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Biomedical subjects

G Pasterkamp

Publications and source records attributed to G Pasterkamp.

At least 37 records · Page 2Linked to original sources

Oral matrix metalloproteinase inhibition and arterial remodeling after balloon dilation: an intravascular ultrasound study in the pig.

BACKGROUND: Inhibition of matrix metalloproteinase (MMP) activity after balloon angioplasty by intraperitoneal injection of batimastat reduces late lumen loss by inhibition of constrictive remodeling. In the present study, we investigated whether the oral MMP inhibitor marimastat inhibits constrictive remodeling in favor of neutral or expansive remodeling. METHODS AND RESULTS: In 26 pigs, balloon dilation was performed in 101 peripheral arteries. Pigs were treated with marimastat or served as controls and were euthanized 42 days after intervention. Intravascular ultrasound was performed at all time points. Vessel area (VA) loss was assessed by calculating the change in VA at termination relative to after intervention. Arteries were divided in 3 categories: expansive remodeling (VA loss < -5%), neutral (-5% +5%). In the marimastat group, a significant reduction (53%) of late lumen loss was observed that was fully explained by impaired constrictive remodeling. In the marimastat group, the prevalence of constrictive remodeling was reduced (38% versus 75% in the control group) in favor of not only neutral but also expansive remodeling (21% and 42% versus 4% and 21% in the control group, respectively, P:<0.01). In contrast to the control group, acute luminal gain in the marimastat group did not correlate with late VA loss. CONCLUSIONS: Irrespective of the acute luminal gain by balloon dilation, the oral MMP inhibitor marimastat inhibited constrictive arterial remodeling in favor of both neutral and expansive remodeling.

Administration, Oral↗

The adventitia of atherosclerotic coronary arteries frequently contains Chlamydia pneumoniae.

The presence of Chlamydia pneumoniae in the human arterial system has mainly been determined in atherosclerotic plaque, whereas the adventitia has remained relatively unexplored. We assessed the presence of C. pneumoniae in all three vessel wall layers of coronary (n=72) and brachial (n=48) arteries in relation to local atherosclerosis. Immunohistochemical staining of C. pneumoniae was observed in plaque and adventitia. Cells stained for C. pneumoniae were detected in the same areas as cells stained for macrophages in adjacent sections. C. pneumoniae staining in the adventitia was associated with the extent and severity of atherosclerosis. Coronary sections with C. pneumoniae staining in both adventitia and plaque more often contained advanced atherosclerosis than sections with staining only in the adventitia. Staining was observed more often in the coronary artery than in the brachial artery (24/72 vs. 5/48 and 51/72 vs. 8/48 for plaque and adventitia, respectively, P=0.004 and P<0.001). PCR confirmed the presence of C. pneumoniae DNA in the adventitia. In summary, the adventitia of atherosclerotic coronary arteries frequently contains C. pneumoniae that seems to be located within macrophages. These results might indicate a possible route for infected circulating macrophages to home into atherosclerotic lesions in the artery via vasa vasorum.

Aged↗

Variability of flow mediated dilation: consequences for clinical application.

