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W Kübler

Publications and source records attributed to W Kübler.

At least 145 records · Page 8Linked to original sources
PubMed1997

Advantages and limitations of radioactive stents.

The concept of radioactive stents was initiated to prevent restenosis after angioplasty in patients with coronary artery disease. We review the modes of fabrication, dosimetry and the biological effects of radioactive stents. Radioactive stents deliver ionizing radiation continuously at very low-dose rates according to the half-life of the incorporated radioisotopes. The activity levels of radioactive stents are up to 10,000 times lower than activity levels of sources used for catheter-based vascular brachytherapy. Radioactive stents allow uniform dose distribution and precise dosimetry because of the direct source contact with the circumference of the vessel. Animal studies show that these stents can potently inhibit smooth muscle cell proliferation and neointimal hyperplasia. A persistent inhibition of neointimal hyperplasia appears to be dose dependent. Local or systemic side effects related to the irradiation were not observed. A limitation of radioactive stents could be the dose-dependent delay in stent endothelialization which, however, did not cause thrombotic vessel occlusion in animal experiments. Whether a delay in stent endothelialization is associated with an increased rate of occlusive stent thrombosis in humans requires further studies.

Animals↗
PubMed1996

Patency trials with reteplase (r-PA): what do they tell us?

Thrombolytic therapy has been shown to reduce mortality and morbidity after acute myocardial infarction. Therapeutic benefit seems to be directly correlated with completeness of reperfusion (Thrombolysis in Myocardial Infarction [TIMI] grade 3 flow) of the infarct-related coronary artery, as well as the timeliness of reperfusion. To determine which regimen of reteplase (r-PA), a deletion mutant of wild-type tissue plasminogen activator (t-PA), is most effective for clinical thrombolysis, several reteplase regimens were compared with the most successful standard regimens of recombinant t-PA (alteplase) in 2 large-scale, randomized studies. All patients received aspirin and intravenous heparin. In the Reteplase Angiographic Phase II International Dose Finding Trial (RAPID-1), results in 606 randomized patients showed that a 10 + 10 U double bolus of reteplase was more effective than a 15 U single bolus, a 10 + 5 double bolus, or conventional alteplase (100 mg over 3 hours). In the Reteplase versus Alteplase Patency Investigation During Acute Myocardial Infarction (RAPID-2) trial, results in 324 patients showed that significantly more patients achieved patency of the infarct-related artery (TIMI grade 2 or 3 flow) at 90 minutes with reteplase (10 + 10 U double bolus) than with accelerated alteplase (100 mg over 90 minutes): 83.4% versus 73.3%, respectively (p = 0.03). The incidence of complete patency (TIMI grade 3 flow) at 90 minutes was likewise greater with reteplase than with accelerated alteplase (59.9% vs 45.2%, respectively; p = 0.01). At 60 minutes, the incidence of TIMI grade 2 or 3 flow was also significantly higher with reteplase than with alteplase (81.8% vs 66.1%, respectively; p = 0.01), as was the incidence of TIMI grade 3 flow (51.2% vs 37.4%, respectively; p < 0.031). The 35-day mortality rate was 4.1% for reteplase and 8.4% for alteplase (p = not significant). Reteplase and alteplase did not differ significantly with regard to the occurrence of severe bleeding (12.4% vs 9.7%, respectively) or hemorrhagic stroke (1.2% vs 1.9%, respectively). The results of these trials show that reteplase, given as a 10 + 10 U double bolus, achieves significantly higher rates of early reperfusion of the infarct-related coronary artery and is associated with significantly fewer acute coronary interventions when compared with front-loaded alteplase. The benefits of reteplase are achieved without any apparent increased risk of complications.

Cerebral Hemorrhage↗
PubMed1996

[Pneumococcal vaccination after heart and liver transplantation. Immune responses in immunosuppressed patients and in healthy controls].

