Chiong M A
Can J Physiol Pharmacol. 1982 Jul;60(7):952-9. doi: 10.1139/y82-134.
The effects of verapamil (VER), at concentrations of 0 X 10(-9) X 10(-8) X 10(-7), and 5 X 10(-7) M (or 0, 0.5, 5, 50, and 250 ng/mL) were studied in the isolated rabbit heart during 70 min of aerobic perfusion with a standard Krebs-bicarbonate medium at 37 degrees C. The studied variables were left ventricular performance (RPP, heart rate times left ventricular (LV) systolic pressure), coronary sinus flow (CSF), oxygen uptake (MVO2), rate of creatine kinase (CK) release, and energy stores (glycogen, creatine phosphate (CP), ATP, and total adenine nucleotides (TAN) ). The results show that (i) VER depressed RPP in a dose-related manner: (ii) MVO2 declined as VER concentration increased except in the 5 x 10(-7) M group which showed a paradoxical increase in O2 uptake; (iii) CSF was only slightly decreased by VER with the exception of the 5 x 10(-7) M group, which showed an increase in flow; (iv) VER was associated with increments in the rates of CK release in a dose-related fashion (2, 4, 15, and 29 times the rate observed in the untreated group), and (v) VER was associated with slight decrease in glycogen levels, but no changes in CP or adenine nucleotides. It is concluded that, in our preparation, VER caused marked increases in the rate of CK loss in the absence of depletion of total energy stores. The data suggest that the drug affects the permeability characteristics of the sarcolemma, perhaps via localized depletion of calcium stores.
在37摄氏度下，用标准的 Krebs - 碳酸氢盐培养基对离体兔心脏进行70分钟的有氧灌注，研究了维拉帕米（VER）在浓度为0×10⁻⁹、0.5×10⁻⁸、5×10⁻⁷和5×10⁻⁷M（即0、0.5、5、50和250 ng/mL）时的作用。研究的变量包括左心室功能（RPP，心率乘以左心室（LV）收缩压）、冠状窦血流量（CSF）、氧摄取量（MVO₂）、肌酸激酶（CK）释放速率以及能量储备（糖原、磷酸肌酸（CP）、三磷酸腺苷（ATP）和总腺嘌呤核苷酸（TAN））。结果表明：（i）VER以剂量相关的方式降低RPP；（ii）除了5×10⁻⁷M组氧摄取量出现反常增加外，MVO₂随着VER浓度的增加而下降；（iii）VER仅使CSF略有下降，但5×10⁻⁷M组除外，该组血流量增加；（iv）VER与CK释放速率的增加呈剂量相关（分别是未处理组观察到速率的2倍、4倍、15倍和29倍）；（v）VER与糖原水平略有下降相关，但CP或腺嘌呤核苷酸无变化。得出的结论是，在我们的实验制剂中，VER在总能量储备未耗尽的情况下导致CK丢失速率显著增加。数据表明该药物可能通过局部钙储备的耗竭影响肌膜的通透性特征。
