Effect of pH and Lidocaine on β-Adrenergic Receptor Binding

Interaction During Resuscitation?

¹ From the Department of Anesthesia, The Bowman Gray School of Medicine of Wake Forest University, Winston-Salem, NC.

Epinephrine and other β-adrenergic receptor (βAR) agonists are often administered during cardiopulmonary resuscitation, a time when acid-base abnormalities and arrhythmias also commonly occur. We tested whether β₂AR binding is influenced by pH or the antiarrhythmic drug lidocaine, and whether pH might influence the interaction of lidocaine with β₂ARs. With institutional review board approval and informed consent, 32 venous blood samples were obtained from volunteers. Lymphocytes (which bear β₂ARS similar to those found in heart) were isolated by density gradient centrifugation. Specific binding of the βAR ligand ³H-dihydroalprenolol (³H-DHA) was determined with lidocaine concentrations ranging from 10⁶ to 10² mol/L (n=18 experiments), and with and without lidocaine (n=10 experiments), 100 µmol/L, and with and without QX314 (a permanently charged lidocaine derivative), 1 mmol/L (n=4 experiments). Data are presented as percent of control-specific binding measured at a pH of 7.4. Statistical analysis consisted of Spearman's rank-test. ³H-DHA-specific binding increased (p<.001) with pH. Thus, alkaline conditions favored binding of ³H-DHA to the receptor. Lidocaine inhibited ³H-DHA binding to β₂ARs in a concentration-dependent manner. The concentration that inhibited specific binding of ³H-DHA by 50% was 3.1x10⁴ mol/L (95% confidence limits, 1.3x10⁴ to 7.5x10⁴ mol/L). Lidocaine potency at inhibiting β₂AR binding also increased with increasing pH; thus, there was limited benefit (in terms of increasing binding to β₂ARs) to increasing pH when lidocaine was present. QX314, despite being present in a 10-fold greater concentration than lidocaine, had no effect on ³H-DHA binding at any tested pH. The affinity of β₂ARs for both ³H-DHA and lidocaine increased with pH. Thus, the response to β₂AR agonists (when no lidocaine is present) might be expected to be greater with normal or alkalotic pH than under acidotic conditions, supporting the correction of metabolic acidosis to achieve optimal effects from β₂AR agonists during resuscitation.

Key Words: acidosis • alkalosis • anesthetic • local • lidocaine • β-adrenergic receptors • receptor binding

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