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Mechanisms of Right-ventricular Dysfunction in a Rat Model of Chronic Neonatal Pulmonary Hypertension

Chronic neonatal pulmonary hypertension (PHT) frequently presents with rightventricular (RV) dysfunction. In neonatal rats exposed to chronic hypoxia, RV dysfunction is reversed by sustained rescue treatment with a Rho-kinase (ROCK) inhibitor – the caveat being systemic hypotension. We therefore examined the reversing effects of pulmonary-selective ROCK inhibition. Rat pups were exposed to air or hypoxia from birth for 21 days and received sustained rescue treatment with aerosolized Fasudil (81 mg/ml t.i.d for 15 min) or i.p. Y27632 (15 mg/kg b.i.d) from days 14-21. Inhaled Fasudil normalized pulmonary vascular resistance, and reversed pulmonary vascular remodeling but did not improve RV systolic function. Systemic, but not pulmonary-selective, ROCK inhibition attenuated increased RV ROCK activity. Our findings indicate that RV dysfunction in chronic hypoxic PHT is not merely a result of increased afterload, but rather may be due to increased activity of ROCK in the right ventricle.

Identiferoai:union.ndltd.org:TORONTO/oai:tspace.library.utoronto.ca:1807/42849
Date22 November 2013
CreatorsGosal, Kiranjot
ContributorsJankov, Robert
Source SetsUniversity of Toronto
Languageen_ca
Detected LanguageEnglish
TypeThesis

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