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Biomedical subjects

B J de Smet

Publications and source records attributed to B J de Smet.

13 recordsLinked to original sources
PubMed2001

Shear-stress and wall-stress regulation of vascular remodeling after balloon angioplasty: effect of matrix metalloproteinase inhibition.

BACKGROUND: Constrictive vascular remodeling (VR) is the most significant component of restenosis after balloon angioplasty (PTA). Whereas in physiological conditions VR is associated with normalization of shear stress (SS) and wall stress (WS), after PTA the role of SS and WS in VR is unknown. Furthermore, whereas matrix metalloproteinase inhibition (MMPI) has been shown to modulate VR after PTA, its effect on the SS and WS control mechanisms after PTA is unknown. METHODS AND RESULTS: PTA was performed in external iliac arteries of 12 atherosclerotic Yucatan pigs, of which 6 pigs (7 vessels) received the MMPI batimastat and 6 pigs (10 vessels) served as controls. Before and after the intervention and at 6-week follow-up, intravascular ultrasound pullback was performed, allowing 3D reconstruction of the treated segment and computational fluid dynamics to calculate the media-bounded area and SS. WS was derived from the Laplace formula. Immediately after PTA, media-bounded area, WS, and SS changed by 20%, 16%, and -49%, respectively, in both groups. VR was predicted by SS and WS. In the control group, SS and WS had been normalized at follow-up with respect to the reference segment. In contrast, for the batimastat group, the SS had been normalized, but not the WS. The latter is attributed to an increase in wall area at follow-up. CONCLUSIONS: Vascular remodeling after PTA is controlled by both SS and WS. MMPI inhibited the WS control system.

Angioplasty, Balloon↗
PubMed2001

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↗
PubMed2000

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↗
PubMed1998

The atherosclerotic Yucatan animal model to study the arterial response after balloon angioplasty: the natural history of remodeling.

OBJECTIVE: Remodeling in de novo atherosclerosis and in restenosis after balloon angioplasty constitutes a change in total arterial circumference which, together with plaque growth or neointimal formation, determines the lumen of the artery. To better understand the fundamental biology of neointimal formation, remodeling and their interaction, animal studies are needed. In this study, we described in detail the methodology used and the natural history of neointimal formation and remodeling after balloon angioplasty in atherosclerotic Yucatan micropigs. METHODS AND RESULTS: Atherosclerosis was induced in 60 peripheral arteries of sixteen Yucatan micropigs by a combination of denudation and atherogenic diet. Balloon angioplasty was performed in 38 arteries, with serial intravascular ultrasound (IVUS) and quantitative angiography before and after intervention and at 2, 4, 7, 14 or 42 days follow-up. Remodeling, expressed as late media-bounded area (MBA) loss, increased progressively over time. At 42 days, late MBA loss after balloon angioplasty was significantly different compared to late MBA loss in control arteries, 2.2 +/- 1.0 versus -0.3 +/- 1.1 mm2 and p = 0.02. Late lumen loss increased over time and was highest at 42 days after balloon angioplasty (2.8 +/- 0.7 mm2). The contribution of neointimal formation to late lumen loss decreased over time and the contribution of late MBA loss to late lumen increased over time and was highest at 42 days (78%). Medial necrosis was 48% at two days after balloon angioplasty and the repopulation of the media was almost completed at seven days. CONCLUSION: Remodeling following balloon angioplasty has an early onset and progresses with neointimal formation to cause restenosis over the standard 42-day time course for Yucatan micropigs. This correlates to six months renarrowing in humans. In this model, atherosclerosis and the natural history of restenosis, both with respect to neointimal formation and remodeling, resemble the human disease quite closely.

Analysis of Variance↗
PubMed1998

The relation between de novo atherosclerosis remodeling and angioplasty-induced remodeling in an atherosclerotic Yucatan micropig model.

