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Modeling Pulmonary Hypertension: A Pig Model of Postcapillary Pulmonary Hypertension

  • Olympia Bikou
  • Kiyotake Ishikawa
  • Kenneth M. Fish
  • Iratxe Zarragoikoetxea
  • Roger J. Hajjar
  • Jaume Aguero
Protocol
Part of the Methods in Molecular Biology book series (MIMB, volume 1816)

Abstract

Pulmonary hypertension (PH) is a pathophysiological condition defined as an increase in mean pulmonary arterial pressure ≥25 mmHg at rest assessed by right heart catheterization.

Based on hemodynamic criteria, precapillary PH is characterized by a mean pulmonary capillary wedge pressure ≤15 mmHg as opposed to the postcapillary PH by >15 mmHg. Postcapillary PH is one of the most common forms of PH, often caused by left ventricular dysfunction and heart failure.

In this chapter, we describe protocols for creating a large animal model of postcapillary PH. It is induced by open chest surgery (lateral thoracotomy) to band the pulmonary veins. The model is characterized by low mortality, relatively easy surgical procedure with well reproducible results, and pulmonary and cardiac remodeling at the structural, functional, and molecular levels. The presence of right ventricular (RV) remodeling is of significant importance since right heart failure is the main cause of death in patients suffering from PH. One of the advantages of the model described in this chapter is that both adaptive and maladaptive forms of RV remodeling can be observed during the progression of the disease. This can help understand the progressive pathophysiology of RV failure in humans. Besides the description of the model, a detailed guidance of the RV functional assessment in pigs for both invasive (heart catheterization) and noninvasive (echocardiography) approaches is provided.

Key words

Pulmonary hypertension Animal model Large animal Postcapillary pulmonary hypertension Right heart failure Right heart echocardiography 

Notes

Acknowledgments

This work is supported by NIH R01 HL139963 (K.I.), HL117505, HL 119046, HL129814, 128072, HL131404, HL135093, a P50 HL112324 (R.J.H.), AHA-SDG 17SDG33410873 (K.I.), and two Transatlantic Fondation Leducq grants. We would like to acknowledge the Gene Therapy Resource Program (GTRP) of the National Heart, Lung, and Blood Institute, National Institutes of Health. J.A. was supported by the Fundacion Alfonso Martin-Escudero. O.B. was supported by the Deutsche Herzstiftung.

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Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2018

Authors and Affiliations

  • Olympia Bikou
    • 1
  • Kiyotake Ishikawa
    • 1
  • Kenneth M. Fish
    • 1
  • Iratxe Zarragoikoetxea
    • 1
    • 2
  • Roger J. Hajjar
    • 1
  • Jaume Aguero
    • 1
    • 2
    • 3
  1. 1.Cardiovascular Research CenterIcahn School of Medicine at Mount SinaiNew YorkUSA
  2. 2.Hospital Universitari i Politecnic La FeValenciaSpain
  3. 3.Centro Nacional de Investigaciones Cardiovasculares Carlos III (CNIC)MadridSpain

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