Left atrial ligation alters intracardiac flow patterns and the biomechanical landscape in the chick embryo

Abstract

Background Hypoplastic left heart syndrome (HLHS) is a major human congenital heart defect that results in single ventricle physiology and high mortality. Clinical data indicate that intracardiac blood flow patterns during cardiac morphogenesis are a significant etiology. We used the left atrial ligation (LAL) model in the chick embryo to test the hypothesis that LAL immediately alters intracardiac flow streams and the biomechanical environment, preceding morphologic and structural defects observed in HLHS. Results Using fluorescent dye injections, we found that intracardiac flow patterns from the right common cardinal vein, right vitelline vein, and left vitelline vein were altered immediately following LAL. Furthermore, we quantified a significant ventral shift of the right common cardinal and right vitelline vein flow streams. We developed an in silico model of LAL, which revealed that wall shear stress was reduced at the left atrioventricular canal and left side of the common ventricle. Conclusions Our results demonstrate that intracardiac flow patterns change immediately following LAL, supporting the role of hemodynamics in the progression of HLHS. Sites of reduced WSS revealed by computational modeling are commonly affected in HLHS, suggesting that changes in the biomechanical environment may lead to abnormal growth and remodeling of left heart structures.

Characterization of zebrafish larvae suction feeding flow using μPIV and optical coherence tomography

“…The interferogram was detected using a linear CCD array-based spectrometer. For further details of our in-house OCT system, please refer to References Kowalski et al 2014). …”

“…Optical coherence tomography (OCT) imaging was performed in a temperature and humidity controlled chamber using an interferometric technique (Kowalski et al 2014). Acquisition was performed at 67 Hz using a spectral domain system with a 4.3-μm resolution (Ganymede, Thorlabs, Germany).…”

“…While we obtained good side view vector fields and verified flow both into and out of the fish, these results are not included in this research paper, as they required the use of tricaine (an anesthesia) to capture flat fish orientation under our microscope setup. Finally, our group has recently developed a "true" OCT-PIV technique, which can track the intensities of the particles from the OCT data Kowalski et al 2014). However, the data acquisition rate of this technique only barely satisfies the imaging requirements for capturing the rapid feeding cycles encountered in the present larval stages.…”

Mechanical regulation of cardiac development

“…Increased right ventricular flow accelerated the onset of RV circumferential strain patterns, and decreased flow in LV abolished these patterns. Kowalski et al investigated immediate alterations in blood flow patterns and WSS levels following LAL through the use of a computational fluid dynamics (CFD) model (Kowalski et al, 2014). Intracardiac flow patterns are immediately altered following LAL, resulting in a decrease in WSS levels at the left AV canal as well as at the left side of the common ventricle (Kowalski et al, 2014).…”

“…Kowalski et al investigated immediate alterations in blood flow patterns and WSS levels following LAL through the use of a computational fluid dynamics (CFD) model (Kowalski et al, 2014). Intracardiac flow patterns are immediately altered following LAL, resulting in a decrease in WSS levels at the left AV canal as well as at the left side of the common ventricle (Kowalski et al, 2014). WSS level decreased from 10 dynes/cm 2 to 5 dynes/cm 2 at these locations for LAL embryos.…”