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Biomedical subjects

S K Peng

Publications and source records attributed to S K Peng.

At least 37 records · Page 2Linked to original sources

Effects of cholestanetriol on cytotoxicity and prostacyclin production in cultured rabbit aortic endothelial cells.

Rabbit aortic endothelial cells in culture were incubated with 10 micrograms/ml of either pure cholesterol or cholestane-3 beta, 5 alpha, 6 beta-triol (triol) for 12 or 24 hours. Cells incubated with triol showed an increased rate of cell death, decreased [3H]-thymidine incorporation and decreased prostacyclin production as compared to either the control or the pure cholesterol group. These effects were more marked at 24 hours than at 12 hours. Pure cholesterol had no significant effects on any of the above parameters at either time interval. These results suggest potential atherogenic mechanisms for cholestanetriol, one of the most biologically active cholesterol oxidation products.

Animals↗

Holmium:YAG laser ablation of vascular tissue.

The ablation of atherosclerotic lesions without collateral thermal or shock wave damage is thought to be a key element for successful laser angioplasty. This study evaluated the effectiveness of pulsed holmium:YAG laser (2.1 microns wavelength) for this application. Fresh normal tissue (n = 139) and arteriosclerotic canine arteries (n = 21) as well as formalin-preserved normal canine (n = 31) and atherosclerotic human arteries (n = 177) were irradiated under saline via a 600 microns diameter fiber placed perpendicular to the intimal surface with 0-10 gm of force. The laser was operated in the free running mode (FRM; 250 microseconds pulsewidth, 5 Hz, 30-7,100 mJ/mm2) and in the Q-switched mode (QSM; 200 nsec pulsewidth, 6 Hz, 30-1,100 mJ/mm2). Following the experiments, the samples were prepared for histologic and morphometric analysis. Ablation thresholds in the FRM were 60 and 180 mJ/mm2 in fresh and preserved canine tissue, respectively. Ablation thresholds in the QSM for fresh and preserved canine tissues were 75 and 180 mJ/mm2, respectively. Thresholds for human atherosclerotic tissue were dependent on the amount of calcification. In the QSM and FRM, there were no samples that could not be penetrated at 1,100 mJ/mm2 and above. Histologic examination of the FRM samples revealed confined columns of tissue ablation, with approximately 55-250 microns and 70-140 microns zones of thermal effect being apparent in the fresh and formalin-preserved samples, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

Angioplasty, Laser↗

The role of internal elastic laminae damage in the development of canine arteriosclerosis.

This study was designed to test the hypothesis that the extent of damage to the internal elastic lamina (IEL) may be a factor in determining the development of atheromatous lesions (lesion area). A bilateral iliac artery arteriosclerotic (AS) model in seven dogs prepared by intimal denudation and fracture of the IEL plus 5% cholesterol diet was investigated. The animals were sacrificed at 10-52 weeks (10, n = 1; 16, n = 3; 20, n = 1; 32, n = 1; 52, n = 1). Histologic analysis of sections (n = 42) of 14 canine iliac AS arteries harvested bilaterally from identical locations along the vessels (2, 7, and 12 cm from the aortic bifurcation) were compared with control segments of caudal and femoral arteries (n = 12) that had intact lamina and no luminal trauma. AS segments at all sites along the length of the traumatized iliac vessels demonstrated significant lesions, while control vessels had no arteriosclerotic changes. AS lesion area was calculated using ocular micrometry and a multiple regression model to test the predictability of the lesion area from the following independent variables: (1) proportion of intact IEL to total IEL (IEL/IELt), (2) sacrifice intervalens (3) frequency of disruptions to the IEL, (4) side and level of the arterial lesion, and (5) respective animals. This analysis revealed that none of the coefficients for the independent variables used in the multiple regression model was significant, suggesting that the extent of AS lesions is not related to the size, frequency, or location of breaks in the IEL, although a break in IEL is required to initiate the lesions. This observation suggests that the migration of cells from the arterial media through the broken laminae or the release of medial biochemical mediators which are normally contained by the elastic lamina is required to develop the AS lesions in this canine model, and that any size break in the lamina initiates the process.