BACKGROUND: Flow mediated vasodilatation (FMD), a non-invasive tool to assess endothelial function, has been shown to have prognostic value for the development of cardiovascular disease. Conventional B-mode ultrasonography has been criticised for its 'limited' resolution in vivo, which complicates reliable detection of the minute diameter changes during reactive hyperaemia. In the present study we evaluated the physical resolution, reproducibility and the capability to detect FMD impairment of a wall tracking system (WTS). METHODS: The resolution of WTS was compared with that of intravascular ultrasound (IVUS) in pig femoral arteries in vivo. Subsequently, intra- and interobserver variability of FMD testing with WTS was evaluated in 75 healthy volunteers. Finally, the effect of smoking as single risk factor for atherosclerosis on FMD in vivo was assessed. RESULTS: WTS and IVUS readings were not different (difference in arterial cross sectional area 1.97 mm(2), r=0.87). Intrasession coefficient of variation in baseline diameter was 1.1% (extremes 0.06--2.0%). Inter-session baseline diameter variation was 3.6 and 3.8% for each observer and 4.1% between observers. Intra-individual variability in FMD between sessions was considerable with coefficients of variation of 13.9% for FMD and 9.3% for NTG. Smokers had impaired FMD responses compared with matched non-smokers (4.7+/-2.4 vs. 9.6+/-4.4%, P<0.001), whereas NTG induced vasodilatation did not differ (13.4+/-6.2 vs. 15.4+/-5.1%; p=ns). CONCLUSION: WTS is a suitable technique for reproducibly assessing the brachial artery diameter in vivo with a accuracy comparable to that of IVUS. Using this sensitive technique the reproducibility of FMD in vivo proves to be poor mainly due to physiological factors. Whereas this seriously limits the use of FMD as follow-up parameter for individual subjects, FMD is demonstrated to be a useful research tool at group level.

Adult↗

Plaque burden, arterial remodeling and plaque vulnerability: determined by systemic factors?

OBJECTIVES: This study was designed to determine whether arterial remodeling and plaque vulnerability are influenced by systemic factors. BACKGROUND: Atherosclerotic luminal narrowing is caused by gradual plaque growth and arterial remodeling. In the acute phase, luminal narrowing may be accelerated by acute thrombus formation, usually precipitated by rupture of a vulnerable plaque. METHODS: Femoral arteries were obtained from elderly individuals at autopsy. Pairs of atherosclerotic femoral arteries from 42 individuals were examined. The arteries were divided in 1-cm intervals. Plaque size, the mode of arterial remodeling and histopathologic characteristics of plaque vulnerability (lipid-rich core and plaque inflammation) were compared between right and left femoral arteries obtained from the same individual. A role for systemic factors was assumed if a phenomenon was equally present in both arteries. RESULTS: There was concordance in average plaque size (r(2) = 0.5, p < 0.001), expansive remodeling (kappa = 0.42, p = 0.007) and occurrence of plaques containing a large lipid-rich core (kappa = 0.60, p = 0.001), but no concordance in plaque inflammation (kappa = 0.067, p = 0.61) between right and left arteries. CONCLUSIONS: These results suggest that not only the amount of atherosclerosis, but also arterial remodeling and lipid deposition in plaques, are influenced by systemic factors. The nonhomogeneous distribution of inflammation in atherosclerotic arteries supports the hypothesis that plaque inflammation is locally affected.

Aged↗

Early lumen diameter loss after percutaneous transluminal coronary angioplasty is related to coronary plaque burden: a role for viscous plaque properties in early lumen diameter loss.

OBJECTIVES: We tested the hypothesis that lumen diameter loss within 1 h after percutaneous transluminal coronary angioplasty is related to plaque volume parameters. BACKGROUND: Early lumen diameter loss after coronary balloon angioplasty may predict restenosis and may paradoxically decrease late lumen diameter loss. Viscous properties of the vessel wall, as would be determined by tissue volume and composition, may be involved in early lumen diameter loss. METHODS: Early lumen diameter loss was measured with quantitative coronary angiography as the loss in lesion lumen diameter (significant loss 0.4 mm) occurring between 5 min and a median of 40 min after successful coronary balloon angioplasty in 68 patients. Thirty-nine patients were evaluated with intravascular ultrasound at the narrowest lumen cross-section of the dilated lesion, 29 patients formed a control group without intravascular ultrasound imaging. We tested the relation between intravascular ultrasound parameters and early lumen diameter loss. RESULTS: Early lumen diameter loss of > or = 0.4 mm was present in eight patients (12%), decreasing lumen diameter from 2.26 +/- 0.36 mm to 1.73 +/- 0.43 mm. There was no difference in the frequency of early lumen diameter loss between the groups with or without intravascular ultrasound imaging. Univariate intravascular ultrasound determinants of early lumen diameter loss were media bounded area (p = 0.01), maximal plaque thickness (p = 0.02), eccentricity index (p = 0.03) and the presence of hard lesions (p = 0.02). CONCLUSION: Early lumen diameter loss in the first hour after successful coronary balloon angioplasty occurs in a small proportion of patients. It is related to hard lesion type, maximal plaque thickness and eccentricity index, favoring a role for viscous plaque properties in early lumen diameter loss.

