Abstract 12271: Stabilizing Effect of Metoprolol on Cholesterol Crystallization and Vulnerable Plaque's

Abstract

Introduction: Cardio-protective effects of B- Blockers have not been fully elucidated. We have demonstrated that cholesterol expands when crystallizing and may trigger plaque rupture. Hypothesis: The present study evaluated the potential direct effects of Metoprolol Tartrate (MT) in altering cholesterol crystallization as a possible mechanism for plaque stabilization independent of its cardio-protective effect.

Method: Cholesterol powder (3 g) was melted in 10-ml graduated cylinders with and without MT using a heat gun and then allowed to cool at room temperature. Doses of MT used were comparable to serum levels achieved in humans after a single dose of MT in graded doses of 100mg, 150mg and 200mg. This yielded a maximum serum concentration of 100ng/ml, 150ng/ml and 200ng/ml respectively. MT was dissolved in 1 ml of H2O and then diluted to the above concentrations and then added to cholesterol powder prior to melting. H2O alone was used as control. Five experiments were conducted at each concentration and change in volume expansion was measured and averaged for each dose and compared with control. Scanning electron microscopy (SEM) was performed on the MT treated and control group for crystal morphology.

Results: MT significantly attenuated change in volume expansion (ΔVE) with crystallization in a dose-dependent manner (Graph) at a drug concentration of 100ng/ml, 150ng/ml and 200ng/ml respectively (p = 0.20, 0.02 and 0.01). On scanning electron microscopy, Crystals exposed to MT were blunted with loss of sharp-tipped and melting morphology (SEM, Fig. bottom) compared to control (SEM, Fig. top).

Conclusion: These findings of attenuation of volume expansion with crystallization and alteration in crystal morphology from pointed tip to blunt with dissolving suggest that MT may have additional cardio-protective action by its stabilizing effect on vulnerable plaques.