Department of Internal Medicine, Kantonsspital Graubünden, Chur, Switzerland.
Division of Transfusion Medicine, Kantonsspital Graubünden, Chur, Switzerland.
Clin Hemorheol Microcirc. 2013;55(3):321-9. doi: 10.3233/CH-2012-1638.
Severe side effects of cocaine consumption are vasoocclusive events such as myocardial infarction and stroke. We have hypothesized that cocaine could affect red blood cells (RBCs) and alter the rheological behaviour of blood. Heparinized blood from healthy volunteers was incubated with a final hematocrit of 45% with increasing cocaine concentrations: 0, 10, 100, 1000, and 10'000 μmol/L plasma. Time dependence of the shape change was tested in phosphate buffered saline containing cocaine. RBCs were fixed in 1% glutaraldehyde for morphological analysis. Blood viscosity was measured with a Couette Viscometer (Contraves LS 30) at 37°C and a shear rate of 69.5 s⁻¹. RBC aggregation was assessed with a Myrenne aggregometer. Cocaine induced a dose-dependent stomatocytic shape transformation of RBCs, which was more pronounced in buffer than in plasma (plasma protein binding of the drug). Stomatocytosis occurs when a drug intercalates preferentially in the inner half of the membrane lipid bilayer. It was a time-dependent process with two components, an almost instant shape change occurring within 1 s, followed by a gradual further shape change during 10 min. Stomatocytosis was reversible by resuspension of the RBCs in cocaine-free buffer. This stomatocytic shape change increased whole blood viscosity at high shear rate from 5.69±0.31 mPa.s to 6.39±0.34 mPa.s for control and 10'000 μmol/L cocaine, respectively (p<0.01). RBC aggregation was not affected by the shape change. These effects occurred at a cocaine concentration, which is several-fold above those measured in vivo. Therefore, it is unlikely that hemorheological factors are involved in vascular events after cocaine consumption.
可卡因消费的严重副作用是血管阻塞性事件，如心肌梗死和中风。我们假设可卡因可能会影响红细胞（RBC）并改变血液的流变行为。将来自健康志愿者的肝素化血液以 45%的最终血细胞比容与逐渐增加的可卡因浓度孵育：0、10、100、1000 和 10000μmol/L 血浆。在含有可卡因的磷酸盐缓冲液中测试形状变化的时间依赖性。将 RBC 固定在 1%戊二醛中进行形态分析。在 37°C 和 69.5 s⁻¹的剪切速率下使用 Couette 粘度计（Contraves LS 30）测量血液粘度。使用 Myrenne 聚集仪评估 RBC 聚集。可卡因诱导 RBC 呈剂量依赖性的口形细胞形状变化，在缓冲液中比在血浆中更为明显（药物在血浆蛋白中的结合）。当药物优先插入膜脂质双层的内半部分时，就会发生口形细胞形成。这是一个具有两个组成部分的时间依赖性过程，即在 1 s 内几乎立即发生形状变化，然后在 10 min 内逐渐进一步发生形状变化。通过将 RBC 重新悬浮在无可卡因的缓冲液中，口形细胞形状变化是可逆的。这种口形细胞形状变化使高剪切率下全血粘度从对照的 5.69±0.31 mPa.s 增加到 10000μmol/L 可卡因的 6.39±0.34 mPa.s（p<0.01）。RBC 聚集不受形状变化的影响。这些效应发生在可卡因浓度高于体内测量值数倍的情况下。因此，在可卡因消费后血管事件中，血液流变学因素不太可能参与其中。
