Implementing preoperative Botulinum toxin A and progressive pneumoperitoneum through the use of an algorithm in giant ventral hernia repair.

BACKGROUND: Repair of large ventral hernias with loss of domain can be facilitated by preoperative Botulinum toxin A (BTA) injections and preoperative progressive pneumoperitoneum (PPP). The aim of this study is to evaluate the outcomes of ventral hernioplasty using a standardized algorithm, including component separation techniques, preoperative BTA and PPP. METHODS: All patients between June 2014 and August 2018 with giant hernias (either primary or incisional) of more than 12 cm width were treated according to a previously developed standardized algorithm. Retrospective data analysis from a prospectively collected dataset was performed. The primary outcome was closure of the anterior fascia. Secondary outcomes included complications related to the preoperative treatment, postoperative complications, and recurrences. RESULTS: Twenty-three patients were included. Median age was 65 years (range 28-77) and median BMI was 31.4 (range 22.7-38.0 kg/m2). The median loss of domain was 29% (range 12-226%). For the primary and secondary endpoints, 22 patients were analyzed. Primary closure of the anterior fascia was possible in 82% of all patients. After a median follow-up of 19.5 months (range 10-60 months), 3 patients (14%) developed a hernia recurrence and 16 patients (73%) developed 23 surgical site occurrences, most of which were surgical site infections (54.5%). CONCLUSION: Our algorithm using both anterior or posterior component separation, together with preoperative BTA injections and PPP, achieved an acceptable fascial closure rate. Further studies are needed to explore the individual potential of BTA injections and PPP, and to research whether these methods can prevent the need for component separation, as postoperative wound morbidity remains high in our study.

Plasma levels of carboxypeptidase U (CPU, CPB2 or TAFIa) are elevated in patients with acute myocardial infarction.

BACKGROUND: Two decades after its discovery, carboxypeptidase U (CPU, CPB2 or TAFIa) has become a compelling drug target in thrombosis research. However, given the difficulty of measuring CPU in the blood circulation and the demanding sample collecton requirements, previous clinical studies focused mainly on measuring its inactive precursor, proCPU (proCPB2 or TAFI). OBJECTIVES: Using a sensitive and specific enzymatic assay, we investigated plasma CPU levels in patients presenting with acute myocardial infarction (AMI) and in controls. METHODS: In this case-control study, peripheral arterial blood samples were collected from 45 patients with AMI (25 with ST segment elevation myocardial infarction [STEMI], 20 with non-ST segment elevation myocardial infarction [NSTEMI]) and 42 controls. Additionally, intracoronary blood samples were collected from 11 STEMI patients during thrombus aspiration. Subsequently, proCPU and CPU plasma concentrations in all samples were measured by means of an activity-based assay, using Bz-o-cyano-Phe-Arg as a selective substrate. RESULTS: CPU activity levels were higher in patients with AMI (median LOD-LOQ, range 0-1277 mU L(-1) ) than in controls (median < LOD, range 0-128 mU L(-1) ). No correlation was found between CPU levels and AMI type (NSTEMI [median between LOD-LOQ, range 0-465 mU L(-1) ] vs. STEMI [median between LOD-LOQ, range 0-1277 mU L(-1) ]). Intracoronary samples (median 109 mU L(-1) , range 0-759 mU L(-1) ) contained higher CPU levels than did peripheral samples (median between LOD-LOQ, range 0-107 mU L(-1) ), indicating increased local CPU generation. With regard to proCPU, we found lower levels in AMI patients (median 910 U L(-1) , range 706-1224 U L(-1) ) than in controls (median 1010 U L(-1) , range 753-1396 U L(-1) ). CONCLUSIONS: AMI patients have higher plasma CPU levels and lower proCPU levels than controls. This finding indicates in vivo generation of functional active CPU in patients with AMI.

Communication between general practitioners and radiologists: opinions, experience, promises, pitfalls.

PURPOSE: Studies encompassing the views and aspirations of general practitioners (GPs) concerning the radiology report are rare. We present the results of a large-scale survey among GPs in Flanders, Belgium, and examine its implications for the communication between radiologists and GPs. MATERIALS AND METHODS: GPs were invited by e-mail to participate in a survey on the radiology report. Respondents could state their degree of agreement with 46 statements. Besides that, they could freely make suggestions to improve the report. Quantitative results were examined to determine majority convictions. Free text suggestions were searched for motives and convictions. RESULTS: Of 1323 GPs invited, 282 completed forms were prepared for analysis. 96.8% considered the report an indispensable tool. 85.5% were satisfied with it. Itemized reporting of complex examinations was favoured by a very large majority. 83 GPs (29.4%) made suggestions for improvement. Much emphasis was put upon the clinical role of the radiologist. The need to mark key images, to mention meaningful normal findings, to structure the report and to facilitate communication was also frequently mentioned. CONCLUSION: GPs expect the radiologist to think as a clinician and offer clinical answers. An automated electronic information chain may contribute to realize this objective but direct communication should always remain possible.

