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T B Clarkson

Publications and source records attributed to T B Clarkson.

At least 73 records · Page 4Linked to original sources
PubMed1991

Coronary heart disease in rhesus monkeys with diet-induced coronary artery atherosclerosis.

Diet-induced coronary artery atherosclerosis develops in rhesus monkeys (Macaca mulatta). The goal of this study was to establish the rhesus monkey as an animal model of coronary heart disease (CHD). From a colony of 160 rhesus monkeys fed an atherogenic diet, we identified 14 monkeys with electrocardiographic and echocardiographic evidence of CHD. When compared with 14 rhesus monkeys matched for age, gender, and dietary history with normal electrocardiograms and echocardiograms, monkeys with CHD had higher arterial blood pressures (mean +/- SEM, 92 +/- 4 mm Hg vs 75 +/- 5 mm Hg, respectively), lower high-density lipoprotein cholesterol concentrations (mean +/- SEM, 1.70 +/- 0.25 mmol/L vs 2.32 +/- 0.28 mmol/L [66 +/- 10 mg/dL vs 90 +/- 11 mg/dl]), and lower A-l apolipoprotein concentrations (mean +/- SEM, 200 +/- 17 mg/dL vs 252 +/- 15 mg/dL). Monkeys with CHD tended to have higher total plasma cholesterol concentrations (mean +/- SEM, 11.6 +/- 1.55 mmol/L vs 9.36 +/- 0.93 mmol/L [450 +/- 60 mg/dL vs 362 +/- 36 mg/dL]) and higher low-density lipoprotein cholesterol concentrations (mean +/- SEM, 8.71 +/- 1.75 mmol/L vs 6.12 +/- 0.90 mmol/L [337 +/- 68 mg/dL vs 237 +/- 35 mg/dl]) than monkeys with normal electrocardiograms and echocardiograms. We conclude that rhesus monkeys, like human beings, develop CHD as a complication of coronary artery atherosclerosis. Furthermore, risk factors for CHD in rhesus monkeys and human beings are similar.

Animals↗
PubMed1990

Oral contraceptives, lipoproteins, and atherosclerosis.

A nonhuman primate model was developed to study the effects of oral contraceptives on lipoproteins and atherosclerosis. Cynomolgus macaques were selected because of their susceptibility to diet-induced atherosclerosis and because their reproductive physiology, menstrual cycle, and circulating sex hormone patterns are similar to those of human females. The first study compared a vaginal ring containing levonorgestrel and estradiol with an oral contraceptive containing norgestrel and ethinyl estradiol. A second study compared two oral combinations: norgestrel-ethinyl estradiol and ethynodiol diacetate-ethinyl estradiol. As predicted, use of all the contraceptives led to lowering of high-density lipoprotein cholesterol levels. However, contrary to what might be expected, use of the ethinyl estradiol-containing oral contraceptives did not lead to an increase in the prevalence or extent of atherosclerosis. We concluded that ethinyl estradiol neutralized the atherogenic influence of the progestin component of oral contraceptives.

Animals↗
PubMed1990

Oral contraceptives and coronary artery atherosclerosis of cynomolgus monkeys.

Studies of both human and nonhuman primates show an inverse relationship between high-density lipoprotein (HDL) cholesterol concentrations and coronary artery atherosclerosis. For this reason, there has been concern that the HDL cholesterol-lowering effect of oral contraceptives might exacerbate coronary artery atherosclerosis. We studied three groups of adult female cynomolgus macaques fed a moderately atherogenic diet: a control group, a group given ethinyl estradiol and norgestrel, and another group given ethinyl estradiol and ethynodiol diacetate. Norgestrel and ethynodiol diacetate, co-administered with ethinyl estradiol, lowered the plasma concentrations of HDL cholesterol. However, the extent of coronary artery atherosclerosis was lessened by both contraceptives, especially among females at high risk based on their plasma lipid profiles.

Animals↗
PubMed1989

Social deprivation and coronary artery atherosclerosis in female cynomolgus monkeys.

Plasma lipid concentrations and coronary artery atherosclerosis extent were compared in a retrospective study of female cynomolgus monkeys consuming a moderately atherogenic diet and housed in single cages or social groups. There was no difference between single caged and socially housed monkeys in plasma lipid concentrations. However, females housed in single cages had significantly more coronary artery atherosclerosis than those housed in social groups. It has been found previously that socially subordinate females have more extensive coronary artery atherosclerosis than social dominants, and that subordinates spend more time alone than dominants. Subsequent analyses of the data presented here revealed that single caged monkeys had significantly more coronary artery atherosclerosis than socially dominant, but not socially subordinate, monkeys. Characteristics of single cage housing which could be disease promoting include restraint and social isolation. These findings should be considered preliminary, and serve as a basis for further study.

