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A Goette

Publications and source records attributed to A Goette.

At least 19 recordsLinked to original sources
PubMed2006

Activation of the calcineurin signaling pathway induces atrial hypertrophy during atrial fibrillation.

Atrial tachyarrhythmia (AF) alters intracellular calcium homeostasis and induces cellular hypertrophy of atrial myocytes. The impact of the calcium-dependent calcineurin pathway on the development of AF-induced atrial hypertrophy has not yet been analyzed. In this study, atrial tissue samples from patients with sinus rhythm and chronic persistent atrial fibrillation (CAF) were used to determine changes in expression and activity of calcineurin A (CnA), and its relation to CnA-regulated transcription factors NFATc1-4, and hypertrophic markers ANP, troponin I, and beta-MHC. CnA phosphatase activity and CnAbeta protein contents were significantly upregulated in patients with CAF. Calcineurin activation led to dephosphorylation, redistribution, and subsequent accumulation of NFATc3 in nuclei during CAF, and expression of hypertrophic genes was increased. CAF-dependent changes were reproduced by ex vivo pacing (2-4 Hz) of human atrial tissue slices. FK506 abolished the hypertrophic response induced by electrical-field stimulation. Atrial tachyarrhythmia causes atrial hypertrophy by activation of the CnA signal pathway, which thereby contributes to structural remodeling of human atria.

Aged↗
PubMed2006

[New antiarrhythmic drugs for therapy of atrial fibrillation: II. Non-ion channel blockers].

The therapeutic approach to atrial fibrillation is difficult and challenging. The effect of "classical" antiarrhythmic agents is based on their inhibitory effects on various ion channels. However, therapeutic benefit of these agents is often limited. The primary goal of this article is to discuss new therapeutic approaches using non-ion channel blocking drugs in the treatment of atrial fibrillation. Some of the substances discussed in this article have been used already in the clinical practice. Others, for example gentherapeutic approaches, are still in the experimental state. In contrast to ion channel blocking agents their efficacy is based on the suppression of structural remodeling. Hence, it can be assumed that due to these effects they may also be beneficial in the primary prevention of atrial fibrillation.

Angiotensin II↗
PubMed2006

[Anticoagulation with atrial fibrillation].

Atrial fibrillation is associated with a relevant risk for ischemic stroke: Observational studies suggest that one in four to five strokes is due to atrial fibrillation. Depending on the risk profile of an individual patient, the yearly risk for a stroke is between 2% and 14%. Continuous oral anticoagulation is indicated if atrial fibrillation is accompanied by at least one additional risk factor for thromboembolic complications. This recommendation is supported by several large randomized trials. Due to their low therapeutic range, vitamin K antagonists (phenprocoumon, warfarin, and others), the most commonly used oral anticoagulants, require regular anticoagulation monitoring. If well-controlled (international normalized ratio 2-3, in elderly patients preferably 2-2.5), oral anticoagulation prevents more than half of ischemic strokes related to atrial fibrillation, while bleeding complications are rare. In the follow-up of low risk patients (CHADS2-Score 0), oral anticoagulation becomes necessary when risk factors for thromboembolic complications develop. If a stroke occurs during oral anticoagulation and an INR>2 in a patient with atrial fibrillation, other causes than thromboembolic events should be considered. New anticoagulants--especially direct thrombin antagonists--are currently evaluated in clinical trials and may in the future facilitate anticoagulation in patients with atrial fibrillation.

Anti-Arrhythmia Agents↗
PubMed2004

[Molecular biology of the heart atrium. New insights into the pathophysiology of atrial fibrillation as well as its clinical implications].

Atrial fibrillation (AF) is the most common clinical arrhythmia and one of the most important factors for embolic stroke. In recent years, a tremendous amount has been learned about the pathophysiology and molecular biology of AF. Thus, pharmacologic interference with specific signal transduction pathways appears promising as a novel antiarrhythmic approach to maintain sinus rhythm and to prevent atrial clot formation. This review highlights the underlying molecular biology of atrial fibrillation, which may also be relevant for AF therapy.

Angiotensin II↗
PubMed2001

Expression and activity of ectopeptidases in fibrillating human atria.

