Effects of Acetylcholine and Noradrenalin on Action Potentials of Isolated Rabbit Sinoatrial and Atrial Myocytes

The autonomic nervous system controls heart rate and contractility through sympathetic and parasympathetic inputs to the cardiac tissue, with acetylcholine (ACh) and noradrenalin (NA) as the chemical transmitters. In recent years, it has become clear that specific Regulators of G protein Signaling proteins (RGS proteins) suppress muscarinic sensitivity and parasympathetic tone, identifying RGS proteins as intriguing potential therapeutic targets. In the present study, we have identified the effects of 1 μM ACh and 1 μM NA on the intrinsic action potentials of sinoatrial (SA) nodal and atrial myocytes. Single cells were enzymatically isolated from the SA node or from the left atrium of rabbit hearts. Action potentials were recorded using the amphotericin-perforated patch-clamp technique in the absence and presence of ACh, NA, or a combination of both. In SA nodal myocytes, ACh increased cycle length and decreased diastolic depolarization rate, whereas NA decreased cycle length and increased diastolic depolarization rate. Both ACh and NA increased maximum upstroke velocity. Furthermore, ACh hyperpolarized the maximum diastolic potential. In atrial myocytes stimulated at 2 Hz, both ACh and NA hyperpolarized the maximum diastolic potential, increased the action potential amplitude, and increased the maximum upstroke velocity. Action potential duration at 50 and 90% repolarization was decreased by ACh, but increased by NA. The effects of both ACh and NA on action potential duration showed a dose dependence in the range of 1–1000 nM, while a clear-cut frequency dependence in the range of 1–4 Hz was absent. Intermediate results were obtained in the combined presence of ACh and NA in both SA nodal and atrial myocytes. Our data uncover the extent to which SA nodal and atrial action potentials are intrinsically dependent on ACh, NA, or a combination of both and may thus guide further experiments with RGS proteins

Totally thoracoscopic ablation for atrial fibrillation:a systematic safety analysis

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Long-term outcome after totally thoracoscopic ablation for atrial fibrillation

Introduction: Totally thoracoscopic ablation for symptomatic atrial fibrillation (AF) refractory to drug or catheter based therapy is indicated as a Class 2A recommendation according to latest guidelines. Evidence for long-term rhythm control and stroke reduction is limited. The aim of this study was to report on long-term outcome after totally thoracoscopic ablation. Methods and Results: In total 82 consecutive patients were included that underwent totally thoracoscopic ablation including left appendage closure (2012-2013). The primary outcome was freedom from atrial arrhythmia recurrence. Secondary outcomes were survival, freedom from cerebrovascular events, freedom from reablation and definite pacemaker implantation. The mean age was 59.9 ± 8.6 years and 71% were male. The mean CHA2DS2-VASc score was 1.2 ± 1.0. The overall freedom from atrial arrhythmia was 60% after a mean follow up of 4.0 ± 0.6 years. Freedom from cerebrovascular events was 98.8% after mean follow-up of 4.4 ± 0.3 years and overall survival was 98.8%, with one noncardiac related death. The observed rate of ischemic stroke, hemorrhagic stroke or transient ischemic attack was 0.3 per 100 patient-years. Conclusions: Totally thoracoscopic ablation is an effective sustainable rhythm control therapy for AF with a reasonable recurrence rate and low stroke rate when performed in dedicated AF centers

A novel intra-ventricular assist device enhances cardiac performance in normal and acutely failing isolated porcine hearts

Background: We recently demonstrated that a novel intra-ventricular membrane pump (IVMP) was able to increase the pump function of isolated beating porcine hearts. In follow-up, we now investigated the impact of the IVMP on myocardial oxygen consumption and total mechanical efficiency (TME) and assessed the effect of IVMP-support in acutely failing hearts. Methods: In 10 ex vivo beating porcine hearts, we studied hemodynamic parameters, as well as arterial and coronary venous oxygen content. We assessed cardiac power (CP), myocardial oxygen consumption (MVO 2), and TME (CP divided by MVO 2) under baseline conditions and during IVMP-support. Additionally, five isolated hearts were subjected to global hypoxia to investigate the effects of IVMP-support on CP under conditions of acute heart failure. Results: Under physiological conditions, baseline CP was 0.36 ± 0.10 W, which increased to 0.65 ± 0.16 W during IVMP-support (increase of 85% ± 24, p < 0.001). This was accompanied by an increase in MVO2 from 18.6 ± 6.2 ml/min at baseline, to 22.3 ± 5.0 ml/min during IVMP-support (+26 ± 31%, p = 0.005). As a result, TME (%) increased from 5.9 ± 1.2 to 8.8 ± 1.8 (50 ± 22% increase, p < 0.001). Acute hypoxia-induced cardiac pump failure reduced CP by 35 ± 6%, which was fully restored to baseline levels during IVMP-support in all hearts. Conclusion: IVMP-support improved mechanical efficiency under physiological conditions, as the marked increase in cardiac performance only resulted in a modest increase in oxygen consumption. Moreover, the IVMP rapidly restored cardiac performance under conditions of acute pump failure. These observations warrant further study, to evaluate the effects of IVMP-support in in vivo animal models of acute cardiac pump failure

