome of elevated blood pressure, rather than preceding the hypertensive state, normotensive offspring of hypertensives and normotensives were administered a test battery. Results showed that with minor exceptions, offspring of hypertensives and offspring of normotensives performed similarly on the tests. These results suggest that the behavioral deficits seen in hypertensives arise subsequent to the onset of elevated blood pressure.

Adolescent↗
PubMed1990

Individual differences in behaviorally evoked cardiovascular response: temporal stability and hemodynamic patterning.

This study evaluates the reproducibility of individual differences in behaviorally evoked cardiovascular reactivity among 39 young adult males. Presented also are initial data describing idiosyncratic patterns of hemodynamic adjustment that may underlie pressor responses to laboratory stressors. Subjects were administered three experimental stressors (mental arithmetic, mirror tracing, and bicycle exercise) on two occasions, four weeks apart. Heart rate, blood pressure, and impedance-derived measurements of cardiac pre-ejection period, stroke index, cardiac index, and total peripheral resistance were obtained during baseline and task periods at each session. To index task-induced "reactivity," residualized (baseline-adjusted) change scores were calculated for all variables; percentage change from baseline was also calculated for impedance-derived hemodynamic measurements. Test-retest (inter-session) correlations were significant for nearly all baseline, task, and change-score measurements. The few exceptions included diastolic blood pressure changes during mirror tracing and bicycle exercise and changes in stroke index and peripheral resistance during mental arithmetic. Although virtually all baseline and task correlations exceeded .60, reactivity indices yielded consistently lower retest correlations (significant r's = .35-.78; median r = .49). In subsequent analyses, subsets of individuals were identified whose reactions to mental arithmetic at the first laboratory session reflected changes in either cardiac output (CI reactors, n = 9) or total peripheral resistance (TPR reactors, n = 6), or a combination of cardiac and vascular influences (Mixed reactors, n = 8). This typology of hemodynamic response: (a) was corroborated by corresponding group differences in heart rate, pre-ejection period, and stroke index; (b) was reproducible on retesting; and (c) showed some generalization to the mirror tracing task, though not to bicycle exercise.

Adolescent↗
PubMed1989

Behavioural consequences of hypertension: effects of age and type of antihypertensive agent.

In order to investigate the effects on behaviour of hypertension, age, and the types of antihypertensive agents, we have conducted a retrospective analysis in 100 hypertensive patients receiving chronic treatment in our Hypertension Clinic. A group of 80 normotensive subjects, matched for age, were included in the study. Half of the hypertensive patients were under the age of 50 (young group) and half were over the age of 50 yrs (old group). The antihypertensive agents had not been administered according to any specific protocol, but represented the choice of the individual clinicians treating the patients in the clinic. All patients had received treatment for at least one year, and usually for two years. The behavioural tests performed were designed to measure sensory-perceptive ability, cognitive ability and psychomotor function and were those employed and described in our previous studies. The results achieved were varied, but indicated that older age was associated with an impairment in performance as was blood pressure. Test performances in the young hypertensives were similar to those achieved by older normotensives. These results were more prominent in cognitive and psychomotor functions than in the sensory-perceptive tests. The antihypertensive drugs used also affected these results; the worst behavioural performances tended to be in patients receiving the central nervous system agonists (methyl-dopa and clonidine) and better performances in patients receiving beta-blockers alone when compared with the other groups. Surprisingly, patients receiving diuretics showed poorer performance levels, but these were better in patients who received a beta-blocker in combination with their diuretic.(ABSTRACT TRUNCATED AT 250 WORDS)

Aging↗
PubMed1988

Effects of stress and the sympathetic nervous system on coronary artery atherosclerosis in the cynomolgus macaque.

