Low atrial septal pacing with dual-chamber pacemakers reduces atrial fibrillation in sick sinus syndrome

SummaryBackgroundSick sinus syndrome (SSS) is often complicated with the additional presence of atrial fibrillation (AF). Atrial septal pacing, compared with right atrial appendage (RAA) pacing, shortens the atrial conduction time and reduces the dispersion of the refractoriness. However, low atrial septal (LAS) pacing's efficacy for preventing AF in SSS remains controversial in Japan.Methods and resultsWe analyzed 95 consecutive patients with SSS who underwent dual-chamber pacemaker implantations. Forty-two patients (44%) had a history of AF at the time of the pacemaker implantation. In the group without a history of AF, LAS pacing was performed in 17 patients, and RAA pacing in 36 patients. In the group with a history of AF, LAS pacing was performed in 15 patients, and RAA pacing in 27 patients. We evaluated whether LAS pacing prevented the development of de novo AF and the persistence of AF after pacemaker implantations. No significant differences were found in the baseline characteristics between the RAA and LAS groups regardless of an AF history. During a 1-year follow-up period, in the SSS patients without a history of AF, 19.0% (7/36) of the RAA group developed de novo AF, however, 5.9% (1/17) of the LAS group developed de novo AF (p=0.20). On the other hand, in the SSS patients with a history of AF, 22.0% (6/27) of the RAA group developed persistent AF, but none of the LAS group developed any persistent AF (p=0.049). There were no post-operative complications related to the LAS pacing.ConclusionsLAS pacing is safe and feasible. LAS pacing may prevent the progression to persistent AF in SSS patients with dual-chamber pacemakers

Myelination and axonal electrical activity modulate the distribution and motility of mitochondria at CNS nodes of Ranvier

Energy production presents a formidable challenge to axons as their mitochondria are synthesized and degraded in neuronal cell bodies. To meet the energy demands of nerve conduction, small mitochondria are transported to and enriched at mitochondrial stationary sites located throughout the axon. In this study, we investigated whether size and motility of mitochondria in small myelinated central nervous system axons was differentially regulated at nodes, and whether mitochondrial distribution and motility are modulated by axonal electrical activity. The size/volume of mitochondrial stationary sites was significantly larger in juxtaparanodal/internodal axoplasm than in nodal/paranodal axoplasm. By 3-dimensional electron microscopy, we observed that axonal mitochondrial stationary sites were composed of multiple mitochondria of varying length, except at nodes where mitochondria were uniformly short and frequently absent altogether. Mitochondrial transport speed was significantly reduced in nodal axoplasm when compared to internodal axoplasm. Increased axonal electrical activity decreased mitochondrial transport and increased the size of mitochondrial stationary sites in nodal/paranodal axoplasm. Decreased axonal electrical activity had the opposite effects. In cerebellar axons of the myelin deficient rat, which contains voltage-gated Na(+) channel clusters but lacks paranodal specializations, axonal mitochondrial motility and stationary site size were similar at Na(+) channel clusters and other axonal regions. These results demonstrate juxtaparanodal/internodal enrichment of stationary mitochondria and neuronal activity-dependent dynamic modulation of mitochondrial distribution and transport in nodal axoplasm. In addition, the modulation of mitochondrial distribution and motility requires oligodendrocyte-axon interactions at paranodal specializations

Mutant huntingtin impairs Ku70-mediated DNA repair

Mutant huntingtin prevents interaction of the DNA damage repair complex component Ku70 with damaged DNA, blocking repair of double-strand breaks