Sanford O. Byers

Plasma catecholamine response of coronary-prone subjects (type A) to a specific challenge☆

Plasma norepinephrine (NE) and epinephrine (E) were assayed in 15 men prone to develop coronary heart disease (type-A behavior pattern) and in 15 coronary-disease-resistant men (type-B behavior pattern) under resting, noncompetitive conditions and also immediately before, during, and after participation in a nonphysical competitive struggle. The average concentration of catecholamines was virtually the same in both groups under resting conditions. Under competitive conditions the NE concentration of the coronary-susceptible group rose an average of 30%, while that of the resistant group remained essentially unchanged. E concentration remained unchanged in both groups.

EXCRETION OF CATECHOLAMINES, 17-KETOSTEROIDS, 17-HYDROXYCORTICOIDS AND 5-HYDROXYINDOLE IN MEN EXHIBITING A PARTICULAR BEHAVIOR PATTERN (A) ASSOCIATED WITH HIGH INCIDENCE OF CLINICAL CORONARY ARTERY DISEASE*†

Several recent studies from this laboratory strongly suggest that a particular overt behavior pattern may be strongly implicated in the pathogenesis of many cases of clinical coronary artery disease. Thus it was observed (1) that when accountants were forced by occupational circumstances to alter acutely their usual behavior pattern of relative calm to an overt behavior pattern in which competitive and excessive drive and an enhanced sense of time urgency were paramount, a marked elevation of serum cholesterol and hastening of blood clotting time occurred. It is of interest that this observed rapid rise of serum cholesterol following change in behavior pattern already has been confirmed by three different groups of investigators (2-4). It was further found (5) that a group of individuals who chronically exhibited an overt behavior pattern (Pattern A) characterized by excessive and competitive drive and an enhanced sense of time urgency not only exhibited notably higher serum cholesterol and faster clotting time than individuals exhibiting a converse type of behavior pattern (Pattern B), but also an approximately sevenfold higher incideuce of clinical coronary artery disease and over three times as much arcus senilis. Finally, we have more recently found (6) that females exhibiting this same Behavior Pattern A exhibit approximately the above same differences in blood and cardiovascular findings, when compared to females showing Pattern B. These women with

Resolution of aortic atherosclerotic infiltration in the rabbit by phosphatide infusion.

Summary Intermittent intravenous infusion of a phosphatide emulsion into 2 series of previously hypercholesteremic rabbits appeared to effect a marked resolution of their atherosclerotic infiltration and cholesterol deposit as judged by the findings in paired, untreated animals.

SERUM LIPIDS AND CONJUNCTIVAL CIRCULATION AFTER FAT INGESTION IN MEN EXHIBITING TYPE-A BEHAVIOR PATTERN.

A group of 12 subjects exhibiting a behavior pattern A, associated with a high incidence of clinical coronary artery disease, and a second group of subjects exhibiting a converse type of behavior pattern B, were fed a standard fat meal, before and after which studies were made of serum lipid and cholesterol changes. In addition, studies were made of their bulbar conjunctival vasculature.It was found that the average fasting serum triglyceride, cholesterol, and phospholipid values of the “A” subjects were significantly greater than those of the “B” subjects. Following the meal, the average serum triglyceride rose much higher and remained relatively much higher and longer in subjects with pattern A than in those with pattern B. The serum free fatty acid content was essentially the same in both groups, both before and after the meal. The observed differences in serum triglyceride behavior did not appear to be due to differences in the circulating phase of the heparininduced lipoprotein-lipase system.Following the meal, marked sludging and capillary ischemia were found in the conjunctival tissue of 10 or 12 subjects with pattern A and in only three of the 12 subjects with pattern B.

