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Biomedical subjects

G Breithardt

Publications and source records attributed to G Breithardt.

At least 127 records · Page 7Linked to original sources
PubMed1999

[Medicamentous prevention after electric cardioversion of chronic atrial fibrillation. Goals and design of the PAFAC Study].

Atrial fibrillation (AF) is the most frequent cardiac arrhythmia. However, despite manifold publications reflecting numerous clinical trials about treatment of AF, the management of this arrhythmia is still under controversial discussion, in daily clinical work as well as in research. The present study concentrates on three major questions: 1. How frequent are recurrences of AF in long-term follow-up? Most of the previous studies used the occurrence of symptoms as a surrogate parameter for recurrences of AF, despite the expected high rate of asymptomatic relapses. In the present study a daily transtelephonic ECG transmission enables a rhythm monitoring independent of symptoms. 2. Is the frequency of AF recurrences significantly reduced by antiarrhythmic medication? A direct comparison of class I and III antiarrhythmic drugs, which still are most frequently used for this indication, and of placebo will answer this question. 3. How safe is the long-term treatment for the prevention of AF recurrences with special respect to proarrhythmic effects? The daily transtelephonic ECG transmission enables a quantitative and qualitative monitoring of tachy- and bradyarrhythmias independent of symptoms. Additionally, the daily analysis of ECG measures may detect parameters predicting subsequent life threatening arrhythmias. The study design provides a prospective, randomised, double-blind, placebo controlled, multicenter parallel group comparison. In Germany and in the Czech Republic about 90 hospitals will include 900 patients with documented chronic AF, age 18 to 80 years, if they are eligible for electrical cardioversion without concomitant antiarrhythmic drug therapy and if they are anticoagulated for at least three weeks prior to inclusion. Neither the size of the left atrium nor the duration of chronic AF are exclusion criteria. A few hours after successful electrical cardioversion the patients are randomised either to sotalol (2 x 160 mg) or quinidine + verapamil (3 x 160 mg + 3 x 80 mg) or placebo. Starting at the day after cardioversion, the patient is asked to record and transmit electrocardiograms of one minute duration at least once a day using his personal transtelephonic ECG recording unit (Tele-ECG recorder, credit card size), in case of symptoms as often as necessary. The ECGs can be transmitted at any time by any regular phone without additional equipment using a toll free number. A custom made, computer based, fully automated receiving centre is handling the patient calls interactively with voice control, including a voice recording of the patient's symptoms. The ECG tracings and the patient's voice messages are subsequently computer based analysed by experienced technicians. All ECG measures are stored in a database. In case of AF recurrence, any other relevant arrhythmia or additional abnormalities (e.g. QT prolongation) the correspondent hospital is immediately informed by fax. In case of AF recurrence, a subsequent Holter recording discriminates in paroxysmal and permanent AF. Study medication is ended if either permanent AF or the third episode of paroxysmal AF are detected or after 12 months of follow-up. Regular follow-up visits are performed monthly. Major endpoints are the time to first recurrence of AF or the time to death, secondary parameters are the number of AF recurrences, the time to end of medication and AF related symptoms. The recruitment started in the last days of 1996. Until the end of June 1998, 424 patients have been randomised. It is expected to end recruitment in spring 1999 and to close the study in spring 2000. Final results will be available in summer 2000.

Adolescent↗
PubMed1999

The LQT syndromes--current status of molecular mechanisms.