Aged↗

Use of a balloon-expandable, radially reinforced ePTFE endograft after remote SFA endarterectomy: a single-center experience.

PURPOSE: To report our experience with endovascular femoropopliteal bypass grafting using a distensible, radially reinforced polytetrafluoroethylene endograft combined with remote endarterectomy. METHODS: Forty-one patients (33 men; mean age 70 years, range 45-79) with symptomatic femoropopliteal occlusive disease underwent remote endarterectomy of the superficial femoral artery (SFA) followed by implantation of a balloon-expandable Enduring endovascular graft. All patients entered an extensive surveillance program, including angiography and duplex scanning at regular intervals. RESULTS: Endarterectomy and endograft implantation were ultimately successful in all patients; 5 (12%) technical difficulties occurred intraoperatively and were treated with additional endovascular techniques. Control angiography at 1 week postoperatively demonstrated a patent endograft in 39 (95%) patients. Mean ankle-brachial index increased significantly from 0.57 to 0.91 (p < 0.001). Including the 2 early failures, 18 occlusions were documented over a median 15-month follow-up (range 3-24), due mainly to significant stenosis at the proximal and distal anastomoses. In 8 of 10 successfully reopened and revised endografts, reocclusion occurred after a median interval of only 1.8 months. Life-table analysis revealed cumulative primary and secondary patency rates of 42% and 56%, respectively, at 18 months. In the last 12 cases, the proximal end of the graft was sutured end-to-end to the transected SFA, which improved the short-term secondary patency rate to 83%. CONCLUSIONS: Insertion of the Enduring endovascular graft following remote endarterectomy effectively results in a less invasive treatment for femoropopliteal occlusive disease. Additional technical refinements of the procedure may be required to avoid early procedure- and graft-related failures.

Aged↗

Pre-existing arterial remodeling is associated with in-hospital and late adverse cardiac events after coronary interventions in patients with stable angina pectoris.

OBJECTIVES: The goal of this study was to investigate the association between the atherosclerotic arterial remodeling and the incidence of cardiac events after coronary interventions in patients with stable angina. BACKGROUND: The local mode of de novo atherosclerotic remodeling is associated with plaque vulnerability and clinical symptoms. It may, therefore, reflect plaque morphology influencing the long-term outcome after coronary interventions. METHODS: Quantitative angiography and intravascular ultrasound were obtained in 244 patients with stable angina before and after single-vessel revascularization. On the basis of the lesion and the reference segment vessel size, patients were categorized into three groups (adaptive [AR], constrictive [CR] and intermediate [IR] remodeling). The lesion was analyzed for lumen, total vessel and plaque areas. Clinical follow-up was obtained at a mean period of 7.7+/-3.7 months. RESULTS: Patients with CR had a higher rate of in-hospital complications (10.9% vs. 2.9% and 2.7% in group CR vs. AR and IR, p = 0.035). In contrast, patients with AR had the highest rate of major adverse cardiac events (MACE) (44.3% vs. 25.5% in IR and 28.1% in CR, p = 0.024) with a predominance of revascularization at follow-up. Both target lesion restenosis (p = 0.036) and nontarget lesion de novo stenosis (p = 0.007) occurred more frequently in this group. Adaptive remodeling was a significant predictor of MACE in multivariate analysis. CONCLUSIONS: Adaptive remodeling is associated with a higher rate of MACE, target lesion restenosis and nontarget de novo stenosis. This finding may be due to differential responses of the adaptively remodeled vessel to revascularization and a generally accelerated course of systemic atherosclerosis.

