title: Acute hemodynamic response of infused fasudil in patients with pulmonary arterial hypertension: a randomized, controlled, crossover study.
abstract: BACKGROUND
  The 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).
  
  
  METHODS
  Using 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 (5 μg) and intravenous fasudil (30 mg over 30 min). Hemodynamic data were collected at baseline and during acute drug exposure.
  
  
  RESULTS
  Comparable decreases were observed in mean pulmonary artery pressure (-4.6 ± 4.3 mmHg vs. -4.8 ± 4.2 mmHg) 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%).
  
  
  CONCLUSIONS
  Infused fasudil improved pulmonary hemodynamics in patients with PAH without significant toxicity.
authors.affiliation: Thrombosis Medicine Center, State Key Laboratory of Cardiovascular Disease, Fu Wai Hospital, Peking Union Medical College and Chinese Academy Medical Science, Beijing, China.
authors.forename: Xin
authors.initials: X
authors.lastname: Jiang
authors.affiliation: Department of Anesthesiology, Fu Wai Hospital, Peking Union Medical College and Chinese Academy Medical Science, Beijing, China.
authors.forename: Yue-Fu
authors.initials: YF
authors.lastname: Wang
authors.affiliation: Department of Cardio-Pulmonary Circulation, Shanghai Pulmonary Hospital, Tongji University School of Medicine, Shanghai, China.
authors.forename: Qin-Hua
authors.initials: QH
authors.lastname: Zhao
authors.affiliation: Department of Cardio-Pulmonary Circulation, Shanghai Pulmonary Hospital, Tongji University School of Medicine, Shanghai, China.
authors.forename: Rong
authors.initials: R
authors.lastname: Jiang
authors.affiliation: Thrombosis Medicine Center, State Key Laboratory of Cardiovascular Disease, Fu Wai Hospital, Peking Union Medical College and Chinese Academy Medical Science, Beijing, China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Wu
authors.affiliation: Thrombosis Medicine Center, State Key Laboratory of Cardiovascular Disease, Fu Wai Hospital, Peking Union Medical College and Chinese Academy Medical Science, Beijing, China.
authors.forename: Fu-Hua
authors.initials: FH
authors.lastname: Peng
authors.affiliation: Thrombosis Medicine Center, State Key Laboratory of Cardiovascular Disease, Fu Wai Hospital, Peking Union Medical College and Chinese Academy Medical Science, Beijing, China.
authors.forename: Xi-Qi
authors.initials: XQ
authors.lastname: Xu
authors.affiliation: Department of Cardio-Pulmonary Circulation, Shanghai Pulmonary Hospital, Tongji University School of Medicine, Shanghai, China.
authors.forename: Lan
authors.initials: L
authors.lastname: Wang
authors.affiliation: Department of Cardio-Pulmonary Circulation, Shanghai Pulmonary Hospital, Tongji University School of Medicine, Shanghai, China.
authors.forename: Jing
authors.initials: J
authors.lastname: He
authors.affiliation: Thrombosis Medicine Center, State Key Laboratory of Cardiovascular Disease, Fu Wai Hospital, Peking Union Medical College and Chinese Academy Medical Science, Beijing, China. Electronic address: jingzhicheng@vip.163.com.
authors.forename: Zhi-Cheng
authors.initials: ZC
authors.lastname: Jing
mesh_terms: D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine / Q000008:administration & dosage / Q000031:analogs & derivatives*; D000280:Administration, Inhalation; D000293:Adolescent; D000328:Adult; D018592:Cross-Over Studies; D004305:Dose-Response Relationship, Drug; D004359:Drug Therapy, Combination; D065627:Familial Primary Pulmonary Hypertension / Q000188:drug therapy* / Q000503:physiopathology; D005260:Female; D006439:Hemodynamics / Q000187:drug effects*; D006801:Humans; D016285:Iloprost / Q000008:administration & dosage; D007262:Infusions, Intravenous; D008297:Male; D008875:Middle Aged; D012189:Retrospective Studies; D016896:Treatment Outcome; D014665:Vasodilator Agents / Q000008:administration & dosage; D055815:Young Adult
chemical_list: D014665:Vasodilator Agents; D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine; D016285:Iloprost; C049347:fasudil
keywords: Acute therapies; Fasudil; Iloprost; Pulmonary arterial hypertension