Early rhythmicity in the fetal suprachiasmatic nuclei in response to maternal signals detected by omics approach.

The suprachiasmatic nuclei (SCN) of the hypothalamus harbor the central clock of the circadian system, which gradually matures during the perinatal period. In this study, time-resolved transcriptomic and proteomic approaches were used to describe fetal SCN tissue-level rhythms before rhythms in clock gene expression develop. Pregnant rats were maintained in constant darkness and had intact SCN, or their SCN were lesioned and behavioral rhythm was imposed by temporal restriction of food availability. Model-selecting tools dryR and CompareRhythms identified sets of genes in the fetal SCN that were rhythmic in the absence of the fetal canonical clock. Subsets of rhythmically expressed genes were assigned to groups of fetuses from mothers with either intact or lesioned SCN, or both groups. Enrichment analysis for GO terms and signaling pathways revealed that neurodevelopment and cell-to-cell signaling were significantly enriched within the subsets of genes that were rhythmic in response to distinct maternal signals. The findings discovered a previously unexpected breadth of rhythmicity in the fetal SCN at a developmental stage when the canonical clock has not yet developed at the tissue level and thus likely represents responses to rhythmic maternal signals.

Beneficial Effects of Adjusted Perfusion and Defibrillation Strategies on Rhythm Control within Controlled Automated Reperfusion of the Whole Body (CARL) for Refractory Out-of-Hospital Cardiac Arrest.

Survival and neurological outcomes after out-of-hospital cardiac arrest (OHCA) remain low. The further development of prehospital extracorporeal resuscitation (ECPR) towards Controlled Automated Reperfusion of the Whole Body (CARL) has the potential to improve survival and outcome in these patients. In CARL therapy, pulsatile, high blood-flow reperfusion is performed combined with several modified reperfusion parameters and adjusted defibrillation strategies. We aimed to investigate whether pulsatile, high-flow reperfusion is feasible in refractory OHCA and whether the CARL approach improves heart-rhythm control during ECPR. In a reality-based porcine model of refractory OHCA, 20 pigs underwent prehospital CARL or conventional ECPR. Significantly higher pulsatile blood-flow proved to be feasible, and critical hypotension was consistently prevented via CARL. In the CARL group, spontaneous rhythm conversions were observed using a modified priming solution. Applying potassium-induced secondary cardioplegia proved to be a safe and effective method for sustained rhythm conversion. Moreover, significantly fewer defibrillation attempts were needed, and cardiac arrhythmias were reduced during reperfusion via CARL. Prehospital CARL therapy thus not only proved to be feasible after prolonged OHCA, but it turned out to be superior to conventional ECPR regarding rhythm control.