William E. Connor

Regression of Coronary Atheromatosis in Rhesus Monkeys

Rhesus monkeys subjected to the atherogenic stimulus of a high-fat, high-cholesterol diet showed significant coronary atheromatosis at the end of 17 months. Smaller fibrotic lesions with scant stainable lipid were found in animals that were subsequently fed either of two cholesterol-free diets for 40 months. The average cross-sectional area of the lumen was more than 80% greater in regression animals than in monkeys with baseline atherosclerosis. The data support the hypothesis that uncomplicated coronary atheromas may regress in primates in appropriate dietary settings.

Platelets, Fatty Acids and Thrombosis

The sodium salts of stearic, oleic, linoleic and linolenic acids were added to human washed platelet suspensions and platelet-rich citrated plasma. Aggregation of the platelets was measured microscopically and with a turbidimetric method. All of the fatty acids had the ability to produce aggregation when added to washed platelets, but stearic acid, a long-chain saturated fatty acid, was more potent than were the unsaturated acids when added to platelet-rich plasma. Aggregation of platelets by fatty acids required the presence of calcium ions and the aggregation was irreversible. The addition of albumin diminished the aggregating effects of fatty acids, but microscopic aggregates still formed in most instances. Subnormal aggregation was noted when sodium stearate was added to platelet-rich plasma from a patient with a severe deficiency of factor XII (Hageman factor). Thus, fatty acids are now known to have two potential thrombogenic effects: platelet aggregation and the activation of clotting factors involved in the early stages of blood coagulation.

Placental transfer of cholesterol into the human fetus.

Abstract In order to study the maternal-fetal transfer of cholesterol in human subjects, a tracer dose of cholesterol-4- 14 C was given intravenously to a woman three months pregnant some 13 days before therapeutic abortion and sterilization were performed. Serial maternal blood samples were obtained thereafter until the date of the operation to determine the decay of cholesterol radiospecific activity in the plasma. Fetal and maternal tissues were analyzed for cholesterol and radioactivity. As in previous subhuman primate studies, the significant amount of radioactivity found in fetal tissues indicated considerable transfer of the cholesterol-4- 14 C molecule from the mother into the fetus. All of the radioactivity in the fetus was found only in the cholesterol molecule. The cholesterol specific activity (S.A.) of the combined fetal tissues was 42 per cent of the S.A. of the maternal serum. With the assumption that the fetal-maternal back-transter of isotopic cholesterol across the placenta is low, our calculations indicated that over the period of 13 days 20.7 per cent of the fetal cholesterol was derived from maternal sources. The mean flux rate of cholesterol into the fetus was 458 μg per day. The cholesterol contents of the fetal organs were 20 and 29 mg. per gram of dried tissue for liver and brain, respectively. Desmosterol, a precursor of cholesterol biosynthesis, constituted 2 per cent of the brain sterois.

The depressant effect of fatty acids on the isolated rabbit heart.

Summary The toxic effects of stearic and oleic acids on the rabbit myocardium were investigated in a plasma-free system using a modified Langendorf isolated heart preparation. A 0.1% stearic acid or 0.1% oleic acid solution was added to the solution which perfused the coronary vessels. The coronary flow, and the rate and amplitude of contractions progressively deteriorated until there was death of the heart. Equimolar albumin incubated with the fatty acid solutions prevented this toxic effect. The time of incubation was important to the blocking of toxicity for stearic acid but not for oleic acid. No incubation period was required to prevent the toxicity of the oleic acid when combined with albumin. This suggested a difference in the rate of albumin-fatty acid binding for different fatty acids. Unbound fatty acids, saturated or unsaturated, were extremely toxic to the heart.

