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J T Fallon

Publications and source records attributed to J T Fallon.

At least 91 records · Page 5Linked to original sources
PubMed1997

Tissue factor in the pathogenesis of atherosclerosis.

TF antigen and activity are found in abundance in human atherosclerotic plaques, particularly in the lipid-rich core. TF is also readily induced in the arterial wall by balloon injury and accumulates in the resulting neointima. In chronic atherosclerosis, the macrophage is likely to be the major source of TF within the plaque. TF accumulates as an early event associated with the migration of monocytes to the vessel wall in response to chemoattractants, such as MCP-1, and their differentiation into macrophages. As SMC become activated in the developing plaque, they provide a second source of TF. Macrophages and SMC accumulate lipid and become foam cells, ultimately degenerating into a necrotic core rich in TF. Spontaneous plaque rupture or acute interventions expose active TF in the core to circulating blood, triggering thrombosis. In acute arterial injury, SMC appear to be the chief source of TF. In normal vessels, the induction of TF in the medial SMC is not sufficient to generate fibrin, presumably because the TF is not readily accessible on the luminal surface. In contrast, endothelial denudation of previously injured arteries may expose intimal TF to circulating blood, resulting in rapid fibrin deposition. In advanced human atherosclerosis, it is likely that even in areas that do not contain "unstable" or "stable" plaques, the vessel wall is not normal and more closely resembles that of a previously injured artery possessing an active intima. Interventions, such as balloon angioplasty, coronary atherectomy, or stent placement may expose intimal TF, leading to fibrin deposition. As the initiator of coagulation, TF is a potential target for inhibiting the thrombotic complications of atherosclerosis. TFPI (reviewed in 52) is currently under clinical investigation as an anticoagulant and its effects on intimal hyperplasia in animal models are being studied. Direct factor Xa inhibitors, such as tick anticoagulant peptide (TAP) and leech anticoagulant peptide (ATS), are also under investigation (53-54). Finally, the recent crystallization of TF (55) and the TF:VIIa (56) should provide important new insights into the design of molecules for directly inhibiting TF.

Animals↗
PubMed1996

Macrophages, smooth muscle cells, and tissue factor in unstable angina. Implications for cell-mediated thrombogenicity in acute coronary syndromes.

BACKGROUND: Macrophage expression of tissue factor may be responsible for coronary thrombogenicity in patients with plaque rupture. In patients without plaque rupture, smooth muscle cells may be the thrombogenic substrate. This study was designed to identify the cellular correlations of tissue factor in patients with unstable angina. METHODS AND RESULTS: Tissue from 50 coronary specimens (1560 pieces) from patients with unstable angina and 15 specimens from patients with stable angina were analyzed. Total and segmental areas (in square millimeters) were identified with trichrome staining. Macrophages, smooth muscle cells, and tissue factor were identified by immunostaining. Tissue factor content was larger in unstable angina (42 +/- 3%) than in stable angina (18 +/- 4%) (P = .0001). Macrophage content was also larger in unstable angina (16 +/- 2%) than in stable angina (5 +/- 2%) (P = .002). The percentage of tissue factor located in cellular areas was larger in coronary samples from patients with unstable angina (67 +/- 8%) than in samples from patients with stable angina (40 +/- 5%) (P = .00007). Multiple linear stepwise regression analysis showed that coronary tissue factor content correlated significantly (r = .83, P < .0001) with macrophage and smooth muscle cell areas only in tissue from patients with unstable angina, with a strong relationship between tissue factor content and macrophages in the atheromatous gruel (r = .98, P < .0001). CONCLUSIONS: Tissue factor content is increased in unstable angina and correlates with areas of macrophages and smooth muscle cells, suggesting a cell-mediated thrombogenicity in patients with acute coronary syndromes.

Adult↗
PubMed1996

Macrophage infiltration predicts restenosis after coronary intervention in patients with unstable angina.