Animals↗
PubMed1989

From menarche to menopause: coronary artery atherosclerosis and protection in cynomolgus monkeys.

The effects on atherogenesis of stress, pregnancy, and oral contraceptive therapy were studied in a nonhuman primate model. The stress of social subordination was associated with ovarian dysfunction, unfavorable lipoprotein changes, and increased coronary artery atherosclerosis compared with nonstressed (socially dominant) or normal monkeys. Although pregnant animals exhibited lower high-density lipoprotein cholesterol concentrations, they had only one half as much diet-induced coronary artery atherosclerosis as their nonpregnant counterparts. Monkeys treated with an Ovral-like regimen also exhibited adverse lipoprotein changes. Nevertheless, prevalence and extent of coronary artery plaques decreased. We conclude that estrogen is an important factor in the animals' "female protection" against diet-induced atherosclerosis. We also suggest that the lowering of high-density lipoproteins by the progestin component of higher-dose contraceptives is not necessarily atherogenic if a sufficiently potent exogenous estrogen is administered concomitantly.

Animals↗
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

Regional obesity and coronary artery atherosclerosis in females: a non-human primate model.

The relationships between regional obesity, atherosclerosis and atherosclerosis risk factors were studied in female cynomolgus monkeys (Macaca fascicularis). In a retrospective necropsy study it was found that females with relatively high central: peripheral fat deposition had three times more extensive coronary artery atherosclerosis. In a second experiment it was found that females with high central fat ratios and females with high levels of whole body obesity were relatively hyperglycemic. In a third experiment it was found that females with relatively high whole body obesity, and females with relatively central fat deposition had higher blood pressures. Females with relatively central fat deposition had higher total and lower high density lipoprotein plasma cholesterol concentrations, and exacerbated coronary artery atherosclerosis. Social subordinates were more likely to exhibit a central fat deposition pattern than dominants. These findings suggest that female cynomolgus macaques may be a potential animal model of the health impact of regional obesity.

Adipose Tissue↗
PubMed1988

The surface morphology of normal and atherosclerotic coronary arteries in male Macaca fascicularis and the effect of coronary angiography.

Selective coronary angiography is one of the procedures used frequently in the diagnosis and management of coronary artery disease. Macaca fascicularis monkeys were used to study the effects of coronary angiography on coronary artery surface morphology. Fourteen M. fascicularis were fed either an atherogenic diet (0.34 mg of cholesterol/kcal and 40 to 43% of the calories as fat) for six to nine months or a control diet. For six of these animals the Judkin method of selective left coronary angiography was done 24 h prior to necropsy. The ascending aorta, right coronary artery, left circumflex (LCX), left anterior descending (LAD) and left main (LM) coronary arteries were examined using scanning electron microscopy (SEM). The animals fed an atherogenic diet had 27% of the ascending aorta and 7% of the coronary arteries covered with raised lesions. The surface of these coronary arteries differed from those of animals fed a control diet in that the surface appeared smoother and often had numerous adherent leukocytes. The animals undergoing coronary angiography had 25% of the ascending aorta and 10% of the LM surface injured by the catheter. These areas were denuded of endothelium and covered with adherent platelets. There were no morphologic changes observed by SEM following angiography within the LCX or LAD arteries. Thus even in a setting of hypercholesterolemia exposure to contrast media during the coronary angiography procedure did not lead to surface alterations.

Angiocardiography↗
PubMed1987

Contraceptive steroids and coronary artery atherosclerosis in cynomolgus macaques.

The influence of two types of steroidal contraception on the extent of coronary, aortic, carotid, and iliaco-femoral atherosclerosis was assessed in 57 cynomolgus macaques with moderate diet-induced hyperlipoproteinemia. Thirteen animals were treated with an intravaginal ring that released 17 beta-estradiol and levonorgestrel. Fifteen females were treated with an oral contraceptive (OC) composed of ethinyl estradiol and norgestrel. Fifteen females received placebo vaginal rings, and 14 males were untreated. The contraceptive treatments resulted in similar large reductions in plasma high-density lipoprotein (HDL) cholesterol concentrations. Neither treatment influenced the prevalence of coronary artery atherosclerosis. However, treatment with the contraceptive vaginal ring was associated with increased extent of coronary artery atherosclerosis (plaque size) relative to untreated females, whereas treatment with the OC was not. The contrasting effects of the two treatments could not be explained by differences in total plasma cholesterol, HDL cholesterol, or blood pressure. The results suggest that the greater estrogenic influence associated with the ethinyl estradiol-containing OC resulted in inhibition of coronary artery atherosclerosis despite a pronounced progestin-induced lowering of plasma HDL cholesterol concentration and, further, that hormonal balance may have a marked influence on the relationship between plasma lipids and atherogenesis.

Animals↗
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↗