Catheter ablation of ventricular tachycardia in 136 patients with coronary artery disease: results and long-term follow-up.

OBJECTIVES: This study attempted to determine the feasibility and long-term efficacy of catheter ablation by means of either radiofrequency or direct current energy in a selected group of patients with coronary artery disease. BACKGROUND: Catheter ablation of ventricular tachycardia has proved to be highly effective in patients with idiopathic and bundle branch reentrant ventricular tachycardia. In patients with coronary artery disease and recurrent sustained ventricular tachycardia resistant to medical antiarrhythmic management, the value of catheter ablation has not yet been established. METHODS: One hundred thirty-six patients with coronary artery disease and one configuration of monomorphic sustained ventricular tachycardia underwent radiofrequency (72 patients) or direct current catheter ablation (64 patients). The mapping procedure to localize an adequate site for ablation included pace mapping during sinus rhythm, endocardial activation mapping, identification of isolated mid-diastolic potentials and pacing interventions during ventricular tachycardia. RESULTS: Primary success was achieved in 102 (75%) of 136 patients (74% of 72 undergoing radiofrequency and 77% of 64 with direct current ablation). Complications were noted in 12% of patients. During a mean (+/- SD) follow-up period of 24 +/- 13 months (range 3 to 68), ventricular tachycardia recurred in 16% of patients. CONCLUSIONS: Catheter ablation of ventricular tachycardia in coronary artery disease is feasible in patients with one configuration of monomorphic sustained ventricular tachycardia. There is no significant difference with respect to the type of energy applied. The follow-up data show that in a selected group of patients with coronary artery disease, catheter ablation offers a therapy alternative.

Copper-induced inflammatory reactions of rat carotid arteries mimic restenosis/arteriosclerosis-like neointima formation.

The pathogenesis of arteriosclerosis and of restenosis after angioplasty is linked with an inflammatory and fibroproliferative response of the arterial tissue. We have induced a non-infectious inflammation by implanting a silicon-copper cuff around rat carotid arteries. The copper ions released from the oxidized copper initiate and mimic all morphological features of post-angioplasty restenotic and arteriosclerotic lesions. The copper-induced lesions were analyzed by electron and light microscopy, immunohistochemical methods and quantified by morphometry. During the first phase of copper-induced tissue reaction (3 days), macrophages and polymorphonuclear leucocytes invaded through the endothelium, accumulated in the subendothelial space and triggered the proliferation of smooth muscle cells which then migrated from the tunica media through the lamina elastica interna into the intima. Within 3 weeks, the accumulated smooth muscle cells, macrophages, leucocytes and newly synthesized extracellular matrix formed a circular mostly eccentric fibrotic thickening that narrows the vessel lumen by 30-40%. The accompanying structural disorganization of the medial layer led to focal rupture and aneurysm-like dilatation of the vessel wall in 3 of 11 animals between day 20 and 43. The neointima progressively increased in thickness over time leading to corresponding reduction of the vessel lumen. The carotid arteries of control animals and animals treated with copper-free silicon cuffs showed no abnormal pathological appearance. Our results show that inflammation-inducing agents can contribute to and simulate restenosis- and arteriosclerosis-like lesions and that the copper-cuff model may be useful in the exploration of new approaches to intervention.

Detection of missense mutations in the genes for lipoprotein lipase and hepatic triglyceride lipase in patients with dyslipidemia undergoing coronary angiography.

Coronary events have a close association with a low HDL/hypertriglyceridemia (LHDL/HTG) phenotype. As enzymes that hydrolyze triglyceride-rich lipoproteins are associated with a modulation of both HDL cholesterol and triglycerides, we have tested the hypothesis that mutations in the genes encoding lipoprotein lipase (LPL) or hepatic lipase (HTGL) may contribute to the formation of coronary atherosclerosis and, thus, of coronary heart disease (CHD). The entire coding and boundary regions of LPL and HTGL genes were analyzed by direct sequencing in 20 patients with both LHDL/HTG and diagnosed CHD. In the LPL gene six different polymorphisms were identified with same frequencies observed in the general population. In the HTGL gene, besides several polymorphisms, we identified three missense mutations: Asn37His, Val73Met, and Ser267Phe. Population screening using allele specific PCR identified Val73Met as a polymorphism while the two others were absent from 100 control individuals. One of the mutations (Ser267Phe) is known to cause HTGL deficiency and is associated with type III hyperlipoproteinemia. Since this dyslipoproteinemia meets the criteria of LHDL/HTG, it is intriguing to speculate that missense mutations in HTGL may play a role in the pathogenesis of this atherogenic phenotype.

