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Biomedical subjects

C Borst

Publications and source records attributed to C Borst.

At least 19 recordsLinked to original sources

Distribution of Chlamydia pneumoniae in the human arterial system and its relation to the local amount of atherosclerosis within the individual.

BACKGROUND: Chlamydia pneumoniae has been suggested to play a role in the origin of atherosclerosis. We studied the prevalence of C pneumoniae at multiple locations in the arterial system within the same individual. Studying the association between atherosclerosis and C pneumoniae within the individual excludes confounding by interindividual variability. METHODS AND RESULTS: Postmortem, the presence in the intima/plaque and media of C pneumoniae membrane protein was determined by use of a C pneumoniae-specific monoclonal antibody. In 24 individuals, 33 arterial locations were studied (n=738 segments). Area stenosis was determined in adjacent cross sections. In all individuals, immunostaining of C pneumoniae was observed in >/=1 artery. The highest prevalences were observed in the abdominal aorta (67%), internal and common iliac arteries (41%), and coronary arteries (33%). The lowest prevalences were observed in the radial (0%) and cerebral (2%) arteries. Within the individual, area stenosis was larger in cross sections with immunoreactivity compared with cross sections without immunoreactivity (31.0+/-11.9% versus 14.3+/-6.1%, respectively; P:<0.001). In the individual, immunoreactivity was observed in 15+/-10% of the arteries (range, 3% to 45%). Between individuals, the percentage of arteries with immunoreactivity to C pneumoniae was associated with the average area stenosis throughout the arterial system (r(2)=0.56, P:<0.001). CONCLUSIONS: C pneumoniae was mostly observed at locations that are related to clinically relevant features. Within the individual, the distribution of C pneumoniae is associated with the distribution of atherosclerosis. The role of the microorganism in atherosclerotic disease remains to be elucidated.

Aged↗

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↗

Metalloproteinase inhibition reduces constrictive arterial remodeling after balloon angioplasty: a study in the atherosclerotic Yucatan micropig.

BACKGROUND: Arterial remodeling after balloon angioplasty has been recognized as a major determinant of restenosis. Perturbation of collagen metabolism might be important. After balloon injury, matrix metalloproteinase (MMP) expression is upregulated. We investigated the effect of Batimastat, a nonspecific MMP inhibitor, on late lumen loss, arterial remodeling, and neointima formation after balloon dilation. METHODS AND RESULTS: In atherosclerotic iliac arteries of 12 Yucatan micropigs, balloon dilation was performed, with intravascular ultrasound and quantitative angiography used before and after balloon dilation and at 42-day follow-up. The animals were randomly divided into 2 groups, the Batimastat group (n=6) and the vehicle group (n=6). All animals were intraperitoneally injected with either Batimastat or a vehicle immediately after balloon dilation and at 2 weeks and 4 weeks after balloon dilation. Angiographic and echographic late lumen loss in the Batimastat group versus the vehicle group was 0.3+/-0.1 versus 0.8+/-0.1 mm (P=0.01) and 2.2+/-0.5 versus 4.9+/-0.7 mm(2) (P=0.004), respectively. Late media-bounded area loss was used as a measure of remodeling after balloon dilation and was 0.9+/-0.6 mm(2) in the Batimastat group compared with 3.8+/-0.8 mm(2) in the vehicle group (P=0.003, mixed model analysis P=0.01). Neointima formation was 1.3+/-0.3 mm(2) in the Batimastat group and 1.0+/-0.2 mm(2) in the vehicle group (P=0. 542). CONCLUSIONS: Metalloproteinase inhibition by Batimastat significantly reduced late lumen loss after balloon angioplasty by inhibition of constrictive arterial remodeling, whereas neointima formation was not inhibited by MMP inhibition.

Angiography↗

Effect of vascular freezing on the histopathology of dissected small vessels in the rat: vascular freezing does induce intimal hyperplasia in arteries and veins.

Intimal hyperplasia is the primary response of a vessel wall after injury. It may be the single most significant factor affecting long-term patency. The purpose of this study was to find out whether freeze injury, inflicted on rat microvessels, would be followed by intimal hyperplasia. Toward this aim, we exposed the superficial femoral vessels in the rat. On one side they were frozen using liquid nitrogen spray. The other side was dissected as the control. Vessel segments, harvested immediately and after 1, 2, 3, and 5 months, were studied light microscopically for the occurrence and content of intimal hyperplasia. In the arteries a considerable intimal hyperplasia was found within a 4-week interval, persisting for at least 5 months, as a result of the freeze injury. In the veins, the intimal hyperplasia was much less marked but was nevertheless demonstrable. These findings are not in agreement with earlier studies, in which freezing of injured rat microarteries with liquid nitrogen spray was followed by complete regeneration of the vessel wall, without intimal hyperplasia taking place. The factors contributing to these differences are discussed. It is concluded that freezing of a vessel wall is followed by intimal hyperplasia, which is part of the normal healing process.

