期刊
HEART AND VESSELS
卷 25, 期 2, 页码 144-149出版社
SPRINGER
DOI: 10.1007/s00380-009-1176-8
关键词
Rho-kinase; Inhalation; Pulmonary arterial hypertension; Pulmonary arterial pressure; Pulmonary vascular resistance
资金
- Japanese Ministry of Education, Culture, Sports, Science, and Technology, Tokyo, Japan [13307024, 13557068, 15256003, 16209027]
- Organization for Pharmaceutical Safety and Research of Japan
- Technology Agency
- CREST, Tokyo, Japan
- Grants-in-Aid for Scientific Research [13557068, 15256003, 16209027, 13307024] Funding Source: KAKEN
We have previously demonstrated that long-term inhibition of Rho-kinase ameliorates pulmonary arterial hypertension (PAH) in animal models. In the present study, we examined acute vasodilator effects of inhaled fasudil, a specific Rho-kinase inhibitor, as a more feasible option to locally deliver the drug for PAH. We examined 15 patients with PAH (13 women and 2 men, 45 +/- 4 years old), including idiopathic PAH (n = 5), PAH associated with connective tissue disease (n = 6), PAH with congenital heart disease (n = 3), and portal PAH (n = 1). In those patients, we performed right heart catheterization with a Swan-Ganz catheter in the two protocols with inhalation of nitric oxide (NO) (40 ppm, 10 min) and fasudil (30 mg, 10 min) with a sufficient interval (> 30 min). Both NO and fasudil inhalation significantly reduced mean pulmonary arterial pressure (PAP) (NO: P < 0.01, fasudil: P < 0.05) and tended to decrease pulmonary vascular resistance (NO: P = 0.07, fasudil: P = 0.1), but did not affect cardiac index. The ratio of pulmonary to systemic vascular resistance was significantly reduced both in NO and fasudil inhalation (NO: P < 0.01, fasudil: P < 0.05), indicating that both NO and fasudil inhalation selectively affect lung tissues. Interestingly, there was no correlation in the vasodilator effects between NO and fasudil, and a positive correlation with serum levels of high-sensitivity C-reactive protein was noted for fasudil but not for NO. These results suggest that inhalation of fasudil is as effective as NO in patients with PAH, possibly through different mechanisms.
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