Skip to main content

Advertisement

SpringerLink
Log in

Acute Effect of Intravenous Sildenafil on Cerebral Blood Flow in Patients with Vasospasm After Subarachnoid Hemorrhage

  • Original Article
  • Published:
Neurocritical Care Aims and scope Submit manuscript

Abstract

Background

The phosphodiesterase-5 inhibitor sildenafil has been shown to attenuate delayed cerebral ischemia (DCI) and improve neurologic function in experimental subarachnoid hemorrhage (SAH). We recently demonstrated that it could improve cerebral vasospasm (CVS) in humans after SAH. However, successful therapies for DCI must also restore cerebral blood flow (CBF) and/or autoregulatory capacity. In this study, we tested the effects of sildenafil on CBF in SAH patients at-risk for DCI.

Methods

Six subjects with angiographically confirmed CVS received 30-mg of intravenous sildenafil (mean 9 ± 2 days after aneurysmal SAH). Each underwent 15O-PET imaging to measure global and regional CBF at baseline and post-sildenafil.

Results

Mean arterial pressure declined by 10 mm Hg on average post-sildenafil (8 %, p = 0.01), while ICP was unchanged. There was no change in global CBF (mean 34.5 ± 7 ml/100g/min at baseline vs. 33.9 ± 8.0 ml/100g/min post-sildenafil, p = 0.84). The proportion of brain regions with low CBF (<25 ml/100g/min) was also unchanged after sildenafil infusion.

Conclusions

Infusion of sildenafil does not lead to a change in global or regional perfusion despite a significant reduction in cerebral perfusion pressure. While this could reflect the ineffectiveness of sildenafil-induced proximal vasodilatation to alter brain perfusion, it also suggests that cerebral autoregulatory function was preserved in this group. Future studies should assess whether sildenafil can restore or enhance autoregulation after SAH.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3

Similar content being viewed by others

References

  1. Macdonald RL. Delayed neurological deterioration after subarachnoid haemorrhage. Nat Rev Neurol. 2014;10:44–58.

    Article  CAS  PubMed  Google Scholar 

  2. Etminan N, Vergouwen MDI, Ilodigwe D, MacDonald RL. Effect of pharmaceutical treatment on vasospasm, delayed cerebral ischemia, and clinical outcome in patients with aneurysmal subarachnoid hemorrhage: a systematic review and meta-analysis. J Cereb Blood Flow Metab. 2011;31:1443–51.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  3. Pluta RM. Dysfunction of nitric oxide synthases as a cause and therapeutic target in delayed cerebral vasospasm after SAH. Acta Neurochirurgica, Supplementum 2008: 139–47.

  4. Vellimana AK, Milner E, Azad TD, et al. Endothelial nitric oxide synthase mediates endogenous protection against subarachnoid hemorrhage-induced cerebral vasospasm. Stroke. 2011;42:776–82.

    Article  CAS  PubMed  Google Scholar 

  5. Atalay B, Caner H, Cekinmez M, Ozen O, Celasun B, Altinors N. Systemic administration of phosphodiesterase V inhibitor, sildenafil citrate, for attenuation of cerebral vasospasm after experimental subarachnoid hemorrhage. Neurosurgery. 2006;59:1102–7.

    PubMed  Google Scholar 

  6. Gokce C, Gulsen S, Yilmaz C, Guven G, Caner H, Altinors N. The effect of the sildenafil citrate on cerebral vasospasm and apoptosis following experimental subarachnoid hemorrhage in rats. J Neurosurg Sci. 2010;54:29–37.

    CAS  PubMed  Google Scholar 

  7. Han BH, Vellimana AK, Zhou ML, Milner E, Zipfel GJ. Phosphodiesterase 5 inhibition attenuates cerebral vasospasm and improves functional recovery after experimental subarachnoid hemorrhage. Neurosurgery. 2012;70:178–86 discussion 86–7.

    Article  PubMed  PubMed Central  Google Scholar 

  8. Washington CW, Derdeyn CP, Dhar R, et al. A Phase I proof-of-concept and safety trial of sildenafil to treat cerebral vasospasm following subarachnoid hemorrhage. J Neurosurg. 2015;110:1–10.

    Google Scholar 

  9. Raichle ME, Martin WR, Herscovitch P, Mintun MA, Markham J. Brain blood flow measured with intravenous H2(15)O. II. Implementation and validation. J Nucl Med. 1983;24:790–8.

    CAS  PubMed  Google Scholar 

  10. Dhar R, Zazulia AR, Videen TO, Zipfel GJ, Derdeyn CP, Diringer MN. Red blood cell transfusion increases cerebral oxygen delivery in anemic patients with subarachnoid hemorrhage. Stroke. 2009;40:3039–44.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  11. Dhar R, Scalfani MT, Blackburn S, Zazulia AR, Videen T, Diringer M. Relationship between angiographic vasospasm and regional hypoperfusion in aneurysmal subarachnoid hemorrhage. Stroke. 2012;43:1788–94.

    Article  PubMed  PubMed Central  Google Scholar 

  12. Yundt KD, Grubb RL, Diringer MN, Powers WJ. Autoregulatory vasodilation of parenchymal vessels is impaired during cerebral vasospasm. J Cereb Blood Flow Metab. 1998;18:419–24.

    Article  CAS  PubMed  Google Scholar 

  13. Choi HA, Ko SB, Chen H, et al. Acute effects of nimodipine on cerebral vasculature and brain metabolism in high grade subarachnoid hemorrhage patients. Neurocrit Care. 2012;16:363–7.

    Article  CAS  PubMed  Google Scholar 

  14. Rosengarten B, Schermuly RT, Voswinckel R, et al. Sildenafil improves dynamic vascular function in the brain: studies in patients with pulmonary hypertension. Cerebrovasc Dis. 2006;21:194–200.

    Article  CAS  PubMed  Google Scholar 

  15. Diomedi M, Sallustio F, Rizzato B, et al. Sildenafil increases cerebrovascular reactivity: a transcranial Doppler study. Neurology. 2005;65:919–21.

    Article  CAS  PubMed  Google Scholar 

Download references

Funding

American Heart Association (SDG3440008 to RD) and Washington University Institute of Clinical and Translational Sciences (UL1 TR000448 to GZ).

Author information

Authors and Affiliations

  1. Division of Neurocritical Care, Department of Neurology, Washington University in St. Louis, 660 S Euclid Avenue, St. Louis, MO, 63110, USA

    Rajat Dhar, Michael Diringer, Allyson Zazulia, Colin Derdeyn & Gregory Zipfel

  2. Department of Neurosurgery, Washington University in St. Louis, St. Louis, MO, 63110, USA

    Chad Washington, Michael Diringer, Colin Derdeyn & Gregory Zipfel

  3. Department of Radiology, Washington University in St. Louis, St. Louis, MO, 63110, USA

    Allyson Zazulia, Hussain Jafri & Colin Derdeyn

Authors
  1. Rajat Dhar
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Chad Washington
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Michael Diringer
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Allyson Zazulia
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Hussain Jafri
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Colin Derdeyn
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Gregory Zipfel
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Rajat Dhar.

Additional information

Rajat Dhar and Chad Washington are co-primary authors.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Dhar, R., Washington, C., Diringer, M. et al. Acute Effect of Intravenous Sildenafil on Cerebral Blood Flow in Patients with Vasospasm After Subarachnoid Hemorrhage. Neurocrit Care 25, 201–204 (2016). https://doi.org/10.1007/s12028-016-0243-0

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12028-016-0243-0

Keywords

Search

Navigation