PubMed Health⌕ Search

Biomedical subjects

J T Fallon

Publications and source records attributed to J T Fallon.

At least 55 records · Page 3Linked to original sources
PubMed2000

High resolution ex vivo magnetic resonance imaging of in situ coronary and aortic atherosclerotic plaque in a porcine model.

Atherosclerotic plaque composition is central to the pathogenesis of plaque disruption and acute thrombosis. Thus, there is a need for accurate imaging and characterization of atherosclerotic lesions. Even though there is no ideal animal model of atherosclerosis, the porcine model is considered to most closely resemble human atherosclerosis. We report the feasibility of MR imaging and characterizing of atherosclerotic lesions from in situ coronary arteries and aortas in an ex vivo setting and validate this with histopathology. Coronary and aortic atherosclerosis was induced in Yucatan mini-swine (n=4) by a combination of atherogenic diet (6 months) and balloon injury. All coronary arteries were imaged ex vivo on the intact heart, preserving the curvature of their course. The aorta also underwent MR imaging. The MR images were correlated with the matched histopathology sections for both the coronary arteries (n=54) and the aortas (n=43). MR imaging accurately characterized complex atherosclerotic lesions, including calcified, lipid rich, fibrocellular and hemorrhagic regions. Mean wall thickness for the coronary arteries (r=0.94, slope: 0.81) and aortas (r=0.94, slope: 0.81) as well as aortic plaque area (r=0.97, slope: 0.90) was accurately determined by MR imaging (P<0.0001). Coronary artery MR imaging is not limited by the curvature of the coronary arteries in the heart. MR imaging accurately quantifies and characterizes coronary and aortic atherosclerotic lesions, including the vessel wall, in this experimental porcine model of complex atherosclerosis. This model may be useful for future study of MR imaging of atherosclerosis in vivo.

Animals↗
PubMed2000

Inhibition of tissue factor reduces thrombus formation and intimal hyperplasia after porcine coronary angioplasty.

OBJECTIVES: We investigated the in vivo effects of tissue factor (TF) inhibition with recombinant tissue factor pathway inhibitor (rTFPI) on acute thrombus formation and intimal hyperplasia and the in vitro effects on smooth muscle cell migration and proliferation. BACKGROUND: Inhibition of TF with TFPI has been shown to reduce intimal hyperplasia in experimental models. However, its effects after coronary angioplasty and the cellular mechanisms involved have not been investigated. METHODS: Twenty-three swine underwent multivessel coronary angioplasty. Fifteen (n = 25 arteries) were euthanized at 72 h to assess thrombus formation and eight (n = 24 arteries) at 28 days to assess intimal hyperplasia. Animals in the 72-h time point received: 1) human rTFPI (0.5 mg bolus plus 25 microg/kg/min continuous infusion for 3 days) plus heparin (150 IU/kg intravenous bolus) plus acetyl salicylic acid (ASA) (325 mg/day); 2) rTFPI regimen plus ASA and 3) heparin (150 IU/kg intravenous bolus) plus ASA. RESULTS: On histology the control group had evidence of mural thrombus (area 0.8+/-0.4 mm2). Treatment with TFPI plus heparin abolished thrombus formation (mean area: 0.0+/-0.0 mm2, p < 0.05) but was associated with prolonged activated partial thromboplastin time and extravascular hemorrhage. Recombinant TFPI alone inhibited thrombosis without bleeding complications (mean area: 0.03+/-0.02 mm2, p < 0.05 vs. control). Animals in the 28-day time point received continuous intravenous infusion of rTFPI or control solution for 14 days. Tissue factor pathway inhibitor reduced neointimal formation with mean intimal area of 1.2+/-0.3 mm2 versus 3.2+/-0.4 mm2 in the control group; p < 0.01. Recombinant TFPI had no effect on human aortic smooth muscle cell growth but inhibited platelet-derived growth factor BB-induced migration. CONCLUSIONS: Inhibition of TF with rTFPI can prevent acute thrombosis and intimal hyperplasia after injury. Tissue factor plasma inhibitor may prove useful as an adjunct to intracoronary interventions.

