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C Bauters

Publications and source records attributed to C Bauters.

At least 91 records · Page 5Linked to original sources
PubMed1996

Morphological changes after percutaneous transluminal coronary angioplasty of unstable plaques. Insights from serial angioscopic follow-up.

OBJECTIVE: To describe the morphological changes occurring in the months following percutaneous transluminal coronary angioplasty (PTCA) of unstable plaques. BACKGROUND: Coronary angioscopy is a relatively new technique to assess plaque morphology. Previous angioscopic studies have shown that unstable coronary lesions are characterized by complex morphology, evidence of plaque rupture, and intraluminal thrombi. No serial angioscopic studies have investigated the effects of PTCA on plaque morphology at such lesions. METHODS: We studied 15 patients who underwent successful PTCA for an unstable coronary syndrome (unstable angina: n = 5; recent myocardial infarction: n = 10). Angioscopy was performed immediately before PTCA in 14 patients, immediately after PTCA in 13 patients, and at follow-up (225 +/- 62 days after PTCA) in all patients. RESULTS: Pre-PTCA, plaque morphology was defined as complex in 18%, ulcerated in 27%; the vessel was totally occluded in 18% of cases. Plaque colour was yellow in 75% of patients. A thrombus was identified at the lesion site in 71% of patients. Immediately post-PTCA, small surface disruptions and dissections were observed in 62% of patients. Plaque colour was yellow in 85% of cases. Seventy-seven percent of patients had an angioscopically visible thrombus at the PTCA site. At follow-up, however, plaque shape was almost uniformly classified as smooth concentric (93%); plaque colour was white in 93%; no thrombus was observed. CONCLUSIONS: These results demonstrate the healing of unstable plaques in the months following PTCA. The angioscopic appearance at 6 months is that of a stable plaque (smooth concentric, white, without thrombus). Whether this stable angioscopic appearance predicts long-term clinical stability remains to be determined.

Adult↗
PubMed1996

Restenosis after coronary angioplasty for rapidly progressive coronary stenosis.

OBJECTIVES: We hypothesized that percutaneous transluminal coronary angioplasty performed on coronary stenoses that have demonstrated rapid angiographic progression would be associated with a high risk of restenosis. BACKGROUND: High rates of restenosis have been documented after percutaneous transluminal coronary angioplasty of unstable lesions and of lesions that recur rapidly after a successful initial angioplasty. This suggests that the "activity' of the plaque at the time of angioplasty may be an important factor determining the risk of restenosis. METHODS: In our institution we recommend angiographic follow-up for all patients with successful percutaneous transluminal coronary angioplasty. In this way we identified 86 consecutive patients who, at the time of angiographic follow-up had not developed restenosis at the dilated site, but required a further percutaneous transluminal coronary angioplasty at a different site. (which was successful). Based on quantitative angiographic measurements, 45 of these lesions (rapidly progressive lesions) had significantly increased in severity in the interval between the two angiograms (7.7 +/- 3.3 months) while 41 (stable lesions) had not. Rapid progression was defined as a > 0.4 mm decrease in minimal lumen diameter between initial angiography and percutaneous transluminal coronary angioplasty. All 86 patients had further angiographic follow-up 6 months later. RESULTS: Baseline clinical and angiographic variables were similar in both groups except that a higher proportion of patients in the rapid progression group had unstable angina (20% vs 5%; P < 0.05). Late loss during follow-up did not differ statistically between groups (0.31 mm) and minimal lumen diameter at follow-up was also similar (stable lesion group = 1.40 +/- 0.48 mm; rapidly progressive lesion group = 1.30 +/- 0.59 mm). The loss index (late loss divided by acute gain) was also similar in both groups (0.45 +/- 0.52 in the stable lesion group, 0.37 +/- 0.76 in the rapidly progressive lesion group). A strong correlation between acute gain and late loss was observed in the stable lesion group (r = 0.61; P < 0.0001); by contrast, there was no relationship between these two variables in the rapidly progressive lesion group (r = 0.20; P = 0.19). CONCLUSIONS: Percutaneous transluminal coronary angioplasty in patients with unstable angina or with early recurrence after a first percutaneous transluminal coronary angioplasty is associated with an increased risk of restenosis. By contrast, this study shows that angiographic instability, as evidenced by rapid stenosis progression, has no deleterious effect on the occurrence of restenosis. Percutaneous transluminal coronary angioplasty thus appears as a reasonable therapeutic option for coronary stenoses that have demonstrated rapid angiographic progression in the months prior to the procedure.