Increased amount of atrial fibrosis in patients with atrial fibrillation secondary to mitral valve disease

Objective: Atrial fibrosis is related to atrial fibrillation but may differ in patients with mitral valve disease or lone atrial fibrillation. Therefore, we studied atrial fibrosis in patients with atrial fibrillation + mitral valve disease or with lone atrial fibrillation and compared it with controls. Methods: Left and right atrial appendages amputated during Maze III surgery for lone atrial fibrillation (n = 85) or atrial fibrillation + mitral valve disease (n = 26) were embedded in paraffin, sectioned, and stained with picrosirius red. Atria from 10 deceased patients without a cardiovascular history served as controls. A total of 1048 images (4-mu m sections, 10-fold magnification, 4 images per appendage) were obtained and digitized. The percentage of fibrous tissue was calculated by quantitative morphometry. Results: Irrespective of the presence or absence of atrial fibrillation or mitral valve disease, more fibrous tissue was present in right atrial appendages than in left atrial appendages (12.7% +/- 5.7% vs 8.2% +/- 3.9%; P <.0001). The mean amount of fibrous tissue in the atria was significantly larger in patients with atrial fibrillation + mitral valve disease than in patients with lone AF and controls (13.6% +/- 5.8%, 9.7% +/- 3.2%, and 8.8% +/- 2.4%, respectively; P <.01). No significant differences existed between patients with lone atrial fibrillation and patients without a cardiovascular history (controls). Conclusions: Atria of patients with atrial fibrillation and mitral valve disease have more fibrosis than atria of patients with lone atrial fibrillation. However, patients with lone atrial fibrillation have an equal amount of atrial fibrosis compared with controls. These findings support the notion that fibrosis plays a more important role in the pathogenesis of atrial fibrillation secondary to mitral valve disease than in lone atrial fibrillation and potentially explains the relatively poor success of antiarrhythmic surgery in patients with mitral valve disease. (J Thorac Cardiovasc Surg 2012;144:327-33

Completely thoracoscopic pulmonary vein isolation with ganglionic plexus ablation and left atrial appendage amputation for treatment of atrial fibrillation

Objective: Percutaneous catheter pulmonary vein isolation (PVI) has been the preferred choice for invasive treatment of symptomatic, drug-refractory lone atrial fibrillation (AF). Incomplete ablation lines, procedure-related morbidity and long-term success remain, however, a problem. A minimally invasive surgical approach can provide an attractive and secure alternative. Surgery offers an epicardial, bipolar approach under direct vision, but the invasiveness of surgery remains a problem. Therefore, we developed a completely thoracoscopic procedure. The objective of this study was to assess the feasibility, safety and effectiveness of a completely thoracoscopic surgical procedure to cure lone AF. Methods: Bilateral 'video-assisted thoracoscopy' was performed to isolate the bilateral pairs of pulmonary veins using bipolar RF-energy, to ablate the ganglionic plexus (GP) and to amputate the left atrial appendage. Preoperative, in-hospital and follow-up data were collected for our first 30 patients. Results: AF was paroxysmal in 63%, persistent in 27% and permanent in 10% of cases. The mean (+/-SD) left atrial diameter was 42.1 +/- 7.4 mm and the mean duration of AF was 79.0 +/- 63.9 months. Freedom from AF was obtained in 77% of the patients during a mean follow-up of 11.6 months. Forty-three percent of the patients had previously undergone a percutaneous PVI and were all free from AF during follow-up. Mean operation time was 137.4 +/- 24.7 min. All patients were extubated in the operating room and left the recovery room within 12 h. The mean hospital stay was 5.1 +/- 1.8 days. Two patients ultimately underwent a median sternotomy. No CVAs or pacemaker implantation were identified and none of the patients died. Conclusion: We report our initial experience of a completely thoracoscopic PVI with GP-ablation and amputation of the left atrial appendage and demonstrate that the procedure is feasible, safe and effective for the treatment of lone AF. (C) 2010 European Association for Cardio-Thoracic Surgery. Published by Elsevier B.V. All rights reserve

