Biomedical subjects

E Teiger

Publications and source records attributed to E Teiger.

At least 19 recordsLinked to original sources

PubMed2001

Impact of coronary plaque morphology as assessed by IVUS computer-aided analysis on mechanisms of balloon angioplasty and stenting.

This study was performed in order to quantitate structural coronary plaque modifications after balloon angioplasty and stenting and to evaluate the impact of plaque morphology on the mechanisms of lumen enlargement during angioplasty. Plaque morphology was studied by computer-aided analysis of 60 cross-sectional intravascular ultrasound (IVUS) images of the target lesion in 20 patients undergoing percutaneous coronary angioplasty. Based on a computer-aided video densitometry classification of plaque morphology, three groups of plaques were defined based on the slope value of a fifth polynomial regression of the plaque gray-level distribution. In groups A and B, balloon angioplasty provided significant increases in lumen area (P < 0.0001) and vessel area (P < 0.05) without a reduction in plaque area; neither parameter increased in group C. In group A, stenting was associated with an additional lumen enlargement (P < 0.0001) due to plaque reduction (P < 0.05). In groups B and C, stenting further increased lumen area (P < 0.0001) by improving vessel area (P < 0.001) but without plaque reduction. Balloon angioplasty and stenting provided a significant decrease in plaque area in group A as compared to groups B (P < 0.05) and C (P < 0.01). Finally, vessel area improvement was greater in group B than in groups A (P < 0.01) and C (P < 0.05). The mechanisms underlying lumen enlargement after coronary angioplasty are highly dependent on plaque morphology as defined by an IVUS computer-aided analysis and may differ between balloon angioplasty and stenting.

Angioplasty, Balloon, Coronary↗

PubMed2001

Gene therapy in heart disease.

Application of gene therapy to the field of cardiovascular disorders has been the subject of intensive work over the recent period. Gene therapy for cardiovascular disorders is now fast developing with most therapies being devoted to the consequences (ischemia) rather than the causes of atherosclerotic diseases. Recent human clinical trials have shown that injection of naked DNA encoding vascular endothelial growth factor promotes collateral vessel development in patients with critical limb ischemia or chronic myocardial ischemia. Promising studies in animals have also fueled enthusiasm for treatment of human restenosis by gene therapy, but clinical applications are warranted. Application of gene transfer to other cardiovascular diseases will require the coordinated development of a variety of new technologies, as well as a better definition of cellular and gene targets.

Genetic Therapy↗

PubMed2001

Adenovirus-mediated transfer of the atrial natriuretic peptide gene in rat pulmonary vascular smooth muscle cells leads to apoptosis.

Atrial natriuretic peptide (ANP) exhibits relaxant and growth-inhibiting effects on vascular smooth muscle cells (VSMCs). To obtain ANP gene expression in VSMCs, we built a recombinant adenovirus containing the ANP cDNA controlled by the adenovirus major late promotor (AdMLP-ANP). After pulmonary VSMC treatment with AdMLP-ANP at a multiplicity of infection ranging from 5 to 100 TCID(50)/cell, immunoreactive ANP was detectable in the cell culture medium at a level that reached 101 +/- 27 pmol/well after 2 days. The newly expressed ANP was biologically active, as evidenced by its ability to induce cyclic guanosine monophosphate accumulation in target cells and to mimic the effect of exogenous ANP (10(-8) to 10(-7) mol/L). Cell growth and survival of AdMLP-ANP-infected cells were decreased and were associated with the promotion of VSMC apoptosis. These effects, which occurred at a multiplicity of infection of 10 to 100 TCID(50)/cell, were observed neither in cells infected with the control adenoviral constructs (AdMLP-betaGAL and AdMLP-gD) nor in cells treated with exogenous ANP (10(-7) to 10(-6) mol/L). These results showing VSMC apoptosis in response to ANP gene expression may have important implications for the prevention of vascular remodeling by gene therapy.

Adenoviridae↗

PubMed2000

Physiologically guided angioplasty in support to a provisional stenting strategy: immediate and six-month outcome.