External beam irradiation inhibits neointimal hyperplasia after injury-induced arterial smooth muscle cell proliferation.

PURPOSE: Restenosis after catheter-based revascularization has been demonstrated to be primarily caused by smooth muscle cell proliferation. This study examines the effects of external beam irradiation on neointimal proliferation after external injury to the central artery of the rabbit ear. METHODS AND MATERIALS: Thirty male New Zealand White rabbits were used in this study. Crush lesions were performed on each ear under general anesthesia and bilateral auricular nerve blockade. A single dose of 1200 cGy (n = 10), 1600 cGy (n = 10), or 2000 cGy (n = 10) gamma radiation was delivered to the left or right central artery of the ear 24 hours after injury; the contralateral central artery served as control. All rabbits were sacrificed after 21 days and the central arteries of both ears were fixed for morphometric measurements. RESULTS: Mean (+/-SD) neointimal area was 0.062 +/- 0.005 mm2 (1200 cGy), 0.022 +/- 0.005 mm2 (1600 cGy), and 0.028 +/- 0.006 mm2 in irradiated arteries compared with 0.081 +/- 0.009 mm2 in the control group. Mean (+/-SD) luminal area was 0.049 +/- 0.004 mm2 (1200 cGy), 0.059 +/- 0.002 mm2 (1600 cGy), and 0.072 +/- 0.006 mm2 (2000 cGy) in irradiated arteries compared with 0.043 +/- 0.008 mm2 in the control group. The differences in neointimal and luminal area between control and irradiated arteries were significant (p < 0.05) for the 1600 and 2000 cGy group only. CONCLUSION: We conclude that in this model, external beam X-ray irradiation was successful in reducing neointimal proliferation after injury of the central artery of the rabbit ear. Marked reductions in neointimal proliferation were demonstrated in vessels subject to 1600 and 2000 cGy radiation; a less prominent effect was noted for 1200 cGy. Whether this approach can be used successfully to inhibit restenosis in the clinical setting requires further investigation.

Haemodynamic profile of an inhibitor of phosphodiesterase III, adibendan (BM 14.478): comparison with nitroprusside and dobutamine in conscious dogs.

1. This study was performed to investigate whether cardiac positive inotropic as well as peripheral vasodilator properties of adibendan contribute to its overall haemodynamic profile in conscious dogs. 2. Haemodynamic measurements were carried out in conscious chronically instrumented dogs after administration of adibendan, sodium nitroprusside or dobutamine. 3. The cardiovascular changes induced by adibendan (0.01 and 0.03 mg kg-1) resembled those of dobutamine (1.0-4.0 micrograms kg-1 min-1): left ventricular dP/dt60 (LV dP/dt60), stroke volume (SV) and cardiac output (CO) increased to a similar extent, but mean arterial pressure (MAP) and heart rate (HR) remained unchanged. 4. In contrast to dobutamine, higher doses of adibendan (0.1-1.0 mg kg-1) decreased MAP and LVEDP. These effects were of a similar magnitude to those observed following nitroprusside administration (0.5-12.5 micrograms kg-1 min-1). In contrast to nitroprusside, adibendan still showed additional effects on LV dP/dt60 and CO. 5. From these results, it is concluded that both the peripheral vasodilator and the cardiac positive inotropic action of adibendan contribute to its overall haemodynamic profile.

Haemodynamic and energetic properties of stunned myocardium in rabbit hearts.

