Pulmonary arterial input impedance reflects the mechanical properties of pulmonary arterial remodeling in rats with pulmonary hypertension

Takuya Nishikawa,Keita Saku,Takuya Kishi,Takeshi Tohyama,Kohtaro Abe,Yasuhiro Oga,Takahiro Arimura,Takafumi Sakamoto,Keimei Yoshida,Kenji Sunagawa,Hiroyuki Tsutsui

doi:10.1016/j.lfs.2018.10.005

Abstract

AimsAlthough pulmonary arterial remolding in pulmonary hypertension (PH) changes the mechanical properties of the pulmonary artery, most clinical studies have focused on static mechanical properties (resistance), and dynamic mechanical properties (compliance) have not attracted much attention. As arterial compliance plays a significant role in determining afterload of the right ventricle, we evaluated how PH changes the dynamic mechanical properties of the pulmonary artery using high-resolution, wideband input impedance (ZPA). We then examined how changes in ZPA account for arterial remodeling. Clarification of the relationship between arterial remodeling and ZPA could help evaluate arterial remodeling according to hemodynamics. Main methodsPH was induced in Sprague–Dawley rats with an injection of Sugen5416 (20 mg/kg) and 3-week exposure to hypoxia (10% oxygen) (SuHx). ZPA was evaluated from pulmonary artery pressure and flow under irregular pacing. Pulmonary histology was examined at baseline and 1, 3, and 8 weeks (n = 7, each) after Sugen5416 injection. Key findingsSuHx progressively increased pulmonary arterial pressure. ZPA findings indicated that SuHx progressively increased resistance (baseline: 9.3 ± 3.6, SuHx1W: 20.7 ± 7.9, SuHx3W: 48.8 ± 6.9, SuHx8W: 62.9 ± 17.8 mm Hg/mL/s, p < 0.01) and decreased compliance (baseline: 11.9 ± 2.1, SuHx1W: 5.3 ± 1.7, SuHx3W: 2.1 ± 0.7, SuHx8W: 1.9 ± 0.6 × 10−3 mL/mm Hg, p < 0.01). The time constant did not significantly change. The progressive reduction in compliance was closely associated with wall thickening of small pulmonary arteries. SignificanceThe finding that changes in resistance were reciprocally associated with those in compliance indicates that resistant and compliant vessels are anatomically inseparable. The analysis of ZPA might help evaluate arterial remodeling in PH according to hemodynamics.

Highlights

Pulmonary hypertension (PH) is a multifactorial complex pulmonary vascular disorder
As we focused on dynamic pulmonary vascular properties in this study, we used a Sugen/Hypoxia model of PH (SuHx) considering that its histological phenotype of pulmonary vascular remodeling is similar to that of PH in humans [17]
Right ventricular hypertrophy (RVH) was consistent with the progression of PH (Fig. 3C)

Summary

Introduction

Pulmonary hypertension (PH) is a multifactorial complex pulmonary vascular disorder. Pulmonary arterial remodeling and functional vasoconstriction have been shown to increase pulmonary resistance and artery pressure and cause life–threatening right ventricular (RV) failure and death [1,2]. Such structural and functional alterations in pulmonary vasculature change its mechanical properties [3]. In the systemic arterial system, aortic input impedance, which is the Abbreviations: PH, pulmonary hypertension; RV, right ventricular; 3-WK, 3-element windkessel; ZPA, pulmonary arterial input impedance; SV, stroke volume; PP, pulse pressure; SuHx, Sugen/hypoxia; RVH, right ventricular hypertrophy; ODs, outer diameters; WT50, arteries with ODs < 50 μm; WT100, arteries with ODs 50–100 μm; PPA, Pulmonary artery pressure; FPA, Pulmonary artery flow

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Conclusion