BACKGROUND: Restenosis remains the major limitation of percutaneous coronary revascularization. Macrophages release cytokines, metalloproteinases, and growth factors that may induce smooth muscle cell migration and proliferation. We tested the hypothesis that primary lesions that develop restenosis after coronary atherectomy have more macrophages and smooth muscle cells than primary lesions that do not develop restenosis. METHODS AND RESULTS: Fifty patients with unstable angina were identified. Total and segmental areas were quantified on trichrome-stained sections of coronary atherectomy tissue. Macrophages and smooth muscle cells were identified by immunohistochemical staining. Restenosis, defined as > 50% stenosis diameter by quantitative cineangiography, was present in 30 patients. The other 20 patients (< 50% stenosis) constitute the "no restenosis" group. The percentages of smooth muscle cell areas were similar in specimens from patients with and without restenosis (57 +/- 5% and 52 +/- 6%) (P = NS). However, macrophage-rich areas were larger in plaque tissue from patients with restenosis (20.4 +/- 2%) than in tissue from patients without restenosis (9.3 +/- 2%) (P = .0007). Multiple stepwise logistic regression analysis identified macrophages as the only independent predictor for restenosis (P = .006). CONCLUSIONS: Macrophages are increased in coronary atherectomy tissue from primary lesions that develop restenosis, suggesting a possible role for macrophages in the restenotic process after percutaneous coronary intervention.

Adult↗
PubMed1996

Identification of active tissue factor in human coronary atheroma.

BACKGROUND: Recent observations suggest that thrombosis in vivo is initiated via the tissue factor (TF) pathway. The TF activity of human coronary atheroma has not been reported. METHODS AND RESULTS: Directional coronary atherectomy (DCA) specimens from 63 lesions were analyzed with the use of a quantitative TF-specific activity assay. The median content of TF was 10 ng/g plaque (95% CI, 6 to 13 ng/g; range, 0 to 47 ng/g). After homogenization of the specimens, TF activity was detected in 28 of 31 lesions (90%). With a polyclonal anti-human TF antibody, the use of immunohistochemistry detected TF antigen in 43 of 50 lesions (86%); TF antigen was expressed in cellular and acellular areas of the plaque. Histologically defined thrombus was present in 19 of the 43 lesions with detectable TF antigen and in none of the 7 lesions without detectable TF antigen (19 of 43 versus 0 of 7; P < .02). TF antigen was undetectable with immunohistochemistry in 4 of 13 restenotic lesions (31%) and in 3 of 37 de novo lesions (8%) (P < .05). CONCLUSIONS: TF contributes to the procoagulant activity of most atherosclerotic lesions treated with DCA. The association of immunohistochemically detectable TF with plaque thrombus suggests that TF plays a role in coronary thrombosis. Diminished TF expression in restenotic lesions may in part account for the lower complication rate that has been associated with DCA of restenotic versus de novo lesions. Inhibition of TF may represent a therapeutic goal for the prevention of thrombotic complications associated with percutaneous coronary interventions.

Antigens↗
PubMed1996

Functional and structural alterations with 24-hour myocardial hibernation and recovery after reperfusion. A pig model of myocardial hibernation.

BACKGROUND: Short-term myocardial hibernation of 3 hours resulting from a moderate resting coronary flow reduction has been reproduced in pigs. This study was designed to determine whether any structural changes accompany short-term hibernation caused by a moderate flow reduction maintained for 24 hours and whether any such structural alterations are reversible after reperfusion. METHODS AND RESULTS: A severe left anterior descending coronary artery (LAD) stenosis was created with a reduction of resting flow to approximately 60% of baseline and maintained for 24 hours. Regional coronary flow was measured by a flowmeter; wall thickening was determined by echocardiography, and local metabolic changes were measured. Of 17 pigs, 11 completed the study protocol of 24 hours. The LAD flow was reduced from 0.91 +/- 0.11 to 0.52 +/- 0.13 mL.min-1.g-1, a 43% mean decrease, at 15 minutes after the LAD stenosis and was maintained at 0.56 +/- 0.11 mL.min-1.g-1 at 24 hours. The reduction of regional coronary flow initially produced acute myocardial ischemia, as evidenced by reduced regional wall thickening (from 37.2 +/- 6.9% at baseline to 11.5 +/- 6.8%), regional lactate production (-0.34 +/- 0.28 mumol.g-1.min-1), and a decrease in regional coronary venous pH (from 7.41 +/- 0.035 at baseline to 7.30 +/- 0.030). At 24 hours, the reductions in coronary flow and wall thickening were maintained relatively constant and the rate-pressure product was relatively unchanged, but lactate production ceased and regional H+ concentration normalized, with a tendency toward a further reduction in regional oxygen consumption, from 3.10 +/- 0.90 mL.min-1.100 g-1 at 15 minutes after stenosis to 2.52 +/- 0.95 mL.min-1.100 g-1 at 24 hours (P = .06), indicating metabolic adaptation of the hypoperfused regions. Of 11 pigs, 6 were free of myocardial infarction; 3 had patchy necrosis involving 4%, 5%, and 6% of the area at risk; and 2 other pigs had a few scattered myocytes with necrosis, detected only by light and electron microscopy. Ultrastructural changes consisted of a partial loss of myofibrils and an increase in mitochondria and glycogen deposition. Regional wall thickening recovered 1 week after reperfusion in most pigs, and the ultrastructural changes reverted to normal. CONCLUSIONS: In this pig model, moderately ischemic myocardium undergoes metabolic and structural adaptations but preserves the capacity to recover both functionally and ultrastructurally after reperfusion.

