Atheromatous Changes Research Articles

Inhibition of the pathogenesis of spontaneous hypertension in spontaneously hypertensive rats by feeding a high fat diet.

Spontaneously hypertensive (Okamoto-Aoki) rats (SHR) and normotensive (Wistar-Kyoto) rats (WKY) were fed a regular or a high fat diet when they were weaned; animals from each group were autopsied at 60, 90, 230, 250, and 180 days of age. SHR fed the high fat diet were cachectic, their pituitary glands were abnormally small, and despite severe hyperlipidemia, hyperglycemia, and adequate corticosterone levels, their zona glomerulosae were completely depleted of lipid, and they did not develop hypertension (110-115 mm Hg) or any manifestation of atheromatous changes. WKY fed the high fat diet became obese, their pituitary glands increased in size, and their normal blood pressure was slightly reduced (90-115 mm Hg). SHR fed the regular diet developed their usual severely elevated hypertension (185-205 mm Hg). It is suggested that the introduction of a high fat diet at an early age will cause hypopituitarism and inhibit the spontaneously appearing hypertension in SHR.

Characterization of the rabbit heart in cholesterol-induced coronary atherosclerosis. Morphometric studies.

Morphometric studies were carried out on 14 hypercholesterolemic rabbits (the animals had been fed 2 g of cholesterol per day over a period of three months) and 15 control animals with a view to measuring structural changes in coronary arteries and in the myocardium and, in a second study, to correlating morphological and biochemical findings with physiological parameters of the myocardial contractility. The results of the morphometric examinations of the coronary arteries and of the myocardium allowed the following conclusions to be drawn: o 1. Unlike subepicardial coronary arteries, the intramural coronary arteries show more frequent atheromatous changes (58% as compared with 34%). In addition, the atherosclerosis of intramural arteries is more severe. Atherosclerosis in the 2nd grade (reduction of the lumen area of more than 50%) and in the 3rd grade (complete coronary occlusion) predominate. They occur in 47 and 24% of the cases, respectively. 2. Intramural coronary arteries show a significant reduction of the mean lumen area by 44%, a significant increase in the vascular diameter and an increase in the vessel wall by 22%. Subepicardial coronary arteries, on the other hand, show a reduction of the mean lumen area by 26% and an increase in the wall area by 31% without a change in their vascular diameters. The increase is attributed mainly to a broadening of the intima. 3. The coronary sclerosis index (ratio of lumen area to wall area) increases in subepicardial coronary arteries by a factor of 1.8 and in intramural coronary arteries by a factor of 4.3. 4. The average of coronary stenosis is 16% in the case of subepicardial coronary arteries and 77% in the case of intramural coronary arteries. 5. The number of small intramural vessels per unit area in the myocardium of the left ventricle is significantly higher than in the case of the controls. 6. The number of heart muscle cell nuclei per unit area (left ventricle) diminishes significantly. 7. There is no morphometric evidence of an increase in the number of interstitial connective tissue cells in the myocardium of the left ventricle. 8. The percentage of myocardial lesions (granulation tissue and scars) is not greater than 4 per cent. Myocardial necroses were not observed. The increase in intramyocardial vessels and the complete absence of myocardial infarctions are regarded as an adaptation to predominantly intramural stenosing coronary atherosclerosis. According to morphological findings cholesterol-induced coronary atherosclerosis of the rabbit as an experimental model of human ischemic heart disease is not suitable without additional measures and should therefore be used for examining local adaptation mechanisms of the myocardium rather than for studying of the pathogenesis of myocardial infarction.

Virus-induced atherosclerosis.

Of four groups of chickens, two (groups I and II) were infected with MDV and two were not (groups III and IV). Groups I and III were fed diets low in lipid, and groups II and IV were fed cholesterol-supplemented diets. Striking grossly visible atherosclerotic lesions were seen in large coronary arteries, aortas, and major aortic branches of infected normocholesterolemic and hypercholesterolemic chickens (groups I and II). In contrast, grossly visible atherosclerotic lesions were not seen in uninfected normocholesterolemic chickens (group III), nor in uninfected hypercholesterolemic chickens (group IV). Microscopically, arterial changes in the infected animals were characterized by occlusive fibromuscular intimal thickening which formed fibrous caps overlying areas of atheromatous change. This change closely resembled chronic atherosclerosis in man. These results may have important bearing on our understanding of the etiology and pathogenesis of human arteriosclerosis since there is widespread and persistent infection of human populations with up to five different herpes-viruses.