Age Factors↗
PubMed1996

Hypersensitivity of human coronary segments to ergonovine 6 months after injury by coronary angioplasty: a quantitative angiographic study in consecutive patients undergoing single-vessel angioplasty.

OBJECTIVE: Multiple studies have been designed to analyse restenosis angiographically but few have studied the vasoreactivity of coronary segments subjected to angioplasty a few months before. In the present study we analysed, with use of quantitative angiography, the vasoreactivity of previously dilated segments to graded doses of ergonovine and of isosorbide dinitrate. PATIENTS: Fifty consecutive patients undergoing follow-up angiography 6 months after a single coronary angioplasty procedure were studied. RESULTS: The vasoconstrictor response at dilated segments (-19.3 +/- 3.0%) was significantly greater than at control proximal and distal sites in dilated (-7.3 +/- 1.1%, -11.0 +/- 2.9%) and non-dilated (-9.1 +/- 1.3%, -8.3 +/- 2.2%) vessels for the lowest dose of ergonovine (100 micrograms). The constrictor response to 100 micrograms ergonovine (-20.2 +/- 5.3%) at restenosed segments (> 50% stenosis, n = 18) was similar to that (-18.8 +/- 3.8%) at non-restenosed sites (n = 32). In contrast, the degree of constrictor response was similar in all segments including dilated segments for the highest dose of ergonovine used. All segments dilated significantly after intracoronary injection of isosorbide dinitrate. CONCLUSION: Our results demonstrate hypersensitivity of the dilated site to ergonovine 6 months after angioplasty at both restenosed and non-restenosed sites. This response may reflect partial dysfunction of endothelium that has regenerated after injury or hypersensitivity of vascular smooth muscle cells at the site of arterial injury.

Aged↗
PubMed1996

Combined antiplatelet therapy with ticlopidine and aspirin. A simplified approach to intracoronary stent management.

Intravascular metallic stents are increasingly used in the non-surgical management of coronary atherosclerosis. Despite intensive anticoagulation, subacute stent thrombosis, which usually has serious clinical consequences, and major haemorrhagic complications remain major problems after stent implantation. In addition, conventional management with anticoagulant therapy requires prolonged hospitalization. In a prospective multicentre study, we investigated the efficacy of a combination of two antiplatelet agents, ticlopidine 500 mg daily and aspirin 200 mg daily, without oral anticoagulation after stent implantation. Since November 1993, 529 consecutive patients, in whom 545 vessels were successfully stented with conventional (non-heparin coated) stents have been enrolled. Stenting was performed as a bailout procedure for failed angioplasty in 112 patients, for a suboptimal result after angioplasty in 314 patients, and electively in the remaining 103 patients. Coronary events related, or possibly related, to stent thrombosis occurred in 5.4% of patients stented as a bailout procedure and in 1.8% of patients stented for a suboptimal result. Serious bleeding complications occurred in 5.4% of patients stented as a bailout procedure and 1.5% of patients stented for a suboptimal result. Neither stent thrombosis nor serious bleeding complications were seen in patients stented electively. Ticlopidine therapy was discontinued in 1.9% of patients due to neutropenia (0.6%) or rash (1.3%). Mean hospital stay decreased from 6.16 +/- 2.14 days to 4.2 +/- 2.15 days during the study period. A combination of two antiplatelet agents can be employed in the vast majority of patients after coronary stent implantation. Subacute stent thrombosis rates and bleeding complications compare favourably with those reported using conventional therapy and the duration of hospitalization is reduced.