Actin Cytoskeleton↗
PubMed1996

Quantitative assessment of stenotic aortic valve area by using intracardiac echocardiography: in vitro validation and initial in vivo illustration.

Quantitative assessment of aortic stenosis (AS) is subject to the limitations of all current noninvasive and invasive methods. The ability to obtain a direct measure of aortic valve area with high resolution by intracardiac echocardiography (ICE) could be of great benefit to catheterized patients. To provide a fixed AS area as an ideal standard for comparison, we performed ICE in 12 sheep hearts with experimentally created AS and five human AS hearts from autopsies. ICE catheters were passed retrograde across the aortic valve, and the minimal orifice area on pullback was planimetered and compared with calibrated video imaging. The entire orifice circumference could be successfully recorded in 16 (94%) hearts. Orifice area from ICE correlated well with actual values (r=0.98; standard error of the estimate [SEE] = 0.06 cm2). To illustrate the applicability in vivo, two canine models and 10 patients with AS were studied. The limiting orifice could be imaged in both animals and in 8 of 10 patients, in whom values agreed well with invasive data (r= 0.95; SEE = 0.04 cm2). ICE can therefore accurately measure AS orifice area in vitro; it can be applied in vivo as well. These validation studies laid the foundation for subsequent clinical studies and applications.

Animals↗
PubMed1996

Cardiac allograft vasculopathy in partially inbred miniature swine. I. Time course, pathology, and dependence on immune mechanisms.

To assess the role of the immune system in cardiac allograft vasculopathy in large animals, heterotopic heart transplantation was done between partially inbred miniature swine, animals in which transplantation can be done across defined major histocompatibility barriers in a reproducible fashion. Porcine hearts transplanted into untreated recipients across a class I, class II, or full major histocompatibility mismatch were acutely rejected in 6 to 8 days (n = 4). Hearts transplanted into untreated recipients across minor histocompatibility barriers survived for 21 to 44 days (n = 5) and showed no evidence of cardiac allograft vasculopathy. When recipients were treated with a 12-day course of cyclosporine, hearts transplanted across minor histocompatibility barriers survived 42, 64, and 56 days and did not develop vascular lesions. However, hearts transplanted into cyclosporine-treated recipients across a full major histocompatibility disparity survived 20, 22, and 23 days and all three developed biopsy-proven vasculopathy. In one animal, the progression of intimal proliferation was followed in vivo by intracoronary ultrasonography. The degree of intimal thickening documented by ultrasonography correlated well with the intimal proliferation found on tissue histologic samples. These results are the first to show that in large animals, an immune response stimulated by donor major histocompatibility antigens is involved in the induction of cardiac allograft vasculopathy. In addition, these studies point out the utility of a large-animal model of cardiac allograft vasculopathy in which transplantation across defined major histocompatibility barriers can be done reproducibly and in which accurate determinations of the progression or regression of coronary vascular lesions in individual animals can be accurately assessed in vivo.

Animals↗
PubMed1996

Innate protection of baboon myocardium: effects of coronary artery occlusion and reperfusion.

