Coronary artery atherosclerosis revisited in Korean war combat casualties.

To confirm earlier studies of a high prevalence of coronary atherosclerosis in combat casualties of the Korean and Vietnam wars, we examined previously uncut coronary arteries from the hearts of 94 American male combat casualties (mean age, 20.5 years) from the Korean War using computerized planimetry and microscopic evaluation. Six (6.4%) men had severe atherosclerosis (75% to 90% cross-sectional area luminal narrowing) in one or more coronary arteries; five of the six had fibrous plaques, and one had a complicated plaque. Our prevalence is similar to that reported previously (5%). Therefore, to determine whether the decrease in the incidence of severe coronary atherosclerosis today is the result of decreased plaque formation in the young, we will need to examine at least 772 men to detect a 50% decline with 85% to 90% confidence.

Arteritis in cardiac rejection after transplantation.

During a 4-year experience with cardiac transplantation, 33 hearts were obtained by autopsy or surgical resection for retransplantation. Arteritis was a feature common to all rejected hearts (14 of 14), but was absent in explanted hearts without rejection (0 of 19) (p = 0.001). Monitoring of acute cardiac rejection by endomyocardial biopsy (863 biopsies) was also reviewed, with special reference to the incidence of arteritis. Among the 16 patients with arteritis on 1 or more biopsies, 44% (7 patients, confidence limits 29 to 60%) suffered fatal rejection or underwent retransplantation because of irreversible rejection. Arteritis was seen in the small vessels obtained by endomyocardial biopsy in 4 of 5 persons who underwent biopsy within 3 days of death or retransplantation due to rejection and on none of the 6 persons who underwent biopsy within 3 days of death or retransplantation for causes other than rejection. Thus, arteritis is an important indicator for severe acute rejection, and although often reversible, may identify patients at higher risk for fatal rejection. Arteritis occurred in transplanted hearts subjected to varying combinations of cyclosporine, azathioprine and steroid therapy and could not be correlated with any drug regimen.

Diabetic cardiomyopathy. A morphological study of intramyocardial arteries.

The mechanism of heart failure in patients with diabetic cardiomyopathy is not clear. Previous studies suggested that vascular lesions specific for diabetes mellitus were present and that the lesions could be the basis for impaired cardiac function. We have investigated the histologic and histochemical characteristics of intramyocardial vessels (20 to 500 microns) in a group of diabetics using comparable groups of patients with hypertension, patients with hypertension and diabetes mellitus, and, as controls, patients with neither hypertension nor diabetes mellitus. Analysis of multiple blocks taken from the 42 study patients disclosed no lesions specific for diabetes mellitus or hypertension. The discrepancy between our findings and earlier reports is probably due to a lack of controls and the use of non-perfusion-fixed material in the earlier studies.

Innervation of brain intraparenchymal vessels in subhuman primates: ultrastructural observations.

Sympathetic innervation of intraparenchymal blood vessels in the basal ganglia was demonstrated by transmission electron microscopy in arteries, arterioles, and capillaries of the subhuman primate brain. Small arteries (40-120 micron) and some arterioles (12-40 micron) are innervated only at branching sites. However, arterioles occasionally may be innervated at points distal to their origin. Capillary innervation was very infrequently observed.

Staining in normal and ischemic human myocardium. A study of myoglobin, IgG, glycogen, and diastase-PAS.

Using the indirect immunofluorescence technique, we studied the distribution of myoglobin in normal and ischemic human myocardium obtained at autopsy and at surgery. Glycogen, diastase-PAS staining of the sarcoplasm, and IgG were also studied and compared with the structure of the lesions and the distribution of myoglobin. The surgical material we used was largely free of autolysis and was the most satisfactory. Prolonged fixation of tissues in formaldehyde solution or perfusion fixation of autopsy specimens both proved to be unsatisfactory as myoglobin was absent from the myocardium. This loss presumably represents diffusion of myoglobin due to autolysis and the method of fixation. Another group of autopsy specimens that was briefly fixed by immersion in formaldehyde solution prior to processing was more satisfactory. Although they showed some extracellular diffusion of myoglobin, the autolyzed normal areas could still be clearly differentiated from the autolyzed ischemic areas.

Computed tomography on invasive thymoma.

We report a case of invasive thymoma invading and occluding the superior vena cava in which the diagnosis was only made by the computed tomography (CT) study. Correlation of CT and autopsy findings of invasive thymoma were made in order to emphasize the usefulness of CT study in the evaluation of thymoma and its relationship with vascular structures.

Morphology of saphenous vein-coronary artery bypass grafts: Seven to 116 months after surgery.

Morphologic changes in saphenous vein-coronary artery bypass grafts in 24 cases (51 grafts) seven to 116 months after surgery were studied. Four pathologic changes were found (1) Fibrous cord lesions were present that represented early postoperative thrombotic occlusion and organization. (2) Diffuse intimal thickening was present in all grafts maintaining long-term patency. (3) Atherosclerosis identified as intimal foam cell accumulation or frank plaques was found only in cases 39 or more months postoperative and was present in 79% of such cases (71% of the vein grafts). (4) Late vein thrombosis was found in three cases and was the presumed cause of death. We concluded that atherosclerosis occurs with a high incidence in vein grafts after three years, and plaque rupture with thrombosis can be a cause for vein occlusion.