Animals↗

Experimental and early clinical evaluation of vascular anastomoses with argon laser fusion and the use of absorbable guy sutures: a preliminary report.

This study investigated the feasibility of forming vascular anastomoses by use of argon laser tissue fusion and absorbable, monofilament polydimethylsiloxane guy sutures. In initial animal studies femoral arteriovenous fistulas approximately 1.5 cm in length were created bilaterally in each of 10 dogs and were studied histologically at 2, 4, 8, 16, and 24 weeks (two animals in each interval). In each animal, one anastomosis (control) was formed with continuous 6-0 polypropylene suture, and the contralateral anastomosis (experimental) was performed with an argon laser (0.5 watt, 5 to 7 minutes exposure, energy fluence 1100 to 1500 joules/cm2 per 1 cm length) with stay sutures of 5-0 polydimethylsiloxane at 0.5 to 0.65 cm intervals. At removal, all anastomoses were patent without hematomas, aneurysms, or luminal narrowing. Histologic examination at 2 to 16 weeks demonstrated resorption of the biodegradable suture material by a local inflammatory reaction. By 24 weeks, laser-fused specimens had no evidence of suture material at the anastomotic line, and healing consisted of a bond between artery and vein wall tissues. Control suture specimens at the same intervals exhibited an organized fibrous tissue response to the suture. Clinical adaptability of this technology has subsequently been evaluated in five patients at 10 to 27 months (21.6 +/- 5.8) by physical examination and duplex scanning and demonstrate no evidence of abnormal healing. This study establishes the experimental and preliminary clinical feasibility of laser-fused anastomoses aligned by biodegradable guy sutures and supports further investigation and refinement of the technique.

Adult↗

Influence of cholesterol oxides on endocytosis of cultured endothelial and smooth muscle cells.

Human umbilical vein endothelial cells and rabbit aortic smooth muscle cells in culture were incubated for intervals up to 24 hrs with varying concentrations of cholesterol, 7-ketocholesterol, 25-hydroxycholesterol, cholestane-3 beta,5 alpha,6 beta-triol or cholesterol-5 alpha, 6 beta-epoxide. Endocytosis, as measured by uptake of horseradish peroxidase (HRP), was inhibited in a dose and time dependent manner in both endothelial and smooth muscle cell cultures by cholestane-3 beta,5 alpha,6 beta-triol and 25-hydroxycholesterol. Inhibition by 7-ketocholesterol in endothelial cells occurred only at higher concentrations, and cholesterol and cholesterol epoxide showed no significant inhibitory effects. The viability of the cells exposed to the cholesterol oxides at the concentrations that inhibited the uptake of HRP was not changed. Cholesterol oxides induce functional endothelial injury, not morphologically apparent, which may be involved in atherogenesis.

Animals↗

Relative specificities of inhibition of acid cholesteryl ester hydrolase and neutral cholesteryl ester hydrolase in cultured rabbit aortic smooth muscle cells by esterastin and cholesteryl oleyl ether.

Rabbit aortic smooth muscle cells in culture were incubated with 0.04-500 M esterastin. Acid cholesteryl ester hydrolase (ACEH) and neutral cholesteryl ester hydrolase (NCEH) activities were inhibited to a comparable degree, with 50% inhibition occurring in the range of 0.4 M esterastin. Cells incubated with cholesteryl oleyl ether showed 50% inhibition of NCEH at 5.0 M, but no inhibition of ACEH over a concentration range of 0.2-20 M. This relative specificity of cholesteryl oleyl ether for NCEH can be employed to study the relative roles of ACEH vs. NCEH in preventing cellular cholesteryl ester accumulation.

Animals↗

Effects of cholesterol oxidation derivatives on cholesterol esterifying and cholesteryl ester hydrolytic enzyme activity of cultured rabbit aortic smooth muscle cells.