To determine whether the extent of myocardial infarction differs in conscious baboons and pigs, both devoid of performed collaterals, the effects of 40 and 90 min of coronary artery (CA) occlusion (O) both followed by 4-7 days of CA reperfusion (R) were examined in both species. CAO reduced subendocardial and subepicardial blood flows similarly, almost to zero, in baboons and pigs for the entire CAO period. At 24 h of CAR, subendocardial blood flow had almost returned to pre-CAO control levels in baboons but remained significantly depressed in pigs. The major difference in hemodynamics during CAO and CAR was in left ventricular end-diastolic pressure, which rose by 6 +/- 1 mmHg in pigs over the initial 24-h reperfusion period but did not change significantly in baboons. These data on recovery of subendocardial blood flow and left ventricular end-diastolic pressure suggest larger infarcts in pigs than in baboons. Indeed, infarct size expressed as a function of area at risk (IF/AAR) was significantly greater (P < 0.05) in pigs (53 +/- 4.9%) than in baboons (17 +/- 2.9%) with 90 min of CAO and 4-7 days of CAR. With 40 min of CAO and 4-7 days of CAR, IF/AAR was 46 +/- 3.6% in pigs, whereas in baboons the IF/AAR was minimal, i.e., 2 +/- 0.6%. Thus pigs and baboons were characterized by minimal coronary collateral circulation, but infarct size was significantly less in conscious baboons than in conscious pigs. Potentially, these differences could be explained, in part, by natural protective mechanisms and/or less reperfusion injury in primates. These results in primates may also help explain the salutary effects of CAR in patients at intervals longer than have been demonstrated to be beneficial in other experimental animals.

Animals↗
PubMed1996

Plaque rupture, thrombosis, and therapeutic implications.

The basic mechanisms of atherosclerotic progression leading to the acute coronary syndromes (ACS) have been elucidated during the last few years. In this brief presentation, we outline 1) Definition of Atherosclerotic Lesions: eight morphologically different lesions are defined (Type I to VI) in various phases of disease. 2) Vulnerable Lipid-Rich Plaques and the ACS: The type IV and Va lesions tend to be relatively small in size, but soft or vulnerable to a "passive" phenomenon of plaque disruption; in addition, an "active" macrophage-dependent enzymatic (genesis of metalloproteinase) phenomenon of plaque disruption is evolving. 3) Thrombosis: we have shown that monocytes/macrophages in lipid-rich plaques may play a detrimental role after plaque disruption, promoting thrombin generation and thrombosis through the tissue factor pathway that can be prevented by tissue factor pathway inhibition; such pathway of thrombosis appears to be critical in the development of the ACS. 4) Effect of Lipid-Modifying Strategies and other Risk Factors on the Vulnerable Lipid-Rich Plaques: when high LDL-cholesterol is reduced therapeutically, efflux from the plaques of the liquid or sterified cholesterol, and also its hydrolysis into cholesterol crystals depositing in the vessel wall, predominate over the influx of LDL-cholesterol; consequently, there is a decrease in the softness of the plaque and so, presumably in the "passive" phenomenon of plaque disruption; modification of other risk factors presumably also favorably affect LDL-cholesterol influx and efflux. 5) Antithrombotic Strategies: the evolving antithrombotic approaches under investigation are briefly outlined.

Anticoagulants↗
PubMed1996

SM-20 is a novel 40-kd protein whose expression in the arterial wall is restricted to smooth muscle.

We have previously reported the identification of a novel cDNA, SM-20, whose corresponding mRNA levels are regulated by growth factors in rat aortic smooth muscle cell (SMC) culture. Affinity-purified polyclonal and monoclonal antibodies were made against a 230 amino acid region of the SM-20 putative peptide expressed in the bacterial vector, pET-3b. Western blot analyses of rat and human SMC lysates detected a single protein species of approximately 40 kd. SM-20 was not detected in concentrates of the culture medium. By immunohistochemistry, SM-20 was localized to filaments in the cytoplasm of cultured SMC. Like SM-20 mRNA, levels of SM-20 protein were increased 1-3 hours after serum stimulation of rat aortic SMC. In rat tissues, SM-20 antigen was detected in abundance in smooth, cardiac, and skeletal muscle. SM-20 was also detected in some epithelial cells of the kidney, pancreas, gastrointestinal tract, and skin, but was not found in the parenchyma of the liver, spleen, or testis. In the rat arterial wall, SM-20 antigen was restricted to the SMC of the media and, after balloon arterial injury, was found most abundantly in the neointima. In human atherosclerotic coronary arteries, SM-20 antigen predominated in the SMC of the intimal plaques and was not detected in macrophages, endothelium, or adventitial cells. Thus, SM-20 encodes a protein which serves as a novel SMC-specific marker within the vessel wall.