Aged↗

Characterization of plaque components with intravascular ultrasound elastography in human femoral and coronary arteries in vitro.

BACKGROUND: The composition of plaque is a major determinant of coronary-related clinical syndromes. Intravascular ultrasound (IVUS) elastography has proven to be a technique capable of reflecting the mechanical properties of phantom material and the femoral arterial wall. The aim of this study was to investigate the capability of intravascular elastography to characterize different plaque components. METHODS AND RESULTS: Diseased human femoral (n=9) and coronary (n=4) arteries were studied in vitro. At each location (n=45), 2 IVUS images were acquired at different intraluminal pressures (80 and 100 mm Hg). With the use of cross-correlation analysis on the high-frequency (radiofrequency) ultrasound signal, the local strain in the tissue was determined. The strain was color-coded and plotted as an additional image to the IVUS echogram. The visualized segments were stained on the presence of collagen, smooth muscle cells, and macrophages. Matching of elastographic data and histology were performed with the use of the IVUS echogram. The cross sections were segmented in regions (n=125) that were based on the strain value on the elastogram. The dominant plaque types in these regions (fibrous, fibro-fatty, or fatty) were obtained from histology and correlated with the average strain and echo intensity. The strain for the 3 plaque types as determined by histology differed significantly (P=0.0002). This difference was mainly evident between fibrous and fatty tissue (P=0.0004). The plaque types did not reveal echo-intensity differences in the IVUS echogram (P=0.882). CONCLUSIONS: Different strain values are found between fibrous, fibro-fatty, and fatty plaque components, indicating the potential of intravascular elastography to distinguish different plaque morphologies.

Arteries↗

Arterial remodeling in atherosclerosis, restenosis and after alteration of blood flow: potential mechanisms and clinical implications.

Arterial remodeling is currently being recognized as an important determinant in vascular pathology in which narrowing of the lumen is the predominant feature. Not only expansive remodeling (enlargement), but also constrictive remodeling (shrinkage) is observed in de novo atherosclerosis, in restenosis and in transplant vasculopathy. Expansive remodeling prevents and constrictive remodeling enhances luminal narrowing by plaque formation or intimal hyperplasia. The mechanisms of the opposite remodeling modes is unknown. Insight into the processes that determine the direction of local arterial remodeling may help to develop new strategies to prevent arterial occlusive disease. In the present paper the current status of research in the field of arterial remodeling in cardiovascular disease is reviewed. Mechanisms of arterial remodeling, potential interventions to influence the mode of remodeling as well as the methodological limitations of remodeling studies are discussed.

Angioplasty, Balloon↗

Atherosclerotic arterial remodeling and the localization of macrophages and matrix metalloproteases 1, 2 and 9 in the human coronary artery.

Atherosclerotic luminal narrowing is determined by plaque mass and the mode of geometrical remodeling. Recently, we reported that the type of atherosclerotic remodeling is associated with the presence of histological markers for plaque vulnerability. Inflammation and matrix degrading proteases (MMPs) may play a role in both plaque vulnerability and in expansive arterial remodeling. The aim of the present study was to investigate the association between the remodeling mode and the localization of macrophages and MMPs in coronary atherosclerotic segments. From 36 atherosclerotic coronary arteries, 45 and 51 segments were selected with a vessel area that was >10% smaller and larger compared with the adjacent segments, respectively. No significant difference in staining for macrophages was observed between segments with expansive and constrictive remodeling. More MMP-2 and MMP-9 staining was observed in plaques of expansively remodeled segments compared with constrictively remodeled segments. In general, MMP-staining was less evident in the adventitial layer compared with the plaque. Zymography revealed more active MMP-2 in expansively remodeled segments compared with constrictively remodeled segments (340+/-319 vs. 199+/-181 (adjusted counts/mm(2)), respectively, P=0.019). Zymography did not show differences in inactive MMP-2 or MMP-9 among groups. It might be postulated that MMPs within the plaque play a causal role not only in plaque vulnerability but also in de novo atherosclerotic remodeling.