Effect of garlic oil in experimental cholesterol atherosclerosis

Addition of cholesterol in the diet of male albino rabbits produced hypercholesterolaemia, increased tissue cholesterol, and atheromatous changes in the aorta. Supplementation of garlic oil along with cholesterol significantly inhibited the hypercholesterolaemia, decreased tissue cholesterol and minimised the atheromatous changes in the aorta. These results show that the active constituent(s) in garlic responsible for its anti-atherogenic action is present in the oily fraction of garlic.

Influence of Tissue Transglutaminase on Fibrin Metabolism

In order to investigate the biological activity of tissue transglutaminase (TGS), extraction techniques and some biochemical and immunological trials were performed and the following results obtained:1) In the procedure for preparation of TGS extract, animals and/or organs were perfused via hearts and/or efferent vessels with 0.25M sucrose-EDTA, 2M KCl and 2M urea solutions before homogenation, and supernatants secured by high speed centrifugation (15, 000g) for 30 minutes were applied as samples as they were. The sucrose-EDTA extract was found most adequate, judging from its activity and handiness of further maneuver.2) Tissue TGS was found to have the following three main differences from plasma FSF sofar.a) Although plasma FSF was activated by thrombin and calcium, tissue TGS had no effect of the addition of these reagents, but showed its activity without them.b) Tissue TGS exhibited no antigenicities of subunits A and S which were proved in plasma FSF and these two enzymes were not found their cross-reaction.c) Plasma FSF was proved its higher affinity to fibrinogen than to α-casein in the MDC incorporation as much as twice, but tissue TGS showed quite contrary tendency of higher reactivity with α-casein than with fibrinogen more than twice as much.3) Tissue TGS activity of liver was highest and those of spleen, heart, lung and kidney were followed in this order. Among the three layers of aorta, intima had the highest TGS activity as much as twice of adventitia and media, which suggested some relationship with the development of atheromatous changes.4) Cross-linked, stabilized fibrin showed rather higher resistance to plasmin and UK fibrinolysis than unstabilized one.

HYPERREACTIVE ARTERIAL ENDOTHELIAL CELLS: A CLUE FOR THE TREATMENT OF ATHEROSCLEROSIS

Arterial endothelial cells, which are capable of phagocytizing carbon particles of the same size as beta- and pre-beta-lipoprotein, were found only in endothelial cells of arterial segments susceptible to atheromatous changes in susceptible animal species, and the distribution closely corresponded to the susceptibility. The distribution of such endothelial cells is dense in large arteries, in the openings to their branches, especially in downstream portions, of rabbits, hens, and cocks; however, the distribution is relatively scanty in arteries of rhesus monkeys and is very scanty in dogs. Carbon particles were also rare in the suckling rabbit and tended to increase with age. They were not found in Wistar rats but were found in spontaneously hypertensive rats, which showed a characteristically diffuse distribution, even in relatively small arteries. The carbon particles, phagocytized, were released to the subendothelial space but were difficult to pass through the internal elastic lamina and tended to stagnate there for more than one month. The authors therefore call these cells hyperreactive endothelial cells. Various vasoactive substances, such as angiotensin II, histamine, and serotonin, significantly enhanced the phagocytic activities of arotic endothelial cells in rabbits; epinephrine and norepinephrine also slightly enhanced these activities. Various smooth muscle relaxants, such as ATP, pyridinol carbamate (ATP synthesis-enhancing substance), cycli-AMP, dibutyryl cycli-AMP, phthalazinol (cyclic-AMP phosphodiesterase inhibitor), iproveratril (calcium entry-inhibiting substance), colchicine, and vinblastine, with their different modes of action, commonly inhibited phagocytic activities, a finding that suggests a significant role for contractile protein in the permeability problem of atherogenesis. The atheromatous lesions of cholesterol-fed rabbits exhibited a striking increase in hyperreactive endothelial cells, accompanied by a marked rise in the activity of low-Km cyclic-AMP phosphodiesterase activity in atheromatous lesions and adjacent muscular layers, especially in rabbits with rapidly progressing atheroma.

The results of carotid angiography in cerebral infarction in normotensive and hypertensive subjects

The results of carotid angiography in 304 cases of cerebral hemisphere infarction have been reviewed. Carotid occlusion was demonstrated in 19% and atheromatous vessel wall change in a further 28%. Hypertensive subjects showed a significantly lower prevalence of carotid occlusion, but a similar prevalence of vessel wall change. There was more likely to be angiographic abnormality if there was a neck bruit or if the ECG showed ischaemic changes. The findings support the concept that the pathogenesis of cerebral infarction differs in normotensive and hypertensive patients.