BASIC PROBLEM AND OBJECTIVE OF STUDY: Among other effects, therapeutic immunosuppression after organ transplantation impairs antibody formation. But because of the increased risk of infection, the efficacy of prophylactic immunization is of particular importance in patients after transplantation. For this reason the immunogenicity after immunization against pneumococcus was investigated in transplanted patients. PATIENTS AND METHODS: A 23-valent vaccine of capsular polysaccharides (Pneumovax 23) was administered to 31 patients 4-85 months after transplantation (16 hearts transplants, 15 liver transplants; age range 22-63 years). The same immunization was given to 23 healthy control subjects. The immune response was measured serologically in all groups. RESULTS: Immunization was well tolerated by all participants, and there were no infectious or systemic side effects. Mean postvaccinal global pneumococcus-specific antibody titres were comparable in the healthy and transplanted subjects (controls: 5490 U/ml, heart transplanted: 5513 U/ml, liver transplanted: 4148 U/ml; differences not significant). Analysis of individual titres for the nine most important serotypes showed comparable results for six serotypes, reduced titres being found for serotypes 3 and 8 after heart transplantation, and for serotypes 8 and 23 after liver transplantation. CONCLUSION: Safe antipneumococcal immunization is possible during therapeutic immunosuppression after heart or liver transplantation. The achieved immune response is comparable to that in healthy controls. The high efficacy of the pneumococcal vaccine, compared with other vaccines, in immunosuppressed patients may be due to T-cell dependent antibody production against polysaccharides.

Adult↗
PubMed1996

Predictive value of lipid profile for salutary coronary angiographic changes in patients on a low-fat diet and physical exercise program.

In this study, 113 patients with modestly elevated levels of low-density lipoprotein cholesterol (<210 mg/dl) and coronary artery disease were randomized to an intervention group (n=56) or a control group (n=57). The intervention program consisted of daily exercise and a low-fat diet according to the American Heart Association's recommendation phase III; patients in the control group received "usual care" rendered by their private physician. After 1 year, complete data were available for all 92 patients (intervention: n=40; control: n=52) who underwent repeat coronary angiography. During the study course, patients in the intervention group showed an increase in apolipoprotein A-I(123 +/- 18 vs 129 +/- 20 mg/dl; p < 0.02) and apolipoprotein A-I/B (1.3 +/- 0.4 vs 1.5 +/- 0.4; p <0.01) and a decrease in apolipoprotein B (99 +/- 20 vs 89 +/- 18 mg/dl; p < 0.01), while apolipoprotein A-II remained unchanged (38 +/- 6 vs 38 +/- 6 mg/dl; p=NS). In the control group, there were no significant changes (apolipoprotein A-I, 124 +/- 17 vs 128 +/- 13 mg/dl; apolipoprotein A-II, 38 +/- 6 vs 39 +/- 6 mg/dl; apolipoprotein B, 100 +/- 21 vs 99 +/- 16 mg/dl; apolipoprotein A-I/B, 1.3 +/- 0.3 vs 1.4 +/- 0.5; all p=NS). As previously reported, there was a significant retardation of progression in patients in the intervention group (progression 23%, no change 45%, regression 32%) compared with the control group (progression 48%, no change 35%, regression 17%) (p < 0.05). Although retardation of progression was significantly associated with an increase in apolipoprotein A-I/B and a decrease in apolipoprotein B (p < 0.05), these gave way in multivariate analysis to changes in total cholesterol/high-density lipoprotein cholesterol, absolute levels of low-density lipoprotein cholesterol, and, in a subgroup of patients, to leisure-time physical activity (all p < 0.05). These data demonstrate that an intervention based on a low-fat diet and intensive physical exercise is capable of improving apolipoprotein levels, associated with retardation of progression of coronary artery disease. However, total cholesterol/high-density lipoprotein cholesterol and low-density lipoprotein cholesterol appear superior to apolipoproteins as metabolic markers for effective treatment in patients with coronary artery disease.

Adult↗
PubMed1996

Pure beta-particle-emitting stents inhibit neointima formation in rabbits.

