In vivo measurement of proximal pulmonary artery elastic modulus in the neonatal calf model of pulmonary hypertension: development and ex vivo validation

Abstract

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 r2= 0.811; thick r2= 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.