Epidemiologic evidence increasingly implicates psychosocial variables in the development of coronary heart disease in human beings, an association that appears to be independent of the effects of other coronary disease risk factors. It has been hypothesized that behavioral influences on coronary heart disease are mediated by activation of the sympathetic nervous system, perhaps through exacerbation of coronary artery atherosclerosis. This article summarizes several studies of the effects of stress and sympathetic arousal on atherosclerosis in a nonhuman primate model of atherogenesis. The application of a behavioral stressor involving periodic reorganization of social group memberships resulted in worsened coronary atherosclerosis among male cynomolgus monkeys (Macaca fascicularis) fed a cholesterol-containing diet, relative to control animals housed in groups of fixed (stable) membership, but only among those monkeys that retained dominant social status during the course of the study. This effect could not be attributed to concomitant variability in blood pressure or serum lipid concentrations. When the same experimental procedures were applied to males fed a diet low in saturated fat and cholesterol, the manipulation of group memberships similarly led to development of greater atherosclerosis in the coronary arteries. In related observations, monkeys that exhibited the largest heart rate responses to a standardized behavioral challenge had more extensive coronary atherosclerosis than animals showing a less pronounced cardiac responsivity to stress. In a final investigation, we observed that the exacerbated atherosclerosis of dominant monkeys consuming an atherogenic diet and housed in unstable social groups could be prevented by long-term administration of a beta-adrenoreceptor-blocking agent, propranolol hydrochloride.

Adrenergic beta-Antagonists↗
PubMed1988

The role of anabolic steroids on baseline and stress heart rate in cynomolgus monkeys.

This investigation examined the role of anabolic steroids on baseline heart rate (HR) and HR responses to the threat of capture in Macaca fascicularis. Ten cynomolgus monkeys were randomly assigned either to a steroid or to a sham control group. Steroid-treated animals were given testosterone injections biweekly for 10 weeks, whereas sham controls received injections of sesame oil on an identical schedule. Pretreatment and posttreatment HRs were evaluated to establish both baseline and acute-stress responses. Results revealed that animals given testosterone experienced a statistically significant increase in baseline HR when contrasted with the sham controls. No difference between the groups was detected in response to the threat of capture.

Animals↗
PubMed1988

Persistent sympathetic nervous system arousal associated with tethering in cynomolgus macaques.

The swivel-tether system has been used extensively in biomedical research involving nonhuman primates, yet there has been little or no investigation into potential adverse influences of this form of restraint on research results. In the study described here, a portable electrocardiographic telemetry system was used for continuous monitoring of the heart rate of 26 cynomolgus monkeys while: (a) pair-caged, 8 weeks prior to tethering; (b) singly-caged, tethered; (c) singly-caged, tethered, administered propranolol (30 mg/kg/day) in the diet; (d) group-housed (five monkeys per group), 1 week after group formation; and (e) group-housed (five monkeys per group), 4 weeks after group formation. Tethering resulted in persistent elevations in heart rate relative to the other conditions. Administration of propranolol, a beta-adrenergic antagonist, resulted in an abrupt, sustained decrease in heart rate indicating that the increase in heart rate associated with tethering was due to persistent stimulation of the sympathetic nervous system. Since multiple aspects of cardiovascular function are influenced by the sympathetic nervous system, and other organs and systems (e.g., pituitary-gonadal) also may be affected, investigators using the swivel-tether system should be cognizant of these potential effects when designing experiments and interpreting the results.

Analysis of Variance↗
PubMed1987

The effects of beta-adrenergic blocking agents on atherosclerosis and its complications.

Epidemiologic and experimental data are reviewed to determine whether treatment with beta-adrenergic blocking agents ('beta blockers') is likely to be antiatherogenic. Both indirect and direct evidence are considered. Indirect evidence is derived from studies of the effects of beta blockers on the risk factors for atherosclerosis, or on the disease sequelae of atherosclerosis. Direct evidence refers to studies in which atherosclerosis is an endpoint. Regarding indirect evidence, the data generally are consistent with a retarding or neutral effect of beta blockers on atherosclerosis. For example stroke incidence is reduced when hypertension is treated with beta blockers. About half of these same studies also show a reduction in the incidence of myocardial infarction, a complication that may be more closely related to atherosclerosis extent and severity than is stroke, which can have a nonatherosclerosis origin. The most important potential negative effect of beta blockers occurs with respect to serum lipid concentrations. However, there is no evidence that atherosclerosis is worsened as a result of pharmacologically induced alterations of serum lipids. The direct evidence more clearly indicates a retarding effect of beta blockers on atherosclerosis, with 11 of 13 studies having outcomes in this direction. However, interpretation of these studies is complicated by the fact that all of the data are derived from animal models, some of which are not similar to human beings in the development of atherosclerosis. Also, the studies are diverse, not only in the research designs and species utilized, but also in the type of beta blocker employed, the degree of beta blockade achieved, and the anatomic location of lesions. In summary, the data suggest that treatment with beta blockers may retard atherosclerosis. A more definitive answer requires efforts in two directions: (a) studies on atherosclerosis in selected populations of human beings, using cineangiography or autopsy material; and (b) additional, well-controlled studies in appropriate animal models.