Geometric remodeling in de novo atherosclerosis and in restenosis after balloon angioplasty constitutes a change in total arterial circumference that, together with plaque growth or neointima formation, determines the lumen of the artery. The heterogeneous nature of arterial obstructions raises the question of whether early and late outcomes (restenosis) of angioplasty are affected by the degree and direction of de novo atherosclerotic remodeling. This study was designed to assess the relationship between atherosclerotic remodeling and the degree and mechanism of restenosis after balloon angioplasty. Atherosclerosis was induced in 27 peripheral arteries of 18 Yucatan micropigs by a combination of denudation and atherogenic diet. Balloon angioplasty was performed, with serial intravascular ultrasound and quantitative angiography before and after intervention and at 42 days' follow-up. We used the relative media-bounded area (MBA), defined as the MBA of the treated site divided by the MBA of the reference, before angioplasty as a measure of remodeling in de novo atherosclerosis and late MBA loss as a measure of remodeling after balloon angioplasty. Relative MBA before angioplasty was not correlated with angiographic and echographic acute gain after balloon angioplasty (r=.22, P=.28 and r=.14, P=.48) or with late lumen loss (r=-.05, P=.81 and r=.19, P=.33). No correlation was found between relative MBA and late MBA loss (r=.14 and P=.48). In the atherosclerotic Yucatan micropig, remodeling during de novo atherosclerosis has no relevance for acute gain and late lumen loss after balloon angioplasty. Both the direction and the extent of remodeling after balloon angioplasty are not related to the direction and extent of remodeling during de novo atherosclerosis.

Angiography↗
PubMed1997

Arterial remodeling after balloon angioplasty or stenting in an atherosclerotic experimental model.

BACKGROUND: Recent studies have indicated that coronary restenosis after balloon angioplasty is the sum of geometric remodeling and neointimal formation. A proportional relationship between acute gain and late lumen loss has been observed in clinical trials. The aims of this study were to evaluate (1) the contribution of geometric remodeling and neointimal formation to the proportional gain-loss relationship after PTA or stenting and (2) the relationship between geometric remodeling and neointimal formation. METHODS AND RESULTS: In atherosclerotic iliac arteries of 29 Yucatan micropigs, PTA or stenting was performed, with serial intravascular ultrasound (IVUS) and quantitative angiography before and after intervention and at 2 or 42 days of follow-up, followed by histomorphometrical analysis. For PTA at 42 days, late lumen loss by IVUS correlated strongly with geometric remodeling, expressed as late media-bounded area (MBA) loss (R2=.843, P<.001, n=20), and correlated weakly with intimal hyperplasia area (R2=.214, P=.02). For stented arteries, however, late lumen loss correlated moderately with intimal hyperplasia (R2=.367, P=.01, n=18) and only weakly with geometric remodeling (R2=.195, P=.04). Late lumen loss and late MBA loss of reference segments were observed at 42 days, especially in PTA arteries. Intimal hyperplasia and geometric remodeling were not correlated. CONCLUSIONS: In this experimental model, the proportional relationship between acute gain and late lumen loss is mainly due to the proportional relationship between acute gain and geometric remodeling for PTA and between acute gain and intimal hyperplasia for stents. Finally, neointimal formation and remodeling seem to be unrelated processes.

Angiography↗
PubMed1997

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↗
PubMed1994

Neurohumoral and hemodynamic effects of ibopamine in a rat model of chronic myocardial infarction and heart failure.

There is increasing evidence that both neurohumoral and hemodynamic factors play a role in disease progression in chronic heart failure (CHF). To examine the influence of the oral dopamine agonist ibopamine on these factors, we studied 20 rats with chronic myocardial infarction and CHF, and compared them with 20 normal rats. After 6 weeks, rats were randomly divided between control treatment (50%) or ibopamine (50%) for 3 weeks. At the end of the study, plasma and tissue neurohumoral parameters, as well as hemodynamics, were determined. In infarcted rats, the elevated plasma norepinephrine (PNE) levels were reduced by ibopamine (251 +/- 19 vs. 138 +/- 32 pg/ml; p < 0.05). Other plasma neurohormones measured (epinephrine, renin, aldosterone, and angiotensin converting enzyme [ACE]) were not significantly increased in rats with myocardial infarction and were not affected by ibopamine. Cardiac (tissue) ACE was increased in infarcted rats (12.1 +/- 1.9 U/l/min) and was significantly lowered by ibopamine (9.6 +/- 1.0 U/l/min; p < 0.05); renal ACE was unaffected. Blood pressure and heart rate were similar in the two groups and were not influenced by ibopamine treatment. In conclusion, in chronic myocardial infarction and CHF in rats, ibopamine reduces the elevated levels of PNE and cardiac ACE. Further research will be needed to determine whether this effect may lead to a favorable influence on disease progression in CHF.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed1993

Clearance of human native, proteinase-complexed, and proteolytically inactivated C1-inhibitor in rats.