Angioplasty, Balloon, Coronary↗
PubMed2000

Accelerated flap prefabrication with vascular endothelial growth factor.

Vascular endothelial growth factor (VEGF) is a potent promoter of angiogenesis that has been shown to enhance revascularization of ischemic tissues, including skin flaps. This study was designed to investigate the value of a single topical application of recombinant human VEGF to accelerate flap viability in a rat model of a non-ischemic prefabricated flap. Prefabricated flaps were created in 48 Sprague-Dawley rats. An autologous tail artery loop was anastomosed to the femoral artery and vein, and implanted subcutaneously in the lower abdomen. Flaps were divided into two groups of 24 each. At the time of loop implantation the control group received 0.9 percent NaCl or a 16 percent vol/wet polyvinyl alcohol (PVA) solution: the treatment group received VEGF in 0.9 percent NaCl or VEGF in PVA. The PVA gel was used to facilitate topical application In each group, 3- x 4-cm flaps nurtured by the tail artery pedicle were elevated and resutured into place after 3, 4, and 5 weeks. The percentage of surviving skin of each flap was determined by planimetry 7 days after flap elevation. Mean skin survival areas at 3, 4, and 5 weeks were control group 0 percent. 8 percent and 17.5 percent; and VEGIF-treated group, 6 percent, 40 percent, and 66.7 percent respectively VEGF significantly improved flap survival by 5 weeks (p = 0.02). These results suggest that VEGF can accelerate maturation of prefabricated flaps. This approach could expand the application of flap prefabrication as a resource for reconstructive surgery.

Animals↗
PubMed2000

Up-regulation of the proteasome subunit LMP7 in tissues of endotoxemic rats.

The proteasome has been implicated in systemic responses to infection or inflammatory stimuli including catabolism of skeletal muscle. Cytokines including tumor necrosis factor-alpha (TNF-alpha) and interferon-gamma (IFN-gamma) are known to be elevated systemically and locally under these conditions. They are also known to be potent inducers of three peptide subunits of the proteasome, including LMP7, that replace constitutively expressed subunits and change enzymatic properties. To determine whether endotoxemia alters the expression of inducible proteasome subunits, we examined the levels of LMP7 in tissues from rats 3 days after the injection of lipopolysaccharide (LPS) or normal saline solution (NS). By both immunoblotting and immunohistochemistry, significant increases in levels of LMP7 were observed in the heart, kidney, and lung of animals given LPS as compared with results in NS-treated animals, whereas immunoblotting revealed no changes in LMP7 levels in skeletal muscle or brain. Increased expression of LMP7 was limited to certain subpopulations of cells and was further localized at the subcellular level. Decreases in organ weight were also documented for organs in which the expression of LMP7 was up-regulated. Systemic or local release of cytokines or other proinflammatory mediators is suggested as the most likely mechanism for changes in LMP7 expression during endotoxemia. Changes in LMP7 expression may have functional consequences that contribute to organ dysfunction during systemic responses to infection and inflammatory stimuli.

Animals↗
PubMed2000

Mouse model of femoral artery denudation injury associated with the rapid accumulation of adhesion molecules on the luminal surface and recruitment of neutrophils.

Techniques of arterial injury commonly used in animals to mimic endovascular procedures are not suitable for small mouse arteries. This has limited examination of the response to arterial injury in genetically modified mice. We therefore sought to develop a model of transluminal injury to the mouse femoral artery that would be reproducible and result in substantial levels of intimal hyperplasia. Mice of the C57BL/6 strain underwent bilateral femoral artery denudation by passage of an angioplasty guidewire. Intimal hyperplasia was observed in 10% of injured arteries at 1 week, in 88% at 2 weeks, and in 90% at 4 weeks. The mean intimal-to-medial area ratio reached 1.1+/-0.1 at 4 weeks. No intimal proliferation was found in control sham-operated arteries. One hour after injury, the denuded surface was covered with platelets and leukocytes, predominantly neutrophils. This was associated with the accumulation of P-selectin, intercellular adhesion molecule-1, and vascular cell adhesion molecule-1. Expression of these adhesion molecules was not seen in the underlying medial smooth muscle cells. At 24 hours, few neutrophils remained on the denuded surface. At 1 week, macrophages and platelets were present in the vessel wall, partially covered by regenerated endothelium. Transluminal wire injury to the mouse femoral artery induces abundant intimal hyperplasia formation by 2 and 4 weeks and elicits the rapid accumulation of leukocytes and adhesion molecules on the denuded luminal surface. This model will be a valuable tool to study arterial injury in genetically modified mouse models.

