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Biomedical subjects

M B Stemerman

Publications and source records attributed to M B Stemerman.

88 records · Page 5Linked to original sources
PubMed1973

Thrombogenesis of the rabbit arterial plaque. An electron microscopic study.

Rabbit arteries, de-endothelialized with an intravascular balloon catheter and allowed to heal for 4 weeks, showed intimal changes that were similar to the preatherosclerotic fibromusculoelastic plaques of man. Reinjury of the healed vessels by balloon catheter produced marked quantitative and qualitative alterations of hemostasis, as compared to that in previously uninjured vessels. The most apparent modification of thrombogenesis 10 minutes after injury to the plaque was a large increase in the size of the thrombotic deposits. Features of this exaggerated response were the major participation of fibrin in thrombus formation and greater platelet accumulation. Some platelets and fibrin strands appeared to penetrate into and beneath the neointima. By 3 hours, these deposits had diminished in size, although the hemostatic mass remained larger in the doubly injured vessels.

Animals↗
PubMed1972

Platelet adhesion.

Explore the source record for details and available documents.

Basement Membrane↗
PubMed1972

Experimental arteriosclerosis. I. Fibrous plaque formation in primates, an electron microscope study.

Arteriosclerotic lesions have been produced in monkeys (Macaca nemestrina) by selective removal of the vascular endothelium with an intra-arterial balloon catheter. Immediately after de-endothelialization a platelet layer covers the denuded area. This thrombus is gradually removed and by 7 days the vessel appears to be largely reendothelialized. Beginning at day 4, smooth muscle cells undergo modification and migrate through fenestrae in the internal elastic lamina into the intima where they proliferate. By 28 days, the intimal lesion consists of multiple layers of smooth muscle cells surrounded by collagen and elastic fibers and basement-like material. After 3 months the lesions are markedly hyperplastic and contain new extracellular connective tissue elements. In contrast, with no further injury after 6 months the lesion has decreased markedly in size suggesting that it may be reversible in the absence of continued endothelial injury. The importance of endothelial "injury" exposing medial smooth muscle to plasma constituents may be the principal factors associated with the migration and proliferation of the smooth muscle cells into the intima resulting in the lesion. The smooth muscle cells do not contain lipid. The similarities of this lesion to the fibromusculo-elastic lesion or preatherosclerotic intimal hyperplasia in man makes it a useful model for the further study of atherosclerosis.

Animals↗
PubMedDate not supplied

Effects of moderate hypercholesterolemia on rabbit endothelium.

We investigated the effects of moderate hypercholesterolemia and endothelial regrowth on the function of vascular endothelium. Groups of rabbits were fed either a high or low cholesterol diet and subjected to removal of the aortic endothelium or sham-operated. Endothelial removal caused diffuse thickening of the myointima. The high cholesterol diet did not affect the extent of endothelial regeneration. To test endothelial function, 1 minute before sacrifice each animal was infused with horseradish peroxidase, which will penetrate the intima in areas of increased permeability. After sacrifice, the aorta was removed en bloc and exposed to diaminobenzidine and H2O2, which produce a brown stain on reaction with horseradish peroxidase. The luminal surface of the aorta was examined, and brown-stained areas, indicating increased permeability, were quantitated by stereology. Rabbits fed the cholesterol-rich diet had a greater percentage of brown-stained areas than did rabbits fed the low cholesterol diet; this was true for both intact and regenerated endothelium. The differences were significant at the p less than 0.01 level. Scanning electron microscopy of brown areas showed that, although the surface characteristics of the endothelium were altered, endothelial sloughing did not occur. Therefore, it appears that hypercholesterolemia can be associated with a functional endothelial defect in the absence of endothelial loss.

Animals↗
PubMedDate not supplied

Native low density lipoprotein. Endothelial cell recruitment of mononuclear cells.

The effect of native low density lipoprotein (LDL) on human umbilical vein endothelial cell (EC) recruitment of mononuclear cells (Monos) was investigated. ECs were exposed to LDL at atherogenic concentrations (240 mg cholesterol [Chol]/dl) for as long as 4 days (LDL-treated ECs). LDL-treated ECs bound substantially greater amounts of freshly isolated human monocytes and U937 cells than did control ECs. The enhanced Mono binding was time and LDL concentration dependent. LDL-induced binding was reduced to control levels when cycloheximide was added together with LDL, indicating that de novo protein synthesis was required. Furthermore, this LDL effect was not a general feature of apolipoproteins, as high density lipoprotein in physiologically relevant concentrations (45 mg Chol/dl, 4 days) had no effect on EC-Mono binding. Conditioned media from LDL-treated EC cultures did not increase EC binding of Monos. In contrast, minimally modified LDL increased EC-Mono binding more than eightfold. In conclusion, LDL in concentrations associated with the premature development of atherosclerosis increased EC affinity for Monos. Such LDL-induced alterations in EC physiology likely represent a proinflammatory response and an early step in atherogenesis.

Arteriosclerosis↗
PubMedDate not supplied

Interaction of platelets and fibrin with injured rabbit aortic neointima. Effect of prostaglandin I2 and heparin.

