Some (piperidinomethylene)bis(phosphonic acid) derivatives were prepared and their activity to inhibit a rise in serum calcium induced by parathyroid hormone in thyroparathyroidectomised rats was evaluated. Several (4-alkylidene-, 4,4-dialkyl-, or 4-alkyl-4-halopiperidinomethylene)bis(phosphonic acid) derivatives showed considerable inhibitory activity. But compounds having aromatic and polar substituents such as azido, hydroxy, amino and amido on the piperidine ring were generally inactive. In this study, two 4-alkylidene compounds (8a and 8b) and a 4,4-cyclic dialkyl compound (61) showed potent activity when administered either intravenously or perorally.
SUMMARYRadiofrequency catheter ablation (RFCA) for supraventricular arrhythmias results in parasympathetic nervous damage. Recently, RFCA around the pulmonary veins (PVs) has become a standardized curative therapy for atrial fibrillation (AF). The aim of the present study was to elucidate the relationship between the degree of vagal denervation and RFCA sites, including the PV areas. In 21 dogs, RFCA was performed at the ostium of the right PV (n = 7), ostium of the left PV (n = 7), and posteroseptal site of the right atrium (n = 7). Electrical stimulation of the cervical vagal trunk (ESCV) was performed and the resultant increase in the P-P interval (PPI) observed on the ECG was measured. The PPI was compared between the different RFCA sites. In another 7 animals, the vagal ganglia located in the fat pads that innervate the sinoatrial (SA) node were also stimulated (ESFP), testing the degree of postganglionic damage. The PPI after RFCA was decreased with right PV RFCA whereas there was no change with left PV RFCA. The ESFP yielded a significantly greater decrease in the PPI than the ESCV. The PPI during ESFP was completely blocked by hexamethonium, injected into the fat pad. The ESCV after the hexamethonium injection did not result in complete disappearance of the PPI. Thus, right PV RFCA markedly damaged the vagal innervation of the SA node, whereas left PV RFCA produced little damage. The major type of damage was partial postganglionic fiber damage. An alternate vagal pathway external to the fat pads is proposed. (Int Heart J 2008; 49: 493-506)
The authors investigated bipolar electrograms recorded from the catheter tip at the actual successful ablation sites in 22 consecutive patients with concealed Wolff-Parkinson-White syndrome to clarify the characteristics of the potentials indicating the optimal site for catheter ablation. In all patients the retrograde transaortic approach to their left-sided accessory pathways, and a temperature-controlled (60 degrees C) energy delivery, were performed. The authors assumed that a shorter dissociation time (time from energy delivery to ventriculoatrial conduction dissociation) indicated more accurate catheter mapping. A significant negative correlation (r = 0.527, p < 0.05) between the AV ratio (ratio of the amplitudes of the atrial to ventricular potentials) recorded at the ablation catheter tip and the dissociation time was observed. When the AV ratio and the dissociation time were compared among the groups classified according to the corresponding Npeak (the number of positive potential peaks in the electrogram obtained from the ablation catheter tip during right ventricular apical pacing) value, they differed significantly (p < 0.05 and p < 0.01, respectively), ie, a higher AV ratio and a shorter dissociation time related to a multipeak electrogram from the ablation catheter tip. The authors conclude that the atrial insertion site of the accessory pathway, exhibiting a multipeak complex electrogram that may represent nonuniform anisotropic characteristics, is an adequate ablation site.
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