The results of an observational multicenter angioplasty study suggested that stenting decisions may be facilitated by physiologic data. The purpose of this study was to evaluate the early and long-term clinical and angiographic outcome of prospective physiologically guided provisional stenting. Coronary angioplasty using a Doppler-tipped angioplasty guidewire was performed in 68 patients. The provisional stent strategy dictated that balloon angioplasty was to be continued until a coronary flow reserve was >/= 2.2 with a residual diameter stenosis by quantitative coronary angiography < 35%. Repeat coronary angiography was obtained at 6 months. Based on the study criteria, 32/68 patients (47%) received a stent. Compared to the stent group, the angioplasty alone group had higher postprocedural stenosis (23% +/- 13% vs. 13% +/- 10%; P < 0. 05) and lower coronary vasodilatory reserve (2.3 +/- 0.4 vs. 2.6 +/- 0.7; P < 0.05). At follow-up (6.0 +/- 1.5 months), the angiographic restenosis rate was 39% in the angioplasty group and 35% in the stent groups (P = NS). Adverse cardiac events (unstable angina, target lesion revascularization, myocardial infarction, death) occurred in 19% and 18% (P = NS) of the angioplasty and stent patients, respectively. A prospective application of a physiologically guided provisional stent strategy for coronary angioplasty indicated that stent implantation may be required in approximately 50% of patients, an approach that produces similar clinical and angiographic long-term outcomes for stenting and guided angioplasty. These data support a role of coronary physiology as an adjunct in conducting an angioplasty procedure without obligatory stenting.

Adult↗

PubMed2000

Effects of bradykinin on coronary blood flow and vasomotion in transplant patients.

OBJECTIVES: To evaluate the effects of exogenous bradykinin on coronary epicardial and microcirculatory tone in transplant patients (HTXs), and to compare them with the effects of acetylcholine. BACKGROUND: Coronary endothelial dysfunction has been reported to occur early after heart transplantation, most notably when acetylcholine was the endothelium-function marker used. The effects of bradykinin on coronary vasomotion are unknown in HTXs. METHODS: Sixteen HTXs were compared 3.6 +/- 1.7 months after transplantation to seven control subjects. Coronary flow velocity was measured using guide-wire Doppler. Diameters (D) of three segments of the left coronary artery and coronary blood flow (CBF) were assessed at baseline, after 3-min infusions of increasing bradykinin doses (50, 150 and 250 ng/min) then of increasing acetylcholine doses (estimated blood concentrations of 10(-8), 10(-7) and 10(-6) M). RESULTS: Bradykinin induced similar dose-dependent increases in D and CBF in both groups: D was 11 +/- 12%, 19 +/- 14% and 22 +/- 16% (all p < 0.0001), and CBF was 50 +/- 40%, 130 +/- 68% and 186 +/- 77% (all p < 0.0001). Acetylcholine induced significant epicardial vasodilation in control subjects and vasoconstriction in HTX, as well as a marked increase in CBF in both groups. Acute allograft rejection, present in 8 of the 16 HTXs, did not modify responses to bradykinin, but was associated with a smaller CBF increase in response to acetylcholine (p < 0.05). CONCLUSIONS: The coronary vasodilating effects of bradykinin are preserved early after heart transplantation, even in the presence of acute allograft rejection. Although there is an abnormal vasoconstricting response to acetylcholine reflecting endothelium dysfunction, the endothelium remains a functionally active organ in heart transplant recipients.

Acetylcholine↗

PubMed2000

Increased expression of gelatinases and alteration of basement membrane in rat soleus muscle following femoral artery ligation.

