A microfluidic platform for probing small artery structure and function.
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.
Günther
Axel
A
Department of Mechanical and Industrial Engineering, University of Toronto, Ontario, Canada. axel.guenther@utoronto.ca
Yasotharan
Sanjesh
S
Vagaon
Andrei
A
Lochovsky
Conrad
C
Pinto
Sascha
S
Yang
Jingli
J
Lau
Calvin
C
Voigtlaender-Bolz
Julia
J
Bolz
Steffen-Sebastian
SS
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
D010656:Phenylephrine; D000109:Acetylcholine