High resolution plasma lipoprotein cholesterol profiles by a rapid, high volume semi-automated method.

A new rapid and sensitive method, the single vertical spin autoprofiler (VAP), has been developed for quantitative profiling of the major plasma lipoproteins. The method involves a combination of single vertical spin separation of plasma and continuous on-line analysis of cholesterol. Plasma lipoproteins are first separated by a 45-min spin in a vertical rotor, after which the amount of cholesterol in the effluent of each tube is monitored continuously by a modification of the BMC automated enzymatic cholesterol method; simultaneously, 80% of the sample is diverted by stream-splitting to a fraction collector for further analysis, if desired. VAP not only resolves very low density lipoprotein (VLDL), low density lipoprotein (LDL), and high density lipoprotein (HDL) peaks quantitatively but also detects the presence of intermediate density lipoprotein (IDL) and other lipoprotein variants. VAP was highly reproducible; the inter-run coefficient of variation for cholesterol concentration in VLDL, LDL, and HDL was 4.8%, 2.9%, and 2.4%, respectively. Cholesterol recovery using VAP was 98.5 +/- 3.5%. Lipoprotein-cholesterol profiles of plasma from three major hyperlipoproteinemia phenotypes examined by VAP were qualitatively and quantitatively different from each other and from profiles of normolipidemic individuals. One significant finding was that IDL could be detected in the plasma of all type IV hyperlipoproteinemic subjects examined thus far. Several variant lipoprotein profiles which did not correspond to known phenotypes have also been detected by VAP using plasma from hyperlipidemic as well as from normolipidemic subjects. We submit that VAP is an accurate and rapid method for lipoprotein analysis, either for routine clinical screening or for detailed experimental studies. In addition, VAP provides a visual display of partially to completely resolved lipoprotein classes that is suitable for computer-assisted analysis.-Chung, B. H., J. P. Segrest, J. T. Cone, J. Pfau, J. C. Geer, and L. A. Duncan. High resolution plasma lipoprotein cholesterol profiles by a rapid, high volume semi-automated method.

Arterial hypertension injures brain capillaries. Definition of the lesions. Possible pathogenesis.

Systemic hypertension (secondary to aortic coarctation) produces in monkeys, multifocal brain lesions where capillaries show increased diameter, endothelial degeneration and deposition of collagen and other substances in the basement membrane. In one animal, capillary changes were detected as early as 8 weeks after induction of hypertension. Similar capillary alterations were demonstrated in brain samples of hypertensive humans obtained at autopsy. We suggest that the above abnormalities may be the result of successive episodes of regional ischemia and/or hyperperfusion. Validation of these observations requires careful evaluation of additional human and animal brains.

Biventricular hypoplasia with myocardial fiber hypertrophy and disarray.

A 25 year old woman with effort intolerance and systemic venous congestion since childhood, and restrictive ventricular filling and severe atrioventricular (A-V) valve regurgitation at cardiac catheterization died after valve replacement surgery. At autopsy, the atria were enlarged and thickened; both ventricles were small. In some areas the right ventricular wall was only a few myofibers thick. The myofibers of both ventricles were hypertrophied, and there was widespread fiber disarray in the left ventricular free wall, the interventricular septum and, focally, the right ventricular free wall. Because the ventricles were not enlarged or thickened despite myocardial fiber hypertrophy and severe chronic A-V valve regurgitation, and the myofiber disarray was widespread, this is a very unusual case of biventricular hypoplasia and dysplasia.

Triglycerides, lipid droplets, and lysosomes in aorta smooth muscle cells during the control of cell proliferation with polyunsaturated fatty acids and vitamin E.

The effects of 8,11,14-eicosatrienoic acid [20:3 (n--6)], 5,8,11,14-eicosatetraenoic acid [20:4 (n--6)], and alpha-tocopherol (vitamin E) on the morphology of smooth muscle cells from the guinea pig were studied in tissue culture. Cells were examined by phase and contrast interference microscopy, histochemistry, and transmission electron microscopy for the appearance of lipid droplets and lysosomes. The addition of 120 microM 20:3 (n--6) to the media produces large increases in the number of both lipid droplets and lysosomes. The addition of 10 microM vitamin E to the media has no effect on the morphology of smooth muscle cells. Large increases in the number of both lipid droplets and lysosomes are produced when vitamin E is added together with 20:3 (n--6). Thus, vitamin E has no effects on the morphologic changes induced by 20:3 (n--6). Lipid analyses showed that 80 per cent of the fatty acid taken into the cells is incorporated into triglyceride. Phospholipids incorporated about 17 per cent of the labeled fatty acid while cholesteryl esters, free fatty acids, and a polar neutral lipid fraction each incorporated less than 1 per cent of the labeled fatty acids. Gas liquid chromatography showed that the labeled fatty acid is recovered from the triglyceride fraction with little chain elongation and desaturation. Vitamin E has not effect on the uptake and distribution of labeled fatty acid in smooth muscle cells. 20:3 (n--6) and 20:4 (n--6) are inhibitors of cell proliferation when they are added to cells seeded at low cell density. 20:3 (n--6) has no effect on cell proliferation when it is added to a confluent monolayer which is subsequently split and grown at low cell density. Lipid droplets disappear as these pretreated cells grow. Vitamin E in the presence or absence of fatty acid enhances cell proliferation. The vitamin E and pretreatment studies show that cell proliferation is not related directly to triglyceride accumulation, the formation of lipid droplets, or enhanced lysosomal enzyme activity.

