Beneficial acute effects of Rho-kinase inhibitor in patients with pulmonary arterial hypertension

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.