C1-inhibitor is the only known inhibitor of the classical pathway of complement and the major inhibitor of the contact pathway of coagulation. Like other serine proteinase inhibitors, C1-inhibitor can exist in three conformations, ie, the native, the proteinase-complexed, and the proteolytically inactivated form. Here we studied the plasma elimination kinetics of these three forms of human C1-inhibitor in rats. The clearance of the complexed form of C1-inhibitor appeared to be the most rapid and depended in part on the proteinase involved (observed plasma t1/2 was 20 minutes for C1s-C1-inhibitor, 32 minutes for kallikrein-C1-inhibitor, and 47 minutes for beta XIIa-C1-inhibitor), whereas that of native C1-inhibitor was the slowest (observed plasma t1/2 4.5 hours). Inactivated C1-inhibitor was cleared with an apparent plasma t1/2 of 1.6 hours. Thus, the short plasma t1/2 of complexed relative to native C1-inhibitor explains why in patients only low concentrations of C1-inhibitor complexes may be observed despite activation of the contact and/or complement systems.

Animals↗
PubMed1993

Endothelium dependent relaxation in two different models of chronic heart failure and the effect of ibopamine.

OBJECTIVES: The purpose was to relate endothelium dependent relaxation to neurohumoral and haemodynamic changes in rats with chronic heart failure. METHODS: Rats were submitted to either coronary ligation causing myocardial infarction or banding of the abdominal aorta (aortic stenosis), and comparisons were made with normal rats (n = 20 per group). Starting six weeks after surgery, half of the experimental animals received ibopamine and the other half served as controls and were given saline for another three weeks. After this, haemodynamic and neurohumoral variables were determined and the rats were killed. Rings of both the thoracic and abdominal aorta were studied in organ baths to measure their response to vasoactive agents. RESULTS: Increased plasma noradrenaline concentrations in rats with myocardial infarction and aortic stenosis were reduced by ibopamine. Blood pressure and heart rate, which were higher in rats with aortic stenosis than in rats with myocardial infarction and in normal rats, were unaffected by ibopamine. The maximal relaxation to sodium nitrite was depressed in the thoracic aorta from rats with myocardial infarction. The pIC50 of metacholine induced relaxation was smaller in the thoracic aorta from rats with myocardial infarction and aortic stenosis. By contrast, both pIC50 and the maximal relaxation (Emax) were increased in the abdominal aorta from rats with aortic stenosis, whereas Emax was smaller in rats with myocardial infarction. Ibopamine had no significant effects on these responses. CONCLUSIONS: Endothelium dependent relaxation to metacholine was selectively altered in rats with chronic heart failure due to aortic stenosis, probably because of differences in regional haemodynamics. In rats with myocardial infarction, however, endothelium dependent relaxation was impaired in both the thoracic and abdominal aorta. Ibopamine acted as a neurohumoral modulator by reducing increased noradrenaline concentrations but had no significant effect on either endothelium dependent or independent relaxation.

Animals↗
PubMed1993

Fish oil increases the release of tumour necrosis factor and interleukin-6, and has no effect on the incidence of multiple organ failure in rats with peritonitis.

OBJECTIVE: To find out if fish oil given intraperitoneally would cause a reduction in the release of tumour necrosis factor and interleukin-6 in abdominal exudate and blood (experiment A), and if it reduces the incidence of organ failure in rats with peritonitis (experiment B). DESIGN: Laboratory experiment. SETTING: University animal laboratory. MATERIAL: Thirty-six selectively decontaminated rats in each experiment. INTERVENTIONS: All rats were pretreated with 2 ml fish oil, lecithin, or saline, intraperitoneally for one or six weeks before intraperitoneal injection of zymosan. Experiment A: Samples of abdominal exudate and plasma were taken regularly for 24 hours after the zymosan had been given. Experiment B: Clinical, biochemical, and histological variables were measured over a 12-day period after the zymosan had been given. MAIN OUTCOME MEASURES: Experiment A: Concentrations of tumour necrosis factor and interleukin-6 in abdominal exudate and plasma. Experiment B: Incidence of multiple organ failure. RESULTS: Experiment A: Concentrations of tumour necrosis factor and interleukin-6 in abdominal exudate and plasma were significantly higher in rats pretreated with fish oil, compared with control rats. This effect was more pronounced after six weeks of pretreatment. Experiment B: There were no significant differences between the groups for any variable. CONCLUSION: Fish oil given intraperitoneally increased rather than reduced local and systemic release of tumour necrosis factor and interleukin-6, and did not reduce the incidence of organ failure in rats with sterile peritonitis.

Animals↗