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Biomedical subjects

S Glagov

Publications and source records attributed to S Glagov.

At least 19 recordsLinked to original sources
PubMed1992

Anastomotic intimal hyperplasia: mechanical injury or flow induced.

All anastomotic intimal thickening may not be the same, and the underlying mechanism(s) regulating the different types may vary. We investigated the localization of experimental anastomotic intimal thickening in relation to known biomechanical and hemodynamic factors. Bilateral iliofemoral saphenous vein and polytetrafluoroethylene grafts were implanted in 13 mongrel dogs. The distal end-to-side anastomotic geometry was standardized, and the flow parameters were measured. After 8 weeks, seven of 10 animals (group I) with patent grafts were killed and the anastomoses fixed by perfusion. Histologic sections from each anastomosis were studied with light microscopy, and regions of intimal thickening were identified and quantitated with use of oculomicrometry. To characterize the anastomotic flow patterns, transparent silicone models were constructed from castings of the distal anastomosis of three animals (group II), and flow was visualized with use of helium-neon laser-illuminated particles under conditions simulating the in vivo pulsatile flow parameters. Histologic sections revealed two separate and distinct regions of anastomotic intimal thickening. The first, suture line intimal thickening, was greater in polytetrafluoroethylene anastomoses (0.35 +/- 0.23 microns) than in vein anastomoses (0.15 +/- 0.03 microns, p less than 0.05). The second distinct type of intimal thickening developed on the arterial floor and was the same in polytetrafluoroethylene (0.11 +/- 0.11 microns) and vein anastomoses (0.12 +/- 0.03 microns). Model flow visualization studies revealed a flow stagnation point along the arterial floor resulting in a region of low and oscillating shear where the second type of intimal thickening developed. High shear and short particle residence time were observed along the hood of the graft, an area devoid of intimal thickening.(ABSTRACT TRUNCATED AT 250 WORDS)

Anastomosis, Surgical↗
PubMed1992

Aneurysmal enlargement of the aorta during regression of experimental atherosclerosis.

We explored the relationship between regression of diet-induced atherosclerosis and aneurysmal enlargement of the aorta in cynomolgus monkeys. Atherosclerotic plaques were induced in 17 monkeys by feeding them a diet containing 2% cholesterol and 25% peanut oil for 6 months (group I, n = 6; group III, n = 6) or 12 months (group II, n = 5). Regression was induced in group III by feeding a regression diet consisting of 0.25% cholesterol and 15% corn oil in a standard chow diet, for 6 months after the 6-month induction period. Serum cholesterol was 788 +/- 80 mg/dl after 6 months of induction, 508 +/- 53 mg/dl after the 12-month induction period, and 198 +/- 15 mg/dl in the regression group at 12 months. Aortas were fixed in situ under conditions of controlled pressure perfusion, and transverse sections of the unopened vessels were taken at standard levels in the midthoracic and abdominal aortic segments. The area encompassed by the internal elastic lamina was taken as a measure of artery size. Plaques were abundant in abdominal and thoracic sections after the 6- and 12-month induction periods, and no significant difference was observed in lumen area or artery size between the groups. The ratio of abdominal to thoracic aortic plaque area was markedly reduced in the regression group (0.3 +/- 0.2 for regression compared with 0.6 +/- 0.3 for 6-month induction and 1.3 +/- 0.2 for 12-month induction animals; p less than 0.05 for both). A twofold increase was observed in abdominal aortic lumen area in the regression group (10.0 +/- 1.5 mm2 for regression compared with 5.6 +/- 0.7 mm2 for the 6-month and 4.2 +/- 0.7 mm2 for the 12-month induction groups; p less than 0.05 for both) as well as a twofold increase in internal elastic lamina area (10.5 +/- 1.5 mm2 compared with 6.0 +/- 0.7 mm2 for the 6-month and 5.9 +/- 0.8 mm2 for the 12-month induction group; p less than 0.05 for both). Aortic enlargement in the regression group was accompanied by a reduction in media thickness in the abdominal aorta. No significant vessel enlargement or alteration in media thickness occurred in the thoracic aorta. One of six regression animals (17%) had a threefold enlargement of the abdominal aorta and was thought to have a manifest aneurysm.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1992

Pulsatile flow visualization in the abdominal aorta under differing physiologic conditions: implications for increased susceptibility to atherosclerosis.