105 mm photofluorography: an adjunct to the study of coronary arterial and vascular disease.

Obtaining high resolution static films through an image intensifier has been made possible by recent developments in radiographic equipment. Serial photofluorography 105 mm spot filming has been used successfully to complement cine coronary arteriography in approximately 700 patients. Many patients with coronary heart disease have diffuse peripheral atheromatous changes which are also suitable to study by serial 105 mm photofluorography. Aortic arch, abdominal aortography, and peripheral studies are easily and quickly performed in conjunction with coronary arteriography. Satisfactory results still depend upon skillful application by the angiographer of this imaging mode and proper processing of the film. Advantages of photofluorographic filming over conventional large film techniques include lower radiation exposure, reduction of costs, and easier film handling and storage. Most important is the facilitation of the performance of angiographic studies since constant television monitoring of the catheter and the contrast injections is possible. Disadvantages include restricted area of coverage and slight decrease in resolution. Our experience indicates that photofluorography may be relied upon in the study of vascular disease eliminating the need for large film changers in a laboratory used primarily for cardiac diagnosis.

Internal mammary artery versus autogenous vein for coronary artery bypass graft.

Aortocoronary venous graft (ACVG) and internal mammary artery graft (IMAG) are currently the two most popular choices for coronary artery bypass. The morphologic alteration and susceptibility to atheromatous degeneration of the IMAG were compared with the ACVG. Six of 12 surviving dogs with IMAGs were fed a hyperlipidemic diet and six were placed on a regular diet. All dogs were sacrificed 3-15 months after surgery. Twelve of 28 long-term surviving dogs with ACVGs were also on hyperlipidemic diets, and all were sacrificed 3-18 months after surgery. Arteriography and electron microscopy were performed in selected cases, and histology was performed in all cases. All long-term IMAGs remained patent; 83 percent (5/6) "regular" diet arteries were normal, with no intimal proliferation, while 33 percent (2/6) "hyperlipidemic" IMAGs had diffuse atheroma. Eighty-two percent of ACVGs revealed significant atherosclerosis. Severity of arteriosclerotic involvement of the ACVG was far greater than that of the native coronary circulation; this was not true for the IMAG. It may be concluded that (1) in the normolipidemic condition the IMAG undergoes significantly less severe histologic change than the ACVG, (2) both the IMAG and the ACVG are more susceptible to atheromatous change than the native coronary circulation. In these series, patency was not influenced by severity of histologic changes, and no grafts were occluded by virtue of the arteriosclerotic process.

Autogenous vein grafts in experimental canine atherosclerosis. Their fate in the abdominal aorta and peripheral arteries.

The fate of autogenous vein grafts inserted into the abdominal aorta and peripheral arteries was studied in experimentally induced canine atherosclerosis. The grafts in the abdominal aorta developed atherosclerotic changes, became dilated, and, in most instances, were surrounded by a moderate to severe fibrous reaction. Microscopically, all three coats of the vein were involved in variable degrees with characteristic morphologic and lipid degenerative changes. The grafts implanted by end-to-side anastomosis into peripheral arteries (femoral, carotid) displayed minimal or no atheromatous changes while those implanted by end-to-end anastomosis become stenosed or occluded by organized thrombi. Among the factors that may contribute to venous atherogenesis are the morphologic changes, turbulence, increased pressure, and filtration factors. When veins are placed artificially in the arterial tree, other factors than the tissue itself appear responsible for the morphologic and lipid degenerative changes.

Internal mammary artery versus autogenous vein for coronary artery bypass graft

Aortocoronary venous graft (ACVG) and internal mammary artery graft (IMAG) are currently the two most popular choices for coronary artery bypass. The morphologic alteration and susceptibility to atheromatous degeneration of the IMAG were compared with the ACVG. Six of 12 surviving dogs with IMAGs were fed a diet and six were placed on a diet. All dogs were sacrificed 3-15 months after surgery. Twelve of 28 long-term surviving dogs with ACVGs were also on diets, and all were sacrificed 3-18 months after surgery. Arteriography and electron microscopy were performed in selected cases, and histology was performed in all cases. All long-term IMAGs remained patent; 83 percent (5/6) regular diet arteries were normal, with no intimal proliferation, while 33 percent (2/6) hyperlipidemic IMAGs had diffuse atheroma. Eighty-two percent of ACVGs revealed significant atherosclerosis. Severity of arteriosclerotic involvement of the ACVG was far greater than that of the native coronary circulation; this was not true for the IMAG. It may be concluded that (1) in the normolipidemic condition the IMAG undergoes significantly less severe histologic change than the ACVG, (2) both the IMAG and the ACVG are more susceptible to atheromatous change than the native coronary circulation. In these series, patency was not influenced by severity of histologic changes, and no grafts were occluded by virtue of the arteriosclerotic process.