Adult↗
PubMed1996

Role of endothelial cells in restenosis after coronary angioplasty.

Percutaneous transluminal coronary angioplasty (PTCA) is today a procedure of choice in many patients with atherosclerotic coronary artery disease. Despite high rates of initial success, restenosis, occurring in 30 to 40 percent of patients within the first six months, remains the major problem limiting the long-term efficacy of the procedure. Animal models have enhanced our knowledge in the understanding of the mechanisms involved in the restenotic process after experimental angioplasty. In fact, the two known determinants of restenosis are the proliferative and migrative response of underlying smooth muscle cells with production of extracellular matrix and the recently highlighted vascular remodeling. Endothelium, which regenerates from the leading edge of the de-endothelialized area within the weeks following arterial injury, is of particular interest in the modulation of the healing process after the procedure. Endothelial dysfunction, as an imbalance between relaxing and contracting factors, between anti- and pro-coagulant mediators or growth-inhibiting and growth-promoting factors, occurs at sites of regenerating endothelium. Experimental studies, using drugs that enhance endothelium-derived relaxing factors release or drugs that diminish endothelium-derived contracting factors production, have often been shown to be effective in the restenosis prevention. Thus, impairment in endothelial cell function may be considered as one of the major regulatory element in the restenotic process. This review discusses the interactions between endothelial and smooth muscle cells and has for aim to point out the major role of endothelial cells in the development of neointimal thickening and arterial remodeling.

Angioplasty, Balloon, Coronary↗
PubMed1996

NO synthesis is involved in structural and functional effects of ACE inhibitors in injured arteries.

Angiotensin-converting enzyme (ACE) inhibitors reduce intimal hyperplasia after balloon injury. A role for nitric oxide (NO) has been suggested in this effect. Because recent data suggest that NO may modulate some features of endothelial cells and because endothelial cells are involved in the control of intimal hyperplasia, we investigated the role of NO synthesis in the effect of an ACE inhibitor, perindopril, on neoendothelial dysfunction and intimal hyperplasia in a rabbit model of unilateral iliac balloon injury. New Zealand White male rabbits received placebo, perindopril, or cotreatment with perindopril and NG-nitro-L-arginine methyl ester (L-NAME) and were evaluated 4 wk after the injury. Fifteen rabbits (5 in each group) were used to assess in vitro vasoreactivity and twenty-four (8 in each group) for morphometric analysis. In injured vessels, neoendothelium-dependent relaxation in ACE inhibitor-treated animals was improved compared with placebo (P < 0.05) and restored to the level of noninjured vessels (NS). The improvement observed with ACE inhibitor was abolished by cotreatment with L-NAME (P < 0.05). In the same vessels, no effect was observed on neoendothelium-independent vasoreactivity. The improved neoendothelial dysfunction with ACE inhibitor was associated with a 66% reduction in intimal thickening (P < 0.01). The effect was also reversed by cotreatment with L-NAME (P < 0.01). In noninjured vessels, treatment did not alter vasoreactivity or morphology of the vessel wall. These results suggest that NO synthesis may play a key role in the improvement of vascular function seen with ACE inhibitor in balloon-injured vessels.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed1996

[Relation between progression of atherosclerosis and the phenomenon of restenosis after coronary angioplasty].