The infrarenal abdominal aorta is a common site for clinically significant atherosclerosis. As has been shown in other susceptible locations, vessel geometry, flow division rates, and pulsatility may result in hemodynamic conditions which influence the preferential localization of disease in the abdominal aorta segment. Pulsatile flow visualization was performed in a glass model of the aorta constructed from measurements of angiograms and cadaver aortas. Flow rates and pulsatile waveforms were varied to reflect typical physiological conditions. Under normal resting conditions, the flow patterns in the infrarenal aorta were more complex than those in the suprarenal location. Time varying vortex patterns appeared at the level of the renal arteries and propagated through the infrarenal aorta into the common iliac arteries. A region of oscillating velocity direction extended from the renal arteries to the aortic bifurcation along the posterior wall. Dye became trapped along the posterior wall, requiring several cardiac cycles for clearance. In contrast, there was rapid clearance of the dye in the anterior aorta. Under postprandial conditions, the flow patterns in the aorta were basically unchanged. Simulated exercise conditions created laminar hemodynamic features very different from the resting conditions, including a decrease in dye residence time. This study reveals significant time-dependent variations in the hemodynamics of the abdominal aorta under differing physiologic conditions. Hemodynamic factors such as low wall shear stress, oscillating shear direction, and high particle residence time may be related to the clinically seen preferential plaque localization in the infrarenal aorta.

Angiography↗
PubMed1992

Hyperoxia-induced airway hyperresponsiveness and remodeling in immature rats.

We exposed 21-day-old rats to either normoxia or hyperoxia (greater than 95% O2) for 8 days and assessed in vivo airway responsiveness to aerosolized and intravenous methacholine (MCh) and airway architecture. Airway responsiveness was determined using a plethysmographic method. Hyperoxia increased airway cholinergic responsiveness, as reflected in a decreased mean ED200 (concentration of MCh required to increase respiratory system resistance by 100%) for both aerosolized MCh [air exposed, 5.94 +/- 2.50 vs. O2 exposed, 0.29 +/- 3.34 (SD) mg/ml, P = 0.0013, unpaired t test] and intravenous MCh (air, 1.40 x 10(-8) vs. O2, 2.45 x 10(-10) mol/kg, P = 0.0002). Airway morphometry was studied in a separate cohort of animals. After fixation by distension with Formalin at 25 cmH2O pressure, each airway cross section was photographed, and airway circumference, epithelial area, and smooth muscle layer area were determined by means of contour tracing using a digitizing pad and microcomputer. For the small airways (circumference less than 1,000 microns), hyperoxia increased both mean epithelial thickness (air, 4.88 +/- 0.53; O2, 8.64 +/- 0.90 microns) and mean smooth muscle layer thickness (air, 2.69 +/- 0.11; O2, 4.79 +/- 0.56 microns; P less than 0.0001 for each). O2 had similar effects on the larger (1,000-3,000 microns) central airways (P less than 0.0001 for both layers). We conclude that chronic hyperoxic exposure induces both airway hyperresponsiveness and airway wall thickening in immature rats.

Aerosols↗
PubMed1992

Experimental atherosclerosis at the carotid bifurcation of the cynomolgus monkey. Localization, compensatory enlargement, and the sparing effect of lowered heart rate.

We have characterized plaque localization, the extent of compensatory artery enlargement, and the effect of heart rate in experimental atherosclerosis at the carotid bifurcation of the cynomolgus monkey. We altered heart rate by sino-atrial node ablation (SNA) and then fed the animals an atherogenic diet for 6 months. Heart rate was measured at four time points by 24-hour telemetry. Of nine animals with SNA, heart rate was reduced significantly in six (from 148 +/- 11 to 103 +/- 20 beats/min, p < 0.001) and was unchanged in three. Sham-operated monkeys had no significant change in heart rate. On the basis of comparison with the preoperative mean for all 17 animals (136 +/- 22 beats/min), animals were separated into a low-heart-rate (LHR) group (111 +/- 16 beats/min, n = 12) and a high-heart-rate (HHR) group (150 +/- 16 beats/min, n = 5). Blood pressure, serum cholesterol level, and body weight did not differ for the two groups. As in the human, plaques formed predominantly in the proximal portion of the internal carotid artery at the lateral wall opposite the flow divider. Plaque cross-sectional area increased progressively from the relatively uninvolved, adjacent common carotid artery to the mid-sinus region of the internal carotid artery and decreased from the mid-sinus region to the internal carotid artery beyond the sinus. Plaque distribution was the same for the LHR and HHR groups, but lesion area and percent stenosis were greater for the HHR group than for the LHR animals (2.01 +/- 1.19 compared with 0.76 +/- 0.42 mm2 for lesion area [p < 0.02] and 30.7 +/- 4.4% compared with 15.2 +/- 7.3% for stenosis [p < 0.002]).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1992

Micro-architecture and composition of artery walls: relationship to location, diameter and the distribution of mechanical stress.