BACKGROUND: Considerable experimental evidence exists that neointimal hyperplasia after angioplasty is inhibited by gamma-irradiation of the treated arteries. A beta-particle radiation is absorbed in tissue within a shorter distance away from the source than gamma-radiation and may be more suitable for localized vessel irradiation. This study outlines a method to implant a beta-particle-emitting radioisotope (32P; half-life, 14.3 days) into metallic stents. The effects of these stents on the inhibition of neointimal hyperplasia was compared with conventional stents in a rabbit model. METHODS AND RESULTS: 32P was produced by irradiation of red amorphous phophorus (31P) with neutrons and was implanted into Palmaz-Schatz stents (7.5 mm in length) after being kept apart from 31P in a mass separator. The radioisotope was tightly fixed to the stents, and the ion implantation process did not alter the surface texture. Stent activity levels of 4 and 13 microCi were chosen for the study. Four and 12 weeks after placement of conventional stents and 32P-implanted stents in rabbit iliac arteries, vascular injury and neointima formation were studied by histomorphometry. Immunostaining for smooth muscle cell (SMC) alpha-actin was performed to determine SMC cellularity in the neointima. SMCs were quantified by computer-assisted counting of alpha-actin immunoreactive cells. Endothelialization of the stents was evaluated by immunostaining for endothelial cell von Willebrand factor. No difference in vessel wall injury was found after placement of conventional and 32P-implanted stents. Neointima formation was potently inhibited by 32P-implanted stents only at an activity level of 13 microCi after 4 and 12 weeks. Neointimal SMC cellularity was reduced in 32P-implanted stents compared with conventional stents. Radioactive stents were endothelialized after 4 weeks, but endothelialization was less dense than in conventional stents. CONCLUSIONS: Neointima formation in rabbits is markedly suppressed by a beta-particle-emitting stent incorporating the radioisotope 32P. In this model, a dose-response relation with this type of radioactive stent was observed, indicating that a threshold radiation dose must be delivered to inhibit neointima formation after stent placement over the long term.

Angioplasty, Balloon↗
PubMed1996

Transesophageal echo phase imaging for localizing accessory pathways during adenosine-induced preexcitation in patients with the Wolff-Parkinson-White syndrome.

Transesophageal phase images and precordial electrocardiography (ECG) were used to localize accessory pathways during adenosine-induced preexcitation in 30 patients (18 men, mean age +/- SD 33 +/- 14 years) undergoing endocardial mapping for suspected Wolff-Parkinson-White syndrome. Digitized 2-dimensional echocardiographic cine loops were mathematically transformed using a first harmonic Fourier algorithm before and after catheter ablation. Endocardial mapping found single accessory pathways with anterograde conduction in 20 patients, concealed pathways in 7, and atrioventricular reentry circuits in 3 patients. At baseline, precordial ECG correctly localized 8 pathways (40%) with anterograde conduction and predicted 5 adjacent locations (25%), but findings were normal in 7 patients (35%). Phase imaging correctly identified only 3 pathway locations (15%), findings were normal in 15 (75%), and could not be obtained in 2 patients (10%). Adenosine augmented manifest but minimal preexcitation in 9 patients and unmasked latent preexcitation in 7. In 4 patients, preexcitation was already maximal at baseline. During adenosine-augmented preexcitation, ECG correctly identified 13 locations (65%), but still predicted 7 adjacent locations (35%). However, phase imaging correctly identified 15 locations (75%) and predicted only 3 adjacent locations (15%). All midseptal (n = 2) and anteroseptal (n = 2) locations were correctly identified by phase imaging, but none by ECG. On follow-up studies in 16 patients, successful catheter ablation (n = 13) was equally well confirmed by ECG and phase imaging. Therefore, transesophageal echocardiographic phase imaging during adenosine-induced preexcitation is a readily available and safe procedure that appears clinically most useful for identifying septal pathways.

Adenosine↗
PubMed1996

Differential regulation of mRNA specific for beta 1- and beta 2-adrenergic receptors in human failing hearts. Evaluation of the absolute cardiac mRNA levels by two independent methods.