Animals↗
PubMed2000

In vivo dynamic real-time monitoring and quantification of platelet-thrombus formation: use of a local isotope detector.

Current methods for monitoring thrombosis and thrombus growth are invasive and provide only single-time-point data. Animal models rely mainly on flow changes as a surrogate of thrombus formation. Our aim was to validate a unique potentially noninvasive system to detect and quantify dynamic thrombus formation in vivo by using a porcine model of carotid artery injury. Thrombus growth was monitored by deposition of autologous (111)In-labeled platelet activity over the injured artery by use of miniaturized gamma detectors and Doppler blood flow. Counts were recorded at 2-minute intervals for 2 hours. The technique was validated by comparing standard antithrombotic agents against controls. Platelet recruitment was detected before significant change in flow. Thrombus formation, calculated as the area under the curve (platelets x minutes x 10(6)), was greatest for control animals (11.7+/-1.28), followed by animals treated with aspirin (6.13+/-0.91, P<0.05), heparin (2.45+/-0.34, P<0.05), and hirudin (0.2+/-0.01, P<0.01 compared with heparin). The rate of platelet deposition was assessed as the slope of the curve in the first 30 minutes (platelets x 10(6) per minute) for the following treatment groups of animals: control, 3.53+/-0.34; aspirin, 1.67+/-0. 34 (P<0.01); heparin, 1.55+/-0.3 (P<0.01); and hirudin, 0.25+/-0.03 (P<0.001). There was no statistical difference between heparin and aspirin treatments. Change in flow was assessed as reduction from baseline: control, >99+/-0.34%; aspirin, 39+/-9.1%; heparin, 36+/-12. 5%; and hirudin, 17+/-5.4%. There was no statistical difference between the aspirin- and heparin-treated groups. Morphometric analysis revealed >99+/-0.63% occlusion of the luminal area with thrombus for the control group, 43+/-14.3% for the aspirin-treated group, 30+/-5.6% for the heparin-treated group, and <10+/-1.8% for the hirudin-treated group. Assessment of platelet-thrombus formation with this technique was more sensitive than change in flow in determining antithrombotic efficacy, and thrombus formation was detected earlier. This study validates a new quantitative, sensitive, potentially noninvasive, portable, in vivo monitoring of dynamic thrombus growth, which appears applicable to phase II studies in humans.

Adenosine Diphosphate↗
PubMed2000

Induction of IG9 monocyte adhesion molecule expression in smooth muscle and endothelial cells after balloon arterial injury in cholesterol-fed rabbits.

The expression of monocyte-specific adhesion molecules and chemokines by cell types within the vessel wall plays an important role in foam cell accumulation during atherosclerotic plaque development. We previously identified IG9, a novel monocyte adhesion protein that is expressed on endothelial cells (ECs) overlying human and rabbit advanced atherosclerotic plaques. The present study was designed to determine the temporal and spatial expression of IG9 and the chemokine, monocyte chemoattractant protein-1 (MCP-1), after balloon injury with (double injury) or without (single injury) prior air desiccation EC injury in the femoral arteries of rabbits fed a high-cholesterol diet. By immunohistochemical analyses, intense reactivity with monoclonal antibodies to IG9 and MCP-1 was detected 24 hours after single injury in medial smooth muscle cells (SMCs) and in SMCs of adventitial microvessels. However, monocyte infiltration of the tunica media was minimal or not detected in these sections. IG9 and MCP-1 antibody reactivity in vessel sections 28 days after single injury and 24 hours, 7 days, and 28 days after double injury was localized to medial and neointimal SMCs, foam cells, and luminal ECs overlying the plaques. Uninjured rabbit (cholesterol or normal diet) vessel sections exhibited minimal IG9 and MCP-1 immunostaining. In vitro studies using human aortic SMCs demonstrated IG9 protein induction after 24 hours of treatment with platelet-derived growth factor-BB and interferon-gamma or epidermal growth factor. IG9 expression was further increased by pretreatment of SMCs with the proatherogenic lipid, minimally oxidized low density lipoprotein. After balloon injury (24 hours), IG9 is induced in vascular SMCs before the detectable accumulation of monocytes within the vessel wall. Thus, the expression of IG9 by SMCs as well as by ECs may be an important factor in the accumulation of foam cells in atherosclerotic plaque development after arterial injury.