Subendocardial ischemic myocardial lesions associated with severe coronary atherosclerosis.

Morphologic changes in the subendocardial myocardium that appeared to be caused by severe, chronic subendocardial ischemia were studied in patients with fatal ischemic heart disease admitted to the Specialized Center of Research for Ischemic Heart Disease at the University of Alabama in Birmingham in the period 1970--1977. Thirteen patients were selected for this report on the basis that they had the lesions in the subendocardial myocardium we believe to have been caused by subendocardial ischemia and had no evidence of acute or remote myocardial infarction or other conditions that may have contributed to their terminal illness or death. Clinical findings were unstable angina, congestive heart failure, usually no increase in plasma enzymes indicative of myocardial damage, and electrocardiographic changes consistent with subendocardial ischemia. All 13 patients had 75% or greater stenosis of the three major coronary arteries; none had acute thrombotic or embolic coronary artery occlusion. The left ventricle in all cases was hypertrophied. The subendocardial myocardium showed circumferential pallor, hyperemia, or focal fibrosis without perceptible loss of volume in papillary muscles or trabeculae carneae. Microscopically, acute lesions showed one to two layers of preserved myofibers adjacent to the endocardium, vacuolar change in the deeper fibers, and focal areas of coagulation necrosis of variable size in the myocardium external to the fibers with vacuolar change. Coagulation necrosis was extensive in some cases and usually was not associated with infiltration of neutrophils. The repair reaction involved removal of necrotic sarcoplasm by mononuclear phagocytes, resulting in a reticular-appearing tissue without evidence of stromal collapse. Granulation tissue was not seen. Collagen fibers appeared to be deposited within the area of previous sarcolemmal sheaths. The distribution and morphology of subendocardial myocardial lesions associated with severe coronary atherosclerosis are distinctive and can be distinguished from myocardial necrosis or fibrosis associated with acute total occlusion of a coronary artery.

Preparative and quantitative isolation of plasma lipoproteins: rapid, single discontinuous density gradient ultracentrifugation in a vertical rotor.

A rapid method has been developed for separation of the major plasma lipoproteins from up to 96 ml of plasma by a single ultracentrifugation step. This separation was achieved by a discontinuous density gradient centrifugation between the density range of 1.006 and 1.30 g/ml in Sorvall vertical rotors. Each lipoprotein fraction was sharply banded with VLDL at the top, LDL in the upper middle, and HDL in the lower middle portion of the tube. Use of authentic 125I-labeled lipoproteins showed that complete separation of the three major classes and partial separation of HDL2 and HDL3 was achieved. The lipoprotein fractions prepared by this technique have properties indistinguishable from those isolated by the sequential flotation method in regard to their equilibrium banding density, electrophoretic mobility, and apolipoprotein composition. This method is suitable for the preparative isolation of lipoproteins as well as for quantitative clinical determinations of cholesterol and triglycerides in VLDL, LDL and HDL fractions of plasma. Used as an analytical tool this method allows samples as small as 1 ml of plasma and spin times as short as 45 min. Cholesterol levels in HDL fractions separated by this method have significantly lower values (P less than 0.05) than those estimated by the heparin-manganese chloride precipitation method.

Experimental aortic lesions of acute serum sickness in rabbits.

The mechanisms by which serum sickness cause lesions in the aortic intima are not known. The early aortic lesions of serum sickness detected by permeability to Evans blue dye were studied morphologically to determine the chronologic sequence of lesion initiation and immunochemically with fluorescein-labeled rabbit IgG and bovine serum albumin to detect the presence of antigen and antibody. The topographic localization of lesions and the morphologic changes observed suggest that endothelial injury occurs first, probably due to immune complex deposition, and that platelets play a secondary or reactive role in the process.

Fatty acids and their prostaglandin derivatives: inhibitors of proliferation in aortic smooth muscle cells.

Prostaglandins are synthesized from eicosa-8,11,14-trienoic acid and eicosa-5,8,11-14-tetraenoic acid by smooth muscle cell cultures from guinea pig aorta. Production is inhibited by indomethacin. The precursor fatty acids and their prostaglandin derivatives inhibit proliferation of the cell cultures. The relative availability of fatty acids for prostaglandin biosynthesis may represent a control mechanism for cell proliferation.