title: A microfluidic platform for probing small artery structure and function.
abstract: Although pathologic changes to the structure and function of small blood vessels are hallmarks of various cardiovascular diseases, limitations of conventional investigation methods (i.e. pressure myography) have prohibited a comprehensive understanding of the underlying mechanisms. We developed a microfluidic device to facilitate assessment of resistance artery structure and function under physiological conditions (37 degrees C, 45 mmHg transmural pressure). The platform allows for on-chip fixation, long-term culture and fully automated acquisition of up to ten dose-response sequences of intact mouse mesenteric artery segments (diameter approximately 250 micrometres and length approximately 1.5 mm) in a well-defined microenvironment. Even abluminal application of phenylephrine or acetylcholine (homogeneous condition) yielded dose-response relationships virtually identical to conventional myography. Unilateral application of phenylephrine (heterogeneous condition) limited constriction to the drug-exposed side, suggesting a lack of circumferential communication. The microfluidic platform allows us to address new fundamental biological questions, replaces a manually demanding procedure with a scalable approach and may enable organ-based screens to be routinely performed during drug development.
authors.affiliation: Department of Mechanical and Industrial Engineering, University of Toronto, Ontario, Canada. axel.guenther@utoronto.ca
authors.forename: Axel
authors.initials: A
authors.lastname: Günther
authors.forename: Sanjesh
authors.initials: S
authors.lastname: Yasotharan
authors.forename: Andrei
authors.initials: A
authors.lastname: Vagaon
authors.forename: Conrad
authors.initials: C
authors.lastname: Lochovsky
authors.forename: Sascha
authors.initials: S
authors.lastname: Pinto
authors.forename: Jingli
authors.initials: J
authors.lastname: Yang
authors.forename: Calvin
authors.initials: C
authors.lastname: Lau
authors.forename: Julia
authors.initials: J
authors.lastname: Voigtlaender-Bolz
authors.forename: Steffen-Sebastian
authors.initials: SS
authors.lastname: Bolz
mesh_terms: D000109:Acetylcholine / Q000494:pharmacology; D000818:Animals; D001775:Blood Circulation / Q000187:drug effects; D004730:Endothelium, Vascular / Q000187:drug effects / Q000502:physiology; D008638:Mesenteric Arteries / Q000033:anatomy & histology* / Q000187:drug effects / Q000502:physiology*; D051379:Mice; D046210:Microfluidic Analytical Techniques / Q000379:methods*; D009130:Muscle, Smooth / Q000187:drug effects / Q000502:physiology; D010656:Phenylephrine / Q000494:pharmacology; D013997:Time Factors; D014661:Vasoconstriction / Q000187:drug effects
chemical_list: D010656:Phenylephrine; D000109:Acetylcholine