OBJECTIVE: To amplify the description of myocardial stunning. DESIGN: Control versus 30 min after a 20 min no flow ischaemia. EXPERIMENTAL ANIMALS: 15 isolated rabbit hearts perfused with erythrocyte suspension. MAIN OUTCOME MEASURES: Left ventricular systolic function in terms of aortic flow, peak systolic pressure (LVPmax), dP/dtmax, and the end systolic pressure-volume relation (ESPVR); early relaxation from dP/dtmin and rate of left ventricular pressure decay (tau). Passive properties: ventricular and myocardial stiffness. Coronary resistance from coronary blood flow and perfusion pressure. Total myocardial oxygen consumption (MVo2tot). Total mechanical energy via pressure-volume area (PVA). Contractile efficiency (Econ) and MVo2 of the unloaded contracting heart (MVo2unl). External mechanical efficiency (Eext) from stroke work and MVo2tot. RESULTS: Systolic variables in stunned myocardium were significantly decreased (mean (SD)): aortic flow: 38 (13) v 9 (11) ml/min; LVPmax: 112 (19) v 74 (18) mm Hg; dP/dtmax: 1475 (400) v 1075 (275) mm Hg/s. ESPVR was not significantly decreased, at 138 (73) v 125 (58) mm Hg/ml, but the volume axis intercept was shifted rightward: 0.30 (0.37) v 0.65 (0.25) ml. Likewise, early relaxation was impaired: dP/dtmin (-1275 (250) v -975 (250) mm Hg/s) and tau (37 (7) v 46 (10) ms). LVPed was significantly decreased at 19 (12) v 12 (7) mm Hg, and both the ventricular (end diastolic pressure-volume relation) and the myocardial stiffness (constant k) were increased by 75% and 31%, respectively. Coronary resistance increased non-significantly from 0.83 (0.31) to 1.04 (0.41) mm Hg/(ml/min/100 g). Decreases in PVA (570 (280) v 270 (200) mm Hg.ml/100 g), MVo2tot (40 (9) v 34 (8) microliters/beat/100 g), and MVo2unl (26 (9) v 22 (6) microliters/beat/100 g) did not reach significance, in contrast to significant decreases in Econ (31 (18) v 14 (7)%) and Eext (0.75 (0.29) v 0.18 (0.25) arbitrary units). CONCLUSIONS: Ventricular systolic function is decreased after brief episodes of ischaemia. The decrease in diastolic function probably amplifies the systolic deterioration during myocardial stunning. Passive diastolic properties are also changed, shown by increases in both ventricular and myocardial stiffness. The increase in coronary resistance indicates stunning at the vascular level which could limit oxygen supply. With maintained MVo2tot during stunning, external efficiency is decreased. Possible candidates for this metabolic stunning are inadequate excitation-contraction coupling and disturbed O2 utilisation by the contractile apparatus.

Failure to confirm ferritin and caeruloplasmin as risk factors for the angiographic extent of coronary arteriosclerosis.

BACKGROUND: It has been suggested that iron overload, as assessed by increased serum ferritin concentration, may be a risk factor for coronary artery disease (CAD). Recent studies have reported conflicting data on the role of ferritin and other parameters of oxidative metabolism in CAD. OBJECTIVE: The aim of this study was to assess the relation between the extent of CAD and parameters of oxidation. METHODS: We studied 275 patients (208 men aged 55.1 +/- 9.6 years and 67 women aged 54.6 +/- 10.0 years) who underwent coronary angiography or percutaneous transluminal coronary angioplasty for the first time. The parameters assessed were: iron, ferritin, transferrin, copper, caeruloplasmin and lipid. Cinefilms were assessed by the use of three scores: (1) Vessel score: 0-3 points; 1 point for each of the three main coronary arteries with a stenosis >70%. (2) Stenosis score: 0-32 points; the coronary artery tree was divided into eight segments that were scored 1-4 points per segment with respect to the maximal degree of stenosis. (3) Extent score: 0-100 points; extent of diffuse coronary lesions in each segment in relation to the length of the vessel. Multiple regression analyses were used to evaluate the results. RESULTS: Total cholesterol and low-density lipoprotein cholesterol (P < 0.001) in women, low-density lipoprotein cholesterol (P < 0.05) in men, and patient age showed a significant correlation with all three scores, but none of the parameters of oxidative metabolism (iron, transferrin, ferritin, copper, caeruloplasmin) correlated significantly with any of the three scores. CONCLUSION: This study demonstrated a correlation between lipoproteins and the angiographic extent of CAD, but did not confirm a role for serum ferritin and other oxidative parameters as risk factors for the extent of CAD.

Expression of connexins 40 and 43 in human left atrium in atrial fibrillation of different aetiologies.