PURPOSE: We reviewed the structural basis of the mechanical properties of the arterial wall, in order to establish a coherent micro-anatomical basis for the differences in compliance among different arteries and a framework for assessing changes in the mechanical properties of specific individual arteries in relation to changing physical stresses. DATA IDENTIFICATION: The data and concepts presented here were derived from both earlier and ongoing work. Features that assure stability and integrity in relation to blood flow (wall shear stress) and pressure (mural tensile stress) were examined. Particular attention was paid to the morphogenetic and biosynthetic means by which arteries adapt to normal or abnormal modifications of these forces, particularly in relation to growth, location in the arterial tree and geometric configuration. RESULTS AND CONCLUSIONS: Thickness, composition and architecture of the artery wall, including thickness and composition of the intima, are normally determined by the stresses imposed by pressure and flow. Vessel radius is closely associated with flow, so that a normal baseline level of mean shear stress of about 15 dyn/cm2 is maintained or restored. Wall thickness and composition are determined by wall tension in relation to pressure and radius. Baseline levels of tensile stress differ with location but appear to be similar for homologous vessels. Changes in flow that modify the radius also modify wall tension. Changes in wall thickness and composition are likely to cause changes in compliance, due to altered flow and/or pressure patterns; these changes in compliance may be adaptive rather than destructive. Changes in the compliance of specific arteries over time may be used to evaluate the progression and severity of the conditions underlying these changes.

Animals↗
PubMed1992

Cryopreserved saphenous vein allogenic homografts: an alternative conduit in lower extremity arterial reconstruction in infected fields.

Autologous saphenous veins are considered the best arterial substitute for lower extremity revascularization in infected fields. The search continues for a vascular conduit in instances when an autologous biologic grafting is not feasible. Herein we report our experience with eight patients in whom cryopreserved saphenous vein allogenic homografts were used in 10 lower extremity arterial reconstructions for limb salvage with coexisting infection. Six patients with eight prosthetic grafts including four femoropopliteal, two femorotibial, a femorofemoral, and a femoroperoneal graft required complete or partial graft excision as a result of overt infection. The two remaining patients included one with an infected femoral pseudoaneurysm and another with extensive chemical burns. All cryopreserved saphenous vein allogenic homografts were of identical match to the ABO/Rh blood groupings of the recipient patients. No immunosuppressive drugs were administered after operation. Mean follow-up was 9.5 months (range, 6.0 to 14.0 months). One patient died 5 weeks after operation with a patent graft. Two grafts occluded during follow-up; in one graft, patency was restored with thrombectomy alone. The remaining seven arterial reconstructions continue to be patent with no evidence of aneurysmal dilation with complete eradication of the primary infection. These preliminary findings suggest that cryopreserved saphenous vein allogenic homografts can serve as interim conduits for lower extremity arterial reconstruction to preserve limb viability when autogenous conduits are unsatisfactory or unavailable. Further definitive reconstruction may thereafter be necessary once sepsis is eradicated and sufficient wound healing is achieved.

Aged↗
PubMed1991

The effect of hypercholesterolemia on early atherosclerotic lesions initiated by fibrinopeptide B.

Hypercholesterolemia and thrombosis have been implicated as factors in the development of atherosclerosis. Fibrinopeptide B (FPB) is a short chain peptide cleaved from fibrinogen during the production of fibrin. FPB is a known chemoattractant and has been shown to produce experimental atherosclerotic lesions in association with hypercholesterolemia. The present study was designed to examine the role of hypercholesterolemia in this process and to study the time course of the development of these lesions. Twelve New Zealand White rabbits were placed on an atherogenic diet and had suture carrying either FPB, fibrinopeptide A (FPA), or saline (controls) implanted in the adventitia of the femoral arteries and were sacrificed at 14 days. An equal number of animals were left on a standard diet and underwent similar treatment. Eleven animals were treated as the hypercholesterolemic group but were sacrificed at 2, 4, and 7 days. The thickness of the intima was measured adjacent to the suture in the animals sacrificed at 14 days, and the hypercholesterolemic FPB sites were thicker (12.23 mu +/- 6.60) than either hypercholesterolemic FPA (6.06 mu +/- 3.72), saline (4.94 mu +/- 1.42), or the normocholesterolemic FPB (5.99 mu +/- 4.61), FPA (3.89 mu +/- 2.20), or saline (3.97 mu +/- 1.83) (P less than 0.05 for all groups). Transmission electron microscopy of the hypercholesterolemic FPB group showed evidence of macrophages, actively secreting smooth muscle cells with newly deposited elastin, and foam cells by 7 days. We conclude that FPB attracts or stimulates macrophages and smooth muscle cells and that the resultant cellular and extracellular proliferation favors early atherosclerotic lesion formation in the presence of hypercholesterolemia.