The Coagulant and Thrombogenic Properties of Human Atheroma

Suspensions of gruel from severely atherosclerotic human aortas and coronary arteries were tested in several coagulation systems. The atheromatous material shortened the clotting time of normal whole blood and plasma and accelerated thrombus formation time in the Chandler apparatus. Normal human platelets in platelet-rich plasma were aggregated by the atheromatous gruel. Aggregation did not occur when the gruel was added to platelet-rich plasma from a patient with a severe factor XII (Hageman) deficiency. The intravenous injection of atheromatous plaque suspensions into rats caused thrombocytopenia, shortening of the whole blood clotting time, and thrombosis. Coagulation of blood from patients with classical hemophilia, with Hageman factor deficiency, and with coumarin-induced anticoagulant effect was accelerated by the addition of the atheromatous gruel. Blood from patients given heparin, however, largely retained its anticoagulant activity. Atheromatous material from both aortic and coronary arteries be...

Identification of β-sitosterol, campesterol, and stigmasterol in human serum

The presence of 3 plant sterols, β-sitosterol, campesterol, and stigmasterol, has been demonstrated in the serum from 2 patients with β-sitosterolemia and xanthomatosis.

Plasma Lipoprotein Lipase after Subcutaneous Heparin

Plasma lipoprotein lipase was measured at intervals after the subcutaneous injection of heparin in 34 men. This enzyme was significantly increased in plasma for as long as 24 hours after a 50-mg. dose. While the initial response was greater after a 200-mg. dose, the 24-hour lipoprotein lipase was similar for both 50 mg. and 200 mg. Plasma lipoprotein lipase produced after intravenous heparin was dissipated after 6 hours. The lipoprotein-lipase response at 16 and 24 hours after the subcutaneous injection of heparin was similar in men with coronary and cerebral atherosclerosis and in healthy men. Age did not affect plasma lipoprotein-lipase response. Patients who had received 50 mg. of heparin subcutaneously each day for an average time of 12 months did not have exhaustion of the lipoprotein-lipase response to a test dose of heparin. It is suggested that the daily administration of heparin is necessary to produce a continuous concentration of plasma lipoprotein lipase. A dose of 50 mg. (5,000 units) given subcutaneously produced a prolonged lipoprotein-lipase response and only a mild anticoagulant effect, unlikely to induce the complication of bleeding.

Use of vitamin K1 in pregnancy

In general, from this double blind study of 204 infants it appeared that prenatal oral administration of vitamin K 1 exerted a beneficial effect on the relative deficiency of prothrombin that normally exists in the newborn infant. There was no evidence of undesirable side effects from doses of vitamin K 1 employed in this study. Bilirubin levels in the newborn infants receiving vitamin K 1 were not increased over the values in the placebo group. It is not possible to conclude from these data that such treatment is to be generally endorsed.

The Accumulation of Serum Lipoprotein Cholesterol by Tissue Culture Cells

Summary β-Lipoprotein isolated from human or bovine serum elicited sudanophilic inclusion bodies within cultured fibroblasts. Such sudanophilia was accompanied by an increase in cellular cholesterol, about 2/3 of which was in the esterified form. The origin of the cholesterol appears to be largely from the deposition of β-lipoprotein-bound cholesterol ester instead of newly esterified cholesterol. Much of the accumulated cholesterol, especially the cholesterol ester, was found within the inclusion bodies. They should be particularly considered as being formed as the result of cholesterol ester uptake. Free cholesterol bound to bovine albumin also elicited intracellular sudanophilic inclusion bodies containing cholesterol ester. Free cholesterol in microcrystalline form did not lead to similar sudanophilia or increase in cellular cholesterol content. This tissue culture system provided analogies to atherosclerosis in that cholesterol accumulated in the cells in both instances when the extracellular medium or plasma contained high concentrations of cholesterol bound to protein. In both instances, also, lipid droplet formation occurred and cholesterol ester accumulation was the chief form of the cholesterol overload.

Influence of Soybean Phosphatide on Blood Coagulation and its Use in the Thromboplastin Generation Test

Summary By its use in a variety of blood clotting systems, soybean phosphatide has been shown to act as a partial thromboplastin in blood coagulation. In vitro, this substance displayed anti-heparin activity in human and dog blood and anti-protamine activity in human plasma. A simplified thromboplastin generation test is described for the study of hemorrhagic disorders. Soybean phosphatide serves as a complete substitute for platelets in this test.