Our knowledge on the molecular genetics of inherited cardiac arrhythmias is very recent in comparison to the advances of genetics achieved in other inherited cardiac disorders. This is related to the high mortality and early disease onset of these arrhythmias resulting in mostly small nucleus families. Thus, traditional genetic linkage studies that are based on the genetic information obtained from large multi-generation families were made difficult. In 1991, the first chromosomal locus for congenital long-QT (LQT) syndrome was identified on chromosome 11p15.5 (LQT1 locus) by linkage analysis. Meanwhile, the disease-causing gene at the LQT1 locus (KCNQ1), a gene encoding a K+ channel subunit of the IKs channel, and three other, major genes, all encoding cardiac ion channel components, have been identified. Taken together, LQT syndrome turned out to be a heterogeneous channelopathy. Moreover, the power of linkage studies to reveal the genetic causes of the LQT syndrome was also important to identify unknown but fundamental channel components that contribute to the ion currents tuning ventricular repolarization. In-vitro expression of the altered ion channel genes demonstrated in each case that the altered ion channel function produces prolongation of the action potential and thus the increasing propensity to ventricular tachyarrhythmias. Since these ion channels are pharmacological targets of many antiarrhythmic (and other) drugs, individual and potentially deleterious drug responses may be related to genetic variation in ion channel genes. Very recently, also in acquired LQT syndrome, which is a frequent clinical disorder in cardiology a genetic basis has been proposed in part since mutations in LQT genes have been specifically found. The discovery of ion channel defects in LQT syndrome represents the major achievement in our understanding and implies potential therapeutic options. The knowledge of the genomic structure of the LQT genes now offers the possibility to detect the underlying genetic defect in 80-90% of all patients. With this specific information, containing the type of ion channel (Na+ versus K+ channel) and electrophysiological alteration by the mutation (loss-of-function versus change-of-function mutation), gene-directed, elective drug therapies have been initiated in genotyped LQT patients. Based on preliminary data, that were supported by in vitro studies, this approach may be useful in recompensating the characteristic phenotypes in some LQT patients. Mutation detection is a new diagnostic tool which may become of more increasing importance in patients with a normal QTc or just a borderline prolongation of the QTc interval at presentation. These patients represent approximately 40% of all familial cases. Moreover, LQT3 syndrome and idiopathic ventricular fibrillation are allelic disorders and genetically overlap. In both mutations in the LQT3 gene SCN5A encoding the Na+ channel alpha-subunit for INa have been reported. Thus, the clinical nosology of inherited arrhythmias may be reconsidered after elucidation of the underlying molecular bases. Meanwhile, genotype-phenotype correlations in large families are on the way to evaluate intergene, interfamilial, and intrafamilial differences in the clinical phenotype reflecting gene specific, gene-site specific, and individual consequences of a given mutation. LQT syndrome is phenotypically heterogeneous due to the reduced penetrance and variable expressivity associated with the mutations. This paper discusses the current data on molecular genetics and genotype-phenotype correlations and the implications for diagnosis and treatment.

Chromosome Mapping↗
PubMed1999

[Brugada-Brugada syndrome. An atypical case].

The Brugada-Brugada syndrome is a rhythmologic disorder which can be diagnosed because of typical ECG criteria. A high-take off descending ST segment localized to the right chest leads, associated with right bundle branch block and ventricular fibrillation or syncopes are characteristic of the syndrome. ECG alterations in the right precordial leads were recorded in a 47 year old female patient who was admitted to hospital because of enteritis and associated syncope. The ECG alterations were initially not realized as Brugada-Brugada syndrome. Because of "recognizing" comparable ECG alterations during a congress lecture, the diagnosis was made. The patient was treated with an ICD.

Ajmaline↗
PubMed1999

Extracardiac contributions to chest pain perception in patients 6 months after acute myocardial infarction.

OBJECTIVES: The amount of perceived anginal pain in patients after infarction deserves the attention of the physician. This study sought to identify the modulating influence of extracardiac factors on persistent angina pectoris after myocardial infarction. METHODS AND RESULTS: A total of 552 male survivors of acute myocardial infarction (age 29 to 65 years, median 54 years) were followed for a period of 6 months; the affective state was assessed immediately after the acute event. The prognostic importance of postinfarction depression on chest pain perception was evaluated 6 months after the cardiac event in 376 patients. After the 6-month follow-up period, 199 (53%) of the patients with myocardial infarction had angina pectoris. Somatic risk factors and electrocardiographic data at initial testing did not contribute to the risk of having chest pain. However, patients with high levels of depression at initial testing had an almost 3-fold risk of having angina pectoris 6 months after the index event. Older age, lower social class status, and preinfarction angina were also significantly related to angina pectoris at the end of the study. Patients who were pain free before the index infarction reported significantly more symptoms of chest pain at the study end point (P </=.02), when they had moderate to high degrees of postinfarction depression. In the logistic regression model, depression, then followed by preinfarction angina pectoris and low social class index, contributed significantly to the prediction of follow-up angina pectoris. CONCLUSIONS: The results of this study add evidence to the hypothesis that the perception of chest pain may be triggered not only by the nociceptive stimulation of the ischemic heart but also by extracardiac sources. Depressive mood state, when concomitant with cardiac disease, is shown to intensify perceived chest pain.

Adult↗
PubMed1999

A prognostic computer model to individually predict post-procedural complications in interventional cardiology: the INTERVENT Project.