Animals↗

Coronary anastomotic devices: theory and patented ideas on micromechanical fastening.

Coronary anastomotic devices are being designed to reduce the laborious, complex suturing approach to endoscopic coronary surgery. An anastomotic device should be safe and reliable, it should allow full view of the vessel parts to be bonded, it must provide a simple and rapid deployment, and should be hemodynamically adequate. Three anastomotic device categories found in the (patent) literature are discussed that use micromechanical fastening techniques. First, devices using individual bonding elements; second, devices using bonding elements anchored to extra-luminal frames; third, devices using an internal frame, often a stent-like structure. Anastomotic devices described in the (patent) literature to date fail to meet all requirements for endoscopic coronary application.

Anastomosis, Surgical↗

Assessment of patented coronary end-to-side anastomotic devices using micromechanical bonding.

BACKGROUND: Despite multiple patented ideas for vascular end-to-side anastomotic devices, and the growing need for them in minimally invasive coronary bypass procedures, no device has been evaluated clinically yet. This study assessed patents of micromechanical end-to-side anastomotic devices with respect to application in coronary artery bypass grafting. METHODS: Patents were categorized with respect to their micromechanical bonding principle. Calculated values for the wall strain during the construction of an anastomosis were compared with the allowable strain for human coronary arteries. RESULTS: From 51 patents describing vascular anastomotic devices, 11 ideas, categorized into four groups (staples, clips, mounting systems, and intraluminal stent structures), are serious candidates for coronary end-to-side anastomoses. Most ideas use an anvil for proper application of the bonding elements. For small (1.5 mm) coronary arteries, the calculated wall strain was 0.87, exceeding the breaking strain (0.45) in 60- to 79-year-old patients. CONCLUSIONS: In a coronary anastomotic device, the concept of using an anvil for the application of micromechanical bonding elements is not attractive, because excessive wall strain is likely to occur.

Anastomosis, Surgical↗

Heart displacement during off-pump CABG: how well is it tolerated?

BACKGROUND: Heart displacement during off-pump coronary artery bypass grafting (CABG) is necessary to expose the anastomosic sites. We analyzed the hemodynamic changes in relation to the grafted arteries. METHODS: The relationship between surgical exposure and hemodynamic management was assessed in 150 consecutive patients undergoing off-pump CABG utilizing the Octopus Tissue Stabilization System (Medtronic, Minneapolis, MN). RESULTS: Surgical exposure by anterolateral thoracotomy showed no significant hemodynamic changes. Through sternotomy, stroke volume was significantly reduced by dislocation at all target sites: by 6% at the left anterior descending artery (LAD), 25% at the diagonal branch artery (D), 14% at the right coronary artery (RCA), and 21% at the obtuse marginal artery (OM). The application of head-down positioning (LAD, 56%; D, 74%; RCA, 90%; OM, 96%) increased not only surgical exposure but also preload, producing correction of ventricular filling pressures and output. In a minority of cases, dopamine (3 to 5 microg x kg(-1) x min(-1)) was added to maintain baseline hemodynamic values (LAD, 5%; D, 15%; RCA, 7%; OM, 28%). CONCLUSIONS: Revascularization during anterolateral thoracotomy was uneventful. The sternotomy approach with heart displacement induced right heart compression. Mainly fluid redistribution was sufficient to correct cardiac output. Once stabilized, systemic circulation remained unchanged during revascularization.

Aged↗

Arteriotomy closure by glued patch in the porcine carotid artery.

BACKGROUND: A thoracoscopic approach to coronary bypass grafting warrants renewed search for facilitated vascular anastomosis methods. We reassessed tissue adhesion, sealing properties, and histotoxicity of iso-butyl-cyanoacrylate, in a simplified anastomosis model. METHODS: In 12 Dutch landrace pigs, five arteriotomies were made in each carotid artery. The arteriotomies were closed by conventional microvascular suturing or by pericardial patch (Peri-Strips) and iso-butyl-cyanoacrylate. The animals were sacrificed at 2 hours (n = 2), 2 days (n = 5), and 4 weeks (n = 5). The arteries were examined by flow measurement, angiography, and histologic analysis. RESULTS: The time required to close arteriotomies by conventional suturing was 257 +/- 43 seconds (mean +/- SD) and by glued patch 51 +/- 27 seconds (p < 0.001). In all arteriotomies covered by glued patch, complete hemostasis was obtained. At 2 days and 4 weeks, with both methods the same histologic results were observed. At follow-up, all carotid arteries were patent without stenoses. CONCLUSIONS: Arteriotomy closure by glued patch was simple, fast, reliable, and without signs of histotoxicity. Adhesives deserve to be reconsidered as an alternative to suturing in closed chest beating-heart coronary surgery.