The authors undertook a retrospective study of medium-term coronary angiographic controls of a group (Gr) of patients (pts) who had undergone coronary angioplasty for rapidly progressive lesions, to determine whether the rate of progression of a coronary stenosis before angioplasty affected the risk of restenosis. 89 pts underwent primary angioplasty with absence of restenosis at 6 months, but required another angioplasty for another lesion. Angiographic follow-up after the 2nd procedure was performed in 86 pts (96%). The coronary lesion dilated at the 2nd angioplasty procedure was analysed quantitatively with four measurements: one immediately before angioplasty, one after, one at the 6 months control, and finally, one measurement 6 months before the angioplasty during the procedure on the 1st site. Multivariate statistical analysis showed that the only predictive factor of post-angioplasty loss in the general population was the immediate gain (F = 11.82; p < 0.005). On the other hand, no correlation was found between progression of the lesion before angioplasty and loss. The rapidly progressive nature of the lesion was defined with a threshold of 0.4 mm, corresponding to the variability of the quantitative angiographic system. Analysis of the procedure parameters showed a lower inflation pressure in the Gr with rapidly progressive lesions (6.58 +/- 21 atm vs 7.63 +/- 1.96 atm; p < 0.05). The immediate gain was significantly greater in the rapidly progressive lesion Gr (0.82 +/- 0.34 vs 0.67 +/- 0.29 mm; p = 0.05). The loss at the 6 months control was identical in the two Gr (0.31 +/- 0.50 vs 0.31 +/- 0.42 mm; p < 0.05). The loss/gain ratio was also comparable (0.37 +/- 0.76 vs 0.45 +/- 0.52; p > 0.05). These results show that rapidly progressive atherosclerosis does not increase the risk of post-angioplasty restenosis.

Aged↗
PubMed1996

[Treatment of pulmonary lymphangioleiomyomatosis using a GnRH agonist].

Pulmonary lymphangioleiomyomatosis is a rare and exclusively female disease which is oestrogen dependent and has a serious prognosis. We present two cases of young women aged 30 and 33 with the same clinical history of renal angiomyolipomas and recurring pneumothoraces. The computerised tomographic scans of the lung were strongly suggestive of LAM (there were fine wall cysts which were disseminated throughout both lung fields). The histological proof was provided by lung biopsy which was carried out during a thoracotomy for pleurectomies. The first patient who is currently asymptomatic and in excellent general health, was treated for three months with tamoxifen (Nolvadex), then for 20 months with 3.75 mg per month of triptoline (Decapeptyl), an agonist of GnRH. The second patient received triptoline in the same dose. After 40 months of treatment this patient was asymptomatic with satisfactory lung function tests. Agonists of GnRH (gonadotropic release hormone) seem to provide a useful alternative in the treatment of LAM.

Adult↗
PubMed1996

Gene transfer of naked DNA encoding for three isoforms of vascular endothelial growth factor stimulates collateral development in vivo.

Vascular endothelial growth factor (VEGF) is a naturally secreted endothelial cell-specific mitogen. We investigated the hypothesis that naked DNA encoding for VEGF could be used in a strategy of arterial gene therapy to stimulate collateral artery development. Plasmid DNA encoding each of the three principal human VEGF isoforms (phVEGF121, phVEGF165, or phVEGF189) was applied to the hydrogel polymer coating of an angioplasty balloon and delivered percutaneously to one iliac artery of rabbits with operatively induced hindlimb ischemia. Compared with control animals transfected with LacZ, site-specific transfection of phVEGF resulted in augmented collateral vessel development documented by serial angiography, and improvement in calf blood pressure ratio (ischemic to normal limb), resting and maximum blood flow, and capillary to myocyte ratio. Similar results were obtained with phVEGF121, phVEGF165, and phVEGF189, which suggests that these isoforms are biologically equivalent with respect to in vivo angiogenesis. The fact that viral or other adjunctive vectors were not required further suggests that secreted gene products may have potential therapeutic utility even when the number of successfully transfected cells remains low. Arterial gene transfer of naked DNA encoding for a secreted angiogenic cytokine, thus, represents a potential alternative to recombinant protein administration for stimulating collateral vessel development.

Animals↗
PubMed1995

Relation of coronary angioscopic findings at coronary angioplasty to angiographic restenosis.