Acute severe muscle ischaemia is characterized by significant remodelling of basement membranes of myofibres. It was hypothesized that peripheral artery insufficiency is accompanied by similar muscle extracellular matrix (ECM) changes involving matrix metalloproteinase gelatinases. Using a model of femoral artery ligation, both gelatinase activity and basement membrane component degradation were studied in hindlimb skeletal muscles. SDS-PAGE zymography of muscle homogenates showed that acute moderate ischaemia was followed by a significant transient increase in expression of 72- and 92-kDa gelatinases during 48 h; the latter probably originated from inflammatory cells. In situ zymography showed that this increase occurred chiefly at the periphery of myofibres. Immunolocalization demonstrated 72-kDa gelatinase in interspaces and at the periphery of myofibres, and suggested that this enzyme may explain the gelatinolytic activities found by in situ zymography. Type IV collagen and laminin staining showed that the gelatinase expression increase correlated with dramatic basement membrane component alterations. Our data show that even moderate ischaemia results in significant muscle basement membrane remodelling due to matrix degrading enzymes matrix metalloproteinases (MMP) gelatinases.

Animals↗

PubMed2000

Imbalance between platelet vascular endothelial growth factor and platelet-derived growth factor in pulmonary hypertension. Effect of prostacyclin therapy.

Focal vascular injury and impaired endothelial function are features of pulmonary hypertension (PH) that lead to enhanced platelet endothelial cell interactions. Vascular endothelial growth factor (VEGF) is contained in platelets and released at sites of vascular injury to promote endothelial repair and wound healing in combination with platelet-derived nonspecific mitogens such as platelet-derived growth factor (PDGF). The overall balance between platelet VEGF and PDGF was investigated in 21 patients with primary PH, 8 with secondary PH, and 27 with chronic hypoxemic lung disease (CHLD), as well as in 29 control subjects. Platelet VEGF content was increased in patients with primary and secondary PH as compared with control subjects (518 +/- 89, 675 +/- 156, and 166 +/- 29 fg/10(5) platelets, respectively; p < 0.01), whereas platelet PDGF content was similar in the three groups (31 +/- 2, 36 +/- 4, and 33 +/- 3 pg/10(5) platelets, respectively; NS). Patients treated with a continuous prostacyclin infusion had a higher platelet VEGF but a similar platelet PDGF content as compared with untreated patients. Moderate increases in platelet VEGF and PDGF contents were observed in the CHLD patients. We conclude that patients with primary or secondary PH have an increase in platelet VEGF content, but not in platelet PDGF content, and that their platelet VEGF content increases further in response to prostacyclin infusion. We suggest that imbalance between platelet VEGF and PDGF is beneficial to patients with PH.

Adolescent↗

PubMed2000

Modulation of angiotensin II receptor expression during development and regression of hypoxic pulmonary hypertension.

Lung vessel muscularization during hypoxic pulmonary hypertension is associated with local renin-angiotensin system activation. The expression of angiotensin II (Ang II) AT1 and AT2 receptors in this setting is not well known and has never been investigated during normoxia recovery. We determined both chronic hypoxia and normoxia recovery patterns of AT1 and AT2 expression and distal muscularization in the same lungs using in situ binding, reverse transcriptase/polymerase chain reaction, and histology. We also used an isolated perfused lung system to evaluate the vasotonic effects of AT1 and AT2 during chronic exposure to hypoxia with and without subsequent normoxia recovery. Hypoxia produced right ventricular hypertrophy of about 100% after 3 wk, which reversed with normoxia recovery. Hypoxia for 2 wk was associated with simultaneous increases (P<0.05) in AT1 and AT2 binding (16-fold and 18-fold, respectively) and in muscularized vessels in alveolar ducts (2. 8-fold) and walls (3.7-fold). An increase in AT2 messenger RNA (mRNA) (P<0.05) was also observed, whereas AT1 mRNA remained unchanged. After 3 wk of hypoxia, muscularization was at its peak, whereas all receptors and transcripts showed decreases (P<0.05 versus hypoxia 2 wk for AT1 mRNA), which became significant after 1 wk of normoxia recovery (P<0.05 versus hypoxia 2 wk). Significant reversal of muscularization (P<0.01) was found only after 3 wk of normoxia recovery in alveolar wall vessels. Finally, the AT1 antagonist losartan completely inhibited the vasopressor effect of Ang II in hypoxic and normoxia-restored lungs, whereas the AT2 agonist CGP42112A had no effect. Our data indicate that in lungs, chronic hypoxia-induced distal muscularization is associated with early and transient increases in AT2 and AT1 receptors probably owing to hypoxia- dependent transcriptional and post-transcriptional regulatory mechanisms, respectively. They also indicate that the vasotonic response to Ang II is mainly due to the AT1 subtype.