Aged↗

Vascular tissue characterisation with IVUS elastography.

Knowledge about the mechanical properties of the vessel wall and plaque is important for guiding intravascular interventional procedures and detection of plaque vulnerability. Rupture of atherosclerotic plaques is associated with acute myocardial infarction and unstable angina pectoris. In a plaque with a lipid core, the stress due to the arterial pulsation will be concentrated in the cap and a thin cap may be unable to bear this stress. In this study, the potential of intravascular elastography to characterise fibrous, fibro-fatty and fatty tissue based on their mechanical properties was investigated. Using a custom-made set-up, intravascular echograms and elastograms of excised human femoral arteries were determined. High frequency r.f. data (30 MHz) were acquired using an intravascular catheter. The tissue was compressed using intravascular pressures of 80 and 100 mmHg. The cross-sections of interest were marked with a needle for matching with histology. Using cross-correlation estimation of gated echosignals, elastograms (images of the local strain) were determined. After the intravascular experiments, the specimens were fixed in formaldehyde and processed for paraffin embedding. Sections were stained with picrosirius red and alpha-actin to counterstain collagen and smooth muscle cells (SMC), respectively. Results of vessel cross-sections with fibrous and fatty plaque regions will be presented. The elastograms of these specimens show that the strain in fatty tissue is higher than the strain in fibrous material. In conclusion, these in vitro experiments on human femoral arteries indicate the potential of intravascular elastography to characterise different plaque components.

Arteriosclerosis↗

Techniques characterizing the coronary atherosclerotic plaque: influence on clinical decision making?

The composition of the atherosclerotic lesion rather than the degree of stenosis is currently considered to be the most important determinant for acute clinical events. Modalities capable of characterizing the atherosclerotic lesion may be helpful in understanding its natural history and detecting lesions with high risk for acute events. Speaking grossly, three histologic features of the vulnerable plaque have been reported: size of the atheroma, thickness of the fibrous cap, and inflammation. Imaging techniques are currently being deployed and are under development to aid visualization of the vulnerable coronary plaque. Most of these diagnostic modalities have the potential to detect locally one or more of the three histologically defined features of vulnerable plaque. This review will focus on imaging techniques that have been developed to characterize the atherosclerotic lesion. Most catheter-based visualization techniques will provide insight into components of the local atherosclerotic plaque which may limit their predictive value for the occurrence of a clinical event. Therefore, the clinical relevance of these imaging tools will be discussed.

Coronary Artery Disease↗

Greater late lumen loss after successful coronary balloon angioplasty in the proximal left anterior descending coronary artery is not explained by extent of vessel wall damage or plaque burden.

OBJECTIVES: We investigated whether the greater late lumen loss after coronary balloon angioplasty in the proximal left anterior descending artery (P-LAD) compared with that in other segments might be related to differences in vascular dimensions or morphology as determined by angiography and intravascular ultrasound imaging. BACKGROUND: The greater late lumen loss after angioplasty in the P-LAD that has been observed in several studies has not been explained. METHODS: We studied 178 patients and 194 coronary artery lesions by quantitative angiography and 30 MHz intravascular ultrasound imaging after successful balloon angioplasty. Vessel wall morphology was compared among three proximal and three nonproximal segments. Follow-up quantitative angiography for late lumen loss calculation was performed in 168 lesions. Multivariate analysis was used to determine predictors of late lumen loss. RESULTS: Absolute and relative late loss were significantly greater at the P-LAD compared with the pooled group of other segments (0.42 +/- 0.60 mm vs. 0.10 +/- 0.48 mm, p = 0.0008 and 0.14 +/- 0.24 vs. 0.03 +/- 0.17, p < 0.001). Also, a greater percentage of calcific lesions (65% vs. 44%, p = 0.034), a lower incidence of rupture (51% vs. 74%, p = 0.009) and a larger reference segment plaque area (5.4 +/- 2.2 mm2 vs. 4.7 +/- 1.9 mm2, p = 0.05) were found in the P-LAD. In multivariate analysis however, these variables were not predictive of late loss. CONCLUSIONS: Greater late lumen loss after coronary balloon angioplasty of the P-LAD is not explained by differences in atherosclerotic plaque burden or in vessel wall damage.

