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Biomedical subjects

G Pasterkamp

Publications and source records attributed to G Pasterkamp.

72 records · Page 4Linked to original sources

Relationship between plaque mass and neointimal hyperplasia after stent placement in Yucatan micropigs.

PURPOSE: To determine whether the amount of neointima found after stent placement is related to the preexistent plaque mass in the peripheral arteries in micropigs. MATERIALS AND METHODS: Twenty-six peripheral arteries were studied in 14 Yucatan micropigs in a denudation and diet-induced atherosclerosis model. Quantitative angiographic and intravascular ultrasound (US) analysis were performed before and after stent placement and at follow-up 6 weeks after stent placement. At follow-up, the peripheral arterial tree was fixed by means of pressure perfusion, processed for histologic analysis, and analyzed morphometrically with a computer-based system. RESULTS: Preexistent plaque correlated strongly with intimal hyperplasia measured on US images (r = .81, P < .001) or in histologic sections (r = .53, P = .006). No correlation was found between dilation ratio and intimal hyperplasia or between balloon-to-lesion ratio and intimal hyperplasia. In multivariate models of intimal hyperplasia, preexistent plaque and early gain in lumen diameter depicted at angiography were independent explanatory variables. CONCLUSION: The amount of plaque present before stent placement was a determinant of the amount of intimal hyperplasia present after stent placement.

Angiography↗

Compensatory enlargement in coronary and femoral arteries is related to neither the extent of plaque-free vessel wall nor lesion eccentricity. A postmortem study.

Arteries may demonstrate compensatory enlargement in response to plaque accumulation. It has been proposed that enlargement is achieved by the expansion of the nondiseased (plaque-free) vessel wall. In this study, we assessed this hypothesis. Post mortem, 32 atherosclerotic coronary arteries (left anterior descending, n = 10; left circumflex, n = 11; and right coronary, n = 11) and 54 atherosclerotic femoral arteries were pressure fixed. Cross sections (coronary arteries, n = 537; femoral arteries, n = 1602) were obtained for analysis every 2.5 mm for the coronary arteries and every 5.0 mm for the femoral arteries. From these cross sections, we determined the degree of remodeling and an eccentricity index. Finally, we measured the extent of plaque-free vessel wall. The plaque-free vessel wall was defined as (1) no plaque present or (2) plaque thickness < 0.5 mm. A very weak, negative correlation was observed between the degree of remodeling and the extent of the plaque-free vessel wall (coronary arteries: no plaque r2 = .13, P < .01; < 0.5 mm plaque r2 = .15, P < .05; femoral arteries: no plaque r2 = .02, P < .01; < 0.5 mm plaque r2 = 0.04, P < .01). The degree of remodeling did not correlate with the eccentricity index (coronary arteries r2 = .002, P > .05 and femoral arteries r2 = .001, P > .05). Thus, compensatory enlarged segments did not reveal a larger circumference of plaque-free vessel wall compared with segments that failed to enlarge. This study provides no support for the hypothesis that nondiseased vessel-wall expansion is responsible for compensatory enlargement in atherosclerotic arteries.

Aged↗

The impact of atherosclerotic arterial remodeling on percentage of luminal stenosis varies widely within the arterial system. A postmortem study.

Luminal stenosis can be based on large atherosclerotic plaques in compensatory enlarged segments or on relatively little plaques in shrunken segments. In the present study, the contribution of plaque formation and remodeling to luminal narrowing was compared among six types of arteries prone to symptomatic atherosclerosis. Cross-sections (n = 5195) were obtained at regular intervals from 329 arteries. For each artery, the cross-section that contained the least amount of plaque was considered to be the reference. For each cross-section, the percentage of lumen area decrease was expressed as a percentage of the lumen area at the reference site (luminal stenosis). Similarly, the area encompassed by the internal elastic lamina (IEL area) was expressed as a percentage of the IEL area at the reference site (relative IEL area). All cross-sections were categorized in three groups: relative IEL area > 105% (enlargement), 95% to 105% (no remodeling), and < 95% (shrinkage). The prevalence of enlargement (50% to 75%) was significantly higher compared with shrinkage (8% to 25%). Shrinkage was observed most frequently in the femoral arteries (25%) and infrequently in the renal arteries (8%). For all types of arteries, the relative IEL area correlated negatively with luminal stenosis (P < .001). Regression analysis of relative IEL area on luminal stenosis, however, showed significant differences in the first-order regression coefficients among artery types. On average, plaque increase was more compensated for by enlargement in the coronary, common carotid, and renal arteries compared with the arteries obtained from the lower extremities. Anatomic regional differences were observed in the impact of arterial wall remodeling on percent luminal stenosis in de novo atherosclerotic lesions.

