Journal of atherosclerosis research最新文献

A Polarographic technique was used to evaluate changes in arterial wall oxygen availability during systemically administered and endogenously released norepinephrine. A 125-μ, diameter bare-tipped platinum electrode was advanced into the media of exposed femoral arteries in 23 anesthetized dogs. Tissue oxygen availability was recorded in terms of current flow through the Polarographic electrode system. Intravenously administered norepinephrine produced a vasopressor response and was associated with significant reductions in the oxygen current in intact and autografted vessels. Similar reductions in intramural oxygen availability were produced by ipsilateral lumbar sympathetic ganglia stimulation. The norepinephrine-induced changes in oxygen availability were produced even when the blood pressure in the femoral artery was held constant by pump perfusion. Furthermore, intramural oxygen availability could not be reduced by passive increases in luminal pressure. These findings indicate that norepinephrine reduced intramural oxygen availability by a direct metabolic effect on the smooth muscle of the vessel wall.

The fibrinoid necrosis developing in the course of experimental malignant hypertension was examined for the presence, localization and appearance of lipids. In the initial stage of hypertension, only sudanophilic droplets were demonstrable in the necrotic muscle cells of the media, but later diffuse sudanophilia was apparent over nearly the entire cell body. The subendothelial fibrinoid developing during the second stage was Sudan negative, whereas the necrotic medial cells exhibited a distinct sudanophilia. At the same time a considerable extra- and intracellular sudanophilia also appeared in the perivascular granulation tissue, but it tended to decrease or entirely disappear during the third stage. At this time, foam cells appeared in the subendothelial fibrinoid. Based on our findings, the sudanophilia of the media has been attributed to lipids rendered visible by phanerosis.

The effect of dietary myristic acid on serum cholesterol of rats was studied using mixtures of trimyristin and groundnut oil. Incorporation of trimyristin in the oil resulted in marked rise in serum cholesterol of rats over the control group fed groundnut oil. A direct relationship between serum cholesterol and the myristic acid content of dietary fat was not apparent. Thus the cholesterol response to a diet containing an interesterified fat, prepared from a mixture of trimyristin and groundnut oil, was lower than that obtained by administering the same fat mixture without treatment.

Mitochondrial fractions from normal and atherosclerotic rat aortae were isolated by differential centrifugation. Oxidative phosphorylation was evaluated on these fractions using a Polarographic method for the measurement of oxygen uptake and the determination of the ADP/O ratio. The results do not indicate any impairment of the mitochondrial oxidative phosphorylation mechanism in the atherosclerotic aorta.

Male C57BL/6J inbred mice started on a high-fat, high-cholesterol diet at age 5–6 weeks survived well (100 % alive after 25 weeks) on the diet provided they were introduced to it gradually. All animals on the diet at least 5 weeks showed marked incorporation of fat into the subendothelial cells and in 7/8 the cells were swollen enough to be designated as foam cells. After 10 weeks on the diet all animals showed foam cells and as the diet continued for 15, 20 and 25 weeks the lesions, in general, increased in extent, in depth (the media was frequently involved) and in numbers. All lesions reported were in the region of the aortic valves.

Platelet size and function have been studied in 192 subjects in equally-sized and carefully-matched groups of controls and patients with either acute or chronic ischaemic heart disease. The data were analysed by computer to determine significant correlations.

The platelets of subjects who have recently suffered acute myocardial necrosis are larger than those of control subjects and they respond less well and more slowly to ADP. They do not differ in numbers nor in behaviour at glass surfaces. The platelets of subjects with chronic ischaemic heart disease have properties intermediate between those of the acutely ill subjects and controls. As the healing of myocardial necrosis proceeds, these platelet abnormalities progressively reduce. The changes are insufficiently large to be of value in individual clinical diagnosis.

Adhesive platelets are smaller than non-adhesive platelets, but this difference is much more marked in control than in diseased subjects. We have not shown any differences between platelets that aggregate with ADP and those which do not.

Male and female rats bred repeatedly develop arteriosclerosis spontaneously. Arteriosclerotic breeder rats and non-arteriosclerotic virgin rats were given chronic injections of cortisone. The arteriosclerotic animals showed the most significant catabolic effects due to overdose with steroid. Most importantly, the excess glucocorticoid caused an acceleration of the usual pattern of development of the arterial disease and increased severity of the pre-existing arteriosclerosis in breeder rats. Chronic injection of steroid did not induce arterial damage in previously non-arteriosclerotic virgin animals. It is believed that the increased activity of the hypothalamic-pituitary-adrenal axis in repeatedly bred rats leads to increased endogenous steroid levels which conditions the arterial wall towards derangement of connective tissue ground substance and elements and to the development of arteriosclerosis. Exogenous steroid treatment causes exacerbation of previously existing arterial lesions.

Atherosclerosis begins in childhood with the appearance of aortic fatty streaks. Aortic fatty streaks of some degree are present in practically all individuals from every human population that has been studied. The average amount of aortic intimai surface involved with fatty streaks does not differ much among human populations.

Coronary fatty streaks begin to form in adolescence. Most persons 20-29 years of age have coronary fatty streaks of some degree, even if they are from low socioeconomic strata.

While fatty streaking is clinically harmless and potentially reversible, the progression of fatty streaks to more advanced lesions is a critical stage of atherosclerosis. This conversion takes place at earlier ages in populations with high morbidity and mortality from coronary heart disease.

The development of fibrous plaques begins in the twenties. Therefore, even though control programs which attempt to reduce coronary heart disease by preventing atherosclerosis may meet some success when applied to middle-aged persons, these programs should be directed toward individuals in the twenties and thirties for maximum benefits. Dietary habits that retard atherosclerosis should be established in childhood.

Male albino rabbits were exposed to short daily periods of systemic hypoxia for 2 weeks. Thirteen out of 16 rabbits showed gross arteriosclerotic changes, while no gross changes were found in 14 controls. The microscopic changes were primarily located to the media and consisted of calcified necrotic foci surrounded by amorphous, metachromatic intercellular substance. Metachromatic intercellular substance was also found in the form of “lakes” between the elastic membranes. A similar increase in the metachromatical intercellular substance was seen in the intima. The meta-chromasia indicated accumulation of acid mucopolysaccharides, which in the present study appeared to be primarily chondroitin-4-sulphate and/or chondroitin-6-sulphate and some dermatan sulphate and/or heparitin sulphate. A distinct calcification of the endothelial lining was observed. The changes probably reflect a damage of the aortic wall following systemic hypoxia and secondary non-specific processes of repair in the vascular connective tissue. The alterations have features in common with human arteriosclerosis.

Dipyridamole in a dosage of 600 mg daily for 2 weeks was given to 17 patients in whom the level of platelet adhesiveness was increased. It was found not to influence this parameter of platelet function.