Animals↗
PubMed2000

Intimal tissue factor activity is released from the arterial wall after injury.

Tissue factor (TF), the initiator of coagulation, has been implicated as a critical mediator of arterial thrombosis. Previous studies have demonstrated that TF is rapidly induced in the normal rodent arterial wall by balloon injury, but is not associated with fibrin deposition. A second injury, however, performed 10-14 days after the first, is followed by small platelet-fibrin microthrombi. This study was undertaken to better localize active TF in balloon-injured rat arteries and to explore possible mechanisms underlying the apparent discrepancy between injury-induced TF expression and the lack of large platelet-fibrin thrombi. By immunohistochemistry, TF antigen was first detected in the media 24 h after injury to rat aortas, and subsequently accumulated in the neointima. Using an ex vivo flow chamber, no TF activity (Factor Xa generation) was found on the luminal surface of normal or injured aortas. Wiping the luminal surface with a cotton swab exposed TF activity in all vessels; levels were increased approximately 3-fold in arteries containing a neointima. The exposed TF activity was rapidly washed into the perfusate, rendering the luminal surface inactive. The loss of luminal TF into the circulation may attenuate thrombosis at sites of arterial injury.

Angioplasty, Balloon, Coronary↗
PubMed2000

Pravastatin: an antithrombotic effect independent of the cholesterol-lowering effect.

Lipid-lowering with statins reduces blood thrombogenicity. However, it is unknown whether this is purely due to LDL-cholesterol reduction, or it is related to a statin or agent specific effect. We investigated the relationship between reduction in blood thrombogenicity and the magnitude of low-density lipoprotein cholesterol (LDL-C) during pravastatin therapy. We prospectively followed for 6 months 57 hyperlipidemic patients who initiated therapy with pravastatin, and 36 patients who were randomized into placebo plus diet. Pravastatin-treated patients were grouped according to the LDL-C reduction at 6 months; (i) "adequate LDL-C reduction": LDL-C reduction >30% from baseline or LDL-C<125 mg/dl (n = 38; LDL-C reduction 74 +/- 4 mg/dl; 6-month LDL-C 119 +/- 5 mg/dl); (ii) "inadequate LDL-C reduction": neither of the above criteria (n = 19; LDL-C reduction 31 +/- 5 mg/dl; 6-month LDL-C 158 +/- 6 mg/dl). Placebo patients were divided into those "with LDL-C reduction" (n = 17, mean reduction 21 +/- 5 mg/dl) and those "without LDL reduction" (n = 19). The following parameters were altered at 6 months in both patients with "adequate" and "inadequate" LDL-C reduction: (1) tissue plasminogen activator decreased by 1.4 +/- 0.4 and 1.5 +/- 0.5 ng/ml respectively (p = NS); (2) plasminogen activator inhibitor-1 decreased by 8.7 +/- 2.0 and 10.1 +/- 2.7 ng/ml respectively (p = NS); (3) thrombus formation under dynamic flow conditions decreased by 3.5 +/- 0.9 and 2.8 +/- 1.2 microm2 x 10(3) respectively (p = NS). In contrast, no significant changes from baseline were noted in placebo-treated patients, regardless of their LDL-C reduction category, and multivariate analysis eliminated LDL-C reduction as an independent predictor of reduction in thrombogenicity. Therefore, the reduction in thrombogenicity was not proportional to the magnitude of LDL-C reduction suggesting that a class or agent specific property is primarily responsible for the pro-fibrinolytic/antithrombotic effects observed.

