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.
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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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Bikou, O., Ishikawa, K., Fish, K.M., Zarragoikoetxea, I., Hajjar, R.J., Aguero, J. (2018). Modeling Pulmonary Hypertension: A Pig Model of Postcapillary Pulmonary Hypertension. In: Ishikawa, K. (eds) Experimental Models of Cardiovascular Diseases. Methods in Molecular Biology, vol 1816. Humana Press, New York, NY. https://doi.org/10.1007/978-1-4939-8597-5_29
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DOI: https://doi.org/10.1007/978-1-4939-8597-5_29
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