AIMS: The purpose of this part of the INTERVENT project was (1) to redefine and individually predict post-procedural complications associated with coronary interventions, including alternative/adjunctive techniques to PTCA and (2) to employ the prognostic INTERVENT computer model to clarify the structural relationship between (pre)-procedural risk factors and post-procedural outcome. METHODS AND RESULTS: In a multicentre study, 2500 data items of 455 consecutive patients (mean age: 61.1+/-8.3 years: 33-84 years) undergoing coronary interventions at three university centres were analysed. 80.4% of the patients were male, 16.7% had unstable angina, and 5.1%/10.1% acute/subacute myocardial infarction. There were multiple or multivessel stenoses in 16.0%, vessel bending >90 degrees in 14.5%, irregular vessel contours in 65.0%, moderate calcifications in 20.9%, moderate/severe vessel tortuosity in 53.2% and a diameter stenosis of 90%-99% in 44.4% of cases. The in-lab (out-of-lab) complications were: 0.4% (0.9%) death, 1.8% (0.2%) abrupt vessel closure with myocardial infarction and 5.5% (4.0) haemodynamic disorders. CONCLUSION: Computer algorithms derived from artificial intelligence were able to predict the individual risk of these post-procedural complications with an accuracy of >95% and to explain the structural relationship between risk factors and post-procedural complications. The most important prognostic factors were: heart failure (NYHA class), use of adjunctive/alternative techniques (rotablation, atherectomy, laser), acute coronary ischaemia, pre-existent cardiac medication, stenosis length, stenosis morphology (calcification), gender, age, amount of contrast agent and smoker status. Pre-medication with aspirin or other cardiac medication had a beneficial effect. Techniques, such as laser angioplasty or atherectomy were predictors for post-procedural complications. Single predictors alone were not able to describe the individual outcome completely.

Adult↗
PubMed1999

Effects of lovastatin on progression of non-dilated and dilated coronary segments and on restenosis in patients after PTCA. The cholesterol lowering atherosclerosis PTCA trial (CLAPT).

OBJECTIVES: The Cholesterol Lowering Atherosclerosis PTCA Trial (CLAPT) is a prospective, randomized trial with blinded angiographic end-points to assess the effect of 2-year's treatment with lovastatin initiated 4 weeks prior to PTCA, compared to usual care on non-dilated coronary segments and on dilated coronary lesions in male patients with total cholesterol between 200 and 300 mg. dl(-1)who underwent elective PTCA. METHODS AND RESULTS: Two hundred and twenty six patients were randomized 4 weeks prior to PTCA to special care (diet plus lovastatin n=112) or usual care (diet; n=114). One hundred and ninety-nine patients underwent PTCA at baseline and were finally included in the study. Quantitative coronary angiographic assessment was performed on blinded cinefilms at baseline (PTCA) and repeated after 4 and 24 months in 91% and 81% of the patients. The primary end-point was a change in the mean segment diameter of non-dilated segments. The mean lovastatin dose was 33 mg. day(-1). Total- and LDL-cholesterol decreased by 21% and 29% in the special care group and by 7% and 11% in the usual care patients. After 2 years, the mean segment diameter of non-dilated segments decreased by 0.03 mm in the usual care group and 0.004 mm in the special care group (P=0.27). The decrease in the mean segment diameter of dilated lesions was 0.17 mm (usual care) and 0.06 mm (special care) (P=0.04) after 4 months; 0.16 mm (usual care) and 0. 002 mm (special care) after 24 months, respectively (P=0.05). In both groups, the mean segment diameter of dilated lesions increased between 4 and 24 months after PTCA compared to a decrease in mean segment diameter of non-dilated segments (P<0.05). Restenosis (>50% diameter stenosis at follow-up) occurred in 28.4% of usual care and 22.2% of special care patients (P=0.17). CONCLUSIONS: Lovastatin reduced the progression of dilated lesions in men with elective PTCA. Independent of treatment allocation, the dilated lesions regressed and the non-dilated segments progressed during the study follow-up. Four weeks of pre-treatment with lovastatin did not influence the rate of restenosis. Lovastatin had no statistically significant effect on non-dilated segments.

Angioplasty, Balloon, Coronary↗
PubMed1999

Radiofrequency catheter ablation of accessory pathways. Outcome and use of antiarrhythmic drugs during follow-up.