Aged↗
PubMed1999

Gender differences in blood thrombogenicity in hyperlipidemic patients and response to pravastatin.

Thrombotic risk in hyperlipidemic women and its response to lipid therapy is unknown. We prospectively studied 28 men and 29 women with high low-density lipoprotein (LDL) cholesterol during 6 months of therapy with pravastatin. Women had significantly higher high-density lipoprotein (HDL) cholesterol (54.2 +/- 1.7 vs 39.5 +/- 2.2 mg/dl, p <0.01), lower prevalence of coronary artery disease (41% vs 67%, p = 0.04), and otherwise similar baseline characteristics compared with men. Both genders achieved a 33% reduction in LDL at 6 weeks (188 +/- 6 to 133 +/- 5 mg/dl) and maintained similar LDL levels throughout the study. Systemic hemostatic markers and thrombus formation under dynamic flow conditions were evaluated at baseline, and at 3 and 6 months of follow-up. Prothrombin fragment F1.2, a marker of thrombin generation, was higher in women versus men at baseline (2.4 +/- 0.2 vs 1.4 +/- 0.3 nmol/L, p = 0.02). The levels decreased in women to 2.0 +/- 0.3 nmol/L at 3 months and to 1.6 +/- 0.2 nmol/L at 6 months (p <0.045, analysis of variance), whereas it remained unchanged in men. Plasminogen activator inhibitor-I significantly decreased at 3 and 6 months of follow-up: by 12.6% and 18.7%, respectively, in women, and by 18.8% and 23.5%, respectively, in men. Similarly, tissue plasminogen activator decreased significantly by 7.4% in women and 11.8% in men at 6 months compared with baseline. Fibrinogen showed an increase in both genders at follow-up. Thrombus formation was similar at baseline between the 2 genders, and decreased at 3 and 6 months compared with baseline by 12.5% and 29.5% in women, and by 18.6% and 19.4% in men (p <0.04 at 6 months vs baseline in both men and women). Other markers, including C-reactive protein, fibrinopeptide A, D-dimer, and factor VIIa, did not differ between genders and did not change with therapy. Thus, despite higher HDL, and lower incidence of coronary disease, women with high LDL had a comparable thrombotic and/or fibrinolytic profile to men and even evidence of increased thrombin generation at baseline. Blood thrombogenicity was reduced with pravastatin in both genders; in addition, thrombin generation was gradually reduced in women to a level similar to that of men by 6 months of follow-up.

Aged↗
PubMed1999

Dietary lipid lowering reduces tissue factor expression in rabbit atheroma.

BACKGROUND: The mechanisms by which lipid lowering reduces the incidence of acute thrombotic complications of coronary atheroma in clinical trials remains unknown. Tissue factor (TF) overexpressed in atheroma may accelerate thrombus formation at the sites of plaque disruption. A cell surface cytokine CD40 ligand (CD40L) enhances TF expression in vitro. METHODS AND RESULTS: To test the hypothesis that lipid lowering reduces TF expression and activity, we produced atheroma in rabbit aortas by balloon injury and cholesterol feeding for 4 months (Baseline group, n=15), followed by either a chow diet (Low group, n=10) or a continued high-cholesterol diet for 16 months (High group, n=5). Immunolocalization of TF, CD40L, and its receptor CD40 was quantified by computer-assisted color image analysis. Macrophages in atheroma of the Baseline and High groups strongly expressed TF. Intimal smooth muscle cells and endothelial cells also contained immunoreactive TF. Regions of expression of CD40L and CD40 colocalized with TF. Protein expression of TF diminished substantially in the Low group in association with reduced expression of CD40L and CD40. In situ binding of TF to factors VIIa and X, detected by digoxigenin-labeled factors VIIa and X, colocalized with TF protein in atheroma and decreased after lipid lowering. We also determined reduced TF biological activity in the Low group by use of a chromogenic assay. The level of TF mRNA detected by reverse transcription-polymerase chain reaction also decreased after lipid lowering. CONCLUSIONS: These results suggest decreased expression and activity of TF as a novel mechanism of reduced incidence of thrombotic complications of atherosclerosis by lipid lowering.