Impaired coronary flow reserve after a recent myocardial infarction: correlation with infarct size and extent of microvascular obstruction.

BACKGROUND: The exact relationship between the coronary flow reserve (CFR) and infarct size remains unknown. In this prospective study the relationship between the CFR both in the infarcted and remote myocardium and infarct size was investigated. Furthermore, the diagnostic value of the CFR to predict the extent of microvascular obstruction (MO) was evaluated. METHODS: In thirty patients the CFR was measured with a Doppler guide wire 6 ± 3 days after a first myocardial infarction (MI) in the infarct related and in a reference coronary artery. MO and infarct size were determined with magnetic resonance imaging. RESULTS: The CFR was inversely related to infarct size in the infarcted and remote myocardium (respectively, r=-0.60, p<0.01 and r=-0.62, p<0.01). In the infarcted myocardium the extent of MO was strongly related to the infarct size and was in a multivariate analysis the single significant determinant of the CFR and the hyperaemic flow. In the remote myocardium no relationship was present between infarct size and hyperaemic flow, but the baseline flow increased as the infarct size became larger (r=0.58, p<0.01). In a receiver operator characteristic (ROC) analysis, a CFR value ≤ 2 in the infarct related coronary artery offered the best sensitivity (65%) and specificity (71%) to detect the presence of MO (p<0.05). CONCLUSIONS: After MI, the CFR both in the infarcted and remote myocardium is inversely related to infarct size. In the infarcted myocardium, a CFR value ≤ 2 predicts the presence of MO with moderate sensitivity and specificity.

Optimizing communication between the radiologist and the general practitioner.

Adequate communication between radiologist and referring general practitioner (GP) is mandatory in a good practice clinical setting. Several hurdles may interfere with good communication. Inappropriate imaging requests or incomplete clinical details conveyed to the radiologist may result in inappropriate imaging and interpretation. GPs may find the radiology report confusing or may feel it takes too much time to receive the reports. Communication issues may dissatisfy GPs and make them look for alternative providers for imaging referrals. In the digital era, electronic radiology request forms, digital access for the GP to radiology images and reports and networks centralizing patient data may all help to improve communication between radiologist and GP. In this paper we outline practical ways of improving this communication.

Structured reporting: if, why, when, how-and at what expense? Results of a focus group meeting of radiology professionals from eight countries.

PURPOSE: To determine why, despite growing evidence that radiologists and referring physicians prefer structured reporting (SR) to free text (FT) reporting, SR has not been widely adopted in most radiology departments. METHODS: A focus group was formed consisting of 11 radiology professionals from eight countries. Eight topics were submitted for discussion. The meeting was videotaped, transcribed, and analyzed according to the principles of qualitative healthcare research. RESULTS: Perceived advantages of SR were facilitation of research, easy comparison, discouragement of ambiguous reports, embedded links to images, highlighting important findings, not having to dictate text nobody will read, and automatic translation of teleradiology reports. Being compelled to report within a rigid frame was judged unacceptable. Personal convictions appeared to have high emotional value. It was felt that other healthcare stakeholders would impose SR without regard to what radiologists thought of it. If the industry were to provide ready-made templates for selected examinations, most radiologists would use them. CONCLUSION: If radiologists can be convinced of the advantages of SR and the risks associated with failing to participate actively in its implementation, they will take a positive stand. The industry should propose technology allowing SR without compromising accuracy, completeness, workflows, and cost-benefit balance. MAIN MESSAGES: Structured reporting offers radiologists opportunities to improve their service to other stakeholders. • If radiologists can be convinced of the advantages of structured reporting, they may become early adopters. • The healthcare industry should propose technology allowing structured reporting. • Structured reporting will fail if it compromises accuracy, completeness, workflows or cost-benefit balance.

Coronary microvascular dysfunction after myocardial infarction: increased coronary zero flow pressure both in the infarcted and in the remote myocardium is mainly related to left ventricular filling pressure.