Animals↗
PubMed1991

Hypertension sustains plaque progression despite reduction of hypercholesterolemia.

To assess the effect of hypertension on diet-induced coronary artery plaques after a return to a nonatherogenic diet, 10 cynomolgus monkeys were fed an induction regimen containing 2% cholesterol and 25% peanut oil for 6 months and then were subjected to midthoracic aortic coarctation to induce hypertension. The animals were then fed a nonatherogenic "prudent" ration for 6 additional months (hypertension-regression group). Twelve additional monkeys were fed the atherogenic diet for 6 months; six were killed (lesion-induction control group) and six were changed to the prudent diet for 6 additional months without coarctation (normotension-regression control group). At the end of the induction period, cholesterol levels averaged 744 +/- 178 mg/dl for the 22 animals and were similar for the three groups throughout the induction period. For the animals restored to the nonatherogenic diet (hypertension-regression and normotension-regression groups), serum cholesterol levels fell to 486 +/- 252 mg/dl at 1 month, to 341 +/- 162 mg/dl at 2 months, and to 234 +/- 78 mg/dl at 6 months. There was no significant difference between the hypertensive and normotensive animals. Six months after coarctation, blood pressure proximal to the coarctations for the hypertension-regression group ranged from 100/60 to 220/145 mm Hg with a mean of 166/103 +/- 36/28 mm Hg. Cross-sectional area of coronary plaques was somewhat lower for the normotension-regression control group compared with the lesion-induction control group, but the difference was not significant. Plaque area was, however, markedly greater in the hypertension-regression group than in either the lesion-induction or the normotension-regression groups (p less than 0.05 for each) despite progressive reduction in hyperlipidemia.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1991

Nonlysosomal cytoplasmic degradation.

Several types of cytoplasmic and nuclear inclusions represent stages in the process of non-lysosomal cytoplasmic degradation. Nonlysosomal degradation takes place in regions where cytoplasmic components are trapped and not accessible to primary and secondary lysosomes. Such trapping occurs within the lumina of the nuclear envelope and of endoplasmic reticulum in the form of inverted vesicles, within the nucleus, within mitochondria and within cavities formed by the process of topolysis in neutral lipid droplets. The concept of the process of nonlysosomal degradation permits dynamic interpretation of various inclusions as the concept of the process of focal cytoplasmic degration (autophagy) leads to dynamic interpretation of the lysosome.

Animals↗
PubMed1990

Role of fibrinopeptide B in early atherosclerotic lesion formation.

The development of atherosclerotic lesions involves many cell types, including macrophages. Fibrinopeptide B (FPB) has been shown to be a potent chemotactic agent for macrophages, which are abundant as intimal foam cells in atherosclerotic lesions, especially in cholesterol-fed rabbits. We hypothesize that intimal low-density lipoproteins also cause fibrinogen in the intima to release FPB and that FPB attracts macrophages in response to the high lipid levels associated with lesion development. To test our hypothesis, we used an atherosclerotic model. Silk sutures containing either FPB, fibrinopeptide A (FPA), lipopolysaccharide (LPS), or saline control were prepared. One suture of each type was placed in the adventitia of the femoral artery of a rabbit. Animals were killed at 1 or 2 weeks. Only vessels exposed to either FPB or LPS showed significant intimal thickening in the region adjacent to the suture site. Semi-thin electron microscopic sections indicated that the intimal wall was highly cellular and that many cells contained lipid vacuoles after 2 weeks. These sections also showed that the endothelium remained intact and that no injury to the media of the artery had occurred. Electron microscopy of the tissue samples showed the proliferation of smooth muscle cells and deposition of extracellular matrix in the 2-week animals, whereas foam cells were present in the 1-week animals. We conclude that FPB does indeed attract macrophages to the intima and that these macrophages may become foam cells. The model we have developed can be used to study possible mechanisms for the entry of macrophages into the intima during early lesion development and to further understand the complex interactions of FPB, fibrinogen, and lipids in atherosclerotic lesion development.

Animals↗
PubMed1990

Aneurysm formation in experimental atherosclerosis: relationship to plaque evolution.

