Parvalbumin (PV)-containing cortical GABA neurons include chandelier cells (PVChCs) and basket cells (PVBCs), which innervate the axon initial segment (AIS) and soma/proximal dendrites of pyramidal cells, respectively. In monkey prefrontal cortex (PFC), the density of PVChC axon cartridges detectable by PV immunoreactivity peaks prior to the onset of puberty before declining markedly to adult levels, whereas the density of PV-immunoreactive (IR) puncta (presumed PVBC boutons) increases during adolescence. These inverse developmental changes in bouton density could explain why an electron microscopy study found no change in the density of symmetric, presumably GABAergic, synapses between infancy and adulthood in monkey PFC. Alternatively, the inverse developmental trajectories of PVChC and PVBC boutons could represent cell type-specific differences in the maturation of PV protein levels. To differentiate between these two alternatives, multilabel confocal microscopy was used to quantify the number of PVChC and PVBC boutons per pyramidal neuron in the PFC of 3-month-old and adult monkeys. The mean number of PVChC boutons per pyramidal neuron AIS was, significantly, 32% lower in adult compared with 3-month-old monkeys, whereas the density of PVBC boutons per pyramidal neuron did not differ between age groups. In contrast, relative levels of PV protein were approximately twofold higher in PVBC boutons in adult animals, whereas PV levels in PVChC boutons did not differ between age groups. These findings suggest cell type-specific mechanisms of maturation of PV-containing GABAergic boutons in monkey PFC.

Background: Atrioventricular block requiring permanent pacemaker (PPM) implantation is a common complication of transcatheter aortic valve replacement (TAVR). The mechanism of atrioventricular (AV) block during TAVR is not fully understood, but it may be due to the mechanical stress of TAVR deployment, resulting in possible injury to the nearby compact AV node. Aortic valve calcification (AVC) may worsen this condition and has been associated with an increased risk for post-TAVR PPM implantation. We performed a retrospective analysis to determine if AVC is predictive for long-term right ventricular (RV) pacing in post-TAVR pacemaker patients at 30 days.Methods: A total of 262 consecutive patients who underwent TAVR with a balloon-expandable valve were analyzed. AVC data were derived from contrast-enhanced computed tomography and characterized by leaflet sector and region.Results: A total of 25 patients (11.1%) required post-TAVR PPM implantation. Seventeen patients did not require RV pacing at 30 days. Nine of these 17 patients had no RV pacing requirement within 10 days. The presence of intra-procedural heart block (P = 0.004) was the only significant difference between patients who did not require PPM and those who required PPM but they were not RV pacing-dependent at 30 days. Non-coronary cusp (NCC) calcium volume was significantly higher in patients who were pacemaker-dependent at 30 days (P = 0.01) and a calcium volume of > 239.2 mm 3 in the NCC was strongly predictive of pacemaker dependence at 30 days (area under the curve (AUC) = 0.813). Pre-existing right bundle branch block (RBBB) (odds ratio (OR) 105.4, P = 0.004), bifascicular block (OR 12.5, P = 0.02), QRS duration (OR 70.43, P = 0.007) and intraprocedural complete heart block (OR 12.83, P = 0.03) were also predictive of pacemaker dependence at 30 days. Conclusions:In patients who required PPM after TAVR, quantification of AVC by non-coronary leaflet calcium volume was found to be a novel predictor for RV pacing dependence at 30 days. The association of NCC calcification and PPM dependence may be related to the proximity of the conduction bundle to the non-coronary leaflet. Further studies are necessary to improve risk prediction for long-term RV pacing requirements following TAVR.

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