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Effect of propranolol as antiadhesive therapy in sickle cell disease.

Publication ,  Journal Article
De Castro, LM; Zennadi, R; Jonassaint, JC; Batchvarova, M; Telen, MJ
Published in: Clin Transl Sci
December 2012

Sickle red blood cells (SSRBCs) adhere to both endothelial cells (ECs) and the extracellular matrix. Epinephrine elevates cyclic adenosine monophosphate in SSRBCs and increases adhesion of SSRBCs to ECs in a β-adrenergic receptor and protein kinase A-dependent manner. Studies in vitro as well as in vivo have suggested that adrenergic stimuli like epinephrine may contribute to vaso-occlusion associated with physiologic stress. We conducted both animal studies and a Phase I dose-escalation study in sickle cell disease (SCD) patients to investigate whether systemically administered propranolol inhibits SSRBC adhesion and to document the safety of propranolol in SCD. Systemically administered propranolol prevented SSRBC adhesion and associated vaso-occlusion in a mouse model. In patients receiving a single oral dose of 10, 20, or 40 mg propranolol, SSRBC adhesion to ECs was studied before and after propranolol, with and without stimulation with epinephrine. Propranolol administration significantly reduced epinephrine-stimulated SSRBC adhesion in a dose dependent manner (p = 0.03), with maximum inhibition achieved at 40 mg. Adverse events were not severe, did not show dose dependence, and were likely unrelated to drug. No significant heart rate changes occurred. These results imply that β-blockers may have a role as antiadhesive therapy for SCD.

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Published In

Clin Transl Sci

DOI

EISSN

1752-8062

Publication Date

December 2012

Volume

5

Issue

6

Start / End Page

437 / 444

Location

United States

Related Subject Headings

  • Propranolol
  • Mice, Nude
  • Mice
  • Injections, Intravenous
  • Humans
  • Heart Rate
  • General Clinical Medicine
  • Female
  • Erythrocytes
  • Epinephrine
 

Citation

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De Castro, L. M., Zennadi, R., Jonassaint, J. C., Batchvarova, M., & Telen, M. J. (2012). Effect of propranolol as antiadhesive therapy in sickle cell disease. Clin Transl Sci, 5(6), 437–444. https://doi.org/10.1111/cts.12005
De Castro, Laura M., Rahima Zennadi, Jude C. Jonassaint, Milena Batchvarova, and Marilyn J. Telen. “Effect of propranolol as antiadhesive therapy in sickle cell disease.Clin Transl Sci 5, no. 6 (December 2012): 437–44. https://doi.org/10.1111/cts.12005.
De Castro LM, Zennadi R, Jonassaint JC, Batchvarova M, Telen MJ. Effect of propranolol as antiadhesive therapy in sickle cell disease. Clin Transl Sci. 2012 Dec;5(6):437–44.
De Castro, Laura M., et al. “Effect of propranolol as antiadhesive therapy in sickle cell disease.Clin Transl Sci, vol. 5, no. 6, Dec. 2012, pp. 437–44. Pubmed, doi:10.1111/cts.12005.
De Castro LM, Zennadi R, Jonassaint JC, Batchvarova M, Telen MJ. Effect of propranolol as antiadhesive therapy in sickle cell disease. Clin Transl Sci. 2012 Dec;5(6):437–444.
Journal cover image

Published In

Clin Transl Sci

DOI

EISSN

1752-8062

Publication Date

December 2012

Volume

5

Issue

6

Start / End Page

437 / 444

Location

United States

Related Subject Headings

  • Propranolol
  • Mice, Nude
  • Mice
  • Injections, Intravenous
  • Humans
  • Heart Rate
  • General Clinical Medicine
  • Female
  • Erythrocytes
  • Epinephrine