Effect of pH and Lidocaine on β-Adrenergic Receptor Binding: Interaction During Resuscitation?

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 β 2 AR binding is influenced by pH or the antiarrhythmic drug lidocaine, and whether pH might influence the interaction of lidocaine with β 2 ARS. With institutional review board approval and informed consent, 32 venous blood samples were obtained from volunteers. Lymphocytes (which bear β 2 ARS similar to those found in heart) were isolated by density gradient centrifugation. Specific binding of the βAR ligand 3 H-dihydroalprenolol ( 3 H-DHA) was determined with lidocaine concentrations ranging from 10 −6 to 10 −2 mol/L (n=18 experiments), and with and without lidocaine (n=10 experiments), 100 pmol/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. 3 H-DHA-specific binding increased (p 3 H-DHA to the receptor. Lidocaine inhibited 3 H-DHA binding to β 2 ARS in a concentration-dependent manner. The concentration that inhibited specific binding of 3 H-DHA by 50% was 3.1×10 −4 mol/L (95% confidence limits, 1.3×10 −4 to 7.5×10 −4 mol/L). Lidocaine potency at inhibiting β 2 AR binding also increased with increasing pH; thus, there was limited benefit (in terms of increasing binding to β 2 ARS) to increasing pH when lidocaine was present. QX314, despite being present in a 10-fold greater concentration than lidocaine, had no effect on 3 H-DHA binding at any tested pH. The affinity of β 2 ARS for both 3 H-DHA and lidocaine increased with pH. Thus, the response to β 2 AR 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 β 2 AR agonists during resuscitation.