Acute hemodynamic response of infused fasudil in patients with pulmonary arterial hypertension: A randomized, controlled, crossover study

Jiang, Xin; Wang, Yuefu; Zhao, Qin‐Hua; Jiang, Rong; Wu, Yan; Peng, Fuhua; Xu, Xi-Qi; Wang, Lan; He, Jing; Jing, Zhi-Cheng

doi:10.1016/j.ijcard.2014.09.101

Cited by 35 publications

(58 citation statements)

References 19 publications

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“…Unlike calcium antagonists, Fasudil competes with adenosine triphosphate (ATP) for the ATP binding site in the catalytic region of Rho kinase to block Rho kinase activity and inhibit myosin light chain (MLC) phosphorylation at the final stage of vascular smooth muscle contraction, thus relaxing the spasmodic and contracted vascular smooth muscle and acting as a vasodilator. The therapeutic effect of Fasudil on pulmonary hypertension was reported in 2006 in Japan and by subsequent studies . Xiao et al also reported the therapeutic effect of Fasudil on congenital heart disease accompanied with severe pulmonary hypertension .…”

Section: Introductionmentioning

confidence: 92%

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The acute effects of 30 mg vs 60 mg of intravenous Fasudil on patients with congenital heart defects and severe pulmonary arterial hypertension

Ruan

Zhang

Liu

et al. 2019

Congenital Heart Disease

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Objective The optimal dose of Fasudil is still controversial in congenital heart disease accompanied with severe pulmonary hypertension (CHD‐PAH). This study aimed to compare acute hemodynamic changes after different doses of Fasudil in 60 consecutive adult patients with CHD‐PAH. Design Prospective randomized controlled trial. Setting Tertiary cardiology center. Patients Adult patients with CHD‐PAH. Interventions Patients were randomized to Fasudil 30 or 60 mg. Outcome Measures The hemodynamic parameters were measured at baseline and after 30 minutes of Fasudil through right cardiac catheterization. Blood gas results were obtained from the pulmonary artery, right ventricle, right atrium, superior and inferior vena cava, and femoral artery. Pulmonary vascular resistance (PVR) and systemic arterial resistance (SVR) were calculated. Results The changes in systolic pulmonary artery pressure (sPAP) (−13.1% vs −9.3%, P < .05), diastolic PAP (dPAP) (−17.6% vs −14.5%, P < .05), mean PAP (mPAP) (−12.4% vs −8.5%, P < .05), and PVR (−35.8% vs −22.2%, P < .05) were more pronounced in the 60‐mg group than in the 30‐mg group. All patients had no obvious adverse reactions related to peripheral blood pressure. Conclusions Fasudil could improve the hemodynamics of patients with CHD‐PAH, especially with the 60‐mg dose. There were no serious adverse reactions.

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Section: Introductionmentioning

confidence: 92%

“…The therapeutic effect of Fasudil on pulmonary hypertension was reported in 2006 in Japan 14 and by subsequent studies. [15][16][17][18] Xiao et al also reported the therapeutic effect of Fasudil on congenital heart disease accompanied with severe pulmonary hypertension. 19 Nevertheless, the optimal dose of Fasudil is still controversial.…”

Section: Introductionmentioning

confidence: 99%

The acute effects of 30 mg vs 60 mg of intravenous Fasudil on patients with congenital heart defects and severe pulmonary arterial hypertension

Ruan

Zhang

Liu

et al. 2019

Congenital Heart Disease

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“…Fasudil is registered for the treatment of pulmonary arterial hypertension in Japan. Infused fasudil has shown to improve pulmonary hemodynamics without significant toxicity . Inhaled fasudil has shown to be at least as effective as iNO .…”

Section: Therapy Of Pphnmentioning

confidence: 99%

Current and Future Treatments for Persistent Pulmonary Hypertension in the Newborn

Maibom

Hedegaard

Simonsen

et al. 2018

Basic Clin Pharma Tox

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Persistent pulmonary hypertension in newborn (PPHN) is a serious and possibly fatal syndrome characterized by sustained foetal elevation of pulmonary vascular resistance at birth. PPHN may manifest secondary to other conditions as meconium aspiration syndrome, infection and congenital diaphragmatic hernia. This MiniReview provides the reader with an overview of current and future treatment options for patients with PPHN without congenital diaphragmatic hernia. The study is based on systematic searches in the databases PubMed and Cochrane Library and registered studies on Clinicaltrials.gov investigating PPHN. Inhaled nitric oxide (iNO) is well documented for treatment of PPHN, but 30% fail to respond to iNO. Other current treatment options could be sildenafil, milrinone, prostaglandin analogues and bosentan. There are several ongoing trials with sildenafil, but evidence is lacking for the other treatments and/or for the combination with iNO. Currently, there is no evidence for effect in PPHN of other treatments, for example tadalafil, macitentan, ambrisentan, riociguat and selexipag used for pulmonary arterial hypertension in adults. Experimental studies in animal models for PPHN suggest effect of a series of approaches including recombinant human superoxide dismutase, L-citrulline, Rho-kinase inhibitors and peroxisome proliferator-activated receptor-γ agonists. We conclude that iNO is the most investigated and the only approved pulmonary vasodilator for infants with PPHN. In the iNO non-responders, sildenafil currently seems to be the best alternative either alone or in combination with iNO. Systematic and larger clinical studies are required for testing the other potential treatments of PPHN.

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“…In PAH, the production of NO and prostacyclin is decreased and increasing the production by nitric oxide, phosphodiesterase 5 inhibitors or prostacyclin analogues beneficially affects vadodilatation and antiproliferation [9]. Fasudil is a Rho kinase inhibitor and regresses PAH disease progression in several animal models and has been proposed as PAH treatment [97][98][99][100]. Due to these many parallels and the safety labeling of these compounds, a safe PAH treatment for both mother as fetus during pregnancy cannot be assured.…”

Section: Other Parallels Between Vasoactive Signals In Fetal Developmmentioning

confidence: 99%

Endothelin-1 receptor antagonists in fetal development and pulmonary arterial hypertension

Raaf

Beekhuijzen²,

Guignabert

et al. 2015

Reproductive Toxicology

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Acute hemodynamic response of infused fasudil in patients with pulmonary arterial hypertension: A randomized, controlled, crossover study

Cited by 35 publications

References 19 publications

The acute effects of 30 mg vs 60 mg of intravenous Fasudil on patients with congenital heart defects and severe pulmonary arterial hypertension

The acute effects of 30 mg vs 60 mg of intravenous Fasudil on patients with congenital heart defects and severe pulmonary arterial hypertension

Current and Future Treatments for Persistent Pulmonary Hypertension in the Newborn

Endothelin-1 receptor antagonists in fetal development and pulmonary arterial hypertension

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