Adrenergic beta-Antagonists↗
PubMed1987

Inhibition of coronary atherosclerosis by propranolol in behaviorally predisposed monkeys fed an atherogenic diet.

We studied the effect of propranolol on the diet-induced coronary artery atherosclerosis (CAA) in 30 adult male cynomolgus monkeys living in social groupings of five animals each. Animals in the "treated" segment (n = 15) consumed propranolol, which was mixed into an atherogenic diet. Animals in the "untreated" group (n = 15) consumed only the atherogenic diet. Finally, the social groupings were subjected to disruption through monthly redistribution of monkeys among the groups within each treatment segment. The experiment lasted 26 months, following which all animals underwent autopsy during which the coronary arteries were evaluated for atherosclerosis. Regarding atherosclerosis, we observed a significant interaction between social status and experimental condition (p less than .03). Socially dominant animals had (as in previous studies) significantly exacerbated CAA, but only in the untreated segment; the effect of social dominance on CAA was abolished by long-term administration of propranolol. The antiatherogenic effect of propranolol on dominant animals was independent of the influences of serum lipid concentrations, blood pressure, and resting heart rate. We conclude that treatment with beta-adrenergic-blocking agents may confer a degree of protection against CAA among individuals behaviorally predisposed to coronary heart disease.

Aggression↗
PubMed1987

The influence of heart rate on coronary artery atherosclerosis.

Elevated "casual" heart rate (HR) has been found to be an independent predictor of coronary heart disease (CHD) in human beings. The current study provides data on the association between coronary artery atherosclerosis (CAA) and naturally occurring individual differences in the casual HRs of cynomolgus macaques (Macaca fascicularis). The data demonstrate that naturally occurring differences in casual HR are related to CAA (plaque area in mm) with high HR monkeys having lesions more than twice as extensive as those of low HR monkeys (high HR; n = 7, 159 beats/min: 0.76 mm2 +/- 0.21 SD; low HR; n = 8, 133 beats/min: 0.31 mm2 +/- 0.30; t = 3.01, p less than 0.01). The data show further that the distribution of individual differences in casual HR is consistent and stable over periods of at least 12 months. Importantly, the relationship between elevated casual HR and CAA was independent of the association between an index of HR "responsivity" to stress and CAA, found in the same monkeys. Similar to a recent finding in human beings, high casual HR also was associated with significantly lowered serum concentrations of high-density lipoprotein cholesterol; differences in CAA were, however, independent of the lipid difference. The CAA differences may depend instead on HR-induced differences in coronary blood flow between high and low HR monkeys. Subsequent work with beta-adrenergic blockade suggested that elevated casual HRs in monkeys are associated with sympathetic arousal.

Animals↗
PubMed1987

Psychosocial influences on the pathogenesis of atherosclerosis among nonhuman primates.

Epidemiologic and clinical evidence derived from studies of human beings suggests that psychosocial phenomena may account for much of the variability in atherosclerosis extent and severity that is unexplained by the "traditional" risk factors (serum lipids, hypertension, and smoking). Animal preparations provide an opportunity to test hypotheses concerning the role of psychosocial phenomena in atherogenesis and to explore the mechanisms by which the effects of such phenomena are mediated. Here we review a relatively large series of studies of cynomolgus monkeys (Macaca fascicularis), a 5 kg animal having a complex social organization. The data indicate that, among male animals, individual behavior characteristics (social status and aggressiveness), physiologic responsiveness to psychological challenge, and stability of the social environment all interact to affect atherogenesis. Among female animals, individual patterns of aggressiveness appear to influence ovarian function, which in turn affects atherosclerosis. Future advances in the behavioral medicine aspects of atherogenesis are likely to arise through elucidation of the pathophysiologic pathways by which these behavioral responses and characteristics contribute to the events (endothelial injury, smooth muscle cell proliferation, lipid accumulation, calcification, and necrosis) associated with plaque pathogenesis. Such research can be pursued in studies utilizing nonhuman primates as well as in complementary studies involving human subjects.

Aggression↗