BACKGROUND: Discordant results have been reported regarding morphological predictors of restenosis after percutaneous transluminal coronary angioplasty (PTCA). These discrepancies may be related to the limitations of angiography in the study of plaque morphology. METHODS AND RESULTS: We studied 117 consecutive patients who underwent successful PTCA and who underwent coronary angioscopy before and immediately after the procedure. Angiographic follow-up was performed in 99 (85%) patients. We analyzed the relationship between angioscopic variables at the time of PTCA and the occurrence of restenosis assessed by quantitative coronary angiography. Plaque shape and color had no effect on late loss in luminal diameter (late loss: smooth lesions, 0.55 +/- 0.68 mm; complex lesions, 0.76 +/- 0.60 mm; white plaques, 0.51 +/- 0.56 mm; yellow plaques, 0.65 +/- 0.72 mm; P = NS). An angioscopic protruding thrombus at the PTCA site was associated with significantly greater loss in luminal diameter (late loss: no thrombus, 0.47 +/- 0.54 mm; lining thrombus, 0.59 +/- 0.67 mm; protruding thrombus, 1.07 +/- 0.77 mm; P < .05). Dissection assessed by angioscopy immediately after PTCA had no effect on late loss in luminal diameter (late loss: no dissection, 0.60 +/- 0.60 mm; simple dissection, 0.82 +/- 0.75 mm; complex dissection, 0.57 +/- 0.80 mm; P = NS). CONCLUSIONS: These results show that coronary angioscopy may be helpful in predicting the risk of restenosis after PTCA. The high rate of angiographic recurrence observed when PTCA is performed at thrombus-containing lesions supports a role for thrombus in the process of luminal renarrowing after PTCA.

Aged↗
PubMed1995

Synergistic effect of vascular endothelial growth factor and basic fibroblast growth factor on angiogenesis in vivo.

BACKGROUND: Recent studies have suggested that vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (bFGF) may have synergistic effects on the induction of angiogenesis in vitro. Therefore, we investigated the hypothesis that the simultaneous administration of VEGF and bFGF, each having been previously shown to independently enhance collateral development in an animal model of hind limb ischemia, could have a synergistic effect in vivo. METHODS AND RESULTS: Ten days after surgical induction of unilateral hind limb ischemia, New Zealand White rabbits were randomized to receive either VEGF 500 micrograms alone (n = 6), bFGF 10 micrograms alone (n = 7), VEGF 500 micrograms, immediately followed by 10 micrograms bFGF (n = 7), or vehicle only (control animals, n = 8) in each case administered intra-arterially via a catheter in the internal iliac artery of the ischemic limb. BP ratio (BPR, ischemic/healthy limb) at day 10 for the VEGF+bFGF group was 0.82 +/- 0.01, much superior (P < .0005) to that of either the VEGF group (0.52 +/- 0.02) or the bFGF group (0.57 +/- 0.02). This outcome persisted at day 30: BPR in the VEGF+bFGF group (0.91 +/- 0.02) exceeded that of the control group (0.49 +/- 0.05, P < .0001), the VEGF group (0.65 +/- 0.03, P < .0005), or the bFGF group (0.66 +/- 0.03, P < .0005). Serial angiography demonstrated a progressive increase in luminal diameter of the stem collateral artery and the number of opacified collaterals in the thigh of the ischemic limbs in all groups. Stem artery diameter with VEGF+bFGF (1.34 +/- 0.07 mm) on day 30 was significantly (P < .05) greater than with either VEGF (1.09 +/- 0.09) or bFGF (1.18 +/- 0.06) alone. Capillary density was significantly greater (P < .05) in VEGF+bFGF animals (275 +/- 20 mm2) compared with VEGF (201 +/- 8) or bFGF (209 +/- 15). CONCLUSIONS: Combined administration of VEGF and bFGF stimulates significantly greater and more rapid augmentation of collateral circulation, resulting in superior hemodynamic improvement compared with either VEGF or bFGF alone. This synergism of two angiogenic mitogens with different target cell specificities may have important implications for the treatment of severe arterial insufficiency in patients whose disease is not amenable to direct revascularization.

