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Estrogen Preserves Pulsatile Pulmonary Arterial Hemodynamics in Pulmonary Arterial Hypertension

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Abstract

Pulmonary arterial hypertension (PAH) is caused by extensive pulmonary vascular remodeling that increases right ventricular (RV) afterload and leads to RV failure. PAH predominantly affects women; paradoxically, female PAH patients have better outcomes than men. The roles of estrogen in PAH remain controversial, which is referred to as “the estrogen paradox”. Here, we sought to determine the role of estrogen in pulsatile pulmonary arterial hemodynamic changes and its impact on RV functional adaption to PAH. Female mice were ovariectomized and replenished with estrogen or placebo. PAH was induced with SU5416 and chronic hypoxia. In vivo hemodynamic measurements showed that (1) estrogen prevented loss of pulmonary vascular compliance with limited effects on the increase of pulmonary vascular resistance in PAH; (2) estrogen attenuated increases in wave reflections in PAH and limited its adverse effects on PA systolic and pulse pressures; and (3) estrogen maintained the total hydraulic power and preserved transpulmonary vascular efficiency in PAH. This study demonstrates that estrogen preserves pulmonary vascular compliance independent of pulmonary vascular resistance, which provides a mechanical mechanism for ability of estrogen to delay disease progression without preventing onset. The estrogenic protection of pulsatile pulmonary hemodynamics underscores the therapeutic potential of estrogen in PAH.

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Abbreviations

CI:

Cardiac index

CO:

Cardiac output

LV:

Left ventricle

mPAP:

Mean pulmonary arterial pressure

OVX:

Ovariectomy

PA:

Pulmonary artery

PAH:

Pulmonary arterial hypertension

PCWP:

Pulmonary capillary wedge pressure

PP:

Pulse pressure

PWV:

Pulse wave velocity

P f :

Forward pressure

P b :

Backward pressure

P b/P f :

Index of global wave reflection

PVR:

Pulmonary vascular resistance

RV:

Right ventricle

SuHx:

Sugen-hypoxia exposure

SV:

Stroke volume

SV/PP:

Global arterial compliance

tPVR:

Total pulmonary vascular resistance

W t :

Total hydraulic power

W o :

Oscillatory hydraulic power

W o/W t :

Oscillatory power fraction

CO/W t :

Transpulmonary vascular efficiency

Z 0 :

Total vascular resistance

Z C :

Characteristic impedance

Γ = (Z 0 − Z C)/(Z 0 + Z C):

Pulse wave reflection

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Acknowledgments

We thank Dr. Guoqing Song for performing in vivo hemodynamic measurement in mice. This work was supported by National Institutes of Health R01HL-086939 (to N.C. Chesler) and American Heart Association 13POST16910091 (to A. Liu).

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Correspondence to Naomi C. Chesler.

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Associate Editor Andreas Anayiotos oversaw the review of this article.

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Liu, A., Hacker, T., Eickhoff, J.C. et al. Estrogen Preserves Pulsatile Pulmonary Arterial Hemodynamics in Pulmonary Arterial Hypertension. Ann Biomed Eng 45, 632–643 (2017). https://doi.org/10.1007/s10439-016-1716-1

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