To determine whether aneurysms form in experimental diet-induced atherosclerosis, we reviewed our experience with cynomolgus monkeys (n = 268) and rhesus monkeys (n = 175) fed an atherogenic diet for various lengths of time. Many animals in long-term experiments were fed "regression" diets and cholestyramine to lower cholesterol levels after lesions were established. No aneurysms were found in animals on normal diet. There were no aneurysms in 252 animals fed an atherogenic diet with or without regression for 12 months or less. However, aneurysms formed in 13% of cynomolgus monkeys (4 of 31) and 1% (1 of 107) rhesus monkeys on an atherogenic regimen for 16 to 24 months. Four of the five animals with aneurysms were on a regression diet and cholestyramine for 4 to 12 months. The fifth was fed the atherogenic diet for 20 months without subsequent regression. Aneurysms were prominent and involved the thoracic and abdominal aorta, innominate artery, carotid arteries, iliac and femoral arteries, and formed in areas most involved with plaque formation in both species. Histologic evidence was found of thinning of the media and atrophy with loss of normal architecture. The higher incidence of aneurysms in cynomolgus monkeys was associated with greater media destruction than was noted in the rhesus. These data support the thesis that aneurysm formation is a manifestation of atherosclerosis. In primate atherosclerosis, aneurysms form only after prolonged exposure to the atherogenic regimen, even in the presence of declining serum cholesterol levels. Matrix fibers in plaques may provide structural support to the aortic wall where there is underlying atrophy of the media. With time or declining serum cholesterol levels or both, plaques may atrophy leaving an aortic wall too thin to support increasing mural tension, leading to aneurysmal enlargement.

Animals↗
PubMed1989

Flow patterns in the abdominal aorta under simulated postprandial and exercise conditions: an experimental study.

Specific hemodynamic factors have been shown to be associated with atherosclerotic plaque localization at the human carotid bifurcation. Flow field characteristics may also determine plaque distribution in the abdominal aorta. We therefore characterized flow patterns in a glass model abdominal aorta that included its major branches under conditions of steady flow. Outflow resistances of the celiac, superior mesenteric, renal, inferior mesenteric, and iliac arteries were varied to produce flow distributions consistent with rest, the postprandial state, and vigorous lower limb exercise. Flow patterns were visualized with three colors of dye injected simultaneously through capillary tubes at selected locations and recorded as still photographs and by cinephotography on videotapes. Under resting conditions a large region of flow separation and stagnation occurred at the posterior wall of the aorta directly opposite the orifices of the superior and inferior mesenteric arteries. Similar separation regions were observed during the simulated postprandial state but diminished markedly when distal outflow was increased to levels consistent with exercise. In the highly susceptible infrarenal aortic segment, beginning about 2 cm below the renal artery orifices, multiple secondary flow patterns with three to four counterrotating vortex formations were observed under both resting and postprandial conditions but disappeared in the exercise state. Secondary flow patterns were not noted in the suprarenal abdominal aorta, which is usually relatively spared. Such features have been related to plaque localization elsewhere, and the disappearance of these patterns with increased flow velocity during exercise is consistent with the previously noted protective effect of unidirectional laminar high-flow states. The beneficial effects of physical fitness programs may be related in part to these hemodynamic modifications.

Aorta, Abdominal↗
PubMed1989

Limited effects of hyperlipidemia on the arterial smooth muscle response to mechanical stress.

Arteries respond to long-term changes in flow rate by alterations in caliber that tend to restore wall shear stress to normal baseline levels. Changes in radius, pressure, or geometric configuration elicit changes in structure and composition of the media in keeping with the altered level and distribution of tensile stresses. Similar stabilizing adaptations occur in the presence of conditions that induce the formation of atherosclerotic plaques, but the ultimate effectiveness of these reactions is variable. Several recent experiments provide information on the possible effects of hyperlipidemia on the smooth muscle cell (SMC) response to normal or increased levels of mechanical stress: (a) Normolipemic serum increases collagen synthesis by SMCs grown on purified elastin membranes compared to synthesis in serum-free medium, but synthesis is not further enhanced by cyclic stretching of the cells. Collagen production increase is less marked in hyperlipemic serum, but cyclic stretching raises synthesis to a degree comparable to that noted for serum-free medium. (b) The increase in artery diameter in response to increased flow rate and the elaboration of media components in relation to the increase in diameter are not hampered by hyperlipidemia. (c) The compensatory enlargement of arteries in response to plaque formation is not prevented by hyperlipidemia even in the presence of hypertension. (d) The healing of a transmural necrotizing injury of the media is, however, retarded and incomplete in the presence of hyperlipidemia. These findings indicate that hyperlipidemia per se does not necessarily interfere with the SMC response to mechanical stimuli. The usual adaptive reactions remain intact.(ABSTRACT TRUNCATED AT 250 WORDS)

Arteries↗