Aged↗

Application of intravascular ultrasound in remodelling studies.

Arterial remodelling is an important determinant of luminal narrowing in de novo atherosclerosis as well as in restenosis following balloon angioplasty. To date, intravascular ultrasound is the best diagnostic modality to study changes in arterial size in vivo. The role of arterial wall remodelling in de novo atherosclerosis and restenosis has been well established by intravascular ultrasound studies. Single intravascular ultrasound studies have demonstrated that the artery may enlarge, fail to enlarge or even shrink if plaque accumulates. In restenosis studies, serial intravascular ultrasound studies have allowed examination of the remodelling process over time and have shown that arterial shrinkage and not intimal hyperplasia is the predominant factor responsible for luminal narrowing after balloon angioplasty. This article will focus on the applicability of intravascular ultrasound to the study of vascular remodelling in de novo atherosclerosis, in restenosis after balloon angioplasty, atherectomy and stenting, in saphenous vein grafts and in the coronary arteries of transplanted hearts.

Angioplasty, Balloon↗

Arterial remodelling by atherosclerosis.

Until recently, plaque formation was considered to be the only determinant of atherosclerotic luminal narrowing. Recent post-mortem and intravascular ultrasound studies, however, revealed that arterial remodelling is another important determinant of luminal narrowing in de novo atherosclerosis. The change in total arterial circumference relative to a reference cross-section ranges from excessive enlargement with an actual increase in lumen to arterial shrinkage contributing to lumen narrowing. The mechanisms responsible for this spectrum of remodelling are unknown, but their identification will be important for the potential development of therapeutic strategies to promote favourable remodelling.

Adaptation, Physiological↗

Quantitative analysis of von Willebrand factor propeptide release in vivo: effect of experimental endotoxemia and administration of 1-deamino-8-D-arginine vasopressin in humans.

The results of studies with cultured endothelial cells have shown that most von Willebrand factor (vWF) synthesized is directly secreted (constitutive pathway) and consists of both mature vWF, its precursor molecule pro-vWF, and the cleaved vWF prosequence. Only fully processed, functionally mature vWF is stored within the cell, together with the propeptide, and leaves the cell only on stimulation (regulated secretion). Both in resting and stimulated cultured endothelial cells, the stoichiometry of the released propeptide to the released mature vWF is essentially equimolar. In the present study, we have measured the molar ratio of propeptide to mature vWF in vivo, both under resting conditions and conditions that reflect activation of the endothelium. To this end, we devised a method that allows the measurement of the propeptide (vW antigen II) on a quantitative, is, molar basis, using purified recombinant propeptide as a standard. Our results show that the molar concentration of the propeptide in normal plasma is about one tenth of the concentration of mature vWF (expressed as half-dimer concentration). This ratio is approximately 1:1 in the medium of cultured endothelial cells. On administration in healthy subjects of either 1-deamino-8-D-arginine vasopressin or endotoxin, both agents being known to elicit an intravascular increase of vWF, the molar ratio of propeptide to mature vWF increased fourfold to fivefold. The propeptide concentration returned to baseline values after about 6 to 7 hours of injection of each stimulus, whereas the increase of mature vWF was much more sustained. Because the respective half-lives of mature vWF and its propeptide clearly differ, measurement of the concentration of these proteins could provide a means to assess the extent of activation of the endothelium under physiological and pathophysiological conditions.