In human heart failure beta-adrenergic receptors are downregulated which contributes to the reduced responsiveness to positive inotropic beta-agonists in the diseased heart. The present study addressed the question whether the number of beta-adrenergic receptors in the failing human heart is regulated at the level of the mRNA and whether the absolute steady-state levels of subtype-specific mRNAs mirror the expression of receptor-subtype proteins in human heart. In a collaborative effort, two different and independent methods, performed in two independent laboratories, reverse transcription followed by polymerase chain reaction (RT-PCR) and RNase protection assays, were used to determine the absolute steady-state levels of beta 1- and beta 2-adrenergic receptor mRNAs in control (NF) and in failing human hearts. As determined by quantitative RT-PCR the beta 1-mRNA was significantly reduced from 0.98 +/- 0.12 (n = 10) to 0.49 +/- 0.11 pg/microgram total RNA in dilated cardiomyopathy (dCMP, n = 7) and to 0.40 +/- 0.11 pg/microgram total RNA in ischemic cardiomyopathy (iCMP, n = 8). The steady-state levels of mRNA specific for beta 2-adrenergic receptors also tended to be decreased but without reaching significance (NF: 0.16 +/- 0.05, dCMP: 0.11 +/- 0.03, iCMP: 0.13 +/- 0.04 pg/microgram total RNA). RNase protection assays revealed similar values. beta 1-mRNA was found to be significantly reduced from 1.22 +/- 0.22 in NF (n = 10) to 0.63 +/- 0.14 pg/microgram total RNA in dCMP (n = 5) and to 0.52 +/- 0.1 pg/microgram total RNA in iCMP (n = 8). The beta 2-mRNA also tended to be lower in dCMP and in iCMP as compared to NF but again without reaching significance (NF: 0.14 +/- 0.02, dCMP: 0.099 +/- 0.02, iCMP 0.107 +/- 0.02 pg/microgram total RNA). This is the first study to demonstrate in parallel by two different methods performed independently in two laboratories that the ratio of beta 1- and beta 2-adrenergic receptor densities in the left ventricle of the normal human heart of about 80/20 is closely related to the absolute steady state concentrations of their specific mRNA. In addition, the magnitude of the decrease in mRNA-levels of beta 1- and beta 2-adrenergic receptors in the failing human heart closely correlates with the decrease of the respective receptor proteins. These data suggest that the predominant regulation of beta-adrenergic receptors occurs at the mRNA level.

Adult↗
PubMed1996

Evidence against a regulation of Na+/K(+)-ATPase by Gi proteins. Failure to detect an influence of G proteins on Na+/Ca(2+)-exchange in cardiac sarcolemmal membranes.

In the myocardium the inhibitory guanine nucleotide-binding regulatory proteins (Gi proteins) mediate negative chronotropic and negative inotropic effects by activation of K+ channels and inhibition of adenylyl cyclase. The concept of a uniform inhibitory action of Gi proteins on myocardial cellular activity has been questioned by the recent observations of adenosine-induced activation of the Na+/Ca(2+) exchange and a carbachol-induced inhibition of the Na+/K(+)-ATPase activity in cardiac sarcolemmal membranes. The aim of the present study, therefore, was to reinvestigate the putative regulation of Na+/Ca(2+) exchange and Na+/K(+)-ATPase activity in purified canine sarcolemmal membranes. These membranes were enriched in adenosine A1 (Maximum number of receptors, Bmax 0.033 pmol/mg) and muscarinic M2 (Bmax 2.9 pmol/mg) receptors and contained Gi2 and Gi3, two Gi protein isoforms, and G0, another pertussis toxin-sensitive G protein, as detected with specific antibodies. The adenosine A1-selective agonist, (-)-N6-(2-phenylisopropyl)-adenosine, and the muscarinic agonist, carbachol, both inhibited isoprenaline-stimulated adenylyl cyclase activity by 25% and 35% respectively, and the stable GTP analogue 5'-guanylylimidodiphosphate inhibited forskolin-stimulated adenylyl cyclase activity by 35% in these membranes. The characteristics of Na+/Ca(2+) exchange and Na+/K(+)-ATPase activity as well as those of the ouabain-sensitive, K(+)-activated 4-nitrophenylphosphatase, an ATP-independent, partial reaction of the Na+/K(+)-ATPase, were in agreement with published data with regard to specific activity, time course of activity and substrate dependency. However, none of these activities were influenced by adenosine, (-)-N6-(2-phenylisopropyl)-adenosine, carbachol, or stable GTP analogs, suggesting that Na+/Ca(2+) exchange and Na+/K(+)-ATPase are not regulated by Gi proteins in canine cardiac sarcolemmal membranes.