OBJECTIVE: To test the hypothesis that atrial fibrillation (AF) is associated with changes in the expression of connexins 40 and 43 in the left atrium with more pronounced changes in mitral valve disease than in lone AF. METHODS: Protein concentrations of connexin 40 and connexin 43 were analysed in left atrial tissue of patients undergoing cardiac surgery. One group of patients had lone AF (n = 41), one group had AF and mitral valve repair (n = 36), and one group in sinus rhythm served as controls (n = 15). RESULTS: Western blot analysis of connexin 40 and connexin 43 expression showed an increase of both gap junctional proteins (connexin 43 > connexin 40) in patients with AF of all forms compared with patients in sinus rhythm (p = 0.01 and p = 0.011, respectively). Subgroup analysis showed increased concentrations of connexin 40 in lone AF and AF with mitral valve disease compared with sinus rhythm (p = 0.06 and p = 0.029, respectively), whereas the same analysis for connexin 43 reached significance only in the mitral valve disease group (p = 0.031). No differences in connexin 40 and connexin 43 expression were detectable between lone AF and AF with mitral valve disease. Within the groups connexin 40 and connexin 43 expression did not differ between patients with paroxysmal AF and patients with chronic AF. CONCLUSION: The present study shows for the first time that AF can induce changes in the left atrium with increased connexin expression. Furthermore, no systematic differences between patients with paroxysmal and chronic AF were detected.

Radiofrequency ablation of accessory pathways. Contemporary success rates and complications in 323 patients.

INTRODUCTION: 17 years ago the first radiofrequency catheter ablation of an accessory pathway (AP) was performed. The aim of this study was to describe the contemporary success rates and procedure related complication rates of radiofrequency (RF) ablation of accessory pathways (APs). In addition, the present study describes the anatomical distribution of APs according to the new nomenclature introduced by NASPE and ESC in 1999. METHODS: The analysis included all patients, who underwent RF ablation of an AP in the Heart Center Leipzig between January 2000 and December 2003. RESULTS: Over a 4 year period 336 APs were ablated in 323 patients. 201 APs (60%) presented with antegrade and retrograde conduction and showed preexcitation on ECG. For the remaining 135 APs (40%), only retrograde conduction over the AP was documented. According to the new nomenclature APs were classified as left-sided, right sided, septal and paraseptal APs. 188 APs (56%) were located on the left, 41 (12%) on the right, 64 (19%) in the paraseptal space and 31 APs (9%) presented with a septal or parahisian localization, respectively. Because of atypical course and/or characteristics 12 APs (4%) could not be classified. Ablation of all pathways were successful in 315 patients (98%). In 289 patients (89%) success was achieved within a single ablation session. The left-sided pathways had a re-intervention rate of 5%, which was significantly lower compared to the remaining localizations. The highest re-intervention rate was observed in the septal APs (23%). Complications were observed in less than 2% of all treated patients. CONCLUSIONS: 17 years after the first RF catheter ablation of an AP this therapy is established as a highly effective procedure. The success rate has improved to 98% and the complication rate has been minimized to less than 2%. The most frequent localization of APs is left posterior. Left sided APs also presented with the lowest re-intervention rate. The introduction of the new nomenclature in 1999 by NASPE and ESC has simplified the description of the exact anatomical localization of an AP.

Methaemoglobinaemia after cardiac catheterisation: a rare cause of cyanosis.

Two young women had unexpected cyanosis a few hours after cardiac catheterisation for electrophysiological investigation. The first patient had atrioventricular septal defect, had undergone repeated surgical interventions, and was referred because of atrial flutter. The second patient had ablation of an accessory pathway in Wolff-Parkinson-White syndrome. Local anaesthesia was performed with 40 ml prilocaine 2%. Cyanosis with oxygen saturation of 85% developed in both patients a few hours after the electrophysiological investigation. The patients were transferred to the intensive care unit and for the first patient a considerable diagnostic effort was made to rule out morphological complication. Finally methaemoglobinaemia of 16.7% and 33.4%, respectively, was found. Cyanosis resolved within 24 hours and did not reappear. Underlying glucose-6-phosphate dehydrogenase deficiency and erythrocyte-methaemoglobin reductase deficiency were ruled out. Physicians should be aware of this rare side effect of local anaesthetics in patients with unexpected cyanosis.

Expression of type VIII collagen after cholesterol diet and injury in the rabbit model of atherosclerosis.

