No abstract

Our results highlight the contribution of Cx43 to the pathophysiology of AF and demonstrate the viability of gene therapy for prevention of atrial arrhythmias.

Knockdown of caspase 3 by atrial Ad-siRNA-Cas3 gene transfer suppresses or delays the onset of persistent AF by reduction in apoptosis and prevention of intra-atrial conduction delay in a porcine model. These results highlight the significance of apoptosis in the pathophysiology of AF and demonstrate short-term efficacy of gene therapy for suppression of AF.

No abstract

Phrenic nerve stimulation occurred in 13% of patients undergoing LV lead placement and was more common at mid-lateral/posterior, and LV apical sites. Most cases (123/139; 88%) of PNS were mitigated via electrical reprogramming, without the need for invasive intervention.

Background-The intriguing monotony in the occurrence of intercaval conduction block during typical atrial flutter suggests an anatomic or electrophysiological predisposition for conduction abnormalities. Methods and Results-To determine the location of and potential electrophysiological basis for conduction block in the terminal crest region, a high-density patch electrode (10ϫ10 bipoles) was placed on the terminal crest and on the adjacent pectinate muscle region in 10 healthy foxhounds. With a multiplexer mapping system, local activation patterns were reconstructed during constant pacing (S 1 S 1 ϭ200 ms) and introduction of up to 2 extrastimuli (S 2 , S 3 ). Furthermore, effective refractory periods were determined across the patch. If evident through online analysis, the epicardial location of conduction block was marked for postmortem verification of its endocardial projection. Marked directional differences in activation were found in the terminal crest region, with fast conduction parallel to and slow conduction perpendicular to the intercaval axis (1.1Ϯ0.4 versus 0.5Ϯ0.2 m/s, PϽ0.01). In the pectinate muscle region, however, conduction velocities were similar in both directions (0.5Ϯ0.3 versus 0.6Ϯ0.2 m/s, PϭNS). Refractory patterns were relatively homogeneous in both regions, with local refractory gradients not Ͼ30 ms. During S 3 stimulation, conduction block parallel to the terminal crest was inducible in 40% of the dogs compared with 0% in the pectinate muscle region. Conclusions-Even in normal hearts, inducible intercaval block is a relatively common finding. Anisotropic conduction properties would not explain conduction block parallel to the intercaval axis in the terminal crest region, and obviously, refractory gradients do not seem to play a role either. Thus, the change in fiber direction associated with the terminal crest/pectinate muscle junction might form the anatomic/electrophysiological basis for intercaval conduction block.

Patient-alert features are a useful additional tool facilitating early detection of serious ICD complications, but they do not substitute for regular ICD follow-up, because of their low sensitivity.

Recent in vitro studies have described regional differences of ion current expression and function, possibly accounting for reduced homogeneity of repolarization in the heart. In 11 intact canine hearts regional disparity of repolarization was determined at baseline and after administration of the I(Kr) blocking agent dofetilide (30 microg/kg) and the I(Ks)-blocking agent chromanol 293b (10 mg/kg). Effective refractory periods (ERPs) were determined through up to 10 needle electrodes inserted into basal, midwall and apical regions of the left ventricular wall using the extrastimulus technique (cycle length [CL] 300 and 850 ms). At baseline (CL of 850 ms), ERPs were significantly longer in epicardial muscle layers of the apex compared to the base. In deeper muscle layers regional differences of ERPs were not detectable. Administration of dofetilide increased apico-basal disparity of repolarization, due to a more marked increase of ERPs in the apex than in the base. In contrast, homogeneous ERPs were evident along the apico-basal axis after administration of chromanol 293b. Transmural dispersion of refractoriness could not be observed in any region at baseline, or after drug-administration. In the intact canine heart, apico-basal disparity of repolarization varies between individual muscle layers. Dependent on their current specificity, antiarrhythmic agents may enhance or diminish regional disparity of repolarization.