AIMS: The purpose of this study was to assess the acute and long-term success of accessory pathway ablation in a single large-volume centre, concentrating on long-term recurrences and the clinical use of antiarrhythmic drugs. METHODS AND RESULTS: A total of 519 consecutive patients (mean age 40+/-14 years) underwent radiofrequency ablation of manifest or concealed accessory pathways. The patients were seen in the hospital or by the referring physician at 6 and 12 months. Long-term follow-up information was obtained by questionnaire. Pathway conduction was abolished in 476 cases (91.7%). 'Redo' procedures, due to recurrence, were performed in 38 patients (7.3%) and were successful in 30 (78.9%). Follow-up data were obtained from 454 patients (87.5%) with a follow-up duration of 22. 6+/-12.4 months. Among the 398 patients with successful ablations who responded to the questionnaire, 340 (85.4%) were asymptomatic with only 10.6% taking antiarrhythmic drugs. An additional 20 patients (5.0%) had symptoms suspicious of recurrence. In total, 66 out of 398 successfully treated patients (16.6%) were taking antiarrhythmic drugs. Twenty-three out of 56 (41.1%) patients with failed ablations were asymptomatic, 12 of whom (21.4% of patients with failed ablations) had not been administered antiarrhythmic drugs. In the total group of 454 patients with ablation attempts and available follow-up data, 99 (21.8%) were still taking antiarrhythmic drugs during follow-up. CONCLUSIONS: Patients with successful ablation of accessory pathways show excellent long-term results. However, 17% of successfully treated patients were still taking antiarrhythmic drugs during the period of long-term follow-up. On the other hand, 21% of patients with failed ablations were symptom-free without antiarrhythmic drugs. On an intention-to-treat basis, 22% of the patients with ablation attempts were still taking antiarrhythmic drugs during follow-up.

Adolescent↗
PubMed1999

Evaluation of antiarrhythmic drug efficacy in patients with an ICD. Unlimited potential or replete with complexity and problems?

A report from a Study group, proposed by A. J. Camm, London, of the Working Groups on Arrhythmias and Cardiac Pacing of the European Society of Cardiology; co-sponsored by the North American Society of Pacing and Electrophysiology. The Study Group was convened on 29 August 1997 at Saltsjöbaden, near Stockholm. The meeting was chaired by A. J. Camm, London, and C. M. Pratt, Houston. Based on the presentation and discussions, a first draft of the documents was prepared by C. Pratt and J. Camm which was then circulated to all members three times for their review. All members of the Study Group approved the final manuscript. This report represents the opinion of the members of this Study Group and does not necessarily reflect the official position of either society.The meeting of the Study Group was made possible by unrestricted educational grants from Medtronic, Guidant, Proctor & Gamble, Berlex and Sanofi.Also, presented, in part, at the Cardio-Renal Drugs Advisory Board meeting of the Food and Drug Administration, Bethesda, Maryland, on 30 April 1999.

Anti-Arrhythmia Agents↗
PubMed1999

Multiple hardware complications in a patient with an ICD.

Hardware-related complications in implantable cardioverter/defibrillators (ICD) are still a common problem. Identifying underlying reasons becomes more and more difficult as the complexity of ICD systems increases. We report a patient with a dual chamber ICD (DDD-ICD) who suffered multiple complications. These included: ventricular oversensing causing inappropriate shocks and episodes of asystole; an insulation defect resulting in ineffective shocks as a consequence of a short circuit between the active can device and a defective high voltage cable; and device dysfunction requiring several hospitalizations and operative system revisions.

Aged↗
PubMed1999

Absence of circulating microemboli in patients with lone atrial fibrillation.

Atrial fibrillation (AF) is a well-recognized independent risk factor of ischemic stroke. The aim of this study was to investigate the amount of microembolic signals (MES) in 15 patients with 'lone' AF representing the subgroup of AF patients with the lowest lifelong risk of stroke. All patients had been put on effective anticoagulation due to a scheduled electric cardioversion. Additional cardiac and arterial sources of embolism were excluded by echocardiography and extracranial color-coded duplex sonography of the carotid arteries. Unilateral one-hour transcranial Doppler monitorings revealed complete absence of MES in this series. This observation fits the concept that the amount of microembolisation is related to the risk of manifest thromboembolism. Further studies on this patient group treated with less intensive antihemostatic therapy should be undertaken to define more clearly the disease-specific microembolic activity.

Aged↗
PubMed1999

Evaluation of antiarrhythmic drug efficacy in patients with an ICD: unlimited potential or replete with complexity and problems?

