Modest V E, Butterworth J F
Department of Anesthesia, Bowman Gray School of Medicine of Wake Forest University, Winston-Salem, NC 27157-1009, USA.
Chest. 1995 Nov;108(5):1373-9. doi: 10.1378/chest.108.5.1373.
Epinephrine and other beta-adrenergic receptor (beta AR) agonists are often administered during cardiopulmonary resuscitation, a time when acid-base abnormalities and arrhythmias also commonly occur. We tested whether beta 2AR binding is influenced by pH or the antiarrhythmic drug lidocaine, and whether pH might influence the interaction of lidocaine with beta 2ARs. With institutional review board approval and informed consent, 32 venous blood samples were obtained from volunteers. Lymphocytes (which bear beta 2ARs similar to those found in heart) were isolated by density gradient centrifugation. Specific binding of the beta AR ligand 3H-dihydroalprenolol (3H-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 mumol/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 beta 2ARs in a concentration-dependent manner. The concentration that inhibited specific binding of 3H-DHA by 50% was 3.1 x 10(-4) mol/L (95% confidence limits, 1.3 x 10(-4) to 7.5 x 10(-4) mol/L). Lidocaine potency at inhibiting beta 2AR binding also increased with increasing pH; thus, there was limited benefit (in terms of increasing binding to beta 2ARs) 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 beta 2 ARs for both 3H-DHA and lidocaine increased with pH. Thus, the response to beta 2AR 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 beta 2AR agonists during resuscitation.
肾上腺素和其他β-肾上腺素能受体（βAR）激动剂常在心肺复苏期间使用，而此时酸碱异常和心律失常也很常见。我们测试了β2AR结合是否受pH值或抗心律失常药物利多卡因的影响，以及pH值是否可能影响利多卡因与β2AR的相互作用。经机构审查委员会批准并获得知情同意后，从志愿者身上采集了32份静脉血样本。通过密度梯度离心分离淋巴细胞（其携带的β2AR与心脏中发现的相似）。在利多卡因浓度范围为10^(-6)至10^(-2) mol/L（n = 18次实验）、有或无100 μmol/L利多卡因（n = 10次实验）以及有或无QX314（一种带永久电荷的利多卡因衍生物）1 mmol/L（n = 4次实验）的情况下，测定βAR配体3H-二氢阿普洛尔（3H-DHA）的特异性结合。数据以在pH 7.4时测得的对照特异性结合百分比表示。统计分析采用Spearman秩检验。3H-DHA特异性结合随pH值升高而增加（p <.001）。因此，碱性条件有利于3H-DHA与受体结合。利多卡因以浓度依赖性方式抑制3H-DHA与β2AR的结合。抑制3H-DHA特异性结合50%的浓度为3.1×10^(-4) mol/L（95%置信限，1.3×10^(-4)至7.5×10^(-4) mol/L）。利多卡因抑制β2AR结合的效力也随pH值升高而增加；因此，当存在利多卡因时，提高pH值（就增加与β2AR的结合而言）的益处有限。尽管QX314的浓度比利多卡因高10倍，但在任何测试的pH值下对3H-DHA结合均无影响。β2AR对3H-DHA和利多卡因的亲和力均随pH值升高而增加。因此，在无利多卡因时，预计正常或碱中毒pH值下对β2AR激动剂的反应比对酸中毒条件下更大，这支持在复苏期间纠正代谢性酸中毒以从β2AR激动剂获得最佳效果。
