Effect of propranolol as antiadhesive therapy in sickle cell disease.
Journal Article
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.
Full Text
Duke Authors
Cited Authors
- De Castro, LM; Zennadi, R; Jonassaint, JC; Batchvarova, M; Telen, MJ
Published Date
- December 2012
Published In
Volume / Issue
- 5 / 6
Start / End Page
- 437 - 444
PubMed ID
- 23253664
Pubmed Central ID
- 23253664
Electronic International Standard Serial Number (EISSN)
- 1752-8062
International Standard Serial Number (ISSN)
- 1752-8054
Digital Object Identifier (DOI)
- 10.1111/cts.12005
Language
- eng