4-Nitrophenylphosphatase↗
PubMed1996

Opioid receptor agonists activate pertussis toxin-sensitive G proteins and inhibit adenylyl cyclase in canine cardiac sarcolemma.

Although both opioid receptors and endogenous opioids are abundant in cardiac tissues, the signal transduction pathways of opioids in cardiac sarcolemmal membranes have yet to be identified. In highly purified canine cardiac sarcolemmal membranes, binding of the opioid receptor antagonist [3H]diprenorphine and effects of mu, delta and kappa agonists on low Km GTPase and adenylyl cyclase were measured. Equilibrium binding of [3H]diprenorphine revealed a maximal binding capacity of 7.2 pmol/mg protein and a Kd of 1.3 nmol/l. In the presence of GTP, (D-Pen2,5, p-Cl-Phe4) enkephalin and (D-Arg6) dynorphin A 1-13 fragment both inhibited adenylyl cyclase by 20-25% (from 206 +/- 30 to 164 +/- 28 pmol.min-1.mg protein-1, EC50 6 mumol/L, and from 254 +/- 109 to 204 +/- 90 pmol.min-1.mg protein-1, EC50 8 mumol/L, respectively; P < 0.001). Both substances stimulated low Km GTPase by 20% and 13%, respectively (from 12.7 +/- 3.0 to 15.2 +/- 3.7 pmol.min-1.mg protein-1, EC50 12 mumol/L, P < 0.01, and from 9.1 +/- 2.8 to 10.4 +/- 3.2 pmol.min-1.mg protein-1, EC50 6 mumol/L, P < 0.05, respectively). These effects were blocked by the opioid receptor antagonist naltrexone and by pretreatment of sarcolemmal membranes with pertussis toxin. The mu opioid receptor agonists (D-Ala2, Me Phe4, Gly-[ol]5)enkephalin and morphiceptin had no effect on either adenylyl cyclase or low Km GTPase activities. These data suggest that in cardiac sarcolemma, opioid receptors are coupled to pertussis toxin sensitive G proteins and mediate inhibition of adenylyl cyclase activity.

Adenylate Cyclase Toxin↗
PubMed1996

Adenovirus-assisted lipofection: efficient in vitro gene transfer of luciferase and cytosine deaminase to human smooth muscle cells.

Smooth muscle cells (SMC) are a central cell type involved in multiple processes of coronary artery diseases including restenosis and therefore are major target cells for different aspects of gene transfer. Previous attempts to transfect primary arterial cells using different techniques like liposomes, CaPO4 and electroporation resulted in only low transfection efficiency. The development of recombinant adenoviruses dramatically improved the delivery of foreign genes into different cell types including SMC. However, cloning and identification of recombinants remain difficult and time-consuming techniques. The present study demonstrates that a complex consisting of reporter plasmid encoding firefly luciferase (pLUC), polycationic liposomes and replication-deficient adenovirus was able to yield very high in vitro transfection of primary human smooth muscle cells under optimized conditions. The technique of adenovirus-assisted lipofection (AAL) increases transfer and expression of plasmid DNA in human smooth muscle cells in vitro up to 1000-fold compared to lipofection. To verify the applicability of AAL for gene transfer into human smooth muscle cells we studied a gene therapy approach to suppress proliferation of SMC in vitro, using the prokaryotic cytosine deaminase gene (CD) which enables transfected mammalian cells to deaminate 5-fluorocytosine (5-FC) to the highly toxic 5-fluorouracil (5-FU). The effect of a transient CD expression on RNA synthesis was investigated by means of a cotransfection with a RSV-CD expression plasmid and the luciferase reporter plasmid. Western blot analysis demonstrated high expression of CD protein in transfected SMC. Cotransfected SMC demonstrated two-fold less luciferase activity in the presence of 5-FC (5 mmol/l) after 48 h compared to cells transfected with a non-CD coding plasmid. The data demonstrate that a transient expression of CD could be sufficient to reduce the capacity of protein synthesis in human SMC. This simple and effective in vitro transfection method may also be applicable to in vivo delivery of target genes to the vascular wall to inhibit SMC proliferation.

