Cardiac forces regulate zebrafish heart valve delamination by modulating Nfat signaling

In the clinic, most cases of congenital heart valve defects are thought to arise through errors that occur after the endothelial–mesenchymal transition (EndoMT) stage of valve development. Although mechanical forces caused by heartbeat are essential modulators of cardiovascular development, their role in these later developmental events is poorly understood. To address this question, we used the zebrafish superior atrioventricular valve (AV) as a model. We found that cellularized cushions of the superior atrioventricular canal (AVC) morph into valve leaflets via mesenchymal–endothelial transition (MEndoT) and tissue sheet delamination. Defects in delamination result in thickened, hyperplastic valves, and reduced heart function. Mechanical, chemical, and genetic perturbation of cardiac forces showed that mechanical stimuli are important regulators of valve delamination. Mechanistically, we show that forces modulate Nfatc activity to control delamination. Together, our results establish the cellular and molecular signature of cardiac valve delamination in vivo and demonstrate the continuous regulatory role of mechanical forces and blood flow during valve formation.

Effect of Combined Etomidate-Ketamine Anesthesia on Perioperative Electrocardiogram and Postoperative Cognitive Dysfunction of Elderly Patients with Rheumatic Heart Valve Disease Undergoing Heart Valve Replacement

Objective. To explore the effect of combined etomidate-ketamine anesthesia on perioperative electrocardiogram (ECG) and postoperative cognitive dysfunction (POCD) of elderly patients with rheumatic heart valve disease (RHVD) undergoing heart valve replacement. Methods. The data of 100 elderly RHVD patients treated in our hospital from May 2019 to May 2020 were selected for the retrospective analysis, and by adopting the double-blind method, the patients were divided into the ketamine group (n = 50) and the combined group (n = 50) according to the anesthesia methods. During the induction of anesthesia, the patients of the two groups were given a small dose of ketamine (0.5 mg/kg) at 5 μg/kg/min continuously via pump injection until the end of surgery, and on this basis, with the same anesthesia measures, those in the combined group were given etomidate (0.3 mg/kg) additionally. The patients’ perioperative ECG indicators, POCD scores, and Numeric Rating Scale (NRS) scores were compared between the two groups. Results. Compared with the ketamine group, the combined group presented significantly lower incidence of ST-T wave changes after anesthesia induction and at the time of intubation and skin incision ( P < 0.05 ), significantly lower average magnitude of ST-segment depression after anesthesia induction ( P < 0.001 ), significantly lower average magnitude of ST-segment elevation after anesthesia induction and extubation ( P < 0.001 ), significantly lower POCD incidence (6.%, P < 0.05 ), and significantly better NRS score after surgery ( P < 0.001 ). Conclusion. Combined etomidate-ketamine anesthesia can stabilize the perioperative ECG indicators of elderly RHVD patients undergoing heart valve replacement, improve their postoperative cognitive function, and reduce their pain sensation, which should be promoted and applied in practice.

Tips and Tricks in Cardiac Surgical Anesthesia

For operations including coronary artery by-pass grafting (CABG), heart valve repair or replacement, ascending aorta surgeries, heart transplantation, and surgical correction of congenital heart defects, anesthesia management shares many similar concepts