The suprachiasmatic nucleus (SCN) is a circadian oscillator and a critical component of the mammalian circadian system. It receives afferents from the retina and the mesencephalic raphe. Retinal afferents mediate photic entrainment of the SCN, whereas the serotonergic afferents originating from the midbrain modulate photic responses in the SCN; however, the serotonin (5HT) receptor subtypes in the SCN responsible for these modulatory effects are not well characterized. In this study, we tested the hypothesis that 5HT1B receptors are located presynaptically on retinal axon terminals in the SCN and that activation of these receptors inhibits retinal input. The 5HT1B receptor agonists TFMPP and CGS 12066A, administered systemically, inhibited light-induced phase shifts of the circadian activity rhythm in a dose-dependent manner at phase delay and phase advance time points. This inhibition was not affected by previous systemic application of either the selective 5HT1A receptor antagonist (+)WAY 100135 or by the 5HT2 receptor antagonist mesulergine, whereas pretreatment with the nonselective 5HT1 antagonist methiothepin significantly attenuated the effect of TFMPP. TFMPP also produced a dose-dependent reduction in light-stimulated Fos expression in the SCN, although a small subset of cells in the dorsolateral aspect of the caudal SCN were TFMPP-insensitive. TFMPP (1 mM) infused into the SCN produced complete inhibition of light-induced phase advances. Finally, bilateral orbital enucleation reduced the density of SCN 5HT1B receptors as determined using [125I]-iodocyanopindolol to define 5HT1B binding sites. These results are consistent with the interpretation that 5HT1B receptors are localized presynaptically on retinal terminals in the SCN and that activation of these receptors by 5HT1B agonists inhibits retinohypothalamic input.

Background-Characterization

The measurement of BNP has significant value in predicting SCD and VA. However, the benefit of BNP testing in addition to other risk stratification tests is unclear and BNP needs to be evaluated prospectively in combination with other complementary risk stratification tools.

Targeted LV endocardial pacing is a potential alternative to CS pacing and warrants a trial to characterize long-term benefits and risks.

AimsApproaches to the risk stratification for sudden cardiac death (SCD) remain unsatisfactory. Although late gadolinium enhancement cardiac magnetic resonance imaging (LGE-CMR) for SCD risk stratification has been evaluated in several studies, small sample size has limited their clinical validity. We performed this meta-analysis to better gauge the predictive accuracy of LGE-CMR for SCD risk stratification. Methods and resultsElectronic databases and published bibliographies were systematically searched to identify studies evaluating the association between the extent of LV scar on LGE-CMR and ventricular arrhythmic events [SCD, resuscitated cardiac arrest, the occurrence of ventricular arrhythmias, or appropriate implantable cardioverter defibrillator (ICD) therapy]. Only studies enrolling patients with CAD or non-ischaemic cardiomyopathy were included. Summary estimates of the relative risk (RR) and likelihood ratios (LRs) were calculated using random effects models. Eleven studies comprising 1105 patients were identified. During a mean/median follow-up of 8.5 -41 months 207 patients had ventricular arrhythmic events. Ventricular arrhythmic events were more common in patients with a greater extent of LV scar: RR 4.33 [95% confidence interval (CI) 2.98-6.29], positive LR 1.98 (95% CI 1.66-2.37), and negative LR 0.33 (95% CI 0.24 -0.46). Conclusion