Stimulation of non-myelinated pulmonary afferents evokes the pulmonary chemoreflex, a triad of apnoea, bradycardia and hypotension that is accompanied by bronchoconstriction (Paintal, 1973;Coleridge & Coleridge, 1984;Coleridge et al. 1989). Injection of the vanilloid compound capsaicin into the pulmonary circulation of numerous species activates pulmonary C fibres (also termed 'J-receptors'; Paintal, 1973) and evokes the pulmonary chemoreflex (Paintal, 1973;Coleridge et al. 1989). The recently developed competitive capsaicin antagonist capsazepine abolishes capsaicin-induced apnoea, bradycardia and hypotension in the adult rat in vivo (Lee & Lundberg, 1994), as well as significantly attenuating capsaicin-induced C fibre activity both in vitro and in vivo (Dickenson & Dray, 1991;Belvisi et al. 1992;Lee & Lundberg, 1994;Fox et al. 1995). Furthermore, capsazepine has been shown to reduce capsaicin-induced activation of the recently cloned non-selective cation channel vanilloid receptor subtype 1 (VR1) (Caterina et al. 1997). Although the endogenous VR1 ligand has not been

Background-Cardiac resynchronization therapy is widely used for the treatment of heart failure. Recent data suggest that electric separation during left ventricular pacing varies within the right ventricle (RV). We hypothesized that placement of the RV lead guided by maximal electric separation (MES) would improve response to cardiac resynchronization therapy compared with standard apical placement. Methods and Results-A single-blind, randomized controlled trial was conducted. Patients eligible for cardiac resynchronization therapy-D were enrolled. Left ventricular lead placement was performed at the coronary sinus branch. The RV outflow tract, septum, and apex were mapped during left ventricular pacing and MES recorded. Patients were randomized to receive either apical placement or RV lead placement at the site mapping MES. Left ventricular ejection fraction, 6-minute walk distance, and New York Heart Association functional class were recorded at baseline and 3 months by blinded observers. Response was defined as at least one of the following: 5% absolute increase in ejection fraction, 50 m increase in 6-minute walk distance, or an increase by >1 functional class. Primary end point was improvement in ejection fraction at 3 months. Fifty patients were randomized (25 MES-guided and 25 apical). Baseline characteristics were similar in the 2 groups. Electric separation was lower in the apex (143±23 versus 168±25 ms in MES group; P=0.01). MES was most commonly septal and rarely apical (4/50 patients). Responders in the MES-guided versus apical group are as follows: Echo 21 versus 13 patients (P=0.032), 6-minute walk distance 19 versus 12 patients (P=0.079), and functional class 22 versus 15 patients (P=0.051). No dislodgment or reposition for suboptimal defibrillation tests was reported. Conclusions-MES-guided PatientsConsecutive patients with conventional indications for CRT were recruited. The indication for CRT was standard according to current clinical guidelines: symptomatic HF despite optimal medical therapy, LV ejection fraction (EF) <35%, sinus rhythm, and QRS ≥120 ms with left bundle branch block morphology. Exclusion criteria were preexisting devices attending for upgrades, atrial arrhythmia, or inability to place the LV lead ( Figure 1). CRT devices were implanted as previously described. 23 Briefly, a 6947 dual-coil, high-voltage lead (Medtronic Inc, Minneapolis, MN) was placed at the RV apex to provide back-up pacing in the event of inadvertent atrioventricular block during CS lead placement. The LV lead was sited in the posterolateral branch (first option), lateral branch (second option), or middle cardiac vein (third option) of the CS. After satisfactory positioning of the LV lead, a deflectable catheter (Polaris, Boston Scientific, Natick, MA) was used to map the RV from RV outflow tract (RVOT) to apex, with care to avoid the anterior free wall. After completion of the protocol, this catheter was removed and replaced with a 5076 or 4076 active fixation pacing lead (Medtronic Inc, Minneapolis, MN) pl...

H1 receptor antagonism with loratadine does not influence physiologic cardiovascular control in young healthy subjects. However, the altered cardiac sympathovagal balance after oral administration of the H2 receptor antagonist ranitidine indicates a shift toward sympathetic predominance in heart rate control. The authors postulate that this could have implications regarding susceptibility to arrhythmias in conditions of heightened sympathetic stimulation.

MES was observed most commonly at the RV septum and rarely at the RV apex. Better correction of electrical and mechanical dyssynchrony by CRT may be achieved by placing the RV lead in a site outside of the apex in the majority of patients. Clinical studies exploring RV septal pacing in CRT seem warranted.