Adult↗
PubMed1996

In situ localization of tissue factor in human atherosclerotic plaques by binding of digoxigenin-labeled factors VIIa and X.

The mechanism responsible for the thrombotic complications of atherosclerotic plaques is not well understood. Although a role for tissue factor (TF) has been hypothesized, there are scant data on the presence, location, quantity, and activity of TF in atherosclerotic plaques. The purpose of this study was to show the localization of TF in human atherosclerotic plaques. Digoxigenin-labeled factors VIIa and X were used to demonstrate their specific binding sites in formalin-fixed, paraffin-embedded human arteries by incubation of sections with the labeled factor and localization of TF:factor(s) complexes by immunohistochemical staining for digoxigenin. In sections of atherosclerotic plaques, diffuse staining was most intense in the relatively acellular, lipid-rich core but was also present intracellularly in macrophages and smooth muscle cells and, to a lesser extent, in the relatively acellular fibrous tissue of the plaque. Endothelial cells overlying plaques and occasional medial smooth muscle cells stained positively as well. The adventitia routinely stained for TF in both normal and diseased artery segments. Staining for labeled factor VIIa was blocked when sections were preincubated with a 10-fold excess of unlabeled factor VIIa or with a polyclonal antihuman TF antibody. Binding of labeled factors VIIa and X was Ca(2+)-dependent. In conclusion, binding of digoxigenin-labeled factors VIIa and X shows that the lipid rich core of atherosclerotic plaques contains high levels of extracellular TF. This location may be responsible for the rapid initiation of thrombosis when lipid rich atherosclerotic plaques rupture and the core contents are exposed to flowing blood.

Animals↗
PubMed1995

Human monocyte-derived macrophages induce collagen breakdown in fibrous caps of atherosclerotic plaques. Potential role of matrix-degrading metalloproteinases and implications for plaque rupture.

BACKGROUND: Rupture of the fibrous cap of the atherosclerotic plaque is a key event that predisposes to coronary thrombosis, leading to acute coronary syndromes. Recent studies have shown that the fibrous caps of vulnerable and ruptured atherosclerotic plaques have reduced collagen and glycosaminoglycan content in association with an increased macrophage density and a reduced smooth muscle cell density. Since collagen breakdown in the fibrous caps may contribute to a thinning and weakening of the cap, increasing its vulnerability to rupture, we tested the hypothesis that monocyte-derived macrophages, by producing matrix-degrading metalloproteinases (MMPs), could induce collagen breakdown in human atherosclerotic fibrous caps. METHODS AND RESULTS: Monocytes were isolated from human blood by Ficoll-Paque density gradient and allowed to grow in cell culture until phenotypic and staining characteristics indicated transformation into macrophages (4 to 7 days). Fibrous caps were dissected from human aortic or carotid plaques and incubated for 48 hours with macrophages in serum-free medium without (n = 21) and with (n = 10) an MMP inhibitor or with cell- and serum-free medium only (n = 9). Hydroxyproline released in the culture medium was measured by a spectrophotometric method and used as evidence of collagen breakdown in the fibrous caps. Immunocytochemistry with specific monoclonal antibodies was used to identify expression of MMP-1 (interstitial collagenase) and MMP-2 (72-kD gelatinase) in cell culture, and zymography was used to detect MMP activity in the culture supernatant. The amount of hydroxyproline released was significantly greater when fibrous caps were incubated with macrophages than when incubated with cell-free medium (0.4 +/- 0.16 micrograms.mL-1.mg-1 versus 0.02 +/- 0.03 micrograms.mL-1.mg-1 of tissue; P < .04 by Mann-Whitney test). There was no hydroxyproline release when fibrous caps were incubated with macrophages in the presence of an MMP inhibitor. Immunocytochemistry demonstrated MMP-1 and MMP-2 expression by macrophages between days 4 and 7, and zymography confirmed the presence of MMP-2 activity in the supernatant. CONCLUSIONS: In this study, human monocyte-derived macrophages were shown to induce collagen breakdown in fibrous caps of human atherosclerotic plaques associated with cellular expression and zymographic evidence of MMP activity; no evidence of collagen breakdown was found in the presence of an MMP inhibitor. These findings support the hypothesis that increased macrophage density and/or activation in the atherosclerotic plaque may induce collagen breakdown in the fibrous cap by secreting MMPs and possibly other proteases, thus contributing to vulnerability to plaque rupture.