Angiography↗
PubMed1995

Accumulation of fetal fibronectin mRNAs after balloon denudation of rabbit arteries.

BACKGROUND: Fibronectin (FN), a component of the extracellular matrix, influences cellular migration and differentiation. It is a prominent component of the extracellular matrix of normal arteries and is thought to play an important role in the pathogenesis of restenosis after angioplasty. FN exists in multiple forms that arise from a single RNA transcript that can be alternatively spliced. EIIIA- and EIIIB-containing FN mRNAs predominate in the embryo, whereas in the adult, most of the normal tissue FN lacks these domains. Since few data were available concerning pattern of expression of the different alternatively spliced forms of FN mRNA in arteries after endoluminal injury, we analyzed the expression of EIIIA and EIIIB FN isoforms at different times after experimental angioplasty. METHODS AND RESULTS: The spatial and temporal alterations in FN expression were studied in an in vivo model of endothelial denudation in the rabbit aorta and iliac artery by a combination of immunochemistry and in situ hybridization methods. Alternatively spliced forms of FN EIIIA and EIIIB were detected in the media and the adventitia of both types of vessels 24 to 48 hours after injury. Two weeks after injury, EIIIA and EIIIB mRNAs were found to accumulate within the luminal layers of the neointima. The cellular form of FN protein was not found until 2 weeks after the injury and accumulated in the inner part of the neointima. CONCLUSIONS: These data demonstrate that FN upregulation is an early and long-lasting process after arterial injury. These results suggest that the induction of the embryonic FN isoforms may be involved in the restenotic process that follows balloon denudation of arteries.

Animals↗
PubMed1995

Relation between the deletion polymorphism of the angiotensin-converting enzyme gene and late luminal narrowing after coronary angioplasty.

BACKGROUND: The insertion/deletion (I/D) polymorphism of the angiotensin-converting enzyme (ACE) gene has been implicated in the pathogenesis of coronary artery disease. The deletion allele is strongly associated with the level of circulating ACE and is a potent risk factor for myocardial infarction. Recently, the deletion allele was also associated with the occurrence of visually diagnosed restenosis after percutaneous transluminal coronary angioplasty (PTCA) in a selected population of patients with acute myocardial infarction. METHODS AND RESULTS: We investigated the influence of the ACE I/D polymorphism on the occurrence of restenosis after PTCA with the use of quantitative coronary angiography. ACE I/D genotypes were characterized in 118 consecutive patients who had one-vessel disease and were undergoing systematic angiographic follow-up. Coronary angiograms were analyzed before and after PTCA and at follow-up (7.4 +/- 3.0 months). Before PTCA, there were no clinical or angiographic differences among the three groups of genotypes (DD, n = 39; ID, n = 62; II, n = 17). After PTCA, the mean differences in minimal luminal diameter between post-PTCA and pre-PTCA angiograms (acute gain) were identical in the three groups, as was the mean percent residual stenosis. At follow-up angiography, the mean difference in minimal coronary luminal diameter between post-PTCA and follow-up angiograms (late loss) was not significantly different in the three groups of genotypes. The percentage of patients with restenosis defined as a > 50% stenosis was identical in the three groups. CONCLUSIONS: In this quantitative study, the I/D polymorphism of the ACE gene had no influence on the occurrence of restenosis after coronary angioplasty.

Adult↗
PubMed1995

Local delivery of vascular endothelial growth factor accelerates reendothelialization and attenuates intimal hyperplasia in balloon-injured rat carotid artery.