The effects of 5 micrograms/ml of 25-hydroxycholesterol; cholestane-3 beta,5 alpha,6 beta-triol; and cholesterol on acyl CoA cholesterol acyltransferase, acid cholesteryl ester hydrolase and neutral cholesteryl ester hydrolase was studied in cultured rabbit aortic smooth muscle cells. After 1 hour incubation, 25-hydroxycholesterol resulted in a fourfold stimulation of acyl CoA cholesterol acyltransferase activity. No stimulation by 25-hydroxycholesterol was noted before 15 minutes or after 5 hours of incubation. Neither cholestane-3 beta,5 alpha,6 beta-triol nor cholesterol influenced acyl CoA cholesterol acyltransferase activity at any time interval. No significant effects of any of the sterols were noted on acid cholesteryl ester hydrolase or neutral cholesteryl ester hydrolase activity. The imbalance between acyl CoA cholesterol acyl transferase and hydrolase activities induced by 25-hydroxycholesterol could result in cholesteryl ester accumulation by arterial smooth muscle cells, which may be associated with atherosclerosis.

Animals↗

Initial human evaluation of argon laser-assisted vascular anastomoses.

Forearm Brescia-Cimino arteriovenous fistulas were chosen for the initial clinical evaluation of argon laser-assisted anastomosis of human vessels. Ten patients with chronic renal failure had side-to-side radial artery/cephalic vein fistulas fused by laser. Incisions 1.2 to 1.5 cm in length were made in adjacent segments of artery and vein and were aligned for application of laser energy by four 6-0 polypropylene sutures. The sutures divided each fistula into four segments that were 5.0 to 6.5 mm long. Each segment was sealed satisfactorily in 75 to 100 seconds by use of 0.5 W, 1130 to 1520 joule/cm2 argon laser energy fluence. Seven (17.5%) of 40 bonds required an additional 7-0 biodegradable suture to close small gaps that did not fuse adequately. Serial prospective follow-up studies of the patients by physical examination and duplex scanning for periods of 12 to 20 months (15.4 +/- 2.8, n = 7) postoperatively have shown uniformly patent, compliant anastomoses with no evidence of hematomas, false aneurysms, or luminal narrowing. Histologic examination of two patent fistulas that were excised during revision procedures at 4 and 5 months postoperatively showed healing of the entire circumference of the anastomosis similar to that noted in extensive preclinical canine studies. We conclude from these preliminary results that argon laser vascular tissue fusion is possible in humans when reliable primary sealing of vascular anastomoses is achieved, and that healing occurs without aneurysmal dilatation during follow-up of up to 20 months.

Adult↗

Direct cocaine cardiotoxicity demonstrated by endomyocardial biopsy.

The morbidity and mortality associated with cocaine abuse has markedly increased in recent years. Although several articles indicate a possible connection of cocaine with coronary spasm and acute myocardial infarction, this study in seven patients with a history of cocaine abuse, who underwent endomyocardial biopsy, suggests that cocaine may cause direct toxicity to the myocardium. Myocardial specimens from five of seven patients showed multifocal myocyte necrosis, of which two specimens revealed focal myocarditis, while three specimens had changes consistent with dilated cardiomyopathy. Ultrastructurally, extensive loss of myofibrils and sarcoplasmic vacuolization were observed. It is postulated that the pathogenesis of acute cocaine-induced toxicity is direct destruction of myofibrils resulting in myocyte necrosis and that these changes may or may not be associated with interstitial inflammatory cell infiltrates. Long-term abuse of cocaine may lead to interstitial fibrosis and eventually congestive heart failure.

Adult↗

Mechanism of tissue fusion in argon laser-welded vein-artery anastomoses.

The mechanism of laser vascular tissue welding remains unknown. This study compared the acute tissue response and long-term healing of sutured and laser-welded anastomoses of vein segments used to bypass ligated canine femoral arteries. For each procedure, one anastomosis was formed using running 6-0 polypropylene suture (control), and the other anastomosis was formed using argon laser tissue welding (experimental). The vein grafts were harvested at 4 (n = 2), 8 (n = 1), 12 (n = 1), and 16 (n = 2) weeks, and selected samples were evaluated by histologic examination, electron microscopy, tensile strength testing, and by measuring the formation of [3H]hydroxyproline as an index of collagen synthesis. Examination of successful laser fusions immediately after they were formed showed bonding of collagen to collagen and elastin to collagen. Follow-up evaluations showed that the precision of tissue apposition affected the rate of healing and tensile strength. Laser-welded anastomoses demonstrated a progression of healing similar to sutured repairs, with remodeling of fibrous tissue and collagen being the primary component of weld integrity. This study demonstrates that sutured and argon laser-welded vein-artery anastomoses heal comparably up to 16 weeks postoperatively, and that laser welding is a satisfactory alternative to sutured anastomoses.

