Becker B F, Bünger R, Permanetter B, Gerlach E
Klin Wochenschr. 1984;62 Suppl 2:67-75.
Tachyphylaxis with respect to the positive inotropic and positive chronotropic effects of nicotine in isolated perfused hearts of guinea pigs was found to persist for 3 and 10 min, respectively, after discontinuation of intracoronary infusion of nicotine (5 X 10(-5) M). The longer duration of chronotropic tachyphylaxis correlated with a slower release of nicotine from the tissue of the right atrium in comparison to the washout from the ventricular myocardium. A similar disparity in washout between atrial and ventricular tissue was found for inulin. Thus, greater perfusion of the ventricular tissue, not a difference in affinity for nicotine, seems to account for the more rapid recovery of the inotropic response to nicotine. The apparent volume of distribution of nicotine in both atrial and ventricular myocardium was about 2 ml/g wet weight; uptake and release of nicotine was rapid. Kinetic analyses of coronary venous washout yielded four components, indicating that nicotine is distributed in at least four (kinetically defined) compartments within the ventricular myocardium. Washout from the largest tissue compartment was controlled by the rate of perfusion of the vascular space, as demonstrated by comparison with washout of erythrocytes, inulin, sucrose, and urea from the heart. Hexamethonium reduced the nicotine content of this fast-emptying compartment from 85-57 nmol/g (prelabeling concentration of nicotine 5 X 10(-5) M), giving an upper estimate for the number of specific nicotine binding sites.(ABSTRACT TRUNCATED AT 250 WORDS)
在豚鼠离体灌注心脏中，冠状动脉内注入尼古丁（5×10⁻⁵M）后停止注入，发现尼古丁的正性肌力和正性变时作用的快速耐受性分别持续3分钟和10分钟。与心室肌中尼古丁的洗脱相比，变时快速耐受性持续时间更长与右心房组织中尼古丁释放较慢有关。对于菊粉，心房和心室组织的洗脱也存在类似差异。因此，似乎是心室组织灌注量更大，而非对尼古丁亲和力的差异，导致对尼古丁的肌力反应恢复更快。尼古丁在心房和心室心肌中的表观分布容积约为2 ml/g湿重；尼古丁的摄取和释放迅速。冠状动脉静脉洗脱的动力学分析产生四个成分，表明尼古丁在心室肌内至少分布于四个（动力学定义的）隔室。与心脏中红细胞、菊粉、蔗糖和尿素的洗脱相比，最大组织隔室的洗脱受血管空间灌注速率控制。六甲铵使这个快速排空隔室的尼古丁含量从85 - 57 nmol/g（预标记尼古丁浓度5×10⁻⁵M）降低，从而给出特定尼古丁结合位点数量的上限估计。（摘要截断于250字）