EFFECT OF CHRONIC HYPOTHALAMIC STIMULATION UPON CHOLESTEROL-INDUCED ATHEROSCLEROSIS IN THE RABBIT

The possible role of the central nervous system (CNS) in the pathogenesis of experimental atherosclerosis has received scant investigative scrutiny. Indeed, it can even be stated that the majority of investigators in the field of experimental atherosclerosis are frankly skeptical of any possible etiological relationship between dysfunction of any central neural mechanisms and peripheral atherosclerosis. Certainly in most of the recent American reviews concerned with atherosclerosis the subject of nervous factors in the etiology of atherosclerosis has either been minimized or totally neglected. Despite this seeming exclusion of the CNS from laboratory studies of atherosclerosis by many investigators, certain experimental and clinical data make this neglect appear rather unfortunate.

The Antiatherogenic Effect of Iridium192 upon the Cholesterolfed Rabbit

A 20-cm length of Ir192 wire was placed for 48 hours in the proximal portion of the aortas of a series of rabbits. The rabbits, when subsequently fed a diet containing excess cholesterol, failed to exhibit significant atherosclerosis, as compared to the control animals, in that pontion of the aorta which received the irradiation. The histological and chemical studies performed upon these rabbits suggest that the antiatherogenic effect of the irradiation was due primarily to the suppression of the intimal hyperplastic response to a persistent hypercholesteremia usually observed in the rabbits aorta.

Observations concerning the metabolism of cholesterol in the hypo- and hyperthyroid rat.

The administration of thiouracil induced a rise and administration of thyroid substance a decrease of the plasma cholesterol concentration in rats. The concentration and daily output of bile cholesterol was markedly reduced in hypothyroid rats and markedly increased in hyperthyroid rats. Evidence is presented which suggests that the rate of synthesis of cholesterol is significantly increased in the hyperthyroid rat and decreased in the hypothyroid rat.

Plasma ACTH and Cortisol Concentration of Coronary-Prone Subjects

Summary The plasma corticotropin and cortisol concentrations of 9 coronary-prone (Type A behavior pattern) and 10 coronary-resistant (Type B behavior pattern) subjects were studied at 6 time intervals during their waking hours. The average plasma corticotropin content of the 9 Type A subjects was significantly greater during the total period measured than that of the 10 Type B subjects. The average daily peak value of plasma corticotropin of the Type A subjects also was found to be significantly increased. No significant differences were found in either the average or peak plasma cortisol values between these 2 groups of subjects. The authors express their thanks to Drs. Berson and Yalow for their ACTH analyses of the plasma samples of these subjects.

Elevated daytime urinary excretion of testosterone glucuronide in men with the type A behavior pattern.

&NA; Urinary excretion of testosterone glucuronide was compared in 13 men with typical Type A behavior pattern (as determined by structured interviews) and 10 age‐matched men with typical Type B behavior pattern. Twenty‐four hour urine collections were divided into three periods: 9AM ‐ 6PM, 6PM to bedtime, and bedtime to 9AM. Type A men showed a significantly higher excretion than Type B men in the daytime (9AM ‐ 6PM ); the geometric mean value was 24 micrograms in Type A and 15 micrograms in Type B (P less than 0.05). There were no significant differences between Type A and Type B men for the other two time periods. Indicating an elevated daytime testosterone secretion in Type A men, this finding is consistent with a recent report that exposure to laboratory tests of reaction time causes an increase in plasma testosterone levels in Type A but not Type B men. Since a role for testosterone in the genesis of coronary heart disease (CHD) is suggested by the much higher incidence of CHD in men and the acceleration of murine atherogenesis by testosterone, the findings of this and the previous report may represent a mechanism for the elevated incidence of CHD in Type A men.

Bile acid metabolism, dietary fats, and plasma cholesterol levels.

Summary 1. Administration of highly unsaturated fats to the rat effected a greater intestinal absorption of cholesterol than similar administration of saturated fats. 2. Following continued ingestion of highly unsaturated fat, there was evidence that the fall in plasma cholesterol observed was accompanied by a marked increase in excretion of both cholesterol and bile acid in the bile. 3. The possible relationship of reduction in plasma cholesterol to the observed change in bile cholesterol and bile acid excretion is discussed.