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Acute Inhibition of Rho-Kinase Attenuates Pulmonary Hypertension in Patients with Congenital Heart Disease

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Abstract

This study aimed to determine whether the Rho-kinase–mediated pathway is involved in the pathogenesis of left-to-right shunt–induced pulmonary hypertension and whether fasudil exhibits acute beneficial effects on the hemodynamics of these patients. A total of 12 patients with a mean age of 12.3 years were enrolled in a self-controlled prospective study. All the patients had a diagnosis of congenital heart disease with slight to moderate pulmonary hypertension and were scheduled for transcatheter closure. After placement of the catheters, 30 mg/kg fasudil was injected intravenously over 30 min under room air conditions. Hemodynamic parameters including pulmonary artery systolic pressure (PASP), pulmonary vascular resistance (PVR), systemic artery pressure (SAP), systemic vascular resistance (SVR), cardiac input, and blood oxygen saturation were measured and calculated at baseline and 30 min after fasudil injection. After fasudil treatment, PASP decreased to a level 33.03 ± 6.64% less than baseline value (p < 0.01), and maximal PVR decreased to a level 33.03 ± 6.64% less than baseline value (p < 0.01). Cardiac input increased to a level 7.7 ± 5.2% more than baseline value (p < 0.05), and mixed venous oxygen saturation significantly increased to a level 7.7 ± 5.2% more than baseline value (p < 0.01). The left-to-right shunt ratio (QP/QS) also tended to increase (16.2 ± 12.5% of baseline value; p < 0.01). Whereas SAP showed only a slight decrease (−1.6 ± 3.1% of baseline value; p = 0.08), SVR significantly decreased (−10.2 ± 12.2% of baseline value; p < 0.01), and the PVR/SVR ratio tended to decrease (−23.9 ± 15.1% of baseline value). In conclusion, Rho-kinase is involved in the pathogenesis of left-to-right shunt–induced pulmonary hypertension, and fasudil is a novel therapeutic approach.

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Acknowledgments

We are grateful to Professor Shuping Ge, a doctor at Texas Children’s Hospital, for his linguistic comments and help with the manuscript.

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Authors and Affiliations

  1. The Key Laboratory of Cardiovascular Remodeling and Function Research, Chinese Ministry of Education, Chinese Ministry of Public Health, Shandong University Qilu Hospital, No. 107 Wen Hua Xi Road, Jinan, 250012, China

    Fuhai Li, Wei Xia & Ruopeng Sun

  2. Department of Radiation Oncology, Shandong Cancer Hospital and Institute, Jinan, China

    Shuanghu Yuan

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  1. Fuhai Li
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  2. Wei Xia
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  3. Shuanghu Yuan
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  4. Ruopeng Sun
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Correspondence to Ruopeng Sun.

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Li, F., Xia, W., Yuan, S. et al. Acute Inhibition of Rho-Kinase Attenuates Pulmonary Hypertension in Patients with Congenital Heart Disease. Pediatr Cardiol 30, 363–366 (2009). https://doi.org/10.1007/s00246-008-9315-z

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  • DOI: https://doi.org/10.1007/s00246-008-9315-z

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