Sildenafil Improves Dynamic Vascular Function in the Brain: Studies in Patients with Pulmonary Hypertension

Vol. 21, No. 3, 2006

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Original Paper

Sildenafil Improves Dynamic Vascular Function in the Brain: Studies in Patients with Pulmonary Hypertension
B. Rosengarten^a, R.T. Schermuly^b, R. Voswinckel^b, M.G. Kohstall^b, H. Olschewski^b, N. Weissmann^b, W. Seeger^b, M. Kaps^a, F. Grimminger^b, H.A. Ghofrani^b

Departments of
^aNeurology and
^bInternal Medicine, University Hospital, Justus Liebig University Giessen, Giessen, Germany

Address of Corresponding Author

Cerebrovasc Dis 2006;21:194-200 (DOI: 10.1159/000090555)

Key Words

Transcranial Doppler
Ultrasound
Pulmonary hypertension
Cerebral vasoreactivity
Neurovascular coupling
Sildenafil
Prostacyclin
Nitric oxide
Phosphodiesterase inhibitor

Abstract

Background: Prostaglandins and nitric oxide play a pivotal role in the regulation of macro- and microcirculatory blood flow distribution. Interference with both mediator systems have been implicated in cerebrovascular dysfunction. Inhaled iloprost (long-acting prostacyclin analogue) and the phosphodiesterase-5 inhibitor sildenafil have recently shown efficacy in the treatment of chronic pulmonary hypertension. We investigated the impact of these agents on cerebral microcirculatory regulation in patients suffering from this disease. Methods: In 11 patients suffering from severe pulmonary hypertension, a functional transcranial Doppler test utilizing a visual stimulation paradigm was undertaken to measure the evoked flow velocity in the posterior cerebral artery. Measurements were performed in parallel to right heart catheterization and pharmacological testing of the pulmonary vasoreactivity. After assessment of baseline measurements, inhaled iloprost and oral sildenafil were given consecutively for testing of cerebral and pulmonary vascular function. The data gained from the Doppler measurements were compared to data from 22 healthy volunteers. Results: Both substances provoked a significant reduction of pulmonary arterial pressure and vascular resistance, accompanied by minor changes in systemic vascular resistance. In contrast to these superimposable hemodynamic profiles opposite effects were observed regarding cerebral vascular tone: cerebral microvascular reactivity, as assessed by attenuation and time rate parameters, was significantly improved by sildenafil, but slightly worsened by iloprost. Conclusions: Sildenafil has beneficial effects on cerebral vascular reactivity indicative of an improvement in neurovascular coupling in patients with pulmonary hypertension. These results warrant further investigations of the influence of sildenafil on dynamic vascular function in the brain independent of the underlying disease.

Author Contacts

Bernhard Rosengarten, MD
Department of Neurology, Am Steg 14
DE-35392 Giessen (Germany)
Tel. +49 641 99 45 301, Fax +49 641 99 45 309
E-Mail bernhard.rosengarten@neuro.med.uni-giessen.de

Article Information

Received: August 4, 2005
Accepted: September 19, 2005
Published online: December 23, 2005
Number of Print Pages : 7
Number of Figures : 1, Number of Tables : 2, Number of References : 41

Medline Abstract (ID 16388195)

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