Adenoviruses, Human↗
PubMed1996

LDL stimulates chemotaxis of human monocytes through a cyclooxygenase-dependent pathway.

Monocyte migration into the vessel wall is an early step in atherogenesis. Even though a number of chemotactic factors have been identified, the regulation of the chemotactic response is not clearly understood. As the release of arachidonic acid has been implicated in monocyte chemotaxis, we studied the influence of LDL, which can supply this fatty acid to cells, on the chemotactic mobility of monocytes. Migration of human monocytic U937 cells was abolished by a 30-hour incubation in medium containing lipoprotein-depleted 10% fetal calf serum. Thereafter, human VLDL, LDL, acetyl LDL, methyl LDL, HDL, free cholesterol, linoleic acid, oleic acid, or arachidonic acid was added. At the end of varying incubation periods (0.5 to 8 hours), chemotaxis, viability, and cellular cholesterol content were measured. In the same experimental setting we also studied the effects of the pharmacological agents chloroquine, indomethacin, and acetylsalicylic acid on LDL-mediated chemotaxis. Chemotaxis was restored by LDL in a dose- and time-dependent manner starting at concentrations as low as 5 micrograms/mL and at incubations as brief as 30 minutes. The other lipoproteins tested (VLDL, HDL, acetyl LDL, and methyl LDL) as well as free cholesterol had no comparable effect on chemotaxis. Viability and total cholesterol content did not differ among the groups. Simultaneous incubation of cells with chloroquine, indomethacin, and acetylsalicylic acid reduced restitution of chemotaxis by LDL by 71%, 82%, and 68%, respectively. In contrast, the agents had only slight inhibitory effects on the chemotactic mobility of serum-fed control cells. Incubation with linoleic acid showed a 60% restoration of chemotaxis, whereas arachidonic acid stimulated chemotaxis by 140% compared with the positive control. Preincubation of LDL with the monoclonal antibody MB47 directed against LDL resulted in a significantly reduced migratory response. The data suggest a novel cyclooxygenase-dependent regulatory mechanism of chemotaxis by LDL.

Cells, Cultured↗
PubMed1996

-Anticoagulation after intracoronary stent implantation-.

The success of percutaneous transluminal coronary angioplasty (PTCA) is limited by vessel dissection with subsequent vessel occlusion in the acute phase and by restenosis chronically. The implantation of intracoronary stents allows to manage acute complications more efficiently and reduce restenosis rate. Anticoagulation and inhibition of platelet function play an important role in reducing the risk of stent thrombosis triggered by the thrombogenic surface of the stents available today. Among the risk factors for stent thrombosis are stent implantations in emergency situations, a low coronary blood flow secondary to more distal stenoses or to small vessel diameter, and several stents implanted in a single vessel region. In 2 large randomized studies (BENESTENT, STRESS), combination therapy using aspirin, dipyridamole, dextrane, and heparin continued by warfarin lead to a high incidence of bleedings and vascular complications at the site of arterial punction. Subsequent studies documented that dipyridamole and dextrane do not improve the outcome after stent implantation. Recently, the combination of aspirin and ticlopidine has been show to reduce the rate of stent thrombosis; with coronary stents implanted optimally anticoagulation may be handled without warfarin. Most stent thromboses occur even if anticoagulation is monitored and controlled accurately. The search for markers to predict stent thrombosis such as the prothrombin fragment F1+2 or the thrombin-antithrombin complex has not been successful so far. The direct antithrombin hirudin, platelet receptor blockers such as the antibody 7E3, and new stents with reduced thrombogenic surface offer new perspectives in anticoagulation with stent implantation.

Angioplasty, Balloon, Coronary↗
PubMed1996

[Calcium antagonists in treatment of ventricular tachycardia].