Animals↗

Canine peripheral vascular arteriosclerosis following myointimal fragmentation and atherogenic diet.

The development of arteriosclerotic peripheral vascular lesions following balloon catheter and mechanical fragmentation of the arterial myointima combined with an atherogenic diet was studied in a canine model. The ileofemoral arteries of five mongrel dogs (mean wt 22 +/- 2 kg) were selectively cannulated and subjected to balloon catheter and mechanical myointimal injury by repeated longitudinal and transverse shearing forces. Twenty grams of hydrogenated coconut oil and a 5.0% cholesterol diet were fed to the animals daily during the study period. Followup angiographic studies obtained at 4 weeks (n = 2), 10 weeks (n = 3), 16 weeks (n = 3), and 24 weeks (n = 2) demonstrated changes of progressive peripheral vascular occlusion. Concurrent duplex Doppler studies correlated well with the angiographic results. At 10 (n = 1), 18 (n = 2), and 24 (n = 2) weeks, the animals were sacrificed and the vessels were perfusion-fixed in situ with 2% glutaraldehyde or formaldehyde solutions and excised. Histological examination demonstrated extensive arteriosclerotic changes including (i) fragmentation and reduplication of the internal elastic membrane, (ii) myointimal hyperplasia with fibroblastic proliferation including the development of fibrous intimal plaques, and (iii) transmigration and proliferation of smooth muscle cells with scattered monohistiocytes. The specimens showed a range of stenotic changes from 25% to total occlusion of the vascular lumen. These preliminary data demonstrate the feasibility of providing intense arteriosclerotic myointimal histologic changes in the canine peripheral vasculature within a 24-week period. Further refinement of this methodology may provide a practical model for studies of localized peripheral vascular occlusive disease.

Animals↗

Light chain cardiomyopathy associated with small-vessel disease.

Intramyocardial small-vessel disease associated with systemic light chain deposition is a rare condition that may occur in patients with monoclonal plasma cell proliferation. This article describes a 39-year-old woman who had experienced several episodes of subendocardial myocardial infarction and was found to have plasma cell dyscrasia. Endomyocardial biopsy revealed kappa light chain deposits along the sarcolemmal and vascular basement membranes, the latter of which resulted in vascular occlusion and myocardial infarction. Postmortem examination showed polyvisceral deposition of kappa light chains. This rare complication of plasma cell proliferative process has a poor prognosis.

Adult↗

Transport of cholesterol autoxidation products in rabbit lipoproteins.

Radiolabeled pure [4-14C]cholesterol was kept at 60 degrees C under air to autoxidize for 5 weeks, after which approximately 12% cholesterol oxidation products were formed. The mixture, suspended in gelatin, was given to rabbits by gastric gavage. Rabbits were killed 4, 24, and 48 h after treatment. Cholesterol and its autoxidation products were separated by thin-layer chromatography into 5 fractions and radioactivities of each fraction were measured. Percentages of each fraction of cholesterol oxidation products and cholesterol in the original mixture before administration and in the rabbit sera after administration were similar, suggesting that the rates of absorption of cholesterol oxidation products are not significantly different from that of cholesterol. Lipoproteins were fractionated by ultracentrifugation into VLDL, LDL and HDL. Radioactivities of each fraction in lipoproteins separated by thin layer chromatography showed that fractions containing cholestane-3 beta,5 alpha,6 beta-triol, 7 alpha- and 7 beta-hydroxycholesterol and 7-ketocholesterol were more selectively transported in VLDL, whereas most of the 25-hydroxycholesterol was present in LDL. HDL contained only minute amounts of cholesterol oxidation products.