Thoracoscopic Video-Assisted Pulmonary Vein Antrum Isolation, Ganglionated Plexus Ablation and Periprocedural Confirmation of Ablation Lesions. First Results of a Hybrid Surgical-Electrophysiological Approach for Atrial Fibrillation

BACKGROUND: -Thoracoscopic pulmonary vein isolation (PVI) and ganglionated plexus (GP) ablation is a novel approach in the treatment of atrial fibrillation (AF). We hypothesize that meticulous electrophysiological confirmation of PVI results in fewer recurrences of AF during follow-up. METHODS AND RESULTS: -Surgery was performed through three ports bilaterally. GPs were localized and subsequently ablated. PVI was performed and entry and exit block was confirmed. Additional left atrial ablation lines (ALAL) were created, and conduction block verified, in patients with non-paroxysmal AF. The left atrial appendage was removed. Freedom of AF was assessed by ECGs and Holter monitoring every 3 months or during symptoms of arrhythmia. Anti-arrhythmic drugs (AAD) were discontinued after 3 months and oral anticoagulants were discontinued according to the guidelines. Thirty-one patients were treated (16 paroxysmal AF, 13 persistent AF, 2 long standing persistent (LSP) AF). Thirteen patients with non-paroxysmal received ALAL. After one year, 19/22 patients (86%) had no recurrences of AF, atrial flutter or atrial tachycardia and were not using AAD (11/12 paroxysmal, 7/9 persistent, 1/1 LSP). Three patients had a sternotomy because of uncontrolled bleeding during thoracoscopic surgery. Four adverse events were; 1 hemothorax, 1 pneumothorax and 2 pneumonia. No thromboembolic complications or mortality occurred. CONCLUSIONS: -Thoracoscopic surgery with PVI and GP ablation for AF is a safe and successful procedure with a single procedure success rate of 86% at one year. Electrophysiological guided thorough PVI and ALAL creation presumably contributes in achieving a high success rate in the surgical treatment of A

Freedom from atrial arrhythmias after classic maze III surgery: A 10-year experience

Objectives: We studied the persistence of favorable outcome, the occurrence of new atrial arrhythmias, and sinus node dysfunction in patients who underwent the maze III procedure. Methods: Preoperative, in-hospital, and follow-up data of 203 patients who underwent the maze III procedure between June 1993 and June 2003 were collected. A total of 139 patients underwent the maze procedure for lone atrial fibrillation, and 64 patients underwent the maze procedure and concomitant cardiac surgery. Results: There was no 30-day postoperative mortality. During a mean follow-up of 4.0 +/- 2.6 years, 12 patients (6%) died (2 cardiac related). At the end of follow-up, freedom from supraventricular arrhythmias was 80% for the lone atrial fibrillation group and 64% for the concomitant atrial fibrillation group. Freedom from stroke during follow-up was 100% in the lone atrial fibrillation group and 97% in the concomitant group. Multivariate analysis revealed that rhythm at 1-year follow-up (P <.001; odds ratio 9.56, 95% confidence limits 3.92-23.31) and preoperative left atrium dimension (P = .028; odds ratio 1.06 for every millimeter, 95% confidence limits 1.01-1.12) were predictors of success at the end of follow-up. Conclusions: This study shows that the favorable results of the maze III procedure in terms of freedom from supraventricular arrhythmias persist in most patients for at least 4 year

Neurokinin-3 receptor activation selectively prolongs atrial refractoriness by inhibition of a background K+ channel

The cardiac autonomic nervous system (ANS) controls normal atrial electrical function. The cardiac ANS produces various neuropeptides, among which the neurokinins, whose actions on atrial electrophysiology are largely unknown. We here demonstrate that the neurokinin substance-P (Sub-P) activates a neurokinin-3 receptor (NK-3R) in rabbit, prolonging action potential (AP) duration through inhibition of a background potassium current. In contrast, ventricular AP duration was unaffected by NK-3R activation. NK-3R stimulation lengthened atrial repolarization in intact rabbit hearts and consequently suppressed arrhythmia duration and occurrence in a rabbit isolated heart model of atrial fibrillation (AF). In human atrial appendages, the phenomenon of NK-3R mediated lengthening of atrial repolarization was also observed. Our findings thus uncover a pathway to selectively modulate atrial AP duration by activation of a hitherto unidentified neurokinin-3 receptor in the membrane of atrial myocytes. NK-3R stimulation may therefore represent an anti-arrhythmic concept to suppress re-entry-based atrial tachyarrhythmias, including AF