Following aortic balloon deendothelialization, rabbits develop a neointima composed of smooth muscle cells and extracellular connective tissue. Injury of this neointima with a balloon catheter results in the accumulation of platelet aggregates and fibrin on the vessel surface. We studied platelet attachment and secretion following injury of the neointima and also the effect of prostaglandin I2 (PGI2) and heparin on these events. Platelet factor 4 was detected within the neointima by indirect immunofluorescence 30 minutes after neointimal injury. By using 51Cr-labeled platelets, it was possible to quantitate total platelet attachment following neointimal injury. When animals were sacrificed 30 minutes after reinjury, there were 4.46 X 10(6) platelets/cm2 of aortic surface in animals injured 10 days after initial balloon deendothelialization, and 3.75 X 10(6) platelets/cm2 of aortic surface in animals injured 29 days after initial injury. In these two groups, infusion of 850 ng/kg/min PGI2, along with a single infusion of 2500 units of heparin, inhibited fibrin deposition and reduced platelet attachment by 71% and 76%, respectively. Although infusion of heparin alone prevented fibrin deposition, neither heparin nor PGI2 individually reduced platelet attachment as profoundly as did their combined use.

Aminophylline↗
PubMedDate not supplied

Transport of 125I-albumin across normal and deendothelialized rabbit thoracic aorta in vivo.

Transmural concentration profiles of 125I-albumin in vivo were measured across the normal and balloon catheter-deendothelialized rabbit descending thoracic aorta as a function of time following intravenous injection. A tracer was injected 5 or 60 minutes after deendothelialization, and the animals were sacrificed after circulation times of 10, 30 or 60 minutes. The aorta was immediately excised and frozen flat between glass slides. Samples were serially sectioned parallel to the intimal surface in a refrigerated microtome, washed with trichloroacetic acid (TCA), and counted. Relative tissue concentration profiles of TCA-precipitable radioactivity from the media of control animals showed entry from both luminal and adventitial sides, as previously found with conscious normal rabbits, but spatial gradients at both luminal and medial-adventitial borders were less steep. Relative concentration levels in ballooned animals were 10- to 40-fold higher than in controls, and the profiles were flatter. Uptake rates at equivalent circulation times were greater in experiments initiated 60 minutes, as compared with 5 minutes, after deendothelialization, suggesting that progressive medial edema may have occurred following balloon injury. These results show that the intact endothelium is the dominant mass transfer resistance for 125I-albumin transport across the aortic wall. The data also suggest that the incomplete monolayer of platelets adherent to the subendothelium after balloon deendothelialization is not a substantial resistance to transport, as compared to that of the media, and that convection plays a more important role than diffusion for 125I-albumin transport across the deendothelialized aortic wall.

Animals↗
PubMedDate not supplied

Local variation in arterial wall permeability to low density lipoprotein in normal rabbit aorta.

Normal rabbits were injected intravenously with horseradish peroxidase (HRP) and 125I-labeled human low density lipoprotein (LDL), and the aortas were perfusion-fixed. Subsequent visualization of HRP in the aortas was produced by reaction of the tissue with diaminobenzidine and hydrogen peroxide. The luminal surface of the aortas showed many small punctate foci of brown reaction product to the HRP, which represented penetration of the HRP into the vessel wall. The foci were scattered over the luminal surface, and most of the focal areas were less than 1 mm in diameter. The concentration of LDL was up to 47 times greater in these focal areas than in surrounding noncolored regions not showing increased permeability to HRP. Small circumscribed foci of heightened permeability to LDL may predispose to the local accumulation of lipid and ultimately to the formation of atherosclerotic plaques.

Animals↗
PubMedDate not supplied

Effect of lovastatin on serum lipids in patients with nonfamilial primary hypercholesterolemia.

The effect of lovastatin on serum lipids and its tolerability in patients with non-familial primary hypercholesterolemia (type II-A and type II-B) during a six-month period were evaluated in this open-label study. Thirty-eight patients were enrolled in the study; tolerability was assessed in all 38 patients. Thirty patients completed the study, and the effect of lovastatin on serum lipids in these patients was assessed. Some patients had been treated for hypercholesterolemia with long-term dietary and other non-pharmacologic means before entry into the study. All patients were unresponsive to a six-week program of intensive dietary therapy and other nonpharmacologic treatment to lower their blood cholesterol levels before receiving lovastatin. While maintaining intensive dietary therapy, administration of lovastatin was instituted at a dosage of 20 mg/day, which was increased by 20-mg increments monthly, as necessary, to a maximum of 80 mg/day. In an effort to achieve goal levels of low-density lipoprotein cholesterol (LDL-C), ten patients received a daily dosage of 20 mg, 12 patients received 40 mg, seven patients 60 mg, and one patient 80 mg. Twenty-nine of the 30 patients achieved significant lowering of serum levels of total cholesterol (TC), LDL-C, and apolipoprotein (apo) B-I; this was demonstrated after the first month of therapy with lovastatin and was maintained throughout the six-month treatment period. One patient failed to demonstrate lowering of these serum lipids, despite receiving the maximum recommended dosage of lovastatin of 80 mg/day. Comparative measurements of serum lipids during dietary therapy alone and after six months of diet plus lovastatin therapy were as follows: TC, 289 +/- 5 versus 216 +/- 9 mg/dl (P less than 0.0005); LDL-C, 206 +/- 4 versus 141 +/- 5 mg/dl (P less than 0.0005); and apo B-I, 112 +/- 3 versus 89 +/- 2 mg/dl (P less than 0.0005). Serum levels of very-low-density lipoprotein cholesterol (VLDL-C) and triglycerides decreased slightly during lovastatin therapy, but the changes were not statistically significant. There were slight but statistically insignificant increases in serum levels of high-density lipoprotein cholesterol (HDL-C), apo A-I, and apo A-II.(ABSTRACT TRUNCATED AT 400 WORDS)

Adult↗