There are a number of novel ways in which implantable cardioverter defibrillator (ICD) endpoints can be used in clinical trials to evaluate antiarrhythmic drugs. The advances in ICD technology (storage, retrieval, and accurate interpretation of ICD electrograms) expand the potential to include the use of an ICD endpoint as a clinical surrogate for sudden death. The ICD also provides the necessary safety net to test new drugs. The frequent need for antiarrhythmic drugs in patients already fitted with an ICD (e.g., for atrial fibrillation) necessitates knowledge of the drugs' effect on defibrillator threshold. There are interpretative problems and challenges associated with all types of ICD trials. A particular difficult issue is the degree to which the results of data on antiarrhythmic drug efficacy and safety acquired in the context of an ICD endpoint trial might be extrapolated to patient populations in which the device is not used. These and other challenging issues are discussed, with the goal of enhancing the design and interpretation of clinical trials featuring ICD endpoints.

Anti-Arrhythmia Agents↗
PubMed1999

Intraoperative radiofrequency ablation of chronic atrial fibrillation: a left atrial curative approach by elimination of anatomic "anchor" reentrant circuits.

INTRODUCTION: The percutaneous approach to radiofrequency (RF) catheter ablation for curative treatment of atrial fibrillation (AF) is an investigational technique, and the optimal composition of lesion lines is unknown. We tested an intraoperative RF ablation concept with elimination of left atrial anatomic "anchor" reentrant circuits. METHODS AND RESULTS: In 12 patients with an indication for valve surgery and chronic AF, a right atrial-transseptal approach was chosen for access to the left atrium. AF had been present for 4.3 +/- 3.9 years; the left atria measured 56 +/- 7 mm. Under direct vision, contiguous lesion lines were placed endocardially with temperature-guided RF energy applications for treatment of AF with a specially designed probe. The lesion lines were placed between the mitral annulus and the left lower pulmonary vein, further to the left upper pulmonary vein, from there to the right upper pulmonary vein, and finally to the right lower pulmonary vein. The antiarrhythmic ablation procedure lasted 19 +/- 4 minutes. One patient died postoperatively of low cardiac output. During follow-up of 11 +/- 6 months, chronic AF was ablated successfully in 9 of 11 patients (82%). Six patients were in stable sinus rhythm or intermittent pacemaker rhythm, and three patients were in sinus rhythm with intermittent atypical atrial flutter. CONCLUSIONS: Intraoperative RF energy application for induction of contiguous lesion lines is feasible. Elimination of anatomically defined "anchor" reentrant circuits within the left atrium prevented chronic AF in > 80% of the patients treated. Intraoperative validation of lesion line concepts for curative treatment of AF may be transferred to percutaneous ablation techniques.

Aged↗
PubMed1999

Efficacy and safety of the initial use of stability and onset criteria in implantable cardioverter defibrillators.

INTRODUCTION: Inappropriate therapies are the most frequent adverse event in patients with implantable cardioverter defibrillators (ICDs). Most ICDs offer a stability criterion to discriminate ventricular tachycardia (VT) from atrial fibrillation and an onset criterion to discriminate VT from sinus tachycardia. The efficacy and safety of these criteria, if used immediately after implantation, is unknown. METHODS AND RESULTS: In a case control study, 87 patients in whom stability and onset criteria had been activated immediately after ICD implantation were matched to 87 patients in whom these criteria had not been activated. The groups were matched for known predictors of inappropriate therapies. With stability and onset criteria off, 24 patients (28%) received inappropriate therapies due to atrial fibrillation (n = 14) or sinus tachycardia (n = 11); with stability and onset on, only 11 patients (13%) were treated by the ICD due to atrial fibrillation (n = 5) or sinus tachycardia (n = 7) (log rank: P = 0.029). Five patients suffered inappropriate therapies despite the fact that onset (n = 4) or stability (n = 1) criteria were not fulfilled once tachycardias continued for a prespecified duration. Only one patient experienced a failure to detect VT due to the onset criterion; none because of stability. CONCLUSION: The immediate use of stability and onset criteria after ICD implantation reduces inappropriate therapies due to atrial fibrillation and sinus tachycardia. Because of the potential for underdetection of VT, this approach should be limited to tachycardia rates hemodynamically tolerated by the patient.

Atrial Fibrillation↗
PubMed1999

Transient local changes in right ventricular monophasic action potentials due to ajmaline in a patient with Brugada Syndrome.