OBJECTIVE: To investigate the underlying mechanisms of a decreased coronary flow reserve after myocardial infarction (MI) by analysing the characteristics of the diastolic hyperaemic coronary pressure-flow relationship. DESIGN: Prospective study. SETTING: Tertiary care hospital. PATIENTS: 68 patients with a recent MI and 27 patients with stable angina pectoris (AP; control group). MAIN OUTCOME MEASURES: The intercept with the pressure axis (the zero flow pressure or Pzf) and slope index of the pressure-flow relationship (SIPF) were calculated from the simultaneously recorded hyperaemic intracoronary blood flow velocity and aortic pressure after successful coronary stenting. RESULTS: A stepwise increase in Pzf from AP (14.6 (8.0) mm Hg), over non-Q-wave MI (22.5 (9.1) mm Hg), to Q-wave MI (37.1 (12.9) mm Hg; p<0.001) was observed. Similar changes in Pzf were found in a reference artery perfusing the non-infarcted myocardium. Multivariate analysis showed that in both regions the left ventricular end-diastolic pressure (LVEDP) was the most important determinant of the Pzf. The SIPF was not statistically different in the treated vessel between patients with MI and AP, but was increased in MI patients with a markedly increased LVEDP. CONCLUSIONS: After an MI, the coronary pressure-flow relationship is shifted to the right both in the infarcted and in the non-infarcted remote myocardium, as shown by the increased Pzf. The correlation with Pzf suggests that elevated left ventricular filling pressures contribute to the impediment of myocardial perfusion in patients with infarction.

[Structure and content of the radiological report: an audit of 94 reports from a university education center]. / Structuur en inhoud van het radiologieverslag: een audit van 94 verslagen uit een universitair opleidingscentrum.

Efficient communication between the radiologist and the referring clinician is an essential feature of high quality radiology practice. The written report, the only result of the radiological investigation most clinicians will see, should therefore comply with a number of quality criteria. As far as reporting in Dutch is concerned, these criteria have not been clearly defined. Articles on the radiology report are scarce and mostly focus on reporting in English. We have investigated the quality of radiology reporting in a university hospital in Flanders, the Dutch speaking part of Belgium. A weighed sample of 94 reports of 24 radiologists (staff members and radiologists-in-training) was blinded and evaluated by a qualified radiologist with ten years of experience as a writer and editor-in-chief medical magazines. A scoring system was applied, based on five criteria: comprehensible, problem-oriented, correct Dutch, concise, and direct. This article gives an overview of the results and takes a closer look at three of the 94 reports examined.

Importance of methodology in determination of Chlamydia pneumoniae seropositivity in healthy subjects and in patients with coronary atherosclerosis.

Enzyme immunoassays (EIAs) for the detection of Chlamydia pneumoniae antibodies were compared to the microimmunofluorescence (MIF) test, the reference method. Furthermore, we assessed the hypothesis that a possible relationship between Chlamydia pneumoniae immunoglobulin G (IgG) antibodies and coronary artery disease is dependent on the type of EIA. Sera from 112 healthy men (mean age, 50.1 years) were tested for antibodies against Chlamydia pneumoniae by five commercial test kits: Focus Chlamydia MIF IgG test, Labsystems Chlamydia pneumoniae IgG EIA (LS EIA), R-Biopharm Elegance Chlamydia pneumoniae IgG EIA (RB EIA), Medac Chlamydia pneumoniae IgG sandwich enzyme-linked immunosorbent assay ELISA (MCp sELISA) and Medac Chlamydia IgG recombinant enzyme-linked immunosorbent assay ELISA (MC rELISA). Sera from 106 consecutive male patients (mean age, 63.6 years) undergoing diagnostic coronary angiography were also examined using the Focus MIF, LS EIA, MCp sELISA, and MC rELISA techniques. The agreement between LS EIA (65 to 83% [controls-patients]) or MC rELISA (49 to 61%) and Focus MIF (78 to 83%) was average to fair (kappa = 0.597 and 0.234, respectively). MCp sELISA and RB EIA showed good agreement with MIF (kappa = 0.686 and 0.665, respectively), with 80 to 89 and 79% of individuals reacting positively. A significant difference in seroprevalence between patients and healthy subjects was observed with the LS EIA, while seropositivities in the two study groups appeared equal when the Focus MIF assay was applied. The MC rELISA and MCp sELISA gave statistically significant differences in antibody seroprevalence in patients with two-vessel disease or when the patient group combined individuals with a two- or a three-vessel disease, respectively. The concordance between MIF and other commonly used serological assays for C. pneumoniae IgG antibody detection is good to fair. The choice of serological assay has important implications for C. pneumoniae antibody seroprevalence, as well as for the relationship between C. pneumoniae seropositivity and coronary artery disease.

