Dataset Information

Blood flow dynamics reflect degree of outflow tract banding in Hamburger-Hamilton stage 18 chicken embryos.

ABSTRACT: Altered blood flow during embryonic development has been shown to cause cardiac defects; however, the mechanisms by which the resulting haemodynamic forces trigger heart malformation are unclear. This study used heart outflow tract banding to alter normal haemodynamics in a chick embryo model at HH18 and characterized the immediate blood flow response versus the degree of band tightness. Optical coherence tomography was used to acquire two-dimensional longitudinal structure and Doppler velocity images from control (n = 16) and banded (n = 25, 6-64% measured band tightness) embryos, from which structural and velocity data were extracted to estimate haemodynamic measures. Peak blood flow velocity and wall shear rate (WSR) initially increased linearly with band tightness (p < 0.01), but then velocity plateaued between 40% and 50% band tightness and started to decrease with constriction greater than 50%, whereas WSR continued to increase up to 60% constriction before it began decreasing with increased band tightness. Time of flow decreased with constriction greater than 20% (p < 0.01), while stroke volume in banded embryos remained comparable to control levels over the entire range of constriction (p > 0.1). The haemodynamic dependence on the degree of banding reveals immediate adaptations of the early embryonic cardiovascular system and could help elucidate a range of cardiac adaptations to gradually increased load.

SUBMITTER: Midgett M

PROVIDER: S-EPMC4191090 | biostudies-other | 2014 Nov

REPOSITORIES: biostudies-other

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Blood flow dynamics reflect degree of outflow tract banding in Hamburger-Hamilton stage 18 chicken embryos.

Midgett Madeline M Goenezen Sevan S Rugonyi Sandra S

Journal of the Royal Society, Interface 20141101 100

Altered blood flow during embryonic development has been shown to cause cardiac defects; however, the mechanisms by which the resulting haemodynamic forces trigger heart malformation are unclear. This study used heart outflow tract banding to alter normal haemodynamics in a chick embryo model at HH18 and characterized the immediate blood flow response versus the degree of band tightness. Optical coherence tomography was used to acquire two-dimensional longitudinal structure and Doppler velocity ...[more]

PMID: 25165602

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Project description:Elevated intraocular pressure is the primary cause of open angle glaucoma. Outflow resistance exists within the trabecular meshwork but also at the level of Schlemm's canal and further downstream within the outflow system. Viral vectors allow to take advantage of naturally evolved, highly efficient mechanisms of gene transfer, a process that is termed transduction. They can be produced at biosafety level 2 in the lab using protocols that have evolved considerably over the last 15-20 years. Applied by an intracameral bolus, vectors follow conventional as well as uveoscleral outflow pathways. They may affect other structures in the anterior chamber depending on their transduction kinetics which can vary among species when using the same vector. Not all vectors can express long-term, a desirable feature to address the chronicity of glaucoma. Vectors that integrate into the genome of the target cell can achieve transgene function for the life of the transduced cell but are mutagenic by definition. The most prominent long-term expressing vector systems are based on lentiviruses that are derived from HIV, FIV, or EIAV. Safety considerations make non-primate lentiviral vector systems easier to work with as they are not derived from human pathogens. Non-integrating vectors are subject to degradation and attritional dilution during cell division. Lentiviral vectors have to integrate in order to express while adeno-associated viral vectors (AAV) often persist as intracellular concatemers but may also integrate. Adeno- and herpes viral vectors do not integrate and earlier generation systems might be relatively immunogenic. Nonviral methods of gene transfer are termed transfection with few restrictions of transgene size and type but often a much less efficient gene transfer that is also short-lived. Traditional gene transfer delivers exons while some vectors (lentiviral, herpes and adenoviral) allow transfer of entire genes that include introns. Recent insights have highlighted the role of non-coding RNA, most prominently, siRNA, miRNA and lncRNA. SiRNA is highly specific, miRNA is less specific, while lncRNA uses highly complex mechanisms that involve secondary structures and intergenic, intronic, overlapping, antisense, and bidirectional location. Several promising preclinical studies have targeted the RhoA or the prostaglandin pathway or modified the extracellular matrix. TGF-? and glaucoma myocilin mutants have been transduced to elevate the intraocular pressure in glaucoma models. Cell based therapies have started to show first promise. Past approaches have focused on the trabecular meshwork and the inner wall of Schlemm's canal while new strategies are concerned with modification of outflow tract elements that are downstream of the trabecular meshwork.

Dataset Information

Blood flow dynamics reflect degree of outflow tract banding in Hamburger-Hamilton stage 18 chicken embryos.

Publications

Blood flow dynamics reflect degree of outflow tract banding in Hamburger-Hamilton stage 18 chicken embryos.

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