15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5↗

PubMed1999

[Description and mechanisms of ischemia in atherosclerosis].

The most common clinical manifestations of atherosclerotic disease are ischaemic syndromes related to an imbalance between tissue oxygen demand and supply, as a consequence of reduced blood perfusion. Atherosclerosis may cause either direct luminal arterial narrowing (stable lesion) or acute thrombus formation (unstable lesion). Atherosclerosis in the coronary artery system may manifest in the form of stable or unstable angina, acute myocardial infarction, or other main clinical manifestations of atherosclerosis are: sudden cardiac death; transient ischaemic attack or cerebral infarction in the brain; and intermittent claudication or acute ischaemia of the extremities in the lower limbs.

Angina Pectoris↗

PubMed1999

Prediction of functional recovery of viable myocardium after delayed revascularization in postinfarction patients: accuracy of dobutamine stress echocardiography and influence of long-term vessel patency.

OBJECTIVES: We sought to evaluate dobutamine stress echocardiography (DSE) for predicting recovery of viable myocardium after revascularization with cineangiography as a gold standard for left ventricular (LV) function. We studied the influence of late vessel reocclusion on regional LV function. BACKGROUND: Dobutamine stress echocardiography is a well established evaluation method for myocardial viability assessment. In previous studies the reference method for assessing LV recovery was echocardiography, long-term vessel patency has not been systematically addressed. METHODS: Sixty-eight patients with a first acute myocardial infarction (AMI) and residual stenosis of the infarct related artery (IRA) underwent DSE (mean +/- standard deviation) 21 +/- 12 days after AMI to evaluate myocardial viability. Revascularization of the IRA was performed in 54 patients by angioplasty (n = 43) or bypass grafting (n = 11). Coronary angiography and LV cineangiography were repeated at four months to assess LV function and IRA patency. RESULTS: Sensitivity and specificity of DSE for predicting myocardial recovery after revascularization were 83% and 82%. In the case of late IRA patency, specificity increased to 95%, whereas sensitivity remained unchanged. In the 16 patients with myocardial viability and late IRA patency, echocardiographic wall motion score index decreased after revascularization from 1.83 +/- 0.15 to 1.36 +/- 0.17 (p = 0.0001), and left ventricular ejection fraction (LVEF) increased from 0.52 +/- 0.06 to 0.57 +/- 0.06 (p = 0.0004), whereas in five patients, reocclusion of the IRA prevented improvement of segmental or global LV function despite initially viable myocardium. CONCLUSIONS: Dobutamine stress echocardiography is reliable to predict recovery of viable myocardium after revascularization in postinfarction patients. Late reocclusion of the IRA may prevent LV recovery and influence the accuracy of DSE.

Adult↗

PubMed1999

Coronary blood flow reserve and wall motion recovery in patients undergoing angioplasty for myocardial infarction.

AIMS: The aim of this study was to evaluate the relationship between coronary flow reserve and the recovery of wall motion contractility in patients with recent myocardial infarction. METHODS AND RESULTS: Nineteen patients (55 +/- 8 years) undergoing balloon angioplasty for recent myocardial infarction were studied. After angioplasty, coronary flow reserve was lower in the infarct-related artery than in a reference artery, 2.2 +/- 0.6 and 2.8 +/- 0.7, respectively, P < 0.05. There was no immediate correlation between coronary blood flow reserve measured after angioplasty and wall motion index. There was a negative correlation between coronary flow reserve and the number of necrotic segments (r = -0.43; P0.006). At the 4 month control angiogram, there was a significant increase in both left ventricular ejection fraction (59 +/- 14% vs 51 +/- 13%; P < 0.05) and wall motion index (-0.63 +/- 1.2 vs -1.94 +/- 0.9 units SD, P = 0.005). In patients in whom wall motion improved (> 1 unit SD), the immediate coronary flow reserve was higher (P < 0.05) than in patients without improved wall motion. In this group, the increase in wall motion index was correlated to the coronary blood flow reserve (r = 0.55; P < 0.02). CONCLUSION: These data show that after myocardial infarction, coronary flow reserve is associated with myocardial viability.

