Extracellular matrix remodeling has been proposed as one mechanism by which proximal pulmonary arteries stiffen during pulmonary arterial hypertension (PAH). Although some attention has been paid to the role of collagen and metallomatrix proteins in affecting vascular stiffness, much less work has been performed on changes in elastin structure-function relationships in PAH. Such work is warranted, given the importance of elastin as the structural protein primarily responsible for the passive elastic behavior of these conduit arteries. Here, we study structure-function relationships of fresh arterial tissue and purified arterial elastin from the main, left, and right pulmonary artery branches of normotensive and hypoxia-induced pulmonary hypertensive neonatal calves. PAH resulted in an average 81 and 72% increase in stiffness of fresh and digested tissue, respectively. Increase in stiffness appears most attributable to elevated elastic modulus, which increased 46 and 65%, respectively, for fresh and digested tissue. Comparison between fresh and digested tissues shows that, at 35% strain, a minimum of 48% of the arterial load is carried by elastin, and a minimum of 43% of the change in stiffness of arterial tissue is due to the change in elastin stiffness. Analysis of the stress-strain behavior revealed that PAH causes an increase in the strains associated with the physiological pressure range but had no effect on the strain of transition from elastin-dominant to collagen-dominant behavior. These results indicate that mechanobiological adaptations of the continuum and geometric properties of elastin, in response to PAH, significantly elevate the circumferential stiffness of proximal pulmonary arterial tissue.
The relationship between cardiac function and the afterload against which the heart muscle must work to circulate blood throughout the pulmonary circulation is defined by a complex interaction between many coupled system parameters. These parameters range broadly and incorporate system effects originating primarily from three distinct locations: input power from the heart, hydraulic impedance from the large conduit pulmonary arteries, and hydraulic resistance from the more distal microcirculation. These organ systems are not independent, but rather, form a coupled system in which a change to any individual parameter affects all other system parameters. The result is a highly nonlinear system which requires not only detailed study of each specific component and the effect of disease on their specific function, but also requires study of the interconnected relationship between the microcirculation, the conduit arteries, and the heart in response to age and disease. Here, we investigate systems-level changes associated with pulmonary hypertensive disease progression in an effort to better understand this coupled relationship.
Developing clinical work suggests that vascular stiffening plays a role in the progression of pulmonary hypertension (PH), while recent studies in animal models of hypoxic PH have found significant proximal vascular stiffening in the diseased population. Here, we develop and validate a minimally invasive, clinically realizable method to estimate the local elastic modulus of the proximal pulmonary arteries from pressure-diameter (PD) data. PD measurements were made in the main pulmonary arteries of 16 calves; lumen diameter was assessed using color M-mode tissue Doppler imaging ultrasound, while pressure was measured via catheter. Two methods corresponding to thin-walled pressure vessel theory ("thin") and Lame's equation for a thick-walled cylinder ("thick") were used to approximate the artery elastic modulus from PD measurements. The harvested arteries were tested independently to determine their "true" ex vivo elastic modulus and stiffness. Both approximations displayed excellent correlation with ex vivo elastic modulus of the calf main pulmonary artery (thin r(2) = 0.811; thick r(2) = 0.844; both P < 0.01). Bland-Altman analysis indicated that the thick-walled approximation has better overall agreement with ex vivo modulus. The approximations displayed quantitatively distinct regression slopes that were statistically different (P = 0.02). The elastic modulus of the main pulmonary artery can be reasonably estimated from combined color M-mode tissue Doppler imaging ultrasound and catheter pressure measurements in calves. Such measurements may be a valuable tool in the diagnosis and treatment of human PH.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.