Animals↗
PubMed1999

Histopathologic comparison of human coronary in-stent and post-balloon angioplasty restenotic tissue.

Histomorphometric studies for smooth muscle cells, macrophages, tissue factor, collagen, and cell proliferation were performed on 20 atherectomy specimens from patients with in-stent restenosis and 20 specimens from patients with post-balloon PTCA restenosis. Smooth muscle cell content was larger and proliferation index was higher in in-stent restenotic tissue; macrophage, tissue factor, and collagen content were larger in post-balloon percutaneous transluminal coronary angioplasty restenotic tissue, suggesting a more cellular and proliferative response with less thrombogenic potential in human tissue from in-stent restenosis than tissue from post-balloon percutaneous transluminal coronary angioplasty restenosis.

Aged↗
PubMed1999

Cardiac resistance to adriamycin in transgenic mice expressing a rat alpha-cardiac myosin heavy chain/human multiple drug resistance 1 fusion gene.

Cardiac toxicity is a major factor that limits the use of anthracyclines in cancer chemotherapy. Heart failure frequently develops in patients treated with doxorubicin (Adriamycin), when they receive a cumulative dose greater than 500 mg/m2. To make a mouse model for gene therapy designed to prevent this toxic effect, we have produced transgenic mice overexpressing the human cDNA for the multiple drug resistance (h-mdr1) gene driven by 2.12 kb of the 5' flanking region of the rat alpha-cardiac myosin (aCM) heavy chain gene. Two lines of transgenic mice expressed the transgene at a high level in heart muscle. Transgenic and control animals were treated with Adriamycin intravenously at either a single dose of 10 mg/kg or a cumulative dose of 30 mg/kg in three injections. Subsequent light and electron microscopic examination of heart tissue demonstrated degenerative changes in control mice that were absent in transgenic animals at both doses. These results show that expression of the alphaCM/h-mdr1 transgene in heart confers protection from the toxic effect of Adriamycin and suggest that such constructs, if employed effectively in cardiac gene therapy protocols, could allow a more aggressive use of anthracyclines in the treatment of cancer.

3T3 Cells↗
PubMed1999

Blood-borne tissue factor: another view of thrombosis.

Arterial thrombosis is considered to arise from the interaction of tissue factor (TF) in the vascular wall with platelets and coagulation factors in circulating blood. According to this paradigm, coagulation is initiated after a vessel is damaged and blood is exposed to vessel-wall TF. We have examined thrombus formation on pig arterial media (which contains no stainable TF) and on collagen-coated glass slides (which are devoid of TF) exposed to flowing native human blood. In both systems the thrombi that formed during a 5-min perfusion stained intensely for TF, much of which was not associated with cells. Antibodies against TF caused approximately 70% reduction in the amount of thrombus formed on the pig arterial media and also reduced thrombi on the collagen-coated glass slides. TF deposited on the slides was active, as there was abundant fibrin in the thrombi. Factor VIIai, a potent inhibitor of TF, essentially abolished fibrin production and markedly reduced the mass of the thrombi. Immunoelectron microscopy revealed TF-positive membrane vesicles that we frequently observed in large clusters near the surface of platelets. TF, measured by factor Xa formation, was extracted from whole blood and plasma of healthy subjects. By using immunostaining, TF-containing neutrophils and monocytes were identified in peripheral blood; our data raise the possibility that leukocytes are the main source of blood TF. We suggest that blood-borne TF is inherently thrombogenic and may be involved in thrombus propagation at the site of vascular injury.

Animals↗
PubMed1999

Pravastatin therapy in hyperlipidemia: effects on thrombus formation and the systemic hemostatic profile.