Aged↗

PubMed1999

Local gene delivery within the media of rabbit iliac arteries by using the infiltrator intramural delivery device.

Percutaneous transluminal angioplasty continues to be limited by restenosis. Prevention of restenosis is now focusing on local delivery of therapeutic agents, such as proliferation-inhibiting genes, directly to the site of arterial injury. We evaluated use of the Infiltrator catheter (IVT, San Diego, CA. U.S.A.) for gene delivery within the arterial media. The goals of our study were to evaluate the histologic effects of the injection and the suitability of the Infiltrator catheter for local delivery of viral therapy. We injected the femoral arteries of 21 New Zealand White rabbits. Six animals were used for an evaluation of the intramural distribution of dextran/rhodamine injected via the Infiltrator catheter. In seven animals, injection site histology and in vitro vasoreactivity were studied after an injection of saline. In the remaining eight animals, a replication-deficient adenovirus encoding for the firefly luciferase gene (Ad RSVLuc) was injected, and luciferase activity was quantified 3 and 8 days later. After injection via the Infiltrator catheter, the fluorescent tracer was distributed throughout the entire circumference and width of the arteries. Histologic examination showed minimal damage with partial endothelial abrasion and disruption of the internal elastic lamina confined to the penetration sites. In vitro endothelium-dependent vasodilation was present at a reduced level after injection via the Infiltrator (maximal endothelium-dependent acetylcholine-induced relaxation, 51.5 +/- 7.4% vs. 23.8 +/- 14.6%; p < 0.05). Significant luciferase expression was found in all the arteries, with a significant increase from day 3 to day 8 (5,392.5 +/- 2,300 vs. 2,012 +/- 471 cpm/mg; p < 0.05). These data obtained in a rabbit iliac artery model show that the Infiltrator catheter is an efficient and safe local intramural delivery device that provides significant transgene expression in the arterial wall without causing significant structural damage.

Adenoviridae↗

PubMed1999

[Ultrasonic imaging of coronary atherosclerosis].

Intra-coronary ultrasonography (ICV) is a technique for in vivo study of the different layers of the arterial wall, the site of atherosclerosis. A qualitative analysis of the composition of the plaque can predict its potential evolutivity (chronic with slow progression or at risk of rupture and causing acute thrombosis) and its response to different types of angioplasty, which could eventually become and essential factor in the choice of appropriate therapeutic strategy. Analysis of the results of B mode ultrasonic scanning has provided correlations with the histological composition of the arterial wall, validating the method and opening up the field of tissue characterisation which hitherto had been limited by the absence of sufficiently reliable, accurate and reproducible quantitative parameters. Magnetic resonance imaging (MRI) is a complementary, non-invasive tool for tissue analysis because its sensitivity to the biophysical and biochemical properties of tissues which makes it a promising method of morphological and functional imaging. Other methods of imaging atheromatous plaques include angioscopy and optic coherence tomography which have also contributed to the improvement in our knowledge of atherosclerosis. These methods of imaging which are slowly overcoming their limitations provide documents which ressemble more and more the histological appearances. Intracoronary ultrasonography is the most promising method and raises hopes that one day we shall be able to predict the outcome and anticipate the risk of rupture of atherosclerotic plaques.

Coronary Artery Disease↗

PubMed1999

[Intra-coronary ultrasonography during angioplastic procedures].