Chlamydia pneumoniae and atherosclerosis.

Chlamydia pneumoniae, a human respiratory pathogen, has been linked to atherosclerotic disease based on sero-epidemiologic studies, direct detection of the organism in atherosclerotic lesions, animal experiments and tissue culture. In this review paper we propose to interpret results in line with the biology of Chlamydia with persistence of Chlamydia pneumoniae antigens in the pathogenesis of atherosclerosis rather than viable bacteriae.

Comparison of antiplatelet effect of loading dose of clopidogrel versus abciximab during coronary intervention.

Randomized clinical trials have evidently shown that the addition of thienopyridines or abciximab to standard aspirin results in a significant reduction of ischaemic complications after coronary stent implantation. A head-to-head comparison of these antithrombotic drug regimens during coronary intervention is, however, lacking, and this was the main aim of the present study. Thirty-nine patients with angina pectoris who were scheduled for coronary stent implantation were assigned to either group 1 (160 mg aspirin + 500 mg ticlopidine post-stent), group 2 (160 mg aspirin + abciximab + 500 mg ticlopidine post-stent) or group 3 (160 mg aspirin + loading dose (375/450 mg) clopidogrel pre-stent and 75 mg clopidogrel post-stent). A loading dose of 450 mg clopidogrel was found to be more effective than the standard loading dose of 375 mg. Platelet aggregation induced by 4 micromol/l adenosine diphosphate (ADP) was assessed in samples collected before intervention and 10 min, 4 h and 20 h after intervention. Before intervention, a moderate antiplatelet effect because of aspirin intake was observed (ADP aggregation level, +/- 50%) in all study groups. After intervention, platelet aggregation tended to be enhanced in group 1 while it was strongly inhibited in the groups pre-treated with clopidogrel or abciximab: ADP induced an aggregation level early after intervention of 60 +/- 12% in group 1 (ticlopidine post-stenting) versus 30 +/- 10% in group 3 (loading dose clopidogrel) versus 3 +/- 6% in group 2 (abciximab). Abciximab achieved a more complete inhibition of aggregation than clopidogrel (P = 0.007). The overall complication rate was low with only one major bleeding and one death due to side-branch occlusion with re-infarction occurring, both in the abciximab group. Platelet aggregation during coronary intervention is strongly inhibited by both abciximab and by high loading dose of clopidogrel. Although abciximab showed a stronger antiplatelet effect than clopidogrel, it remains to be established whether this ex vivo superiority of abciximab also translates into an overall clinical benefit in patients with elective stent implantation.

Reliability of fractional flow reserve measurements in patients with associated microvascular dysfunction: importance of flow on translesional pressure gradient.

Fractional flow reserve (FFR) has been applied with success as a lesion-specific functional indicator of stenosis severity, at least in patients with normal microcirculation. This study sought to assess the reliability of FFR calculations in patients with associated microvascular dysfunction (e.g., post myocardial infarction, or post-MI). First, the effect of coronary flow changes on translesional pressure gradient was assessed. Therefore, intracoronary pressure and flow was recorded simultaneously across 19 non-infarct-related lesions (both pre- and postinterventional lesions with a mean diameter stenosis of 47% +/- 12%). Measurements were performed by means of a pressure and Doppler wire during maximal hyperemia and also during submaximal hyperemia induced by low-dose adenosine. The drop of coronary flow from 48 +/- 23 ml/min during maximal hyperemia to 36 +/- 18 ml/min during submaximal hyperemia was associated with a small decrease in translesional pressure gradient (from 22 +/- 12 mm Hg to 19 +/- 12 mm Hg; P = 0.02) and a small increase in the mean distal/arterial pressure ratio (Pd/Pa) going from 77% +/- 11% to 81% +/- 11% (P = 0.003). Then, intracoronary pressure and flow measurements were compared across 21 non-infarct-related lesions vs. 22 matched infarct-related lesions. For a similar angiographic stenosis severity (% DS = +/- 44%), maximal flow was 48 +/- 22 ml/min in the non-infarct arteries and 37 +/- 26 ml/min in the infarct arteries (P = 0.03), confirming the presence of severe microvascular dysfunction in infarct regions. Similar to the earlier findings, this hyperemic flow reduction in MI patients was associated with a small increase of FFR (= Pd/Pa): 79% +/- 12% in no MI vs. 83% +/- 12% in MI patients (P = 0.3). A reduction of hyperemic flow by +25%, [correction] such as can be found in patients with severely impaired microvascular function, has a limited effect on FFR calculations (+ 5%). This finding allows the application of standard FFR calculations in a more general population of ischemic heart disease, including patients with recent MI.