Anastomosis, Surgical↗

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↗

The Octopus Study: rationale and design of two randomized trials on medical effectiveness, safety, and cost-effectiveness of bypass surgery on the beating heart.

The Octopus Study consists of two multicenter randomized clinical trials in which coronary artery bypass grafting on the beating heart (off-pump CABG) using the Utrecht Octopus Method is compared to intracoronary stent implantation and conventional CABG. The primary endpoint in the comparison of off-pump CABG versus stent implantation (OctoStent Trial) is medical effectiveness (i.e., absence of reintervention and major adverse cardiac and cerebrovascular events at 1 year after treatment). The primary endpoint in the comparison of off-pump CABG versus conventional CABG (OctoPump Trial) is cerebral safety (i.e., absence of cognitive deficits and cerebrovascular events at 3 months after treatment). Secondary endpoints in both trials include presence and severity of angina, quality of life, exercise capacity, and cost-effectiveness. A total of 560 patients will be enrolled. A random sample of 210 patients will undergo repeat angiography at 1 year to assess angiographic restenosis rate and graft patency. Including 1-year follow-up, the study will last for 3 years. Control Clin Trials 2000;21:595-609

Angioplasty, Balloon, Coronary↗

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↗

Temporary luminal arteriotomy seal: III. Postmortem arteriosclerotic human coronary artery.

BACKGROUND: Recently, we described a temporary luminal arteriotomy seal that provided a bloodless arteriotomy without obstructing recipient artery blood flow during bypass grafting in nonarteriosclerotic porcine arteries. This postmortem study assessed the sealing properties in irregular arteriosclerotic human coronary arteries. METHODS: Three hearts were obtained from donated corpses within 24 hours of death. The coronary arteries were pressure-perfused at 60 mm Hg with citrated porcine blood. At 15 anastomosis sites in four different coronary arteries, an end-to-side anastomosis was created using a 200-microm-thick polyurethane seal. Adequacy of sealing was determined at perfusion pressures of 60, 40, and 20 mm Hg. RESULTS: After insertion, the arteriotomy was sealed instantaneously in 10 of 15 anastomoses. After repositioning, complete sealing with a bloodless operative field was obtained in all cases. Low intracoronary transmural pressure did not impede sealing. In 8 of 15 anastomoses, minor leakage without obscuring the arteriotomy edges was observed during anastomotic suturing. Histologic examination revealed no intimal tear or dissection caused by the anastomotic procedure. CONCLUSIONS: In postmortem-obtained arteriosclerotic human coronary arteries, the temporary luminal arteriotomy seal provided optimal visualization of the coronary anastomosis site in combination with persistent distal perfusion.

Aged↗

Angioscopic complex lesions are predominantly compensatory enlarged: an angioscopy and intracoronary ultrasound study.

OBJECTIVES: Atherosclerotic remodeling of the coronary artery may lead to compensatory enlargement or to shrinkage. Post-mortem data suggest a relation between compensatory enlargement and histopathological markers of plaque vulnerability. In patients that required a coronary intervention, we investigated retrospectively the relation between the angioscopic appearance and the remodeling mode of the culprit lesion. METHODS: In 34 patients, coronary angioscopy and intracoronary ultrasound (ICUS) imaging was performed across the culprit lesion before the intervention. Only single de novo lesions were included. With angioscopy, lesions with a smooth surface without thrombus were classified as smooth, whereas lesions with an irregular surface with or without thrombus were classified as complex. With ICUS, remodeling of the culprit lesions was determined by the relative cross-sectional vessel area (lesion vessel area/reference vessel area) x 100%. Lesions were divided into three groups: compensatory enlargement (relative vessel area > or = 105%), no-remodeling (relative vessel area between 95 and 105%) and shrinkage (relative vessel area < or = 95%). RESULTS: In 22 patients good images were obtained with both imaging modalities. More complex lesions were compensatory enlarged compared to shrunken lesions, whereas more smooth lesions were shrunken compared to compensatory enlarged lesions, 8/9 versus 2/7 and 5/7 versus 1/9, respectively (p = 0.035). CONCLUSIONS: In patients selected for coronary intervention, angioscopic complex atherosclerotic lesions were found predominantly in compensatory enlarged arterial segments, whereas smooth lesions were found predominantly in shrunken arterial segments.

Adult↗