Aortic Dissection↗

Videodensitometric quantitative angiography after coronary balloon angioplasty, compared to edge-detection quantitative angiography and intracoronary ultrasound imaging.

AIMS: To assess the value of videodensitometric quantification of the coronary lumen after angioplasty by comparison to two other techniques of coronary artery lumen quantification. METHODS AND RESULTS: Videodensitometric quantitative angiography, edge detection quantitative angiography and 30 MHz intracoronary ultrasound imaging were performed after successful balloon angioplasty in 161 patients. Lumen cross-sectional areas were mean (SD) 2.82 (1.15) mm(2)for edge detection quantitative angiography, 3.67 (1.5) mm(2)for videodensitometric quantitative angiography and 5.32 (1.75) mm(2)for intracoronary ultrasound imaging (P<0.001). The correlation between intracoronary ultrasound imaging and videodensitometric quantitative angiography (r=0.44) was almost similar to that of intracoronary ultrasound imaging and edge detection quantitative angiography (r=0. 47). The correlation between the three techniques was not significantly influenced by the presence of ruptures and dissections on intracoronary ultrasound imaging. The absence of calcifications improved the correlation between videodensitometry and intracoronary ultrasound imaging. CONCLUSIONS: The luminal dimensions as measured by videodensitometric quantitative angiography matched intracoronary ultrasound imaging derived dimensions more closely than edge detection quantitative angiography. Videodensitometric quantitative angiography represents an on-line alternative to intracoronary ultrasound imaging for quantitative analysis regardless of the degree of vessel damage.

Absorptiometry, Photon↗

[Tumor simulating primary pulmonary cryptococcosis in an immunocompetent patient. A contribution to differential diagnosis].

Case report of a primary cryptococcosis of the lung in a 78-year old non-immunocompromised female. The patient presented with a mass in the right upper lobe, highly suspicious of lung cancer. Cryptococcus finally was detected on repeated biopsies from ulcerated and necrotic bronchial mucosa. A clinical work-up showed no evidence of dissemination and no signs of immunoinsufficiency. Mass reduction in the lung was achieved under therapy with fluconazol.

Aged↗

Characterization of plaque components and vulnerability with intravascular ultrasound elastography.

Intravascular ultrasound elastography is a method for measuring the local elastic properties using intravascular ultrasound (IVUS). The elastic properties of the different tissues within the atherosclerotic plaque are measured through the strain. Knowledge of these elastic properties is useful for guiding interventional procedures (balloon dilatation, ablation) and detection of the vulnerable plaque. In the last decade, several groups have applied elastography intravascularly with various levels of success. In this paper, the approaches of the different research groups will be discussed. The focus will be on our approach to the application of intravascular elastography. Elastograms were acquired in vitro and in vivo using the relative local displacements between IVUS images acquired at two levels of intravascular pressure with a 30 MHz mechanical or a 20 MHz array echo catheter. These displacements were estimated from the time shift between gated radiofrequency echo signals using cross-correlation algorithms with interpolation around the peak. Experiments on gel-based phantoms mimicking atherosclerotic vessels demonstrated the capability of elastography to identify soft and hard tissues independently of the echogenicity contrast. In vitro experiments on human arteries have demonstrated the potential of intravascular elastography to identify different plaque types based on their mechanical properties. These plaques could not be identified using the IVUS image alone. In vivo experiments revealed that reproducible elastograms could be obtained near end-diastole. Partial validation using the echogram was performed. Intravascular elastography provides information that is frequently unavailable or inconclusive from the IVUS image and which may therefore assist in the diagnosis and treatment of atherosclerotic disease.

Arteriosclerosis↗