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 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.

Distal vessel stiffening is an early and pivotal mechanobiological regulator of vascular remodeling and pulmonary hypertension

“…Several modalities to estimate PA stiffness in patients have been developed, including right heart catheterization (7), intravascular ultrasound (6, 48), cardiac magnetic resonance (CMR) imaging (5, 10, 11, 49), and echocardiography (8, 50, 51). In animal models, stiffness measurements have focused on isolated vessel mechanical testing (15–17, 19–22), pressure-flow measurements (18), and — more recently — Doppler imaging (21). However, clinical studies (5, 7, 8, 11, 50, 51) and animal models (15, 16, 19, 22, 52) have primarily focused on PA stiffness measured at the macroscopic scale in established disease.…”

Pulmonary Vascular Stiffness: Measurement, Modeling, and Implications in Normal and Hypertensive Pulmonary Circulations

“…Quite recently, PD measurements were used to obtain elastic modulus approximations using both thin- and thick-walled theories, and compared to in vitro determined elastic modulus (82). It was shown (perhaps unsurprisingly) that elastic moduli computed from the thick-walled theory were superior estimates of ex vivo mechanics compared to those estimated with the thin-walled theory; these expressions are…”

Surgical placement of a wireless telemetry device for cardiovascular studies of bovine calves

“…The bovine calf ( Bos taurus ) has provided invaluable insight into the structural, mechanical, and hemodynamic changes that occur during the onset and progression of pulmonary arterial hypertension (PAH) 1– 4 . Hemodynamic studies of calves conducted to date, however, have typically required the calf to be manually restrained while laterally recumbent 2, 4 .…”

“…Hemodynamic studies of calves conducted to date, however, have typically required the calf to be manually restrained while laterally recumbent 2, 4 .…”