BACKGROUND: Most strategies designed to reduce restenosis by the use of pharmacological or biological reagents involve direct inhibition of vascular smooth muscle cell (SMC) proliferation. Alternatively, SMC proliferation might be indirectly inhibited if reendothelialization could be specifically facilitated at sites of balloon-induced arterial injury. Accordingly, we investigated the hypothesis that application of an endothelial cell (EC)-specific mitogen to a freshly denuded intimal surface could accelerate reendothelialization and thereby attenuate intimal hyperplasia. METHODS AND RESULTS: The left carotid artery of 31 Sprague-Dawley rats was subjected to balloon injury, after which 16 rats were treated with a 30-minute incubation with 100 micrograms of vascular endothelial growth factor (VEGF), an EC-specific mitogen. Control animals (n = 15) received a 30-minute incubation with 0.9% saline. At 2 weeks after balloon injury, carotid artery reendothelialization was markedly superior in the VEGF-treated group compared with the control group (14.59 +/- 1.12 versus 7.96 +/- 0.51 mm2, P < 0.005). The extent of reendothelialization measured at 4 weeks after balloon injury remained superior for arteries treated with VEGF (18.04 +/- 0.90 mm2) versus saline (13.42 +/- 0.84 mm2, P < .005). Neointimal thickening was correspondingly attenuated to a statistically significant degree in arteries treated with VEGF versus the control group at both the 2-week and 4-week time points. Immunostaining for proliferating cell nuclear antigen (PCNA) disclosed a threefold increase in PCNA-positive cells in the neointima of control arteries versus VEGF-treated arteries at 2 weeks after injury. CONCLUSIONS: Application of VEGF, an EC-specific growth regulatory molecule, may be effectively used in vivo to promote reendothelialization and thereby indirectly attenuate neointimal thickening due to SMC proliferation.

Animals↗
PubMed1995

Recovery of disturbed endothelium-dependent flow in the collateral-perfused rabbit ischemic hindlimb after administration of vascular endothelial growth factor.

BACKGROUND: Disturbed endothelium-dependent blood flow has been shown to be a feature of native collateral vessels. Recent studies have shown that recombinant angiogenic growth factors augment collateral development in animal models of hindlimb ischemia. We therefore investigated the hypothesis that the administration of an angiogenic growth factor, in this case vascular endothelial growth factor (VEGF), may promote recovery of disturbed endothelium-dependent blood flow in a rabbit model of hindlimb ischemia. METHODS AND RESULTS: Ischemia was induced by ligation of the external iliac artery and excision of the femoral artery in one limb of New Zealand White rabbits (day 0). Flow velocity was measured using a Doppler guide wire at rest and after administration of serotonin and acetylcholine. Blood flow (in mL/min) was calculated assuming a circular lumen geometry. In untreated control animals with an ischemic limb, serotonin administered at day 10 or 40 produced a decrease in hindlimb blood flow (71 +/- 2% and 33 +/- 6% reduction from baseline, respectively); in contrast, among animals treated with a single 500-micrograms bolus dose of VEGF administered selectively into the internal iliac artery at day 10 and studied at day 40, serotonin produced an increase in flow (119 +/- 8% from baseline; P < .05 versus control animals). Acetylcholine induced only a moderate increase in flow in control animals (152 +/- 15% at day 10 and 177 +/- 14% at day 40) in contrast to a profound increase among VEGF-treated animals studied at day 40 (254 +/- 25%; P < .05 versus control animals). CONCLUSIONS: To our knowledge, these findings constitute the first demonstration of successful pharmacological modulation of disturbed endothelium-dependent flow in the arterial circulation subserved by collateral vessels. This physiological benefit complements previously reported anatomic findings suggesting a favorable impact of angiogenic growth factors on collateral-dependent limb ischemia.

Acetylcholine↗
PubMed1995

Restenosis after delayed coronary angioplasty of the culprit vessel in patients with a recent myocardial infarction treated by thrombolysis.

