Abstract
BackgroundThe Rho-kinase pathway has been shown to be involved in the pathogenesis of PAH. As yet, however, the acute effects of the Rho-kinase inhibitor fasudil have not been compared with established pulmonary selective vasodilators in patients with PAH. We compared the acute effects of intravenous fasudil with inhaled iloprost in patients with pulmonary arterial hypertension (PAH). MethodsUsing a crossover design, 50 patients with PAH (idiopathic PAH, PAH associated with repaired left-to-right cardiac shunts, or connective tissue disease) were randomized to iloprost inhalation (5μg) and intravenous fasudil (30mg over 30min). Hemodynamic data were collected at baseline and during acute drug exposure. ResultsComparable decreases were observed in mean pulmonary artery pressure (−4.6±4.3mmHg vs. −4.8±4.2mmHg) and pulmonary vascular resistance (−3.0±3.0 Wood U vs. −2.2±2.7 Wood U) with fasudil infusion and iloprost inhalation, respectively, during acute challenge. However, fasudil infusion resulted in a more pronounced increase in mean cardiac output and mixed venous oxygen saturation compared with iloprost inhalation (13.7±17.1% vs. 6.9±15.0%; p=0.044 and 4.5±5.3% vs. 2.7±8.2%; p=0.044, respectively). Whereas inhaled iloprost resulted in a non-significant increase in mean systemic arterial oxygen saturation (0.8±3.6%), infused fasudil resulted in a non-significant reduction (−0.6±1.1%). ConclusionInfused fasudil improved pulmonary hemodynamics in patients with PAH without significant toxicity.
Published Version
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