Oxytocin-monomeric red fluorescent protein 1 synthesis in the hypothalamus under osmotic challenge and acute hypovolemia in a transgenic rat line.

We generated a transgenic rat line that expresses oxytocin (OXT)-monomeric red fluorescent protein 1 (mRFP1) fusion gene to visualize the dynamics of OXT. In this transgenic rat line, hypothalamic OXT can be assessed under diverse physiological and pathophysiological conditions by semiquantitative fluorometry of mRFP1 fluorescence intensity as a surrogate marker for endogenous OXT. Using this transgenic rat line, we identified the changes in hypothalamic OXT synthesis under various physiological conditions. However, few reports have directly examined hypothalamic OXT synthesis under hyperosmolality or hypovolemia. In this study, hypothalamic OXT synthesis was investigated using the transgenic rat line after acute osmotic challenge and acute hypovolemia induced by intraperitoneal (i.p.) administration of 3% hypertonic saline (HTN) and polyethylene glycol (PEG), respectively. The mRFP1 fluorescence intensity in the paraventricular (PVN) and supraoptic nuclei (SON) was significantly increased after i.p. administration of HTN and PEG, along with robust Fos-like immunoreactivity (co-expression). Fos expression showed neuronal activation in the brain regions that are associated with the hypothalamus and/or are involved in maintaining water and electrolyte homeostasis in HTN- and PEG-treated rats. OXT and mRFP1 gene expressions were dramatically increased after HTN and PEG administration. The plasma OXT level was extremely increased after HTN and PEG administration. Acute osmotic challenge and acute hypovolemia induced upregulation of hypothalamic OXT in the PVN and SON. These results suggest that not only endogenous arginine vasopressin (AVP) but also endogenous OXT has a key role in maintaining body fluid homeostasis to cope with hyperosmolality and hypovolemia.

Non-Reentrant Fascicular Tachycardia: Clinical and Electrophysiological Characteristics of a Distinct Type of Idiopathic Ventricular Tachycardia.

BACKGROUND: The most common form of idiopathic Purkinje-related ventricular tachycardia (VT) is the reentrant type. We describe the clinical and electrophysiological characteristics of focal non-reentrant fascicular tachycardia. METHODS AND RESULTS: Among 530 idiopathic VT patients who were referred for ablation, we identified 15 (2.8%) with non-reentrant fascicular tachycardia (11 men, 45±21 years). Sinus rhythm ECG showed normal conduction intervals with a His-ventricular interval of 41±4 ms. All patients had monomorphic VT (cycle length: 337±88 ms) with a relatively narrow QRS (123±12 ms), and they did not respond to verapamil during the initial presentation. VT exhibited right bundle-branch block/superior axis configuration in 11 patients (73%) and inferior axis in 3 (20%). In 1 patient (7%), VT exhibited left bundle-branch block/superior axis configuration. During ablation, spontaneous VT occurred in 3 patients (20%) and nonentraintable VT or identical premature ventricular complex was induced in 9 (60%). A high-frequency presystolic Purkinje potential was recorded during VT/premature ventricular complex, preceding the QRS by 25±16 ms. VT recurrence was observed in 4 patients (27%), and among them, 3 underwent pacemap-guided ablation during the first session. A second ablation with activation mapping guidance eliminated the VT during the 88±8-month follow-up. CONCLUSIONS: Among idiopathic VT cases referred for ablation, 2.8% were focal non-reentrant fascicular tachycardia, which had distinct clinical characteristics and usually originated from the left posterior fascicle, and less commonly from the left anterior fascicle and right ventricular Purkinje network. Catheter ablation is effective, whereas pacemap-guided approach is less efficacious.