Recent studies have demonstrated that atrial fibrillation (AF) occurs in the presence of degenerative changes of atrial tissue. In contrast, bradykinin (BK) appears to have cardioprotective effects diminishing myocardial hypertrophy and fibrosis. It is unknown, however, whether AF has direct effects on BK metabolism. Therefore, the purpose of this study was to determine the atrial expression of the membrane-bound peptidases, also referred to as ectopeptidases, carboxypeptidase M (CPM), dipeptidyl peptidase IV (DPIV), and alanyl-aminopeptidase (APN) in patients with and without AF. Atrial tissue samples of 35 patients undergoing open heart surgery were examined. Seventeen patients had chronic persistent AF (> or = 6 months; CAF), the remaining 18 patients (controls) had no history of AF. Peptidase expression was analyzed at the mRNA (quantitative RT-PCR) level and apparent changes were confirmed at the protein level. In case of unaltered mRNA levels, enzyme activity was determined. Reduced amounts of CPM-mRNA were found in patients with CAF (41.3+/-9.7 U nu controls: 86.1+/-17.5 U P<0.05). CPM protein was decreased to 47.5% in patients with CAF compared with controls (P<0.01). DPIV and APN mRNA amounts were similar in both groups. DPIV activity, however, was increased during CAF (219.6+/-30 pkat/mg protein v controls: 195.8+/-21.8 pkat/mg P<0.05). APN activity was unchanged. In conclusion, atrial bradykinin metabolizing activities are significantly altered during AF in humans. The observed alterations in ectopeptidase expression/activity may play a role in the structural remodeling of fibrillating atria.

Atrial Fibrillation↗
PubMed2001

Case report: severe skin burn at the site of the indifferent electrode after radiofrequency catheter ablation of typical atrial flutter.

Although radiofrequency (RF) catheter ablation has been shown to be an effective treatment strategy in patients with supraventricular tachycardia, RF ablation may lead to potentially serious complications. We describe a case of a 65-year old man who was transferred for catheter ablation of typical atrial flutter. 21 RF applications (mean energy: 81+/-9 watts) were applied in the temperature-controlled mode (70 degrees C) between a 8-mm tip electrode and an indifferent electrode using a high-power RF generator (100 watts) until bi-directional atrial isthmus block was achieved. After the procedure, a third-degree skin burn (10x2 cm) was observed at the lateral edge of the adhesive indifferent electrode whereas the medial edge of the electrode was not fully attached to the skin surface. This case is one out of 1128 ablation procedures (0.09 %) at our institution using a high-power RF generator. The present study demonstrates a severe skin burn induced by mal-attachment of an indifferent electrode during RF ablation. Long RF energy application times, high-power settings, and heavy sedation may have contributed to the observed severity of skin damage.

Aged↗
PubMed2000

Regulation of angiotensin II receptor subtypes during atrial fibrillation in humans.

BACKGROUND: Previous studies have suggested that atrial fibrillation (AF) is associated with the activation of the atrial angiotensin system. However, it is not known whether the expression of angiotensin II receptors changes during AF. The purpose of this study was to determine the atrial expression of angiotensin II type 1 and type 2 receptors (AT(1)-R and AT(2)-R) in patients with AF. METHODS AND RESULTS: Atrial tissue samples from 30 patients undergoing open heart surgery were examined. Eleven patients had chronic persistent AF (> or =6 months; cAF), 8 patients had paroxysmal AF (pAF), and 11 patients were in sinus rhythm. AT(1)-R and AT(2)-R were localized in the atrial tissue by immunohistochemistry and quantified at the protein and mRNA level by Western blotting and quantitative polymerase chain reaction. Both types of AT-R were predominantly expressed in atrial myocytes in all groups. The amount of AT(1)-R was reduced to 34.9% during cAF (P<0.01) and to 51.7% during pAF (P<0.05) compared with patients in sinus rhythm. In contrast, AT(2)-R was increased during cAF (246%; P=NS) and pAF (505%; P<0.01). AT(1)-R/AT(2)-R mRNA content was similar in all groups. CONCLUSIONS: AF is associated with the down-regulation of atrial AT(1)-R and the up-regulation of AT(2)-R proteins. These findings may help define the pathophysiological role of the angiotensin system in the structural remodeling of the fibrillating atria.

Adult↗
PubMed2000

Increased expression of extracellular signal-regulated kinase and angiotensin-converting enzyme in human atria during atrial fibrillation.