This study presents an analysis of the expression of type VIII collagen mRNA in response to cholesterol diet and balloon injury in the rabbit iliac artery. The design of the animal experiments was as follows: 28 male New Zealand White rabbits were divided into the 3 different treatment groups. Group 1 received regular chow; group 2 was fed with a 1% cholesterol diet for 6 weeks and normal chow for 5 weeks; and group 3 underwent balloon injury, then 6 weeks of a 1% cholesterol diet, which was followed by 5 weeks of normal chow. The expression pattern of type VIII collagen mRNA was compared with that of the fibrillar collagen types I and III, transforming growth factor-beta1, a factor known to exert the most potent stimulatory effect on collagen synthesis in vitro, and matrix metalloproteinase 1, a collagen-degrading enzyme. The cholesterol diet resulted in an upregulation of type VIII collagen, fibrillar collagens, transforming growth factor-beta1, and matrix metalloproteinase I in the adventitia. Although the number of type VIII collagen mRNA-expressing cells in the media increased, no significant difference in overall expression levels was detectable by northern blot analysis. The ratio of medial smooth muscle cells expressing type VIII collagen mRNA to those expressing type I and type III collagen mRNA (CVIII:CI:CIII) changed from 1:1.88:0.03 in the normal media to 1:0.78:0.29. When cholesterol feeding was preceded by balloon injury, type VIII collagen mRNA expression concomitant with the fibrillar collagens was further upregulated over and above that level reported after cholesterol diet alone. In general, low levels of transforming growth factor-beta1 mRNA correlated with high expression of matrix metalloproteinase I. Our study indicates that a cholesterol diet resulted in a balanced reorganization of the collagen composition but did not result in marked collagen accumulation. This may provide an extracellular environment that favors migration and proliferation processes during early atherogenesis. It also demonstrates that type VIII collagen is highly expressed and deposited at later stages, and this may be linked to processes such as tissue reorganization during vascular repair and plaque stabilization.

Syncope in a child owing to intramural course of the left coronary artery.

UNLABELLED: Coronary abnormalities are a rare cause of syncope or sudden death in childhood or adolescence. We report on a 14-y-old girl who had suffered for many years from repeated syncope after or during exertion. She had to be resuscitated twice. The left coronary artery arose from the right coronary aortic sinus and took a proximal intramural course. After successful reimplantation, the patient has now been free of symptoms for 12 mo. The pitfalls of differential diagnosis of this rare anomaly are discussed. CONCLUSION: Investigation of the coronary anatomy is indicated in otherwise unexplained chest pain, syncope or life-threatening events.

Fractally coated defibrillation electrodes: is an improvement in defibrillation threshold possible?

AIMS: In patients with implantable cardioverter-defibrillators (ICD), the goals of lowering the defibrillation threshold (DFT) can be achieved by means of higher defibrillation safety margins, more rapid charging of capacitors, improved battery longevity, implying smaller devices. Whether an increase in the electrically active surface of ICD leads by fractal coating results in decreased DFTs is unknown. METHODS AND RESULTS: In this prospective randomized cross-over study the defibrillation efficacy of a novel right ventricular endocardial defibrillation electrode fractally coated with iridium was compared with an uncoated but otherwise identical electrode in 30 patients undergoing ICD implantation. In each patient, DFT testing was performed twice according to a binary search protocol introducing the two different electrodes in a random order. The mean DFT was 8.4 +/- 4.1 J with the fractally coated lead and 9.6 +/- 3.6 J using the uncoated lead. The improvement of 1.2 J was statistically not significant (P = 0.11). No differences were observed between the patients with an improved DFT (n =12) and those with an unchanged or worsened DFT (n = 18) concerning age, underlying cardiac disease, NYHA class, or left ventricular ejection fraction, respectively. CONCLUSION: Increasing the electrical surface of defibrillation leads by fractal coating does not lead to a substantial clinically relevant reduction in defibrillation thresholds. Defibrillation impedance is not influenced by the increased electrical surface of the defibrillation lead.

Vasodilation by urapidil in the treatment of chronic congestive heart failure in addition to angiotensin-converting enzyme inhibitors is not beneficial: results of a placebo-controlled, double-blind study.

BACKGROUND: The therapeutic benefit of an angiotensin-converting enzyme (ACE) inhibitor in combination with a different type of vasodilator is unknown. METHODS AND RESULTS: To evaluate the effects of a combined therapy on quality of life, exercise tolerance, and hemodynamic parameters, patients with severe heart failure (New York Heart Association classes III and IV, ejection fraction below 35%) who were on ACE inhibitor therapy were randomly assigned to additional double-blind treatment with urapidil (60-120 mg/d) or placebo for 12 weeks. After enrollment of 36 patients, the study was terminated early because no beneficial effects on exercise tolerance and hemodynamic parameters could be shown for the urapidil treatment, and a trend toward increased mortality of the urapidil group was observed (odds ratio, 4.92 [0.49-49.6]; P = .167). CONCLUSION: The combination of urapidil with an ACE inhibitor in the treatment of severe chronic congestive heart failure does not seem to offer any advantages over therapy with an ACE inhibitor alone and may have potentially harmful effects.