Adult↗

Atherosclerotic arterial remodeling in the superficial femoral artery. Individual variation in local compensatory enlargement response.

BACKGROUND: In previous studies on atherosclerotic arterial remodeling, compensatory enlargement of the artery in response to plaque accumulation was inferred from pooled data based on one cross section per artery. We assessed local arterial remodeling individually by analyzing 45 artery segments at 0.5-cm intervals over a length of 10 to 15 cm. METHODS AND RESULTS: Twenty patients were studied by 30-MHz intravascular ultrasound (IVUS) before balloon angioplasty of the superficial femoral artery (370 cross sections), and 25 femoral artery segments were studied postmortem (551 cross sections). In each cross section, the area surrounded by the internal elastic lamina (IEL area) and the plaque area were measured. The IEL area was larger in the cross section with the largest plaque area than in the cross section with the smallest plaque area (32.5+/-13.0 and 32.0+/-11.5 mm2 versus 28.9+/-9.7 [P=NS] and 26.7+/-10.1 [P<.05] mm2 for IVUS and histology, respectively [mean+/-SD]). A significant positive correlation was found between plaque area and IEL area for the pooled data (r=.61 and r=.47 and slope=1.07 and 0.90 for IVUS and histology, respectively; both P<.001). In 12 of 20 and 16 of 25 individual arterial segments, however, no significant correlation was observed between plaque area and IEL area for IVUS and histology, respectively. A large variation was found in the correlation of the regression of plaque to IEL area (IVUS, r=-.40 to .89; histology, r=-.13 to .91) and slope (IVUS, -0.28 to 1.29; histology, -0.18 to 1.32). CONCLUSIONS: In the majority of atherosclerotic femoral arteries, significant compensatory enlargement could not be determined. It is inferred that arterial remodeling in response to plaque formation may vary among individuals.

Aged↗

Computation of a location shift between two subsequent intra vascular ultrasound registrations by cross-correlation analysis of the lumen area functions.

For longitudinal studies on atherosclerosis and restenosis after angioplasty by intravascular ultrasound (IVUS), it is essential that repeated studies are performed at exactly the same location along an arterial section. In human femoral arteries, lumen and plaque area functions of two subsequent IVUS pullback maneuvers were compared by cross-correlation analysis. In cross-correlation analysis of two functions with equal abscissa values, the data sets are repetitively correlated after incremental shifts of the two functions along the abscissa. This results in multiple correlation coefficients with a maximum at the relative position where the two functions show the closest match. In group A (12 patients), both pullbacks were performed after angioplasty and in group B (17 patients) one pullback was performed before angioplasty and the second immediately after angioplasty. In group A, cross-correlation showed a shift between lumen area functions of 5 mm in one patient and no shift in the other patients. Maximum correlation coefficients in group A ranged from 0.644 to 0.978. Four patients from group B showed shifts from 2.5 to 35 mm. Maximum coefficients were significantly smaller than in group A: 0.259-0.864 (p < 0.01). Plaque area functions in group B showed higher correlations (0.468-0.862, p = 0.034) and only two shifts. Cross-correlation of lumen and plaque area functions may be used to compute location shifts between two subsequent IVUS registrations and to correct such shifts.

Aged↗

Interobserver reproducibility of qualitative and quantitative analysis of intravascular ultrasound images before and after peripheral balloon angioplasty.

In this study, interobserver agreement on intravascular ultrasound data obtained before and after balloon angioplasty (PTA) of the superficial femoral artery was assessed. Two observers analyzed intravascular ultrasound cross-sections from 38 patients. Interobserver agreement was good for soft and hard lesions, dissection and vascular damage (kappa values 0.61, 0.67, 0.69 and 0.66, respectively); moderate for eccentric lesions (kappa 0.45); fair for media ruptures (kappa 0.25); and poor for lipid deposits and plaque ruptures (kappa 0.0 and 0.04, respectively). Differences for the arc of normal wall and hard lesion were not significant, but were for dissection. There were no significant interobserver differences between area measurements. The coefficient of variation for free lumen area and media-bounded area before PTA was 17.2% and 10.5% and after PTA 11.2% and 9.2%, respectively. This study identified the intravascular ultrasound parameters that are reproducible.