Arteriosclerosis↗
PubMed1995

Incremental doses of dobutamine induce a biphasic response in dysfunctional left ventricular regions subtending coronary stenoses.

BACKGROUND: Dobutamine stress echocardiography has been proposed as a diagnostic tool to identify viable myocardium. How regional wall thickening responds to dobutamine in the ischemic or short-term hibernating myocardium has not been adequately defined. We hypothesized that regional wall thickening would improve initially and subsequently deteriorate with incremental doses of dobutamine in viable myocardial regions supplied by a stenotic coronary artery. This study was undertaken to determine whether this biphasic pattern of regional function characterizes the response of ischemic or hibernating myocardium to dobutamine and to explore the factors and mechanisms that determine this response. METHODS AND RESULTS: Twenty-six pigs in four groups were studied: a control group (n = 5) to assess the response of myocardium perfused by nonstenotic coronary artery to incremental doses of dobutamine, and three experimental groups with a left anterior descending coronary artery stenosis producing acute myocardial ischemia (n = 7), short-term myocardial hibernation for 90 minutes (n = 7), and short-term hibernation for 24 hours (n = 7) to determine the functional and metabolic response to dobutamine under these conditions. Regional coronary flow was reduced to 40% to 60% of baseline, with significant reductions of regional wall thickening as measured by two-dimensional echocardiography and sonomicrometers. An incremental dobutamine infusion from 2.5 to 25 micrograms.kg-1.min-1 increased wall thickening and coronary flow without lactate production in the control group. In the other three groups, during the incremental dobutamine infusion, regional wall thickening improved initially, from 11.4 +/- 7.5% to 19.8 +/- 11.4%, P < .01, at dobutamine doses of 2.5 to 10 (4.5 +/- 2.2) micrograms.min-1.kg-1 but deteriorated subsequently to 5.0 +/- 5.8% at the maximal dose of dobutamine of 12.6 +/- 4.1 micrograms.min-1.kg-1. The initial improvement of regional wall thickening was associated with a small increase in regional coronary flow (from 0.53 +/- 0.18 to 0.68 +/- 0.25 mL.min-1.g-1 myocardium, P < .05) and with regional lactate production. High doses of dobutamine did not further increase regional coronary flow but markedly increased lactate production and induced regional myocardial acidosis (pH 7.26 +/- 0.07). The biphasic pattern of response to dobutamine was observed in each of the three experimental groups. Both peak improvement and peak deterioration occurred earlier and at lower dobutamine dose levels in the group with acute ischemia compared with the group with short-term hibernation for 24 hours (P < .05). CONCLUSIONS: A biphasic response of wall thickening to incremental dobutamine with initial improvement and subsequent deterioration is characteristic of ischemic or short-term hibernating myocardium. The initial low-dose dobutamine infusion improved wall thickening in the ischemic or hibernating myocardial region to a modest level. This initial modest improvement was transient and at the expense of metabolic deterioration of myocardial ischemia, so that at higher doses during prolonged dobutamine infusion, wall thickening deteriorated, lactate accumulated, and myocardial acidosis developed.

Animals↗
PubMed1995

Quantitative three-dimensional reconstruction of aneurysmal left ventricles. In vitro and in vivo validation.