A 48-year-old patient with recurrent episodes of palpitations and syncope presented with transient ST segment elevation in the right precordial ECG leads. Structural heart disease was excluded. No arrhythmias were inducible by programmed ventricular stimulation. Parallel to ST elevation after intravenous ajmaline, a gradual and reversible delay in the upstroke of right ventricular (RV) monophasic action potentials (MAPs) occurred that was most marked in the RV outflow tract and nearly absent at right free-wall recordings. Ajmaline led to a cycle length-dependent increase in RV dispersion of repolarization. Thus, right endocardial MAPs may demonstrate regionally different action potential changes that may contribute to the ECG changes in Brugada syndrome.

Action Potentials↗
PubMed1999

Systemic inflammatory parameters in patients with atherosclerosis of the coronary and peripheral arteries.

Plasma concentration of markers of inflammation are increased in patients with atherosclerosis. However, it is unclear whether the pattern and magnitude of this increase vary with the site and extent of disease. In 147 patients undergoing semiquantitative coronary angiography, we measured the acute-phase reactants C-reactive protein (CRP) or serum amyloid A (SAA); the proinflammatory cytokine interleukin 6 (IL-6); the active and total fractions of the anti-inflammatory cytokine transforming growth factor-beta (TGF-beta); the macrophage activation marker neopterin; and the infection marker procalcitonin. Compared with 62 patients without either coronary artery disease (CAD) or peripheral artery disease (PAD), 57 patients with CAD but no PAD showed greater median CRP (0. 4 versus 0.2 mg/dL, P=0.004) and IL-6 (3.8 versus 1.6 pg/mL, P=0. 007) levels and a lower level of active-TGF-beta (57 versus 100 ng/mL, P=0.038). Moreover, CRP, IL-6, and neopterin levels showed a positive and the active TGF-beta level a negative correlation with the extent of coronary atherosclerosis. Compared with these 57 patients with CAD alone, 15 patients with PAD and CAD had higher median levels of SAA (17 versus 7 mg/mL, P=0.008), IL-6 (12 versus 4 pg/mL, P=0.002), neopterin (14 versus 11 mg/dL, P=0.006), and total TGF-beta (11834 versus 6417 ng/L, P=0.001). However, these strong univariate associations of markers of inflammation and atherosclerosis were lost in multivariate analysis once age, sex, and high density lipoprotein cholesterol or fibrinogen were taken into account. Increased plasma levels of CRP, SAA, IL-6, TGF-beta, neopterin, and procalcitonin constitute an inflammatory signature of advanced atherosclerosis and are correlated with the extent of disease but do not provide discriminatory diagnostic power over and above established risk factors.

Acute-Phase Reaction↗
PubMed1999

Cholesterol-induced changes of type VIII collagen expression and distribution in carotid arteries of rabbit.

Lipoproteins play a major role in cardiovascular disease and atherosclerosis. In the vascular wall, they strongly influence the organization of extracellular matrix. The present study set out to investigate the changes in the extracellular matrix of the vessel wall induced by atherogenic diet, focusing on type VIII collagen, a vascular collagen that has not previously been investigated in detail. The influence of cholesterol diet on the expression, distribution, and deposition of type VIII collagen was examined in carotid arteries of New Zealand White rabbits. Carotid arteries of rabbits receiving diet supplemented with 1% cholesterol for 6 weeks and those on the same regimen followed by normal chow for 1 day, 10 days, 5 weeks, and 12 weeks were studied and compared with controls not exposed to the cholesterol diet. Carotid arteries of normocholesterolemic rabbits contained type VIII collagen-expressing cells in all layers, with focal accumulations of expressing cells in the subendothelial areas, the outer medial zone, and the adventitia. In response to cholesterol diet, type VIII collagen synthesis was reduced in media and adventitia and the distribution patterns changed. Expressing cells were found predominantly in the endothelium, and type VIII collagen accumulated in the intimal space. Immunogold labeling for electron microscopy revealed that type VIII collagen in the intima is associated with microfibrils extending from the internal elastic lamina. Withdrawal of cholesterol resulted in reestablishment of the normal distribution pattern. Northern and Western blot analyses supported the immunoconfocal and in situ hybridization data, demonstrating decreased type VIII collagen expression in response to cholesterol diet and progressive recovery to normal levels with time after withdrawal of cholesterol. Our study demonstrates that type VIII collagen is modulated in the presence of cholesterol. The data indicate that type VIII collagen is specifically remodeled during early experimental atherosclerosis, implying a role for this extracellular matrix component in neointimal growth.

Animals↗