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How valid are animal models to evaluate treatments for pulmonary hypertension?

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Abstract

Various animal models of pulmonary hypertension (PH) exist, among which injection of monocrotaline (MCT) and exposure to hypoxia are used most frequently. These animal models have not only been used to characterize the pathophysiology of PH and its sequelae such as right ventricular hypertrophy and failure, but also to test novel therapeutic strategies. This manuscript summarizes the available treatment studies in animal models of PH, and compares the findings to those obtained in patients with PH. The analysis shows that all approaches which have proven successful in patients, most notably prostacyclin and its analogs and endothelin receptor antagonists, are also effective in various animal models. However, the opposite it not always true. Therefore, promising results in animals have to be interpreted carefully until confirmed in clinical studies.

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Abbreviations

ACE:

angiotensin converting enzyme

ET:

endothelin

IPAH:

idiopathic pulmonary arterial hypertension

5-HT:

(5-hydroxytryptamine); serotonin

5-HTT:

serotonin plasmatic membrane transporter

MCT:

monocrotaline

PAP:

pulmonary aterial pressure

PASMCs:

pulmonary artery smooth muscle cells

PDE5:

phosphodiesterase 5

PH:

pulmonary hypertension

RV:

right ventricle

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Acknowledgements

Dr. Tan was supported by the Royal Netherlands Academy of Arts and Sciences (KNAW) and the Netherlands Heart Foundation (NHS 2002B191).

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Authors and Affiliations

  1. Department of Clinical and Experimental Cardiology, Academic Medical Center, University of Amsterdam, Meibergdreef 9, 1105 AZ, Amsterdam, The Netherlands

    Maria E. Campian, Maxim Hardziyenka & Hanno L. Tan

  2. Department of Pharmacology and Pharmacotherapy,Academic Medical Center, University of Amsterdam, Amsterdam, Netherlands

    Maria E. Campian & Martin C. Michel

  3. Department of Cardiology, Academic Medical Center, University of Amsterdam, Amsterdam, Netherlands

    Hanno L. Tan

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  1. Maria E. Campian
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  2. Maxim Hardziyenka
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  3. Martin C. Michel
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  4. Hanno L. Tan
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Correspondence to Hanno L. Tan.

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Campian, M.E., Hardziyenka, M., Michel, M.C. et al. How valid are animal models to evaluate treatments for pulmonary hypertension?. Naunyn-Schmied Arch Pharmacol 373, 391–400 (2006). https://doi.org/10.1007/s00210-006-0087-9

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