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  • Title: Beneficial acute effects of rho-kinase inhibitor in patients with pulmonary arterial hypertension.
    Author: Ishikura K, Yamada N, Ito M, Ota S, Nakamura M, Isaka N, Nakano T.
    Journal: Circ J; 2006 Feb; 70(2):174-8. PubMed ID: 16434811.
    Abstract:
    BACKGROUND: Pulmonary arterial hypertension (PAH) is a poor prognostic disease with limited treatment options. Rho-kinase is involved in the pathophysiology of several diseases underlying smooth muscle hypercontraction, so the purpose of this study was to investigate the efficacy of fasudil, a Rho-kinase inhibitor, in patients with PAH. METHODS AND RESULTS: Fasudil 30 mg was intravenously injected over 30 min in 8 patients (all female, mean +/- SD, 41+/-11 years) with PAH. The lowest total pulmonary resistance (TPR) time was within 30-60 min after administration. Administration of fasudil decreased TPR from 1,069+/-573 dyne . s . cm (-5) to 809+/-416 dyne . s . cm(-5) (p<0.005) and mean pulmonary arterial pressure from 41.3+/-12.8 mmHg to 37.9+/-14.6 mmHg (p<0.05). The cardiac index was increased from 2.42+/-0.73 L . min(-1) . m(-2) to 2.84+/-0.79 L . min(-1) . m(-2) (p<0.02). Systemic vascular resistance and systolic systemic arterial pressure (SAP) were decreased (p<0.005, p=0.09, respectively), but the decrease in SAP was small (-6.4+/-9.1 mmHg). CONCLUSION: These results suggest that Rho-kinase is involved in the pathogenesis of human PAH and that fasudil is a novel therapeutic agent.
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