BACKGROUND: Clinical follow-up after percutaneous transluminal coronary angioplasty (PTCA) of an infarct-related lesion has demonstrated a low incidence of recurrent symptoms and repeated revascularization. In the absence of systematic angiographic follow-up, this low rate of clinical restenosis may reflect either a truly lower incidence of anatomic restenosis or the lack of recurrent symptoms in patients with extensive infarction in the territory of the restenotic vessel. METHODS AND RESULTS: We studied 300 consecutive patients who, after a thrombolysis for myocardial infarction, underwent delayed (10.5 +/- 6 days after the myocardial infarction) PTCA of the infarct-related lesion. Procedural success was obtained in 253 patients (84%), and angiographic follow-up was performed in 205 of this group (81%) at a mean of 7.3 +/- 1.9 months. Restenosis (defined as the recurrence of > 50% stenosis) was present in 105 patients (51%). Only 34 of the 105 patients (32%) with angiographic restenosis were symptomatic; the other 68% had clinically silent restenosis. Of these 105 patients, 27 (13% of the total population undergoing follow-up angiography) had reocclusion at the dilated site at follow-up. The severity of the stenosis at follow-up and the late loss in minimal lumen diameter followed a nearly Gaussian distribution if the lesions that were totally occluded at follow-up were excluded. By multivariate analysis, two independent predictors of reocclusion were identified: a small reference diameter (P < .0005) and the presence of collateral vessels before the procedure (P < .01). Only one factor was associated with restenosis in the 178 patients who did not have reocclusion at follow-up; a Thrombolysis in Myocardial Infarction grade < or = 2 before the procedure (P < .0001). At follow-up, there was a significantly (P < .01) higher ejection fraction in patients without restenosis (56.1 +/- 13.4%) and in patients with restenosis without total occlusion (56.0 +/- 13.8%) than in patients with reocclusion (46.4 +/- 13.0%). CONCLUSIONS: Despite a satisfactory clinical outcome, delayed PTCA of an infarct-related lesion is associated with a high rate of angiographic recurrence. Two distinct mechanisms account for recurrent stenosis: progressive luminal renarrowing as documented after angioplasty of stable lesions and reocclusion of the infarct-related lesion. Only reocclusion is associated with a deterioration in left ventricular function at follow-up.

Angioplasty, Balloon, Coronary↗
PubMed1995

Local lesion-related factors and restenosis after coronary angioplasty. Evidence from a quantitative angiographic study in patients with unstable angina undergoing double-vessel angioplasty.

BACKGROUND: Restenosis rates are high when coronary angioplasty is performed in patients with unstable angina. The relative contributions of local and systemic factors to this excess risk of restenosis are unclear. To assess these, we compared changes in minimal lumen diameter and the incidence of restenosis, determined by quantitative coronary angiography, after coronary angioplasty at culprit and nonculprit lesions dilated in the course of a single procedure in patients with unstable angina. METHODS AND RESULTS: We identified 67 consecutive patients with unstable angina in whom two lesions, in different vessels, were dilated during the same procedure. Lesions were designated as culprit or nonculprit on the basis of the location of ECG changes during chest pain combined with assessment of the angiographic characteristics of the lesions. With these criteria, 43 patients had identifiable culprit lesions. Stenosis severity before and immediately after angioplasty and at follow-up was assessed with quantitative angiography. Angiographic follow-up was performed in 91% (39 patients) of this subgroup. Culprit lesions were more severe (P < .02) than nonculprit lesions. The late loss at culprit lesions (0.87 +/- 0.75 mm) was significantly (P < .01) greater than the equivalent value for nonculprit lesions (0.33 +/- 0.69 mm). With a categorical definition (> 50% stenosis at follow-up), restenosis occurred at 67% of culprit lesions and at 32% of nonculprit lesions (P < .01). CONCLUSIONS: The greater loss in minimal lumen diameter and the consequent higher rate of restenosis at culprit compared with nonculprit lesions suggest that local "lesion-related" factors are an important determinant of the high rate of restenosis when coronary angioplasty is performed in patients with unstable angina.

Angina, Unstable↗