Beneficial Acute Effects of Rho-Kinase Inhibitor in Patients With Pulmonary Arterial Hypertension

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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 hypercon-traction, 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 30mg was intravenously injected over 30min 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±12.8mmHg to 37.9±14.6mmHg (p<0.05). The cardiac index was increased from 2.42±0.73L・min^<-1>・m^<-2> to 2.84±0.79L・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±9.1mmHg). Conclusion These results suggest that Rho-kinase is involved in the pathogenesis of human PAH and that fasudil is a novel therapeutic agent.
社団法人日本循環器学会の論文
2006-01-20