Thanks to miniaturization and constant improvement of technologies, intracoronary ultrasound (ICUS) progressively takes its place as the best tool to accurately analyze arterial wall structure. However, its routine use during interventional procedures remains limited. ICUS provides precious informations, complementary to angiography, and guide interventional procedures on the basis of a more accurate analyze of the components of the plaque, thus improving their success rate. Since its use favorized the understanding of the different devices mechanisms (angioplasty, stents, directional and rotational atherectomy), ICUS contributed to reduce the incidence of their complications. Many studies have emphasized ICUS interest during these procedures: their results seem to be significantly improved by the way of prompting the operator to adopt an aggressive strategy (additional inflations using high pressures, combination of different techniques...) which tend to reduce the complication rate and the restenosis incidence. Actually, the restenosis rate was in all these studies [OARS (29%), ABACAS (21%) and MUSIC (8.3%)] directly associated to ICUS parameters measured immediately after treatment, particularly the residual plaque burden. Whether its use, that engender substantial cost, cannot be systematic, trained centers will probably demonstrate that a rational and suitable use lead to adopt optimal strategies and achieve improved results.

Angioplasty, Balloon, Coronary↗

PubMed1999

[Coronary microcirculation. Physiologic and pathologic aspects].

The coronary circulation has a protective regulation system which, in extreme haemodynamic conditions, compensates increased myocardial oxygen demand. The coronary reserve, based on this concept defines the capacity of the system to increase flow temporally, and, thereby, myocardial oxygen supply. The introduction of new methods of investigating the coronary microcirculation has enabled the study of this phenomenon in several cardiovascular pathologies. Two types of investigation are used currently for studying the coronary microcirculation: 1) invasive methods, especially the recently developed intracoronary Doppler and pressure guide, 2) non-invasive methods, and, in particular, contrast echocardiography, position emission tomography and magnetic nuclear resonance. These investigations allow measurement of the coronary reserve or the assessment of the myocardial consequences of abnormalities of the microcirculation. Some workers use these methods to investigate pathological coronary microcirculation in different cardiomyopathies, in the presence of different cardiovascular risk factors (hypertension, diabetes, smoking, hypercholesterolaemia) and after cardiac transplantation.

Coronary Circulation↗

PubMed1999

Coronary microcirculation and cardiovascular pathology.

The recent arrival of new techniques for exploring the coronary microcirculation has facilitated assessment of both the incidence and consequences of disorders of this network in a large number of cardiovascular diseases. The microcirculation is affected in numerous cardiomyopathies in the presence of different cardiovascular risk factors and also following cardiac transplantation. Dysfunction of the microcirculation may correspond to a reduction in the surface of the maximum section of coronary arterioles, which involves multiple mechanisms, although this phenomenon does not appear to play a role in ischaemic heart disease. Reduced coronary flow is most frequently related to vascular rarefaction of multifactorial origin, including greater or lesser degrees of intimal proliferation, perivascular fibrosis, hypertrophy of the media and extrinsic compression.

Cardiovascular Diseases↗

PubMed1999

Coronary microcirculation and cardiovascular pathology.

Cardiovascular Diseases↗

PubMed1999

[Percutaneous suture of femoral artery after diagnostic coronary angiography].

UNLABELLED: Complete local haemostasis after femoral artery catheterization can be performed using percutaneous suture devices. To evaluate efficacy and safety of these systems after diagnostic coronary angiography, we performed a randomized study where patients were treated either with a manual compression (group C) or a percutaneous suture (group T). Fifty patients were included in each group. Patients in group C had to rest at bed during 24 hours while patients in group T had to stand up and walk immediately after complete haemostasis was obtained. All angiographies were performed using a 6 F sheath. All patients had a clinical evaluation and an echography 24 hours after the procedure and all were reached by phone call at 15 days. Both groups were similar in term of age, sex ratio, diabetes, height and weight. Complete haemostasis was obtained in 20 +/- 6 mn in group C and in 6 +/- 10 mn in group T (p < 0.001). Device technical success rate in group T was 90%; 70% of patients walked immediately down the X ray table and 90% before the 4 hours. Ambulation delay was 24 +/- 5 hours in group C and 5 +/- 9 hours in group T (p < 0.0001). Clinical and echographic complications rate were similar in both groups (8%). There was no post procedure complication in group T (especially after ambulation) nor at the phone call. CONCLUSION: Femoral artery percutaneous suture after diagnostic coronary angiography is as safe and working than manual compression. It allows an immediate mobilization and ambulation, far earlier than compression.

Aged↗