How to approach sleep disordered breathing in heart failure patients.

Sleep disordered breathing (SDB) is a major public health problem and is highly prevalent in patients with heart failure (HF) disease. In these patients, a thorough pre-test probability evaluation and appropriate selection of overnight sleep study should be performed before treatment evaluation. A high index of suspicion for SDB should exist when an HF patient presents with the associated clinical features or risk factors for SDB. With a high index of suspicion, polysomnography (PSG), as a gold standard, is able to confirm or rule out the disease; however, portable monitoring devices may also be appropriate and represent more cost effective diagnosis strategies to confirm the diagnosis in adequately selected patients among a HF cohort. The choice of treatment largely depends on the type and severity of SDB demonstrated by validated sleep recording. The treatment of OSA in HF with CPAP is well established, while the optimal treatment of CSA still to be defined.

Negative allosteric modulation of nicotinic acetylcholine receptors blocks nicotine self-administration in rats.

Drugs that antagonize nicotinic acetylcholine receptors (nAChRs) can be used to inhibit nicotine-induced behavior in both humans and animals. The aim of our experiments is to establish a proof-of-principle that antagonism of nAChRs by negative allosteric modulation can alter behavior in a relevant animal model of addiction, nicotine self-administration. We have identified a novel, negative allosteric modulator of nAChRs, UCI-30002 [N-(1,2,3,4-tetrahydro-1-naphthyl)-4-nitroaniline], with selectivity for the major neuronal nAChR subtypes over muscle-type nAChRs. After systemic administration, UCI-30002 significantly reduces nicotine self-administration in rats on both fixed ratio and progressive ratio schedules of reinforcement. The minimum effective dose that significantly alters nicotine self-administration corresponds to brain concentrations of UCI-30002 that produce at least 30% inhibition of the major neuronal nAChR subtypes measured in vitro. UCI-30002 has no effect on responding for food reinforcement in rats on either type of schedule, indicating that there is no effect on general responding or natural reward. UCI-30002 represents validation of the concept that negative allosteric modulators may have significant benefits as a strategy for treating nicotine addiction and encourages the development of subtype-selective modulators.