Angioplasty, Balloon↗

Residual stenosis determined by intravascular ultrasound and duplex ultrasound after balloon angioplasty of the superficial femoral artery.

Exact determination of the percentage luminal stenosis after balloon angioplasty is essential when deciding to redilate or not, especially since the percentage luminal stenosis may be a predictor for long-term outcome. Conflicting percentage residual stenosis is frequently observed when angiography is compared with duplex or intravascular ultrasound measurements. The aim of the present study was to compare the percentage luminal stenosis after balloon angioplasty determined by duplex and intravascular ultrasound. In 22 patients, balloon angioplasty was performed in the superficial femoral artery to treat disabling claudication. Intravascular ultrasound studies were performed immediately after balloon angioplasty; duplex studies were performed 24-36 h after intervention. Intravascular ultrasound percentage luminal stenosis was calculated with respect to a proximal reference lumen. Duplex percentage luminal stenosis was determined by two methods: first, by assuming that the increase in peak flow velocity is directly related to lumen area; and second, by considering a peak flow velocity ratio of 1.6 and 2.4 is representative for > 30% and > 50% diameter stenosis, respectively. The percentage luminal stenosis calculated from duplex measurements was higher compared with intravascular ultrasound measurements (y = 0.38x + 20.1, r = 0.57). Excluding cross-sections with vascular wall damage (dissection or plaque fracture) over more than 60 degrees of the circumference improved the slope and correlation coefficient of intravascular ultrasound measurements versus duplex measurements (y = 0.88x + 7.8, r = 0.70). Thus, after balloon angioplasty, conflicting percentage luminal stenosis is frequently observed using intravascular ultrasound and duplex measurements. These differences in percentage luminal stenosis may partly be explained by the extent of vascular wall damage visualized on the intravascular ultrasound image.

Angioplasty, Balloon↗

Paradoxical arterial wall shrinkage may contribute to luminal narrowing of human atherosclerotic femoral arteries.

BACKGROUND: This study was done to assess how local changes in vessel size, together with plaque load, determine luminal narrowing in atherosclerotic arteries. Fifty-one human femoral arteries were analyzed: 32 postmortem and 19 in vivo by 30-MHz intravascular ultrasound. METHODS AND RESULTS: Histological and intravascular ultrasound cross sections were examined every 0.5 cm over an arterial segment 10 to 15 cm long. In each cross section we measured the lumen area and the area circumscribed by the internal elastic lamina (the IEL area). In each arterial segment, the cross section that contained the least amount of plaque was the reference site. For each cross section, the lumen area stenosis was expressed as percent of the lumen area in the reference site. Similarly, the IEL area was expressed as percent of the IEL area in the reference site (the relative IEL area). There was a significant negative correlation between the relative IEL area and the lumen area stenosis percentage (r = -.62, P < .001 for histology and r = -.66, P < .001 for intravascular ultrasound). When lumen area stenosis was less than about 25%, mainly compensatory enlargement was observed. When lumen area stenosis exceeded about 25%, however, mainly a decrease of the IEL area was observed, which is consistent with arterial wall shrinkage. Furthermore, the increase in plaque area does not account for the total loss of luminal area. There was a moderate correlation between an increase in plaque area and reduction of the corresponding lumen area (r = .49 and r = .56 for histology and intravascular ultrasound, respectively). CONCLUSIONS: The decrease in luminal area cannot be attributed to plaque increase alone. Arterial wall shrinkage is a paradoxical mechanism that may contribute to severe luminal narrowing of the atherosclerotic human femoral artery.

Aged↗

Intravascular ultrasound image subtraction: a contrast enhancing technique to facilitate automatic three-dimensional visualization of the arterial lumen.