OBJECTIVES: The purpose of this study was to determine whether atrial expression of the extracellular signal-regulated kinases Erk1/Erk2 and of the angiotensin-converting enzyme (ACE) is altered in patients with atrial fibrillation (AF). BACKGROUND: Recent studies have demonstrated that atrial fibrosis can provide a pathophysiologic substrate for AF. However, the molecular mechanisms responsible for the development of atrial fibrosis are unclear. METHODS: Atrial tissue samples of 43 patients undergoing open heart surgery were examined. Seventeen patients had chronic persistent AF (> or =6 months; CAF), 8 patients had paroxysmal AF (PAF) and 18 patients had no history of AF. Erk expression was analyzed at the mRNA (quantitative reverse transcription polymerase chain reaction), the protein (immunoblot techniques) and atrial tissue (immunohistochemistry) levels. Erk-activating kinases (MEK1/2) and ACE were analyzed by immunoblot techniques. RESULTS: Increased amounts of Erk2-mRNA were found in patients with CAF (75 +/- 20 U vs. sinus rhythm: 31 +/- 25 U; p < 0.05). Activated Erk1/Erk2 and MEK1/2 were increased to more than 150% in patients with AF compared to patients with sinus rhythm. No differences between CAF and PAF were found. The expression of ACE was three-fold increased during CAF. Amounts of activated Erk1/Erk2 were reduced in patients treated with ACE inhibitors. Patients with AF showed an increased expression of Erk1/Erk2 in interstitial cells and marked atrial fibrosis. CONCLUSIONS: An ACE-dependent increase in the amounts of activated Erk1/Erk2 in atrial interstitial cells may contribute as a molecular mechanism for the development of atrial fibrosis in patients with AF. These findings may have important impact on the treatment of AF.

Aged↗
PubMed2000

Changes in AV node conduction curves following slow pathway modification.

Dual AV node physiology often persists after successful slow pathway (SP) ablation, and the mechanism of tachycardia elimination is unresolved. Therefore, AV node conduction curves were analyzed following successful ablation (4 +/- 1 energy applications) in 85 consecutive patients (58 women, age 50 +/- 2 years) with typical AVNRT. Twenty-seven patients (32%) had complete elimination (group 1) whereas 58 (68%) patients had persistence (group 2) of dual AV node physiology. A significant increase in the AV node Wenckebach cycle length (WB-CL) was observed in both groups (310 +/- 9 to 351 +/- 15 ms in group 1, and 325 +/- 8 to 369 +/- 9 ms in group 2, P < 0.05). A decrease in the fast pathway (FP) ERP (339 +/- 15 to 279 +/- 12 ms) and an increase in the maximum FP AH interval (141 +/- 5 to 171 +/- 7) were observed only in group 1 (P < 0.05). In group 2, no change in the SP ERP (267 +/- 7 to 280 +/- 10 ms) was observed, and the change in the maximum SP-AH following ablation showed a significant inverse relation to the maximum SP-AH at baseline in group 2. In conclusion, (1) an increase in the WB-CL is observed independent of the persistence or elimination of dual physiology after successful ablation; (2) when dual physiology is eliminated, significant changes in the FP ERP and the maximum FP-AH occur; (3) when dual physiology persists, FP physiology and the SP ERP remain unchanged, and a significant inverse relation between the change in the maximum SP-AH following ablation and the maximum baseline SP-AH is observed.

Atrioventricular Node↗
PubMed2000

Increased expression of P-selectin in patients with chronic atrial fibrillation.

Previous studies have shown that platelets are activated during atrial fibrillation (AF). However, prophylactic therapy with aspirin is not associated with a reduction of thromboembolic complications in patients with AF. Stimulation of platelet thrombin and ADP receptors causes a release of P-selectin, which is not affected by aspirin. The purpose of this study was to assess the influence of AF on platelet P-selectin expression. Blood samples from 30 patients were studied ex vivo. Nineteen patients had chronic AF (> 3 months), 11 patients were in sinus rhythm (SR). P-selectin expression was determined by flow cytometry (antibody binding capacity [BC]) at baseline and after platelet stimulation with adenosine diphosphate (ADP) and thrombin receptor activating peptide (TRAP). To determine the effect of heart rate and atrial pressure (RAP), measurements were repeated after 10 minutes of ventricular pacing (120 beats/min) in patients with SR. P-selectin expression was increased in patients with AF at baseline (AF: 1329 +/- 81 BC vs SR: 968 +/- 108 BC; P < 0.05) and after stimulation with ADP (AF: 1445 +/- 101 BC vs SR: 1061 +/- 109 BC; P < 0.05) and TRAP (AF: 13,783 +/- 2442 BC vs SR: 5977 +/- 800 BC; P < 0.05). RAP (2.0 +/- 0.5 vs 6.0 +/- 0.8 mmHg; P < 0.01) and atrial rate (75 +/- 5 vs 114 +/- 5 beats/min; P < 0.001) increased during ventricular pacing. However, P-selectin levels remained stable. AF was accompanied by increased P-selectin expression. In contrast, increased ventricular rate and elevated atrial pressure alone had no effect on platelet activity. Further studies are needed to determine if platelet ADP receptor inhibitors offer a therapeutic benefit in patients with AF.

Adenosine Diphosphate↗
PubMed1999

Persistent T-wave changes after radiofrequency catheter ablation of an accessory connection (Wolff-parkinson-white syndrome) are caused by "cardiac memory".