Unsuccessful long-term outcome after treatment of a vein graft false aneurysm with a polytetrafluoethylene-coated Jostent.

We describe a case in which a stented ulcerated plaque in an old vein graft ruptured to a huge false aneurysm. By the use of a PTFE-coated Jostent, the false aneurysm could be percutaneously closed. However, 6 months later, a new false aneurysm, probably due to focal perforation of the covered Jostent, developed.

Continuous perivascular L-arginine delivery increases total vessel area and reduces neointimal thickening after experimental balloon dilatation.

The aim of this study was to evaluate whether vascular remodeling and neointimal thickening occur after balloon dilatation of the nonatherosclerotic rabbit carotid artery, and whether both processes are influenced by continuous perivascular delivery of L-arginine or the nitric oxide synthase inhibitor NG-nitro-L-arginine methyl ester (L-NAME). In the first experiment, histological and morphometric evaluation of arteries was performed at different time points after balloon dilatation: 10 minutes (n=7), and 1 (n=7), 2 (n=9), 3 (n=20), or 10 (n=5) weeks. Neointimal thickening progressively contributed to luminal narrowing for at least 10 weeks after angioplasty. During the first 2 weeks after dilatation, a significant decrease of the total vessel area was measured. Ten weeks after dilatation, both the neointimal and total vessel area were increased without further changing of the luminal area. In the second experiment, endothelial injured rabbits were randomly assigned to receive 2 weeks of continuous local perivascular physiological salt solution (n=6), L-arginine (n=8), or L-NAME (n=7), starting immediately after balloon dilatation (ie, local drug delivery during the first phase of the biphasic vascular remodeling process). Perivascular L-arginine delivery significantly reduced the neointimal area, despite an increased number of neointimal Ki-67-positive smooth muscle cells. Both the luminal area and total vessel area were significantly increased. Serum L-arginine levels remained unchanged. L-NAME administration had no effect on the neointimal area, nor on the luminal and total vessel area. Neointimal formation and biphasic vascular remodeling occur after experimental balloon dilatation of the nonatherosclerotic rabbit carotid artery, and can be influenced by continuous local perivascular delivery of L-arginine.

Inducible nitric oxide synthase colocalizes with signs of lipid oxidation/peroxidation in human atherosclerotic plaques.

OBJECTIVE: Advanced human atherosclerotic plaques are characterized by the abundant presence of the autofluorescent non-soluble lipid pigment ceroid, consisting of oxidized lipoproteins. The aim of the present study was to examine the topographical and cellular distribution of inducible nitric oxide synthase (iNOS or NOS II) within different stages of atherosclerosis and its colocalization with ceroid deposits and nitrotyrosine. METHODS AND RESULTS: Different stages of atherosclerosis were studied by immunohistochemistry on whole-mount longitudinal sections of carotid endarterectomy specimens. In the adaptive intimal thickening the predominant cell type were smooth muscle cells. The fatty streaks contained both smooth muscle cells and macrophages with an extremely low NOS II immunoreactivity. The advanced atherosclerotic plaques however, showed a very dense infiltration by macrophages, of which a subpopulation expressed NOS II as a vesicular immunoreactivity in their cytoplasm. These were mainly present around the necrotic core, in association with ceroid accumulation and nitrotyrosine. Fluorescence quenching microscopy showed the presence of NOS II on autofluorescent ceroid vesicles in the macrophages. Large extracellular ceroid granules were not NOS II immunoreactive. NOS II mRNA was detected by RT-PCR and the protein by Western blot in the plaque tissue but not in mammary arteries used as controls. CONCLUSION: Ceroid, nitrotyrosine and NOS II colocalized in late stages of atherosclerosis and were found around the necrotic core in the plaque. This could suggest that NOS II expression in macrophages is involved in oxidation and peroxidation of lipids, leading to ceroid formation.

Coronary artery spasm complicating anaphylaxis secondary to skin disinfectant.

