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Biology subjects

Emani, S.

Publications and source records attributed to Emani, S..

2 recordsLinked to original sources

Parametric Engineering of Atrioventricular Living Valve Transplants

Diseases of the (mitral and tricuspid) atrioventricular valves (AVV), which regulate inflow from the atria to the ventricles, can result in severe obstruction to inflow (stenosis) or valvular leakage (regurgitation), requiring surgical intervention. In patients with small annulus diameters (< 19 mm), valve replacement is a clinical challenge limited by prosthesis size constraints, lack of growth potential, suboptimal durability, and elevated thrombosis and bleeding risk. While living valve transplantation (LVT) has re-opened the possibility of using allogeneic valve tissue capable of growth and remodeling, translating this to the AVV has been challenging given the anatomical complexity of the sub-valvular apparatus. Here, we propose a strategy using a replacement bi-leaflet cylindrical valve fabricated from donor AVV tissue and artificial chordae, with a geometry designed to mimic the native AVV and engineered to satisfy predefined clinical targets. Pulse duplicator experiments allowed characterization of valve dynamics in terms of clinically important attributes framed as dimensionless parameters. A multi-objective optimization allowed us to identify an optimal design which we implemented in porcine AVV replacements (n=6). Our results demonstrated favorable hemodynamics with minimal regurgitation and stenosis, suggesting a promising method for patient-optimized valve replacements.

bioengineering↗

Neutrophil extracellular traps formation is associated with postoperative complications in neonates and infants undergoing congenital cardiac surgery

Pediatric patients with congenital heart diseases (CHD) often undergo surgical repair on cardiopulmonary bypass (CPB). Despite a significant medical and surgical improvement, the mortality of neonates and infants remains high. Damage-associated molecular patterns (DAMPs) are endogenous molecules released from injured/damaged tissues as danger signals. We examined 101 pediatric patients who underwent congenital cardiac surgery on CPB. The mortality rate was 4.0%, and the complication rate was 31.6%. We found that neonates/infants experienced multiple complications most, consistent with the previous knowledge. Neonates and infants in the complication group had received more transfusion intraoperatively than the non-complication arm with lower maximum amplitude (MA) on rewarming CPB thromboelastography (TEG). Despite TEG profiles were comparable at ICU admission between the two groups, the complication arm had higher postoperative chest tube output, requiring more blood transfusion. The complication group showed greater neutrophil extracellular traps (NETs) formation at the end of CPB and postoperatively. Plasma histones and high mobility group box 1 (HMGB1) levels were significantly higher in the complication arm. Both induced NETs in vitro and in vivo. As histones and HMGB1 target Toll-like receptor (TLR)2 and TLR4, their mRNA expression in neutrophils was upregulated in the complication arm. Taken together, NETs play a major role in postoperative complication in pediatric cardiac surgery and would be considered a target for intervention. Key pointsO_LINeonates and infants showed highest postoperative complications with more upregulation of inflammatory transcriptomes of neutrophils. C_LIO_LINeonates and infants with organ dysfunction had more NETs formation with higher plasma histones and HMGB1 levels. C_LI

immunology↗