Plastic Surgery Research Council
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PSRC 60th Annual Meeting
Program and Abstracts

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Propranolol Alters IH Development Via Beta2-adrenergic Receptor Blockade
Ryan W. England, BS, Naikhoba C.O. Munabi, BA, Jan K. Kitajewski, PhD, Carrie J. Shawber, PhD, June K. Wu, MD.
Columbia University, New York, NY, USA.

PURPOSE:
Propranolol is efficacious in treating infantile hemangiomas (IHs). Our lab has demonstrated that propranolol acted on hemangioma stem cells (HemSCs) via β2-adrenergic receptors (β2ARs) in vitro to affect cell proliferation and viability. We hypothesize that propranolol effects on IH development in vivo is mediated via β2ARs.
METHODS:
HemSCs, resuspended in Matrigel, were injected into nude mice and treated for 3 weeks with: vehicle, low-dose propranolol (0.2mg/kg/day), high-dose propranolol (equivalent to clinical dose; 2mg/kg/day), or ICI, a selective β2AR antagonist (equivalent to clinical dose of propranolol; 2mg/kg/day). IH development was monitored by weekly ultrasound (US) Doppler. US Doppler detected blood flow within abnormal dilated vasculature, while normal capillary flow was beyond its sensitivity. Matrigels were harvested at 3 weeks, analyzed by H&E, and quantified by ImageJ.
RESULTS:
At 3 weeks, US Doppler detected flow in the ectatic vessels of control implants. Doppler-detectable flow was reduced in all treatment groups, with minimal blood flow observed in high-dose propranolol- and ICI-treated implants. H&E staining of harvested implants confirmed development of dilated IH-like vessels in control implants, while vessel caliber was significantly decreased in high-dose propranolol and ICI treated mice (Fig. 1).
CONCLUSION:
Low-dose propranolol caused minimal changes in murine IH development. High-dose propranolol, equivalent to dosage used in clinical treatment, resulted in normalized blood flow by US Doppler and inhibition of ectatic vessel formation, and this was mimicked by the selective β2 antagonist. These results suggest selectively targeting the β2-adrenergic receptor may have equivalent clinical efficacy as propranolol, while avoiding β1AR-mediated effects of hypotension and bradycardia that have been reported during IH treatment.


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