BACKGROUND: Current two-dimensional (2D) echocardiographic measures of left ventricular (LV) volume are most limited by aneurysmal distortion, which restricts application of simple geometric models that assume symmetrical shape. 2D methods also fail to provide separate volumes of the aneurysm and nonaneurysmal residual LV cavity, which could help assess the stroke volume wasted by dyskinesis and the potential residual LV body to guide surgical approaches and predict their outcome. Three-dimensional (3D) echocardiographic reconstruction has potential advantages for assessing aneurysmal left ventricles because it is not dependent on geometric assumptions, does not require standardized views that may exclude portions of the aneurysm, and can potentially measure separate aneurysm and nonaneurysm cavity volumes of any shape. The purpose of this study was first, to validate the accuracy of 3D echocardiographic reconstruction for quantifying total LV and separate LV body and aneurysm volumes in vitro so as to provide direct standards for the separate volumes; and second, to determine the feasibility and accuracy of 3D echocardiographic reconstruction for quantifying the total volume and function of aneurysmal left ventricles in an animal model, providing a reference standard for instantaneous LV volume. METHODS AND RESULTS: A recently developed 3D system that automatically combines 2D images and their locations was applied (1) to reconstruct 10 aneurysmal ventricular phantoms and 12 gel-filled autopsied human hearts with aneurysms, comparing cavity volumes (total and aneurysm) to those measured by fluid displacement; and (2) to reconstruct the left ventricle during 19 hemodynamic stages in four dogs with surgically created LV aneurysms, comparing total volumes with actual instantaneous values measured by an intracavitary balloon attached to an external column for validation and also calculating the stroke volume wasted by aneurysmal dyskinesis. 3D reconstruction reproduced the distorted aneurysmal LV shapes. In vitro, calculated volumes (aneurysm, nonaneurysm, and total) agreed well with actual values, with correlation coefficients of .99 and SEEs of 3.2 to 6.1 cm3 for phantoms and 3.4 to 4.2 cm3 for autopsied hearts (mean error, < 4% for both). In vivo, LV end-diastolic, end-systolic, and stroke volumes as well as ejection fraction calculated by 3D echocardiography correlated well with actual values (r = .99, .99, .95, and .99, respectively) and agreed closely with them (SEE = 4.3 cm3, 3.5 cm3, 1.7 cm3, and 2%, respectively). The stroke volumes wasted by the aneurysm were -20.1 +/- 19.3% of LV body (nonaneurysm) stroke volume. CONCLUSIONS: Despite distorted ventricular shapes, a recently developed 3D echocardiographic system and surfacing algorithm can accurately reconstruct aneurysmal left ventricles and quantify total LV volume (validated in vivo and in vitro) as well as the separate volumes of the aneurysm and residual LV body (validated in vitro). This should improve our ability to evaluate such ventricles and guide surgical approaches.

Algorithms↗
PubMed1995

Endothelial cell seeding fails to attenuate intimal thickening in balloon-injured rabbit arteries.

BACKGROUND: Restenosis of arteries or bypass grafts after vascular reconstruction is a common clinical entity that significantly limits long-term patency. This process, termed intimal hyperplasia (IH), is characterized by smooth muscle cell proliferation in the intima and subsequent accumulation of intercellular matrix. This study was designed to test the hypothesis that endothelial cell (EC) seeding of acutely injured arteries accelerates reendothelialization of the flow surface and limits the development of IH. METHODS: ECs were harvested from jugular veins of New Zealand white rabbits (n = 13) and were amplified in tissue culture. Each animal subsequently underwent bilateral balloon catheter injury of the iliofemoral arteries; one side was immediately seeded with cultured autologous ECs at supraconfluent density, whereas the contralateral vessel served as a nonseeded control. Animals were killed 33 +/- 5 days after balloon injury. Intimal thickening was quantitated on histologic sections of vessels (three sections per vessel, total of 60 sections) and percent endothelialization was assessed by SEM; measurements were obtained by use of computer-aided morphometry performed by a blinded observer. Data were analyzed by use of a paired t test for comparison between seeded and control vessels. RESULTS: Seeded vessels exhibited a greater degree of reendothelialization (93.9% +/- 7.6% of the surface) than their unseeded counterparts (65.1% +/- 22.5%, p < 0.01). Intimal cross-sectional area and the ratio of intimal area to medial area were not significantly different between seeded and control vessels (intima: 0.32 +/- 0.19 vs 0.37 +/- 0.11 mm2, p = 0.28; intimal area to medial area ratio: 0.84 +/- 0.35 vs 1.02 +/- 0.2, p = 0.24). CONCLUSIONS: We conclude that seeding with autologous venous ECs accelerated restoration of the endothelial monolayer but failed to attenuate IH in balloon-injured rabbit arteries. Further studies are necessary to determine the functional properties of seeded endothelium and to examine the effect of EC seeding on intimal thickening in other clinically relevant models.

Animals↗