Absorption↗

Laser vascular welding--how does it work?

This study evaluated the histology and electron microscopy of four samples of 2 cm long venotomies and artery-vein anastomoses formed in canine femoral arteries and veins using the argon laser (0.5 W power, 1 800 J/cm2, 4 min exposure/1 cm length of anastomosis). Welds were continuously irrigated with saline during the procedure to limit maximal temperatures to 44.2 +/- 1.6 degrees C (mean +/- SD), and the specimens were removed immediately following fusion and preserved for examination. Histologic and electron microscopic examination of different areas of the welds revealed various mechanisms of fusion including a) apposition of denatured collagen and elastin in the media and adventitia; b) bonding of vein medial collagen and elastin to the internal elastic membrane of the artery; and c) fusion consisting of a coagulum of platelets and fibrin depending on the alignment and apposition of the vessel edges. This study demonstrates that vascular tissue fusion by the argon laser occurs by various mechanisms. Future experiments should delineate which types of seal produce the optimal strength at the time of fusion, and enhance long-term healing.

Animals↗

Aortitis presenting as Buerger's disease.

Buerger's disease is frequently diagnosed in young smokers, based on clinical presentation rather than histologic criteria. This report describes a young male with idiopathic aortitis who had been managed for 10 years as Buerger's disease solely on the basis of clinical manifestations. This case emphasizes the need for establishing histopathologic, and perhaps biochemical, criteria to identify the underlying arteriopathy.

Adult↗

Effects on membrane function by cholesterol oxidation derivatives in cultured aortic smooth muscle cells.

Autoxidation derivatives of cholesterol known to affect cholesterol content of the cells were shown to alter some membrane associated functions in cultured aortic smooth muscle cells. For study of membrane-bound enzymes, Na+,K+-ATPase and 5'-nucleotidase were measured cytochemically by electron microscopy. Cells incubated with 10 ug/ml of cholestane-3 beta,5 alpha,6 beta-triol and 25-hydroxycholesterol for 24 to 48 hours showed marked inhibition of both enzyme activities. For study of carrier-mediated hexose transport, radiolabeled 2-deoxy-D-glucose was utilized. The uptake of this labeled compound was measured in the cells preincubated with oxidation derivatives of cholesterol for various time periods. Cholestane-3 beta,5 alpha,6 beta-triol had a rapid inhibitory effect on hexose transport, which was reversible after removal of the sterol from the medium. Hexose transport was not significantly altered by 25-hydroxycholesterol after up to 8 hours incubation. Two underlying mechanisms are possible. The prompt onset of the effect of cholestane-3 beta,5 alpha,6 beta-triol may be attributable to an incorporation of the sterol into the cell membranes. On the other hand, 25-hydroxycholesterol, a potent inhibitor of cholesterol biosynthesis, may have a delayed effect on membrane function by depleting the cholesterol available for membrane synthesis.

5'-Nucleotidase↗

Poloxalene 2930, a hydrophobic surfactant that prevents atherosclerosis, alters composition of rabbit lipoproteins.

Poloxalene 2930, a hydrophobic surfactant, was incorporated into an atherogenic diet at dose levels, 0.5% and 1% of the diet, and fed to rabbits for 10 weeks. Another group received plain atherogenic diet alone and a control group was fed chow. After this period, serum lipoproteins were separated by centrifugation and analyzed. The composition of lipoproteins from rabbits on atherogenic diet was abnormal. The cholesterol: triglyceride ratio of every lipoprotein fraction was significantly increased as was the cholesterol: protein ratio of very low density lipoproteins. Supplementing the diet with Poloxalene 2930 prevented these alterations. In all groups on the atherogenic diet the percentage of apolipoprotein E in VLDL and HDL increased. In the case of Poloxalene-treated rabbits this developed even though serum cholesterol levels were normal or slightly increased. It is concluded that Poloxalene 2930 has a systemic effect on lipoproteins which may contribute to its antiatherogenic action.

Animals↗