A stepwise mapping approach for localization and ablation of ectopic right, left, and septal atrial foci using electroanatomic mapping.

AIMS: We describe a new strategic stepwise mapping approach for fast and accurate identification and ablation of ectopic atrial foci using an electroanatomic mapping system. METHODS AND RESULTS: Mapping procedures started with the acquisition of four points at the superior/septal part of the tricuspid annulus. According to this activation sequence, maps were continued towards the right atrial free wall if relatively early activation was shown at the superior part of the initial map or towards the triangle of Koch and, if necessary, to the left atrium, in cases of relatively early activation at the septum. High density mapping and detailed electrogram analysis only of the target area allowed identification and ablation of 34 foci in 30 of the 32 studied consecutive patients. A small number of mapping points were sufficient within a procedure time of 90 +/- 41 min for right 148 +/- 68 min and for left sided foci and a total fluoroscopy time of 9.6 +/- 7.2 min and 24.8 +/- 16.4 min respectively. Sixteen foci were located at the right free wall, eight at the left free wall, and 10 at the right or left side of the septum. CONCLUSION: Strategic electroanatomic mapping with fast identification of the area of tachycardia origin and high density mapping only of this target area allowed fast and successful localization and ablation of right and left free wall and septal ectopic atrial foci.

[Transvenous-subcutaneous implantation of a cardioverter-defibrillator after bioprosthetic replacement of a tricuspid valve]. / Transvenös-subkutane Implantation eines Kardioverter-Defibrillators nach biologischem Trikuspidalklappenersatz.

The implantation of transvenous devices in patients who underwent tricuspid valve replacement represents problems, especially if an epicardial position is not available. The implantation of a "pace-sense" lead via the coronary sinus is a safe and feasible procedure. For experienced surgeons in implantation of biventricular devices, the implantation of leads via the coronary sinus is a routine procedure. Bipolar leads are essential for the correct sensing and pacing of the implantable cardioverter-defibrillator (ICD). In patients who underwent tricuspid valve replacement who have the indication of an ICD implantation postoperatively, the combination of a shock electrode placed in the superior vena cava, a subcutaneous array positioned on the left posterior close to the spine and an active can, placed subpectorally in the left infraclavicular region, is an alternative solution.

Management of patients after catheter ablation of ventricular tachycardia.

The management of patients after catheter ablation of ventricular tachycardia is not well defined. In this article we summarize recently published results and report our own experience. Factors influencing the clinical outcome of these patients and methods to identify patients with an increased risk of recurrence of ventricular tachycardia are discussed. Furthermore, a review is given on current concomitant therapeutic tools including antiarrhythmic drugs and the implantation of an automatic cardioverter defibrillator.

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.

Implantation of a dual chamber pacing and sensing single pass defibrillation lead.

Dual-chamber ICDs are increasingly used to avoid inappropriate shocks due to supraventricular tachycardias. Additionally, many ICD patients will probably benefit from dual chamber pacing. The purpose of this pilot study was to evaluate the intraoperative performance and short-term follow-up of an innovative single pass right ventricular defibrillation lead capable of bipolar sensing and pacing in the right atrium and ventricle. Implantation of this single pass right ventricular defibrillation lead was successful in all 13 patients (age 63 +/- 8 years; LVEF 0.44 +/- 0.16; New York Heart Association [NYHA] 2.4 +/- 0.4, previous open heart surgery in all patients). The operation time was 79 +/- 29 minutes, the fluoroscopy time 4.7 +/- 3.1 minutes. No perioperative complications occurred. The intraoperative atrial sensing was 1.7 +/- 0.5 mV, the atrial pacing threshold product was 0.20 +/- 0.14 V/ms (range 0.03-0.50 V/ms). The defibrillation threshold was 8.8 +/- 2.7 J. At prehospital discharge and at 1-month and 3-month follow-up, atrial sensing was 1.9 +/- 0.9, 2.1 +/- 0.5, and 2.7 +/- 0.6 mV, respectively, (P = NS, P < 0.05, P < 0.05 to implant, respectively), the mean atrial threshold product 0.79, 1.65, and 1.29 V/ms, respectively. In two patients, an intermittent exit block occurred in different body postures. All spontaneous and induced ventricular arrhythmias were detected and terminated appropriately. Thus, in a highly selected patient group, atrial and ventricular sensing and pacing with a single lead is possible under consideration of an atrial pacing dysfunction in 17% of patients.