Evaluation of a new ultralow-dose radiation protocol for electrophysiological device implantation: A near-zero fluoroscopy approach for device implantation.

BACKGROUND: Radiation is one of the main hazards of electrophysiological device implantation, and insertion of cardiac resynchronization therapy (CRT) devices in particular is associated with high radiation doses. OBJECTIVE: The purpose of this study was to evaluate the impact of a new ultralow-dose radiation protocol on radiation doses, success rate, and safety of electrophysiological device implantations. METHODS: In 2018, we established a new ultralow-dose radiation protocol (reduced pulse width, increased thickness of minimum copper filters, reduced detector entrance dose, reduced pulse rate, optimized image postprocessing settings) for de novo device implantation at our hospital. A total of 1173 patients (11% single-chamber devices, 69% dual-chamber devices, 20% CRT devices) were analyzed. Five hundred twelve patients (44%) in the ultralow-dose group were compared to 661 patients (66%) treated during 2017 with a conventional low-dose protocol. RESULTS: With the ultralow-dose radiation protocol, effective doses could be reduced by 59% (median 0.25 [interquartile range: 0.11-0.63] vs median 0.10 [interquartile range: 0.03-0.28] mSv; P <.0001) per procedure without a significant change in procedure time (P = .5). This dose reduction could be achieved without decreasing procedure success (P = 1) or increasing complication rate (P = .8). Male gender, higher body mass index, increased procedure and fluoroscopy times, and use of the conventional radiation protocol were independent predictors of higher radiation doses in multivariate regression analysis. CONCLUSION: By establishing a new ultralow-dose radiation protocol, we could significantly decrease radiation exposure, reaching the lowest radiation doses for electrophysiological device implantation reported to date.

Identification of amino acids involved in histamine potentiation of GABA A receptors.

Histamine is a neurotransmitter involved in a number of physiological and neuronal functions. In mammals, such as humans, and rodents, the histaminergic neurons found in the tuberomamillary nucleus project widely throughout the central nervous system. Histamine acts as positive modulator of GABAA receptors (GABAARs) and, in high concentrations (10 mM), as negative modulator of the strychnine-sensitive glycine receptor. However, the exact molecular mechanisms by which histamine acts on GABAARs are unknown. In our study, we aimed to identify amino acids potentially involved in the modulatory effect of histamine on GABAARs. We expressed GABAARs with 12 different point mutations in Xenopus laevis oocytes and characterized the effect of histamine on GABA-induced currents using the two-electrode voltage clamp technique. Our data demonstrate that the amino acid residues ß2(N265) and ß2(M286), which are important for modulation by propofol, are not involved in the action of histamine. However, we found that histamine modulation is dependent on the amino acid residues α1(R120), ß2(Y157), ß2(D163), ß3(V175), and ß3(Q185). We showed that the amino acid residues ß2(Y157) and ß3(Q185) mediate the positive modulatory effect of histamine on GABA-induced currents, whereas α1(R120) and ß2(D163) form a potential histamine interaction site in GABAARs.

Direct action and modulating effect of (+)- and (-)-nicotine on ion channels expressed in trigeminal sensory neurons.

Nicotine sensory perception is generally thought to be mediated by nicotinic acetylcholine (nACh) receptors. However, recent data strongly support the idea that other receptors (e.g., transient receptor potential A1 channel, TRPA1) and other pathways contribute to the detection mechanisms underlying the olfactory and trigeminal cell response to nicotine flavor. This is in accordance with the reported ability of humans to discriminate between (+)- and (-)- nicotine enantiomers. To get a more detailed understanding of the molecular and cellular basis underlying the sensory perception of nicotine, we studied the activity of (+)- and (-)-nicotine on cultured murine trigeminal sensory neurons and on a range of heterologously expressed receptors. The human TRPA1 channel is activated by (-)-nicotine. In this work, we show that (+)-nicotine is also an activator of this channel. Pharmacological experiments using nicotinic acetylcholine receptors and transient receptor potential blockers revealed that trigeminal neurons express one or more unidentified receptors that are sensitive to (+)- and/or (-)-nicotine. Results also indicate that the presence of extracellular calcium ions is required to elicit trigeminal neuron responses to (+)- and (-)-nicotine. Results also show that both (+)-nicotine and (-)-nicotine can block 5-hydroxytryptamine type 3 (5-HT3) receptor-mediated responses in recombinant expression systems and in cultured trigeminal neurons expressing 5-HT3 receptors. Our investigations broaden the spectra of receptors that are targets for nicotine enantiomers and give new insights into the physiological role of nicotine.