OBJECTIVES: The study sought to determine the effects of lipid-lowering with pravastatin on the systemic fibrinolytic profile and on thrombus formation under dynamic flow conditions. BACKGROUND: Lowering cholesterol (C) decreases clinical events in coronary artery disease (CAD) patients, but an analysis of the effects of lipid-lowering on the entire hemostatic and thrombotic profile has not been conducted. METHODS: We prospectively studied 93 stable patients with untreated low-density lipoprotein cholesterol (LDL-C) >145 mg/dl. The CAD patients received pravastatin, and non-CAD patients were randomized to pravastatin versus placebo (double-blind). Thrombus formation upon an injured vascular surface was assessed in a substudy of 40 patients with a previously validated ex vivo perfusion chamber system. Systemic hemostatic markers and thrombus formation were evaluated at baseline, three and six months. RESULTS: Placebo produced no changes in either the lipid profile, any of the hemostatic markers, or the ex vivo thrombus formation. Both pravastatin groups (CAD and non-CAD) showed decreased LDL-C by 30% within 6 weeks (188 to 126 mg/dl, p < 0.001 vs. baseline), and decreased plasminogen activator inhibitor-1 at 3- and 6-month follow-up compared to baseline (15% to 18% decrease at 3 months and 21% to 23% at 6 months). For the tissue plasminogen activator antigen, CAD and non-CAD groups showed significant decreases at 6 months compared to baseline (10% and 13%, respectively). No significant changes were observed with treatment in d-dimer, fibrinopeptide A, prothrombin fragment F1.2, factor VIIa, von Willebrand factor, or C-reactive protein. Fibrinogen levels were significantly increased at 6 months compared to baseline, though still below the upper normal limit. In the perfusion chamber substudy, there was a decrease in thrombus area in non-CAD patients treated with pravastatin at both 3 and 6 months compared to baseline (by 21% and 34%, respectively). The CAD patients showed decreases in thrombus formation by 13% at 3 months, and by 16% at 6 months. The change in LDL-C- correlated modestly with the change in thrombus formation (r = 0.49; p < 0.01). CONCLUSIONS: Pravastatin therapy significantly decreased thrombus formation and improved the fibrinolytic profile in patients with and without CAD. These early effects may, in part, explain the benefit rendered in primary and secondary prevention of CAD.

Aged↗
PubMed1999

Tissue characteristics of restenosis after percutaneous transluminal coronary angioplasty in diabetic patients.

OBJECTIVES: The purposes of this study were to analyze coronary specimens from patients with diabetes mellitus (DM) and to compare them with specimens from patients without DM. BACKGROUND: Diabetes mellitus is associated with an increased incidence of restenosis after percutaneous transluminal coronary angioplasty (PTCA). Increased hypercellular smooth muscle cell proliferation with exaggerated intimal hyperplasia formation may be responsible for this predisposition. METHODS: Eighteen coronary atherectomy specimens with restenosis after PTCA from patients with DM were compared with 18 coronary atherectomy specimens with restenosis after PTCA from patients without DM. Total and segmental areas were quantified on trichrome-stained tissue of hypercellular tissue, collagen-rich sclerotic tissue, atheroma and thrombus. Demographic and angiographic data were similar in both groups. RESULTS: The percentage of total plaque area composed of hypercellular tissue was lower in restenotic specimens from patients with DM than in restenotic specimens from patients without DM (19 +/- 6% vs. 44 +/- 5%; p = 0.003). The percentage of collagen-rich sclerotic tissue area was larger in restenotic specimens from patients with DM than in restenotic specimens from patients without DM (77 +/- 9% vs. 53 +/- 4%; p = 0.004). The percentages of atheroma and thrombus were similar in both groups. CONCLUSIONS: Intimal hypercellular tissue content is reduced in restenotic tissue from patients with DM. Collagen-rich sclerotic content is increased in restenotic lesions from patients with DM. These results suggest an accelerated fibrotic rather than a proliferative response in diabetic lesions from patients with restenosis after PTCA.

Aged↗