At 30 MHz, the intravascular ultrasound backscatter of blood confounds the discrimination of the lumen from the arterial wall. This study validates a subtraction method which creates a still-frame image with a sharp demarcation of the lumen. The method involves subtraction of consecutive images and 2D ensemble averaging of the absolute pixel values. Subtraction exploits the dynamic properties of flowing red blood cells. Three phantom arteries were used, with erythrocytes in their lumens and wall. For this reason, it was not possible, in one single original image, to discriminate the blood in the lumen from the phantom wall. Based on 26 consecutive original images, in the mean subtraction image contrast between lumen and phantom wall grey values increased eightfold from 10.9 (5.3-19.2) (mean and range) in the original image to 87.7 (73.6-107.0) (P < 0.001). A sufficiently large contrast increase to allow automatic segmentation was obtained by using five original images (0.3-s acquisition time) for any single mean subtraction image. Low blood flow velocities (down to 0.5 cm/s) did not alter this result. Automatic segmentation of the lumen allowed fast 3D reconstruction of the lumen in all three phantom arteries. In phantom arteries, the intravascular ultrasound image subtraction technique improved contrast between lumen and wall which enabled automated lumen segmentation and fast 3D visualization of both the lumen and defects in the wall.

Arteries↗

Remodeling of De Novo atherosclerotic lesions in femoral arteries: impact on mechanism of balloon angioplasty.

OBJECTIVES: Using 30-MHz intravascular ultrasound in the human femoral artery, we related the mode of arterial remodeling to the immediate result and the mechanism of balloon angioplasty. BACKGROUND: The atherosclerotic femoral artery may undergo three modes of remodeling in response to plaque formation: compensatory enlargement, failure of compensatory enlargement and paradoxic shrinkage. METHODS: In 83 patients an ultrasound catheter pullback maneuver was performed before and after balloon angioplasty. For each lesion (n = 121), the cross section with the narrowest lumen was selected for further analysis. For each cross section, the lumen area stenosis was expressed as percent of the lumen area at an adjacent reference site. Similarly, the media-bounded area was expressed as percent of the media-bounded area at the reference site. Cross sections were classified into one of three groups based on percent relative media-bounded area: 1) > 105% (group A, compensatory enlargement, n = 24); 2) 95% to 105% (group B, failure of compensatory enlargement, n = 26); and 3) < 95% (group C, arterial wall shrinkage, n = 71). The power of the present study was 99.3% to demonstrate a difference in lumen gain of 2.5 mm2 among groups. RESULTS: The gain in lumen area induced by balloon angioplasty did not differ significantly among the three groups (group A, 7.0 +/- 4.0 mm2 [mean +/- SD]; group B, 8.6 +/- 4.8 mm2; group C, 8.9 +/- 4.9 mm2). Stretch of the media-bounded area was observed in all three groups, but it was significantly larger in group C (7.5 +/- 5.2 mm2) than in the other two groups (group A, 3.9 +/- 5.1 mm2; group B, 5.1 +/- 4.1 mm2). A significantly positive correlation between balloon/media-bounded area ratio and elastic recoil was observed for cross sections in groups A and B (r = 0.71 and r = 0.69, respectively). However, no correlation was observed between balloon/media-bounded area ratio and elastic recoil for cross sections in group C (r = 0.17). CONCLUSIONS: We conclude that lumen gain by balloon angioplasty is not related to the mode of atherosclerotic arterial remodeling. However, the mode of arterial remodeling affects the dilation mechanism.

Aged↗

Discrimination of intravascular lumen and dissections in single intravascular ultrasound images using subtraction, conventional averaging and saline flush.

With current 30-MHz intravascular ultrasound systems, flowing blood may cause considerable backscatter which in real-time images is characterized by dynamic speckle. However, in a single intravascular ultrasound image (still-frame) the discrimination between arterial lumen and wall may be difficult due to the frozen intraluminal speckle, particularly in the presence of dissections. We compared subtraction, averaging and saline flush as methods to improve the discrimination between arterial lumen and wall in a single image. The real-time images served as gold standard. In 22 patients who underwent peripheral balloon angioplasty, ultrasound images obtained from 84 sites were examined. The sensitivity and specificity of detecting dissections were in the subtraction image 85% and 100%, in the averaged image 57% and 96%, and in the saline flush image 58% and 86%, respectively. Subtraction is a promising method to outline the irregular lumen in a single image.