Of the traditional antiarrhythmic agents administered in the treatment of ventricular tachycardias, those belonging to Class III are most commonly used. However, some ventricular tachycardias displaying special clinical, electrocardiographic and/or electrophysiologic characteristics have been successfully treated with calcium antagonists. Otherwise, Class IV antiarrhythmic agents are primarily used in the treatment of supraventricular tachyarrhythmias. It is reasonable to suspect that calcium-dependent phenomena underlie ventricular tachyarrhythmias in a number of patients. Verapamil-sensitive sustained left ventricular tachycardias represent a typical example. Sufficient response to calcium antagonists has also been demonstrated for exercise-induced ventricular tachycardias and repetitive monomorphic ventricular tachycardias. Characteristically, these arrhythmias occur in young patients with no structural heart disease. The long-term prognosis of these patients is in fact very good, but because of intrusive symptoms, pharmacological or nonpharmacological (radiofrequency ablation) treatment is often indicated. Through correct diagnosis and implementation of a short- and long-term therapy with calcium antagonists, and excellent alternative to the potentially harmful therapy with Class I and Class III antiarrhythmic agents can be offered.

Anti-Arrhythmia Agents↗
PubMed1996

[New aspects of defibrillator therapy].

The implantable cardioverter defibrillator is currently a therapy of first choice in patients with malignant therapy refractory ventricular arrhythmias. The occurrence of malignant ventricular tachycardia cannot be suppressed by the defibrillator but is treated using antitachycardia pacing, cardioversion or defibrillation. During recent years, electrodes, defibrillation shockforms and device size were continuously optimized. The development of transvenous lead systems resulted in significant reduction of perioperative mortality and morbidity. With the availability of biphasic shockforms and single-lead unipolar devices marked reduction of defibrillation thresholds were achieved and transvenous lead systems without subcutaneous could be implanted. Improvements in device technology lead to smaller devices which can be implanted subpectorally even using local anaesthesia. But there is still enormous potential to develop an ideal antiarrhythmic device. One of the most significant problems of the defibrillator therapy represents the delivery of inappropriate shocks due to supraventricular tachyarrhythmias and sinustachycardia. To solve this problem different approaches are currently developed. Extension in memory allows to store several data logs and intracardiac electrograms for individual adapted adjustment of the therapy. Intracardiac electrogram width measurement for discrimination between ventricular and supraventricular arrhythmias is currently evaluated. Dual-chamber arrhythmia discrimination algorithms of an integrated dual-chamber pacemaker and defibrillator are clinically studied. Hemodynamic sensors for determining the severity of the arrhythmia are currently under experimental evaluation. The combination of latissimus dorsi dynamic cardiomyoplasty and ICD therapy may improve survival in patients with severely depressed left ventricular function and malignant ventricular arrhythmias. Several randomized prospective trials are currently in progress potentially expanding the use of the ICD in patients at risk for sudden cardiac death. The high costs of defibrillator therapy is still a limitation for its use, but higher production figures and advancing technology could reduce the system prize.

Anti-Arrhythmia Agents↗
PubMed1996

[Recognition of cardiac normal variants as the cause of cerebral ischemia: significance of transesophageal echocardiography].

The significance of cardiac normal variants such as patent foramen ovale (PFO), mitral valve prolapse (MVP) and atrial septal aneurysm (ASA) as potential intracardiac sources of embolism in patients with cerebral ischemia is still discussed controversially. In the present study, we determined the prevalence of PFO, MVP and ASA in patients with suspected embolic cerebral events after exclusion of cerebrovascular disease. Therefore, 164 consecutive patients with suspected embolic cerebral events as suggested by cranial computer tomography or clinical neurological examination were divided into two groups: patients with "classical" potential cardiac source of embolism (group I, n = 81, age 52 +/- 10 years) and patients without such potential cardiac sources of embolism (group II, n = 83, age 56 +/- 12 years). The prevalence of PFO, but not that of MVP and ASA, was significantly higher in group I than in group II (group I: 33.3% vs. group II: 2.4%; chi-square 88.5, p < 0.0001). In the absence of "classical" potential cardiac sources of embolism transesophageal echocardiography reveals a PFO in approximately 30% of the cases. This finding supports the significance of PFO as a potential cardiac source of embolism.

Adult↗