Pulmonary artery relative area change is inversely related to ex vivo measured arterial elastic modulus in the canine model of acute pulmonary embolization

Abstract

A low relative area change (RAC) of the proximal pulmonary artery (PA) over the cardiac cycle is a good predictor of mortality from right ventricular failure in patients with pulmonary hypertension (PH). The relationship between RAC and local mechanical properties of arteries, which are known to stiffen in acute and chronic PH, is not clear, however. In this study, we estimated elastic moduli of three PAs (MPA, LPA and RPA: main, left and right PAs) at the physiological state using mechanical testing data and correlated these estimated elastic moduli to RAC measured in vivo with both phase-contrast magnetic resonance imaging (PC-MRI) and M-mode echocardiography (on RPA only). We did so using data from a canine model of acute PH due to embolization to assess the sensitivity of RAC to changes in elastic modulus in the absence of chronic PH-induced arterial remodeling. We found that elastic modulus increased with embolization-induced PH, presumably a consequence of increased collagen engagement, which corresponds well to decreased RAC. Furthermore, RAC was inversely related to elastic modulus. Finally, we found MRI and echocardiography yielded comparable estimates of RAC. We conclude that RAC of proximal PAs can be obtained from either MRI or echocardiography and a change in RAC indicates a change in elastic modulus of proximal PAs detectable even in the absence of chronic PH-induced arterial remodeling. The correlation between RAC and elastic modulus of proximal PAs may be useful for prognoses and to monitor the effects of therapeutic interventions in patients with PH.

Pulmonary arterial strain- and remodeling-induced stiffening are differentiated in a chronic model of pulmonary hypertension

“…Chronic PH was generated in adult beagles (n=4; body weight=12±1 kg) using a modified version of previously described embolization procedures (Bellofiore et al, 2013; Hori et al, 2012; Roldan-Alzate et al, 2014; Tian et al, 2014). Briefly, animals were anesthetized, an indwelling catheter was implanted, and baseline mean, systolic, and diastolic PA pressures were measured using right heart catheterization (RHC).…”

“…Terminal studies were performed at least two weeks after PH was established and before RV dysfunction was evident. At the terminal point, pressure measurements were repeated, and phase-contrast magnetic resonance imaging (MRI) was used to measure in vivo PA radii and PA relative area change (RAC) using the PA area at systole (A max ) and diastole (A min ) (Tian et al, 2014): $$\mathit{RAC}=\frac{A_{\mathit{max}}-A_{\mathit{min}}}{A_{\mathrm{italicmax}}}$$ which is a non-invasively attainable predictor of mortality in PH (Gan et al, 2007). …”

“…Using acute pulmonary embolization, PA stiffening was investigated through the arterial nonlinear elastic response of the tissue during mechanical testing (Tian et al, 2014). To describe this mechanism in simple terms, we and others have referred to the nonlinearly elastic response of arteries that gives rise to increased stiffness at increased strain as strain-induced stiffening (Kamenskiy et al, 2012; Tian et al, 2014).…”

“…Using acute pulmonary embolization, PA stiffening was investigated through the arterial nonlinear elastic response of the tissue during mechanical testing (Tian et al, 2014). To describe this mechanism in simple terms, we and others have referred to the nonlinearly elastic response of arteries that gives rise to increased stiffness at increased strain as strain-induced stiffening (Kamenskiy et al, 2012; Tian et al, 2014). In contrast, the increase in stiffness that occurs due to changes in extracellular matrix (ECM) content and arterial geometry during disease progression (Dajnowiec and Langille, 2007; Wang and Chesler, 2011) is referred to as remodeling-induced stiffening.…”

Letter to the Editor

“…Distensibility, compliance, stiffness, and RAC require an area or diameter measurement, which in humans4, 5 and in an animal models of pulmonary hypertension6 are measured by the gold standard of MRI. Only the first three require an invasive pressure measurement, which is typically obtained by right heart catheterization 4, 5.…”