Aged↗

Intravascular ultrasound predictors of outcome after peripheral balloon angioplasty.

OBJECTIVE: This study investigates the potential role of intravascular ultrasound (IVUS) in the outcome in patients undergoing percutaneous transluminal angioplasty (PTA) of the superficial femoral artery. MATERIALS: Angiographic and the qualitative and quantitative IVUS data obtained at the narrowest site derived from 39 patients before and after PTA were analysed. RESULTS: Angiographically the diameter of the remaining stenosis seen after PTA was classified as < 50% in 31 patients (success); in eight patients a failure was encountered. Evaluating at 6 months the functional and anatomic results of the PTA in 31 patients, the intervention was a success in 14 patients (Group I) and a failure in 17 patients (Group II). The remaining eight patients defined as angiographic failure following PTA comprised Group III. Neither qualitative nor quantitative IVUS data obtained before PTA could predict outcome. Conversely, after PTA, the extent of dissection was significantly more severe in Groups II and III than in Group I. Similarly, significant differences were found between Groups I and II for mean free lumen area (13.2 vs. 9.7 mm2, respectively) and mean free lumen diameter (4.1 vs. 3.5 mm, respectively). Quantitative data obtained in Group II were similar to those in Group III. CONCLUSION: This preliminary study demonstrates that following PTA the extent of dissection, free lumen area and diameter seen with IVUS are predictive factors of patency. Future studies with more patients are mandatory to further highlight the sensitivity of these observations.

Adult↗

Arterial remodeling in atherosclerosis and restenosis: a vague concept of a distinct phenomenon.

Geometric remodeling in atherosclerosis and restenosis comprises a change of the total arterial circumference that, together with plaque growth or neointima formation, determine the lumen of the artery. The change in total arterial circumference relative to a reference cross section ranges from excessive enlargement with an actual increase in lumen to a shrinkage contributing to lumen narrowing. The forces that determine whether an artery shrinks or is able to enlarge as a consequence of atherosclerotic lesions or of post-interventional intimal hyperplasia are unknown but are likely to affect matrix and specifically collagen redistribution. Identifying these forces is of importance because they might be used to promote favorable remodeling. The cellular and humoral triggers of collagen degradation and synthesis, as well as conformation changes of collagen matrices after their deposition, need to be investigated. As with injury-induced intimal hyperplasia and plaque growth in de novo atherosclerosis, injury models may serve as a paradigm for geometric remodeling in atherosclerosis.

Angioplasty↗

Discrimination of the intravascular lumen and dissections in a single 30-MHz US image: use of "confounding" blood backscatter to advantage.

At 30-MHz intravascular ultrasound, the high-intensity backscatter of blood confounds discrimination of the intravascular lumen from the arterial wall. The authors developed and used a subtraction method to visualize the lumen and dissections through cancellation of backscatter from static areas. In two patients who underwent angioplasty of the superficial femoral artery, the residual hyperechoic pattern created by moving blood allowed good differentiation between the wall and lumen or dissections.

Aged↗

Tumor necrosis factor induces von Willebrand factor release in healthy humans.

Tumor necrosis factor (TNF) is an important mediator of the host responses to systemic infection. To investigate the effect of TNF on the release of von Willebrand factor (vWF) into the circulation, we performed a controlled study in six healthy men, sequentially measuring the plasma concentrations of vWF antigen after a bolus intravenous injection of recombinant human TNF (50 micrograms/m2). TNF induced a marked increase in vWF antigen plasma levels, becoming significant after 45 min and peaking after 4 h (percentage increase from base line: 351 +/- 46; p less than 0.0001, TNF versus saline). The multimeric organization of circulating vWF was not affected by TNF. We conclude that TNF may be an early mediator of increased vWF secretion in systemic infection.

Adult↗