Comparison of effects of high cholesterol intake on viscoelastic properties of the thoracic aorta in rats and rabbits.

Abstract The influence of high cholesterol intake on elastic properties of segments of the descending aorta of rabbits and rats was studied by means of in-vitro preparations. Each species was equally divided in a diet-group and a control group. Cholesterol was administered to both diet-groups during a period of 2 months. The age of the animals could be described as young. Tangential dynamic Young's moduli were found to be increased by more than 50% in cholesterol-fed rabbits. An average value of 6.5 × 106 dynes/cm2 was found in this group, vs. an average value of 4.0 × 106 dynes/cm2 in the control group. In specimens from the rats the longitudinal dynamic Young's modulus was measured at two values of length: the in-vivo (natural) length and 1.2 times the in-vivo length. Although an increase of Young's modulus was found in the diet-group (from 0.31 × 106 to 0.54 × 106 dynes/cm2 at the natural length, and from 2.4 × 106 to 3.2 × 106 dynes/cm2 at the extended length) no statistically significant differences could be demonstrated. Also, in both species, no significant differences in the amounts of retraction were found. Values of several serum lipids were determined and correlated to the obtained Young's moduli. There was found to be a positive correlation between the increases of serum lipids and Young's modulus in the rabbits, but (probably due to the limited number of animals) this correlation was not yet found to be significant. It is discussed that the arterial load to the heart is increased to a rather high degree when atheromatous changes of the arterial wall are induced.

Embolism of the central retinal artery secondary to metastatic carcinoma.

A 54‐year‐old man experienced sudden loss of vision of one eye and was admitted four hours later for treatment of typical occlusion of the central retinal artery. The patient died three weeks later and the autopsy revealed bronchial carcinoma of the epidermoid type with metastasis in most visceral organs. Microscopic examination of the eye disclosed the central retinal artery to be patent but with atheromatous changes at the level of the lamina cribrosa. The retina showed evidence of acute ischaemic infarction of the inner retinal layers. Tumour emboli were observed in the retinal arterioles. Trypsin‐digest preparations were also employed to demonstrate tumour cells in the retinal arterioles.

The intimal proliferation in aortic-coronary saphenous vein grafts: Light and electron microscopic studies

The pathologic features of 16 aortic-coronary saphenous vein grafts which had been in place from 2 days to 29 months were reviewed. Thirteen cases came to autopsy and three vessels were surgically re-excised. The nine cases which had been in place for two months or longer showed considerable intimal fibrosis. Four were stenosed and five were occluded. One of the vessels, 29 months after grafting, showed atheromatous changes within the thickened, fibrosed intima. The ultrastructure of one of the occlusive fibrotic lesions demonstrated the presence of histiocytes, newly-formed capillary blood vessels, fibroblasts, and characteristic smooth muscle cells, some of which contained lipid vacuoles in the cytoplasm.

Tissue response to an arterial substitute of bovine origin.

Tissue responses in and to a heterograft collagen tube, used as an arterial substitute in 27 patients, demonstrated by biopsies at intervals from three days to 32 months that this graft was inert and became incorporated within a tube of living collagenous host tissue. Within five weeks of implantation, the operative debris was cleared and the host collagenous tissue surrounding the graft was well developed. Incorporation of the graft by the host tissue continues so that at eight months the graft collagen was difficult to identify in the adventitial layer. Atheromatous changes appeared after several months in areas which histologically appeared to be evolution of lesions of small dissections of blood into the media. Four grafts with aneurysms showed atheromatous changes; however, other factors may have been involved in their cause.

Coagulation defects and atherosclerosis induced in rabbits by a diet containing medium chain triglyceries (MCT).

