SK channels are present in human atria where they participate in repolarization. SK2 and SK3 were down-regulated and had reduced functional importance in chronic AF. As SK current was not found to contribute substantially to the ventricular AP, pharmacological inhibition of SK channels may be a putative atrial-selective target for future antiarrhythmic drug therapy.

Background Recent evidence suggests that atrial fibrillation (AF) is maintained by high-frequency reentrant sources with a left-to-right–dominant frequency gradient, particularly in patients with paroxysmal AF (pAF). Unequal left-to-right distribution of inward rectifier K+ currents has been suggested to underlie this dominant frequency gradient, but this hypothesis has never been tested in humans. Methods and Results Currents were measured with whole-cell voltage-clamp in cardiomyocytes from right atrial (RA) and left (LA) atrial appendages of patients in sinus rhythm (SR) and patients with AF undergoing cardiac surgery. Western blot was used to quantify protein expression of IK1 (Kir2.1 and Kir2.3) and IK,ACh (Kir3.1 and Kir3.4) subunits. Basal current was ≈2-fold larger in chronic AF (cAF) versus SR patients, without RA-LA differences. In pAF, basal current was ≈2-fold larger in LA versus RA, indicating a left-to-right atrial gradient. In both atria, Kir2.1 expression was ≈2-fold greater in cAF but comparable in pAF versus SR. Kir2.3 levels were unchanged in cAF and RA-pAF but showed a 51% decrease in LA-pAF. In SR, carbachol-activated (2 μmol/L) IK,ACh was 70% larger in RA versus LA. This right-to-left atrial gradient was decreased in pAF and cAF caused by reduced IK,ACh in RA only. Similarly, in SR, Kir3.1 and Kir3.4 proteins were greater in RA versus LA and decreased in RA of pAF and cAF. Kir3.1 and Kir3.4 expression was unchanged in LA of pAF and cAF. Conclusions Our results support the hypothesis that a left-to-right gradient in inward rectifier background current contributes to high-frequency sources in LA that maintain pAF. These findings have potentially important implications for development of atrial-selective therapeutic approaches.

Background and purpose: This study was designed to establish the pathology-specific inhibitory effects of the I Kur /I to /I K,ACh blocker AVE0118 on atrium-selective channels and its corresponding effects on action potential shape and effective refractory period in patients with chronic AF (cAF). Experimental approach: Outward K þ -currents of right atrial myocytes and action potentials of atrial trabeculae were measured with whole-cell voltage clamp and microelectrode techniques, respectively. Outward currents were dissected by curve fitting. Key results: Four components of outward K þ -currents and AF-specific alterations in their properties were identified. I to was smaller in cAF than in SR, and AVE0118 (10 mM) apparently accelerated its inactivation in both groups without reducing its amplitude. Amplitudes of rapidly and slowly inactivating components of I Kur were lower in cAF than in SR. The former was abolished by AVE0118 in both groups, the latter was partially blocked in SR, but not in cAF, even though its inactivation was apparently accelerated in cAF. The large non-inactivating current component was similar in magnitude in both groups, but decreased by AVE0118 only in SR. AVE0118 strongly suppressed AF-related constitutively active I K,ACh and prolonged atrial action potential and effective refractory period exclusively in cAF. Conclusions and implications: In atrial myocytes of cAF patients, we detected reduced function of distinct I Kur components that possessed decreased component-specific sensitivity to AVE0118 most likely as a consequence of AF-induced electrical remodelling. Inhibition of profibrillatory constitutively active I K,ACh may lead to pathology-specific efficacy of AVE0118 that is likely to contribute to its ability to convert AF into SR.

Our data suggest that B19V but not HBoV demonstrates a lifelong persistence in the heart. The detection of B19V DNA in heart tissue showed no correlation with clinical symptoms. We strongly recommend that serological testing become a standardized procedure for future studies, to obtain representative data concerning the prevalence of B19V in the heart.

No abstract

Rate-dependent block of Na(+) channels represents the main antiarrhythmic mechanism of vernakalant in the fibrillating atrium. Open channel block of early transient outward currents and IK,ACh could also contribute.

The PAS-Port proximal anastomotic device produces an effective anastomosis with a 9-month patency rate that is comparable with that of a hand-sewn anastomosis. It allows for construction of a proximal anastomosis without aortic clamping and requires less time than a hand-sewn anastomosis.

Redo coronary artery bypass grafting (CABG) is still associated with increased morbidity and mortality compared to primary operation. Myocardial protection is one of the key issues in redo on pump CABG and is still a matter of debate. Off pump redo CABG seems to be an attractive alternative as native coronary blood flow remains and cross clamping of the aorta is avoided. The aim of this retrospective study was to compare the outcome of redo CABG with and without CPB. From 1/1998 to 5/2004 redo CABG was performed in 195 patients (pts): 162 male (83.1%) and 33 female (16.9%) pts, age 66 +/- 9 years. In 160 pts, CPB with isolated antegrade myocardial protection was used for redo CABG. Off pump redo CABG was performed in 35 pts (30 male (85.7%) and 5 female (14.3%), age 67 +/- 8 years). Perioperative overall mortality rate was 3.6% (n = 7) and comparable in both groups (on pump 3.8% versus off pump 2.9%; p = 0.90), as well as perioperative myocardial infarction, intraaortic balloon pump implantation rate and secondary morbidity. Complete revascularization was achieved in 139 pts (86.9%) after on pump CABG and in 17 pts (48.6%) of the off pump group (p < 0.01). The average number of grafts was significantly higher in the on pump group (2.8 +/- 0.78 versus 1.6 +/- 0.6; p = 0.04).Furthermore, 20 pts (12.5%) in the on pump group died during follow-up (50 +/- 16 months). Five pts (25.0%) died due to cardiac reasons. In the off pump group 3 pts (8.6%) died during follow-up (44 +/- 13 months), noncardiac related. Overall survival was 83.8% in the on pump group and 88.6% in the off pump group (p = 0.92). On pump redo CABG and off pump redo CABG can be safely performed with low mortality and morbidity. Off pump redo CABG might be limited due to incomplete revascularization.