Hypothalamic gonadotropin-releasing hormone (GnRH) receptor neurons fire in synchrony with the female reproductive cycle.

Gonadotropin-releasing hormone (GnRH) controls mammalian reproduction via the hypothalamic-pituitary-gonadal (hpg) axis, acting on gonadotrope cells in the pituitary gland that express the GnRH receptor (GnRHR). Cells expressing the GnRHR have also been identified in the brain. However, the mechanism by which GnRH acts on these potential target cells remains poorly understood due to the difficulty of visualizing and identifying living GnRHR neurons in the central nervous system. We have developed a mouse strain in which GnRHR neurons express a fluorescent marker, enabling the reliable identification of these cells independent of the hormonal status of the animal. In this study, we analyze the GnRHR neurons of the periventricular hypothalamic nucleus in acute brain slices prepared from adult female mice. Strikingly, we find that the action potential firing pattern of these neurons alternates in synchrony with the estrous cycle, with pronounced burst firing during the preovulatory period. We demonstrate that GnRH stimulation is sufficient to trigger the conversion from tonic to burst firing in GnRHR neurons. Furthermore, we show that this switch in the firing pattern is reversed by a potent GnRHR antagonist. These data suggest that endogenous GnRH acts on GnRHR neurons and triggers burst firing in these cells during late proestrus and estrus. Our data have important clinical implications in that they indicate a novel mode of action for GnRHR agonists and antagonists in neurons of the central nervous system that are not part of the classical hpg axis.

Effects of circumferential ostial radiofrequency lesions on pulmonary vein activation recorded with a multipolar basket catheter.

AIMS: Two different ablation procedures are performed to cure patients of atrial fibrillation (AF): (1) the electrophysiological pulmonary vein (PV) isolation, and (2) the anatomical circumferential ablation of all four PV ostia. The aim of this study was to determine the effects of circumferential radiofrequency lesions around the ostia on PV activation. METHODS AND RESULTS: In 34 patients with drug refractory paroxysmal (N = 22) or persistent (N = 12) AF a 31-mm basket catheter (BC) was introduced transseptally in the PVs. After creating a circumferential ablation line around the PV ostia using a nonfluoroscopic 3D-navigation system, electrical isolation was achieved in 46% of the PVs, and prolongation of conduction time (+39 +/- 34 ms) was observed in 30%. PVs with persistent conduction (54%) were isolated by ablating the remaining conduction pathways using the BC. At 12 months follow-up, 62% of the patients were in stable sinus rhythm without antiarrhythmic drug therapy. Six patients had developed left atrial flutter. CONCLUSIONS: Anatomically guided, circumferential lesions around the PV ostia resulted in isolation in only 46% of the veins. At 12 months, 62% of the patients were free of AF without antiarrrhythmic drug treatment, however, 6 patients (18%) developed left atrial flutter.

Feasibility and safety of pulmonary vein isolation using a new mapping and navigation system in patients with refractory atrial fibrillation.

BACKGROUND: Ostial pulmonary vein (PV) isolation by radiofrequency (RF) catheter ablation can cure patients with atrial fibrillation (AF); however, this procedure carries the risk of PV stenosis. The aim of this study was to assess the feasibility of a new mapping and navigation technique using a multipolar basket catheter (BC) for PV isolation in patients with refractory AF and to analyze its safety with regard to PV stenosis at long-term follow-up. METHODS AND RESULTS: We studied 55 patients (mean age, 53+/-11 years; 40 male) with drug-refractory AF (paroxysmal, n=37; persistent, n=18). A 64-pole BC was placed transseptally into each of the accessible PVs. By use of a nonfluoroscopic navigation system, the ablation catheter was guided to the BC electrodes at the PV ostium, with earliest activation during sinus rhythm. RF was delivered by use of maximum settings of temperature at 50 degrees C and power at 30 W. The end point of the procedure was the complete elimination of all distal and fragmented ostial PV potentials. Of 165 targeted veins, 163 were successfully isolated with a mean RF duration of 720+/-301 seconds per vein. At 1-year follow-up, 62% of the patients were in sinus rhythm without antiarrhythmic drugs. Contrast-enhanced magnetic resonance angiography revealed 2 PV stenoses of >25% out of 165 treated vessels. CONCLUSIONS: The use of a multipolar BC allowed effective and safe PV isolation by combining 3D mapping and navigation. At 1-year follow-up, 62% of the patients were in sinus rhythm without antiarrhythmic drugs, and the incidence of relevant diameter reduction of the treated PVs was 1.2%.