Abstract In recent years medium chain triglycerides (MCT) have been widely used in the treatment of various diseases, such as different forms of malabsorption and certain types of hyperlipaemia. Only a few animal experimental studies and hardly any long‐term studies had been available before the introduction of this agent as a therapeutic in clinical medicine. In experiments on rabbits a semisynthetic diet containing 20% MCT produced a remarkable rise in serum cholesterol, a certain increase of the triglycerides and distinct atheromatous changes in the aorta. The level of linoleic acid decreased markedly in the neutral lipids of serum, liver and adipose tissue. There was also an influence on the relative proportions of saturated and monounsaturated long chain fatty acids in the serum lipids. The phospholipids of serum and liver retained relatively high levels of linoleic acid. An incidental finding was that MCT caused a defect of the coagulation of the same type as that seen in severe diseases of the liver, such as liver cirrhosis in man. At postmortem examination considerable changes were found in the liver, probably a manifestation of a toxic effect. In two cases MCT was replaced by an equivalent amount of corn oil after 32 weeks. This resulted in a rapid normalization of the serum cholesterol and triglyceride values. The coagulation of the blood also became normal. Postmortem examination of these two cases, after they had been fed corn oil for 18 weeks, revealed a normal or practically normal liver.

Metabolism of L-Ascorbic Acid-l-14C in Guinea Pigs with Alimentary Cholesterol Atheromatosis

A diet containing 0.3% cholesterol fed to guinea pigs for 18 weeks caused an accumulation of cholesterol in blood serum, liver and adrenals, atheromatous changes in coronary arteries and a marked increase in the weight of liver and spleen, in comparison with controls fed the same diet without cholesterol. Ascorbic acid intake was the same in these two groups (10 mg per animal per day, given through a stomach tube). Ascorbic and dehydroascorbic acid concentration in liver and adrenals was not changed in the cholesterol-fed animals, but the total quantity of ascorbic acid in their liver and spleen was substantially higher. Urinary excretion of ascorbic, dehydroascorbic and diketogulonic acids was decreased in this group while oxidation of intraperitoneally administered ascorbic acid-1-14C to 14CO2 remained unaltered. Urinary excretion of 14C was lower in the cholesterol-fed group. Specific activity of ascorbic acid in the tissues of cholesterol-fed guinea pigs was found to be significantly decreased at 96 hours after administration of labeled ascorbic acid compared to that at 48 hours. Guinea pigs with experimental atheromatosis had a significantly larger body pool and a moderately, though significantly, prolonged biological half-life of ascorbic acid. In guinea pigs with dietary cholesterol atheromatosis, an increased ascorbic acid retention exists.

Turbulence in human intracranial saccular aneurysms.

✓ Preliminary experiments with glass model bifurcation aneurysms demonstrated that turbulent flow pattern occurs in the sac of an aneurysm at a low flow rate (critical Reynolds number, 400 ± 10 S.E.M.). A prediction that flow is turbulent in the sac of human intracranial saccular aneurysms was confirmed in a clinical study. Bruits, indicative of turbulence, were recorded with a phonocatheter from the sacs of 10 out of 17 intracranial aneurysms exposed at surgery where the mean arterial pressures were above 50 mm Hg. The amplitude of the bruits varied with the pressure. All of the patients in whom no bruit was found had profound Arfonad hypotension at the time of recording. Turbulence causes vibration in the wall of a vessel. This vibration produces and accelerates degenerative changes in vascular tissue by a process similar to the structural fatigue of metals by vibration. The author proposes that the turbulent blood flow within an aneurysm contributes to the degeneration of the elastica, and the production of the atheromatous changes, characteristically seen in its wall. This weakens the wall causing continuing enlargement and eventual rupture.

The effect of (−) N-[α-phenyl-β-( p-tolyl)ethyl] linoleamide on experimental atherosclerosis in rabbits

Optically active (−) N-[α-phenyl-β-( p-tolyl)ethyl] linoleamide (PTLA) was found to have a remarkable hypocholesterolaemic effect in rabbits. Administration of PTLA (5–10 mg/day/animal) significantly lowered serum and liver cholesterol and significantly prevented formation of aortic atheromatous changes in rabbits that had been given 1.6 g cholesterol daily.

Ultrastructural studies of the medial aortic sclerosis in rats with experimentally induced chronic renal disease

Ultrastructure of rat aortic medial sclerosis developing after experimental production of chronic renal disease is described. The calcium deposit in the medial layer of the aortic wall occurs with a predilection for the elastic fibers and more precisely the microfibrils of the elastic fibers. The calcification occurs in variable ultrastructural configurations. It appears that microfibrils and collagen fibers can act as a core of calcification. Ultrastructural modifications of smooth muscle cells such as increased cytoplasmic organelles, cytoplasmic cysternae, or vacuoles, and extension of many cytoplasmic processes are present without any atheromatous change of the wall.