BACKGROUND: The purpose of this study was to determine the incidence and origin of T-wave changes after ablation of an accessory atrioventricular connection (AC), which could either be a sign of damage to the coronary circulation or a result of persistent abnormal repolarization secondary to previously abnormal ventricular activation ("cardiac memory"). METHODS AND RESULTS: Ninety of 107 consecutive patients (33 women and 57 men, mean age 36 +/- 5 years) undergoing successful catheter ablation of an AC were studied. Patients with bundle branch block or more than 1 AC were excluded. Sixty-four patients had manifest preexcitation (group 1) and 26 had a concealed AC (group 2). Immediately after loss of preexcitation, 38 (59%) patients with a manifest AC showed T-wave abnormalities. In contrast, none of the patients with a concealed AC had T-wave abnormalities after ablation (P <.05). The T-wave changes (1) did not correlate with the number or duration of energy applications or with markers of tissue injury; (2) correlated with the location of the AC and the degree of preexcitation, respectively; and (3) completely resolved over a period of weeks to months. None of the patients had recurrence of preexcitation or tachycardia during a mean follow-up of 16 +/- 7 months. CONCLUSIONS: T-wave changes after ablation are most likely caused by "cardiac memory" and are not a sign of myocardial or coronary injury.

Adult↗
PubMed1998

An increase in sinus rate following radiofrequency energy application in the posteroseptal space.

An increase in sinus rate has been previously described in patients with AV node reentry (AVNRT) following successful AV node modification. This increase could either be a specific sign of elimination of slow pathway conduction or it could be a consequence of energy application in the posteroseptal area. Thus, we compared the changes in sinus cycle length following successful slow pathway ablation (defined as complete elimination of dual AV node physiology) in patients having AVNRT with those in patients undergoing successful ablation of a posteroseptal atrioventricular accessory connection. Twenty five patients (16 women and 9 men, mean age 41 +/- 4 years) with typical AVNRT (cycle length 378 +/- 12 ms) and 29 patients (16 women and 13 men, age 34 +/- 5 years) with an accessory connection (17 manifest and 12 concealed) were studied. The electrophysiology study was performed during sedation with Fentanyl and Midazolam. The mean number of energy applications was 3 +/- 1 for successful slow pathway ablation and 4 +/- 1 for successful ablation of the accessory connection (p:NS). Following the successful energy application, the sinus cycle length decreased significantly 776 ms at baseline to 691 ms in patients with AVNRT. Following successful ablation of the posteroseptal AC, sinus cycle length decreased from 755 ms at baseline to 664 ms (p < 0.05 in both groups [difference between groups not significant]). The decrease in sinus cycle length did not correlate with the number of RF energy applications required for successful ablation or the total energy delivered. In conclusion, ablation of the AV node slow pathway and a posteroseptal accessory connection results in similar increases in the sinus rate. Thus, the increase in sinus rate is probably due to energy application in the posteroseptal space, possibly due to concomitant destruction of vagal inputs, and it is not specific for elimination of slow pathway conduction.

Adult↗
PubMed1996

Electrical remodeling in atrial fibrillation. Time course and mechanisms.

BACKGROUND: Atrial fibrillation is self-perpetuating, suggesting that the tachyarrhythmia causes electrophysiological changes that contribute to the progressive nature of the disease. In animal models, pacing-induced rapid atrial rates result in sustained atrial fibrillation. This is mediated by shortening of refractory periods termed electrical remodeling. The purpose of the present study was to characterize the time course of electrical remodeling and to define mechanisms of the phenomenon. METHODS AND RESULTS: Closed-chest dogs were anesthetized, pretreated with atropine and propranolol, and subjected to 7 hours of atrial pacing at 800 bpm. The effective and absolute refractory periods (ARP and ERP) were measured during and after rapid pacing, and transvenous endocardial biopsy specimens were examined using electron microscopy. Despite autonomic blockade and the absence of change in right atrial pressure, persistent atrial tachycardia caused ARP and ERP to fall by > 10%. Electrical remodeling developed quickly, with more than half of the phenomenon occurring during the first 30 minutes of high-rate pacing. Pretreatment with glibenclamide in doses sufficient to block the ATP-sensitive potassium current had no effect. Atrial electrical remodeling was blocked by verapamil and accentuated by hypercalcemia. Biopsy specimens from controls subjected to rapid pacing showed mitochondrial swelling consistent with calcium overload. Biopsies from verapamil-treated animals were normal. CONCLUSIONS: Atrial electrical remodeling develops quickly, is progressive, and may be persistent. Shifts in autonomic tone, atrial stretch, or depletion of high-energy phosphates do not contribute significantly to the phenomenon. Results of the study suggest that atrial electrical remodeling is mediated by rate-induced intracellular calcium overload.

Animals↗