We report a patient in whom presumed vasospasm of an angiographically normal coronary artery led to severe transmural myocardial ischemia. To our knowledge, this is the first case in which an allergic reaction to locally applied chlorhexidine caused such a severe reaction.

Primary pulmonary hypertension in a patient with HIV infection.

Several case-reports and small series suggest a causal relationship between human immunodeficiency virus (HIV) infection and pulmonary hypertension. We report on a HIV seropositive man with a high and stable CD4 lymphocyte count (+/- 600/mm3) who developed severe pulmonary hypertension, not attributable to other known causes. This case report underscores the fact that the degree of immunosuppression secondary to the HIV-infection seems to be of little relevance in the pathophysiology of the syndrome. HIV-infected patients with dyspnoea, not related to pulmonary infection, with exercise intolerance, syncope or precordial pain should receive an electrocardiogram and echocardiographic assessment. The exact pathogenetic mechanism of this rapidly progressive disease and whether anti-viral therapy should be promoted is still under investigation.

Fibrin(ogen) and von Willebrand factor deposition are associated with intimal thickening after balloon angioplasty of the rabbit carotid artery.

The aim of the study was to assess the contribution of thrombus incorporation into neointimal thickening in the rabbit carotid artery after deep vascular injury induced by balloon angioplasty compared with superficial vascular injury induced by a perivascular collar. Besides CD 31 (PECAM 1), vimentin, alpha-smooth muscle actin, rabbit anti-macrophage monoclonal antibody and proliferating cell nuclear antigen, fibrin(ogen) and von Willebrand factor (vWF) deposition was assessed immunohistochemically. Angioplasty was performed in 47 rabbits and evaluated immediately (n = 7), after 6 hours (n = 4), and after 1 (n = 7), 2 (n = 9), or 3 (n = 20) weeks. A collar was placed in 29 rabbits and evaluated immediately (n = 5), after 6 hours (n = 5), and after 1 (n = 7), 2 (n = 10), or 3 (n = 2) weeks. After dilatation, the arteries were extensively denuded of endothelium, the internal elastic membrane was ruptured and blood-filled clefts were present in the media, pointing to deep vascular (type III) injury. Six hours later, mural fibrin(ogen) thrombi were formed, specially at sites with severe damage. This fibrin(ogen) matrix became infiltrated by phagocytes and smooth muscle cells. A luminal cap covered by regenerating endothelium was formed, demonstrating increased immunoreactivity to vWF. vWF was deposited in the extracellular neointimal spaces. Fibrin(ogen) thrombus deposition and incorporation appeared to be protracted phenomena for at least 2 weeks. After collar placement, minimal endothelial denudation was documented, pointing to focal superficial (type I) vascular injury. In subsequent weeks, neointimal thickening was associated with vWF deposition but not with fibrin(ogen) thrombus incorporation. In conclusion, mural fibrin(ogen) thrombus formation and incorporation contribute to neointima formation after deep vascular injury and seem to occur for several weeks after the initial insult.

Balloon angioplasty and induction of non-endothelial nitric oxide synthase in rabbit carotid arteries.

The purpose of the study was to evaluate whether balloon angioplasty is associated with changes in nitric oxide synthase (NO synthase) activity. Normal rabbit carotid arteries were examined 10 min or 1, 2, 3 or 10 weeks after angioplasty with 2 or 2.5-mm balloons. Immunohistology was used to evaluate intimal thickening and endothelial cell regeneration. The NO synthase activity was studied functionally using isolated segments in organ chambers. Immunohistochemistry of the endothelial cell markers von Willebrand factor and platelet endothelial cell adhesion molecule-1 indicated that the regeneration of endothelial cells from patchy islands that remained after angioplasty was virtually complete within 2 weeks. However, the endothelium-dependent relaxations elicited by acetylcholine remained impaired up to 10 weeks after dilation. Contractions elicited by 5-hydroxytryptamine (5-HT) were attenuated, but were significantly augmented by the NO synthase blocker, nitro-L-arginine. Furthermore, in contrast to normal arteries, the balloon-treated arteries developed marked contractions in response to nitro-L-arginine methyl ester (L-NAME), contractions which could be reversed by L-arginine. The latter contractions and relaxations were not influenced by endothelial removal. These results suggest that although the endothelium quickly regenerates after severe balloon injury, the endothelium-dependent release of nitric oxide remains disturbed. However, the functional data also suggest that angioplasty led to a significant induction of NO synthase in 'non-endothelial' cells of the artery.